Practical stereoselective synthesis of conformationally constrained unnatural proline-based amino acids and peptidomimetics

A practical synthetic scheme was developed to prepare both the cis- and trans-fused stereoisomers of N-Boc-L-octahydroindole-2-carboxylic acid (L-Oic) methyl ester. Key event of the synthetic sequence was the ring-closing metathesis of a suitable diallylated proline derivative. This is the first reported practical synthesis of the trans-fused isomer. Functionalization of the octahydroindole nucleus by electrochemical oxidation followed by acid-catalysed allylation paved the way for the preparation of reverse-turn dipeptide mimics.