BIOMOLECULES & ANALOGUES AS ANTIVIRAL/ANTITUMOR AGENTS

该计划的主旨是合成化合物， 已知或有潜力作为抗肿瘤/抗病毒剂， 适当的后续生物学筛查。 总体目标 是： (i)开发了几种合成多环芳烃的有效方法 不寻常的，天然存在的核苷类似物， 抗肿瘤和/或抗病毒活性。 (ii)新型核苷类似物的合成与筛选 通过类比设计为可能的抗肿瘤/抗病毒剂， 已知的生物活性物质或基于已知的或可能的 酶途径 (iii)多种化合物的合成及抗肿瘤活性筛选 前列腺素类和前列腺素类代谢物的类似物。 (iv)开发高效的生产方法， 光学纯的原料，特别是 二烷氧基环戊烯酮，其应广泛用于 多种生物活性物质的对映体特异性合成。 (v)具有普遍意义的新合成方法的开发 有机合成 (vi)进一步证明材料的适用性 以及通过合成选择的另外的 生物学感兴趣的目标。 优先目标包括基于碳环核苷类似物 在neplanocin A的碳环上，设计新的核苷， 作为甲基转移酶的抑制剂， 终止核苷类药物叠氮胸苷和双脱氧胞苷 目前对艾滋病治疗的兴趣，最近发现， 抗病毒核苷氧杂环丁烷和各种亲电子 与前列腺素类相关的环戊烯酮， DNA聚合酶抑制剂。

The thrust of the program is the synthesis of compounds which are known or have potential as antitumor/antiviral agents with appropriate followup biological screening. The overall objectives are: (i) Development of efficient methods for the synthesis of several unusual, naturally occurring nucleosides analogues which have antitumor and/or antiviral activity. (ii) Synthesis and screening of novel nucleoside analogues designed as possible antitumor/antiviral agents by analogy with known bioactive substances or on the basis of known or probable enzymatic pathways. (iii) Synthesis and screening for antitumor activity of a variety of analogues of prostanoids and prostanoids metabolites. (iv) Development of efficient methods for the production of optically pure starting materials, particularly dialkoxycyclopentenones, which should be widely useful in enantiospecific syntheses of a variety of bioactive substances. (v) Development of new synthetic methods of general interest for organic synthesis. (vi) Further demonstration of the applicability of the materials and methods developed by synthesis of a selection of additional targets of biological interest. Targets of priority include carbocylic nucleoside analogues based on the carbocycle of neplanocin A, novel nucleosides designed to be inhibitors of methyltransferases, novel variations of the chain terminator nucleosides drugs azidothymidine and dideoxycytodine of current interest in AIDS therapy, the recently discovered antiviral nucleoside oxetanocin and a variety of electrophilic cyclopentenones related to prostanoids and designed to serve as DNA polymerase inhibitors.