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

QS-21 合成中的 Baylis-Hillman/羟醛环化

• 批准号: 7013672
• 负责人: REEMA K THALJI
• 金额: $ 1.32万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7013672
• 关键词: AIDS vaccines; biological products; chemical reaction; chemical synthesis; cyclic compound; drug design /synthesis /production; immunomodulators; method development; neoplasm /cancer vaccine; postdoctoral investigator; triterpenes

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.

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，并将其应用于天然产物的合成。该方法包括乙烯类的Morita-Baylis-Hillman反应和随后的羟醛缩合，在单一步骤中使用单一催化剂进行。这种方法的意义将在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艾滋病毒疫苗佐剂。合成策略包括在一个优雅的环化步骤中使用所提出的方法，该步骤应该在一个步骤中生成五个环系中的三个。虽然为期两年的博士后任命的时间限制不允许申请者合成整个QS-21，但预计赞助者小组最终可能使用他们的糖苷方法完成该分子的完全合成。除了对合成结构复杂的五环三萜的有限文献作出贡献外，这一重要分子的全合成将为广泛的生物学研究提供足够的材料。