3-ACYLTETRAMIC ACID ANTIBIOTIC AND APLYSIATOXIN SYNTHESE

这项工作的长期目标是发展有效的合成方法 对于天然存在的抗生素替兰霉素/链霉菌素， BU2313A&B和海洋毒素Aaplasiatoxin。 的组成部分 我们将努力使用这些合成程序来构建 这些生物活性化合物的非天然类似物。 为 抗生素tirandamycin/streptolydigin，初始特异性靶向类似物 将是其中特特拉姆酸部分变化的那些。 海洋 黄曲霉毒素是一种具有抗白血病活性的药物， 一种致癌物质 在开发出通向该分子的途径后， 将探讨结构性变化。 最初的变化将涉及 附加到核螺缩酮系统的侧链的修饰。 模拟工作将被引导，以帮助定义抗肿瘤 该分子的活性。 替兰霉素/利迪霉素合成策略的开发进展良好 这些抗生素的高级和数量应该很快 随时待命 关于BU 2313 A和B以及阿氏毒素的初步工作 综合定义了每个系统的可行方法，这些方法将 追求。

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.