Two synthetic routes to 2′,3′-dideoxy-3′-C-(hydroxymethyl)-4′-thionucleosides

Abstract

A number of 2′,3′-dideoxy-3′-C-(hydroxymethyl)-4′-thionucleosides have been prepared from either (4R, 5S)-4,5-bis(tert-butyldimethylsiloxymethyl)tetrahydrofuran-2-one or from (2R, 3R)-1-benzyloxy-3-(benzyloxymethyl)hex-5-en-2-ol. The former was converted into methyl (3R, 4S)-4-acetylsulfanyl-5-(tert-butyldimethylsiloxy)-3-(tert-butyldimethylsiloxymethyl)pentanoate and then into 1-O-acetyl-2,3-dideoxy-3-C-(tert-butyldimethylsiloxymethyl)-5-O-(tert-butyldimethylsilyl)-4-thio-D-erythro-pentofuranose prior to coupling with silylated pyrimidines. The second key intermediate was converted into (2R, 3R)-1-benzyloxy-3-benzyloxymethyl-5,5-bis(benzylsulfanyl)pentan-2-ol and thence via the mesyl ester into 1-S-benzyl-5-O-benzyl-3-C-(benzyloxymethyl)-2,3-dideoxy-1,4-dithio-D-erythro-pentofuranose prior to coupling with silylated pyrimidines.