Synthesis of 2’-Deoxy-4’-C-hydroxymethyl-4’-thioribonucleosides and Their 2’,3’-Dideoxy and 2’,3’-Didehydro-2’,3’-dideoxy Analogues

Abstract

- (±)-2'-Deoxy-4'-C-hydroxymethyl-4'-thioribonucleosides (1) and their 2', 3'-dideoxy- (2) and 2', 3'-didehydro-2', 3 '-dideoxy- (3) analogues have been prepared from hydrothiophene derivatives 2,2-bis(benzyloxymethyl)-3-benzyloxytetrahydrothiophene (4), 2,2-bis-(acetoxymethyl)tetrahydrothiophene (5) and 2,2-bis(acetoxymethyl)-2,5-dihydrothiophene (6), respectively. Preparation of the compound 1 has been carried out via N-glycosylation of the corresponding sulfoxide 9, derived from 4 by m-CPBA oxidation, with trimethylsilylated pyrimidines and trimethylsilyl triflate (Kita-O'Niel-Matsuda's method; modified Pummerer rearrangement). On the other hand, the compounds 2 and 3 have been obtained via N-glycosylation of the corresponding 4'-thiofuranoses 7 and 8 with trimethylsilylated pyrimidines and SnCl 4 , respectively, while the compounds 7 and 8 have been prepared from compounds 5 and 6 by an electrochemical 2-acetoxylation, respectively.