Polyketides via Redox-Triggered Alcohol C-H Functionalization.

通过氧化还原触发的醇 C-H 官能化的聚酮化合物。

• 批准号: 10394725
• 负责人: MICHAEL J KRISCHE
• 金额: $ 31.11万
• 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 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10394725
• 关键词: Alcohols; Anti-Bacterial Agents; Ants; Area; Bacteria; Carbon; Collaborations; Complex; Data; Family; Fermentation; Funding; Glycols; Human; Industrialization; Laboratories; Mediating; Medicine; Methodology; Methods; Natural Products; Nature; Oxidation-Reduction; Pharmaceutical Chemistry; Pharmaceutical Preparations; Plants; Property; Research; Rifamycins; Route; Science; Site; Soil; Streptomyces; Structure; Technology; Tubulin; United States National Institutes of Health; analog; anti-cancer; bryostatin; cycloaddition; design; fungus; improved; innovation; novel; pathogen; professor; programs; small molecule

Polyketides are used extensively in human medicine and account for approximately 20% of the top-selling small molecule drugs. While the majority of polyketide drugs derive from soil bacteria, less than 5% of soil bacteria are amenable to culture. These data suggest that as methods for the culture of soil bacteria improve, the use of polyketides in human medicine will increase, as will the need for concise manufacturing routes to these complex structures and their functional analogues. Under the aegis of NIH support, we have developed a family of catalytic methods for the direct stereo- and site-selective conversion of lower alcohols to higher alcohols. These alcohol-mediated C-C couplings were conceived and developed exclusively in our laboratory and we remain the foremost group exploring this area of research. This technology has enabled total syntheses of diverse type I polyketides, including 6-deoxyerythronolide B, bryostatin 7, trienomycins A and F, cyanolide A, roxaticin, cryptocaryol A, SCH 351448, swinholide, as well as formal syntheses of rifamycin S and scytophycin C. In all cases, our syntheses were significantly more concise than preexisting routes. These methods are finding increasingly frequent use across both academic and industrial laboratories. In the proposed funding period, two main objectives are proposed: (a) catalytic methods for type II polyketide construction will be developed and (b) simplified polyketide analogues possessing anti-cancer and anti-bacterial properties will be evaluated in ongoing collaborations. These studies advance an integrated program in which methodological innovation informs synthesis, and synthesis informs medicinal chemistry.

聚酮类化合物在人类医学中被广泛使用，约占总用量的20%