Secondary metabolites from Ganoderma

8 downloads 21 Views 1MB Size Report
May 11, 2015 - from Ganoderma (Boh et al., 2007; Kim and Kim, 1999; Paterson, ...... Cheng, C.R., Yue, Q.X., Wu, Z.Y., Song, X.Y., Tao, S.J., Wu, X.H., Xu, P.P., ...

Phytochemistry 114 (2015) 66–101

Contents lists available at ScienceDirect

Phytochemistry journal homepage: www.elsevier.com/locate/phytochem

Secondary metabolites from Ganoderma Sabulal Baby ⇑, Anil John Johnson, Balaji Govindan Phytochemistry and Phytopharmacology Division, Jawaharlal Nehru Tropical Botanic Garden and Research Institute, Pacha-Palode, Thiruvananthapuram 695 562, Kerala, India

a r t i c l e

i n f o

Article history: Available online 11 May 2015 Keywords: Ganoderma Ganodermataceae Lanostane type triterpenoids Ganoderic acids Lucidenic acids Meroterpenoids Steroids Volatiles Biological activities

a b s t r a c t Ganoderma is a genus of medicinal mushrooms. This review deals with secondary metabolites isolated from Ganoderma and their biological significance. Phytochemical studies over the last 40 years led to the isolation of 431 secondary metabolites from various Ganoderma species. The major secondary compounds isolated are (a) C30 lanostanes (ganoderic acids), (b) C30 lanostanes (aldehydes, alcohols, esters, glycosides, lactones, ketones), (c) C27 lanostanes (lucidenic acids), (d) C27 lanostanes (alcohols, lactones, esters), (e) C24, C25 lanostanes (f) C30 pentacyclic triterpenes, (g) meroterpenoids, (h) farnesyl hydroquinones (meroterpenoids), (i) C15 sesquiterpenoids, (j) steroids, (k) alkaloids, (l) prenyl hydroquinone (m) benzofurans, (n) benzopyran-4-one derivatives and (o) benzenoid derivatives. Ganoderma lucidum is the species extensively studied for its secondary metabolites and biological activities. Ganoderma applanatum, Ganoderma colossum, Ganoderma sinense, Ganoderma cochlear, Ganoderma tsugae, Ganoderma amboinense, Ganoderma orbiforme, Ganoderma resinaceum, Ganoderma hainanense, Ganoderma concinna, Ganoderma pfeifferi, Ganoderma neo-japonicum, Ganoderma tropicum, Ganoderma australe, Ganoderma carnosum, Ganoderma fornicatum, Ganoderma lipsiense (synonym G. applanatum), Ganoderma mastoporum, Ganoderma theaecolum, Ganoderma boninense, Ganoderma capense and Ganoderma annulare are the other Ganoderma species subjected to phytochemical studies. Further phytochemical studies on Ganoderma could lead to the discovery of hitherto unknown biologically active secondary metabolites. Ó 2015 Elsevier Ltd. All rights reserved.

1. Genus Ganoderma Ganoderma is a group of wood degrading mushrooms with hard fruiting bodies. They belong to the kingdom of Fungi, division of Basidiomycota, class of Homobasidiomycetes, order of Aphyllophorales, family of Polyporaceae (Ganodermataceae) and genus of Ganoderma. A search for ‘Ganoderma’ in the database Index Fungorum displayed 428 species records, including synonyms. Taxonomic studies reported more than 300 species in genus Ganoderma, and most of them are distributed in the tropical regions (Richter et al., 2015; Seo and Kirk, 2000). Phytochemical and other studies reported varying species numbers in the genus (Li et al., 2013a; Peng et al., 2014b; Yan et al., 2013). Ganoderma species are generally not listed among edible mushrooms because their fruiting bodies are thick, corky and tough and do not have the fleshy texture characteristics (Jonathan et al., 2008; Jong and Birmingham, 1992). It is a genus of traditionally used medicinal mushrooms. Crude extracts of Ganoderma species are used as remedies for the treatment of a number of ailments including

⇑ Corresponding author. Tel.: +91 472 2869226x214; fax: +91 472 2869646. E-mail address: [email protected] (S. Baby). http://dx.doi.org/10.1016/j.phytochem.2015.03.010 0031-9422/Ó 2015 Elsevier Ltd. All rights reserved.

cancer. A recent search for ‘Ganoderma’ in SciFinder Scholar gave more than 6500 publications of which nearly half were written in the Chinese language (Adams et al., 2010). Ganoderma lucidum is the best known medicinal mushroom (Leung et al., 2002; Paterson, 2006; Ríos et al., 2012; Sanodiya et al., 2009; Ziegenbein et al., 2006). It is known as ‘Lingzhi’ in Chinese, ‘Reishi’ in Japanese and ‘Yeongji’ in Korean. It occurs in different colors and shapes. In the Chinese medical texts, six strains of G. lucidum are described. Their names are derived from the colors of their fruit bodies: Sekishi (red), Shishi (violet), Kokushi (black), Oushi (yellow), Hakushi (white) and Seishi (blue) (Hirotani et al., 1993; Wang et al., 1993). G. lucidum, highly ranked in oriental traditional medicine, has been used as a panacea for chronic diseases such as hepatopathy, nephritis, hypertension, arthritis, insomnia, bronchitis, asthma, diabetes and cancer (Fatmawati et al., 2010; Mizushina et al., 1998a; Nishitoba et al., 1988b; Wasser, 2005; Wasser and Weis, 1999). It is a well known crude drug which has long been used in Traditional Chinese Medicine for the promotion of longevity and maintenance of vitality (Adams et al., 2010; Liew et al., 1992; Wang et al., 2006). Owing to its ‘‘magical’’ medicinal properties, G. lucidum was considered as an ‘elixir that could revive the dead’ (Cheng et al., 2010; Leung et al., 2002).

S. Baby et al. / Phytochemistry 114 (2015) 66–101

The use of G. lucidum even to cure major disease conditions prompted extensive phytochemical and biological studies (Ríos et al., 2012). So far, over 240 secondary compounds have been isolated from G. lucidum (Chen et al., 2012; Paterson, 2006; Qiao et al., 2007; Shiao, 2003) (Table 1, Fig. 1). Triterpenoids are the major constituents in G. lucidum and they play a critical role in its biological effects. G. lucidum has a strong bitterness which originates from its triterpenes and it depends on the strain, cultivation conditions and manufacturing processes (Seo et al., 2009). Several recent systematic studies have established the therapeutic potential of this mushroom as an anticancer agent (Gao et al., 2002; Joseph et al., 2011b; Kimura et al., 2002; Liu et al., 2009a; Muller et al., 2006; Ríos et al., 2012; Yuen and Gohel, 2005). G. lucidum was also found to possess antiviral especially anti-HIV (El-Mekkawy et al., 1998; Eo et al., 1999a,b; Min et al., 1998), immunomodulating (Chen et al., 2006), antiinflammatory (Joseph et al., 2009, 2011b; Ko et al., 2008), antiandrogenic (Fujita et al., 2005; Liu et al., 2007), cholesterol synthesis inhibitory (Hajjaj et al., 2005; Komoda et al., 1985), hypoglycemic (Hikino et al., 1989), hepatoprotective (Kim et al., 1999), inhibition of lipid peroxidation/oxidative DNA damage (Joseph et al., 2009; Lee et al., 2001), antimicrobial (Yoon et al., 1994) and anti-aging (Shie et al., 2001) activities. G. lucidum is also safe because oral administration of its extracts did not show any toxicity (Kim et al., 1986). Dried powder of G. lucidum is currently used worldwide as a dietary supplement. The annual sale of products derived from G. lucidum was estimated to be more than 2.5 billion U.S. dollars (Cao et al., 2012; Li et al., 2013a). The genome sequence of G. lucidum has been recently elucidated by next generation sequencing and optical mapping approaches (Chen et al., 2012). The 43.3 Mb G. lucidum genome sequence revealed an array of genes encoding cytochrome P450s (CYPs), transporters and regulatory proteins that cooperate in secondary metabolism. The genome encoded one of the richest sets of wood degradation enzymes among the sequenced basidiomycetes. G. lucidum genome analysis led to the identification of 24 CYP gene clusters. Totally 78 CYP genes were found to be co-expressed with lanosterol synthase and 16 of them showed high similarity with fungal CYPs that specifically catalyze the hydroxylation of testosterone, suggesting their possible roles in triterpenoid biosynthesis (Chen et al., 2012). Recent molecular studies found the commercially cultivated ‘G. lucidum’ (‘Lingzhi’) in East Asia as a different species from the G. lucidum originally described from Europe. Cao et al. proposed a new species Ganoderma lingzhi Sheng H. Wu, Y. Cao & Y. C. Dai for ‘Lingzhi’ which has an East Asia distribution (Cao et al., 2012; Liu et al., 2012a). Medicinal properties of Ganoderma applanatum are antitumor (Boh et al., 2000), aldose reductase inhibition (Lee et al., 2006), inhibition of Epstein–Barr virus activation (Chairul et al., 1994) and antibacterial activities (Smania et al., 1999). Ganoderma australe and Ganoderma capense showed antimicrobial (Smania et al., 2007) and mitogenic (Ngai and Ng, 2004) activities, respectively. Ganoderma colossum was reported to possess anti-HIV-1 protease activity (El Dine et al., 2008a). Ganoderma neo-japonicum showed radical scavenging and antihepatotoxic activities (Lin et al., 1995). Ganoderma pfeifferi possessed antimicrobial (Mothana et al., 2000) and antiviral (Mothana et al., 2003) activities. An Indonesian unidentified Ganoderma species was reported to have antitumor promoting activity (Chairul et al., 1990). Ganoderma tsugae showed cytotoxicity (Gan et al., 1998a; Su et al., 2000), anti-inflammatory (Ko et al., 2008), antitumor (Wang et al., 1993) and antioxidant activities (Mau et al., 2005). Recent reviews on the chemical constituents and biological activities of Ganoderma described the genus as a therapeutic biofactory (Paterson, 2006). This review is a compilation of secondary metabolites isolated from various Ganoderma species. Biological activities of secondary

67

compounds, chemotaxonomical and biosynthetic aspects are also described briefly.

2. Secondary metabolites of Ganoderma G. lucidum, G. applanatum, G. colossum, Ganoderma sinense, Ganoderma cochlear, G. tsugae, Ganoderma amboinense, Ganoderma orbiforme, Ganoderma resinaceum, Ganoderma hainanense, Ganoderma concinna, G. pfeifferi, G. neo-japonicum, Ganoderma tropicum, G. australe, Ganoderma carnosum, Ganoderma fornicatum, Ganoderma lipsiense (synonym G. applanatum), Ganoderma mastoporum, Ganoderma theaecolum, Ganoderma boninense, G. capense and Ganoderma annulare are the Ganoderma species subjected to phytochemical studies so far (Table 1, Fig. 1). Most studies for biologically active molecules in Ganoderma species were carried out on the extracts of their fruiting bodies, spores and cultured mycelia. Triterpenes, steroids and polysaccharides are the major constituents in Ganoderma species (Boh et al., 2007). Proteins, peptides, amino acids, nucleosides, fatty acids, alkaloids and inorganic elements are also biologically significant constituents in Ganoderma (Li et al., 2013b). Secondary metabolites are a diverse group of organic molecules biosynthesized by plants, fungi, bacteria and algae. They are not involved in the normal growth, development and reproduction of an organism, but they contribute to its survival through signaling and defense. Triterpenoids are a major group of secondary metabolites found in terrestrial and marine flora and fauna (Hill and Connolly, 2012, 2013). They are composed of six isoprene units (C30) and they exist as acyclic, mono-, di-, tri-, tetra- or pentacyclic carbon skeletons. Among these pentacyclic triterpenoids are the widely distributed and most studied group (Mahato and Kundu, 1994). Triterpenoids occur in free form or as either their ether, ester, or glycoside derivatives. Many studies established the potential pharmacological effects of triterpenoids (Hill and Connolly, 2012, 2013). Triterpene structures in Ganoderma evolved from the intermediate lanosterol skeleton. Cyclization of squalene-2,3-epoxide leads to a protosterol, which on subsequent backbone rearrangement gives rise to lanosterol. Lanostane skeleton (C30H54) is tetracyclic (Hill and Connolly, 2013). It acts as the intermediate molecule in the biosynthesis of various lanostane type triterpenoids (Ríos et al., 2012). Squalene and lanosterol synthases are the two major enzymes controlling the formation of squalene and lanosterol, respectively (Shi et al., 2010; You et al., 2013). Lanostane type triterpenoids are characteristic of the trans junction of rings A/B, B/C and C/D, b-oriented methyls at C10, C13, a-oriented methyl at C14, b-oriented sidechain at C17 and R configuration for C20. Most lanostanes isolated from Ganoderma species show a high degree of oxidation (Fig. 1). Secondary metabolites isolated from various Ganoderma species belong to the following groups, (a) C30 lanostanes (ganoderic acids) (1–171), (b) C30 lanostanes (aldehydes, alcohols, esters, glycosides, lactones, ketones) (172–284), (c) C27 lanostanes (lucidenic acids) (285–319), (d) C27 lanostanes (alcohols, lactones, esters) (320–343), (e) C24, C25 lanostanes (344–353), (f) C30 pentacyclic triterpenes (354–357), (g) meroterpenoids (358–365), (h) farnesyl hydroquinones (meroterpenoids) (366–370), (i) C15 sesquiterpenoids (371–379), (j) steroids (380–413), (k) alkaloids (414– 420), (l) prenyl hydroquinone (421), (m) benzofurans (422–423), (n) benzopyran-4-one derivatives (424–428) and (o) benzenoid derivatives (429–431). Several compounds were reported from more than one Ganoderma species (Table 1, Fig. 1). Previous studies reported inconsistent numbers of secondary metabolites isolated from Ganoderma (Boh et al., 2007; Kim and Kim, 1999; Paterson, 2006; Ríos et al., 2012; Shiao, 2003). Of the 431 secondary compounds reported from various Ganoderma species (Table 1, Fig. 1), 240 were isolated from

68

S. Baby et al. / Phytochemistry 114 (2015) 66–101

Table 1 Compound names, species (source) and literature listings of secondary metabolites isolated from genus Ganoderma. Compound number

Compound name

(a) C30 lanostanes, ganoderic acids 1 Ganoderic acid A

2

Ganoderic acid B

3

Ganoderic acid C1

4

Ganoderic acid C2

5

Ganoderic acid D1

6

Ganoderic acid E

7

Ganoderic acid F

8

Ganoderic acid G

9

Ganoderic acid H

10

Ganoderic acid I

11 12 13

Ganoderic acid J Ganoderic acid K Ganoderic acid K

14 15 16

Ganoderic acid L Ganoderic acid M Ganoderic acid N

17 18

Ganoderic acid O Ganoderic acid AM1

19 20 21

Ganoderic acid AP Ganoderic acid AP3 Ganoderic acid B8

22

Ganoderic acid C6

23 24 25 26 27 28 29 30 31 32

Ganoderic acid Df Ganoderic acid a 12-Hydroxy ganoderic acid C2 20-Hydroxy ganoderic acid G 20-Hydroxy ganoderic acid AM1 3-O-Acetyl ganoderic acid B 3-O-Acetyl ganoderic acid H 3-O-Acetyl ganoderic acid K 12-Acetoxy ganoderic acid D Ganolucidic acid A

33

Ganolucidic acid B

34 35

Compound B9 12b-Hydroxy-3,7,11,15,23-pentaoxo-5a-lanosta-8-en-26-oic acid

36 37

12,15-Bis(acetyloxy)-3-hydroxy-7,11,23-trioxo-lanost-8-en-26-oic acid Ganoderic acid O

Ganoderma species

References

Ganoderma lucidum, G. lucidum, G. sinense G. lucidum, G. lucidum, G. lucidum, G. lucidum G. lucidum, G. lucidum, G. lucidum, G. lucidum, G. lucidum G. lucidum, G. lucidum G. lucidum, G. lucidum, G. sinense G. lucidum, G. lucidum, G. lucidum, G. sinense G. lucidum, G. lucidum, G. amboinense G. lucidum, G. lucidum, G. lucidum G. lucidum, G. lucidum, G. lucidum, G. lucidum, G. lucidum, G. amboinense G. lucidum, G. lucidum G. lucidum G. lucidum G. lucidum, G. lucidum G. lucidum G. lucidum G. lucidum, G. lipsiense G. lucidum G. amboinense, G. lucidum G. applanatum G. applanatum G. lucidum, G. applanatum, G. lucidum G. lucidum, G. lucidum G. lucidum G. lucidum G. lucidum G. lucidum G. theaecolum G. lucidum G. lucidum G. lucidum G. lucidum G. lucidum, G. lucidum G. lucidum, G. lucidum, G. sinense G. lucidum G. lucidum, G. lucidum G. lucidum G. lucidum

Kubota et al. (1982); El-Mekkawy et al. (1998); Liu et al. (2012b) Kubota et al. (1982); Nishitoba et al. (1985c); Morigiwa et al. (1986); El-Mekkawy et al. (1998) Nishitoba et al. (1984); Nishitoba et al. (1985a); Nishitoba et al. (1985c); El-Mekkawy et al. (1998); Seo et al. (2009) Kikuchi et al. (1986a); Min et al. (2000) Nishitoba et al. (1985a); Nishitoba et al. (1985b); Qiao et al. (2007) Kikuchi et al. (1985a); Komoda et al. (1985); Kikuchi et al. (1986a); Liu et al. (2012b) Kikuchi et al. (1985a); Komoda et al. (1985); Yang et al. (2012) Komoda et al. (1985); Kikuchi et al. (1985b); Kikuchi et al. (1986b) Kikuchi et al. (1985a); Kikuchi et al. (1986b); Morigiwa et al. (1986); Nishitoba et al. (1987c); El-Mekkawy et al. (1998); Yang et al. (2012) Kikuchi et al. (1985b); Kikuchi et al. (1986a) Nishitoba et al. (1985b) Morigiwa et al. (1986) Kikuchi et al. (1986a); Nishitoba et al. (1987c) Nishitoba et al. (1986a) Nishitoba et al. (1987c) Nishitoba et al. (1987c); Rosecke and Konig (2000) Nishitoba et al. (1987c) Lin et al. (1993); Cheng et al. (2010) Nishitoba et al. (1989) Wang and Liu, (2008) Kikuchi et al. (1986a); Nishitoba et al. (1989); Gao et al. (2002) Kikuchi et al. (1986b); Min et al. (2001) Fatmawati et al. (2010) El-Mekkawy et al. (1998) Yang et al. (2007) Ma et al. (2002) Liu et al. (2014b) Li et al. (2009) Yang et al. (2007) Li et al. (2009) Yang et al. (2007) Kikuchi et al. (1985b); Kikuchi et al. (1986c) Kikuchi et al. (1985b); Kikuchi et al. (1986c); Liu et al. (2012b) Kikuchi et al. (1986a) Komoda et al. (1985); Cheng et al. (2010) Yang et al. (2007) Hirotani et al. (1987)

69

S. Baby et al. / Phytochemistry 114 (2015) 66–101 Table 1 (continued) Compound number

Compound name

Ganoderma species

References

38 39

Ganoderic acid U Ganoderic acid V

40

Ganoderic acid W

41 42 43 44 45 46 47 48 49 50 51

Ganoderic Ganoderic Ganoderic Ganoderic Ganoderic Ganoderic Ganoderic Ganoderic Ganoderic Ganoderic Ganoderic

52

7-O-Methyl ganoderic acid O

53 54

7-O-Ethyl ganoderic acid O 7-Oxo-ganoderic acid Z

55 56 57 58 59 60 61 62 63 64 65 66

7-Oxo-ganoderic acid Z2 7-Oxo-ganoderic acid Z3 Ganorbiformin B Ganorbiformin C Ganorbiformin D Ganorbiformin E Ganorbiformin F 3a,22b-Diacetoxy-7a-hydroxyl-5a-lanost-8,24E-dien-26-oic acid 3b,15a-Diacetoxy lanosta-8,24-dien-26-oic acid 11a-Hydroxy-3,7-dioxo-5a-lanosta-8,24(E)-dien-26-oic acid 11b-Hydroxy-3,7-dioxo-5a-lanosta-8,24(E)-dien-26-oic acid Ganoderic acid P

67 68

Ganoderic acid Q Ganoderic acid R

69

Ganoderic acid S

70

Ganoderic acid S

71

Ganoderic acid T

72

Ganoderic acid X

73

Ganoderic acid Y

74 75 76 77

Ganoderic acid Me Ganoderic acid Mf Ganoderic acid TR1 15-Hydroxy ganoderic acid S

78 79 80 81 82 83 84

Ganodermic Ganodermic Ganodermic Ganodermic Ganodermic Ganodermic Ganodermic

85 86 87

Ganorbiformin G Lanosta-7,9(11),24-trien-3a-acetoxy-15a,22b-dihydroxy-26-oic acid Lanosta-7,9(11),24-trien-3b,15a,22b-triacetoxy-26-oic acid

88

3a,15a,22a-Trihydroxylanosta-7,9(11),24-trien-26-oic acid

G. lucidum G. lucidum, G. orbiforme G. lucidum, G. lucidum G. lucidum G. sinense G. sinense G. lucidum G. lucidum G. lucidum G. lucidum G. lucidum G. lucidum G. lucidum G. lucidum, G. sinense G. lucidum, G. orbiforme G. lucidum G. lucidum, G. resinaceum G. resinaceum G. resinaceum G. orbiforme G. orbiforme G. orbiforme G. orbiforme G. orbiforme G. lucidum G. lucidum G. lucidum G. lucidum G. lucidum, G. orbiforme, G. amboinense G. lucidum G. lucidum, G. orbiforme G. lucidum, G. orbiforme G. lucidum, G. lucidum G. lucidum, G. lucidum, G. lucidum, G. lucidum, G. orbiforme G. lucidum, G. lucidum, G. amboinense, G. orbiforme G. lucidum, G. lucidum, G. concinna, G. resinaceum, G. hainanense G. lucidum G. lucidum G. lucidum G. lucidum, G. amboinense G. lucidum G. lucidum G. lucidum G. lucidum G. lucidum G. lucidum G. lucidum, G. hainanense G. orbiforme G. lucidum G. lucidum, G. amboinense G. lucidum

