Practical Synthesis of a Renin Inhibitor via a Diastereoselective Dieckmann Cyclization

A scalable synthesis of a potent renin inhibitor (1) is described. The absolute stereochemistry is set via an unprecedented diastereoselective Dieckmann cyclization directed by a remote chiral protecting group. This transformation enables preparation of chiral 1,3-[3.3.1]-diazabicyclononenes by desy...

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Bibliographic Details
Published in:	Organic letters Vol. 12; no. 22; pp. 5146 - 5149
Main Authors:	Gauvreau, Danny, Hughes, Greg J, Lau, Stephen Y. W, McKay, Daniel J, O’Shea, Paul D, Sidler, Rick R, Yu, Bing, Davies, Ian W
Format:	Journal Article
Language:	English
Published:	United States American Chemical Society 19-11-2010
Subjects:	Azo Compounds - chemical synthesis Azo Compounds - chemistry Bridged Bicyclo Compounds, Heterocyclic - chemical synthesis Bridged Bicyclo Compounds, Heterocyclic - chemistry Crystallography, X-Ray Cyclization Molecular Conformation Molecular Structure Protease Inhibitors - chemical synthesis Protease Inhibitors - chemistry Protease Inhibitors - pharmacology Renin - antagonists & inhibitors Stereoisomerism Toluene - analogs & derivatives Toluene - chemical synthesis Toluene - chemistry Toluene - pharmacology
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Summary:	A scalable synthesis of a potent renin inhibitor (1) is described. The absolute stereochemistry is set via an unprecedented diastereoselective Dieckmann cyclization directed by a remote chiral protecting group. This transformation enables preparation of chiral 1,3-[3.3.1]-diazabicyclononenes by desymmetrization of alkyl-esters, with selectivities ranging from 4 to 17:1.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1523-7060 1523-7052
DOI:	10.1021/ol102131e