Total Synthesis of (+)-Haperforin G

Zhenyu Zhang; Wei Zhang; Jun Chen Tang; Jin Teng Che; Zhongchao Zhang; Jia Hua Chen; Zhen Yang

doi:10.1021/acs.joc.3c00542

Total Synthesis of (+)-Haperforin G

J Org Chem. 2023 Aug 4;88(15):10539-10554. doi: 10.1021/acs.joc.3c00542. Epub 2023 Jul 16.

Authors

Zhenyu Zhang¹, Wei Zhang¹, Jun Chen Tang¹, Jin Teng Che¹, Zhongchao Zhang¹, Jia Hua Chen¹, Zhen Yang^{1

2

3}

Affiliations

¹ Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education and Beijing National Laboratory for Molecular Science (BNLMS), and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
² Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
³ Shenzhen Bay Laboratory, Shenzhen 518055, China.

PMID: 37455391
DOI: 10.1021/acs.joc.3c00542

Abstract

(+)-Haperforin G was synthesized in 20 steps from commercially available starting materials. A Co-catalyzed intramolecular Pauson-Khand reaction was used for stereoselective construction of cyclopentanone bearing an all-carbon quaternary stereogenic center at the bridge-head position. Light-initiated photocatalysis was used for convergent and asymmetric cross-coupling of the unstabilized C(sp³) radical with an enone. The developed chemistry paves the way to the synthesis of structurally diverse analogs of haperforin G (6).