TOTAL SYNTHESIS OF THE GPI-ANCHORING INHIBITOR YW3548

该研究旨在完成最近表征的glyypphosphatidylinositol （GPI）锚定抑制剂YW3548的聚合、立体选择性全合成。YW3548由一种特殊的三碳环酯萜-内酯框架组成，是一种非常有效的真核细胞GPI合成抑制剂。提出的会聚合成方法将在乙烯基碳离子上进行连续的分子间羰基加成，然后由二碘钐介导的分子内亲核试剂酰基取代，形成功能化的八元碳环b。这种方法的独特之处在于，它可以产生烯基、氧基和二醇取代基，这将为生成的八元环的合成精化提供线索。在测序反应中所涉及的分子的形成策略与完成YW3548的途径一起描述。

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.