SYNTHESIS OF ANTIBIOTICS

抗生素的合成

• 批准号: 7770888
• 负责人: K. C. NICOLAOU
• 金额: $ 60.3万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7770888
• 关键词: Alkenes; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics; Arts; Biological; Biological Factors; Development; Drug Design; Evaluation; Funding; Knowledge; Lead; Methodology; Molecular; Molecular Structure; Palladium; Reaction; Research; Research Activity; Technology; Testing; Thiostrepton; Work; advanced disease; analog; antibiotic design; chemical synthesis; complement C4c; complement C4d; design; design and construction; hydroxyindole; member; nocathiacin I; programs

The competitive renewal proposal describes a research program directed at the total synthesis of naturally occurring antibiotics and designed antibacterial agents. The proposed work represents continuation of our NIH-funded (AI55475) research activities and will specifically involve molecular design and synthetic work toward thiostrepton (1), nocathiacin I (2), marinomycin A (3) and abyssomycin C (4c) and their analogs. In the thiostrepton project, we plan to optimize a biologically active lead compound representing the didehydropiperidine domain of the molecule that we have discovered during our successful total synthesis of this antibiotic. In the nocathiacin I project we will follow our recently developed methodology for W-hydroxyindole synthesis to achieve a total synthesis of the natural product and apply the technology to the construction of designed analogs for the purposes of SAR studies. The total synthesis of marinomycin A is designed to test the scope and limitations of the palladium-catalyzed cross-coupling and olefin metathesis reactions. The designed total synthesis of abysommycin C relies on a biosynthetic hypothesis cascade and is expected to deliver other members of the class, including designed analogs for biological evaluation. Overall, this research program aims to generate new knowledge for the treatment of anti- infective diseases, advance the art of chemical synthesis as applied to drug design and development, and, possibly, result in the synthesis of new potential antibacterial agents.

竞争性更新提案描述了一项针对总数的研究计划