Synthesis and solid state conformation of phenylalanine mimetics constrained in a proline-like conformation

Abstract

We present the synthesis of five- and six-membered cyclic phenylalanine mimics ( 1, 9, 16, and 17) that are constrained in a proline-like conformation. The five-membered mimetic 16 was prepared by Ring Closing Metathesis (RCM) of diene 15, itself prepared by α-benzylation of the L-methionine derived oxazolidinone 10, followed by oxidative elimination, ring hydrolysis and N-allylation. The six-membered mimetic 1 was prepared by allylating the L-phenylalanine-derived oxazolidinone 5, followed by hydrolysis, N-allylation and RCM. Olefins 1 and 16 were catalytically hydrogenated to give 9 and 17, respectively. The solid state structures of 9 and 16 were determined by X-ray crystallography and their conformations compared with that of 1.