Current Organic Chemistry - Volume 4, Issue 6, 2000

The synthetic potential of low molecular weight carbohydrates in the form of their hydrazones or bishydrazones as precursors for heterocyclic compounds and acyclic nucleosides, which could be degraded into functionalized heterocycles without polyol residues, is the subject of this review. The inherent functionalities in such hydrazone derivatives make them suitable for building the skeleton of heterocyclic compounds. This strategy also offers the possibility for the synthesis of heterocycles possessing chiral centers. This review covers the synthesis of various classes of heterocyclic compounds and their nucleoside analogues. Thus, ring system of type perhydro-furans and pyrans, pyrazoles, pyrazolines, isoxazolines, triazoles, oxadiazoles, oxadiazolines, thiadiazoles, thiadiazolines, tetrazoles, pyridazines, 1,2,4-triazines, as well as their condensed analogues (condensed azoles, pyrazoles, 1,2,3-triazoles, 1,2,4-triazoles, diazines, quinoxalines, and furans) can be prepared.

This account is devoted to a discussion of synthetic applications of olefin metathesis in carbohydrate chemistry.Olefin metathesis has emerged as a highly promising and exciting area in the contemporary organic synthesis of carbon-carbon bonds. Metathetic ring-closure (RCM) of diene precursors is advancing into one of the most useful and frequently applied transformations in modern organic chemistry. The development has been particularly rapid in recent years following the introduction of efficient transition metal carbene catalysts as reflected by the number of reviews on the general field of olefin metathesis in recent years.Cross-metathesis of suitably functionalized carbohydrates with well-defined metal carbene complexes is yet another of the big promises in carbohydrate synthesis for years to come. Compared with the ring-closing metathesis, this variation of the theme has, to date, received much less attention from the scientific community despite the fact that it has proved to be of tremendous synthetic value in the area of organometallic chemistry.

Numerous methods for preparation of C-glycosylic compounds (C-glycosides) have been developed. One general approach to the synthesis of these important O-glycoside analogs is based on the use of three-membered cyclic intermediates. The review is focused on the application of glycal and exo-glycal derived epoxides and episulfonium and iodonium ions for preparation of C-glycosides. Reactions of glycal epoxides with organocuprates, Grignard and organolithium reagents, allylsilane, sodio malonate, and lithium alkynyl derivatives have been shown to be convenient for stereoselective synthesis of both a- and b-C-glycosides. The unprotected C(2)-hydroxyl group in the products can be removed in two steps providing an easy excess to 2-deoxy-C-glycosides. Electrophilic addition of arylsulfenyl chloride (ArSCl) to glycals has afforded 2-(arylthio)pyranosyl chlorides. Upon the treatment with a Lewis acid, the chlorides have been converted to episulfonium-like intermediates. Reactions of the latter species with silyl enol ethers, TMSCN, allylsilanes, vinyl ethers, and heteroaromatic compounds have opened a new synthetic route to 2-(arylthio)-b-C-glycosides having a variety of functional groups in the lateral chain. The 2-arylthio group in the products can be selectively removed using Raney Ni or n-Bu3SnH/AIBN. Episulfonium ions generated from ArSCl adducts of 1-methylene sugars have reacted with O- and C-nucleophiles to afford O-ketopyranosides and 1,1-dialkyl C-glycosides, respectively. Acid catalyzed and nucleophilic ring openings of spiro epoxides obtained from exo-glycals have occurred with opposite stereoselectivity. Iodonium-promoted reactions of exo-glycals have led to O-ketopyranoside derivatives.

Vaccination is the most cost-efficient and the most powerful medical intervention in the control, prevention and eradication of many diseases that affect human population. Capsular polysaccharide based vaccines have been in use for many decades providing immunity against various bacterial infections. The advent of new efficient and sensitive analytical and synthetic methods in carbohydrate chemistry, together with our increased understanding of glycobiology and glycoim-munology, makes the development of carbohydrate based vaccines against various cancers possible. This review article describes the biological basis of vaccination and summarizes the recent progress in the development of carbohydrate based glycoconjugate vaccines with particular emphasis on structure, function and chemistry of glycoconjugates.