Radical acylation of carbohydrates and its solid phase reaction

Abstract

We have studied free radical C-acylation of carbohydrate derivatives. C-Branched glycoside and C-glycoside derivatives with new functional groups were synthesized by treatment of sulfonyloxime ether derivatives with halo or xanthate glycoside derivatives under radical conditions. New C(2), C(3), and C(6)-branched glycoside derivatives was prepared by reaction of adequate iodo derivatives with sulfonyloxime ether in reasonable yield. Especially, only beta-isomers were obtained in case of C(3)-branched glycoside derivatives and C(6)-acylated glycoside derivatives were obtained in high yield. New five C-nucleoside derivatives were synthesized from 5-O-acetyl-2,3-isopropylidene-1-S-methoxythiocarbonyl-1-thio-D-ribofuranose. We found that thio compound was more useful than 5-O-acetyl-2,3-isopropylidene-D-ribofuranosyl bromide as a stable radical precursor. The usefulness of the free radical-mediated acylation reactions using sulfonyloxime ether derivatives as carbonyl equivalent radical acceptors was proven by the application to solid-phase synthesis. The removal of excess tin reagent or dimeric by-products was easily accomplished by simple washing of the resin with solvents before cleavage. As would be expected from the nature of the radical reaction on solution phase, the reaction worked well with primary or secondary alkyl iodides but somewhat less efficiently with tertiary alkyl iodide. We have developed the first radical acylation approach on solid phase environment which we believe has great synthetic potential as new carbon-carbon bond forming method on solid phase for combinatorial chemistry.