A general approach to (5S,6R)-6-alkyl-5-benzyloxy-2-piperidinones: application to the asymmetric syntheses of neurokinin substance P receptor antagonist (-)-L-733,061 and (-)-deoxocassine.
A general approach to (5S,6R)-6-alkyl-5-benzyloxy-2-piperidinones based on the regio- and diastereoselective reductive alkylation of (S)-3-benzyloxyglutarimide 7 is described. This method opens an entrance to chiral nonracemic substituted 3-piperidinols. The versatility of the method is illustrated by the asymmetric syntheses of neurokinin substance P receptor antagonist L-733,061 (ent-1), (-)-deoxocassine (4), and an inhibitor of HIV proteases (5a).
Liu
Liang-Xian
LX
Department of Chemistry and The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian 361005, P. R. China.
Ruan
Yuan-Ping
YP
Guo
Zheng-Qing
ZQ
Huang
Pei-Qiang
PQ
D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D015394:Molecular Structure; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013373:Substance P / Q000037:antagonists & inhibitors*
D017320:HIV Protease Inhibitors; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; C492728:deoxocassine; C103788:3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine; D013373:Substance P