REGIO- AND STEREOSPECIFIC SYNTHESIS OF 7-DEAZAPURINE 2'-DEOXYRIBONUCLEOSIDES AND INCORPORATION OF NUCLEOSIDE ISOSTERES INTO OLIGONUCLEOTIDES

Abstract

2'-Deoxytubercidin and 7-deaza-2'-deoxyguanosine, isosteres of the parent nucleosides 2'-deoxyadenosine and 2'-deoxyguanosine have been synthesized via phase-transfer glycosylation of appropriately protected pyrrolo[2,3-d]pyrimidines with 1-chloro-2-deoxy-3 ,5-di-O-p-toluoy1-Derythro- pentofuranose via a regio- and stereospecific route. The nuclecside isosteres were provided with suitable protecting groups and converted into their O-3'-phosphoramidites. Application of these compounds in solid-support oligonucleotide synthesis yielded self-complementary oligomers with alternating d(TuT) or d(c’Gc) sequences. Additionally the incorporation of the 7-deazapurine 2'-deoxyribofuranosides into the Eco RI sequence was accomplished. Applying phosphite triester condensation in solution, (2',5')- and (3',5')-tubercidylyl-tubercidins were synthesized.