Synthesis of Bioactive Natural Products

描述：（由申请人提供）本研究的主要目标 未来四年的计划是：（一）完成全合成 抗癌剂（+）-替丹诺和（+）-13-脱氧替丹诺， 统一的合成策略;（B）设计对映选择性全合成 有效的杀虫剂（+）-节孢酸;和（C）以实现 新的、结构上具有挑战性的大环内酯类抗生素的全合成 囊兰菌素A此外，我们的二噻烷化学的新创新方向 将包括：（D）二噻烷与含氮亲电试剂的反应 (e.g.,氮丙啶和烯丙基氮丙啶）用于开发新的 多组分组装策略;（E）二噻烷与烯丙基的反应 环氧化物，利用SN 2和SN 2 '加成流形;以及（F）合并的SN 2 和SN 2 '关键二噻烷偶联。最后，我们将（G）展示 2-锂-2-三烷基甲硅烷基-1，3-二噻烷与 氮杂环丙烷和乙烯基环氧化物，分别与有利的全合成 Mantella生物碱223 AB和（+）-rimocidin的糖苷配基。 除了这些具体的综合目标之外， 程序是负责识别分子结构 生物活性因此，当我们开发针对每个靶结构的方法时， 我们还将制备模型化合物，用于阐明 构效关系

DESCRIPTION: (provided by applicant) The principal goals of this research program for the next four years are: (A) to complete the total synthesis of the anticancer agents (+)-tedanolide and (+)-13-deoxytedanolide, exploiting a unified synthetic strategy; (B) to devise an enantioselective total synthesis of the potent insecticidal agent (+)-nodulisporic acid; and (C) to achieve a total synthesis of the novel, architecturally challenging macrolide antibiotic sorangicin A. In addition, new innovative directions for our dithiane chemistry will indude: (D) reaction of dithianes with nitrogen-containing electrophiles (e.g., aziridine and allylic aziridines) for the development of new multicomponent assembly tactics; (E) reaction of dithianes with allylic epoxides, exploiting the SN2 and SN2' addition manifolds; and (F) merged SN2 and SN2' linchpin dithiane couplings. Finally, we will (G) showcase the multicomponent linchpin coupling of 2-lithio-2-trialkylsilyl-1,3-dithianes with aziridines and vinyl epoxides, respectively with expedient total syntheses of the Mantella alkaloid 223 AB and the aglycon of (+)-rimocidin. Beyond these specific synthetic objectives, a general, long-range goal of this program is the identification of the molecular architecture responsible for biological activity. Thus, as we develop an approach to each target structure, we will also prepare model compounds designed to permit the elucidation of structure-activity relationships.