Strategies and Tactics for Natural Products Synthesis

描述（由申请人提供）：本研究项目的长期目标是促进复杂分子合成的实践。特别强调的是含有氮的天然产物，因为异常大量的药理活性化合物在其结构中含有这种元素。尽管有机合成在过去的20世纪取得了许多进步，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。我们的计划是向有机合成领域引入新的廉价的构建模块，用于氮杂环的不对称合成。这些构件将加速稀有海洋生物碱上胺、茎草生物碱和2取代胡椒碱生物碱的化学合成。我们还提出了一个计划，合成Iomaiviticins a和B，从海洋来源的放线菌发酵分离的次级代谢产物。Lomaiviticins A和B是抗革兰氏阳性细菌金黄色葡萄球菌和屎肠球菌的有效抗生素（MIC 6-25 ng/spot）。Iomaiviticins的一个不寻常的结构特征是在它们的结构中结合了两个重氮基团。

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.