A regio and stereoselective synthesis of 2',2',3',4'-tetradeuterio-2'-deoxy nucleosides

Abstract

Methyl β-D-arabinopyranoside (1) has been stereoselectively deuterated, by the treatment of deuterated Raney N1 in D₂O, to give the 2,3,4-trideutereo-βD-arabinopyranoside 2 in 33% yield. It was then converted to 3,4-isopropylidene derivative 3b in 90% yield and subsequently derivatized to 2-0-phenylthiocarbonate 4 (85%). Compound 4 was deoxygenated at C-2 and was isolated as 2:8 (α:β) anomeric mixture 6 in 70% yield (based on 4 in two steps). Compound 6 was converted to the free sugar 7, by the treatment of 0.8 M aqueous HCl, which was then successively converted to pentofuranosides: 8 → 9 → 10; the crystalline α-chlorosugar 10 was thus obtained 1n 60% yield in four steps starting from 6. Subsequently α-chlorosugar 10 was coupled to different nucleobases of DNA to give 2',2',3',4'-tetradeuterio-2'-deoxynucleosides in moderate yields.