Synthesis of anticancer agents using Prins cyclization

该方案的目标是开发基于Prins环化的新反应，并应用这些新的 合成复杂天然产物的反应。将开发的新方法包括第二代 Mukayama Aldol Prins(MAP)与未活化的烯烃的反应。一种新的烯酮级联环化反应 还发现了烯醇醚，将对其进行调查。我们将研究Prins环化的机理， 并将研究2-羟基酮Cope重排的作用。Prins环化反应中令人惊讶的轴向选择性 在TMSBr的推动下，环化反应将从力学和实际制备过程两个方面进行研究。 基于这种新方法的合成包括通向花蕾蛋白I的路线，这是一种新的合成方法 银杏内酯A、拉索内酯A和肯德霉素。银杏内酯A和拉索内酯A都显示出有效的 对人类癌细胞的细胞毒性，计划中的合成比目前任何一种合成都更简洁和有效 对这些重要化合物进行了报道。本文所述的工作将推动合成化学和 为有机化学家提供新的工具。这些工具将促进许多新结构的合成，这些结构可能 作为新的药剂很重要。

The goals of this proposal are to develop new reactions based on the Prins cyclization and to apply these new reactions to the synthesis of complex natural products. New methods to be developed include the second generation Mukayama aldol Prins (MAP) reaction with unactivated alkenes. A new cascade cyclization reaction between enones and enol ethers has been discovered that will be investigated. The mechanism of the Prins cyclization will be studied, and the role of 2-oxonia Cope rearrangements will be investigated. The surprising axial selective in Prins cyclizations promoted by TMSBr cyclization will be studied both mechanistically and as a practical preparative procedure. Syntheses based on this new methodology include routes to calyxin I, a second-generation synthesis of leucascandrolide A, lasonolide A and kendomycin. Both leucascandrolide A and lasonolide A have shown potent cytotoxicity against human cancer cell lines, and the planned syntheses are more concise and efficient than any yet reported for these important compounds. The work described herein will advance the state of synthetic chemistry and provide new tools for organic chemists. These tools will facilitate the synthesis of many new structures that may be important as new pharmaceutical agents.