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Reaction of Me3Al with the 3',4'-epoxides derived from 9-(3-deoxy-beta-D-glycero-pent-3-enofuranosyl)adenine is investigated in detailed. Results reveal that the stereoselectivity of epoxide ring opening varied significantly upon changing the amount of Me2Al, the solvent, the O-silyl protecting group, and the reaction temperature.

Epoxidation of 3',5'-O-(di-tert-butylsilylene)-1',2'-unsaturated uridine with dimethyldioxirane proceeded from the alpha-face to give the 1', 2'-alpha-epoxide. Findings show that protection of the N(super3)-position of 3',5'-O-(di-tert-butylsilylene)-1',2'-unsaturated uridine either with a benzyloxymethyl or benzoyl group led to the exclusive formation of the desired beta-anomers.

Upon reaction of the 3',4'-unsaturated adenosine derivative 2 with N-iodosuccinimide (NIS) and thiophenol, an unexpected electrophilic hydrophenyisulfanylation proceeded to provide 4'-phenyisulfanylcordycepin 7 in 79% yield with the ratio 7a/7b = 6.6/1. A study of the reaction mechanism revealed that hydrogen iodide (HI) generated from NIS and PhSH acted as an active species. On the basis of a deuterium experiment using PhSD, initial protonation occurred at the β face of the double bond to furnish the β-π complex III, which underwent and addition of PhSH as a major pathway. Nucleophilic substitution of N6-pivaloylated 9 with various alcohols in the presence of W-bromosuccinimide (NBS)gave the respective 4'-α-alkoxycordycepins 15a-21a as the major stereoisomers. Use of DAST in place of an alcohol gave the 4 -α-fluoro analogue 23a stereoselectively. Radical-mediated carbon--carbon bond construction was also applicable to 7, giving 4'-α-allylcordycepin (24a) and 4'-α-cyanoethylcordycepin (25) derivatives. [ABSTRACT FROM AUTHOR]

Nucleophilic substitution between the 4′-benzoyloxy derivative of cordycepin (3′-deoxyadenosine) and A1Me3 proceeds mostly with retention of configuration at the 4′-position: the 4′-benzoyloxy substrate having the β-D-configuration (8a) gave the 4′-methylated β-D-nucleoside (9a) with a high diastereomeric excess, while the substrate 8b having the opposite 4′-configuration gave the corresponding α-L-isomer (9b) with a comparatively lower stereoselectivity. The SNi mechanism is proposed for this reaction (from 8 to 9). The polarity of the solvent has a significant influence on the stereoselectivity, especially for the formation of 9b. [ABSTRACT FROM AUTHOR]

Upon epoxidation with dimethyldioxirane, the 2′,5′-bis-O-silyl derivatives of 9-(3-deoxy-β-D-glycero-pent-3-enofuranosyl)adenine gave the respective ‘3′,4′-up’ epoxides exclusively. Reaction between these epoxides and Me3Al was investigated in detail. It was found that the stereoselectivity of epoxide ring opening (anti versus syn) varied significantly upon changing the amount of Me3Al, the solvent, the O-silyl protecting group, and the reaction temperature. A possible reaction mechanism is proposed. [ABSTRACT FROM AUTHOR]