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.

Total synthesis and structure–antifouling activity relationship of scabrolide F

“…27,28 In the same year, Lee et al achieved the enantioselective total synthesis of (+)- 4 (an enantiomer of 4 ), which revealed the absolute configuration of natural (−)-10- epi -gyrosanolide E to be 4 . 29 Synthetic efforts toward polycyclic norcembranolides have culminated in recent reports of the enantioselective total synthesis of (−)-scabrolide A ( 8 ) by the groups of Stoltz, 30 a , b Fürstner, 31 Sarlah, 32 and Zhang; 33 (−)-yonarolide ( 9 ) by the groups of Stoltz 30 b and Sarlah; 32 and (+)-ineleganolide ( 10 ) by the groups of Wood 34 and Stoltz. 30 c In our work on the chemical synthesis and biological evaluation of cembranolides 35 and norcembranolides, we reported the first total synthesis of (−)-scabrolide F ( 7 ) as a communication in 2022.…”