Strategies and Tactics for Natural Products Synthesis

天然产物合成的策略和策略

• 批准号: 7157615
• 负责人: GARY ALLEN SULIKOWSKI
• 金额: $ 22.91万
• 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 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7157615
• 关键词: 2-cyclohexen-1-one; Acids; Actinobacteria class; Actinomyces; Alkaloids; Antibiotics; Area; Biological; Biological Factors; Carbon; Class; Complex; Development; Diels Alder reaction; Elements; Enterococcus faecium; Fermentation; Goals; Gram-Positive Bacteria; Halogens; Marines; Methods; Nitrogen; Numbers; Object Attachment; Organic Synthesis; Parents; Reporting; Research; Rest; Route; Spottings; Staphylococcus aureus; Stemona; Structure; Universities; Utah; base; chemical synthesis; interest; lomaiviticin A; lomaiviticin B; neotuberostemonine; novel; novel strategies; piperidine; programs; stenine; upenamide

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提高复杂分子合成的实践。特别重点放在含有氮的天然产品上，因为异常数量的药理学活性化合物将该元素纳入其结构中。尽管在过去20世纪，有机合成方面取得了许多进步，但复杂天然产物的有效和经济合成仍然是一项艰巨的努力。我们的计划是将新的廉价构建块引入有机合成领域，以用于氮异环的不对称合成。这些构建块将加快稀有海洋生物碱Upenamide，Stememona生物碱和2个取代的哌啶生物碱的化学合成。我们还提出了合成Iomaiviticins A和B的计划，该计划是从海洋衍生的放线菌发酵中分离出来的继发代谢产物。 Lomaiviticin A和B是针对金黄色葡萄球菌和粪肠球菌（MIC 6-25 ng/sp）的革兰氏阳性细菌的有效抗生素。 Iomaiviticin的一个异常的结构特征是将两个重氮组掺入其结构中。