A PRACTICAL SYNTHETIC ROUTE TO THE TETRACYCLINES

描述：(主要调查人员摘要)本提案的目标 是开发第一个实用、高效、对映选择性的实验室 合成路线(S)为四环素类抗生素。我们的目标是设计一种 由12个或更少的合成步骤组成的路线，可能只有8个步骤， 以苯甲酸为起始原料。一种约束，即 合成路线也是多才多艺的，允许引入 后期的实质性结构可变性，特别是在C 和四环素结构的D环，先前的研究表明 抗生素的发展有很大的机会。一种广谱化合物的合成 一系列新的四环素类药物，作为改进的抗生素进行评估， 提出了潜在的抗肿瘤药物。一个特别的焦点是发展 针对四环素耐药微生物的有效抗生素。 调整和/或修改这些合成路线以针对新的 具有抗肿瘤活性的四环素结构，如SF-2575(TAN-1518 X) 也将尝试。

DESCRIPTION: (Principal Investigator's Abstract) The objective of this proposal is to develop the first practical, efficient, and enantioselective laboratory synthetic route(s) to the tetracycline antibiotics. The goal is to devise a route of twelve or fewer synthetic steps, perhaps as few as eight steps, beginning with benzoic acid as a starting material. A constraint that the synthetic route be versatile is also imposed, allowing for the introduction of substantive structural variability at a late stage, particularly within the C and D rings of the tetracycline structure, where prior research has shown that there is great opportunity for antibiotic development. Synthesis of a wide range of new tetracyclines for evaluation as improved antibiotics and, potentially antitumor agents is proposed. A particular focus is the development of effective antibiotics against tetracycline-resistant microorganisms. Adaptation and/or modification of these synthetic routes to target new tetracycline structures with antitumor activity, such as SF-2575 (TAN-1518 X) will also be attempted.