Synthesis of Bioactive Natural Products

描述：(申请人提供)本研究的主要目的 今后四年的方案是：(A)完成总合成 抗癌药物(+)-tedanolide和(+)-13-deoxtedanolide，利用 统一的合成策略；(B)设计一种不对称的全合成 有效的杀虫剂(+)--根瘤孢子酸；和(C)实现 具有结构挑战性的新型大环内酯类抗生素的全合成 此外，我们的二硫杂环戊烷化学的新的创新方向 将包括：(D)二硫杂环戊烷与含氮亲电体的反应 (例如，氮杂环丙烷和烯丙基氮杂环丙烷)用于开发新的 多组分组装策略；(E)二硫杂环戊烷与烯丙基的反应 环氧化合物，利用SN2和SN2‘加成流形；和(F)合并SN2 和SN2‘关键的二硫代偶联剂。最后，我们将(G)展示 2-锂-2-三烷基硅基-1，3-二硫杂环戊烷的多组分关键偶联 分别合成了氮杂环丙烷和乙烯基环氧化合物 Mantella生物碱223AB和(+)-Rimoidin的苷元。 在这些具体的综合目标之外，这一总体的、长期的目标 程序是识别分子的结构，负责 生物活性。因此，当我们开发出针对每个目标结构的方法时， 我们还将准备模型化合物，以允许澄清 结构-活性关系。

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.