SYNTHESIS OF MACROCYCLIC ANTITUMOR ANTIBIOTICS

原型大环、双环和螺环单元的合成路线 存在于新型大环特窗酸类抗肿瘤抗生素中， Kijanimicin，将进行检查。 糖苷配基基是起始的 这个项目的目标。 将特别注意 tetronic酸亚结构和糖苷配基的大环。 的 这里开发的合成方法将在合成中具有通用性。 其他复杂的碳环物质，包括三氯杀螨素和 河豚毒素A 单个单元及其组合代表新颖的 具有潜在的抗肿瘤生物活性的结构， 抗生素领域 Kijanimicin显示出抗厌氧菌的活性 并在小鼠中起到抗疟疾的作用。 Tetrocarin-A，一种类似于 kijanimicin抑制B中的RNA合成。枯草芽孢杆菌和抑制生长 小鼠实验性肉瘤180和白血病P338肿瘤。

Synthetic routes to prototype macrocyclic, bicyclic, and spirocyclic units present in the novel macrocyclic tetronic acid antitumor antibiotic, kijanimicin, will be examined. The aglycone kijanolide is the initial target of this project. Particular attention will be accorded to the tetronic acid substructure and the macrocyclic ring of the aglycon. The synthetic methods developed here will have general utility in the synthesis of other complex carbocyclic substances, including chlorothricolide and tetrocarin-A. The individual units and their combinations represent novel structures with potential biological activity in the antitumor and antibiotic areas. Kijanimicin shows activity against anaerobic bacteria and acts as an antimalarial in mice. Tetrocarin-A, a close analog of kijanimicin, suppresses RNA synthesis in B. subtilis and inhibits growth of experimental sarcoma 180 and leukemia P338 tumors in mice.