Strategies and Tactics for Natural Products Synthesis

天然产物合成的策略和策略

• 批准号: 7340231
• 负责人: GARY ALLEN SULIKOWSKI
• 金额: $ 5.49万
• 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/7340231
• 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

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.

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，因为大量 药理学活性化合物将此元素纳入其结构中。尽管有很多 在过去20世纪，有机合成的进步是复杂的有效和经济综合 天然产品仍然是一项具有挑战性的努力。我们的计划是引入新的廉价构建块 到有机合成领域，用于用于氮杂环的不对称合成。这些建筑物 块将加快稀有海洋生物碱Upenamide的化学合成，即stemona生物碱 和2个取代的哌啶生物碱。我们还提出了合成Iomaiviticins A和B的计划 从海洋衍生的放线菌发酵中分离出的次生代谢产物。 Lomaiviticins A和B 是针对革兰氏阳性细菌葡萄球菌和肠球菌的有效抗生素 （MIC 6-25 ng/lot）。 iomaiviticin的一个不寻常的结构特征是掺入两个重氮基团 在它们的结构内。

项目成果

A concise Diels-Alder strategy leading to congeners of the ABC ring system of the marine alkaloid 'upenamide.

简明的 Diels-Alder 策略导致海洋生物碱 upenamide 的 ABC 环系统的同系物。

• DOI: 10.1016/j.tetlet.2016.05.102
• 发表时间: 2016
• 期刊: Tetrahedron letters
• 影响因子: 1.8
• 作者: Wenzler,MartaE;Melancon,BruceJ;Sulikowski,GaryA
• 通讯作者: Sulikowski,GaryA

An unexpected effect of acetal stereochemistry on the course of its reductive cleavage.

缩醛立体化学对其还原裂解过程的意外影响。

• DOI: 10.1016/j.tetlet.2016.06.067
• 发表时间: 2016
• 期刊: Tetrahedron letters
• 影响因子: 1.8
• 作者: Wenzler,MartaE;Sulikowski,GaryA
• 通讯作者: Sulikowski,GaryA

Formation of the BC ring system of upenamide via a Staudinger/aza-Wittig reaction.

通过 Staudinger/aza-Wittig 反应形成奥佩酰胺的 BC 环系统。

• DOI: 10.1021/ol702255k
• 发表时间: 2007
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: Luo,Zhushou;Peplowski,Katherine;Sulikowski,GaryA
• 通讯作者: Sulikowski,GaryA