Total Synthesis of (-)-Spinosyn A via Carbonylative Macrolactonization.

ABSTRACT: Spinosyn A (1), a complex natural product featuring a unique 5,6,5,12-fused tetracyclic core structure, is the major component of spinosad, an organic insecticide and an FDA-approved agent used worldwide. Herein, we report an efficient total synthesis of (-)-spinosyn A with 15 steps in the longest linear sequence and 23 steps total from readily available compounds 14 and 23. The synthetic approach features several important catalytic transformations including a chiral amine-catalyzed intramolecular Diels-Alder reaction to afford 22 in excellent diastereoselectivity, a one-step gold-catalyzed propargylic acetate rearrangement to convert 28 to ?-iodoenone 31, an unprecedented palladium-catalyzed carbonylative Heck macrolactonization to form the 5,12-fused macrolactone in one step, and a gold-catalyzed Yu glycosylation to install the challenging ?-forosamine. This total synthesis is highly convergent and modular, thus offering opportunities to synthesize spinosyn analogues in order to address the emerging cross-resistance problems.

SUBMITTER: Bai Y 

PROVIDER: S-EPMC5322741 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature