SYNTHESIS OF POLYETHER ANTIBIOTICS--MONENSIN/ANALOGS

该计划的目标是开发高效、实用(在 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 物质起着离子/胺运输的作用，并具有 显著改变细胞新陈代谢的能力。聚醚 抗生素作为抗球虫药和抗球虫药具有商业价值 合成代谢药物，也已被证明是有效的强心剂 探员们。聚醚作为人类的治疗价值 强心剂受到它们的高效力和 无法控制它们的毒性。在化学上相对惰性 聚醚分子，其难以生物降解性导致 系统中的可变药物积聚问题。进入 相关的化学结构仍然保持着螯合能力 金属/胺但不同于有毒的天然产品可能 为制备有用的治疗剂提供了洞察力。它 这项调查的目的是探索 这类系统的合成。目前的努力将是 集中在莫能菌素及其类似物上。

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.