Total Synthesis of Haliclonin A. (11th March 2021)

• Record Type: Journal Article
• Authors: Jin, Yuan; Orihara, Kensuke; Kawagishi, Fumiki; Toma, Tatsuya; Fukuyama, Tohru; Yokoshima, Satoshi
• Is Part Of: Angewandte Chemie. Volume 133:Number 17(2021)
• Page Start: 9752
• Page End: 9757
• Publication Date: 2021-03-11
• Subjects: alkaloids -- macrocycles -- marine natural products -- metathesis -- stereoselective reactions; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202016343
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: The total synthesis of haliclonin A was accomplished. Starting from 3, 5‐dimethoxybenzoic acid, a functionalized cyclohexanone fused to a 17‐membered ring was prepared through a Birch reduction/alkylation sequence, ring‐closing metathesis, intramolecular cyclopropanation, and stereoselective 1, 4‐addition of an organocopper reagent to an enone moiety. Reductive C−N bond formation via an N, O ‐acetal forged the 3‐azabicyclo[3.3.1]nonane core. The allyl alcohol moiety was constructed by a sequence involving stereoselective α‐selenylation of an aldehyde via an enamine, syn ‐elimination of a selenoxide, and allylation of the aldehyde with an allylboronate. Formation of the 15‐membered ring containing a skipped diene was achieved by ring‐closing metathesis, and final transformations led to the synthesis of haliclonin A. Abstract : A synthesis of a tetracyclic natural product, haliclonin A, was achieved. The cyclohexane ring was derived from 3, 5‐dimethoxybenzoic acid, which was elaborated via Birch reduction, intramolecular cyclopropanation, and a reaction with an organocopper reagent. The lactam ring was constructed via reductive C−N bond formation. The two macrocyclic rings were formed via ring‐closing metathesis.