The major objective of this proposal is the total synthesis of the antibiotic, thermorubin. A synthetic plan is outlined. Secondary objectives are (a) the synthesis of sample homologs of thermorubin with a view to defining the pharmacophoric group of the molecule and (b) the pursuit of a lead that should allow solubilization of the molecule for systemic use. The total synthesis studies should be materially aided by the work on the sample homologs. Thermorubin is a potent antibiotic comparable to penicillin G in biological activity whose only drawback is its poor solubility in physiological fluids. It is low in mammalian toxicity and has no cross-resistance with other antibiotics. Its mechanism of action-inhibition of initiation of protein synthesis is different from known antibacterial agents. Therefore from the point of view of health-related objectives we believe it merits attention.