SYNTHESIS AND REACTIONS OF UNSATURATED SUGARS

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Publisher Summary

This chapter discusses the synthesis and reactions of unsaturated sugars. Sugar derivatives that contain double bonds have been developed and used so extensively that they almost certainly constitute the most versatile category of carbohydrate compounds available for use in synthesis of unsaturated sugars. They may be applied both in the synthesis of complex members of the family and of a myriad enantiomerically pure noncarbohydrate compounds—notably, many of interest in medicinal chemistry. In addition, some unsaturated sugar derivatives have themselves been found to possess important therapeutic properties. The unnatural L-nucleoside inhibits reverse transcriptase and shows potent and selective anti-AIDS activity. This chapter surveys the chemistry of most of the important types of monosaccharide derivatives that contain single alkene groups—notably, the glycols that are extremely valuable starting materials for a vast range of synthetic transformations. It also discusses the preparation of the reactions of glycols, elaborates the synthesis of pyranoid and furanoid 2- and 3-Enes, and explains the chemistry of endo-Enes and exo-Enes.

Introduction

Sugar derivatives that contain double bonds have been developed and used so extensively that they almost certainly constitute the most versatile category of carbohydrate compounds available for use in synthesis. They may be applied both in the synthesis of complex members of the family and of a myriad enantiomerically pure noncarbohydrate compounds—notably, many of interest in medicinal chemistry. Furthermore, some unsaturated sugar derivatives have themselves been found to possess important therapeutic properties. For example, the unnatural l-nucleoside 1 inhibits reverse transcriptase and shows potent and selective anti-AIDS activity,1 and the unsaturated neuraminic acid analogue 2 is the sialidase-inhibitory anti-influenza drug Relenza which was developed by a team of university and industrial chemists using rational design.2

Only occasionally are compounds with unsaturated carbohydrate components found in Nature. A well-known example is blasticidin S (3) which inhibits blast disease of rice,3 and a most unusual case is that of a 2,6-dideoxy-trisaccharide “glycal” (1,2-unsaturated cyclic compound) isolated from a plant in India.4

This article surveys the chemistry of most of the important types of monosaccharide derivatives that contain single alkene groups—notably the glycals, which are extremely valuable starting materials for a vast range of synthetic transformations. A highly diversified group of compounds, which can vary in the position of, and in the substituents on the double bonds, are discussed; only occasional reference will be made to dienes, enones, alkynes, and compounds having unsaturation in the sugar substituents. Several reviews have covered the basic chemistry of carbohydrate compounds having unsaturation within their carbon skeletons.5., 6., 7. Recent developments have been appreciable.

Section snippets

Glycals

Compounds of this category are vinyl ethers having double bonds between C-1 and C-2 of pyranoid or furanoid aldose derivatives. Analogues with exocyclic C-1C-2 double bonds in cyclic 2-ketoses are sometimes referred to as “exo-glycals” and are covered briefly in Section IV.3; isomers with C-2C-3 unsaturation in 2-ketoses can be considered as C-1-substituted glycals and are referred to in Section II.3.a. Together the glycals and their derivatives constitute the most useful set of unsaturated

Pyranoid and Furanoid 2- and 3-Enes

Unsaturated cyclic sugar derivatives having 2,3- or 3,4-double bonds are also an extensive class of compounds widely used as synthetic building blocks and as nucleoside analogues. Both synthetic and naturally occurring nucleosides of this type, such as 1 and 3, show important biological properties.

Relevant pyranoid and furanoid compounds (with the exception of the furanoid 3-enes that, as enol ethers, are noted in Section IV.1) have “isolated” double bonds in the sense that they are not

Pyranoid 4-Enes and Furanoid 3-Enes (endo-Enes)

Compounds such as 247 (R=CH2OH) are enol ethers closely related to the glycals (especially C-1 C-substituted glycals; Section II.3.a), but they differ significantly in retaining the acetal anomeric center. They are readily available from saturated hexopyranosides with unsubstituted hydroxyl groups at the primary positions and good leaving groups at C-4 simply by oxidation of the alcohol moieties to the aldehydes and spontaneous β-elimination. Thus, methyl 2,3-di-O-benzyl-4-O-methylsulfonyl-α-d

Other Unsaturated Derivatives

Acyclic carbohydrate derivatives containing unsaturation, with some exceptions, exhibit much of the chemistry already described for cyclic analogues, and their usefulness should not be overlooked. Unsaturated derivatives of alditols can be made, for example, by standard eliminations from alditol vic-disulfonates or epoxides or by β-eliminations from O-substituted 1-deoxy-1-nitroalditols and 1-deoxy-1-sulfonylalditols. Additions of hydrogen and ammonia to the unsaturated nitroalditols made in

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