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

Liang-Xian Liu; Yuan-Ping Ruan; Zheng-Qing Guo; Pei-Qiang Huang

doi:10.1021/jo049166z

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

J Org Chem. 2004 Sep 3;69(18):6001-9. doi: 10.1021/jo049166z.

Authors

Liang-Xian Liu¹, Yuan-Ping Ruan, Zheng-Qing Guo, Pei-Qiang Huang

Affiliation

¹ Department of Chemistry and The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian 361005, P. R. China.

PMID: 15373484
DOI: 10.1021/jo049166z

Abstract

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).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Catalysis
Combinatorial Chemistry Techniques*
HIV Protease Inhibitors / chemical synthesis
HIV Protease Inhibitors / pharmacology
Molecular Structure
Neurokinin-1 Receptor Antagonists*
Piperidines / chemical synthesis*
Piperidines / pharmacology
Stereoisomerism
Substance P / antagonists & inhibitors*

Substances

HIV Protease Inhibitors
Neurokinin-1 Receptor Antagonists
Piperidines
deoxocassine
3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine
Substance P