Stereochemistry of the benzodiazepine based Ras farnesyltransferase inhibitors

Chiral benzodiazepine I is the preferred dipeptide turn mimic enantiomer employed in a series of Ras farnesyltransferase inhibitors. It was resolved as the camphorsulfonic acid salt of its methyl ester via a directed crystallization process. Crystallographic analysis of a derivative established R stereochemistry at C-3. The stereochemistry of the additional two chiral centers in derived inhibitor II is addressed.