Chemical synthesis of 13C labeled anti-HIV nucleosides as mass-internal standards

Synthesis of [13C5]-labeled anti-HIV nucleosides, e.g. d4T, ddI, ddA, is described. The methodology used has been optimized due to the very high cost of the starting compound. The key step of this approach was the stereoselective dehomologation of 1,2:5,6-di-O-isopropylidene-3-oxo-α-d-glucofuranose (2) with periodic acid and sodium borohydride, which gave optically pure ribose derivative as the exclusive product. Nucleoside derivatives 6a–c were obtained from ribosylation of 5 with persilylated nucleobases under Vorbru¨ggen conditions. Deoxygenation of 9a–c under Corey-Winter conditions afforded the desired labeled nucleoside analogues 12a–c. [Copyright &y& Elsevier]