Synthesis of trans-Configurated Spacered Nucleoside Analogues Comprising a Difluorocyclopropane Moiety

Abstract

A novel class of trans-configurated difluorinated cyclopropanoic nucleoside analogues containing a methylene spacer between the cyclopropane ring and the heterocycle has been prepared. Some of these compounds showed weak anti-HIV activity in preliminary screenings.

Recent advances in the synthesis of fluorinated nucleosides

“…It should be noted that Csuk's group also synthesized the trans-configurated difluorocyclopropyl carbocyclic nucleosides 995 from the intermediate, (E)-4-(benzyloxy)-2-butenyl acetate 994, using a similar procedure. 353 Starting from the alkene intermediate 997, itself available through oxidation of the alcohol 996 followed by olefination with triethyl phosphonoacetate (TEPA), reduction and acetylation, the Csuk group also described an entry into the difluorinated cyclopropane nucleoside analogues 999, which were provided by the difluorocyclopropanation of the acetate 997, deacetylation, Mitsunobu reactions between the alcohol 998 with various nucleic bases followed by two consecutive deprotection steps (Scheme 148). 354 Additionally utilizing the alkylation-elimination method, Zemlicka and co-workers synthesized the methylene-gem-difluorocyclopropane nucleoside analogues 1004 and 1005 from the gem-difluorocyclopropane 991, which was first converted into the methylene-gem-difluorocyclopropane 1000 in three steps (Scheme 149).…”