Secondary Metabolites from Plants Plant Secondary Metabolites

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3. Plant Secondary Metabolites. • Plants produce as amazing diversity of low molecular weight compounds. • Of the estimated 400,000 – 500,000 plant species ...

Secondary Metabolites from Plants

David S.-Y. Wang Assistant Professor Department of Forestry, NCHU

Plant Secondary Metabolites • Secondary metabolites are those metabolites which are often produced in a phase of subsequent to growth, have no function in growth (although they may have survival function), are produced by certain restricted taxonomic groups of microorganisms, have unusual chemicals structures, and are often formed as mixtures of closely related members of a chemical family. • The simplest definition of secondary products is that they are not generally included in standard metabolic charts.

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Plant Secondary Metabolites • A metabolic intermediate or product, found as a differentiation product in restricted taxonomic groups, not essential to growth and the life of the producing organism, and biosynthesis from one or more general metabolites by a wider variety of pathways than is available in general metabolism. • Secondary metabolites are not essential for growth and tend to be strain specific. They have a wide range of chemical structures and biological activities. They are derived by unique biosynthetic pathways from primary metabolites and intermediates.

Plant Secondary Metabolites • Biochemical pathways that are not necessary for growth or reproduction of an organism, but which can be demonstrated genetically, physiologically or biochemically.

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Plant Secondary Metabolites • Plants produce as amazing diversity of low molecular weight compounds. • Of the estimated 400,000 – 500,000 plant species around the globe, only a small percentage has been investigated phytochemically and the fraction subjected to biological or pharmacological screening is even lower.

Plant Secondary Metabolites • The ability to synthesize secondary metabolites has been selected through the course of evolution in different plant lineage when such compounds address specific needs. – Floral scent volatiles and pigments have evolved to attract insect pollinators and thus enhance fertilization. – To synthesize toxic chemical has evolved to ward off pathogens and herbivores or to suppress the growth of neighboring plants.

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Plant Secondary Metabolites – Chemicals found in fruits prevent spoilage and act as signals (in the form of color, aroma, and flavor) of the presence of potential rewards (sugars, vitamins and flavor) for animals that eat the fruit and thereby help to disperse the seeds. – Other chemicals serve cellular functions that are unique to the particular plant in which they occur (e.g. resistance to salt or drought).

Natural Products Drug Discovery and Development • Over the ages, human have relied on nature fro their basic needs for the production of foodstuffs, shelters, clothing, means of transportations, fertilizers, flavors and fragrances, and not least medicine. • Plants have formed the basis of sophisticated traditional medicine system that have been in existence thousands of years in countries such as China and India.

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Natural Products Drug Discovery and Development • About 25% of all prescriptions sold in the US are for natural products, while another 25% are for structural modifications of a natural products. • According to Fransworth (1990) claims that 119 characterized drugs are still obtained commercially from higher plants and that 74% were found from ethnobotanical information. . Fransworth, N.R. (1990) In bioactive compounds from plants. John and Wiley Co..

Primary and Secondary Metabolism • Primary metabolism – The biological reactions are essential to maintain life in living organisms and are known as primary metabolism. – Plant convert sunlight energy to chemical energy, such as ATP, NADPH, by the mediation of chlorophyll in chloroplasts and synthesize sugars and starch from CO2 by using ATP and NADPH+. – These carbohydrates are stored and used for differentiation and formation of plant tissues.

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Primary and Secondary Metabolism

• Secondary metabolism – The metabolisms which are not directly related to maintaining life, are known as secondary metabolisms. – The products formed by secondary metabolism are called secondary metabolites. – Secondary metabolite play a role in reinforcement of tissue and tree body (e.g. cellulose, lignin, suberin), protection against insects, dieses, and plant regulation (plant hormones).

