Synthesis of Isoaminile Mediated by Enzymes

Abstract

A lipase-mediated synthesis of all four enantiomers of isoaminile is reported. The key issues of the paper are: (i) enantioselective acetylation of allylic alcohol (E)-(±)-5 to give (E,S)-5 (ee = 92%) and (E,R)-6 (ee >99%); (ii) Claisen-Johnson rearrangement of R and S enantiomers of 5 to generate the quaternary benzylic stereocenter; (iii) chromatographic separation of aldehyde diastereo­isomers; (iv) X-ray structure of aldehyde (2R,4R)-10; (v) unpredicted formation of lactone 12 during the hydrolysis of 11.

Key words

drugs - enzymes - enantiomeric resolutions - rearrangements - lactones

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