Biocatalytic asymmetric rearrangement of a methylene-interrupted bis-epoxide: simultaneous control of four asymmetric centers through a biomimetic reaction cascade.
Asymmetric enzyme-catalyzed hydrolysis of methylene-interrupted bis-epoxides 1 a and 1 b catalyzed by bacterial epoxide hydrolases furnished tetrahydrofuran derivatives 2 a and 2 b through a hydrolysis-rearrangement cascade. Whereas racemic bis-oxiranes 1 b-d underwent kinetic resolution with moderate stereoselectivities to yield products with up to 92 % ee and 66 % de: meso-bis-oxirane cis,cis-1 a was transformed into (6R,7R,9S,10S)-2 a in 94 % ee and 89 % de at high conversion (85 %) by Rhodococcus sp. CBS 717.73 as the major product. The reaction sequence resembles a biomimetic reaction cascade and provides an efficient entry into the structural core of annonaceous acetogenins with simultaneous control of four stereocenters.
Glueck
Silvia M
SM
Department of Chemistry, Organic & Bio-Organic Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria.
Fabian
Walter M F
WM
Faber
Kurt
K
Mayer
Sandra F
SF
D000192:Actinomycetales / Q000201:enzymology; D032701:Biomimetics; D002384:Catalysis; D003500:Cyclization; D004851:Epoxide Hydrolases / Q000378:metabolism*; D004852:Epoxy Compounds / Q000737:chemistry* / Q000378:metabolism*; D006838:Hydrocarbons / Q000737:chemistry / Q000378:metabolism; D006868:Hydrolysis; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D013237:Stereoisomerism
D004852:Epoxy Compounds; D006838:Hydrocarbons; C030011:carbene; D004851:Epoxide Hydrolases; D008697:Methane