Synthesis and anti-HIV-1 activities of novel N-O bond incorporataed nucleosides.

摘要

A series of 2',3'-dideoxy-2 '-beta-fluoro-3'-(N-hydroxy- N-methylamino)-D-arabinofuranosyl nucleoside analogues were efficiently prepared through a novel "concerted" conjugate addition of N-methythydroxylainine to a 2-fluorobutenolide. This method introduced the fluorine atom in the beta-configuration that was well correlated to the antiviral activities of 2'-fluorinated nucleosides. Further modifications of substituents, on the nitrogen atom allowed synthesizing various analogues with different substituted amino groups at the 3 ' position for their biological activity evaluations. Several analogues showed significant activities against HIV-1 in vitro.;Substituted imidazo[1,2-a]pyridine isoxazolinyl C-nucleosides were also prepared via well-studied 1,3-dipolar cycloaddition for testing their biological activities. This was the first example of C-nucleoside analogues in which an N-O bond was incorporated into the aglycon unit.