Toth et al. (1983b) Toth et al. (1983b); Isaka et al. (2013) Toth et al. (1983b); Nishitoba et al. (1987a) Toth et al. (1983b) Sato et al. (2009b) Sato et al. (2009b) Nishitoba et al. (1987a) Nishitoba et al. (1987a) Nishitoba et al. (1987a) Nishitoba et al. (1987b) Nishitoba et al. (1987b) Nishitoba et al. (1987b) Nishitoba et al. (1987b) Min et al. (1998); Sato et al. (2009b) Hirotani et al. (1987); Isaka et al. (2013) Wang et al. (2010b) Li et al. (2006); Peng et al. (2013) Peng et al. (2013) Peng et al. (2013) Isaka et al. (2013) Isaka et al. (2013) Isaka et al. (2013) Isaka et al. (2013) Isaka et al. (2013) Li et al. (2013c) Lin et al. (1988a) Cheng et al. (2010) Cheng et al. (2010) Hirotani et al. (1987); Isaka et al. (2013); Yang et al. (2012) Hirotani et al. (1987) Hirotani et al. (1987); Isaka et al. (2013) Hirotani et al. (1987); Isaka et al. (2013) Morigiwa et al. (1986); Adams et al. (2010) Toth et al. (1983b); Hirotani et al. (1987); Nishitoba et al. (1987a); Shiao et al. (1988b); Isaka et al. (2013) Toth et al. (1983b); Shiao et al. (1988a); Li et al. (2005b); Isaka et al. (2013) Toth et al. (1983b); Morigiwa et al. (1986); Gonzalez et al. (2002); Peng et al. (2013); Ma et al. (2013) Nishitoba et al. (1987a) Nishitoba et al. (1987a) Adams et al. (2010) Li et al. (2006); Yang et al. (2012) Shiao et al. (1987) Shiao et al. (1988a) Shiao et al. (1988a) Shiao et al. (1988a) Lin et al. (1988b) Lin et al. (1988b) Lin et al. (1988b); Ma et al. (2013) Isaka et al. (2013) Shiao et al. (1988b) Shiao et al. (1988b); Yang et al. (2012) Lin et al. (1988a)

acid acid acid acid acid acid acid acid acid acid acid

Z GS-1 GS-2 Ma Mc Md Mg Mh Mi Mj b

acid acid acid acid acid acid acid

S Ja Jb P2 T-N T-O T–Q

(continued on next page)

70

S. Baby et al. / Phytochemistry 114 (2015) 66–101

Table 1 (continued) Compound number

Compound name

Ganoderma species

References

89

3b,15a,22b-Trihydroxylanosta-7,9(11),24-trien-26-oic acid

90 91 92 93 94 95 96 97 98

3a,15a-Diacetoxy-22a-hydroxylanosta-7,9(11),24-trien-26-oic acid 3b,15a-Diacetoxy-22a-hydroxylanosta-7,9(11),24-trien-26-oic acid 22b-Acetoxy-3a,15a-dihydroxylanosta-7,9(11),24-trien-26-oic acid 22b-Acetoxy-3b,15a-dihydroxylanosta-7,9(11),24-trien-26-oic acid Ganoderic acid AP2 Ganoderic acid LM2 Ganoderic acid c Ganoderic acid d Ganoderic acid e

99 100 101 102

Ganoderic acid n Ganoderic acid g Ganoderic acid h Ganolucidic acid D

103 104 105 106

Ganolucidic acid E Ganolucidic acid ca Ganolucidate F Ganoderic acid DM

107 108 109 110 111 112 113 114 115

Ganoderic acid GS-3 Ganoderic acid V1 Ganoderic acid XL1 Ganoderic acid XL2 Ganoderic acid Jc Lanosta-7,9(11),24-trien-3a-acetoxy-15a-hydroxy-23-oxo-26-oic acid Lanosta-7,9(11),24-trien-15a-acetoxy-3a-hydroxy-23-oxo-26-oic acid Lanosta-7,9(11),24-trien-3a,l5a-diacetoxy-23-oxo-26-oic acid Ganoderic acid Sz

116

Ganoderic acid TR

117 118 119 120 121

23-Hydroxy ganoderic acid S 8b,9a-Dihydroganoderic acid C 8b,9a-Dihydroganoderic acid J Ganosporeric acid A Ganolucidic acid C

122 123 124 125

Ganorbiformin A 3b,7b,20,23n-Tetrahydroxy-11,15-dioxolanosta-8-en-26-oic acid 7b,20,23n-Trihydroxy-3,11,15-trioxolanosta-8-en-26-oic acid Ganoderenic acid A

126 127 128

Ganoderenic acid B Ganoderenic acid C Ganoderenic acid D

G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G.

lucidum, amboinense lucidum lucidum lucidum lucidum applanatum lucidum lucidum lucidum lucidum, lucidum lucidum lucidum lucidum lucidum, lucidum lucidum sinense sinense lucidum, lucidum, amboinense sinense lucidum theaecolum theaecolum sinense lucidum lucidum lucidum lucidum, hainanense lucidum, lucidum lucidum lucidum lucidum lucidum lucidum, sinense orbiforme applanatum applanatum lucidum, applanatum, lipsiense lucidum lucidum lucidum, lipsiense,

129 130 131 132 133 134 135 136 137 138 139

Ganoderenic acid E Ganoderenic acid F Ganoderenic acid G Ganoderenic acid H Ganoderenic acid I Ganoderenic acid K Elfvingic acid A 12b-Acetoxy-7b-hydroxy-3,11,15,23-tetraoxo-5a-lanosta-8,20-dien-26-oic acid Ganoderenic acid AM1 7b,23n-Dihydroxy-3,11,15-trioxolanosta-8,20E(22)-dien-26-oic acid Applanoxidic acid A

140 141 142

Applanoxidic acid B Applanoxidic acid E Applanoxidic acid F

G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G.

applanatum lucidum applanatum applanatum applanatum applanatum lucidum lucidum lucidum theaecolum applanatum applanatum, annulare, pfeifferi, australe applanatum applanatum applanatum, australe, annulare

Lin et al. (1988a); Yang et al. (2012) Lin et al. (1988a) Lin et al. (1988a) Lin et al. (1988a) Lin et al. (1988a) Wang and Liu, (2008) Luo et al. (2002) Min et al. (2000) Min et al. (2000) Min et al. (2000); Chen et al. (2009a) Min et al. (2000) Min et al. (2000) Min et al. (2000) Nishitoba et al. (1986a); Min et al. (2000) Nishitoba et al. (1988a) Liu et al. (2012b) Liu et al. (2012b) Wang et al. (1997a); Adams et al. (2010); Yang et al. (2012) Sato et al. (2009b) Hirotani et al. (1993) Liu et al. (2014b) Liu et al. (2014b) Liu et al. (2012b) Shiao et al. (1988b) Shiao et al. (1988b) Shiao et al. (1988b) Li et al. (2005a); Ma et al. (2013) Liu et al. (2006); Adams et al. (2010) Adams et al. (2010) Li et al. (2009) Ma et al. (2002) Chen and Yu, (1993) Nishitoba et al. (1985b); Liu et al. (2012b) Isaka et al. (2013) Shim et al. (2004) Shim et al. (2004) Komoda et al. (1985); Ming et al. (2002); Rosecke and Konig (2000) Komoda et al. (1985) Komoda et al. (1985) Komoda et al. (1985); Rosecke and Konig (2000); Ming et al. (2002) Nishitoba et al. (1987c) Nishitoba et al. (1989) Nishitoba et al. (1989) Nishitoba et al. (1989) Nishitoba et al. (1989) Yang et al. (2007) Yang et al. (2007) Cheng et al. (2010) Liu et al. (2014b) Shim et al. (2004) Chairul et al. (1991); Smania et al. (2003); Niedermeyer et al. (2005); León et al. (2003) Chairul et al. (1991) Chairul et al. (1994) Chairul et al. (1994); León et al. (2003); Smania et al. (2003)

71

S. Baby et al. / Phytochemistry 114 (2015) 66–101 Table 1 (continued) Compound number

Compound name

Ganoderma species

References

143

Applanoxidic acid C

144 145

Applanoxidic acid D Applanoxidic acid G

146

Applanoxidic acid H

147 148 149 150 151 152 153 154 155 156

3b,7b-Dihydroxy-11,15,23-trioxo-lanost-8,16-dien-26-oic acid 3b,7b,15b-Trihydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid 12b-Acetoxy-3b,7b-dihydroxy-11,15,23-trioxo-lanost-8,16-dien-26-oic acid Ganoderesin C Ganodermacetal Ganosinensic acid B Colossolactone V Colossolactone VI Furanoganoderic acid 3a-Carboxyacetoxy-24-methyl-23-oxolanost-8-en-26-oic acid (carboxyacetylquercinic acid)

157 158 159 160

3a-Carboxyacetoxy-24-methylene-23-oxolanost-8-en-26-oic acid (carboxyacetylquercinic acid derivative 01) Carboxyacetylquercinic acid derivative 02 8a,9a-Epoxy-3,7,11,15,23-pentaoxo-5a-lanosta-26-oic acid Tsugaric acid A

161 162 163

Tsugaric acid D 3b-Hydroxy-5a-lanosta-8,24-dien-21-oic acid 3-Oxo-5a-lanosta-8,24-dien-21-oic acid

164 165 166 167 168

Tsugaric acid B Tsugaric acid C Tsugaric acid E 3a-Acetoxy-16a-hydroxy-24-methylene-5a-lanost-8-en-21-oic acid (3-epipachymic acid) 3a-(3-Hydroxy-5-methoxy-3-methyl-1,5-dioxopentyloxy)-24-methylene-5a-lanost-8-en-21-oic acid 3a,16a-Dihydroxylanosta-7,9(11),24-trien-21-oic acid 3a,16a,26-Trihydroxylanosta-7,9(11),24-trien-21-oic acid 16a-Hydroxy-3-oxolanosta-7,9(11),24-trien-21-oic acid

G. applanatum, G. australe, G. annulare, G. pfeifferi G. applanatum G. applanatum, G. pfeifferi, G. australe, G. annulare G. applanatum, G. annulare G. lucidum G. tropicum G. lucidum G. theaecolum G. amboinense G. sinense G. colossum G. colossum G. applanatum Ganoderma spp., G. applanatum Ganoderma spp., G. applanatum Ganoderma spp. G. lucidum G. tsugae, G. fornicatum G. tsugae G. tsugae G. tsugae, G. resinaceum G. tsugae G. tsugae G. tsugae G. resinaceum G. resinaceum

Chairul et al. (1991); León et al. (2003); Smania et al. (2003); Niedermeyer et al. (2005) Chairul et al. (1991) Chairul et al. (1994); Mothana et al. (2003); León et al. (2003); Smania et al. (2003) Chairul et al. (1994); Smania et al. (2003) Guan et al. (2007) Hu et al. (2013) Guan et al. (2007) Liu et al. (2014b) Yang et al. (2012) Wang et al. (2010a) El Dine et al. (2008a) El Dine et al. (2008a) Nishitoba et al. (1989) Chairul et al. (1990); de Silva et al. (2006) Chairul et al. (1990); de Silva et al. (2006) Chairul et al. (1990) Joseph et al. (2011a) Lin et al. (1997); Qiao et al. (2006) Lin et al. (2013) Lin et al. (1997) Lin et al. (1997); Niu et al. (2007) Lin et al. (1997) Su et al. (2000) Lin et al. (2013) Niu et al. (2007) Niu et al. (2007)

G. applanatum G. applanatum G. applanatum

de Silva et al. (2006) de Silva et al. (2006) de Silva et al. (2006)

G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G.

Morigiwa et al. (1986); Gan et al. (1998b); Gonzalez et al. (2002); Niedermeyer et al. (2005) Gao et al. (2002); Gonzalez et al. (2002) Adams et al. (2010) Arisawa et al. (1986); Morigiwa et al. (1986); Gao et al. (2002); Gonzalez et al. (2002); Niedermeyer et al. (2005) Morigiwa et al. (1986); Niedermeyer et al. (2005); Peng et al. (2013) Arisawa et al. (1986); Gonzalez et al. (2002); Liu et al. (2012b); Yang et al. (2012) Liu et al. (2012b) Sato et al. (1986); Gonzalez et al. (2002) Nishitoba et al. (1988a); Gonzalez et al. (2002); Sato et al. (2009b); Ma et al. (2013); Yang et al. (2012) Gonzalez et al. (2002); Cheng et al. (2010) Qiao et al. (2006) Ma et al. (2013)

169 170 171

(b) C30 lanostanes (aldehydes, alcohols, esters, glycosides, lactones, ketones) 172 Ganoderal A

173

Lucialdehyde A (5a-Lanosta-7,9(11),24-triene-3b-hydroxy-26-al)

174 175

Ganoderic aldehyde TR Ganoderol A (ganodermenonol)

176

Ganoderol B

177

Ganodermatriol

178 179

Ganodermatetraol Ganoderiol B

180

Ganoderiol F

181

5a-Lanosta-7,9(11),24-triene-15a-26-dihydroxy-3-one

182 183

Polycarpol Agnosterol (lanosta-7,9(11),24-trien-3b-ol)

lucidum, neo-japonicum, concinna, pfeifferi lucidum, concinna lucidum lucidum, lucidum, lucidum, concinna, pfeifferi lucidum, pfeifferi, resinaceum lucidum, concinna, sinense, amboinense sinense lucidum, concinna lucidum, concinna, sinense, hainanense, amboinense concinna, lucidum fornicatum hainanense

(continued on next page)

72

S. Baby et al. / Phytochemistry 114 (2015) 66–101

Table 1 (continued) Compound number

Compound name

Ganoderma species

References

184 185 186

Ganoderal B Lucidal Lucialdehyde B

187

Lucialdehyde D

188 189 190 191 192

Lucialdehyde E Ganoderic aldehyde A Ganoderone A 16a,26-Dihydroxy lanosta-8,24-dien-3-one Ganodermanondiol

193

Lucidumol B

194 195 196

Ganoderitriol M Lucidumol A Ganodermanontriol

197

Ganoderiol A

198 199

Ganoderiol C Ganoderiol D

200 201 202

Ganoderiol G Ganoderiol H Ganoderiol E

203 204 205 206 207 208 209 210 211 212 213

Ganoderiol I Ganoderiol J Ganoderiol A triacetate 26-Nor-11,23-dioxo-5a-lanost-8-en-3b,7b,15a,25-tetrol Lanosta-7,9(11),24-trien-3b,21-diol 3b,22S-Dihydroxylanosta-7,9(11),24-triene 26-Hydroxy-5a-lanosta-7,9(11),24-triene-3,22-dione 26,27-Dihydroxy-5a-lanosta-7,9(11),24-triene-3,22-dione 26,27-Dihydroxylanosta-7,9(11),24-trien-3,16-dione Colossolactone A Lucidadiol

214 215 216 217 218 219 220 221 222 223 224 225

Fornicatin C Epoxyganoderiol A Ganoderone C Epoxyganoderiol B Epoxyganoderiol C Ganodercochlearin A Ganodercochlearin B Ganodercochlearin C Ganosinensin A Ganosinensin B Ganosinensin C Methyl ganoderate A

226

Methyl ganoderate B

227 228 229

Methyl ganoderate C Methyl ganoderate D Methyl ganoderate E

230 231 232 233 234 235 236 237 238 239 240 241

Methyl ganoderate F Methyl ganoderate H Methyl ganoderate J Methyl-O-acetyl ganoderate C 3b,7b-Dihydroxy-12b-acetoxy-11,15,23-trioxo-5a-lanosta-8-en-26-oic acid methyl ester Ethyl ganoderate J Ethyl 3-O-acetyl ganoderate B 12b-Acetoxy-3,7,11,15,23-pentaoxo-5a-lanosta-8-en-26-oic acid ethyl ester Butyl ganoderate A Butyl ganoderate B Butyl ganoderate H 12b-Acetoxy-3b,7b-dihydroxy-11,15,23-trioxolanost-8-en-26-oic acid butyl ester

G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G.

Nishitoba et al. (1988b) González et al. (1999) Gao et al. (2002); Niedermeyer et al. (2005) Niedermeyer et al. (2005); Ma et al. (2012) Ma et al. (2012) Lin et al. (1990) Niedermeyer et al. (2005) Ma et al. (2013) Fujita et al. (1986); Adams et al. (2010); Ma et al. (2013) Min et al. (1998); Liu et al. (2012b) Chen et al. (2009a) Min et al. (1998) Fujita et al. (1986); Gonzalez et al. (2002); Sato et al. (2009b); Yang et al. (2012) Sato et al. (1986); Gonzalez et al. (2002); Sato et al. (2009a) Nishitoba et al. (1988a) Nishitoba et al. (1988a); Sato et al. (2009a) Nishitoba et al. (1988a) Nishitoba et al. (1988a) Nishitoba et al. (1988a); Liu et al. (2012b) Nishitoba et al. (1988b) Liu et al. (2012b) Qiao et al. (2007) Hu et al. (2014) Jain and Gupta (1984) Peng et al. (2014b) Ha et al. (2000) Ha et al. (2000) Keller et al. (1997) Kleinwächter et al. (2001) González et al. (1999); Mothana et al. (2003); Liu et al. (2012b) Qiao et al. (2006) Nishitoba et al. (1988b) Niedermeyer et al. (2005) Nishitoba et al. (1988b) Nishitoba et al. (1988b) Peng et al. (2014b) Peng et al. (2014b) Peng et al. (2014b) Sato et al. (2009a) Sato et al. (2009a) Sato et al. (2009a) Seo et al. (2009); Lee et al. (2011a) Lee et al. (2010b); Yang et al. (2012) Yang et al. (2012) Lee et al. (2010b) Lee et al. (2010b); Yang et al. (2012) Iwatsuki et al. (2003) Lee et al. (2010b) Tung et al. (2013) Li et al. (2009) Cheng et al. (2010) Li et al. (2009) Li et al. (2009) Cheng et al. (2010) Lee et al. (2010b) Lee et al. (2010b) Lee et al. (2011a) Liu et al. (2014a)

lucidum lucidum lucidum, pfeifferi pfeifferi, lucidum lucidum lucidum pfeifferi hainanense lucidum, lucidum, hainanense lucidum, sinense lucidum lucidum lucidum, concinna, sinense, amboinense lucidum, concinna, sinense lucidum lucidum, sinense lucidum lucidum lucidum, sinense lucidum sinense sinense tropicum australe cochlear lucidum lucidum carnosum colossum lucidum, pfeifferi, sinense fornicatum lucidum pfeifferi lucidum lucidum cochlear cochlear cochlear sinense sinense sinense lucidum, lucidum lucidum, amboinense amboinense lucidum lucidum, amboinense lucidum lucidum lucidum lucidum lucidum lucidum lucidum lucidum lucidum lucidum lucidum lucidum

73

S. Baby et al. / Phytochemistry 114 (2015) 66–101 Table 1 (continued) Compound number

Compound name

Ganoderma species

References

242 243 244 245 246 247 248 249 250 251 252

12b-Acetoxy-3,7,11,15,23-pentaoxolanost-8-en-26-oic acid butyl ester Methyl 8b,9a-dihydroganoderate J Ganoderesin B Methyl ganoderate A acetonide Ganoderesin A 3b,7b,15b-Trihydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid methyl ester 3b,15b-Dihydroxy-7,11,23-trioxo-lanost-8,16-dien-26-oic acid methyl ester 3b,7b-Dihydroxy-11,15,23-trioxo-lanost-8,16-dien-26-oic acid methyl ester 7b-Hydroxy-3,11,15,23-tetraoxolanosta-8,20E(22)-dien-26-oic acid methyl ester Ganosinoside A Tsugarioside A (3a-acetoxy-5a-lanosta-8,24-dien-21-oic acid ester b-D-glucoside)

253 254 255

Tsugarioside B Tsugarioside C Ganosporelactone A

256

Ganosporelactone B

257

Colossolactone I

Liu et al. (2014a) Ma et al. (2002) Peng et al. (2013) Lee et al. (2011a) Peng et al. (2013) Hu et al. (2013) Hu et al. (2013) Guan et al. (2007) Shim et al. (2004) Liu et al. (2012b) Gan et al. (1998a); Su et al. (2000); Liu et al. (2012b) Su et al. (2000) Su et al. (2000) Chen and Yu (1991); Jin-Ming (2006) Chen and Yu (1991); Jin-Ming (2006) El Dine et al. (2008b); Lakornwong et al. (2014)

258 259

Colossolactone II Colossolactone B

G. lucidum G. lucidum G. resinaceum G. lucidum G. resinaceum G. tropicum G. tropicum G. lucidum G. applanatum G. sinense G. tsugae, G. tsugae, G. sinense G. tsugae G. tsugae G. lucidum, G. lucidum G. lucidum, G. lucidum G. colossum, Ganoderma sp. KM01 G. colossum G. colossum,

260

Ganoderma lactone E

261 262

Colossolactone III Colossolactone IV

263

Ganoderma lactone C

264 265

Colossolactone VII Colossolactone VIII (23-hydroxycolossolactone E)

266 267

Colossolactone D Colossolactone E

Ganoderma sp. KM01 Ganoderma sp. KM01 G. colossum G. colossum, Ganoderma sp. KM01 Ganoderma sp. KM01 G. colossum G. colossum, G. colossum G. colossum G. colossum,

268 269 270a

Colossolactone F Schisanlactone A Colossolactone G

G. colossum, Ganoderma sp. KM01 G. colossum G. colossum G. colossum,

270b

Colossolactone G (revised structure)

271

Colossolactone C (ganoderma lactone B)

272

Ganoderma lactone A

273

Ganoderma lactone D

274

Ganoderma lactone F

275

Ganoderma lactone G

276 277 278 279 280 281 282 283

Ganoboninketal A Ganoboninketal B Ganoboninketal C Inonotsuoxide B Australic acid Methyl australate Austrolactone Schisanlactone B

284

24n-Methyl-5a-lanosta-25-one

G. colossum Ganoderma sp. KM01 G. colossum, Ganoderma sp. KM01 Ganoderma sp. KM01 Ganoderma sp. KM01 Ganoderma sp. KM01 Ganoderma sp. KM01 G. boninense G. boninense G. boninense G. cochlear G. australe G. australe G. australe Ganoderma sp. KM01 G. applanatum

El Dine et al. (2008b) Kleinwächter et al. (2001); Lakornwong et al. (2014) Lakornwong et al. (2014) El Dine et al. (2008b) El Dine et al. (2008b); Lakornwong et al. (2014) Lakornwong et al. (2014) El Dine et al. (2008a) El Dine et al. (2008a); Ofodile et al. (2012) Kleinwächter et al. (2001) Kleinwächter et al. (2001); El Dine et al. (2008a); Lakornwong et al. (2014) Kleinwächter et al. (2001) El Dine et al. (2008a) Kleinwächter et al. (2001); El Dine et al. (2008a) Lakornwong et al. (2014) Kleinwächter et al. (2001); Lakornwong et al. (2014) Lakornwong et al. (2014) Lakornwong et al. (2014) Lakornwong et al. (2014) Lakornwong et al. (2014) Ma et al. (2014) Ma et al. (2014) Ma et al. (2014) Peng et al. (2014b) León et al. (2003) Smania et al. (2007) León et al. (2003) Lakornwong et al. (2014) Gan et al. (1998b) (continued on next page)

74

S. Baby et al. / Phytochemistry 114 (2015) 66–101

Table 1 (continued) Compound number

Compound name

(c) C27 lanostanes, lucidenic acids 285 Lucidenic acid A (lucidenate A) 286 287 288 289

Lucidenic Lucidenic Lucidenic Lucidenic

acid acid acid acid

B C D1 D2

290 291 292

Lucidenic acid E1 Lucidenic acid E2 Lucidenic acid F

293

Lucidenic acid N

294 295 296 297 298 299

Lucidenic acid P 20-Hydroxy lucidenic 20-Hydroxy lucidenic 20-Hydroxy lucidenic 20-Hydroxy lucidenic 20-Hydroxy lucidenic

