SYNTHESIS OF MESOIONIC NUCLEOSIDES AS ANTINEOPLASTIC AND ANTIMICROBIAL AGENTS

一系列新的基于黄嘌呤的中离子杂环核苷将被 潜在抗原虫的合成、表征及研究 体内外药物和体外潜在的抗肿瘤药物。 核苷类似物，通过修饰酶的活性 为核酸生物合成提供了一些最强大和最有用的 病毒复制和肿瘤组织生长的抑制剂。肥沃 虽然核苷领域已经有了，但现有的大多数抗生素 嘌呤和嘧啶核苷具有严重的毒性。 此外，对它们的抵抗正在成为一个日益严重的问题。 密集努力寻找与结构相关的更具选择性和 有效的治疗替代方案已经在各种不同的 实验室在过去十年里，它仍然是一个未得到满足的抗病毒需求 上世纪90年代的癌症化疗。 虽然一些中离子黄嘌呤核苷类似物具有 在杂环碱和/或糖部分中进行改性 以前曾被研究过其抗病毒或细胞抑制作用 活性，含有无环碳水化合物部分的介离子衍生物 如本研究中所提议的，没有被描述。介离子 化合物将通过适当保护的环缩合反应制备 具有丙二酸酯、取代丙二酸酯或 氯羰基苯基乙酮，然后用二甲胺解除保护。 合成的化合物将通过光谱分析进行表征。 质子核磁共振(1H核磁共振)、碳13核磁共振(13C 核磁共振)、质谱学(MS)、紫外谱学(UV)、红外光谱 光谱(IR)和碳、氢、氮元素分析。

A novel series of mesoionic xanthine-based acyclonucleosides will be synthesized, characterized and investigated as potential antiprotozoan agents in vitro and in vivo and as potential antitumor agents in vitro. The nucleoside analogues, by modification of the activity of the enzymes of nucleic acid biosynthesis, provide some of the most powerful and useful inhibitors of viral replication and neoplastic tissue growth. Fertile though the nucleoside field has been, most of the existing antibiotic purine and pyrimidine nucleosides are associated with serious toxicity. In addition, resistance to them is becoming an increasing problem. Intensive efforts to find structurally-related more selective and effective therapeutic alternatives have been underway in various laboratories in the past decade and it remains an unmet need of antiviral and cancer chemotherapy in the 1990s. Although a number of mesoionic xanthine nucleoside analogues with modifications being made in the heterocyclic base and/or the sugar moiety have been previously investigated for their antiviral or cytostatic activities, mesoionic derivatives containing acyclic carbohydrate moiety as proposed in the present study, have not been described. The mesoionic compounds will be prepared by cyclocondensation of appropriate protected glycoside precursors with malonic ester, substituted malonic esters or chlorocarbonylphenyl ketene followed by deprotection with dimethylamine. The synthesized compounds will be characterized spectroscopically by proton magnetic resonance (1 H NMR), carbon-13 magnetic resonance (13C NMR), mass spectrometry (MS), ultraviolet spectroscopy (UV), infrared spectroscopy (IR) and carbon, hydrogen, nitrogen elemental analysis.