Strategies and Tactics for Natural Products Synthesis

天然产物合成的策略和策略

• 批准号: 7241965
• 负责人: GARY ALLEN SULIKOWSKI
• 金额: $ 2.95万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7241965
• 关键词: Enterococcus; Staphylococcus aureus; alkaloids; antineoplastics; biological products; carbamates; chemical synthesis; diazo compound; nitrogen; piperidine; quinolizine; spirane; stereochemistry

DESCRIPTION (provided by applicant): The long-term objective of this research program is to advance the practice of complex molecule synthesis. Special emphasis is placed on natural products that contain nitrogen since an unusually large number of pharmacologically active compounds incorporate this element within their structure. Despite the many advances in organic synthesis in the past 20th century the efficient and economical synthesis of complex natural products remains a challenging endeavor. Our plan is to introduce new inexpensive building blocks to the field of organic synthesis for use in asymmetric synthesis of nitrogen heterocycles. These building blocks would expedite the chemical synthesis of the rare marine alkaloid upenamide, the stemona alkaloids and 2-substituted piperidine alkaloids. We also present a plan for the synthesis of Iomaiviticins A and B, secondary metabolites isolated from fermentation of a marine derived actinomycetes. Lomaiviticins A and B are potent antibiotics against Gram-positive bacteria Staphylococcus aureus and Enterococcus faecium (MIC 6-25 ng/spot). An unusual structural feature of the Iomaiviticins is the incorporation of two diazo groups within their structure.

描述（由申请人提供）：该研究计划的长期目标是推进复杂分子合成的实践。特别强调含有氮的天然产物，因为异常大量的药理活性化合物在其结构中结合了这种元素。尽管在过去的 20 世纪有机合成取得了许多进展，但复杂天然产物的高效且经济的合成仍然是一项具有挑战性的工作。我们的计划是将新的廉价结构单元引入有机合成领域，用于氮杂环的不对称合成。这些结构单元将加速稀有海洋生物碱乌佩酰胺、百部生物碱和 2-取代哌啶生物碱的化学合成。我们还提出了 Iomaiviticins A 和 B 的合成计划，它们是从海洋来源的放线菌发酵中分离出来的次级代谢产物。 Lomaiviticins A 和 B 是针对革兰氏阳性菌金黄色葡萄球菌和屎肠球菌的强效抗生素（MIC 6-25 ng/点）。 Iomaiviticins 的一个不寻常的结构特征是在其结构中掺入了两个重氮基团。