300 301 302 303 304 305 306 307 308 309 310

20-Hydroxy lucidenic acid P 3b-Hydroxy-4,4,14-trimethyl-7,11,15-trioxochol-8-en-24-oic acid Lucidenic acid G Lucidenic acid H Lucidenic acid I Lucidenic acid J Lucidenic acid K Lucidenic acid L Lucidenic acid M Lucidenic acid O 20(21)-Dehydrolucidenic acid A

311 312 313 314 315 316

20(21)-Dehydrolucidenic acid N Ganoderic acid Jd 4,4,14a-Trimethyl-5a-chol-7,9(11)-dien-3-oxo-24-oic acid 4,4,14a-Trimethyl-3,7-dioxo-5a-chol-8-en-24-oic acid Fornicatin A Fornicatin B

317 318 319

Fornicatin D Cochlate B Ganosinensic acid A

acid acid acid acid acid

A D2 E2 F N

(d) C27 lanostanes (alcohols, lactones, esters) 320 Lucidenic lactone 321 Lucidenolactone (ganolactone) 322 323 324 325 326

Ganolactone B Fornicatin E Fornicatin F Cochlate A Methyl lucidenate A

327 328

Methyl lucidenate C Methyl lucidenate F

329

Methyl lucidenate N

330 331 332 333 334 335 336 337 338 339 340 341 342 343

Methyl lucidenate P Methyl lucidenate Q Methyl lucidenate D2 Ethyl lucidenate A Butyl lucidenate A Butyl lucidenate N t-Butyl lucidenate B Butyl lucidenate P Butyl lucidenate Q Butyl lucidenate D2 Butyl lucidenate E2 Methyl lucidenate Ha Methyl 20(21)-dehydrolucidenate A Methyl ganosinensate A

Ganoderma species

References

G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G.

lucidum, hainanense lucidum lucidum lucidum lucidum, lucidum, sinense lucidum lucidum lucidum, lucidum lucidum, lucidum, hainanense lucidum sinense lucidum lucidum lucidum lucidum, sinense lucidum lucidum lucidum lucidum lucidum lucidum lucidum lucidum lucidum lucidum lucidum, sinense sinense sinense lucidum lucidum fornicatum fornicatum, cochlear cochlear cochlear sinense

Nishitoba et al. (1985c); Ma et al. (2013) Nishitoba et al. (1985c) Nishitoba et al. (1985c) Nishitoba et al. (1985a) Kikuchi et al. (1985a); Komoda et al. (1985); Sato et al. (2009b) Nishitoba et al. (1985a) Kikuchi et al. (1985a) Kikuchi et al. (1985a); Kikuchi et al. (1986a) Wu et al. (2001); Min et al. (2001); Ma et al. (2013) Iwatsuki et al. (2003) Sato et al. (2009b) Akihisa et al. (2005) Akihisa et al. (2005) Akihisa et al. (2005) Akihisa et al. (2005); Sato et al. (2009b) Akihisa et al. (2005) Yang et al. (2007) Nishitoba et al. (1986a) Nishitoba et al. (1987c) Nishitoba et al. (1987c) Nishitoba et al. (1987c) Nishitoba et al. (1987c) Nishitoba et al. (1987c) Nishitoba et al. (1987c) Mizushina et al. (1999) Akihisa et al. (2005); Sato et al. (2009b) Sato et al. (2009b) Liu et al. (2012b) Zhang et al. (2011b) Cheng et al. (2010) Niu et al. (2004) Niu et al. (2004); Peng et al. (2014b) Peng et al. (2014b) Peng et al. (2014b) Wang et al. (2010a)

G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G. G.

lucidum lucidum, lucidum sinense cochlear cochlear cochlear lucidum, hainanense lucidum lucidum, lucidum lucidum, hainanense lucidum lucidum lucidum lucidum lucidum lucidum lucidum lucidum lucidum lucidum lucidum sinense lucidum sinense

Mizushina et al. (1999) Wang et al. (1997b); Wu et al. (1997) Qiao et al. (2007) Peng et al. (2014b) Peng et al. (2014b) Peng et al. (2014b) Iwatsuki et al. (2003); Ma et al. (2013) Cheng et al. (2010) Wu et al. (2001); Zhang et al. (2011a) Lee et al. (2010a); Ma et al. (2013) Iwatsuki et al. (2003) Iwatsuki et al. (2003) Iwatsuki et al. (2003) Li et al. (2013b) Lee et al. (2010b) Lee et al. (2010b) Lee et al. (2010a) Tung et al. (2013) Tung et al. (2013) Tung et al. (2013) Tung et al. (2013) Liu et al. (2012b) Akihisa et al. (2005) Wang et al. (2010a)

75

S. Baby et al. / Phytochemistry 114 (2015) 66–101 Table 1 (continued) Compound number

Compound name

(e) C24, C25 lanostanes 344 Lucidone A

345 346 347

Lucidone B Lucidone C Lucidone D

348 349 350 351 352 353

Lucidone E Lucidone F Lucidone G Lucidone H 8a,9a-Epoxy-4,4,14a-trimethyl-3,7,11,15,20-pentaoxo-5a-pregnane Ganosineniol A

(f) C30 pentacyclic triterpenes 354 Friedelin 355 356 357

Alnusenone b-Amyrenone b-Amyrin acetate

(g) Meroterpenoids 358 Fornicin A 359 Fornicin B 360 Fornicin C 361 Ganocin A 362 Ganocin B 363 Ganocin C 364 Ganocin D 365 Lingzhiol (h) Farnesyl hydroquinones (meroterpenoids) 366 Farnesyl hydroquinone 367 Ganomycin A 368 Ganomycin B 369 370

Ganomycin I Ganomycin K

(i) C15 sesquiterpenoids 371 Ganosinensine 372 Ganomastenol A 373 Ganomastenol B 374 Ganomastenol C 375 Ganomastenol D 376 Echinolactone D 377 Ganodermycin 378 Cryptoporic acid H 379 Cryptoporic acid I (j) Steroids 380

Ergosterol

381

Ergosta-7,22-dien-3b-ol (stellasterol; 5,6-dihydroergosterol)

382 383

22,23-Dihydroergosterol Ergosterol peroxide (5,8-epidioxy-5a-8a-ergosta-6,22E-dien-3-bol)

Ganoderma species

References

G. G. G. G. G. G. G. G. G. G. G. G. G. G.

lucidum, amboinense, applanatum, resinaceum lucidum lucidum resinaceum, tropicum resinaceum resinaceum resinaceum resinaceum concinna sinense

Nishitoba et al. (1985a); Lin et al. (1993); Gan et al. (1998b); Peng et al. (2013) Nishitoba et al. (1985a) Nishitoba et al. (1986a) Peng et al. (2013); Hu et al. (2014) Peng et al. (2013) Peng et al. (2013) Peng et al. (2013) Peng et al. (2013) Gonzalez et al. (2002) Liu et al. (2012b)

G. G. G. G. G.

applanatum, cochlear applanatum applanatum applanatum

Nishitoba et al. (1989); Peng et al. (2014b) Nishitoba et al. (1989) Ming et al. (2002) Ming et al. (2002)

G. G. G. G. G. G. G. G.

fornicatum fornicatum fornicatum cochlear cochlear cochlear cochlear lucidum

Niu et al. (2006) Niu et al. (2006) Niu et al. (2006) Peng et al. (2014a) Peng et al. (2014a) Peng et al. (2014a) Peng et al. (2014a) Yan et al. (2013)

G. G. G. G. G. G.

pfeifferi pfeifferi pfeifferi, colossum colossum pfeifferi

Niedermeyer et al. (2013) Mothana et al. (2000) Mothana et al. (2000); El Dine et al. (2009) El Dine et al. (2009) Niedermeyer et al. (2013)

G. G. G. G. G. G. G. G. G.

sinense mastoporum mastoporum mastoporum mastoporum applanatum applanatum neo-japonicum neo-japonicum

Liu et al. (2012b) Hirotani et al. (1995) Hirotani et al. (1995) Hirotani et al. (1995) Hirotani et al. (1995) Fushimi et al. (2010) Jung et al. (2011) Hirotani et al. (1991) Hirotani et al. (1991)

G. lipsiense, G. applanatum, G. australe, G. fornicatum, G. colossum, G. lucidum, Ganoderma sp. KM01 G. lucidum, G. amboinense, G. carnosum, G. tsugae, G. applanatum, G. neo-japonicum, G. lipsiense, G. australe, G. annulare, G. pfeifferi, G. lucidum, G. sinense G. lucidum G. amboinense, G. carnosum, G. lucidum, G. concinna,

Rosecke and Konig (2000); Ming et al. (2002); León et al. (2003); Qiao et al. (2006); El Dine et al. (2008b); Seo et al. (2009); Lakornwong et al. (2014) Lin et al. (1990); Lin et al. (1993); Keller et al. (1997); Lin et al. (1997); Gan et al. (1998b); Gan et al. (1998b); Rosecke and Konig (2000); León et al. (2003); Smania et al. (2003); Niedermeyer et al. (2005); Seo et al. (2009); Sato et al. (2009b) González et al. (1999) Lin et al. (1993); Keller et al. (1997); Mizushina et al. (1998b); Gonzalez et al. (2002); (continued on next page)

76

S. Baby et al. / Phytochemistry 114 (2015) 66–101

Table 1 (continued) Compound number

Compound name

Ganoderma species

References

G. australe, G. annulare, G. pfeifferi, G. applanatum, G. fornicatum, G. sinense, G. lucidum, G. tsugae G. amboinense, G. applanatum, G. lucidum, G. tsugae G. lucidum G. lucidum, G. applanatum G. lucidum, G. applanatum G. lucidum, G. tsugae, G. neo-japonicum G. applanatum G. lucidum, G. applanatum, G. sinense G. lucidum G. lucidum G. amboinense G. lucidum G. lucidum G. lucidum G. lucidum G. lucidum G. lucidum G. lucidum G. applanatum, G. neo-japonicum, G. lucidum, G. pfeifferi G. australe, G. lucidum, G. applanatum, G. neo-japonicum, G. lipsiense, G. concinna G. lucidum G. lucidum, G. applanatum, G. neo-japonicum G. lucidum, G. amboinense, G. lipsiense G. lipsiense G. lucidum G. lipsiense,

(24S)-24-Methyl-5a-cholest-7-ene-3b-ol (24S)-24-Methyl-5a-cholest-7,l6-diene-3b-ol b-Sitosterol Daucosterol

G. G. G. G. G. G. G. G. G.

lucidum lucidum, concinna, annulare, australe applanatum applanatum lucidum applanatum

León et al. (2003); Smania et al. (2003); Niedermeyer et al. (2005); Lee et al. (2006); Qiao et al. (2006); Sato et al. (2009b); Wu et al. (2012); Lin et al. (2013) Lin et al. (1993); Gan et al. (1998b); Chen et al. (2009b); Lin et al. (2013) El-Mekkawy et al. (1998) Zhang et al. (2008); Lee et al. (2011b) Zhang et al. (2008); Lee et al. (2011b) Lin et al. (1991); Gan et al. (1998a); Gan et al. (1998b) Lee et al. (2011b) El-Mekkawy et al. (1998); Lee et al. (2006); Sato et al. (2009b) Zhang et al. (2008) Zhang et al. (2008) Lin et al. (1993) Nishitoba et al. (1988b) Nishitoba et al. (1988b) Hirotani et al. (1987) Weng et al. (2010) Weng et al. (2010) Weng et al. (2011) Weng et al. (2011) Gan et al. (1998b); Gan et al. (1998b); González et al. (1999); Niedermeyer et al. (2005) Jain and Gupta (1984); Lin et al. (1990); Gan et al. (1998b); Gan et al. (1998b); Rosecke and Konig (2000); Gonzalez et al. (2002) Ziegenbein et al. (2006) Lin et al. (1990); Gan et al. (1998b); Gan et al. (1998b) Lin et al. (1991); Lin et al. (1993); Rosecke and Konig (2000) Rosecke and Konig (2000) Lin et al. (1991) Rosecke and Konig (2000); Ziegenbein et al. (2006) González et al. (1999); Gonzalez et al. (2002); Smania et al. (2003); Smania et al. (2007) Strigina et al. (1971) Strigina et al. (1971) Joseph et al. (2011a) Lee et al. (2005)

Ganoderma alkaloid A Ganoderma alkaloid B Sinensine Sinensine B Sinensine C Sinensine D Sinensine E

G. G. G. G. G. G. G.

capense capense sinense sinense sinense sinense sinense

Yang and Yu (1990) Yang and Yu (1990) Liu et al. (2010) Liu et al. (2011) Liu et al. (2011) Liu et al. (2011) Liu et al. (2011)

384

5a,8a-Epidioxyergosta-6,9(11),22-trien-3b-ol (9,11-Dehydroergosterol peroxide)

385 386

3b,5a-Dihydroxy-6b-methoxy ergosta-7,22-diene 3b,5a-Dihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (6-dehydrocerevisterol)

387

3b,5a,9a-Trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one

388

Ergosta-7,22-diene-2b,3a,9a-triol

389 390

3b,5a,6b,8b,14a-Pentahydroxy-(22E,24R)-ergost-22-en-7-one 22E,24R-Ergosta-7,22-diene-3b,5a,6b-triol (cerevisterol)

391 392 393 394 395 396 397 398 399 400 401

22E,24R-Ergosta-7,22-diene-3b,5a,6b,9a-tetraol 22E,24R-Ergosta-7,22-diene-3b,5a,6b,9a,14a-pentol 2b-Methoxyl-3a,9a-dihydroxyergosta-7,22-diene 6a-Hydroxy-ergosta-4,7,22-trien-3-one 6b-Hydroxy-ergosta-4,7,22-trien-3-one Ergosta-4,7,22-triene-3,6-dione Ganodermaside A Ganodermaside B Ganodermaside C Ganodermaside D Ergosta-4,6,8(14),22-tetraen-3-one

402

Ergosta-7,22-dien-3-one

403 404

Ergosta-7,22-diene-3b-yl pentadecanoate Ergosta-7,22-dien-3b-yl palmitate

405

Ergosta-7,22-dien-3b-yl linoleate

406 407 408

3b-Linoleyloxyergosta-7,24(28)-diene 5a,8a-Epidioxy ergosta-6,22-dien-3b-yl linoleate Ergosta-7-ene-3b-yl linoleate

409

Fungisterol (5a-ergost-7-en-3b-ol)

410 411 412 413 (k) Alkaloids 414 415 416 417 418 419 420

77

S. Baby et al. / Phytochemistry 114 (2015) 66–101 Table 1 (continued) Compound number

Compound name

Ganoderma species

References

(l) Prenyl hydroquinone 421 Ganoderma aldehyde

G. applanatum

Ming et al. (2002)

(m) Benzofurans 422 423

G. tsugae G. lucidum

La Clair et al. (2011) Adams et al. (2010)

(n) Benzopyran-4-one derivatives 424 Applanatine A 425 Applanatine B 426 Applanatine C 427 Applanatine D 428 Applanatine E

G. G. G. G. G.

Fushimi Fushimi Fushimi Fushimi Fushimi

(o) Benzenoid derivatives 429 2,5-Dihydroxy benzoic acid 430 2,5-Dihydroxyacetophenone 431 Protocatechualdehyde

G. applanatum G. applanatum G. applanatum

Ganodone Ganofuran B

applanatum applanatum applanatum applanatum applanatum

et et et et et

al. al. al. al. al.

(2010) (2010) (2010) (2010) (2010)

Ming et al. (2002) Lee et al. (2005) Lee et al. (2005)

Naming issues and other related facts on secondary metabolites from Ganoderma are listed in Table S1. In Table S1, compounds are listed in the order of their trivial names, keeping the compound numbers same as in this Table. Author citations in bold indicate references with NMR data, and the citations which are not in bold indicate repeated reports of compounds, and they do not list NMR data. G. applanatum and G. lipsiense are synonyms.

G. lucidum (C30 ganoderic acids 112, other C30 lanostanes 55, C27 lucidenic acids 27, other C27 lanostanes 18, C24 lanostanes 3, meroterpenoid 1, steroids 23, benzofuran 1). Only 63, 49, 22, 19, 18, 16, 16, 15, 14, 13, 10 and 2 secondary metabolites were reported from G. applanatum/G. lipsiense (C30 ganoderic acids 28, other C30 lanostanes 2, C24 lanostane 1, C30 pentacyclic triterpenes 4, C15 sesquiterpenoids 2, steroids 17, prenyl hydroquinone 1, benzopyran-4-one derivatives 5, benzenoid derivatives 3), G. sinense, G. amboinense, G. colossum, G. pfeifferi, G. resinaceum, G. cochlear, G. concinna, G. australe, G. orbiforme, G. fornicatum and G. capense, respectively (Table 1, Fig. 1). C30 lanostanes, ganoderic acid A (1) and B (2) were first isolated by Kubota and co-workers from G. lucidum fruiting bodies in 1982 (Kubota et al., 1982). The second major group of triterpenoid constituents isolated from Ganoderma was lucidenic acids with the C27 skeleton. Nishitoba and co-workers isolated bitter C27 lucidenic acids for the first time from the mycelial part of G. lucidum in 1984 (Nishitoba et al., 1984). Their structures were elucidated as lucidenic acid A (285), B (286) and C (287) (Nishitoba et al., 1985a,c). Further, highly oxygenated lanostane type triterpenoids ganoderic acids C1 (3) to O (17), O (37), P (66) to T (71), U (38) to W (40), X (72), Y (73), Z (41) and lucidenic acids D1 (288), D2 (289), E1 (290), E2 (291), F (292), G (302) to M (308), N (293), O (309), P (294) were isolated from the fruiting bodies and cultured mycelia of various Ganoderma species (Table 1, Fig. 1). Another group of structurally very similar ganoderenic acids A (125), B (126), C (127) and D (128) were isolated from the dried fruiting bodies of G. lucidum by Komoda and co-workers in 1985 along with ganoderic acid E (6), F (7), G (8) and lucidenic acid D (lucidenic acid D2, 289) (Table 1, Fig. 1) (Komoda et al., 1985). Several other lanostane type terpenoids were also isolated from various Ganoderma species (Table 1, references therein). Ganoderic alcohols named ganoderiol A (197), B (179), C (198), D (199), E (202), F (180), G (200), H (201), I (203), J (204) were isolated from G. lucidum, G. concinna, G. sinense, G. hainanense and G. amboinense (Table 1, Fig. 1). Epoxyganoderiol A (215), B (217), C (218) having epoxy functionalities at the side-chain of ganoderiols were reported by Nishitoba et al. (1988b). C30 lanostanes with aldehydic functionality at the side-chain, ganoderal A (172), B (184), ganoderic aldehyde A (189) and TR (174), were also reported (Adams et al., 2010; Lin et al., 1990; Morigiwa et al., 1986; Nishitoba et al., 1988b). Similarly, lucidal (185) and lucialdehydes A (173), B (186), C (lucidal, 185), D (187), E (188) with an aldehydic group in the side-chain were reported from G. lucidum, G. pfeifferi and

G. concinna (Gao et al., 2002; González et al., 1999; Ma et al., 2012; Niedermeyer et al., 2005). So far, 284 C30 lanostane compounds (1–284) were identified from genus Ganoderma (Table 1, Fig. 1). Most C30 lanostanes (1–284) have a C8–C9 double bond, and a second group has two double bonds at C7–C8 and C9–C11 in their tetracyclic skeleton (Table 1, Fig. 1). 8b,9a-Dihydroganoderic acid C (118), 8b,9a-dihydroganoderic acid J (119), ganosporeric acid A (120), methyl 8b,9a-dihydroganoderate J (243), ganoderesin B (244) and 24n-methyl-5a-lanosta-25-one (284) have no double bonds in their four skeletal rings (Fig. 1). 8a,9a-Epoxy3,7,11,15,23-pentaoxo-5a-lanosta-26-oic acid (159), instead of a double bond, has an epoxy group between C8 and C9. Ganorbiformin A (122), tsugaric acid E (166), fornicatin C (214) and ganoderesin A (246) have unusual double bonds at C8–C14, C6–C7, C13–C17 and C16–C17, respectively. Applanoxidic acid A (139), B (140), C (143), D (144), E (141), F (142), G (145), H (146), australic acid (280) and methyl australate (281) have epoxy groups between C7 and C8 along with C9–C11 double bonds (Table 1, Fig. 1). In most cases, the acid groups in ganoderic acids are found at the end of the side-chain (C26). In some cases, however, acid groups are found at C21 (tsugaric acid A (160), B (164), C (165), D (161), E (166), 3b-hydroxy-5a-lanosta-8,24-dien-21oic acid (162), 3-oxo-5a-lanosta-8,24-dien-21-oic acid (163), 3aacetoxy-16a-hydroxy-24-methylene-5a-lanost-8-en-21-oic acid or 3-epipachymic acid (167), 3a-(3-hydroxy-5-methoxy-3methyl-1,5-dioxopentyloxy)-24-methylene-5a-lanost-8-en-21-oic acid (168), 3a,16a-dihydroxylanosta-7,9(11),24-trien-21-oic acid (169), 3a,16a,26-trihydroxylanosta-7,9(11),24-trien-21-oic acid (170), 16a-hydroxy-3-oxolanosta-7,9(11),24-trien-21-oic acid (171)). Double bonds in ganoderic acid side-chains are found at C24–C25, and at C20–C22 in relatively few cases. Ganoderic acid I (10), L (14), N (16), O (17), AP (19), AP3 (20), V1 (108), XL1 (109), XL2 (110), 20-hydroxy ganoderic acid G (26), 20-hydroxy ganoderic acid AM1 (27), 3b,7b,20,23n-tetrahydroxy11,15-dioxolanosta-8-en-26-oic acid (123), 7b,20,23n-trihydroxy3,11,15-trioxolanosta-8-en-26-oic acid (124), applanoxidic acid C (143), D (144), G (145) and H (146) have hydroxyl substitutions at C20 along with carboxyl groups in their side-chains. Similarly, ganoderic acid LM2 (95), c (96), d (97), e (98), n (99), g (100), h (101), Jc (111), ganolucidic acid D (102), ca (104), ganolucidate F (105), 23-hydroxy ganoderic acid S (117), 3b,7b,20,23n-tetrahydroxy-11,15-dioxolanosta-8-en-26-oic acid (123), 7b,20,23n-trihydroxy-3,11,15-trioxolanosta-8-en-26-oic acid (124) and 7b, 23n-dihydroxy-3,11,15-trioxolanosta-8,20E(22)-dien-26-oic acid (138)

