3-ACYLTETRAMIC ACID ANTIBIOTIC AND APLYSIATOXIN SYNTHESE

3-乙酰四酸抗生素和海螺毒素的合成

• 批准号: 3278041
• 负责人: ROBERT E IRELAND
• 金额: $ 11.26万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-02-01 至 1986-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3278041
• 关键词: acyl group; antineoplastic antibiotics; chemical structure function; chemical synthesis; cocarcinogen; diene; drug design /synthesis /production; ionophores; polyhydroxy compound; toxicant screening

The long range goal of this work is the development of efficient syntheses for the naturally occurring antibiotics tirandamycin/streptolydigin and BU2313A&B and the marine toxin aplysiatoxin. An integral part of this effort will be to use these synthetic procedures for the construction of non-natural analogs of these biologically active compounds. For the antibiotics tirandamycin/streptolydigin, initial specific target analogs will be those in which the tetramic acid portion is varied. The marine toxin, aplysiatoxin, is an activity anti-Leukemic agent and has been shown to a co-carcinogen. After a route to this molecule is developed, selected structural changes will be explored. Initial changes will involve modification of the side-chains appended to the nuclear spiroketal system. The analog work will be directed to help define the anti-neoplastic activity of this molecule. The development of tirandamycin/streptolydigin synthetic strategy is well advanced and quantities of the top portion of these antibiotics should soon be available. Preliminary work on the BU2313A&B and the aplysiatoxin syntheses has defined viable approaches to each system, and these will be pursued.

这项工作的长期目标是开发高效的合成方法 对于自然产生的抗生素替兰霉素/链球菌素和 BU2313A&B和海洋毒素Aplysiatoxin。这是其中不可或缺的一部分 将努力使用这些合成程序来建造 这些生物活性化合物的非天然类似物。对于 抗生素替兰霉素/溶链菌素，最初的特异性靶标类似物 将是其中四酸部分不同的那些。海军陆战队 毒素，Aplysiatoxin，是一种有效的抗白血病药物，已被证明 与一种致癌物质有关。在开发出通向该分子的路线后，选择 将探索结构性变化。最初的变化将涉及 核螺酮系统附加侧链的修饰。 模拟工作将被用于帮助定义抗肿瘤 这种分子的活性。 替兰霉素/链霉菌素合成策略进展良好 这些抗生素的最高部分的先进和数量应该很快 有空。BU2313A&B和Aplysiatoxin的初步研究 综合已经为每个系统定义了可行的方法，这些方法将是 被追捕。