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

Abstract

Herein we report a structure-unit-based asymmetric total synthesis of sinulochmodin C, a norcembranoid diterpenoid bearing a transannular strained ether bridge β-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 γ-keto enone intermediate, a Lewis acid/Brønsted acid mediated transannular oxa-Michael addition to fuse the β-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.