78

S. Baby et al. / Phytochemistry 114 (2015) 66–101

(a) C30 lanostanes, ganoderic acids R4 R3

12

19

1

R1

9

3

5

29

28

21 18

R6 20

23 25

O

17

COOH

27 8

30

R2

R5

32

R1 = O, R2 = H, R3 = O, R4 = H, R5 = α-OH, R6 = H

33

R1 = β-OH, R2 = H, R3 = O, R4 = H, R5 = α-OH, R6 = H

34

R1 = β-OH, R2 = α-OH, R3 = O, R4 = H, R5 = α-OH, R6 = H

35

R1 = O, R2 = O, R3 = O, R4 = β-OH, R5 = O, R6 = H

36

R1 = OH, R2 = O, R3 = O, R4 = OAc, R5 = OAc, R6 = H R5

1

R1 = O, R2 = β-OH, R3 = O, R4 = H, R5 = α-OH, R6 = H

2

R1 = β-OH, R2 = β-OH, R3 = O, R4 = H, R5 = O, R6 = H

3

R1 = O, R2 = β-OH, R3 = O, R4 = H, R5 = O, R6 = H

COOH

R3

R1

R2

R4

4

R1 = β-OH, R2 = β-OH, R3 = O, R4 = H, R5 = α-OH, R6 = H

5

R1 = O, R2 = β-OH, R3 = O, R4 = β-OH, R5 = O, R6 = H

37

R1 = α-OAc, R2 = α-OH, R3 = H, R4 = α-OAc, R5 = β-OAc

6

R1 = O, R2 = O, R3 = O, R4 = H, R5 = O, R6 = H

38

R1 = α-OH, R2 = α-OH, R3 = H, R4 = H, R5 = H

7

R1 = O, R2 = O, R3 = O, R4 = β-OAc, R5 = O, R6 = H

39

R1 = O, R2 = α-OH, R3 = H, R4 = α-OAc, R5 = H

8

R1 = β-OH, R2 = β-OH, R3 = O, R4 = β-OH, R5 = O, R6 = H

40

R1 = α-OAc, R2 = α-OH, R3 = H, R4 = α-OAc, R5 = H

9

R1 = β-OH, R2 = O, R3 = O, R4 = β-OAc, R5 = O, R6 = H

41

R1 = β-OH, R2 = H, R3 = H, R4 = H, R5 = H

10

R1 = β-OH, R2 = β-OH, R3 = O, R4 = H,R5 = O, R6 = ξ-OH

42

R1 = O, R2 = β-OH, R3 = O, R4 = O, R5 = H

11

R1 = O, R2 = O, R3 = O, R4 = H, R5 = α-OH, R6 = H

43

R1 = O, R2 = β-OH, R3 = O, R4 =α-OH, R5 = H

12

R1 = β-OH, R2 = β-OH, R3 = O, R4 = β-OAc,R5 = O, R6 = H

44

R1 = α-OAc, R2 = α-OAc, R3 = H, R4 = α-OH, R5 = H

13

R1 = β-OH, R2 = O, R3 = O, R4 = H, R5 = α-OH, R6 = H

45

R1 = α-OAc, R2 = α-OAc, R3 = H, R4 = α-OH, R5 = ξ-OAc

14

R1 = β-OH, R2 = β-OH, R3 = O, R4 = H,R5 = α-OH, R6 = ξ-OH

46

R1 = α-OAc, R2 = α- OMe, R3 = H, R4 = H, R5 = ξ-OAc

15

R1 = O, R2 = β-OH, R3 = O, R4 = α-OH, R5 = O, R6 = H

47

R1 = α-OAc, R2 = α- OMe, R3 = H, R4 = α-OH, R5 = ξ-OAc

16

R1 = O, R2 = β-OH, R3 = O, R4 = H, R5 = O, R6 = ξ-OH

48

R1 = α-OAc, R2 = α-OH, R3 = H, R4 = α-OH, R5 = ξ-OAc

17

R1 = O, R2 = O, R3 = O, R4 = H, R5 = O, R6 = ξ-OH

49

R1 = α-OAc, R2 = α-OMe, R3 = H, R4 = α-OH, R5 = H

18

R1 = β-OH, R2 = O, R3 = O, R4 = H, R5 = O, R6 = H

50

R1 = α-OH, R2 = α-OMe, R3 = H, R4 = H, R5 = ξ-OAc

19

R1 = O, R2 = O, R3 = O, R4 = β-OH, R5 = α-OH, R6 = ξ-OH

51

R1 = β-OH, R2 = β-OH, R3 = O, R4 = O, R5 = H

20

R1 = O, R2 = O, R3 = O, R4 =H, R5 = α-OH, R6 = ξ-OH

52

R1 = α-OAc, R2 = α-OMe, R3 = H, R4 = α-OAc, R5 = β-OAc

21

R1 = O, R2 = α-OH, R3 = O, R4 = H, R5 = α-OH, R6 = H

53

R1 = α-OAc, R2 = α-OEt, R3 = H, R4 = α-OAc, R5 = ξ-OAc

22

R1 = β-OH, R2 = O, R3 = O, R4 = β-OH, R5 = O, R6 = H

54

R1 = β-OH, R2 = O, R3 = H, R4 = H, R5 = H

23

R1 = O, R2 = β-OH, R3 = β-OH, R4 = H, R5 = O, R6 = H

55

R1 = β-OH, R2 = O, R3 = O, R4 = H, R5 = H

24

R1 = β-OH, R2 = O, R3 = O, R4 = β-OAc, R5 = β-OH, R6 = H

56

R1 = β-OH, R2 = O, R3 = H, R4 = α-OH, R5 = H

25

R1 = β-OH, R2 = β-OH, R3 = O, R4 = OH, R5 = α-OH, R6 = H

57

R1 = β-OAc, R2 = O, R3 = H, R4 = H, R5 = β-OAc

26

R1 = β-OH, R2 = β-OH, R3 = O, R4 = β-OH, R5 = O, R6 = OH

58

R1 = β-OH, R2 = O, R3 = H, R4 = H, R5 = β-OAc

27

R1 = β-OH, R2 = O, R3 = O, R4 = H, R5 = O, R6 = ξ-OH

59

R1 = O, R2 = α-OH, R3 = H, R4 = α-OAc, R5 = β-OAc

28

R1 = β-OAc, R2 = β-OH, R3 = O, R4 = H, R5 = O, R6 = H

60

R1 = O, R2 = α-OH, R3 = H, R4 = H, R5 = β-OAc

29

R1 = β-OAc, R2 = O, R3 = O, R4 = β-OAc, R5 = O, R6 = H

61

R1 = O, R2 = α-OMe, R3 = H, R4 = H, R5 = β-OAc

30

R1 = β-OAc, R2 = O, R3 = O, R4 = H, R5 = α-OH, R6 = H

62

R1 = α-OAc, R2 = α-OH, R3 = H, R4 = H, R5 = β-OAc

31

R1 = O, R2 = β-OH, R3 = O, R4 = OAc, R5 = O, R6 = H

63

R1 = β-OAc, R2 = H, R3 = H, R4 = α-OAc, R5 = H

Fig. 1. Secondary metabolites isolated from various Ganoderma species.

79

S. Baby et al. / Phytochemistry 114 (2015) 66–101

64

R1 = O, R2 = O, R3 = α-OH, R4 = H, R5 = H

65

R1 = O, R2 = O, R3 = β-OH, R4 = H, R5 = H

R1 = β-OH, R2 = α-OH, R3 = β-OAc

93

R3 COOH

O

R3

R5

COOH R2

R1

R1

R2

R4

94

R1 = β-OH, R2 = H, R3 = β-OAc, R4 = α-OAc, R5 = H

95

R1 = O, R2 = β-OH, R3 = H, R4 = O, R5 = OH

66

R1 = α-OH, R2 = α-OAc, R3 = β-OAc

96

R1 = O, R2 = β-OH, R3 = H, R4 = α-OH, R 5 = β-OH

67

R1 = α-OAc, R2 = α-OH, R3 = β-OAc

97

R1 = O, R2 = α-OH, R3 = H, R4 = α-OH, R 5 = β-OH

68

R1 = α-OAc, R2 = H, R3 = β-OAc

98

R1 = β-OH, R2 = β-OH, R3 = H, R4 = O, R 5 = β-OH

69

R1 = α-OH, R2 = H, R3 = β-OAc

99

R1 = β-OH, R2 = O, R3 = H, R4 = O, R 5 = β-OH

70

R1 = O, R2 = H, R3 = H

100

R1 = β-OH, R2 = β-OH, R3 = β-OH, R4 = O, R 5 = β-OH

71

R1 = α-OAc, R2 = α-OAc, R3 = β-OAc

101

R1 = β-OH, R2 = O, R3 = β-OH, R4 = O, R5 = β-OH

72

R1 = α-OH, R2 = α-OAc, R3 = H

102

R1 = O, R2 = H, R3 = H, R4 = α-OH, R 5 = β-OH

73

R1 = β-OH, R2 = H, R3 = H

103

R1 = O, R2 = H, R3 = H, R4 = α-OH, R 5 = H

74

R1 = α-OAc, R2 = α-OAc, R3 = H

104

R1 = β-OH, R2 = β-OH, R3 = H, R4 = α-OH, R 5 = OH

75

R1 = α-OAc, R2 = α-OH, R3 = H

105

R1 = β-OH, R2 = H, R3 = H, R4 = α-OH, R5 = OH

76

R1 = O, R 2 = β-OH, R3 = H

77

R1 = O, R 2 = α-OH, R3 = H

78

R1 = β-OAc, R2 = α-OAc, R3 = H

79

R1 = α-OH, R2 = α-OH, R3 = H

80

R1 = β-OH, R2 = α-OH, R3 = H

81

R1 = β-OH, R2 = α-OAc, R3 = β-OAc

82

R1 = β-OH, R2 = α-OAc, R3 = H

83

R1 = β-OAc, R2 = α-OH, R3 = H

84

R1 = O, R2 = α-OAc, R3 = H

85

R1 = O, R2 = H, R3 = β-OAc

86

R1 = α-OAc, R2 = α-OH, R3 = β-OH

87

R1 = β-OAc, R2 = α-OAc, R3 = β-OAc

88

R1 = α-OH, R2 = α-OH, R3 = α-OH

89

R1 = β-OH, R2 = α-OH, R3 = β-OH

90

R1 = α-OAc, R2 = α-OAc, R3 = α-OH

91

R1 = β-OAc, R2 = α-OAc, R3 = α-OH

R1

92

R1 = α-OH, R2 = α-OH, R3 = β-OAc

111

COOH

O

O

106

R4

R2

COOH

O

HO

R1

R3

107

R1 = β-OH, R2 = β-OAc, R3 = O, R4 = H

108

R1 = O, R2 = H, R3 = O, R4 = OH

109

R1 = β-OH, R2 = H, R3 = α-OH, R4 = OH

110

R1 = α-OH, R2 = H, R3 = α-OH, R4 = OH

COOH R3 R2

R1 = O, R2 = OH, R3 = OH

Fig. 1 (continued)

have hydroxyl group substitutions at C23 along with carboxyl groups in their side-chains. Lanosta-7,9(11),24-trien-3a-acetoxy15a,22b-dihydroxy-26-oic acid (86), 3a,15a,22a-trihydroxylanosta-7,9(11),24-trien-26-oic acid (88), 3b,15a,22b-trihydrox

ylanosta-7,9(11),24-trien-26-oic acid (89), 3a,15a-diacetoxy22a-hydroxylanosta-7,9(11),24-trien-26-oic acid (90), 3b,15a-diacetoxy-22a-hydroxylanosta-7,9(11),24-trien-26-oic acid (91), 3b,22S-dihydroxylanosta-7,9(11),24-triene (208), colossolactone

80

S. Baby et al. / Phytochemistry 114 (2015) 66–101

124

R=O

R1 = α-OAc, R2 = OH, R3 = O

112

R3 O

113

R1 = α-OH, R2 = OAc, R3 = O

114

R1 = α-OAc, R2 = OAc, R3 = O R2

R1

R3

115

R1 = O, R2 = H, R3 =H

116

R1 = O, R2 = α-OH, R3 =H

117

R1 = OH, R2 = H, R3 =OH R1 O H H

O

COOH

O

O

R2

118

R1 = H, R2 = O

119

R1 = H, R2 = α-OH

120

R1 = O, R2 = O

R4

125

R1 = O, R2 = β-OH, R3 = H, R4 = α-OH

126

R1 = β-OH, R2 = β-OH, R3 = H, R4 = O

127

R1 = β-OH, R2 = β-OH, R3 = H, R4 = α-OH

128

R1 = O, R2 = β-OH, R3 = H, R4 = O

129

R1 = O, R2 = β-OH, R3 = β-OH, R4 = O

130

R1 = O, R2 = O, R3 = H, R4 = O

131

R1 = O, R2 = O, R3 = H, R4 = α-OH

132

R1 = β-OH, R2 = O, R3 = H, R4 = O

133

R1 = β-OH, R2 = O, R3 = H, R4 = α-OH

134

R1 = β-OH, R2 = β-OH, R3 = β-OAc, R4 = O

135

R1 = O, R2 = O, R3 = α-OH, R4 = β-OH

136

R1 = O, R2 = β-OH, R3 = β-OAc, R4 = O

COOH

R2

R1

O O

COOH

O

HO

O

O

COOH

O

137

OH

HO

COOH

O

O

OH

COOH HO

121

O

COOH

138

HO

O

OH O

OH

O

OAc

OH

O O

122

R1

COOH

R2

OH COOH

O OH

R

123

OH

O

139

R1 = O, R2 = α-OH

140

R1 = β-OH, R2 = O

141

R1 = O,R2 = β-OH

R = β-OH Fig. 1 (continued)

A (212) and ganodercochlearin C (221) have hydroxyls at C22 and tsugaric acid C (165), ganodermanondiol (192), ganoderitriol M (194), ganodermanontriol (196), ganoderiol A (197), C (198), D (199), G (200), H (201), lucidumol A (195), B (193) and ganoderesin

B (244) have hydroxyls at C24. Ganoderic acid (C30 lanostane) side-chains also have keto, acetyl, furano (furanoganoderic acid (155)) and ethylenic (3a-carboxyacetoxy-24-methylene-23oxolanost-8-en-26-oic acid (157)) substitutions along with

81

S. Baby et al. / Phytochemistry 114 (2015) 66–101

142

R1 = O,R2 = O R2

153 OH

OAc

COOH

O O R1

AcO HOOC

R3

MeOOC

143

R1 = O, R2 = O, R3 = O

144

R1 = β-OH, R2 = O, R3 = O

145

R1 = O, R2 = O, R3 = β-OH

146

R1 = β-OH, R2 = α-OH, R3 = O

HO

154 COOH O

O

R1 COOH

O

O

O HO

OH

O

OH

R2

155 147

R1 = H, R2 = O

148

R1 = H, R2 = β-OH

149

R1 = β-OAc, R2 = O

R

O O O

O

COOH

156

H O

HO

COOH

O

H

OH

R=

O

O COOH

157

150

R=

O

OH COOH

O

COOH

O

158

R=

O

O

HO

O

O O

O

151 O O

H OH

152

O

COOH

O

OH

O

159

HOOC

O

OAc

R1

AcO HOOC MeOOC

HO

Fig. 1 (continued)

160

R1 = α-OAc, R2 = H

161

R1 = α-OAc, R2 = O

R2

COOH

82

S. Baby et al. / Phytochemistry 114 (2015) 66–101

162

R1 = β-OH, R2 = H

172

R1 = O, R2 = H, R3 = Me, R4 = CHO

163

R1 = O, R2 = H

173

R1 = β-OH, R2 = H, R3 = Me, R4 = CHO

174

R1 = O, R2 = α-OH, R3 = CHO, R4 = Me

175

R1 = O, R2 = H, R3 = Me, R4 = CH2OH

176

R1 = β-OH, R2 = H, R3 = Me, R4 = CH2OH

177

R1 = β-OH, R2 = H, R3 = CH2OH, R4 = CH2OH

178

R1 = β-OH, R2 = α-OH, R3 = CH2OH, R4 = CH2OH

179

R1 = O, R2 = α-OH, R3 = CH2OH, R4 = CH2OH

180

R1 = O, R2 = H, R3 = CH2OH, R4 = CH2OH

181

R1 = O, R2 = α-OH, R3 = Me, R4 = CH2OH

182

R1 = β-OH, R2 = α-OH, R3 = Me, R4 = Me

183

R1 = β-OH, R2 = H, R3 = Me, R4 = Me

R2

HOOC

R1

AcO

164

R1 = α-OH, R2 = Me

165

R1 = H, R2 = OH HOOC

OH

O

R3

166

CHO

HOOC

R1

R2

R4

R2

R1

167

R1 = α-OAc, R2 = α-OH O HO

168

R1 = α-

O OMe ,

O

R2 = H

184

R1 = O, R2 = α-OH, R3 = H, R4 = H

185

R1 = β-OH, R2 = O, R3 = H, R4 = H

186

R1 = O, R2 = O, R3 = H, R4 = H

187

R1 = O, R2 = O, R3 = O, R4 = H

188

R1 = O, R2 = β-OH, R3 = O, R4 = α-OH

HOOC

O CHO

R2

OH

HO

R1

189 169

R1 = α-OH, R2 = H

170

R1 = α-OH, R2 = OH

171

R1 = O, R2 = H

R2

O

(b) C30 lanostanes, others (aldehydes, alcohols, esters, glycosides, lactones, ketones)

OH

R1

190

R1 = O, R2 = H

191

R1 = H, R2 = α-OH OH

R4 R3 R1

OH

R2

R

Fig. 1 (continued)

83

S. Baby et al. / Phytochemistry 114 (2015) 66–101

205 192

R=O

193

R = β-OH

OH

O O

OH OH

HO

OH

OH

206 R

O

194

R = β-OH

195

R=O

R2

R1

R2 HO

OH OH

207

R1 = CH2OH, R2 = H

208

R1 = Me, R2 = α-OH

R1

196

R1 = O, R2 = α-OH

197

R = β-OH, R2 = OH

O

OH

O

OH R1

R2

198

R1 = O, R2 = α-OEt

199

R1 = O, R2 = O

200

R1 = O, R2 = α-OMe

201

R1 = β-OH, R2 = O

OH

R

OH

209

R = Me

210

R = CH2OH

OH

O OH O

211

OH

OH

OH R3

R1

R2

202

R1 = β-OH, R2 = O, R3 = H

203

R1 = O, R2 = α-OMe, R3 = α-OH

204

R1 = O, R2 = O, R3 = H

AcO OH HO

212 OAc

OH

OH

OAc HO

O

AcO

Fig. 1 (continued)

carboxylic (acid) groups. Other C30 lanostanes (other than ganoderic acids) such alcohols, esters, aldehydes, epoxy-alcohols, ketones (24n-methyl-5a-lanosta-25-one (284)), glycosides (ganosinoside A (251), tsugarioside A (252), B (253), C (254)),

lactones and farnesylhydroquinone adducts (ganosinensin A (222), B (223), C (224)) were also isolated from various Ganoderma species (Table 1, Fig. 1). These C30 lanostanes also show variations in double bond positions and substitutions in their

84

S. Baby et al. / Phytochemistry 114 (2015) 66–101

213

OH

221

COOH

OH

HO O HO

O

O OH

214

OH

H

O

O CH2OH

222 R

O

OH HO

215

R = α-OH

216

R=O

O

O

O OH

H

O

OH

CH2OH

OH

O

R

223 217 218

OH

R=O HO

R = β-OH

O

O

O

OH

OH

OH

HO

O

219

224 O

OH

R3 O

OH

R1

HO

O

R2

COOR 5

R4

225

R1 = O, R2 = β-OH, R3 = H, R4 = α-OH, R5 = Me

226

R1 = β-OH, R2 = β-OH, R3 = H, R4 = O, R5 = Me

227

R1 = β-OH, R2 = β-OH, R3 = H, R4 = α-OH, R5 = Me

228

R1 = O, R2 = β-OH, R3 = H, R4 = O, R5 = Me

229

R1 = O, R2 = O, R3 = H, R4 = O, R5 = Me

230

R1 = O, R2 = O, R3 = β-OAc, R4 = O, R5 = Me

231

R1 = β-OH, R2 = O, R3 = β-OAc, R4 = O, R5 = Me

220 OH

OMe

HO

Fig. 1 (continued)

85

S. Baby et al. / Phytochemistry 114 (2015) 66–101

249 232

R1 = O, R2 = O, R3 = H, R4 = α-OH, R5 = Me

233

R1 = β-OAc, R2 = O, R3 = β-OAc, R4 = O, R5 = Me

234

R1 = β-OH, R2 = β-OH, R3 = β-OAc, R4 = O, R5 = Me

R1 = β-OH, R2 = O O

O

235

R1 = Ο, R2 = O, R3 = H, R4 = α-OH, R5 = Et

236

R1 = β-OAc, R2 = β-OH, R3 = H, R4 = O, R5 = Et

237

R1 = O, R2 = O, R3 = β-OAc, R4 = O, R5 = Et

238

R1 = O, R2 = β-OH, R3 = H, R4 = α-OH, R5 = Bu

239

R1 = β-OH, R2 = β-OH, R3 = H, R4 = O, R5 = Bu

240

R1 = β-OH, R2 = O, R3 = β-OAc, R4 = O, R5 = Bu

241

R1 = β-OH, R2 = β-OH, R3 = β-OAc, R4 = O, R5 = Bu

242

R1 = O, R2 = O, R3 = β-OAc, R4 = O, R5 = Bu

O

H H R1

O

O

OH

250 R2OOC

R1

251

R1 = O, R2 = β-D-glucopyranosyl

252

R1 = α-OAc, R2 = β-D-glucosyl ROH2C

R2 O

COOM e

O

COOM e

OH

AcO

253

243

R1 = O, R2 = H

244

R1 = β-OH, R2 = β-OH

R = β-D-xylosyl ROOC

COOM e

O

AcO

O O

O

254

O

R = β-D-xylosyl OH O

245

O

O

O

H H HO

O

R

COOM e

OH

OH

255

R=O

256

R = OH

O

O

O O

246 R2

O

O

COOM e R1 HO

HO

R1

R2

247

R1 = β-OH, R2 = β-OH

248

R1 = O, R2 = β-OH Fig. 1 (continued)

257

R1 = H, R2 = H

258

R1 = β-OH, R2 = H

259

R1 = H, R2 = OAc

86

S. Baby et al. / Phytochemistry 114 (2015) 66–101

R1 = H, R2 = OH

260

270b O O

O

AcO

H

MeO

O

O

O

O

261

271 R

O

O

O

O

HO

O

O

O

262

R=H

263

R = β-OH

272 HO

O O

O

AcO

AcO

MeOOC HO

Ac O HO

264

273 R4 R2

O

O

O

O

O

R3 O

R1

265

R1 = H, R2 = H, R3 = OAc, R4 = β-OH

266

R1 = H, R2 = H, R3 = OH, R4 = H

267

R1 = H, R2 = H, R3 = OAc, R4 = H

268

R1 = H, R2 = β-OH, R3 = OAc, R4 = H

269

R1 = H, R2 = H, R3 = H, R4 = H

270a

R1 = OH, R2 = H, R3 = OAc, R4 = H

O

O

274

O H O O

O O

O

OAc O

O

O OH

Fig. 1 (continued)

O

O

O

87

S. Baby et al. / Phytochemistry 114 (2015) 66–101

275

282

O MeOOC

O

O

O

O

H O R

276

R = β-OAc

277

R=O

O

283

O

O

O

O

O

MeOOC

284

H OAc

(c) C27 lanostanes, lucidenic acids 278 R3 12

O

O 1

R1

HO

O O

ROOC O

280

R=H

281

R = Me

OAc

OH

O

O

OH

Fig. 1 (continued)

