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.
