Polyketides via C-C Coupling of Alcohols: Green Chemistry

通过醇 C-C 偶联的聚酮化合物：绿色化学

• 批准号: 8884268
• 负责人: MICHAEL J KRISCHE
• 金额: $ 28.51万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8884268
• 关键词: 6-deoxyerythronolide B; Accounting; Alcohols; Aldehydes; Anti-Bacterial Agents; Area; Bacteria; Biological Assay; Biological Factors; Bypass; Cancer Biology; Chemistry; Collaborations; Complex; Coupling; Data; Development; Diagnostic; Family; Funding; Glycols; HIV; Human; Hydrogen; Institutes; Investigation; Laboratories; Letters; Mediating; Medicine; Methods; Molecular; Oxidation-Reduction; Pharmaceutical Chemistry; Pharmaceutical Preparations; Process; Reaction; Reporting; Research; Rifamycins; Route; Soil; Structure; Technology; Texas; Tumor Promotion; Viral; Work; analog; bryostatin; bryostatin 7; cancer genetics; cycloaddition; improved; innovation; interest; member; methicillin resistant Staphylococcus aureus; programs; public health relevance; small molecule; trienomycin A

DESCRIPTION (provided by applicant): Our laboratory has discovered a broad, new class of catalytic processes that promote C-C bond formation via direct alcohol C-H functionalization. In the prior funding period, this technology enabled total syntheses of 6-deoxyerythronolide B, bryostatin 7, trienomycins A and F, cyanolide A, roxaticin, and formal syntheses of rifamycin S and scytophycin C, availing the most concise routes to any member of these respective natural products families. In the proposed funding period, these routes will be adapted to prepare functional analogues of bryostatin and trienomycin. Our bryostatin analogues will be evaluated in an ongoing collaboration with Dr. Peter M. Blumberg, who is Chief, Molecular Mechanisms of Tumor Promotion Section in the Laboratory of Cancer Biology and Genetics at the NCI. The bryostatin analogues also will be evaluated in HIV viral reactivation assays in collaboration with colleagues at GlaxoSmithKline. Trienomycin analogues will be evaluated at the Texas Institute for Drug and Diagnostics Development (TI-3D). Having utilized alcohol C-C coupling to streamline the synthesis of several type I polyketides, we will now begin to evolve a suite of methods to assemble therapeutically relevant type II polyketide natural products, such as (+)-lactonamycin, which displays potent antibacterial activity against MRSA.

描述（由申请人提供）：我们的实验室发现了一种广泛的新型催化过程，可通过直接醇 C-H 官能化促进 C-C 键形成。在之前的资助期间，该技术实现了全合成 6-脱氧赤藓内酯 B、苔藓抑素 7、三烯霉素 A 和 F、氰内酯 A、罗沙星以及利福霉素 S 和细胞霉素 C 的正式合成，利用最简洁的途径合成这些各自天然产物家族的任何成员。在拟议的资助期内，这些路线将用于制备苔藓抑素和三烯霉素的功能类似物。我们的苔藓抑素类似物将与 Peter M. Blumberg 博士持续合作进行评估，Peter M. Blumberg 博士是 NCI 癌症生物学和遗传学实验室肿瘤促进分子机制科主任。苔藓抑素类似物还将与葛兰素史克的同事合作，在 HIV 病毒再激活测定中进行评估。三烯霉素类似物将在德克萨斯药物和诊断开发研究所 (TI-3D) 进行评估。在利用醇 C-C 偶联简化了几种 I 型聚酮化合物的合成后，我们现在将开始开发一套方法来组装治疗相关的 II 型聚酮化合物天然产物，例如 (+)-内霉素，它对 MRSA 显示出有效的抗菌活性。