Synthesis of Bioactive Natural Products

生物活性天然产物的合成

• 批准号: 6707011
• 负责人: Amos B Smith
• 金额: $ 27.35万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6707011
• 关键词: alkaloids; alkenes; antineoplastic antibiotics; aziridines; biological products; chemical structure function; conformation; diterpenes; drug design /synthesis /production; epoxides; indoles; insecticides; macrolide antibiotics; quinolizine; stereochemistry; sulfur compounds

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.

描述：（由申请人提供）本研究的主要目标 接下来四年的计划是：（a）完成总合成 抗癌剂（+） - 泰烷醇和（+） - 13-脱氧烷酚，利用A 统一的合成策略； （b）设计一种对映选择性总合成 有效的杀虫剂（+） - 结节酸; （c）实现 小说，建筑具有挑战性的大花环抗生素的总合成 Sorangicin A.此外，我们的Dithiane化学的新创新方向 会纵接：（d）二雄反应与含氮的电力物的反应 （例如，氮杂氨酸和烯丙基阿齐丁丁）用于开发新的 多组分组装策略； （e）双雄与烯丙基的反应 环氧化物利用SN2和SN2'添加歧管； （f）合并SN2 和sn2'Linchpin dithiane耦合。最后，我们将（g）展示 2-Lithio-2- trialkylsilyl-1,3-迪西亚人的多组分Linchpin耦合与 氮杂氨酸和乙烯基环氧化物，分别具有方便的总合成 Mantella生物碱223 AB和（+） - rimocidin的AglyCon。 除了这些特定的综合目标，这是一个一般的远程目标 程序是识别负责的分子体系结构 生物活性。因此，当我们为每个目标结构开发一种方法时， 我们还将准备旨在阐明的模型化合物 结构活动关系。