Total Synthesis of (−)‐Enigmazole A. Issue 18 (24th March 2018)

• Record Type: Journal Article
• Authors: Sakurai, Keisuke; Sasaki, Makoto; Fuwa, Haruhiko
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 18(2018)
• Page Start: 5143
• Page End: 5146
• Publication Date: 2018-03-24
• Subjects: macrocycles -- metathesis -- natural products -- rearrangement -- total synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201801561
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Total synthesis of (−)‐enigmazole A, a marine macrolide natural product with cytotoxic activity, has been accomplished. The tetrahydropyran moiety was constructed by means of a domino olefin cross‐metathesis/intramolecular oxa‐Michael addition of a δ‐hydroxy olefin. After coupling of advanced intermediates, the macrocycle was formed through gold‐catalyzed rearrangement of a propargylic benzoate, followed by ring‐closing metathesis of the resultant α, β‐unsaturated ketone. Abstract : An enigma resolved : Total synthesis of (−)‐enigmazole A has been achieved. Highlights of the synthesis include olefin cross‐metathesis/intramolecular oxa‐Michael addition for stereoselective construction of the tetrahydropyran ring and gold‐catalyzed propargylic benzoate rearrangement/ring‐closing metathesis for closure of the macrocycle.