Baylis-Hillman/Aldol Cyclization in Synthesis of QS-21

描述（由申请人提供）： 提出了一种合成重要的双环和多环体系的新方法，沿着其在天然产物合成中的应用。所述方法包括乙烯基醇Morita-Baylis-Hillman反应和随后的羟醛缩合，在单一步骤中并使用单一催化剂进行。该方法的重要性将在QS-21的五环三萜部分的合成中得到证明，QS-21是一种有效的癌症和HIV疫苗佐剂。该合成策略涉及所提出的方法在一个优雅的环化步骤，这应该在一个单一的步骤中产生五个环系统中的三个。虽然两年博士后任命的时间限制不允许申请人合成整个QS-21，但预计申办方小组最终可能使用其糖苷方法完成该分子的全合成。除了对结构复杂的五环三萜合成的有限文献做出贡献外，这种重要分子的全合成将为广泛的生物学研究提供足够的必要材料。

DESCRIPTION (provided by applicant): A novel methodology for the synthesis of important bicyclic and polycyclic ring systems is proposed, along with its application to a natural product synthesis. The method includes a vinylogous Morita-Baylis-Hillman reaction and subsequent aldol condensation, performed in a single step and using a single catalyst. The significance of this method will then be demonstrated in the synthesis of the pentacyclic triterpene portion of QS-21, a potent cancer and HIV vaccine adjuvant. The synthetic strategy involves the proposed method in an elegant cyclization step, which should generate three of the five ring systems in a single step. While time constraints of a two-year postdoctoral appointment will not allow synthesis of the entirety of QS-21 by the applicant, it is anticipated that the sponsor's group may ultimately complete the total synthesis of this molecule using their glycoside methodology. In addition to contributing to the limited literature on the synthesis of the structurally complex pentacyclic triterpenes, a total synthesis of this important molecule would provide sufficient material necessary for extensive biological investigations.