Primary and Secondary Metabolism • All organisms need to transform and interconvert a vast number of organic compounds to enable them to live, grow and reproduce. • All organisms need to provide themselves with energy in the form of ATP, and a supply of building blocks to construct their own tissues. • An integrated network of enzyme-mediated and carefully regulated chemical reactions in used for this purpose, collectively referred to as intermediary metabolism, and the pathways involved are termed metabolic pathway.

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Primary and Secondary Metabolism • The pathways for generally modifying and synthesizing carbohydrates, proteins, fats, and nucleic acids are found to be essentially to same in all organisms, apart from minor variations. – These processes demonstrate the fundamental unity of all living matter, and are collectively described as primary metabolism, with the compounds involved in pathways being termed primary metabolites.

Primary Metabolisms • Degradation of carbohydrates and sugars generally proceeds via the well characterized pathways, known as glycolysis and the kerbs / citricacid / tricarboxylic acid cycle, which release energy from the organic compounds by oxidative reactions. • Oxidation of fatty acids from fats by the sequence called β-oxidation also provides energy.

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Primary Metabolisms

• Aerobic organisms are able to optimize these processed by adding on a further process, oxidative phosphorylation. This improves the effeiciency of oxidation by incorporating a more general process applicable to oxidation of a wide variety of substrates rather then having to provide specific process for each individual substrate.

Primary Metabolisms • Proteins taken in via the diet provide amino acids, but the proportions of each will almost certainly vary from the organism’s requirements. • Most organisms can synthesize only a proportion of the amino acids they actually require for protein synthesis. Those structures not synthesized, so-called essential amino acids, must be obtained from external sources.

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Secondary Metabolisms • The compounds which synthesized from the secondary metabolisms are so-called secondary metabolites. • Secondary metabolites are formed in only specific organisms, or groups of organisms, ane are expressioin of the individuality of species. • Secondary metabolites are not necessarily produced under all conditions, and in the vast majority of cases the function of these compounds and their benefit to the organism is not yet known. • It is this area of secondary metabolism that provides most of the pharmacologically active natural products.

Secondary Metabolisms • To make such compounds as sugars, waxes, lignin starch, pigments, or alkaloids, plants utilize very specific enzymes, each of which catalyzes a specific metabolic reaction. – The enzymes are proteins called organic catalysts. – These enzymes are coded by specific genes in the plants DNA and are made via processed we call transcription and traslation. – When there is a series of enzymatically catalyzed reaction in a welldefined sequence of step, we have what is termed a metabolic pathway.

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Biosynthetic Pathway • Nucleoside diphosphate sugar pathway: cellulose, hemicellulose, glycosides. • Shikimate-cinnamate pathway: lignin, lignans, hydrolyzed tannins. • Mixed pathways of 3 and 4: some prenylflavonoids, quinones and stilbenes.

Primary and Secondary Metabolism • Primary and secondary metabolites leave a “grey area” at the boundary, so that some groups of natural products could be assigned to either divisions. • Primary metabolites → Biochemistry Secondary metabolites → Natural products Chemistry

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The Classes of Secondary Metabolites • The majority of secondary metabolites belong to one of a number of families, each of which have particular structural characteristics arising from the way in which they are built up in nature (biosynthesis). • The classes of secondary metabolites are: – Polyketides and fatty acids – Terpenoids and steroids – Phenylpropanoids – Alkaloids – Others (specialize amino acids and carbohydrates)

Polyketide and Fatty acids • Polyketides are formed by the linear combination of acetate units derived from the “building block” acetyl coenzyme A. • The acetate origin of these compounds leads to a preponderance of even-numbered carbon chains. • Many plant oils and animal fats contain long-chain monocarboxylic acids know as fatty acids. • In the fatty acids, the carbonyl group of the acetate units is reduced during the course of the chain assembly process. Dehydrogenation and oxidative processed may subsequently give the unsaturated fatty acids.

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Polyketide and Fatty acids • The common fatty acids have an even number of carbon atoms, typically C12 – C20, linked together in a straight chain with up four double bonds. • In plants the fatty acids and the corresponding alcohol are found in leave waxes and seed coating: – Myristic acid (C14) is found in nutmeg seeds. – Palmitic acid (C16) is found in almost all plant oils. – Stearic acid (C18) occurs in long amounts in animal fat.