25

27

R2

COOH

O

286

R1 = O, R2 = β-OH, R3 = β-OH, R4 = H

287

R1 = β-OH, R2 = β-OH, R3 = β-OH, R4 = H

288

R1 = O, R2 = O, R3 = O, R4 = H

289

R1 = O, R2 = O, R3 = β-OAc, R4 = H

290

R1 = O, R2 = β-OH, R3 = α-OH, R4 = H

291

R1 = β-OH, R2 = O, R3 = β-OAc, R4 = H

292

R1 = O, R2 = O, R3 = H, R4 = H

293

R1 = β-OH, R2 = β-OH, R3 = H, R4 = H

294

R1 = β-OH, R2 = β-OH, R3 = β-OAc, R4 = H

295

R1 = O, R2 = β-OH, R3 = H, R4 = ξ-OH

296

R1 = O, R2 = O, R3 = β-OAc, R4 = ξ-OH

297

R1 = β-OH, R2 = O, R3 = β-OAc, R4 = ξ-OH

298

R1 = O, R2 = O, R3 = H, R4 = ξ-OH

299

R1 = β-OH, R2 = β-OH, R3 = H, R4 = ξ-OH

300

R1 = β-OH, R2 = β-OH, R3 = β-OAc, R4 = ξ-OH

O

HO

26

8

23

R1 = O, R2 = β-OH, R3 = H, R4 = H

O O

5

22

285

279 O

9

3

20 17

19

OH

R4

21 18

88

S. Baby et al. / Phytochemistry 114 (2015) 66–101

301

314

R1 = β-OH, R2 = O, R3 = H, R4 = H

O

COOH

O

COOH

HOOC

OH

O

HO

OH

O

315

OH

302

COOH

O R4

ROOC

COOH

O

OH R3

R1

R5

316

R=H

317

R = Me

R2

303

R1 = β-OH, R2 = OH, R3 = β-OH, R4 = H, R5 = O

COOH O

304

R1 = β-OH, R2 = OH, R3 = O, R4 = H, R5 = O

305

R1 = β-OH, R2 = OH, R3 = O, R4 = β-OH, R5 = O

306

R1 = O, R2 = H, R3 = O, R4 = α-OH, R5 = O

307

R1 = β-OH, R2 = H, R3 = O, R4 = β-OH, R5 = O

308

R1 = β-OH, R2 = H, R3 = α-OH, R4 = H, R5 = α-OH

O

318

O

COOH

O

H OH COOH

OH

R1

MeOOC

R3

O

OH

319

R2

309

R1 = β-OH, R2 = OH, R3 = α-OH

310

R1 = O, R2 = H, R3 = O

311

R1 = β-OH, R2 = H, R3 = O

(d) C27 lanostanes (alcohols, lactones, esters) O O O

COOH

HO

R

O

CH2OH

OH

320 312

R = α-OH

313

R=H

O O O COOH

O O

O

Fig. 1 (continued)

OH

O

OH

89

S. Baby et al. / Phytochemistry 114 (2015) 66–101

R1 = β-OH, R2 = O, R3 = β-OAc, R4 = O, R5 = Bu

340 O

321

COOMe

O

O O

HO

OH

O

OH

HO O

OH

322

341

COOMe

O

COOMe

O

ROOC

O

OH

O

OH

342 323

R=H

324

R = Me COOMe

H OH

O

COOMe

O HOOC

O

OH

O

343 325 (e) C24, C25 lanostanes R3

21

COOR5

O

18

O

12

19

R1

R2

1

R4

3

9 5

24

R2 23

O

17

8

R1

20

R3

22

326

R1 = Ο, R2 = β-OH, R3 = H, R4 = O, R5 = Me

327

R1 = β-OH, R2 = β-OH, R3 = β-OH, R4 = O, R5 = Me

344

R1 = β-OH, R2 = β-OH, R3 = O

328

R1 = O, R2 = O, R3 = H, R4 = O, R5 = Me

345

R1 = O, R2 = β-OH, R3 = O

329

R1 = β-OH, R2 = β-OH, R3 = H, R4 = O, R5 = Me

346

R1 = β-OH, R2 = β-OH, R3 = α-OH

330

R1 = β-OH, R2 = β-OH, R3 = β-OAc, R4 = O, R5 = Me

347

R1 = β-OH, R2 = O, R3 = O

331

R1 = O, R2 = β-OH, R3 = H, R4 = α-OH, R5 = Me

348

R1 = β-OH, R2 = O, R3 = α-OH

332

R1 = O, R2 = O, R3 = β-OAc, R4 = O, R5 = Me

349

R1 = O, R2 = β-OH, R3 = α-OH

333

R1 = Ο, R2 = β-OH, R3 = H, R4 = O, R5 = Et

350

R1 = O, R2 = H, R3 = α-OH

334

R1 = O, R2 = β-OH, R3 = H, R4 = O, R5 = Bu

351

R1 = O, R2 = O, R3 = O

335

R1 = β-OH, R2 = β-OH, R3 = H, R4 = O, R5 = Bu

336

R1 = O, R2 = β-OH, R3 = β-OH, R4 = O, R5 = Bu

337

R1 = β-OH, R2 = β-OH, R3 = β-OAc, R4 = O, R5 = Bu

338

R1 = O, R2 = β-OH, R3 = H, R4 = α-OH, R5 = Bu

339

R1 = O, R2 = O, R3 = β-OAc, R4 = O, R5 = Bu

O O O

O

Fig. 1 (continued)

O

O

90

S. Baby et al. / Phytochemistry 114 (2015) 66–101

359 352

OH

OH

O

HO

OH

OH

OH

O

COOH

360 353 O

(f) C30 pentacyclic triterpenes HO

O CHO

361 O

O

HO

354 O

362 O HO

O O

355

363 O HO

O

R

364

356

R=O

357

R = β-OAc

OH

OH

O OH

O

O

(g) Meroterpenoids 365

OH

OH

(h) Farnesyl hydroquinones (meroterpenoids)

O

O

OH

358 OH OH

OCH3 OH

O

O

Fig. 1 (continued)

91

S. Baby et al. / Phytochemistry 114 (2015) 66–101

375

366

OH

O

OH

O

R

HO COOH

367

R = OH

368

R=H

376 O

OH

O

HO O

HOOC

O

O H

369 OH

377 OH

OH

OH

O

H

H O

R2 R2 R2

O R1

370

(i) C15 sesquiterpenoids

378

R1 = H, R2 = COOH

379

R1 = β-OH, R2 = COOH

H

HO

(j) Steroids

OH

28

21

O

18 12

19

371

R

1

H

HO

OH

3

8

9 5

380 OH

H

372

R = α-OH

373

R = β-OH

HO

381 HO

H

OH OH

H

HO

374 382 H

HOH2C

H

OH OH

HO

Fig. 1 (continued)

O

O

20 17

26

23 27

92

S. Baby et al. / Phytochemistry 114 (2015) 66–101

393

383

O

HO

O

O

R

394

R = α-OH

395

R = β-OH

396

R=O

384

HO

R1 OH R2

385

R1 = H, R2 = β-OMe

386

R1 = H, R2 = O

387

R1 = α-OH, R2 = O

R1 O

HO OH HO

R2

397

R1 = H, R2 = α-OH

398

R1 = H, R2 = β-OH

399

R1 = α-OH, R2 = O

400

R1 = α-OH, R2 = H

401

R1 = H, R2 = H

388

OH OH HO

OH OH

R

O

389

R1 HO

402

R=O

403

R = β-O-pentadecanoyl

404

R = β-O-palmitoyl

405

R = β-O-linoleoyl

R2

OH OH

390

R1 = H, R2 = H

391

R1 = α-OH, R2 = H

R

392

R1 = α-OH, R2 = α-OH

406

R = β-O-linoleoyl

H3CO OH

R

HO

O

O

Fig. 1 (continued)

skeletons and side-chains (as in C30 ganoderic acids) (Table 1, Fig. 1). In most C27 lanostanes (lucidenic acids), a single double bond in the tetracyclic ring was found at C8–C9 (Fig. 1). Only ganoderic

acid Jd (312) and 4,4,14a-trimethyl-5a-chol-7,9(11)-dien-3-oxo24-oic acid (313) showed two double bonds at C7–C8 and C9–C11 in their tetracyclic skeleton. Lucidenic acid O (309), 20(21)-dehydrolucidenic acid A (310) and 20(21)-

93

S. Baby et al. / Phytochemistry 114 (2015) 66–101

407

415

R = β-O-linoleoyl

HO

HO

N HO

416

R

408

R = β-O-linoleoyl

409

R = β-OH

HO R

N HO

417

R=H

418

R = OH

HO

O

410

OH

N HO

419 O HO

OH

N HO

411

420

(l) Prenyl hydroquinone RO O

412

R=Η

413

R = β-D-glucopyranosyl

HO O

O OH

CHO

H

421 (k) Alkaloids

OHC

(m) Benzofurans

O

N

HO

O

OH O

OH

O

414 422 OHC

N

O

OH

HO

COOH

Fig. 1 (continued)

dehydrolucidenic acid N (311) showed ethylenic groups at C20. Hydroxyl substitutions at C20 were observed in 20-hydroxy lucidenic acid A (295), D2 (296), E2 (297), F (298), N (299) and P (300). Other side-chain substitutions are relatively few,

because the side-chains in C27 lanostanes are shorter compared to the C30s. Double bonds in the ring systems of C27 lanostanes (esters, alcohols, lactones) are also found at C8–C9 (Table 1, Fig. 1).

94

S. Baby et al. / Phytochemistry 114 (2015) 66–101

423

428

(n) Benzopyran-4-one derivatives

(o) Benzenoid derivatives

O

R

OH

OH

O

HO

424

429

R = COOH

430

R = COCH3

O OH O

CHO

425 O HO

OH OH

O

431

426 O

H

O

O

(Structures of isolated secondary metabolites are drawn in O

varying stereochemical patterns by authors. In lanostanes and steroids, the following stereochemical patterns are followed for uniformity, (i) α-H at C5, C17 or equivalent positions is

427 O O

suppressed, (ii) C17 side-chain β, (iii) C10, C13 methyls β, (vi) C21 H

OH

α, (iv) C14 methyl α (lanostanes) and (v) C29/C28 β/α (C30

OH

lanostanes), C26/C25 β/α (C27 lanostanes), C24/C23 β/α (C25 lanostanes), C23/C22 β/α (C24 lanostanes)). Fig. 1

C30 and C27 lanostanes show more unique types of double bonds and substitutions in their four ring skeletons and side-chains. Ganoderic acid Df (23) has a rare hydroxyl substituent at C11 in the C30 lanostane skeleton (Fatmawati et al., 2010). Ganoderic acid L (14) has a hydroxyl group at C20 and it can be a possible precursor of lucidone C (346) (Nishitoba et al., 1986a). Ganoderic acid T (71) and lanosta-7,9(11),24-trien-3b,15a,22b-triacetoxy-26-oic acid (87) are lanostane type triterpenoids having heteroannular diene moieties and three acetoxyl groups each (Hirotani et al., 1986). 7O-Ethyl ganoderic acid O (53) isolated from G. lucidum has a rare ethoxy group at C7 (Wang et al., 2010b). Most lanostanoids have a keto group at C23, but Ha et al. isolated two lanostanoids (26-hydroxy-5a-lanosta-7,9(11),24-triene-3,22-dione (209), 26,27-dihydroxy-5a-lanosta-7,9(11),24-triene-3,22-dione (210)) with ketonic groups at C22 (Ha et al., 2000). Lee et al. recently reported a lanostane analog, methyl ganoderate A acetonide (245), with an acetal carbon connected to C7 and C15 through oxygen atoms, forming a seven-membered 1,3-dioxepane moiety (Lee et al., 2011a). This compound isolated from the fruiting bodies of G. lucidum is most likely not of natural origin but an artifact (Yang et al., 2012). Ganodermacetal (151) isolated from G. amboinense fruiting bodies with a similar acetonide group is a natural product resulting from the acetalization of ganoderic acid C (ganoderic acid C2, 4), as acetone was not used during the isolation procedure (Yang et al., 2012). Triterpene–farnesyl hydroquinone conjugates, ganosinensin A (222), B (223), C (224), isolated under mild conditions from the methanol extract of G. sinense, are natural products only and not artifacts formed through extraction processes (Sato et al., 2009a). Niu

et al. reported a C30 lanostane triterpenoid (168) with a 3-hydroxy-5-methoxy-3-methyl-1,5-dioxopentyloxy group at C3 from G. resinaceum fruiting bodies (Niu et al., 2007). Ganolucidic acid D (102) has an allylic alcohol group in the side-chain and it can be a possible biogenetic intermediate between the mycelial components and terpenoids of the fruiting body of G. lucidum (Min et al., 2000; Nishitoba et al., 1986a). Ganosporeric acid A (120) has five keto groups in the lanostane skeleton and a sixth group in the side-chain (Chen and Yu, 1993). Ganoderic acid E (6), F (7), 12b-hydroxy3,7,11,15,23-pentaoxo-5a-lanosta-8-en-26-oic acid (35), 8b,9a-dihydroganoderic acid C (118), methyl ganoderate E (229), F (230) and 12b-acetoxy-3,7,11,15,23-pentaoxo-5a-lanosta-8-en-26-oic acid ethyl ester (237) have four keto groups in their lanostane skeletons and a fifth in their side-chains (Table 1, Fig. 1). 8a,9a-Epoxy3,7,11,15,23-pentaoxo-5a-lanosta-26-oic acid (159) has four keto groups in the lanostane skeleton, a fifth group in the side-chain and an epoxy group between C8 and C9 (Joseph et al., 2011a). Ganoderenic acids A (125) to I (133), K (134), elfvingic acid A (135), 12b-acetoxy-7b-hydroxy-3,11,15,23-tetraoxo-5a-lanosta8,20-dien-26-oic acid (136), 7b,23n-dihydroxy-3,11,15-trioxolanosta-8,20E(22)-dien-26-oic acid (138), applanoxidic acid A (139), B (140), E (141), F (142), 7b-hydroxy-3,11,15,23-tetraoxolanosta-8,20E(22)-dien-26-oic acid methyl ester (250), australic acid (280) and methyl australate (281) have 20E-double bonds on their ganoderic acid side-chains (Komoda et al., 1985). Lakornwong et al. recently revised the structure of colossolactone G (270a) to (270b) (El Dine et al., 2008a; Kleinwächter et al., 2001; Lakornwong et al., 2014) (Table 1, Fig. 1). Colossolactone I (257), II

S. Baby et al. / Phytochemistry 114 (2015) 66–101

(258), III (261), IV (262), VII (264), VIII (265), colossolactone B (259), C (271), D (266), E (267), F (268), G (270a, b), ganoderma lactone A (272), C (263), D (273), E (260), F (274), G (275) and schisanlactone A (269), B (283) are characterized by the presence of a six membered a,b-unsaturated d-lactone group in their side-chain with or without a seven membered lactone ring A. Colossolactone VIII (265), colossolactone D (266), E (267), F (268), G (270a, b), ganoderma lactone A (272), F (274), G (275) and schisanlactone A (269) have three double bonds in their first two seven/six membered rings. Ganolucidic acid C (121) isolated from G. lucidum and G. sinense possesses an unusual b-hydroxymethyl group at C4 (Liu et al., 2012b; Nishitoba et al., 1985b, 1987c). Applanoxidic acid A (139), E (141) and G (145) have hydroxyl substitutions at C15 whereas applanoxidic acid B (140), C (143), D (144), F (142) and H (146) are 15-keto analogs (Chairul et al., 1994). Several other C30 lanostanes also have hydroxyl or keto substitutions at C15 (Table 1, Fig. 1). Among the C27 lucidenic acids, lucidenic acid G (302) has a hydroxyl group at C26, not found in other isolates (Nishitoba et al., 1986a). Lucidenic acid O (309) isolated from G. lucidum has an exo-methylene group at C20, an acid group at C24 and a hydroxyl group at C25 (Mizushina et al., 1999). Lucidenic acid D1 (288) has five keto groups in its tetracyclic lanostane skeleton (Table 1, Fig. 1). Akihisa et al. and Sato et al. isolated C20 hydroxylated analogs of lucidenic acid A (G. sinense) (295), lucidenic acid D2 (G. lucidum) (296), E2 (G. lucidum) (297), F (G. lucidum) (298), N (G. lucidum/ G. sinense) (299) and P (G. lucidum) (300) (Akihisa et al., 2005; Sato et al., 2009b). Ganosinensic acid B (152), ganosinensic acid A (319) and methyl ganosinensate A (343) isolated from G. sinense have triterpenoid skeletons with a unique four membered ring (Wang et al., 2010a). Fornicatin A (G. fornicatum) (315), B (G. fornicatum, G. cochlear) (316) and D (G. cochlear) (317) are naturally occurring unique 25,26,27-trinorlanostane triterpenoids with the cleavage of the bond between C3 and C4 in ring A (Niu et al., 2004; Peng et al., 2014b). Two novel trinorlanostanes, cochlate A (325) and B (318), with 3,4-seco-9,10-seco-9,19-cyclo skeletons, were isolated from the fruiting bodies of G. cochlear (Peng et al., 2014b). Cochlate A (325) and B (318) could be derived by enzymatic modification of fornicatin B (316) (Peng et al., 2014b) (Table 1, Fig. 1). A series of C24 lanostanes, lucidone A (344), B (345), C (346), D (347), E (348), F (349), G (350), H (351), were isolated from G. lucidum, G. amboinense, G. applanatum, G. resinaceum and G. tropicum (Gan et al., 1998b; Hu et al., 2014; Lin et al., 1993; Nishitoba et al., 1985a, 1986a; Peng et al., 2013) (Table 1, Fig. 1). Nishitoba et al. first isolated lucidone A (344) from G. lucidum (Nishitoba et al., 1985a). Thereafter, similar C24 terpenoids (lucidone B (345) to H (351)) and their lactones (lucidenic lactone (320), lucidenolactone (321), ganolactone B (322)) were isolated by various groups (Table 1, Fig. 1). Substitutions in lanostanes (C30, C27, C24/C25) particularly at C3, double bonds, type of the side-chain and the number of hydroxyl groups play important roles in their structure–activity relationships (Cheng et al., 2010). Lanostanes and other secondary metabolites could provide chemotaxonomic clues in the genus Ganoderma (Cheng et al., 2010). Chemotaxonomy of genus Ganoderma has been recently reviewed (Richter et al., 2015). As in Table 1 and Fig. 1, most phytochemical studies in the genus are on G. lucidum, and relatively less chemical data are available on G. applanatum/G. lipsiense and G. sinense. Very limited studies are available on a few other Ganoderma species (Table 1, Fig. 1) and the remaining species are chemically not studied so far. Chemical profiling of standardized extracts using advanced liquid chromatography–mass spectrometry-based techniques or isolation of chemotaxonomically relevant compounds (ganoderic acids, lucidenic acids, triterpenes, applanatines, ganomastenols, steroids) could help in resolving the existing taxonomic issues in genus Ganoderma (Chen et al., 1999; Cheng et al., 2010; Paterson, 2006; Richter et al., 2015).

95

C30 pentacyclic triterpenoids (friedelin (354), alnusenone (355), b-amyrenone (356), b-amyrin acetate (357)) were isolated from G. applanatum and G. cochlear (Ming et al., 2002; Nishitoba et al., 1989; Peng et al., 2014b). Meroterpenoids fornicin A (358), B (359), C (360), ganocin A (361), B (362), C (363), D (364) and lingzhiol (365) were isolated from G. fornicatum, G. lucidum and G. cochlear (Niu et al., 2006; Peng et al., 2014a; Yan et al., 2013). Meroterpenoids are natural products biosynthesized from polyketide and terpenoid precursors. Peng and co-workers recently isolated ganocins A (361), B (362), C (363) possessing a spiro[4,5]decane substructure and ganocin D (364) with an eightmembered carbon ring from the fruiting bodies of G. cochlear (Peng et al., 2014b). Lingzhiol (365) isolated from G. lucidum has a novel 5/5/6/6 ring system and its three rings sharing a C-3–C-7 axis gives it a rotary door like structure (Yan et al., 2013). Niedermeyer et al. first reported the isolation of farnesyl hydroquinone (366) from G. pfeifferi (Niedermeyer et al., 2013). Farnesyl hydroquinone (366) could be the biosynthetic precursor of ganomycin A (G. pfeifferi) (367), B (G. pfeifferi; G. colossum) (368), I (G. colossum) (369) and K (G. pfeifferi) (370) (El Dine et al., 2009; Mothana et al., 2000; Niedermeyer et al., 2013). Farnesyl hydroquinone (366) and ganomycin A (367), B (368), I (369) and K (370) also fall into the group of meroterpenoids (Table 1, Fig. 1). Sesquiterpenoids such as ganosinensine (G. sinense) (371), ganomastenol A (372), B (373), C (374), D (375) (G. mastoporum), echinolactone D (G. applanatum) (376), ganodermycin (G. applanatum) (377), cryptoporic acid H (G. neo-japonicum) (378) and cryptoporic acid I (G. neo-japonicum) (379) were isolated from various Ganoderma species (Fushimi et al., 2010; Hirotani et al., 1991, 1995; Jung et al., 2011; Liu et al., 2012b). Several steroids and steroidal esters were isolated from G. lucidum and other Ganoderma species. Major steroidal metabolites isolated from Ganoderma include ergosterol (380), ergosta-7,22-dien3b-ol (381), ergosterol peroxide (383), ergosta-7,22-diene-3-one (402), ergosta-7,22-diene-3b-yl pentadecanoate (403), ergosta7,22-dien-3b-yl palmitate (404) and ergosta-7,22-dien-3b-yl linoleate (405) (Gan et al., 1998a,b; Ko et al., 2008; Lin et al., 1993, 1997; Nishitoba et al., 1988b; Rosecke and Konig, 2000; Seo et al., 2009; Smania et al., 1999; Strigina et al., 1971; Ziegenbein et al., 2006) (Table 1, Fig. 1). Steroid isolates showed one, two or three double bonds at C5–C6, C6–C7, C7–C8 (most common), C5–C6/C7–C8, C4–C5/C7–C8, C6–C7/C9–C11, C7–C8/ C16–C17 and C4–C5/C6–C7/C8–C14 in their ring systems. Ergosterol peroxide (383), 5a,8a-epidioxyergosta-6,9(11),22trien-3b-ol (384) and 5a,8a-epidioxy ergosta-6,22-dien-3b-yl linoleate (407) have C6-C7 double bonds and an epidoxy group linked to C5 and C8 (Fig. 1). 5a,8a-Epidioxyergosta-6,9(11),22trien-3b-ol (384) also has a C9–C11 double bond (Table 1, Fig. 1). Ganodermasides A (397), B (398), C (399), D (400) isolated from G. lucidum have four double bonds, three within three six membered rings (C4–C5, C6–C7, C8–C14) of their steroid skeletons and a fourth at C22 in side-chains (Weng et al., 2010, 2011). Most steroids (Table 1, Fig. 1) have C22–C23 double bonds in their side-chains, but some of them have no side-chain double bonds. 3b-Linoleyloxyergosta-7,24(28)-diene (406) isolated from G. lipsiense has an ethylene linkage at C24 (Rosecke and Konig, 2000). Ganoderma alkaloids A (414) and B (415) were isolated from the fruiting bodies of G. capense in 1990 (Liu et al., 2011; Yang and Yu, 1990). More alkaloids, sinensine (416), sinensine B (417), C (418), D (419), E (420) were isolated recently from G. sinense (Liu et al., 2010, 2011). Prenyl hydroquinone (ganoderma aldehyde (421)), benzofurans (ganodone (422), ganofuran B (423)), benzopyran-4-one derivatives (applanatine A (424), B (425), C (426), D (427), E (428)) and benzenoid derivatives (429–431) were also isolated from various Ganoderma species (Table 1, Fig. 1). Flavonoids, a widely distributed group of secondary metabolites, are not reported from genus Ganoderma so far.

