Synthesis of HIV-Maturation Inhibitor BMS-955176 from Betulin by an Enabling Oxidation Strategy

A concise and scalable second generation
synthesis of HIV maturation
inhibitor BMS-955176 is described. The synthesis is framed by an oxidation
strategy highlighted by a CuI mediated aerobic oxidation
of betulin, a highly selective PIFA mediated dehydrogenation of an
oxime, and a subsequent Lossen rearrangement which occurs through
a unique reaction mechanism for the installation of the C17 amino
functionality. The synthetic route proceeds in 7 steps with 47% overall
yield and begins from the abundant and inexpensive natural product
betulin.