Synthetic Studies Towards The Total Synthesis Of Amaryllidaceae AlkaloidGracilamine And XestospongiaMeroterpenoids Xestosaprol N And O

Part 1:total synthesis of gracilamine.Gracilamine is an Amaryllidaceae alkaloid which has a five-ring skeleton, and it also can be regarded as a hydrofluorenone containing natural product. In the course of our synthetic studies, the hexahydrofluorene skeleton (rings A-B-C) was constructed via a mild photo-Nazarov reaction. We originally employed the HLF reaction to form the D ring, which gave an unexpected regioisome. Then, the D ring was constructed by a Michael addition strategy. Formation of the E ring was achieved via an intramolecular Mannich reaction after testing the intramolecular oxidative coupling. We also synthesized many natural product analogues based on this transformation. Our synthetic route towards gracilamine was over 16 steps, in 1.3% yield. This work further confirm the C-6 stereochemistry of natural gracilamine, and it also laid foundations to their biological studies.Part 2:total synthesis of xestosaprol N and O.We developed two generations of synthetic approaches towards xestosaprol N and O. The first synthetic route was based on an intramolecular Heck reaction. However, we were not satisfied with the synthetic efficiency of this approach, such as the difficult starting material preparation, poor selectivity and redox economy. In the second generation route, we improved synthetic efficiency through a convergent approach. Wherein, the C-D ring fragment was prepared via a carbonyl α-arylation reaction and intramolecular Aldol condensation. The necessary oxidation state was introduced in the process of coupling step, and the core structure was built via Heck reaction. After a Mn(III) promoted radical reduction transformation, we finally got the key intermediate, which was prepared in the first generation. This work laid the foundation for the total synthesis of halenaquinones and exiguaquinol.