96

S. Baby et al. / Phytochemistry 114 (2015) 66–101

In most cases, the genus name (Ganoderma) or source species names were used to coin trivial names of isolated secondary metabolites (ganoderic acid (Ganoderma), lucidenic acid (lucidum), cochlate (cochlear), fornicatin (fornicatum), australic acid (australe)) (Table 1, Fig. 1, Table S1). In some cases, compounds with sequential trivial names do not show structural similarities (ganoderic acid Jd (312) isolated from G. sinense is not a C30 lanostane, but a C27 lucidenic acid type molecule) (Liu et al., 2012b). Moreover, trivial names of ganoderic acids and lucidenic acids are confusing because identical compounds were given different names or different compounds were named identically. These naming issues are mostly in papers published by four research groups in the 1980s (Hirotani et al., 1985, 1986, 1987; Hirotani and Furuya, 1986; Kikuchi et al., 1985a,b, 1986a,b,c; Kohda et al., 1985; Nishitoba et al., 1984, 1985a,b,c, 1986a,b, 1987a,b,c, 1988a,b, 1989) (Table 1, Fig. 1, Table S1). For example, Nishitoba et al. (1984, 1985a,c) reported (3) as ganoderic acid C. Kohda et al., 1985 reported (3) as ganoderic acid D, but later (3) was renamed as ganoderic acid C1 by Kikuchi et al. (1986a). Kohda et al. (1985) named (4) as ganoderic acid C and Kikuchi et al. (1985a) named (4) as ganoderic acid D. It (4) was later renamed as ganoderic acid D2 by Nishitoba et al. (1985b) and as ganoderic acid C2 by Kikuchi et al. (1986a). Hirotani and Furuya (1986) reported (4) as ganoderic acid E. Hirotani et al., 1985 reported (9) as ganoderic acid C. Nishitoba et al. (1985a) reported (5) as ganoderic acid D and Nishitoba et al. (1985b) renamed it as ganoderic acid D1. Kikuchi et al. (1986b) reported (5) as compound C50 . Some attempts were made to rectify these naming issues (see Kikuchi et al., 1986a; Nishitoba et al., 1985a, 1986a), but these problems are not fully resolved (see Table S1 ganoderic acid C1 (3), ganoderic acid C2 (4), ganoderic acid D1 (5), ganoderic acid K (12, 13), ganoderic acid O (17, 37), ganoderic acid Q (67), ganoderic acid S (69, 70), ganoderic acid B8 (21), ganoderic acid C6 (22), ganoderol B (176), lucidenic acid D1 (288), lucidenic acid D2 (289), lucidenic acid E1 (290), lucidenic acid E2 (291), lucidenic acid N (293), etc.). Another observation is, in several papers published in the 1980s, G. lucidum extracts were methylated (with diazomethane) during isolation, and ganoderic acids and lucidenic acids were obtained as their methyl derivatives (see Hirotani and Furuya, 1986; Kikuchi et al., 1985a,b, 1986a,b,c; Nishitoba et al., 1987c). In Table 1, Fig. 1, these methyl derivatives are compiled as their free acids. Most phytochemical studies on genus Ganoderma reported isolation, structure elucidation and biological activities of secondary metabolites. Similar studies are still being continued in genus Ganoderma, and new isolates in various systematic and trivial names are periodically added to the Ganoderma literature (Hu et al., 2013, 2014; Isaka et al., 2013; Lakornwong et al., 2014; Li et al., 2013b,c; Lin et al., 2013; Liu et al., 2014a; Ma et al., 2013, 2014; Niedermeyer et al., 2013; Peng et al., 2013, 2014a,b; Tung et al., 2013; Yan et al., 2013). Secondary metabolites isolated from various Ganoderma species (mostly first reports) and the literature describing their isolation and structure elucidation are given emphasis in this compilation (Table 1, Fig. 1). Most triterpenoids isolated from Ganoderma showed significant biological activities. Ganoderic acids from G. lucidum showed anticancer, antiviral, hepatoprotective, antiplatelet aggregation, antioxidant, hypocholesterolemic and inhibition of histamine release activities (Chairul et al., 1991; Gonzalez et al., 2002; Komoda et al., 1989; Lin et al., 2003; Min et al., 2000; Ríos et al., 2012; Sonoda et al., 1988; You et al., 2013). Ganoderic acid A (1) and methyl ganoderate A (225) were reported to have an inhibitory effect against farnesyl protein transferase (Lee et al., 1998). Inhibitors of farnesyl protein transferase have been shown to inhibit Ras (oncoprotein)-dependent cell transformation and thus lead to a potential therapeutic strategy for the treatment of human cancers (Lee et al., 1998). Ganoderic acid B (2), C2 (4) and their derivatives

were reported to have anticholesterol activity (Komoda et al., 1989; Sonoda et al., 1988). Ganoderic acid C1 (3) showed inhibition of the glycosyl transferase from the cariogenic bacterium Streptococcus mutans (Gao et al., 2004). Kohda et al. showed histamine releasing inhibitory activity for ganoderic acid C2 (4) and D1 (5) (Kohda et al., 1985). Yue and co-workers recently showed inhibition of the proliferation of HeLa human cervical carcinoma cells by ganoderic acid B (2), D (ganoderic acid C1, 3), F (7), K (12) and AM1 (18) (Yue et al., 2010). Ganoderic acids A (1), B (2), G (8) and H (9) isolated from G. lucidum exhibited antinociceptive activity (Koyama et al., 1997). Morigiwa et al. showed inhibitory effect on angiotensin converting enzyme for ganoderic acid F (7) isolated from G. lucidum (Morigiwa et al., 1986). Ganoderic acid Df (23) showed aldose reductase inhibitory activity (Fatmawati et al., 2010). Ganoderic acids U (38), V (39), W (40), X (72), Y (73), Z (41) were found to have cytotoxicity against hepatoma cells in vitro (Hirotani et al., 1987; Toth et al., 1983a,b,c). Six ganoderic acids c (96), d (97), e (98), n (99), g (100) and h (101) isolated from G. lucidum spores showed cytotoxic effects against Meth-A (sarcoma) and LLC (lung) tumor cell lines (Camargo and Kaneno, 2011; Min et al., 2000). Iwatsuki et al. reported inhibitory effect on Epstein–Barr virus activation for ganoderic acids E (6), F (7), ganodermic acid T–Q (84), lucidenic acid A (285), C (287), D2 (289), E2 (291), F (292) and their ester derivatives (Iwatsuki et al., 2003). Recently, ganoderic acid T (71) has been demonstrated to inhibit tumor metastasis by suppression of NF-kB activation (You et al., 2013). G. lucidum isolates ganolucidic acid A (32), ganoderic acid b (51), ganodermanondiol (192), lucidumol B (193) and ganodermanontriol (196) showed anti-HIV-1 protease activity (Min et al., 1998). Ganoderiol F (180), ganodermanondiol (192) and ganodermanontriol (196) showed anti-HIV and anticomplement activities (ElMekkawy et al., 1998; Min et al., 1998, 2001). Lucidenic acid O (309) and lucidenic lactone (320) showed inhibitory effect on eukaryotic DNA polymerase (Mizushina et al., 1999). Lin and coworkers reported cytotoxicity against hepatoma PLC/PRF/5 and KB cells for ganoderic aldehyde A (189) (Lin et al., 1990, 1991). Kim et al. reported b-glucosidase inhibitory and hepatoprotective activities for ganoderenic acid A (125) (Kim et al., 1999). Ganoderiol A (197)-enriched G. lucidum extract was found to suppress cell migration and cell adhesion by inactivation of focal adhesion kinase and disrupting of focal adhesion kinase/SRC complex formation, which subsequently inhibited paxillin activation. Moreover, ganoderiol A (197)-enriched extract downregulated the expression of Rho GTPases and influenced actin polymerization. Thus ganoderiol A (197)-enriched extract showed the potential for treatment of breast cancer metastasis (Wu et al., 2013). Lucidal (lucialdehyde C, 185), lucialdehyde B (186), ganodermanonol (ganoderol A or ganodermenonol, 175) and ganodermanondiol (192) showed cytotoxicity against Lewis lung carcinoma, T-47D, Sarcoma 180 and Meth-A tumor cell lines. Lucidal (185) exhibited the most potent cytotoxicity against these tumor cells (Gao et al., 2002). Butyl ganoderate A (238), B (239), butyl lucidenate A (334) and N (335) showed antiobesity effects through inhibition of adipocyte differentiation in 3T3-L1 cells in vitro (Lee et al., 2010b). Adams et al. reported in vitro antiplasmodial activity for ganoderic acid S (70), 23-hydroxy ganoderic acid S (117) and ganoderic aldehyde TR (174) (Adams et al., 2010). These reports revealed the pharmacological potentials of various lanostanes isolated from Ganoderma. Similarly, other secondary metabolites (steroids, alkaloids, ganomycins, fornicins, ganocins) isolated from Ganoderma are biologically active molecules. Ganoderic acids, highly oxygenated C30 lanostane-type triterpenoids, are the prominent bioactive constituents in genus Ganoderma. Ganoderic acid skeleton shows oxidative modifications with hydroxyl, oxo, acetoxyl and other functional groups especially at C3, C7, C15 and C22 positions (Fig. 1). Table 1, Fig. 1 lists 171

S. Baby et al. / Phytochemistry 114 (2015) 66–101

ganoderic acids isolated from various Ganoderma species. Regulation of ganoderic acid biosynthesis and enhancing ganoderic acid production are critical in utilizing Ganoderma species for medicinal applications. G. lucidum is the key species used for medicinal purposes. However, so far the pathways of ganoderic acid biosynthesis are not fully understood. Biogenetic investigation of triterpenoids demonstrated that ganoderic acids are biosynthesized via the mevalonate–isoprenoid pathway (Chen et al., 2012; Xu et al., 2010). Ganoderic acids and their derivatives are synthesized from lanosterol by a series of oxidation, reduction, hydroxylation and acetylation steps (Liang et al., 2010; Ríos et al., 2012; Xu et al., 2010; You et al., 2013). Ganoderic acids are extracted mainly from the cultivated fruiting bodies of Ganoderma species. Cultivation of Ganoderma fruiting bodies is time consuming and ganoderic acid production fluctuates depending on various factors (Seo et al., 2009). Xu and co-workers recently reviewed the biotechnological interventions made in enhancing the production of ganoderic acids (Xu et al., 2010). New strategies for accelerated mycelia growth, enhancing ganoderic acid production by mycelia fermentation and varying fermentation conditions were studied by various groups (Wagner et al., 2003; Xu et al., 2010). Submerged fermentation is a promising technology for the enhanced production of ganoderic acids from Ganoderma (Wagner et al., 2003). The application of various inducers such as methyl jasmonate and phenobarbital has been used to enhance ganoderic acid production in submerged cultures (You et al., 2013). Zhu and co-workers reported the enhanced production of ganoderic acids under induction by a microbial polysaccharide in the submerged culture of G. lucidum (Zhu et al., 2008; Liang et al., 2010). More recently, enhanced production of individual ganoderic acids was demonstrated in a two stage culture of G. lucidum (Xu et al., 2010). Metabolic engineering of Ganoderma species is a very promising approach to enhance ganoderic acid production. In the postgenomic era (Chen et al., 2012), the integration of transcriptomic, proteomic and metabolomic tools could be utilized to elucidate the regulatory mechanism of ganoderic acid biosynthesis. The regulation of metabolic pathways along with the optimization of fermentation processes could lead to enhanced production of ganoderic acids from Ganoderma species (Xu et al., 2010). 3. Volatiles from Ganoderma Volatile oils were also reported in Ganoderma species. Ziegenbein et al. isolated volatile oil from the fruit bodies of G. lucidum by hydrodistillation and characterized it by GC-FID and GC– MS. Of the 65 constituents identified in G. lucidum essential oil, major ones were trans-anethole (9.1%), R-()-linalool (4.4%), S(+)-carvone (4.4%), 2-pentylfuran (2.8%), a-terpineol (2.7%) and n-nonanal (2.3%) (Ziegenbein et al., 2006). Volatile oil was isolated from the mycelia of G. japonicum by hydrodistillation and characterized by GC–MS. The main components of the oil were (E)-nerolidol (17.6%), (2E,4E)-decadienal (6.2%) and linalool (4.5%) (Liu et al., 2009b). 4. Conclusions Phytochemical studies led to the isolation of 431 secondary metabolites from genus Ganoderma. The major isolates are lanostane type triterpenoids (ganoderic acids, lucidenic acids), meroterpenoids, steroids and their various derivatives. More and more new molecules are being added periodically to the Ganoderma literature by various research groups. Most secondary metabolites isolated from Ganoderma showed biological potentials. However, the majority of the fungi in genus Ganoderma are not subjected to systematic studies so far. These factors reflect the need for more

phytochemical and biological activity studies on Ganoderma, particularly on the least investigated species.

97

genus

Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.phytochem.2015. 03.010. References Adams, M., Christen, M., Plitzko, I., Zimmermann, S., Brun, R., Kaiser, M., Hamburger, M., 2010. Antiplasmodial lanostanes from the Ganoderma lucidum mushroom. J. Nat. Prod. 73, 897–900. Akihisa, T., Tagata, M., Ukiya, M., Tokuda, H., Suzuki, T., Kimura, Y., 2005. Oxygenated lanostane-type triterpenoids from the fungus Ganoderma lucidum. J. Nat. Prod. 68, 559–563. Arisawa, M., Fujita, A., Saga, M., Fukumura, H., Hayashi, T., Shimizu, M., Morita, N., 1986. Three new lanostanoids from Ganoderma lucidum. J. Nat. Prod. 49, 621– 625. Boh, B., Hodzar, D., Dolnicar, D., Berovic, M., Pohleven, F., 2000. Isolation and quantification of triterpenoid acids from Ganoderma applanatum of Istrian origin. Food Technol. Biotechnol. 38, 11–18. Boh, B., Berovic, M., Zhang, J., Zhi-Bin, L., 2007. Ganoderma lucidum and its pharmaceutically active compounds. Biotechnol. Annu. Rev. 13, 265–301. Camargo, M.R., Kaneno, R., 2011. Antitumor properties of Ganoderma lucidum polysaccharides and terpenoids. Annu. Rev. Biomed. Sci. 13, 1–8. Cao, Y., Wu, S.H., Dai, Y.C., 2012. Species clarification of the prize medicinal Ganoderma mushroom ‘‘Lingzhi’’. Fungal Divers. 56, 49–62. Chairul, Tokuyama, T., Nishizawa, M., Shiro, M., Tokuda, H., Hayashi, Y., 1990. Malonate half-esters of homolanostanoid from an Asian Ganoderma fungus. Phytochemistry 29, 923–928. Chairul, Tokuyama, T., Hayashi, Y., Nishizawa, M., Tokuda, H., Chairul, S.M., Hayashi, Y., 1991. Applanoxidic acids A, B, C and D, biologically active tetracyclic triterpenes from Ganoderma applanatum. Phytochemistry 30, 4105–4109. Chairul, Chairul, S.M., Hayashi, Y., 1994. Lanostanoid triterpenes from Ganoderma applanatum. Phytochemistry 35, 1305–1308. Chen, R.Y., Yu, D.Q., 1991. Application of 2d NMR techniques in the structure determination of ganosporelactone A and B. Yao Xue Xue Bao 26, 430–436. Chen, R.Y., Yu, D.Q., 1993. Studies on the triterpenoid constituents of the spores from Ganoderma lucidum Karst. J. Chin. Pharm. Sci. 2, 91–96. Chen, D.H., Shiou, W.Y., Wang, K.C., Huang, S.Y., Shie, Y.T., Tsai, C.M., Shie, J.F., Chen, K.D., 1999. Chemotaxonomy of triterpenoid pattern of HPLC of Ganoderma lucidum and Ganoderma tsugae. J. Chin. Chem. Soc. 46, 47–51. Chen, X., Hu, Z.P., Yang, X.X., Huang, M., Gao, Y., Tang, W., Chan, S.Y., Dai, X., Ye, J., Ho, P.C., Duan, W., Yang, H.Y., Zhu, Y.Z., Zhou, S.F., 2006. Monitoring of immune response to a herbal immune-modulator in patients with advanced colorectal cancer. Int. J. Immunopharmacol. 6, 499–508. Chen, M., Zhang, M., Sun, S., Xia, B., Zhang, H.Q., 2009a. A new triterpene from the fruiting bodies of Ganoderma lucidum. Yao Xue Xue Bao 44, 768–770. Chen, Y.K., Kuo, Y.H., Chiang, B.H., Lo, J.M., Sheen, L.Y., 2009b. Cytotoxic activities of 9,11-dehydroergosterol peroxide and ergosterol peroxide from the fermentation mycelia of Ganoderma lucidum cultivated in the medium containing leguminous plants on Hep 3B cells. J. Agric. Food Chem. 57, 5713– 5719. Chen, S., Xu, J., Liu, C., Zhu, Y., Nelson, D.R., Zhou, S., Li, C., Wang, L., Guo, X., Sun, Y., Luo, H., Li, Y., Song, J., Henrissat, B., Levasseur, A., Qian, J., Li, J., Luo, X., Shi, L., He, L., Xiang, L., Xu, X., Niu, Y., Li, Q., Han, M.V., Yan, H., Zhang, J., Chen, H., Lv, A., Wang, Z., Liu, M., Schwartz, D.C., Sun, C., 2012. Genome sequence of the model medicinal mushroom Ganoderma lucidum. Nat. Commun. 3, 913. Cheng, C.R., Yue, Q.X., Wu, Z.Y., Song, X.Y., Tao, S.J., Wu, X.H., Xu, P.P., Liu, X., Guan, S.H., Guo, D.A., 2010. Cytotoxic triterpenoids from Ganoderma lucidum. Phytochemistry 71, 1579–1585. de Silva, E.D., van der Sar, S.A., Santha, R.G., Wijesundera, R.L., Cole, A.L., Blunt, J.W., Munro, M.H., 2006. Lanostane triterpenoids from the Sri Lankan basidiomycete Ganoderma applanatum. J. Nat. Prod. 69, 1245–1248. El Dine, R.S., El Halawany, A.M., Ma, C.M., Hattori, M., 2008a. Anti-HIV-1 protease activity of lanostane triterpenes from the Vietnamese mushroom Ganoderma colossum. J. Nat. Prod. 71, 1022–1026. El Dine, R.S., El Halawany, A.M., Nakamura, N., Ma, C.M., Hattori, M., 2008b. New lanostane triterpene lactones from the Vietnamese mushroom Ganoderma colossum (FR.) C. F. BAKER. Chem. Pharm. Bull. 56, 642–646. El Dine, R.S., El Halawany, A.M., Ma, C.M., Hattori, M., 2009. Inhibition of the dimerization and active site of HIV-1 protease by secondary metabolites from the Vietnamese mushroom Ganoderma colossum. J. Nat. Prod. 72, 2019–2023. El-Mekkawy, S., Meselhy, M.R., Nakamura, N., Tezuka, Y., Hattori, M., Kakiuchi, N., Shimotohno, K., Kawahata, T., Otake, T., 1998. Anti-HIV-1 and anti-HIV-1 protease substances from Ganoderma lucidum. Phytochemistry 49, 1651–1657. Eo, S.K., Kim, Y.S., Lee, C.K., Han, S.S., 1999a. Antiviral activities of various water and methanol soluble substances isolated from Ganoderma lucidum. J. Ethnopharmacol. 68, 129–136. Eo, S.K., Kim, Y.S., Lee, C.K., Han, S.S., 1999b. Antiherpetic activities of various protein bound polysaccharides isolated from Ganoderma lucidum. J. Ethnopharmacol. 68, 175–181.

