Enantioselective Total Synthesis of Hyperforin and Pyrohyperforin

被引：17

作者：

Ji, Yunpeng ^{[1
]}

Hong, Benke ^{[1
]}

Franzoni, Ivan ^{[3
]}

Wang, Mengyang ^{[1
]}

Guan, Weiqiang ^{[1
]}

Jia, Hongli ^{[1
]}

Li, Houhua ^{[1
,2
]}

机构：

[1] Peking Univ, State Key Lab Nat & Biomimet Drugs, Chem Biol Ctr, Sch Pharmaceut Sci, Xue Yuan Rd 38, Beijing 100191, Peoples R China

[2] Nankai Univ, State Key Lab Med Chem Biol, 38 Tongyan Rd, Tianjin 300350, Peoples R China

[3] NuChem Sci Inc, 2350 Rue Cohen Suite 201, Saint Laurent, PQ H4R 2N6, Canada

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2022年 / 61卷 / 16期

基金：

中国国家自然科学基金;

关键词：

Dienes; Hydrogenation; Natural Products; Reaction Mechanisms; Total Synthesis; POLYCYCLIC POLYPRENYLATED ACYLPHLOROGLUCINOLS; ST-JOHNS-WORT; STEREOSELECTIVE TOTAL-SYNTHESIS; ALKYLATIVE DEAROMATIZATION-ANNULATION; ABSOLUTE-CONFIGURATION ASSIGNMENT; BIOMIMETIC TOTAL-SYNTHESIS; ALPHA-ALKYLATION; NATURAL-PRODUCTS; STEREOSPECIFIC 1,4-CIS-HYDROGENATION; TRISUBSTITUTED OLEFINS;

D O I：

10.1002/anie.202116136

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 alpha-alkylation of alpha,beta-unsaturated acid using chiral lithium amides as noncovalent stereodirecting auxiliaries; 2) a HfCl4-mediated carbonyl alpha-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.

引用

页数：7