Synthesis of 4-substituted-3-aminopiperidin-2-ones: application to the synthesis of a conformationally constrained tetrapeptide N-acetyl-Ser-Asp-Lys-Pro.
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)-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).
Kumar
Sukeerthi
S
Institut de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-Yvette Cedex, France.
Flamant-Robin
Céline
C
Wang
Qian
Q
Chiaroni
Angèle
A
Sasaki
N André
NA
D000586:Amination; D001952:Bridged-Ring Compounds / Q000737:chemistry*; D007769:Lactams / Q000737:chemistry*; D008956:Models, Chemical; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D010084:Oxidation-Reduction; D010881:Piperidones / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism
C016997:3-aminopiperidine-2-one; D001952:Bridged-Ring Compounds; D007769:Lactams; D009842:Oligopeptides; D010881:Piperidones; C058504:goralatide