2‐C‐Formyl Glycals: Emerging Chiral Synthons in Organic Synthesis

Abstract

Naturally occurring carbohydrates and their derivatives have been useful during the last few decades as “chiral pool” constituents in the enantioselective synthesis of biologically active natural and non‐natural products. The ready availability of a wide range of carbohydrates in nature and their multichiral architecture, coupled with their well defined stereochemistry, make them attractive starting materials in organic synthesis. The synthesis of key intermediates by incorporation of suitable functional groups onto carbohydrates, which can then be further exploited, has always been a challenging task. In this context, 2‐C‐formyl glycals, a new class of carbohydrates incorporating an α,β‐unsaturated carbonyl system, have recently emerged as potential synthons for numerous organic transformations. Four different syntheses of 2‐C‐formyl glycals have been reported so far. However, the importance of 2‐C‐formyl glycals has become well established after our development of a more general, one‐step synthesis, employing the well known Vilsmeier−Haack reaction. Synthetic transformations of these 2‐C‐formyl glycals have resulted in a variety of new compounds of significant synthetic and biological interest. 2‐C‐Formyl glycals have been shown to be ideal substrates for chemo‐, regio‐ and stereoselective glycosidation, nucleophilic addition/substitution and cycloaddition reactions. The reported syntheses and applications of these important “chiral intermediates” are presented. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Synthetic Approaches to Small Cluster Oligosaccharide Mimetics

“…Glycals are versatile chiral building blocks in the synthesis of natural products and biologically relevant oligosaccharides [26], because of the ease of their chemical transformation [27][28][29][30]. Synthetic oligosaccharides derived from glycals have been tested as antigens in anti-cancer vaccination [26,31].…”

Pyrimidine Acyclo-C-Nucleosides by Ring Transformations of 2-Formyl-L-arabinal

“…Because of their push-pull activated carbon-carbon double bond [1,2,3], 2-formylglycals [4,5,6] synthesized by a Vilsmeier-Haack reaction of O -benzyl protected hexose glycals are a versatile class of compounds which allowed a nucleophilic attack of dinucleophiles at C-1 under ring opening of the glycals followed by recyclization involving the formyl group to give acyclo- C -nucleoside analogues [6,7,8,9,10,11,12]. The protected 2-formyl- L -arabinal 2 was easily prepared from O -benzylated L -arabinal ( 1 ) by treatment with phosphoryl chloride and N,N- dimethylformamide [12].…”

Ring Transformations of Pentose Glycals with Push-Pull Butadiene Functionality

“…[1][2][3][4][5] We have previously reported the ring transformation reactions of 2-formyl glycals in the hexose series. [6][7][8][9][10][11][12] Recently, the first reactions of pentose glycals with nitrogen nucleophiles to yield acyclo-C-nucleoside analogues were described. 13 The double bond of these branched chain enesugars was push-pull activated and, therefore, susceptible to nucleophilic attack by different N-nucleophiles.…”