Chemical Synthesis Using Carbon-Carbon Bond Activation/Cleavage of Carvone Derivatives

利用碳-碳键活化/裂解的化学合成香芹酮衍生物

• 批准号: 1566430
• 负责人: Richmond Sarpong
• 金额: $ 45万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1566430&HistoricalAwards=false
• 关键词: Chemical; Synthesis; Using; Carbon; Bond

In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Richmond Sarpong of the Department of Chemistry at the University of California, Berkeley is developing new strategies to build complex organic compounds called natural products. Many natural products possess important biological activities that may be useful for developing treatments for a variety of diseases, including cancer, and understanding biochemical processes. Prof. Sarpong is studying how to start with an organic compound called carvone, that is found in caraway seeds, spearmint, mandarin orange peels and dill, and transform it into more complex, biologically-active compounds phomactin and taxagifine. Phomactin has activity against the proteins that lead to blood clotting, and taxagifine is closely related to the anticancer agent, taxol. The chemical methods and strategies for molecule synthesis under investigation provide new ways to make these two natural products that may be applicable to preparing other natural product compounds. Professor Sarpong's group has a continuing commitment to introducing the principles of green chemistry to under-represented minority students at the middle school, high school and college level. Hydroxylated pinene derivatives that are easily accessed in two steps from carvone can be applied in either rhodium- or palladium-catalyzed carbon-carbon bond activation reactions. The products of these reactions are cyclohexenones bearing an alpha quaternary center. These structural motifs map onto myriad natural products including the phomactins and taxoids, taxinine and taxagifine. Applications of this carbon-carbon bond activation methodology to the syntheses of these molecules are being pursued. A plan for the synthesis of phomactin A is being studied that utilizes a "carvone molding" strategy employing carbon-carbon bond activation and carbon-hydrogen bond activation steps. A stereospecific total synthesis of taxagifine from carvone is being developed that provides a blueprint for the syntheses of other taxoids bearing unusual hydroxylation at carbon atoms C16 and C17.

在这个由化学部化学合成项目资助的项目中，加州大学伯克利分校化学系的Richmond Sarpong教授正在开发新的策略来构建被称为天然产物的复杂有机化合物。许多天然产物具有重要的生物活性，可能有助于开发各种疾病的治疗方法，包括癌症，以及了解生化过程。萨蓬教授正在研究如何从一种名为香芹酮的有机化合物开始，将其转化为更复杂的、具有生物活性的化合物，这种化合物存在于香芹籽、薄荷、橘子皮和莳萝中。Phomactin对导致血液凝固的蛋白质有活性，而taxagifine与抗癌剂紫杉醇密切相关。正在研究的分子合成化学方法和策略为制备这两种天然产物提供了新的途径，可能适用于制备其他天然产物化合物。萨蓬教授的小组一直致力于向初中、高中和大学的少数族裔学生介绍绿色化学的原理。羟基化蒎烯衍生物很容易从香豆酮两步获得，可以应用于铑或钯催化的碳-碳键活化反应。这些反应的产物是带有α -季中心的环己酮。这些结构基序映射到无数的天然产物，包括光动素和类taxoids，紫杉碱和紫杉碱。这种碳-碳键活化方法在这些分子合成中的应用正在研究中。目前正在研究一种合成phomactin A的计划，该计划利用碳-碳键激活和碳氢键激活步骤的“香芹酮成型”策略。以香芹酮为原料合成紫杉醇的立体特异性全合成方法正在开发中，这为在碳原子C16和C17上具有异常羟基化的其他类紫杉醇的合成提供了蓝图。