Structure-Unit-Based Total Synthesis of (-)-Sinulochmodin C

By: Yi-Peng Zhang, Shufei Du, Ying Ma, Weixin Zhan, Wen Chen, Xiaodong Yang, Hongbin Zhang

Angewandte Chemie - International Edition

DOI：https://doi.org/10.1002/anie.202315481

Published：2023-11-27

Abstract

Herein we report a structure-unit-based asymmetric total synthesis of sinulochmodin C, a norcembranoid diterpenoid bearing a transannular strained ether bridge beta-keto tetrahydrofuran moiety. Our synthetic route features an intramolecular double Michael addition to construct stereospecifically the [7,6,5,5] tetracyclic skeleton, a vinylogous hydroxylation/oxidation procedure or a stereospecific epoxide opening/oxidation sequence to establish the gamma-keto enone intermediate, a Lewis acid/Bronsted acid mediated transannular oxa-Michael addition to fuse the beta-keto tetrahydrofuran moiety, a Mukaiyama hydration/Pd-C hydrogenation to reverse the C1-configuration of the isopropenyl unit, and a bioinspired transformation of sinulochmodin C into scabrolide A.