Total Synthesis of Bioactive Natural Products

摘要 这项计划的目标是定义合成的新战略和方法 含有七元环的生物活性天然产物。我们所研究的分子 Make将提供研究许多生物过程的工具，并可能最终用于 开发新的治疗方法，特别是治疗癌症。具体地说，我们打算开发一种 重排甾体化合物皮质抑素A合成的一般策略 以及石松属植物中的生物碱。皮质酮是一种有效的血管生成药物 抑制剂，应该可以用来对抗肿瘤细胞的转移。我们提出了一项战略 利用环庚二烯前体合成这些天然产物。这些 环庚二烯是由新的金属介导法生成的。这是我们的 期望七元环的这些新的方法学发展 形成将简化复杂分子的合成。全合成 皮质素和石松生物碱将推动新的发展，这反过来将是 应用于其他生物和结构感兴趣的分子的合成。这些 捐款将帮助人类医学和化学生物学的进步，使用 分子。

Abstract The goal of this program is to define new strategies and methods for the synthesis of bioactive natural products that contain a seven-membered ring. The molecules we make will provide tools to study many biological processes and may ultimately be used to develop new therapeutics, especially for cancer. Specifically, we intend to develop a general strategy for the synthesis of the rearranged steroidal compounds cortistatin A and alkaloids in the Lycopodium family. The cortistatins are potent angiogenesis inhibitors and should find use in combating tumor cell metastasis. We present a strategy to synthesize these natural products using cycloheptadiene precursors. These cycloheptadienes are in turn generated from novel metal-mediated methods. It is our expectation that these new methodological developments for seven-membered ring formation will streamline the synthesis of complex molecules. The total synthesis of the cortistatins and Lycopodium alkaloids will drive new developments, which will in turn, be applied to the synthesis of other molecules of biological and structural interest. These contributions will aid advances in human medicine and chemical biology using small molecules.