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里士满·萨蓬教授正在开发新的策略，以构建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，可用于开发各种疾病（包括癌症）的治疗方法，并了解生物化学过程。 Sarpong教授正在研究如何从一种名为carvone的有机化合物开始，这种化合物存在于香菜种子，绿薄荷，柑橘橙子皮和莳萝中，并将其转化为更复杂，生物活性的化合物phomactin和taxagifine。 Phomactin对导致血液凝固的蛋白质具有活性，而taxagifine与抗癌剂紫杉醇密切相关。 所研究的化学方法和分子合成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在初中、高中和大学一级向代表性不足的少数民族学生介绍绿色化学的原则。羟基化的蒎烯衍生物，可以很容易地从香芹酮在两个步骤中获得，可以应用在铑或钯催化的碳-碳键活化反应。这些反应的产物是带有α季中心的环己烯酮。这些结构基序映射到无数的天然产物，包括phomactins和taxoid，taxinine和taxagifine。 这种碳-碳键活化方法在合成这些分子中的应用正在进行中。 正在研究一个计划的合成phomactin A，利用“香芹酮成型”的策略，采用碳-碳键活化和碳-氢键活化步骤。 正在开发从香芹酮立体定向全合成taxagifine的方法，该方法为合成在C16和C17碳原子上具有不寻常羟基化的其他紫杉烷提供了蓝图。

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.