title: 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 α-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 β-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.
authors: Department of Chemistry and Center for Cancer Research, Purdue University , West Lafayette, Indiana 47907, United States.
authors: Yu
authors: Y
authors: Bai
authors: Department of Chemistry and Center for Cancer Research, Purdue University , West Lafayette, Indiana 47907, United States.
authors: Xingyu
authors: X
authors: Shen
authors: Department of Chemistry and Center for Cancer Research, Purdue University , West Lafayette, Indiana 47907, United States.
authors: Yong
authors: Y
authors: Li
authors: Department of Chemistry and Center for Cancer Research, Purdue University , West Lafayette, Indiana 47907, United States.
authors: Mingji
authors: M
authors: Dai
mesh_terms: D000588:Amines / Q000737:chemistry; D002384:Catalysis; D060326:Chemistry Techniques, Synthetic; D007783:Lactones / Q000737:chemistry*; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000588:Amines; D007783:Lactones; D018942:Macrolides; C114883:spinosyn A