Polyketide and Fatty acids • Unsaturated fatty acids are important to us in food. – Oleic acid is the most widely distributed, and a major constituent of olive oil. – Linoleic and linolenic acids are most highly unsaturated and are found in linseed oil. – Linolenic acid is easily oxidized by air, and is one of the “drying oil” used in paint and varnishes.

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Polyketide and Fatty acids – Linolenic acid is oxidized by plants to jasmonic acid, which is a signaling substances that stimulates plant defense mechanisms. – Arachidonic acid (C20) is a precursors of the prostaglandin hormones.

Polyketide and Fatty acids • Polyacetylenes – They are a group of naturally

Falcarinol OH

occurring hydrocarbon derivatives characterized by

O

one or more acetylenic groups

O

COOH

Wyerone acid

in their structures. – Araliaceae(五加科), OH

Campanulaceae(桔梗科),

HO

Safynol

Apiaceae(繖形花科), Asteraceae, Pittosporaceae(海 桐科), and some fungi.

OH 1,2-dihdroxytrideca-5,7,9,11-tetrayne

OH

13

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Terpenes • The terpenes are among the most widespread and chemically diverse groups of natural products. • Terpenes are a unique group of hydrocarbon-based natural products whose structures may be derived from isoprene. • Terpenes are classified by the number of 5-carbon units.

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Terpenes • Isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) combined to yield geranyl pyrophosphate (GPP), leading to monoterpenes. Similarly, compounds derived from farnesyl pyrophosphate (IPP) lead to sesquiterpenes, and triterpenes are formed from two equivalents of FPP, and triterpenes are formed from two equivalents of FPP.

Terpenes • The function of terpenes in plants is generally considered to be both ecological and physiological – Allelophathy – Insecticidal – Insect pollinators – Plant hormone (Abscisic acid, gibberlellin)

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Myrcene

Greek Bay (Laurus nobilis)

Hops (Humulus lupulus)

Myrcene is found in the essential oil of bay leaves as well as hops. It is used as an intermediate in the manufacture of perfumes.

Geraniol and Linalool

OH

Geraniol

OH

Linalool

Geraniol is isomeric with linalool, constitutes the major part of the oil of roses and is also found in

citronella

essential oils of citronella, lemon grass, and others.

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Menthol

OH

Menthol is a well-known monoterpenewhich is found in the essential oil of peppermint and other members of the mint family.

Sesquiterpenoids • More than 10000 sesquiterpenoids have been identified, representing a wide variety compounds of different skeletal types from acyclic to tetra cyclic systems.

α-cedrene α-muurolene

logifloene

δ-cadinene

juniperol

α-cadinol

nootkatin

chanootin

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cadinenes

Wormwood (Artemisia maritima)

O O O santonin

caryophyllene Cloves (Syzygium aromaticum)

Dandelion (Taraxacum officinale ) OH

O O

tetrahydroridentin B

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Bioactive Compounds Contributing to Decay Resistance of Taiwania Wood • Fungi and termites are two of the most harmful organisms to wooden structures worldwide • To develop methods for prolonging the service life of wood is one of challenges of wood utilization researchers

• As regards decay resistance, Taiwania is classified as the species with an excellent durability in Taiwan • There are several papers dealing with the antifungal and antitermitic activities of Taiwania: .For. Prod. Industries. 1998, 17, 287. .Holzforschung. 1999, 53, 487. .Holzforschung. 2000, 54, 241. . J. Chem. Eco. 2001, 27, 717.

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Commonly Occurring Brown-rot and White-rot Fungi White rot fungi

Brown rot fungi

Coriolus versicolor

Laetiporus sulphureus

Lenzites betulina

Antrodia taxa

Pycnoporus coccineus

Fomitopsis pinicola

Trichaptum abietinum

Phaeolus schweinitzii

Oligoporus lowei

Extractives of Taiwania against Whiterot Fungi Taiwania Heartwood MeOH extraction MeOH Extractives

Hex Fr. Chl. Fr. EtoAc Fr. MeOH Fr.

