SYNTHESIS OF POLYETHER ANTIBIOTICS--MONENSIN/ANALOGS

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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.