TOTAL SYNTHESIS OF THE ANTIBIOTIC THERMORUBIN

本提案的主要目标是全面综合 抗生素，嗜热红菌素 一个综合计划概述。 二次 目的是（a）合成热菌红素的样品同系物， 定义分子的药效基团的观点，和（B） 追求一个铅，应该允许溶解的分子， 系统使用。 全合成研究应得到以下方面的物质帮助： 对样品同系物的研究 嗜热菌红素是一种强效抗生素 在生物活性上与青霉素G相当，其唯一的缺点是 在生理液体中溶解性差。 在哺乳动物中含量较低 与其他抗生素无交叉耐药性。 其机制 蛋白质合成起始的抑制作用不同于 已知的抗菌剂。 因此，从 与健康有关的目标，我们认为值得关注。

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.