Chemoenzymatic Asymmetric Total Synthesis of Nonanolide (Z)‐Cytospolides D, E and Their Stereoisomers. Issue 4 (26th November 2013)

• Record Type: Journal Article
• Authors: Rej, Rohan Kalyan; Nanda, Samik
• Is Part Of: European journal of organic chemistry. Issue 4(2014)
• Page Start: 860
• Page End: 871
• Publication Date: 2013-11-26
• Subjects: Natural products -- Asymmetric synthesis -- Hydrocyanation -- Ring closing metathesis -- Chiral resolution -- Enzymes -- Enantioselectivity; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201301365
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: Chemoenzymatic asymmetric total synthesis of the ( Z )‐isomer of the naturally occurring decanolide cytospolides D, E and six stereoisomers is reported. The main highlight of the synthetic venture involves ring‐closing metathesis (RCM) reaction of a suitably functionalized ester compound, which was assembled by the Yamaguchi coupling of the required acid and alcohol fragments. The alcohol fragment was accessed by two alternative chemoenzymatic processes, one being hydroxynitrile lyase mediated hydrocyanation, whereas lipase‐catalyzed transesterification was the key sep in the second route. The acid fragment was constructed by an enantioselective enzymatic desymmetrization (EED) of prochiral 2‐methyl‐1, 3‐propanediol and Corey–Bakshi–Shibata (CBS) mediated stereoselective carbonyl reduction. Abstract : Stereochemically pure nonanolides ( Z )‐cytospolides D, E and a number of analogues have been synthesized by a chemoenzymatic approach. Lipase‐mediated enantioselective enzymatic desymmetrization (EED) reaction and hydroxynitrile lyase mediated enzymatic hydrocyanation was successfully applied to access advanced intermediates for cytospolides. Yamaguchi esterification followed by ring‐closing metathesis reaction afforded the ( Z )‐cytospolides.