Particularly, the class I FruA isolated from rabbit muscle, which for long was the ... Ac.,ra, and .... Indeed, from the enzymatic reaction with FruA catalysis relatively.
Tandem Asymmetric C-C Bond Formations by Enzyme Catalysis M i c h a e l P e t e r s e n 9 Maria Teresa Z a n n e t t i 9Wolf-Dieter F e s s n e r * Institut ffir Organische Chemie der Rheinisch-Westf'~ilischen Technischen Hochschule Aachen, Professor-Pirlet-Str. 1, D-52056 Aachen, Germany
Catalytic aldol reactions are among the most useful synthetic methods for highly stereocontrolled asymmetric synthesis. In this account we discuss the recent development of a novel synthetic technique which uses tandem enzyme catalysis for the bi-directional chain elongation of simple dialdehydes and related multi-step procedures. The scope and the limitations of multiple one-pot enzymatic C-C bond formations is evaluated for the synthesis of unique and structurally complex carbohydrate-related compounds that may be regarded as metabolically stable mimetics of oligosaccharides and that are thus of interest because of their potential bioactivity.
Table of Contents 1
Introduction
1.1 1.2 1.3
N u c l e o s i d e antibiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . Stereodivergent Enzymatic C-C Bond Formations Synthetic Utility of Aldolases . . . . . . . . . . . . . . . . . . . . . . .
2
Open-Chain Precursors
2.1 2.2
Simple Aliphatic Dialdehydes . . . . . . . . . . . . . . . . . . . . . . . D i h y d r o x y - a , co-Dienes . . . . . . . . . . . . . . . . . . . . . . . . . .
3
Cyclic P r e c u r s o r s
3.1 3.2 3.3 3.4
C y c l o p e n t e n e Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . C y c l o h e x e n e Derivatives ......................... Azido S u b s t i t u t e d Substrates . . . . . . . . . . . . . . . . . . . . . . . Bicycloalkene Derivatives . . . . . . . . . . . . . . . . . . . . . . . . .
101 104 105 106
4
Spirosugars
107
5
M i s c e l l a n e o u s Systems
5.1 5.2 5.3
2 - D e o x y - D - r i b o s e 5 - P h o s p h a t e Aldolase ................ Transketolase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . In vitro Biosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . .
109 110 111
6
Summary and Outlook
114
References
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88 ...........
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94 94 94 101
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88 90 92
109
114 Topics in Current Chemistry, VoI. 186 9 Springer Verlag Berlin Heidelberg 1997
88
M. Petersen 9M.T.Zannetti 9W.-D.Fessner
1 Introduction
A growing number of intercellular communication events are being identified to be encoded in oligosaccharide structures, which involve the specific binding of particular types of oligosaccharides on one cell surface to (glyco)protein receptors on the surface of another cell. Not the least by the medicinal importance of such cellular interactions through oligosaccharide structures in central biological recognition phenomena - such as cell adhesion, viral infection, or cell differentiation in organ development and tumor metastasis [ 1-7] - this has shaped the highly interdisciplinary new field of"glycobiology" and has underscored the increasing demand for novel, more efficient approaches to the synthesis and chemistry of complex carbohydrates and glycoconjugates. However, because natural oligosaccharides and glycoconjugates are chemically labile and orally inactive, a currently prominent area of research is dedicated to the development of potential mimetics of natural oligosaccharide effectors that will procure a therapeutic utility by reasonable metabolic stability as well as oral bioavailability. Of particular interest are C-disaccharides [8-10],a class of compounds in which the glycosidic oxygen is replaced by a methylene group. These compounds hold promise to be potentially active agonists or unreactive antimetabolites, i.e. inhibitors of glycoside processing enzymes, by virtue of their resistance to chemical and enzymatic hydrolysis of the "glycosidic" linkage and their ability to interact with protein receptors analogously to their O-linked counterparts [8, 10]. 1.1
Nucleoside antibiotics
In this respect it is revealing to note that Nature itself, in fact, has evolved very similar strategies in the design of chemical weaponry. Especially illustrative for this principle are the various nucleoside antibiotics [11-13] that have been isolated from different microorganisms and that are aimed against competing organisms (Scheme 1). The core structure of these natural products typically consists of a conjugate of one of the common pyrimidine or purine bases (or analogs thereof) glycosidically linked to a larger carbohydrate backbone. In addition to the primary glycosidic ring moiety, the residual chain of the latter may extend to mimic further saccharides (e.g. hikizimycin) or amino acid conjugates (e.g. mildiomycin, sinefungin, miharamycin, amipurimycin), or alternatively may be conformationally locked into linked (e.g. tunicamycin) or joined (e.g. herbicidin, derivatives of octosyl acid) furanose/pyranose ring systems that rather seem to mimic disaccharide moieties. Although so far most of these biologically active agents have proved not to be useful for human therapeutic purposes, the highly specific nature of these entities have made them to important tools in glycobiology research. The tunicamycins [14], for example, in prokaryotic systems block the exchange of UDP activated N-acetylmuramic acid pentapeptide with a phospholipid carrier, thus inhibiting cell wall biosynthesis [15]; in eukaryotic systems, they block the
TandemAsymmetricC-CBondFormationsbyEnzymeCatalysis
89
O H~
OH
H
HO-.!.-'~--....~OH t~.OH )",,OH
OH HO~~..~.~
OH AcHNo . ~ - o ~~ O" O R--'k~ Hb~H ~ O HO OH Tunicamyr Corynetoxins,
H~N~.O'"_'~, o ~'~,~.NH~ Ho - ~ ~ ~ ~r " - - "o~---y"
O
Hikizimyr
Streptovirudins
X HN~_. HN NH2 OH HO~
HOOC H2N.~.~kS.__~H~~_~
NH2 O.~~
~,N %
~NH~
~H ~O2C~
