Asymmetric synthesis of a novel conformationally constrained D-lysine analogue with a piperidine skeleton

A practical asymmetric synthesis of enantiomerically pure(2R,4R)-1-(tert-butoxycarbonyl)-4-[2-(methoxycarbonylamino)ethyl]pipecolic acid starting from easily accessible (R)-2-[(S)-1,2-bis(benzyloxy)ethyl]-1-[(S)-1-phenylethyl]-4-piperidone in around 33 % overall yield has been performed. The efficiency of the synthetic strategy developed for the synthesis of this novel conformationally constrained D-lysine analogue relies on the high-yielding Wadsworth–Emmons reaction of a 2-substituted 4-piperidone and the diastereoselective reduction of the exocyclic C=C double bond at the 4-position of the piperidine ring.This work was supported by the Gobierno de Aragón. P. E. is thankful for a predoctoral fellowship from the Spanish Ministerio de Ciencia y Tecnología (MCYT).Peer reviewe