3,8-diazabicyclo[3.2.1]octan-2-one peptide mimetics: Synthesis of a conformationally restricted inhibitor of farnesyltransferase

[GRAPHICS] A new synthesis of the 3,8-diazabicyclo[3.2.1]octan-2-one framework is described. Transannular enolate alkylation of piperazinone derivatives provides a flexible route to highly constrained bicyclic peptidomimetic synthons with substitution at the C alpha position. The chemistry was used to produce a conformationally constrained farnesyltransferase inhibitor, which aided the elucidation of enzyme-bound conformation.