Document Detail


Epoxide-hydrolase-initiated hydrolysis/rearrangement cascade of a methylene-interrupted bis-epoxide yields chiral THF moieties without involvement of a "cyclase".
MedLine Citation:
PMID:  19496106     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In contrast with electrophilic enzyme-catalysed cyclisations in terpenoid biosynthesis, cyclisations of tetrahydrofuran moieties found in several groups of natural products, such as annonaceous acetogenins, neurofurans and phytooxylipins, appear to proceed through a nucleophilic cascade mechanism starting from bis-epoxy fatty acid precursors. This hypothesis was verified by epoxide-hydrolase-catalysed hydrolytic ring-opening/cyclisation cascades starting from a methylene-interrupted meso-bis-epoxide model substrate, which furnished the corresponding THF products with excellent de and ee values. Molecular modelling showed that the points of enzyme attack were consistent with the stereospecificities of the enzymes, whereas the stereochemical courses of the cyclisation were solely governed by Baldwin's rules and did not invoke the involvements of a "cyclase".
Authors:
Barbara T Ueberbacher; Gustav Oberdorfer; Karl Gruber; Kurt Faber
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chembiochem : a European journal of chemical biology     Volume:  10     ISSN:  1439-7633     ISO Abbreviation:  Chembiochem     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-07-14     Completed Date:  2009-10-08     Revised Date:  2011-04-06    
Medline Journal Info:
Nlm Unique ID:  100937360     Medline TA:  Chembiochem     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1697-704     Citation Subset:  IM    
Affiliation:
Department of Chemistry, Organic and Bioorganic Chemistry, University of Graz, Heinrichstrasse 28, Graz, Austria.
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MeSH Terms
Descriptor/Qualifier:
Biocatalysis
Biotransformation
Catalytic Domain
Computer Simulation
Cyclization
Epoxide Hydrolases / chemistry,  metabolism*
Epoxy Compounds / chemistry*,  metabolism
Furans / chemistry*,  metabolism
Hydrolysis
Protein Structure, Tertiary
Stereoisomerism
Grant Support
ID/Acronym/Agency:
W 901-B12//Austrian Science Fund FWF
Chemical
Reg. No./Substance:
0/Epoxy Compounds; 0/Furans; 109-99-9/tetrahydrofuran; EC 3.3.2.-/Epoxide Hydrolases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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