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Extractives of Taiwania against Brown-rot Fungi Taiwania Heartwood MeOH extraction MeOH Extractives

Hex Fr. Chl. Fr. EtoAc Fr. MeOH Fr.

Antifungal Indices of Compounds Isolated from Taiwania Heatwood

Suginol Hinokiol C. v.

Ferruginol α-Cedrol α-Cadinol Helioxanthin Taiwanin C

L. s.

Savinin Taiwanin A 0

20

40 60 Antifungal index

80

100

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Effectiveness of α-Cadinol against White-rot and Brown-rot Fungi • Among the compounds isolated from Taiwania heartwood, α-cadinol has demonstrated to possess the highest antifungal effectiveness.

H

H O

H

H

H

H O H

H O

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Quantification of the Cadinane Skeletal Sesquiterpenoids Distribution in Different Parts of Taiwania H O H

T-cadinol

H O H

The amounts of hexane extractives and essential oils distilled from various parts of Taiwania

1

H

T-muurolol H O

H

2

H

α-cadinol 3

GC chromatograms of essential oils distilled from Taiwania heartwood.

Amounts of Cadinanes in Various Parts of Taiwania Amounts of cadinanes (mg/kg)

8 t-cadinol

6

6.49

t-muurolol α-cadinol total cadinols

4

1.77

2

0

0.04

0.36 n-Hex extracts Heartwood Heartwood

Essential oil Leafs

Sapwood

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Antifungal Indices of α-Cadinol, T-Cadinol, and T-Muurolol equatorial hydroxyl group

trans ring junction

Fungi

α-Cadinol

C. v.

100

L. s.

100

T-Cadinol 47.1 100

T-Muurolol 38.8 82

Diterpenoids • Diterpenoids constitute a major part of oleoresin. • This group can be divided into

geranyl-linalool

β-epimanool

acylic, bicyclic, tricyclic, tetracyclic, and macrocyclic structural types. cis-abienol

manoyloxide

• Diterpenoids are present either as hydrocarbons or as derivatives with hydroxyl, carbonyl, or carboxyl groups.

pimaral pimarol

cembrene

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Phenolic Constituents • Heartwood and bark contain a large variety of complex aromatic extractives. Most of them are phenolic compounds, and many are derived from the phenylpropanoid structure.

Classification of Phenolic Compounds Numbers of C 6

Basic skeleton

Name

C6

Benzoquinones

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C6-C4

Naphthoquinones

14

C6-C2-C6

Stilbenes

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C6-C3-C6

Flavonoids

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C6-C3-C2-C6

Norlignans

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(C6-C3)2

Lignans

(C6-C3-C6)n

Condensed tannins

n

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Phenolic Compounds H2COH CH CH

CHO

OCH3 OH

CH2 CH CH2 OCH3

OCH3

O GLUCOSE

Vanillin

Coniferin

OH

Eugenol

O

CHO

OCH3

CH3O OCH3

OCH3

CH3O OH

OH

Syringaldehyde

Guaiacol

O

2,6-Dimethoxy benzoquinone

Summery of the Biogenetic Connection between a Selection of Familiar Phenolic metabolites

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Summery of the Biogenetic Connection between a Selection of Familiar Phenolic metabolites

Summery of the Biogenetic Connection between a Selection of Familiar Phenolic metabolites

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Lignans Isolation Procedures • Lignans can be isolated from the bark, fruit, heartwood, leaves, roots and resin of plants • Most isolation procedures involve solvent extraction, chromatography separations, and crystallization • Lignan yields can vary from 0-30%

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Lignans Commercialization • Large amount of research devoted to investigating medicinal properties of lignans – Particularly from tropical hardwoods and grasses • Example 1999 reference: 35 lignans isolated from the twigs of Tazus mairei

– Antiviral – Antitumor – Biocidal – Bioactive Agents

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The heartwood of Taiwania is yellowish red with distinguished purplish pink streaks, which fascinates people very much.