98

S. Baby et al. / Phytochemistry 114 (2015) 66–101

Fatmawati, S., Shimizu, K., Kondo, R., 2010. Ganoderic acid Df, a new triterpenoid with aldose reductase activity from the fruiting body of Ganoderma lucidum. Fitoterapia 81, 1033–1036. Fujita, A., Arisawa, M., Saga, M., Hayashi, T., Morita, N., 1986. Two new lanostanoids from Ganoderma lucidum. J. Nat. Prod. 49, 1122–1125. Fujita, R., Liu, J., Shimizu, K., Konishi, F., Noda, K., Kumamoto, S., Ueda, C., Tajiri, H., Kaneko, S., Suimi, Y., Kondo, R., 2005. Anti-androgenic activities of Ganoderma lucidum. J. Ethnopharmacol. 102, 107–112. Fushimi, K., Horikawa, M., Suzuki, K., Sekiya, A., Kanno, S., Shimura, S., Kawagishi, H., 2010. Applanatines A–E from the culture broth of Ganoderma applanatum. Tetrahedron 66, 9332–9335. Gan, K.H., Fann, Y.F., Hsu, S.H., Kuo, K.W., Lin, C.N., 1998a. Mediation of the cytotoxicity of lanostanoids and steroids of Ganoderma tsugae through apoptosis and cell cycle. J. Nat. Prod. 61, 485–487. Gan, K.H., Kuo, S.H., Lin, C.N., 1998b. Steroidal constituents of Ganoderma applanatum and Ganoderma neo-japonicum. J. Nat. Prod. 61, 1421–1422. Gao, J.J., Min, B.S., Ahn, E.M., Nakamura, N., Lee, H.K., Hattori, M., 2002. New triterpene aldehydes, lucialdehyde A–C, from Ganoderma lucidum and their cytotoxicity against murine and human tumor cells. Chem. Pharm. Bull. 50, 837–840. Gao, J.J., Nakamura, N., Min, B.S., Hirakawa, A., Zuo, F., Hattori, M., 2004. Quantitative determination of bitter principle in specimens of Ganoderma lucidum using high-performance liquid chromatography and its application to the evaluation of Ganoderma products. Chem. Pharm. Bull. 52, 688–695. González, A.G., León, F., Rivera, A., Muñoz, C.M., Bermejo, J., 1999. Lanostanoid triterpenes from Ganoderma lucidum. J. Nat. Prod. 62, 1700–1701. Gonzalez, A.G., Leon, F., Rivera, A., Padron, J.I., Gonzalez-Plata, J., Zuluaga, J.C., Quintana, J., Estevez, F., Bermejo, J., 2002. New lanostanoids from the fungus Ganoderma concinna. J. Nat. Prod. 65, 417–421. Guan, S.H., Yang, M., Wang, X.M., Xia, J.M., Zhang, Z.M., Liu, X., Guo, D.A., 2007. Structure elucidation and complete NMR spectral assignments of three new lanostanoid triterpenes with unprecedented D16,17 double bond from Ganoderma lucidum. Magn. Reson. Chem. 45, 789–791. Ha, T.B.T., Gerhäuser, C., Zhang, W.D., Ho-Chong-Line, N., Fourasté, I., 2000. New lanostanoids from Ganoderma lucidum that induce NAD(P)H:qui-none oxidoreductase in cultured Hepalclc7 murine hepatoma cells. Planta Med. 66, 681–684. Hajjaj, H., Mace, C., Roberts, M., Niederberger, P., Fay, L.B., 2005. Effect of 26oxygenosterols from Ganoderma lucidum and their activity as cholesterol synthesis inhibitors. Appl. Environ. Microbiol. 71, 3653–3658. Hikino, H., Ishiyama, M., Suzuki, Y., Konno, C., 1989. Mechanisms of hypoglycaemic activity of ganoderan B: a glycan of Ganoderma lucidum fruit bodies. Planta Med. 55, 423–428. Hill, R.A., Connolly, J.D., 2012. Triterpenoids. Nat. Prod. Rep. 29, 780–818. Hill, R.A., Connolly, J.D., 2013. Triterpenoids. Nat. Prod. Rep. 30, 1028–1065. Hirotani, M., Furuya, T., 1986. Ganoderic acid derivatives, highly oxygenated lanostane-type triterpenoids, from Ganoderma lucidum. Phytochemistry 25, 1189–1193. Hirotani, M., Furuya, T., Shiro, M., 1985. A ganoderic acid derivative, a highly oxygenated lanostane-type triterpenoid from Ganoderma lucidum. Phytochemistry 24, 2055–2061. Hirotani, M., Ino, C., Furuya, T., Shiro, M., 1986. Ganoderic acids T, S and R, new triterpenoids from the cultured mycelium of Ganoderma lucidum. Chem. Pharm. Bull. 34, 2282–2285. Hirotani, M., Asaka, I., Ino, C., Furuya, T., Shiro, M., 1987. Ganoderic acid derivatives and ergosta-4,7,22-triene-3,6-dione from Ganoderma lucidum. Phytochemistry 26, 2797–2803. Hirotani, M., Furuya, T., Shiro, M., 1991. Cryptoporic acids H and I, drimane sesquiterpenes from Ganoderma neo-japonicum and Cryptoporus volvatus. Phytochemistry 30, 1555–1559. Hirotani, M., Ino, C., Furuya, T., 1993. Comparative study on the strain-specific triterpenoid components of Ganoderma lucidum. Phytochemistry 33, 379–382. Hirotani, M., Ino, C., Hatano, A., Takayanagi, H., Furuya, T., 1995. Ganomastenols A, B, C and D, cadinene sesquiterpenes, from Ganoderma mastoporum. Phytochemistry 40, 161–165. Hu, L.L., Ma, Q.Y., Huang, S.Z., Guo, Z.K., Ma, H.X., Guo, J.C., Dai, H.F., Zhao, Y.X., 2013. Three new lanostanoid triterpenes from the fruiting bodies of Ganoderma tropicum. J. Asian Nat. Prod. Res. 15, 357–362. Hu, L.L., Ma, Q.Y., Huang, S.Z., Guo, Z.K., Ma, H.X., Guo, J.C., Dai, H.F., Zhao, Y.X., 2014. A new nortriterpenoid from the fruiting bodies of Ganoderma tropicum. Phytochem. Lett. 7, 11–13. Isaka, M., Chinthanom, P., Kongthong, S., Srichomthong, K., Choeyklin, R., 2013. Lanostane triterpenes from cultures of the basidiomycete Ganoderma orbiforme BCC 22324. Phytochemistry 87, 133–139. Iwatsuki, K., Akihisa, T., Tokuda, H., Ukiya, M., Oshikubo, M., Kimura, Y., Asano, T., Nomura, A., Nishino, H., 2003. Lucidenic acid P and Q, methyl lucidenate P and other triterpenoids from the fungus Ganoderma lucidum and their inhibitory effects on Epstein–Barr Virus activation. J. Nat. Prod. 66, 1582–1585. Jain, A.C., Gupta, S.K., 1984. The isolation of lanosta-7,9(11),24-trien-3b,21-diol from the fungus Ganoderma australe. Phytochemistry 23, 686–687. Jin-Ming, G., 2006. New biologically active metabolites from Chinese higher fungi. Curr. Org. Chem. 10, 849–871. Jonathan, S.G., Kigigha, L.T., Ohimain, E., 2008. Evaluation of the inhibitory potentials of eight higher Nigerian fungi against pathogenic microorganisms. Afr. J. Biomed. Res. 11, 197–202.

Jong, S.C., Birmingham, J.M., 1992. Medicinal benefits of the mushroom Ganoderma. Adv. Appl. Microbiol. 37, 101–134. Joseph, S., Sabulal, B., George, V., Smina, T.P., Janardhanan, K.K., 2009. Antioxidative and antiinflammatory activities of the chloroform extract of Ganoderma lucidum found in south India. Sci. Pharm. 77, 111–121. Joseph, S., Janardhanan, K.K., George, V., Sabulal, B., 2011a. A new epoxidic ganoderic acid and other phytoconstituents from Ganoderma lucidum. Phytochem. Lett. 4, 386–388. Joseph, S., Sabulal, B., George, V., Antony, K.R., Janardhanan, K.K., 2011b. Antitumor and anti-inflammatory activities of polysaccharides isolated from Ganoderma lucidum. Acta Pharm. 61, 335–342. Jung, M., Liermann, J.C., Opatz, T., Erkel, G., 2011. Ganodermycin, a novel inhibitor of CXCL10 expression from Ganoderma applanatum. J. Antibiot. 64, 683–686. Keller, A.C., Keller, J., Maillard, M.P., Hostettmann, K., 1997. A lanostane-type steroid from the fungus Ganoderma carnosum. Phytochemistry 46, 963–965. Kikuchi, T., Matsuda, S., Kadota, S., Murai, Y., Ogita, Z.I., 1985a. Ganoderic acid D, E, F and H and lucidenic acid D, E and F, new triterpenoids from Ganoderma lucidum. Chem. Pharm. Bull. 33, 2624–2627. Kikuchi, T., Matsuda, S., Murai, Y., Ogita, Z., 1985b. Ganoderic acid G and I and ganolucidic acid A and B, new triterpenoids from Ganoderma lucidum. Chem. Pharm. Bull. 33, 2628–2631. Kikuchi, T., Kanomi, S., Kadota, S., Murai, Y., Tsubono, K., Ogita, Z.I., 1986a. Constituents of the fungus Ganoderma lucidum (FR.) KARST. I. Structures of ganoderic acids C2, E, I, and K, lucidenic acid F and related compounds. Chem. Pharm. Bull. 34, 3695–3712. Kikuchi, T., Kanomi, S., Murai, Y., Kadota, S., Tsubono, K., Ogita, Z.I., 1986b. Constituents of the fungus Ganoderma lucidum (FR.) KARST. II. Structures of ganoderic acids F, G and H, lucidenic acids D2 and E2, and related compounds. Chem. Pharm. Bull. 34, 4018–4029. Kikuchi, T., Kanomi, S., Murai, Y., Kadota, S., Tsubono, K., Ogita, Z.I., 1986c. Constituents of the fungus Ganoderma lucidum (Fr.) Karst. III. Structure of ganolucidic acids A and B, new lanostane-type triterpenoids. Chem. Pharm. Bull. 34, 4030–4036. Kim, H.W., Kim, B.K., 1999. Biomedicinal triterpenoids of Ganoderma lucidum (Curt.:Fr.) P. Karst. (Aphyllophoromycetideae). Int. J. Med. Mushrooms 1, 121–138. Kim, M.J., Kim, H.W., Lee, Y.S., Shim, M.J., Choi, E.C., Kim, B.K., 1986. Studies on safety of Ganoderma lucidum. Korean J. Mycol. 14, 49–59. Kim, D.H., Shim, S.B., Kim, N.J., Jang, I.S., 1999. Beta-glucuronidase-inhibitory activity and hepatoprotective effect of Ganoderma lucidum. Biol. Pharm. Bull. 22, 162–164. Kimura, Y., Taniguchi, M., Baba, K., 2002. Antitumor and antimetastatic effects on liver of triterpenoid fractions of Ganoderma lucidum: mechanism of action and isolation of an active substance. Anticancer Res. 22, 3309–3318. Kleinwächter, P., Anh, N., Kiet, T.T., Schlegel, B., Dahse, H.M., Härtl, A., Gräfe, U., 2001. Colossolactones, new triterpenoid metabolites from a Vietnamese mushroom Ganoderma colossum. J. Nat. Prod. 64, 236–239. Ko, H.H., Hung, C.F., Wang, J.P., Lin, C.N., 2008. Antiinflammatory triterpenoids and steroids from Ganoderma lucidum and G. tsugae. Phytochemistry 69, 234–239. Kohda, H., Tokumoto, W., Sakamoto, K., Fujii, M., Hirai, Y., Yamasaki, K., Komoda, Y., Nakamura, H., Ishihara, S., Uchida, M., 1985. The biologically active constituents of Ganoderma lucidum (Fr.) Karst. Histamine release-inhibitory triterpenes. Chem. Pharm. Bull. 33, 1367–1374. Komoda, Y., Nakamura, H., Ishihara, S., Uchida, M., Kohda, H., Yamasaki, K., 1985. Structures of new triterpenoid constituents of Ganoderma lucidum (Fr.) Karst (Polyporaceae). Chem. Pharm. Bull. 33, 4829–4835. Komoda, Y., Shimizu, M., Sonoda, Y., Sato, Y., 1989. Ganoderic acid and its derivatives as cholesterol synthesis inhibitors. Chem. Pharm. Bull. 37, 531–533. Koyama, K., Imaizumi, T., Akiba, M., Kinoshita, K., Takahashi, K., Suzuki, A., Yano, S., Horie, S., Watanabe, K., Naoi, Y., 1997. Antinociceptive components of Ganoderma lucidum. Planta Med. 63, 224–227. Kubota, T., Asaka, Y., Miura, I., Mori, H., 1982. Structures of ganoderic acid A and B, two new type bitter triterpenes from Ganoderma lucidum (Fr.) Karst. Helv. Chim. Acta 65, 611–619. La Clair, J.J., Rheingold, A.L., Burkart, M.D., 2011. Ganodone, a bioactive benzofuran from the fruiting bodies of Ganoderma tsugae. J. Nat. Prod. 74, 2045–2051. Lakornwong, W., Kanokmedhakul, K., Kanokmedhakul, S., Kongsaeree, P., Prabpai, S., Sibounnavong, P., Soytong, K., 2014. Triterpene lactones from cultures of Ganoderma sp. KM01. J. Nat. Prod. 77, 1545–1553. Lee, S., Park, S., Oh, J.W., Yang, C., 1998. Natural inhibitors for protein prenyltransferase. Planta Med. 64, 303–308. Lee, J.M., Kwon, H., Jeong, H., Lee, J.W., Lee, S.Y., Baek, S.J., Surh, Y.J., 2001. Inhibition of lipid peroxidation and oxidative DNA damage by Ganoderma lucidum. Phytother. Res. 15, 245–249. Lee, S., Shim, S.H., Kim, J.S., Shin, K.H., Kang, S.S., 2005. Aldose reductase inhibitors from the fruiting bodies of Ganoderma applanatum. Biol. Pharm. Bull. 28, 1103–1105. Lee, S.H., Shim, S.H., Kim, J.S., Kang, S.S., 2006. Constituents from the fruiting bodies of Ganoderma applanatum and their aldose reductase inhibitory activity. Arch. Pharm. Res. 29, 479–483. Lee, I., Kim, H., Youn, U., Kim, J., Min, B., Jung, H., Na, M., Hattori, M., Bae, K., 2010a. Effect of lanostane triterpenes from the fruiting bodies of Ganoderma lucidum on adipocyte differentiation in 3T3-L1 cells. Planta Med. 76, 1558–1563. Lee, I., Seo, J., Kim, J., Kim, H., Youn, U., Lee, J., Jung, H., Na, M., Hattori, M., Min, B., Bae, K., 2010b. Lanostane triterpenes from the fruiting bodies of Ganoderma lucidum and their inhibitory effects on adipocyte differentiation in 3T3-L1 cells. J. Nat. Prod. 73, 172–176.

S. Baby et al. / Phytochemistry 114 (2015) 66–101 Lee, I., Ahn, B., Choi, J., Hattori, M., Min, B., Bae, K., 2011a. Selective cholinesterase inhibition by lanostane triterpenes from fruiting bodies of Ganoderma lucidum. Bioorg. Med. Chem. Lett. 21, 6603–6607. Lee, S.Y., Kim, J.S., Lee, S., Kang, S.S., 2011b. Polyoxygenated ergostane-type sterols from the liquid culture of Ganoderma applanatum. Nat. Prod. Res. 25, 1304– 1311. León, F., Valencia, M., Rivera, A., Nieto, I., Quintana, J., Estévez, F., Bermejo, J., 2003. Novel cytostatic lanostanoid triterpenes from Ganoderma australe. Helv. Chim. Acta 86, 3088–3095. Leung, S.W.S., Yeung, K.Y., Ricky, Y.L.S., Man, Y.K., 2002. Lingzhi (Ganoderma) research: the past, present and future perspectives. In: Lin, Z.B. (Ed.), Ganoderma: Genetics, Chemistry, Pharmacology and Therapeutics. Beijing Medical University Press, Beijing, pp. 1–9. Li, C.H., Chen, P.Y., Chang, U.M., Kan, L.S., Fang, W.H., Tsai, K.S., Lin, S.B., 2005a. Ganoderic acid X, a lanostanoid triterpene, inhibits topoisomerases and induces apoptosis of cancer cells. Life Sci. 77, 252–265. Li, C., Yin, J., Guo, F., Zhang, D., Sun, H.H., 2005b. Ganoderic acid Sz, a new lanostanoid from the mushroom Ganoderma lucidum. Nat. Prod. Res. 19, 461– 465. Li, C., Li, Y., Sun, H.H., 2006. New ganoderic acids, bioactive triterpenoid metabolites from the mushroom Ganoderma lucidum. Nat. Prod. Res. 20, 985–991. Li, Y.-Y., Mi, Z.-Y., Tang, Y., Wang, G., Li, D.-S., Tang, Y.-J., 2009. Lanostanoids isolated from Ganoderma lucidum mycelium cultured by submerged fermentation. Helv. Chim. Acta 92, 1586–1593. Li, J., Zhang, J., Chen, H., Chen, X., Lan, J., Liu, C., 2013a. Complete mitochondrial genome of the medicinal mushroom Ganoderma lucidum. PLoS One 8, e72038. Li, P., Deng, Y.P., Wei, X.X., Xu, J.H., 2013b. Triterpenoids from Ganoderma lucidum and their cytotoxic activities. Nat. Prod. Res. 27, 17–22. Li, Y.B., Liu, R.M., Zhong, J.J., 2013c. A new ganoderic acid from Ganoderma lucidum mycelia and its stability. Fitoterapia 84, 115–122. Liang, C.X., Li, Y.B., Xu, J.W., Wang, J.L., Miao, X.L., Tang, Y.J., Gu, T., Zhong, J.J., 2010. Enhanced biosynthetic gene expressions and production of ganoderic acids in static liquid culture of Ganoderma lucidum under phenobarbital induction. Appl. Microbiol. Biotechnol. 86, 1367–1374. Liew, C.W., Lee, S.S., Wang, S.Y., 1992. The effect of Ganoderma lucidum on induction of differentiation in leukemia U937 cells. Anticancer Res. 12, 1211–1216. Lin, L.J., Shiao, M.S., Yeh, S.F., 1988a. Seven new triterpenes from Ganoderma lucidum. J. Nat. Prod. 51, 918–924. Lin, L.J., Shiao, M.S., Yeh, S.F., 1988b. Triterpenes from Ganoderma lucidum. Phytochemistry 27, 2269–2271. Lin, C.N., Tome, W.P., Won, S.J., 1990. A lanostanoid of formosan Ganoderma lucidum. Phytochemistry 29, 673–675. Lin, C.N., Tome, W.P., Won, S.J., 1991. Novel cytotoxic principles of Formosan Ganoderma lucidum. J. Nat. Prod. 54, 998–1002. Lin, C.N., Kuo, S.H., Won, S.J., 1993. Steroids of formosan Ganoderma amboinense. Phytochemistry 32, 1549–1551. Lin, J.M., Lin, C.C., Chen, M.F., Ujiie, T., Takada, A., 1995. Radical scavenger and antihepatotoxic activity of Ganoderma formosanum, Ganoderma lucidum and Ganoderma neo-japonicum. J. Ethnopharmacol. 47, 33–41. Lin, C.N., Fann, Y.F., Chung, M.I., 1997. Steroids of formosan Ganoderma tsugae. Phytochemistry 46, 1143–1146. Lin, S.B., Li, C.H., Lee, S.S., Kan, L.S., 2003. Triterpene-enriched extracts from Ganoderma lucidum inhibit growth of hepatoma cells via suppressing protein kinase C, activating mitogen-activated protein kinase and G2-phase cell cycle arrest. Life Sci. 72, 2381–2390. Lin, K.W., Chen, Y.T., Yang, S.C., Wei, B.L., Hung, C.F., Lin, C.N., 2013. Xanthine oxidase inhibitory lanostanoids from Ganoderma tsugae. Fitoterapia 89, 231– 238. Liu, J., Shimizi, K., Kondo, R., 2006. Ganoderic acid TR, a new lanostanoid with 5areductase inhibitory activity from the fruiting body of Ganoderma lucidum. Nat. Prod. Commun. 1, 345–350. Liu, J., Shimizu, K., Konishi, F., Noda, K., Kumamoto, S., Kurashiki, K., Kondo, R., 2007. Antiandrogenic activities of the triterpenoids fraction of Ganoderma lucidum. Food Chem. 100, 1691–1696. Liu, Y.W., Gao, J.L., Guan, J., Qian, Z.M., Feng, K., Li, S.P., 2009a. Evaluation of antiproliferative activities and action mechanisms of extracts from two species of Ganoderma on tumor cell lines. J. Agric. Food Chem. 57, 3087–3093. Liu, D., Hu, Z., Liu, Z., Yang, B., Tu, W., Li, L., 2009b. Chemical composition and antimicrobial activity of essential oil isolated from the cultured mycelia of Ganoderma japonicum. J. Nanjing Med. Univ. 23, 168–172. Liu, C., Zhao, F., Chen, R., 2010. A novel alkaloid from the fruiting bodies of Ganoderma sinense Zhao, Xu et Zhang. Chin. Chem. Lett. 21, 197–199. Liu, J.Q., Wang, C.F., Peng, X.R., Qiu, M.H., 2011. New alkaloids from the fruiting bodies of Ganoderma sinense. Nat. Prod. Bioprospect. 1, 93–96. Liu, J., Shimizu, K., Tanaka, A., Shinobu, W., Ohnuki, K., Nakamura, T., Kondo, R., 2012a. Target proteins of ganoderic acid DM provides clues to various pharmacological mechanisms. Sci. Rep. 2, 905. Liu, J.Q., Wang, C.F., Li, Y., Luo, H.R., Qiu, M.H., 2012b. Isolation and bioactivity evaluation of terpenoids from the medicinal fungus Ganoderma sinense. Planta Med. 78, 368–376. Liu, D.Z., Zhu, Y.Q., Li, X.F., Shan, W.G., Gao, P.F., 2014a. New triterpenoids from the fruiting bodies of Ganoderma lucidum and their bioactivities. Chem. Biodivers. 11, 982–986. Liu, L.Y., Chen, H., Liu, C., Wang, H.Q., Kang, J., Li, Y., Chen, R.Y., 2014b. Triterpenoids of Ganoderma theaecolum and their hepatoprotective activities. Fitoterapia 98, 254–259.

