Design and synthesis of stereochemically defined novel spirocyclic p2-ligands for hiv-1 protease inhibitors

Abstract

(Chemical Equation Presented) The synthesis of a series of stereochemically defined spirocyclic compounds and their use as novel P2-ligands for HIV-1 protease inhibitors are described. The bicyclic core of the ligands was synthesized by an efficient nBu3SnH-promoted radical cyclization of a 1,6-enyne followed by oxidative cleavage. Structure-based design, synthesis of ligands, and biological evaluations of the resulting inhibitors are reported. © 2008 American Chemical Society.