The yellowish red color in Taiwania is susceptible to change to dull black after exposure it to nature environment.

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Optical Micrographs of Different Parts of Taiwania

Optical Micrograph Observation of Discoloration in Red Taiwania Heartwood

2 weeks

4 weeks

After exposed Taiwania heartwood under indoors condition, its color changed from red to dull black.

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Color Compounds Isolated from Taiwania Heartwood O

O

O O

O

O O

O

O

HO

O

O

O HO

O O

O

O

O

Taiwanin A

O

O

O

Savinin

O

O

Helioxanthin

Pluviatolide OH

OH H

HO HO

OH

O H OMe O

Taiwanin I

CHO CHO

O

Ferruginol

T-Cadinol

Secoabietane dialdehyde

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Cytotoxicity of Lignans and Sesquiterpenoids from Taiwania Heartwood (ED50 values in mM)

Taiwanin A

Taiwanin E

Dimethylmatairesinol

α-Cadinol

Cytotoxicity of Dibenzyl-γ-butyrolactone Type of Lignans Isolated from Taiwania Heartwood O

O O

O

O

O

O

O

O

O O R

O R

R R

O

• An unsaturated double bond between C7-C8 and/or C7’-C8’ is associated with stronger cytotoxicity. • The presence of two 3, 4dimethoxyphenyl groups in lignans may increase the cytotoxicity, as dimethylmatairesinol was stronger than arctigenin and hinokinin

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Cytotoxicity of Dibenzyl-γ-butyrolactone Type of Lignans Isolated from Taiwania Heartwood O

O O

O

O

O

O

O

O

O

O

• An unsaturated double bond between C7-C8 and/or C7’-C8’ is associated with stronger cytotoxicity. • The presence of two 3, 4dimethoxyphenyl groups in lignans may increase the cytotoxicity, as dimethylmatairesinol was stronger than arctigenin and hinokinin

O R

O R

R R

Cytotoxicity of Dibenzyl-γ-butyrolactone Type of Lignans Isolated from Taiwania Heartwood O

O O

O

O

O

O

O

O

O

O MeO

O MeO

OMe MeO

O

• An unsaturated double bond between C7-C8 and/or C7’-C8’ is associated with stronger cytotoxicity. • The presence of two 3, 4dimethoxyphenyl groups in lignans may increase the cytotoxicity, as dimethylmatairesinol was stronger than arctigenin and hinokinin

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Cytotoxicity of Arylnaphthalide Type of Lignans Isolated from Taiwania Heartwood

OH

O

O

O

O

O

O

O

O

O

O

O

O

O O

O

O

O

O

• Taiwanin E showed the strongest cytotoxicity in this group. • It appears that the hydroxyl group at the C7 position enhances the cytotoxicity.

Cytotoxicity of Arylnaphthalide Type of Lignans Isolated from Taiwania Heartwood

OH

O

O

O

O

O

O

O

O

O

O

O

O

O

O O

O

O

O

• Taiwanin E showed the strongest cytotoxicity in this group. • It appears that the hydroxyl group at the C7 position enhances the cytotoxicity.

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Flavonoids/Tannins Isolation of Flavonoids • Isolation of flavonoids accomplished through solvent extraction – Hot water – Alcohols

• Solvent fractionation of extract • Salting out • Crystallization

Flavonoids/Tannins Isolation of Flavonoids • Flavonoids concentrated in certain parts of plants • Plant sources – Pulp of fruits – Broccoli, green peppers, onions, etc. – Green tea, red wine – Herbs – Tree bark

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Blockade of tumor induction by EGCG OH OH O

