Enantioselective Total Synthesis of Berkeleyone A and Preaustinoids. Issue 27 (24th May 2021)

• Record Type: Journal Article
• Authors: Zhang, Yang; Ji, Yunpeng; Franzoni, Ivan; Guo, Chuning; Jia, Hongli; Hong, Benke; Li, Houhua
• Is Part Of: Angewandte Chemie international edition. Volume 60:Issue 27(2021)
• Page Start: 14869
• Page End: 14874
• Publication Date: 2021-05-24
• Subjects: biomimetic rearrangements -- hidden symmetry -- meroterpenoids -- natural products -- total synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202104014
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Herein we report the first enantioselective total synthesis of 3, 5‐dimethylorsellinic acid‐derived meroterpenoids (−)‐berkeleyone A and its five congeners ((−)‐preaustinoids A, A1, B, B1, and B2) in 12–15 steps, starting from commercially available 2, 4, 6‐trihydroxybenzoic acid hydrate. Based upon the recognition of latent symmetry within D‐ring, our convergent synthesis features two critical reactions: 1) a symmetry‐breaking, diastereoselective dearomative alkylation to assemble the entire carbon core, and 2) a Sc(OTf)3 ‐mediated sequential Krapcho dealkoxycarbonylation/carbonyl α‐ tert ‐alkylation to forge the intricate bicyclo[3.3.1]nonane framework. We also conducted our preliminary biomimetic investigations and uncovered a series of rearrangements (α‐ketol, α‐hydroxyl‐β‐diketone, etc.) responsible for the biomimetic diversification of (−)‐berkeleyone A into its five preaustinoid congeners. Abstract : Based upon the recognition of latent symmetry within D‐ring, we accomplished the first enantioselective total synthesis of (−)‐berkeleyone A and its five preaustinoid congeners. Meanwhile, we also uncovered a series of biomimetic rearrangements that would lend credence to the proposed biosynthetic sequence of DMOA‐derived meroterpenoids.