Synthesis of 4-Substituted-3-aminopiperidin-2-ones:Application to the Synthesis of a Conformationally Constrained Tetrapeptide N-Acetyl-Ser-Asp-Lys-Pro

摘要

A new and practical synthetic strategy is developed for the synthesis of six-membered lactam-bridged dipeptides,4-substituted-3-aminopiperidin-2-ones,featuring two key steps:(a) a diaste-reoselective addition of cuprate to (E)-alpha,beta-unsaturated ester (3) and (b) racemization-free reductive amination.On the basis of this methodology,conformationally constrained tetrapeptide N-acetyl-Ser-Asp-Lys-Pro (AcSDKP) (2) has been successfully synthesized from 3-amino-4-vinylpiperidin-2-one (22).