David P. Sebesta

Stereoselective synthesis of 2-deoxy-β-glycosides from glycal precursors. 2. Stereochemistry of glycosidation reactions of 2-thiophenyl- and 2-selenophenyl-α-d-gluco-pyranosyl donors

Abstract We have demonstrated that 4-O-acetyl-6-bromo-3-O-(tert-butyldimethylsilyl)-2-deoxy-2-thiophenyl-1-trichloroacetimido-α- d -glucopyranose 11b is the most efficient and selective donor for use in the synthesis of 2-deoxy-β-glycosides of the series of glycosyl donors examined. Unlike the 2-selenophenyl substituted donors 8 which proved to be configurationally unstable under standard TMS-OTf promoted glycosylation conditions, giving rise to α-manno glycosides 14 , 17 and 20 from β-gluco donors 8 , the 2-thiophenyl substituted donors 9 and 11 appeared to be completely configurationally stable (at C(2)). The main problem with imidates 11 is that the stereoselectivity of their reactions with alcohols is substrate dependent, with best selectivity for the desired β-glycosides 35 and 42 being obtained with the least sterically hindered alcohols. The fact that the α-glycosides 36 and 43 comprise up to 20–50% of the product in glycosidation reactions of hindered secondary alcohols supports the thesis that the reaction stereoselectivity is not governed by the intermediacy of episulfonium ions ( 47 and 47′ ), but rather that substitution reactions of oxonium ions 46 and its conformationally inverted isomer 46′ play a dominant role.

Stereoselective synthesis of 2-deoxy-β-glycosides from glycal precursors. 1. Stereochemistry of the reactions of d-glucal derivatives with phenylsulfenyl chloride and phenylselenenyl chloride

Abstract The stereoselectivity of the reactions of d -glucal derivatives with PhSCl and PhSeCl is dependent on the presence of an electronegative heteroatom substituent at C(6) and the nature of the functionality at C(4). The C(6)-substituent influences the conformational preferences of the d -glucal derivatives, and greatest stereoselectivity is obtained with those glycals that preferentially exist in the inverted 5 H 4 half-chair conformation 28b . A polar substituent at C(4) increases the selectivity by stabilizing the episulfonium/episelenonium ion intermediates 31b and 33 .

2′-Deoxy-2′-alkoxylaminouridines: Novel 2′-substituted uridines prepared by intramolecular nucleophilic ring opening of 2,2′-O-anhydrouridines

Abstract Natural and unnatural modified nucleosides and nucleotides play important roles in biology, medicine, and as biomedical research tools. Reported herein is an application of synthetic methodology developed for the stereo- and regiospecific introduction of structural modifications at the 2′-position of uridine nucleosides. A novel class of modified nucleosides, 2′-alkoxylamino-2′-deoxy uridines, are prepared by intramolecular nucleophilic addition of a 3′-tethered alkoxycarbamate nucleophile to the 2′-position with concomitant opening of a 2,2′-anhydrouridine.