PYRAZOLO[3,4-D]PYRIMIDINE 2'-DEOXYRIBONUCLEOSIDE AND 2',3'-DIDEOXYRIBONUCLEOSIDES - STUDIES ON THE GLYCOSYLATION OF 4-METHOXYPYRAZOLO[3,4-D]PYRIMIDINE

Abstract

The glycosylation of the 4-methoxypyrazolo[3,4-d]pyrimidine (5) anion with 1-halo-2-deoxyribose 6 in MeCN/TDA-1 gives N2-deoxynucleoside 9 (29%) together with N1-isomer 7 (48%) and its anomer 8 (6%) [7]. The alpha-D-anomer 8 is not formed and the yield of the beta-D-anomer 7 increased to 62% when dimethoxyethane is used as solvent and [18]crown-6 as catalyst. Employing 1-halo-2,3-dideoxyribose 10 instead of halogenose 6, the 2',3'-dideoxynucleosides 12 and 14 were formed which were desilylated (--> 1b and 2b) and converted into the ddI and ddA derivatives 3b (c7z8I(dd)), 15b (c7z8A(dd)), and 17 (c7z8A(dd)'). Contrary to 7-deazapurine nucleotides, the triphosphates of 3b and 15b showed no appreciable activity against HIV-reverse transcriptase.