Increased understanding of the important roles that oligosaccharides and glycoconjugates play in biological processes has led to a demand for significant amounts of these materials for biological, medicinal, and pharmacological studies. Therefore, tremendous effort has been made to develop new procedures for the synthesis of glycosides, whereby the main focus is often the formation of the glycosidic bonds. Accordingly, quite a few review articles have been published over the past few years on glycoside synthesis; however, most are confined to either a specific type of glycoside or a specific strategy for glycoside synthesis. In this Review, new principles for the formation of glycoside bonds are discussed. Developments, mainly in the last ten years, that have led to significant advances in oligosaccharide and glycoconjugate synthesis have been compiled and are evaluated.

New principles for glycoside-bond formation.

Considerable problems attend the synthesis of biologically important natural products whose carbohydrate components display a greater or lesser degree of complexity. The present progress report surveys recent developments in the formation of O-glycosidic bonds starting from 1-halo sugars and from sugar 1,2-orthoesters. Particular emphasis is placed on attempts to reach a better understanding of the steric course of glycosylation reactions on the basis of mechanistic considerations. Studies on the silver-salt dependence of the Koenigs-Knorr synthesis led to improvements in preparative applications and to new concepts concerning the reaction course. The introduction of sugar 1,2-orthoesters as glycosylation components has greatly enriched our preparative armoury for the synthesis of trans glycosides. Remarkable progress has also been made in the synthesis of cis glycosides, in part by exploiting novel neighbouring group effects.

Results and Problems of O-Glycoside Synthesis

Recent trends in the synthesis of O-glycosides of 2-amino-2-deoxysugars.

Catalytic glycosylation has been a central reaction in carbohydrate chemistry since its introduction by Fischer 125 years ago, but it is only in the past three to four decades that catalytic methods for synthesizing oligosaccharides have appeared. Despite the development of numerous elegant and ingenious catalytic glycosylation methods, only a few are in general use. This review covers all methods of catalytic glycosylation with the focus on the development and application in oligosaccharide synthesis and provide an overview of the scope and limitations of these. The review also includes relevant mechanistic studies of catalytic glycosylations. The future of catalytic glycosylation chemistry is discussed, including specific, upcoming methods and possible directions for the field of research in general.

Catalytic Glycosylations in Oligosaccharide Synthesis

The discovery of important roles of C-nitroso compounds in various biological metabolic processes has generated a renewed interest in the general chemical properties of nitrosoalkanes (R–N=O; R =alkyl) and nitrosoarenes (ArNO; Ar =aryl), two important subsets of this general class of compounds. For example, the identification of the nitrosobenzene adduct of hemoglobin as a product of nitrobenzene poisoning1,2 and the realization that some amine-containing drugs may be metabolized to nitroso derivatives3–6 led to an increased desire to study the fundamental biochemical properties of this fascinating class of C-nitroso compounds. To this end, many studies have been reported on the fundamental chemistry of C-nitroso compounds under conditions that either stabilize the C-nitroso functionality or enhance their reactivity toward isomerization or reactivity with substrates.

A major difficulty in C-nitroso chemistry, however, is that the high reactivity of these compounds necessarily imposes constraints upon the methods employed for their preparation, particularly with regard to the yield of the desired product. For example, the ease of oxidation of the desired nitroso compound (if oxidation of a suitable precursor is the chosen synthetic route) to its nitro derivative can significantly reduce the yield of the nitroso product. Similarly, the ease of isomerization of R2C(H)NO compounds to the corresponding oximes R2C=NOH can restrict the choice of solvent for the preparation of primary and secondary nitrosoalkanes. A further consideration to be borne in mind is the possibility of reaction of the C-nitroso compound with the starting material and/or preparative reagents. There is, however, a considerable variety of synthetic routes available for the high-yield preparations of C-nitroso compounds (monomers or dimers; Figure 1), some of which have been in regular use for well over 100 years.




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Figure 1



Some earlier reviews of this area have been published. Book chapters by Sandler and Karo (in 1986)7 and by Williams (in 1988)8 present the most detail to date on the experimental techniques for preparations of C-nitroso compounds. Other useful earlier reviews are those by Touster,9 Boyer,10 Metzger and Meier,11 Seidenfaden,12 and Katritzky et al.13

Given the renewed interest in the study of the biological and environmental consequences of C-nitroso compound formation, it is not surprising that many new and/or improved procedures for the preparations of these compounds have been developed over the last two decades. In this review, we present a comprehensive review of the synthetic procedures for the preparation of C-nitroso compounds and place these procedures in proper historical context. We also include a small number of routes to the production of C-nitroso compounds that may have preparative possibilities or which require improved workup methods. We indicate, when known, whether the method of preparation is applicable to all types of C-nitroso compounds or only to separate classes such as nitrosoarenes, nitrosoalkanes, nitrosohomocycles, or nitrosoheterocycles. Nitrosoalkenes are considered in a separate section. The coordination chemistry of C-nitroso compounds with metals has been reviewed recently.6,14

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Preparations of C-Nitroso Compounds

Reaction of nitrosyl chloride with acetylated glycals affords, with a high degree of stereospecificity, dimeric acetylated 1,2-cis-2-deoxy-2-nitroso-α-D-aldopyranosyl chlorides. Reaction of acetylated glycals with dinitrogen tetroxide, depending on the reaction conditions, can give either acetylated 2-deoxy-2-nitroso-α-D-aldopyranosyl nitrates as dimers or acetylated 2-nitroglycals. The mechanisms of these reactions are discussed.

The reactions of nitrosyl chloride and dinitrogen tetroxide with acetylated glycals. Acetylated 2-deoxy-2-nitroso-α-D-hexopyranosyl chlorides and nitrates and acetylated 2-nitroglycals

T. L. Nagabhushan

Papers

The reactions of nitrosyl chloride and dinitrogen tetroxide with acetylated glycals. Acetylated 2-deoxy-2-nitroso-α-D-hexopyranosyl chlorides and nitrates and acetylated 2-nitroglycals