HO

OH OH O OH

C

OH

O OH

(-)-epigallocatechin-3gallate RH: procarcinogens (aflatoxins, poly-cyclic aromatic hydrocarbons, and nitrosamines) GST: glutathione S-transferase GlcT: UDP-glucuronyl transferase ROS: reactive oxygen (superoxide anion, hydrogen peroxide, hydroxyl radical, nitric oxide, peroxynitrite, and nitric dioxide anion)

Chemical Composition of Tea • Caffein: 3-4 % • Catechins (including Tannin): 15-30 % • Flavonols and Metal: 5 % ¾P,K, Ca, Mg, Mn, Zn, Cu, Al • Vitamins: A, B1, B2, C, E, Nicotinic acid

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Flavonoids/Tannins Polymerization Reactions • Condensed tannins are formed through the polymerization of flavan-3-ol (catechin) and flavan–3,4diols (leucoanthocyanidins)

O OH OH

Flavan-3,4-diols (Leucoanthocyanidins)

– In tree, polymerization through acidic enzymatic non-oxidative coupling

O OH

– 2-50 units

Flavan-3-ols (Catechins)

• Typically 2-8

– Linkages can be through a variety of sites

Flavonoids/Tannins Polymerization Reactions 3'

• Examples of linkages – 4 alpha – 8 – 4 beta – 8 – 4 beta – 6

• Stereochemistry • A variety of monomers

2' 8 7

O

A

C

5

4

6

2

B

4' 5'

6' 3

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Flavonoids/Tannins Polymerization Reactions OH

OH OH

O

HO

O

O

HO OH

+

(H )

OH

OH

O

-H2O

OH OH

OH OH

OH

OH

OH OH OH

OH

HO

OH

OH

OH

OH OH

O

HO

+

+H

O OH

OH

-H

O

HO

OH +

O

HO

OH

OH OH

OH

(+)

OH

Flavonoids/Tannins Polymerization Reactions • Flavan-3-ols are incapable of

OH O

HO

polymerizing without flavan 3,4-diol

OH OH

HO

OH

HO

• Flavan-3-ol form terminating unit

O

OH O

OH

HO OH

OH OH

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Flavonoids/Tannins Polymerization Reactions OH OH

• All 4-8 linkages

O

HO

OH

• This structure has been isolated from

OH

OH

OH O

HO

pine bark

OH

OH

OH

OH O

HO

OH OH

Flavonoids/Tannins Polymerization Reactions • Flavan-3-ols can polymerize through an oxidative enzymatic coupling reaction forming oligo and polymeric materials – Linkages 8-6’

OH OH O

HO

OH OH

O

OH

O

HO

OH

O

– Causes loss of brightness in wood

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Flavonoids/Tannins Location in Tree: Tannins • Western hemlock – Bark: 18% tannins – Wood: 2% tannins

• Quebracho – In wood, tannins found in heartwood – Majority (80%) located in vessel lumina – Tannins deposit in dead cell starting at CML and ending in secondary wall

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Condensed Tannins Properties • The term condensed tannins refers to a mixture of polyflavonoids of different MW (500-5000) characterized by different linkages, functional groups, and stereochemistry. • Protein binding capacity: tannins will bind with proteins causing them to precipitate. – This was the definition of tannins: compound which will precipitate proteins.

Condensed Tannins Sources • Condensed tannins more prevalent in hardwoods but present in softwoods – Wattle (Acacia - Southern Africa) – Quebracho (Schnopsis - South America) – Mangrove (Rhizophora -) – Hemlock (North America)

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Condensed Tannins Biological Significance – Insects/Animals • Protection of plants against insects/animals – Some evidence for/some against

• Bad Taste/Astringency (bitter taste) • Appears to be major factor • Particularly bad for insects not used to tannins

