TOTAL SYNTHESIS OF THE GPI-ANCHORING INHIBITOR YW3548

这项拟议的研究旨在完成最近表征的糖基磷脂酰肌醇(GPI)锚定抑制剂YW3548的收敛、立体选择性全合成。YW3548是一种非常有效的真核细胞中GPI合成的抑制剂，它含有不寻常的三碳环倍半萜-内酯骨架。所提出的收敛合成方法将包括乙烯基碳负离子与分子间的连续羰基加成，然后在二碘钐的介导下进行分子内亲核酰基取代，以形成功能化的八元碳环B。这种方法的独特之处在于它产生了烯基、氧代和二醇取代基，这将为合成精制生成的八元环提供处理。描述了序列反应中涉及的分子的形成策略以及完成YW3548的路线。

The proposed research is aimed at completing a convergent, stereoselective total synthesis of a recently characterized glycoslyphosphatidylinositol (GPI)-anchoring inhibitor YW3548. YW3548 consists of unusual tricarbocyclic sesterterpenoid delta-lactone framework and is a very potent inhibitor of GPI synthesis in eukaryotic cells. The proposed convergent synthesis will feature a sequential intermolecular carbonyl addition to a vinyl carbanion followed by an intramolecular nucleophile acyl substitution mediated by diiododsamarium to form the functionalized eight-membered carbocyclic ring B. This approach is unique in that it produces alkenyl, oxo and diol substituents, which will provide handles for synthetic elaboration of the generated eight-membered ring. The strategies for formation of the molecules involved in the sequenced reaction are described along with a route to the completion of YW3548.