SYNTHESIS OF POLYETHER ANTIBIOTICS--MONENSIN/ANALOGS

聚醚类抗生素--莫能菌素/类似物的合成

• 批准号: 3297308
• 负责人: ROBERT E IRELAND
• 金额: $ 19.24万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3297308
• 关键词: amines; cardiotonic agents; chelating agents; chemical structure function; drug adverse effect; drug design /synthesis /production; drug screening /evaluation; growth factor; ion transport; ionophores; monensin

The goal of this program is to develop efficient, practical (within the context of the complexity of the molecules involved) syntheses of the polyether ionophore antibiotics. These substances function as agents for ion/amine transport and have the capacity to alter significantly cell metabolism. The polyether antibiotics are commercially valuable as coccidiostats and anabolic agents and have also proven to be potent cardiotonic agents. The therapeutic value of the polyethers as human cardiotonic agents is limited by their high potency and the inability to control their toxicity. As relatively chemically inert polyetheral molecules, their difficult biodegradability leads to problems with variable drug build-up in the system. Access to related chemical structures that still retain the ability to chelate metals/amines but differ from the toxic natural products may lead to insight for the preparation of useful therapeutic agents. It is the purpose of this investigation to explore means for the synthesis of such systems. The current effort will be concentrated on monensin and its analogs.

该计划的目标是开发高效，实用（内 所涉及的分子的复杂性的背景） 聚醚类离子载体抗生素的合成。 这些 这些物质作为离子/胺转运剂起作用， 显著改变细胞代谢的能力。 聚醚 抗生素作为抗球虫药具有商业价值， 合成代谢剂，也被证明是有效的强心药 剂. 聚醚类化合物对人体的治疗价值 强心剂受限于其高效力， 无法控制其毒性。 相对化学惰性 聚醚醛分子，它们难以生物降解， 药物在系统中积聚的问题。 获得 仍然保留螯合能力的相关化学结构 金属/胺，但不同于有毒的天然产品， 导致对制备有用的治疗剂的了解。 它 本次调查的目的是探索 这些系统的合成。 目前的努力将是 专注于莫能菌素及其类似物。