Strategies and Tactics for Natural Products Synthesis

描述(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。特别强调的是含有氮的天然产品，因为大量的药理活性化合物在其结构中加入了这种元素。尽管有机合成在过去的20世纪取得了许多进展，但高效、经济地合成复杂的天然产物仍然是一项具有挑战性的工作。我们的计划是在有机合成领域引入新的廉价的构建单元，用于氮杂环的不对称合成。这些构件将加快稀有海洋生物碱丁苯酰胺、球茎生物碱和2-取代哌啶生物碱的化学合成。我们还提出了合成Iomaiviticin A和B的计划，Iomaiviticin A和B是从海洋来源放线菌发酵中分离出来的次生代谢物。洛麦维菌素A和B对革兰氏阳性菌、金黄色葡萄球菌和粪肠球菌具有较强的抗菌活性(MIC6-25 ng/斑点)。Iomaiviticins的一个不寻常的结构特征是在其结构中结合了两个重氮基。

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.