Enantioselective Total Synthesis of Hyperforin and Pyrohyperforin

作者：Yunpeng Ji, Benke Hong, Ivan Franzoni, Mengyang Wang, Weiqiang Guan, Hongli Jia, Houhua Li · 发表于：Angewandte Chemie · 年份：2022 · DOI：10.1002/ange.202116136 · 被引用次数：6 · 研究领域：Natural Compound Pharmacology Studies、Biological Activity of Diterpenoids and Biflavonoids、Phytochemistry and biological activities of Ficus species

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 HfCl 4 ‐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.