Total Synthesis Of Wortmannins Via Reductive Heck Reaction

This dissertation focuses on the total synthesis of wortmannin-type natural products,using a Reductive Heck reaction as the key reaction to construct all-carbon quaternary stereocenters.These natural products include wortmannines,which are rearranged steroid natural products,and wortmannins,which are furanosteroids natural products.In 2016,the Yang group reported the isolation and structural identification of wortmannine A,which was obtained from the culture broth of Talaromyces wortmannii LGT-4,the wortmannine B and wortmannine C was also reported.We used commercially available ascorbic acid as the starting material and adopted a convergent synthesis strategy to construct key reaction precursors.Considering the structural characteristics of this class of natural products,we designed a diastereoselective intramolecular Reductive Heck reaction as the key reaction and constructed the C-ring and C-10 quaternary stereocenters in one step through this reaction.Finally,starting from known compounds,the core structure of wortmannine A could be synthesized in seven steps.After completing the exploration of the synthesis of wortmannine A,we further explored the synthesis of wortmannin.In 1957,the Brain group reported the isolation and structural identification of wortmannin,which was isolated from the culture broth of Penicillium wortmannii.This natural product exhibits good antibacterial activity and excellent inhibitory activity against PI3 K receptors.For the synthesis of this natural product,we further screened the conditions of the Reductive Heck reaction based on the previous study of our research group,and then adjusted the protective groups of the substrate and adjusted the functional groups,finally obtained the cyclization precursor of the lactone ring of this natural product,laid a foundation for further exploration of this natural product.