Application - Nucleophilic Epoxide Ring Opening in Crixivan Synthesis

The protease inhibitor, Indinivar Sulfate (Crixivan) for HIV treatment, is synthesized via a convergent synthesis in which two larger pieces are condensed to form the Crixivan penultimate.

Indinivar Silfate (Crixivan)

The epoxide is ring opened with chiral piperazine carboxamide (shown on right in scheme below).  The nucleophilic nitrogen of the chiral amide is colored red and the epoxide is colored in blue.  The condensation is conducted by heating the two together.  The addition of acid (H+) in step 2, deprotects the acetonide (green) and the t-BOC protected nitrogen (purple).