Enantioselective Total Synthesis of Hyperforin and Pyrohyperforin. Issue 16 (19th February 2022)

• Record Type: Journal Article
• Authors: Ji, Yunpeng; Hong, Benke; Franzoni, Ivan; Wang, Mengyang; Guan, Weiqiang; Jia, Hongli; Li, Houhua
• Is Part Of: Angewandte Chemie international edition. Volume 61:Issue 16(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-19
• Subjects: Dienes -- Hydrogenation -- Natural Products -- Reaction Mechanisms -- Total Synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202116136
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Capitalizing on the late‐stage diversification of an essential 1, 3‐diene intermediate, we describe herein a 9‐step enantioselective total synthesis of (+)‐hyperforin and (+)‐pyrohyperforin, starting from commercially available allylacetone. Our convergent synthesis features a series of critical reactions: 1) an enantioselective deconjugative α‐alkylation of α, β‐unsaturated acid using chiral lithium amides as noncovalent stereodirecting auxiliaries; 2) a HfCl4 ‐mediated carbonyl α‐ tert ‐alkylation to forge the intricate bicyclo[3.3.1]nonane framework; 3) an abiotic cascade pyran formation; and 4) a selective 1, 4‐semihydrogenation of polyenes. During the course of our synthesis, we also identified a 1, 2‐cyclopropanediol overbred intermediate which was responsible for the 1, 3‐diene precursor formation through a controlled fragmentation. Abstract : A 9‐step enantioselective total synthesis of both (+)‐hyperforin and its pyran congener (+)‐pyrohyperforin is described herein. The synthesis highlights a late‐stage 1, 3‐diene diversification, including an abiotic cyclization cascade for pyran formation, and a selective 1, 4‐semihydrogenation of polyenes.