SYNTHESIS OF ANTITUMOR/VIRAL PYRIMIDINE C NUCLEOSIDES

化学方法将被开发用于制备六类 C-核苷，其是天然存在的 核苷或合成核苷，其具有确定的抗肿瘤和/或 抗病毒活性。 将开发新的环转化反应 并应用于抗肿瘤抗生素显多霉素的简便合成， 恶嗪霉素和它们的类似物（1类和2类）。 胸苷和2 '-脱氧胞苷的C-核苷类似物（3类和4类） 将应用我们最近的研究成果，以β-尿苷为原料， 发展了嘧啶到吡啶环的转化反应。 有效抗疱疹病毒的C-核苷类似物（第5类和第6类）， 潜在的抗白血病药物FMAU将通过以下方法合成： 在糖部分修饰预先形成的C-核苷（β-尿苷）， 或由适当的2-氟-阿拉伯-呋喃糖衍生物 合成. “内部”生化和化疗协作 描述了正确评价靶向C-核苷的研究 简要 从这些研究中，结构-活性关系应该是 即将到来的援助，在发展新的代理上级那些 目前可用于治疗癌症和/或病毒感染， 伙计

Chemical methods will be developed for the preparation of six classes of C-nucleosides which are close analogs of either naturally-occurring nucleosides or synthetic nucleosides with established antitumor and/or antiviral activity. New ring transformation reactions will be developed and applied to facile synthesis of antitumor antibiotics, showdomycin and oxazinomycin, and their analogs (Classes 1 and 2) from Psi-uridine. C-Nucleoside analogs (Classes 3 and 4) of thymidine and 2'-deoxycytidine will be synthesized from Psi-uridine by application of our recently developed pyrimidine to pyridine ring transformation reaction. C-Nucleoside analogs (Classes 5 and 6) of the potent antiherpetic and potential antileukemic agent, FMAU, will be synthesized either by modification of a preformed C-nucleoside (Psi-uridine) at the sugar moiety, or from an appropriate 2-fluoro-arabino-furanose derivative by total synthesis. "In house" biochemical and chemotherapeutic collaborative studies for proper evaluation of the targeted C-nucleosides are described briefly. From these studies, structure-activity relationships should be forthcoming to aid in the development of new agents superior to those currently available for the treatment of cancer and/or viral infection in man.