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

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journal contribution
posted on 22.07.2005 by Sukeerthi Kumar, Céline Flamant-Robin, Qian Wang, Angèle Chiaroni, N. André Sasaki
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 diastereoselective addition of cuprate to (E)-α,β-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).