Document Detail


The N-acyloxyiminium ion aza-Prins route to octahydroindoles: total synthesis and structural confirmation of the antithrombotic marine natural product oscillarin.
MedLine Citation:
PMID:  15137772     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The first enantiocontrolled total synthesis of the marine natural product oscillarin is described. The proposed structure and absolute configuration of oscillarin is thus confirmed, and a previously assigned structure of a subunit was shown to be incorrect. The X-ray structure of an oscillarin-thrombin complex was resolved at 2.0 A resolution, which validated its potent inhibitory activity against the enzyme with an IC(50) = 28 nM. Methodology was developed for the synthesis of enantiopure octahydroindole-2-carboxylic acids with usable functionality at C-6. The method consists of the halocarbocyclization of N-acyloxyiminium ions containing an olefinic tether in the presence of tin tetrachloride or tin tetrabromide. This N-acyloxyiminium ion aza-Prins carbocyclization proved to be general for the construction of octahydroindole and perhydroquinoline 2-carboxylic acids. Mechanistic rationales are based on an antiperiplanar attack of the terminal alkene on the iminium ion, leading to an incipient secondary carbocation which is trapped by halide via an equatorial attack. X-ray crystal structures of products corroborate the expected stereochemistry.
Authors:
Stephen Hanessian; Martin Tremblay; Jens F W Petersen
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  126     ISSN:  0002-7863     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-05-12     Completed Date:  2004-08-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6064-71     Citation Subset:  IM    
Affiliation:
Department of Chemistry, Université de Montréal, C.P. 6128, Station Centre-ville, Montréal, P.Q., H3C 3J7 Canada. stephen.hanessian@umontreal.ca
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MeSH Terms
Descriptor/Qualifier:
Alkylation
Aza Compounds / chemistry*
Biological Factors / chemical synthesis*,  chemistry
Crystallography, X-Ray
Cyclization
Fibrinolytic Agents / chemical synthesis*,  chemistry
Indicators and Reagents
Magnetic Resonance Spectroscopy
Marine Biology
Models, Molecular
Molecular Conformation
Oligopeptides / chemical synthesis*,  chemistry
Chemical
Reg. No./Substance:
0/Aza Compounds; 0/Biological Factors; 0/Fibrinolytic Agents; 0/Indicators and Reagents; 0/Oligopeptides; 0/Pla-Phe-Choi-Adc

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