Synthesis and evaluation of a series of 1-(3-alkyl-2,3-dideoxy-alpha,beta-D-erythro-pentofuranosyl)thymines.

A series of 1-(3-alkyl-2,3-dideoxy-alpha,beta-D-erythro-pentofuranosyl)thymines (3'-alkyl-3'-deoxythymidines) has been prepared from 5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-D-glycero-pent-2- enono-1,4-lactone ((S)-5-[(tert-butyldiphenylsilyl)oxymethyl]-2(5H)- furanone) by Michael addition of the appropriate organocopper reagent, followed by reduction of the lactone, acetylation of the resulting hemiacetal, and trimethylsilyl triflate-catalyzed coupling with 2,4-di-O-(trimethylsilyl)thymine. The protected nucleosides were desilylated by using tetrabutylammonium fluoride to give anomeric mixtures of the free nucleosides. The unsubstituted 2',3'-dideoxynucleoside analog was similarly prepared from 5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-D-glycero-pentono- 1,4-lactone ((S)5-[(tert-butyldiphenylsilyl)-oxymethyl]-dihydro-2(3H)-fu r anone).