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

在这个由化学系化学合成计划资助的项目中，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，以构建被称为天然产品的复杂有机化合物。许多天然产物具有重要的生物活性，可能有助于开发包括癌症在内的各种疾病的治疗方法，并了解生化过程。萨尔邦教授正在研究如何从香芹酮开始，并将其转化为更复杂的生物活性化合物phomactin和紫杉醇。香芹酮存在于香菜籽、留兰、橘皮和小茴香中。Phomactin具有对抗导致血液凝结的蛋白质的活性，而紫杉醇与抗癌药物紫杉醇密切相关。正在研究的分子合成的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。Sarpong教授的小组继续致力于将绿色化学的原则介绍给初中、高中和大学水平上代表不足的少数族裔学生。香芹酮的两步反应即可方便地获得羟基萜烯衍生物，可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-四元中心的环己酮。这些结构基序映射到无数的天然产物上，包括假单胞菌素和紫杉醇，紫杉碱和紫杉酯。将这种碳-碳键活化方法应用于这些分子的合成正在进行中。一项合成鱼腥草素A的计划正在研究中，该计划采用了采用碳-碳键活化和碳-氢键活化步骤的“香芹酮成型”策略。从香芹酮到紫杉醇的立体专一性全合成正在开发中，这为合成其他在碳原子C16和C17上具有不寻常的羟化作用的紫杉醇提供了蓝图。

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.