• Animals: tannins reduce digestion of food – Interaction with digestion enzymes

• Toxic to bacteria

Condensed Tannins Biological Significance - Fungus • Pine calluses: created by fungal invasion – Tree forms calluses as protective tissue – Calluses contain high levels of tannins (Chinese 50-80%) – Concentrations of tannins as low as 0.1% or 0.8 % have been shown to retard the growth of a large number of parasitic fungi • Quote: Edwin Haslam (tannin chemist) – “serious and nagging fear that a part at least of (their) scientific career(s) has been spent inspecting the loot in the garbage bin of plant metabolism”

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Hydrolyzable Tannins Structure • Polymers of a sugar (usually glucose) with one or more polyphenolic carboxylic acids: linked through ester linkages • Gallotannins: Gallic acid polymer • Ellagitannins: Ellagic Acid polymer OH OH

HO

OH HO

O C

OH HO

O

OH

O

OH HOOC

COOH

C

C

O

O

OH

OH

OH

Ellagic Acid

Digallic Acid

Gallic Acid

O

Hydrolyzable Tannins Polymer Structure Example OH OH OH

O

HO

Sugar

OH O

HO

O

O O

O

O

O

OH

O

OH OH

O

HO HO OH

O

HO OH

OH

O

n

OH O

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Hydrolyzable Tannins Tree Information • Rare to nonexistent in softwoods • Hardwoods which contain large amounts: – Oak (gallic and ellagic tannins) – Eucalyptus (Ellagitannins) – Chestnut (gallic tannins) – Myrobalan fruits (cherry plum) • Hydrolyzable tannins located in heartwood

Condensed Tannins Uses • Leather tanning: 10,000+ year old industry – Vegetable tannins & chrome – Tannins interacting with proteins in hides

• Adhesives – In phenol formaldehyde systems, tannins speed up the set:

• Oil well drilling fluids: old but effective use: taken over by chrome lignosulfonates

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Stilbene

二苯乙烯類之化合物是以α,β-Diphenyl ethylene 為骨架之化合物稱之,廣泛地分 佈在針葉樹皮及闊葉樹之許多樹種。由於 具有共軛雙鍵,此類化合物為反應性極強 之化合物,除了在製漿蒸煮過程中會與藥 劑反應外,並會阻止可溶性之木質素磺酸 鹽的形成,阻礙木質素的溶解。此外,二 苯乙烯類亦與木材之抗蟻性有密切的關 係。

Alkaloids • Derived from plants • With a basic character (hence the term alkaloid from alkali) • Contained a nitrogen based heterocylic ring within their molecules

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• Alkaloids can be sub-categorized according to: – Monocyclic alkaloids – Bicyclic alkaloids – Polycyclic alkaloids

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Narcotic analgesics

Opium Papaver somniferum - used for 5000 years. Arabs introduced opium to China in 7th century. Opium addiction became a problem so Chinese officials outlawed it. England traded opium to China for goods even though it was illegal in their own country and in China. China and England fought two wars over the English import of opium, China lost both, ceded Hong Kong to British at end of first war. Use of opium in China did not drop until Communist Revolution in 1949. Most opium is currently grown in SE Asia. Morphine is purified from opium and is a very potent painkiller.

OR

O N CH3

R=H R = CH3

HO

morphine codeine

Ma Huang or Ephedra has been used in China since 2800 BC It was used primarily for colds, asthma, hayfever, bronchitis, edema, arthritis, fever, hypotension and hives. Potency is based upon the herb's alkaloid content. Side effects include increased blood pressure, heart rate and anxiety. FDA suggest that those with heart

Ma huang

(disease or high blood pressure), thyroid,

Ephedra sinica,

diabetes or prostrate problems may be

Ephedra intermedia,

affected adversely. It should definitely NOT

Ephedra equisetina

be taken with antihypertensive or antidepressant drugs. CH3

CH3

H C N CH3 H H C OH

l-ephedrine

H C N CH3 H HO C H

d-pseudoephedrine

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Catharanthus roseus 長春花

Vinblastine is a drug used in the treatment of cancer. It interferes with the multiplication of cancer cells and slows or stops their growth and spread in the body.

Berberis fremontii 小檗

50

51

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