title: Epoxide-hydrolase-initiated hydrolysis/rearrangement cascade of a methylene-interrupted bis-epoxide yields chiral THF moieties without involvement of a "cyclase".
abstract: 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.affiliation: Department of Chemistry, Organic and Bioorganic Chemistry, University of Graz, Heinrichstrasse 28, Graz, Austria.
authors.forename: Barbara T
authors.initials: BT
authors.lastname: Ueberbacher
authors.forename: Gustav
authors.initials: G
authors.lastname: Oberdorfer
authors.forename: Karl
authors.initials: K
authors.lastname: Gruber
authors.forename: Kurt
authors.initials: K
authors.lastname: Faber
mesh_terms: D055162:Biocatalysis; D001711:Biotransformation; D020134:Catalytic Domain; D003198:Computer Simulation; D003500:Cyclization; D004851:Epoxide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D004852:Epoxy Compounds / Q000737:chemistry* / Q000378:metabolism; D005663:Furans / Q000737:chemistry* / Q000378:metabolism; D006868:Hydrolysis; D017434:Protein Structure, Tertiary; D013237:Stereoisomerism
chemical_list: D004852:Epoxy Compounds; D005663:Furans; C018674:tetrahydrofuran; D004851:Epoxide Hydrolases