99

Luo, J., Zhao, Y.Y., Lin, Z.B., 2002. A new lanostane-type triterpene from the fruiting bodies of Ganoderma lucidum. J. Asian Nat. Prod. Res. 4, 129–134. Ma, J., Ye, Q., Hua, Y., Zhang, D., Cooper, R., Chang, M.N., Chang, J.Y., Sun, H.H., 2002. New lanostanoids from the mushroom Ganoderma lucidum. J. Nat. Prod. 65, 72–75. Ma, B.J., Zhou, Y., Ruan, Y., Ma, J.C., Ren, W., Wen, C.N., 2012. Lanostane-type triterpenes from the sporoderm-broken spores of Ganoderma lucidum. J. Antibiot. 65, 165–167. Ma, Q.Y., Luo, Y., Huang, S.Z., Guo, Z.K., Dai, H.F., Zhao, Y.X., 2013. Lanostane triterpenoids with cytotoxic activities from the fruiting bodies of Ganoderma hainanense. J. Asian Nat. Prod. Res. 15, 1214–1219. Ma, K., Ren, J., Han, J., Bao, L., Li, L., Yao, Y., Sun, C., Zhou, B., Liu, H., 2014. Ganoboninketals A–C, antiplasmodial 3,4-seco-27-norlanostane triterpenes from Ganoderma boninense Pat. J. Nat. Prod. 77, 1847–1852. Mahato, S.B., Kundu, A.P., 1994. 13C NMR spectra of pentacyclic triterpenoids – a compilation and some salient features. Phytochemistry 37, 1517–1575. Mau, J.L., Tsai, S.Y., Tseng, Y.H., Huang, S.J., 2005. Antioxidant properties of methanolic extracts from Ganoderma tsugae. Food Chem. 93, 641–649. Min, B.S., Nakamura, N., Miyashiro, H., Bae, K.W., Hattori, M., 1998. Triterpenes from the spores of Ganoderma lucidum and their inhibitory effect against HIV-1 protease. Chem. Pharm. Bull. 46, 1607–1612. Min, B.S., Gao, J.J., Nakamura, N., Hattori, M., 2000. Triterpenes from the spores of Ganoderma lucidum and their cytotoxicity against meth-A and LLC tumor cells. Chem. Pharm. Bull. 48, 1026–1033. Min, B.S., Gao, J.J., Hattori, M., Lee, H.K., Kim, Y.H., 2001. Anticomplement activity of terpenoids from the spores of Ganoderma lucidum. Planta Med. 67, 811–814. Ming, D., Chilton, J., Fogarty, F., Towers, G.H., 2002. Chemical constituents of Ganoderma applanatum of British Columbia forests. Fitoterapia 73, 147–152. Mizushina, Y., Hanashima, L., Yamaguchi, T., Takemura, M., Sugawara, F., Saneyoshi, M., Matsukage, A., Yoshida, S., Sakaguchi, K., 1998a. A mushroom fruiting bodyinducing substance inhibits activities of replicative DNA polymerases. Biochem. Biophys. Res. Commun. 249, 17–22. Mizushina, Y., Watanabe, I., Togashi, H., Hanashima, L., Takemura, M., Ohta, K., Sugawara, F., Koshino, H., Esumi, Y., Uzawa, J., Matsukage, A., Yoshida, S., Sakaguchi, K., 1998b. An ergosterol peroxide, a natural product that selectively enhances the inhibitory effect of linoleic acid on DNA polymerase b. Biol. Pharm. Bull. 21, 444–448. Mizushina, Y., Takahashi, N., Hanashima, L., Koshino, H., Esumi, Y., Uzawa, J., Suqawara, F., Sakaquchi, K., 1999. Lucidenic acid O and lactone, new terpene inhibitors of eukaryotic DNA polymerases from a basidiomycete, Ganoderma lucidum. Bioorg. Med. Chem. 7, 2047–2052. Morigiwa, A., Kitabatake, K., Fujimoto, Y., Ikekawa, N., 1986. Angiotensin converting enzyme-inhibitory triterpenes from Ganoderma lucidum. Chem. Pharm. Bull. 34, 3025–3028. Mothana, R.A.A., Jansen, R., Julich, W.D., Lindequist, U., 2000. Ganomycins A and B, new antimicrobial farnesyl hydroquinones from the basidiomycete Ganoderma pfeifferi. J. Nat. Prod. 63, 416–418. Mothana, R.A.A., Awadh Ali, N.A., Jansen, R., Wegner, U., Mentel, R., Lindequist, U., 2003. Antiviral lanostanoid triterpenes from the fungus Ganoderma pfeifferi. Fitoterapia 74, 177–180. Muller, C.I., Kumagai, T., Okelly, J., Seeram, N.P., Heber, D., Koeffler, H.P., 2006. Ganoderma lucidum causes apoptosis in leukemia, lymphoma and multiple myeloma cells. Leuk. Res. 30, 841–848. Ngai, P.H.K., Ng, T.B., 2004. A mushroom (Ganoderma capense) lectin with spectacular thermostability, potent mitogenic activity on splenocytes and antiproliferative activity toward tumor cells. Biochem. Biophys. Res. Commun. 314, 988–993. Niedermeyer, T.H.J., Lindequist, U., Mentel, R., Gördes, D., Schmidt, E., Thurow, K., Lalk, M., 2005. Antiviral terpenoid constituents of Ganoderma pfeifferi. J. Nat. Prod. 68, 1728–1731. Niedermeyer, T.H.J., Jira, T., Lalk, M., Lindequist, U., 2013. Isolation of farnesylhydroquinones from the basidiomycete Ganoderma pfeifferi. Nat. Products Bioprospect. 3, 137–140. Nishitoba, T., Sato, H., Kasai, T., Kawagishi, H., Sakamura, S., 1984. New bitter C27 and C30 terpenoids from the fungus Ganoderma lucidum (Reishi). Agric. Biol. Chem. 48, 2905–2907. Nishitoba, T., Sato, H., Sakamura, S., 1985a. New terpenoids from Ganoderma lucidum and their bitterness. Agric. Biol. Chem. 49, 1547–1549. Nishitoba, T., Sato, H., Sakamura, S., 1985b. New terpenoids, ganoderic acid J and ganolucidic acid C, from the fungus Ganoderma lucidum. Agric. Biol. Chem. 49, 3637–3638. Nishitoba, T., Sato, H., Kasai, T., Kawagishi, H., Sakamura, S., 1985c. New bitter C27 and C30 terpenoids from the fungus Ganoderma lucidum (Reishi). Agric. Biol. Chem. 49, 1793–1798. Nishitoba, T., Sato, H., Sakamura, S., 1986a. New terpenoids, ganolucidic acid D, ganoderic acid L, lucidone C and lucidenic acid G, from the fungus Ganoderma lucidum. Agric. Biol. Chem. 50, 809–811. Nishitoba, T., Sato, H., Shirasu, S., Sakamura, S., 1986b. Evidence on the strainspecific terpenoid pattern of Ganoderma lucidum. Agric. Biol. Chem. 50, 2151– 2154. Nishitoba, T., Sato, H., Shirasu, S., Sakamura, S., 1987a. Novel triterpenoids from the mycelia mat at the previous stage of fruiting of Ganoderma lucidum. Agric. Biol. Chem. 51, 619–622. Nishitoba, T., Sato, H., Sakamura, S., 1987b. Novel mycelia components, Ganoderic acid Mg, Mh, Mi, Mj and Mk, from the fungus Ganoderma lucidum. Agric. Biol. Chem. 51, 1149–1153.

100

S. Baby et al. / Phytochemistry 114 (2015) 66–101

Nishitoba, T., Sato, H., Sakamura, S., 1987c. Triterpenoids from the fungus Ganoderma lucidum. Phytochemistry 26, 1777–1784. Nishitoba, T., Oda, K., Sato, H., Sakamura, S., 1988a. Novel triterpenoids from the fungus Ganoderma lucidum. Agric. Biol. Chem. 52, 367–372. Nishitoba, T., Sato, H., Oda, K., Sakamura, S., 1988b. Novel triterpenoids and a steroid from the fungus Ganoderma lucidum. Agric. Biol. Chem. 52, 211–216. Nishitoba, T., Goto, S., Sato, H., Sakamura, S., 1989. Bitter triterpenoids from the fungus Ganoderma applanatum. Phytochemistry 28, 193–197. Niu, X., Qiu, M., Li, Z., Lu, Y., Cao, P., Zheng, Q., 2004. Two novel 3,4-secotrinorlanostane triterpenoids isolated from Ganoderma fornicatum. Tetrahedron Lett. 45, 2989–2993. Niu, X.M., Li, S.H., Sun, H.D., Che, C.T., 2006. Prenylated phenolics from Ganoderma fornicatum. J. Nat. Prod. 69, 1364–1365. Niu, X.M., Li, S.H., Xiao, W.L., Sun, H.D., Che, C.T., 2007. Two new lanostanoids from Ganoderma resinaceum. J. Asian Nat. Prod. Res. 9, 659–664. Ofodile, L.N., Uma, N., Grayer, R.J., Ogundipe, O.T., Simmonds, M.S.J., 2012. Antibacterial compounds from the mushroom Ganoderma colossum from Nigeria. Phytother. Res. 26, 748–751. Paterson, R.R.M., 2006. Ganoderma – a therapeutic fungal biofactory. Phytochemistry 67, 1985–2001. Peng, X.R., Liu, J.Q., Han, Z.H., Yuan, X.X., Luo, H.R., Qiu, M.H., 2013. Protective effects of triterpenoids from Ganoderma resinaceum on H2O2-induced toxicity in HepG2 cells. Food Chem. 141, 920–926. Peng, X.R., Liu, J.Q., Wan, L.S., Li, X.N., Yan, Y.X., Qiu, M.H., 2014a. Four new polycyclic meroterpenoids from Ganoderma cochlear. Org. Lett. 16, 5262–5265. Peng, X.R., Liu, J.Q., Wang, C.F., Li, X.Y., Shu, Y., Zhou, L., Qiu, M.H., 2014b. Hepatoprotective effects of triterpenoids from Ganoderma cochlear. J. Nat. Prod. 77, 737–743. Qiao, Y., Zhang, X.M., Dong, X.C., Qiu, M.H., 2006. A new 18(13 ? 12b)-abeolanostadiene triterpenoid from Ganoderma fornicatum. Helv. Chim. Acta 89, 1038–1041. Qiao, Y., Zhang, X.M., Qiu, M.H., 2007. Two novel lanostane triterpenoids from Ganoderma sinense. Molecules 12, 2038–2046. Richter, C., Wittstein, K., Kirk, P.M., Stadler, M., 2015. An assessment of the taxonomy and chemotaxonomy of Ganoderma. Fungal Divers. 71, 1–15. Ríos, J.L., Andújar, I., Recio, M.C., Giner, R.M., 2012. Lanostanoids from fungi: a group of potential anticancer compounds. J. Nat. Prod. 75, 2016–2044. Rosecke, J., Konig, W.A., 2000. Constituents of various wood-rotting basidiomycetes. Phytochemistry 54, 603–610. Sanodiya, B.S., Thakur, G.S., Baghel, R.K., Prasad, G.B., Bisen, P.S., 2009. Ganoderma lucidum: a potent pharmacological macrofungus. Curr. Pharm. Biotechnol. 10, 717–742. Sato, H., Nishitoba, T., Shirasu, S., Oda, K., Sakamura, S., 1986. Ganderiol A and B, new triterpenoids from the fungus Ganoderma lucidum (Reishi). Agric. Biol. Chem. 50, 2887–2890. Sato, N., Ma, C.M., Komatsu, K., Hattori, M., 2009a. Triterpene–farnesyl hydroquinone conjugates from Ganoderma sinense. J. Nat. Prod. 72, 958–961. Sato, N., Zhang, Q., Ma, C.M., Hattori, M., 2009b. Anti-human immunodeficiency virus-1 protease activity of new lanostane-type triterpenoids from Ganoderma sinense. Chem. Pharm. Bull. 57, 1076–1080. Seo, G.S., Kirk, P.M., 2000. Ganodermataceae: nomenclature and classification. In: Flood, J., Bridge, P.D., Holderness, P. (Eds.), Ganoderma Disease of Perennial Crops. CABI Publishing, Wallingford, UK, pp. 3–22. Seo, H.W., Hung, T.M., Na, M., Jung, H.J., Kim, J.C., Choi, J.S., Kim, J.H., Lee, H.K., Lee, I., Bae, K., Hattori, M., Min, B.S., 2009. Steroids and triterpenes from the fruit bodies of Ganoderma lucidum and their anti-complement activity. Arch. Pharm. Res. 32, 1573–1579. Shi, L., Ren, A., Mu, D., Zhao, M., 2010. Current progress in the study on biosynthesis and regulation of ganoderic acids. Appl. Microbiol. Biotechnol. 88, 1243–1251. Shiao, M.S., 2003. Natural products of the medicinal fungus Ganoderma lucidum: occurrence, biological activities, and pharmacological functions. Chem. Rec. 3, 172–180. Shiao, M.S., Lin, L.J., Yeh, S.F., Chou, C.S., 1987. Two new triterpenes of the fungus Ganoderma lucidum. J. Nat. Prod. 50, 886–890. Shiao, M.S., Lin, L.J., Yeh, S.F., 1988a. Triterpenes in Ganoderma lucidum. Phytochemistry 27, 873–875. Shiao, M.S., Lin, L.J., Yeh, S.F., 1988b. Triterpenes from Ganoderma lucidum. Phytochemistry 27, 2911–2914. Shie, Y.H., Liu, C.F., Huang, Y.K., Yang, J.Y., Wu, I.L., Lin, C.H., Li, S.C., 2001. Evaluation of the hepatic and renal protective effects of Ganoderma lucidum in mice. Am. J. Chin. Med. 29, 501–507. Shim, S.H., Ryu, J., Kim, J.S., Kang, S.S., Xu, Y., Jung, S.H., Lee, Y.S., Lee, S., Shin, K.H., 2004. New lanostane-type triterpenoids from Ganoderma applanatum. J. Nat. Prod. 67, 1110–1113. Smania Jr., A., Monache, F.D., Smania, E.F.A., Cuneo, R.S., 1999. Antibacterial activity of steroidal compounds isolated from Ganoderma applanatum (Pers.) Pat. (Aphyllophoromycetideae) fruit body. Int. J. Med. Mushrooms 1, 325–330. Smania, E.F.A., Monache, F.D., Smania Jr., A., Yunes, R.A., Cuneo, R.S., 2003. Antifungal activity of sterols and triterpenes isolated from Ganoderma annulare. Fitoterapia 74, 375–377. Smania, E.F.A., Monache, F.D., Yunes, R.A., Paulert, R., Smania Jr., A., 2007. Antimicrobial activity of methyl australate from Ganoderma australe. Braz. J. Pharmacog. 17, 14–16. Sonoda, Y., Sekigawa, Y., Sato, Y., 1988. In vitro effects of oxygenated lanosterol derivatives on cholesterol biosynthesis from 24,25-dihydrolanosterol. Chem. Pharm. Bull. 36, 966–973.

Strigina, L.I., Elkin, Y.N., Elyakov, G.B., 1971. Steroid metabolites of Ganoderma applanatum basidiomycete. Phytochemistry 10, 2361–2365. Su, H.J., Fann, Y.F., Chung, M.I., Won, S.J., Lin, C.N., 2000. New lanostanoids of Ganoderma tsugae. J. Nat. Prod. 63, 514–516. Toth, J.O., Luu, B., Beck, J.-P., Ourisson, G., 1983a. Chemistry and biochemistry of oriental drugs. Part IX. Cytotoxic triterpenes from Ganoderma lucidum (Polyporaceae): structures of ganoderic acids U–Z. J. Chem. Res., 2722–2787 Toth, J.O., Luu, B., Ourisson, G., 1983b. Ganoderic acid T and Z: cytotoxic triterpenes from Ganoderma lucidum. Tetrahedron Lett. 24, 1081–1084. Toth, J.O., Luu, B., Beck, J.P., Ourisson, G., 1983c. Bitter triterpenoids from the fungus Ganoderma lucidum. J. Chem. Res., 2792–2795 Tung, N.T., Cuong, T.D., Hung, T.M., Lee, J.H., Woo, M.H., Choi, J.S., Kim, J., Ryu, S.H., Min, B.S., 2013. Inhibitory effect on NO production of triterpenes from the fruiting bodies of Ganoderma lucidum. Bioorg. Med. Chem. Lett. 23, 1428–1432. Wagner, R., Mitchell, D.A., Sassaki, G.L., Amazonas, M.A.L.D., Berovic, M., 2003. Current techniques for the cultivation of Ganoderma lucidum for the production of biomass, ganoderic acid and polysaccharides. Food Technol. Biotechnol. 41, 371–382. Wang, F., Liu, J.K., 2008. Highly oxygenated lanostane triterpenoids from the fungus Ganoderma applanatum. Chem. Pharm. Bull. 56, 1035–1037. Wang, G., Zhang, J., Mizuno, T., Zhuang, C., Ito, H., Mayuzumi, H., Okamoto, H., Li, J., 1993. Antitumor active polysaccharides from the Chinese mushroom Songshan Lingzhi, the fruiting body of Ganoderma tsugae. Biosci. Biotechnol. Biochem. 57, 894–900. Wang, F.S., Cai, H., Yang, J.S., Zhang, Y.M., Hou, C.Y., Liu, J.Q., Zhao, M.J., 1997a. Studies on the ganoderic acid, a new constituents from the fruiting body of Ganoderma lucidum (Fr.) Karst. Yao Xue Xue Bao 32, 447–450. Wang, F.S., Cai, H., Yang, J.S., Zhang, Y.M., Zhao, Y.J., 1997b. Triterpenoids from the fruiting body of Ganoderma lucidum. JCPS (J. Chin. Pharm. Sci.) 6, 192–197. Wang, X.M., Yang, M., Guan, S.H., Liu, R.X., Xia, J.M., Bi, K.S., Guo, D.A., 2006. Quantitative determination of six major triterpenoids in Ganoderma lucidum and related species by high performance liquid chromatography. J. Pharm. Biomed. Anal. 41, 838–844. Wang, C.F., Liu, J.Q., Yan, Y.X., Chen, J.C., Lu, Y., Guo, Y.H., Qiu, M.H., 2010a. Three new triterpenoids containing four-membered ring from the fruiting body of Ganoderma sinense. Org. Lett. 12, 1656–1659. Wang, J.L., Li, Y.B., Liu, R.M., Zhong, J.J., 2010b. A new ganoderic acid from Ganoderma lucidum mycelia. J. Asian Nat. Prod. Res. 12, 727–730. Wasser, S.P., 2005. Reishi or Ling Zhi (Ganoderma lucidum), Encyclopedia of Dietary Supplements. Marcel Dekker, New York, USA, pp. 603–622. Wasser, S.P., Weis, A.L., 1999. Therapeutic effects of substance occurring in higher Basidiomycetes mushrooms: a modern perspective. Crit. Rev. Immunol. 19, 65– 96. Weng, Y., Xiang, L., Matsuura, A., Zhang, Y., Huang, Q., Qi, J., 2010. Ganodermasides A and B, two novel anti-aging ergosterols from spores of a medicinal mushroom Ganoderma lucidum on yeast via UTH1 gene. Bioorg. Med. Chem. 18, 999–1002. Weng, Y., Lu, J., Xiang, L., Matsuura, A., Zhang, Y., Huang, Q., Qi, J., 2011. Ganodermasides C and D, two new anti-aging ergosterols from spores of the medicinal mushroom Ganoderma lucidum. Biosci. Biotechnol. Biochem. 75, 800– 803. Wu, T.S., Shi, L.S., Kuo, S.C., Cherng, C.Y., Tung, S.F., Teng, C.M., 1997. Platelet aggregation inhibitor from Ganoderma lucidum. J. Chin. Chem. Soc. 44, 157–161. Wu, T.S., Shi, L.S., Kuo, S.C., 2001. Cytotoxicity of Ganoderma lucidum triterpenes. J. Nat. Prod. 64, 1121–1122. Wu, Q.P., Xie, Y.Z., Deng, Z., Li, X.M., Yang, W., Jiao, C.W., Fang, L., Li, S.Z., Pan, H.H., Yee, A.J., Lee, D.Y., Li, C., Zhang, Z., Guo, J., Yang, B.B., 2012. Ergosterol peroxide isolated from Ganoderma lucidum abolishes microRNA miR-378-mediated tumor cells on chemoresistance. PLoS One 7, e44579. Wu, G.S., Song, Y.L., Yin, Z.Q., Guo, J.J., Wang, S.P., Zhao, W.W., Chen, X.P., Zhang, Q.W., Lu, J.-J., Wang, Y.T., 2013. Ganoderiol A-enriched extract suppresses migration and adhesion of MDA-MB-231 cells by inhibiting FAK-SRC-paxillin cascade pathway. PLoS One 8, e76620. Xu, J.W., Zhao, W., Zhong, J.J., 2010. Biotechnological production and application of ganoderic acids. Appl. Microbiol. Biotechnol. 87, 457–466. Yan, Y.M., Ai, J., Zhou, L.L., Chung, A.C., Li, R., Nie, J., Fang, P., Wang, X.L., Luo, J., Hu, Q., Hou, F.F., Cheng, Y.X., 2013. Lingzhiols, unprecedented rotary door-shaped meroterpenoids as potent and selective inhibitors of p-Smad3 from Ganoderma lucidum. Org. Lett. 15, 5488–5491. Yang, J.J., Yu, D.Q., 1990. Synthesis of ganoderma alkaloid A and B. Yao Xue Xue Bao 25, 555–559. Yang, M., Wang, X.M., Guan, S.H., Xia, J.M., Sun, J.H., Guo, H., Guo, D.A., 2007. Analysis of triterpenoids in Ganoderma lucidum using liquid chromatography coupled with electrospray ionization mass spectrometry. J. Am. Soc. Mass Spectrom. 18, 927–939. Yang, S.X., Yu, Z.C., Lu, Q.Q., Shi, W.Q., Laatsch, H., Gao, J.M., 2012. Toxic lanostane triterpenes from the basidiomycete Ganoderma amboinense. Phytochem. Lett. 5, 576–580. Yoon, S.Y., Eo, S.K., Kim, Y.S., Lee, C.K., Han, S.S., 1994. Antimicrobial activity of Ganoderma lucidum extract alone and in combination with some antibiotics. Arch. Pharm. Res. 17, 438–442. You, B.J., Lee, M.H., Tien, N., Lee, M.S., Hsieh, H.C., Tseng, L.H., Chung, Y.L., Lee, H.Z., 2013. A novel approach to enhancing ganoderic acid production by Ganoderma lucidum using apoptosis induction. PLoS One 8, e53616. Yue, Q.X., Song, X.Y., Ma, C., Feng, L.X., Guan, S.H., Wu, W.Y., Yang, M., Jiang, B.H., Liu, X., Cui, Y.J., Guo, D.A., 2010. Effects of triterpenes from Ganoderma lucidum on protein expression profile of HeLa cells. Phytomedicine 17, 606–613.

S. Baby et al. / Phytochemistry 114 (2015) 66–101 Yuen, J.W., Gohel, M.D., 2005. Anticancer effects of Ganoderma lucidum: a review of scientific evidence. Nutr. Cancer 53, 11–17. Zhang, C.R., Yang, S.P., Yue, J.M., 2008. Sterols and triterpenoids from the spores of Ganoderma lucidum. Nat. Prod. Res. 22, 1137–1142. Zhang, L., Ding, Z., Xu, P., Wang, Y., Gu, Z., Qian, Z., Shi, G., Zhang, K., 2011a. Methyl lucidenate F isolated from the ethanol-soluble-acidic components of Ganoderma lucidum is a novel tyrosinase inhibitor. Biotechnol. Bioprocess Eng. 16, 457–461. Zhang, X.Q., Ip, F.C., Zhang, D.M., Chen, L.X., Zhang, W., Li, Y.L., Ip, N.Y., Ye, W.C., 2011b. Triterpenoids with neurotrophic activity from Ganoderma lucidum. Nat. Prod. Res. 25, 1607–1613. Zhu, L.W., Zhong, J.J., Tang, Y.J., 2008. Significance of fungal elicitors on the production of ganoderic acid and Ganoderma polysaccharides by the submerged culture of medicinal mushroom Ganoderma lucidum. Process Biochem. 43, 1359–1370. Ziegenbein, F.C., Hanssen, H.P., Konig, W.A., 2006. Secondary metabolites from Ganoderma lucidum and Spongiporus leucomallellus. Phytochemistry 67, 202– 211.

Dr. Sabulal Baby is Senior Scientist and Head at the Phytochemistry and Phytopharmacology Division of Jawaharlal Nehru Tropical Botanic Garden and Research Institute at Palode, Thiruvananthapuram in India. Dr. Sabulal received his doctorate in Chemistry from the Indian Institute of Technology Bombay in 1997. He did postdoctoral research at the University of Pennsylvania, USA and the University of Toronto, Canada. His research areas are phytochemistry and biochemistry. He published over forty five peer reviewed publications in these research areas.

101 Dr. Anil John Johnson obtained his Ph. D. in Chemistry from Gandhigram Rural University, Tamil Nadu, India in 2009. He is currently working as Technical Officer at the Phytochemistry and Phytopharmacology Division of Jawaharlal Nehru Tropical Botanic Garden and Research Institute at Palode, Thiruvananthapuram in India. His research work is focused on chemistry of medicinal and aromatic plants. He has published over twenty five peer reviewed research papers.

Mr. Balaji Govindan is a postgraduate in Biotechnology from Kalasalingam University, Tamil Nadu, India. Presently he is doing doctoral research in phytochemistry at the Jawaharlal Nehru Tropical Botanic Garden and Research Institute at Palode, Thiruvananthapuram in India. His research interests are in secondary metabolites, their nutritional and biological aspects.

Suggest Documents