3'4'-ALKYL NUCLEOSIDES--PROSPECTS FOR AIDS THERAPY

该计划的总体目标是发展小说 在治疗中显示出感兴趣的生物活性的化合物 爱滋病患者。该方案的具体目标是：(一)发展 高效、创新的化学合成改性糖 与核糖和脱氧核糖有关。(Ii)这些设施的使用 修饰糖在新型核苷类似物合成中的应用 抗艾滋病药物。(二)增进对关系的认识 核苷类似物的结构与生物活性之间的关系 通过发挥逆转录酶抑制剂的作用来表现出这种活性 和/或病毒DNA合成过程中的链终止子。在某些情况下， 合成将从常见的糖或其衍生物开始，如 双丙酮葡萄糖，在其他情况下，起始材料将是 环戊二烯及其在合成中的应用 介观导数的不对称化。许多新的化合物 提出了支链糖与甲基的衍生物， 三氟乙基和其他烷基处于战略位置。方法： 4-C-烷基核糖衍生物的生产，特别是4-C-甲基和 重点介绍了4-C-三氟乙基衍生物。应用程序 三氟乙基-三甲基硅烷用于三氟乙基的引入 将探索适当碳水化合物衍生物中的基团。 核糖核素、2-脱氧核糖核酸和2，3-双脱氧核糖核苷的衍生物 将准备课程并提交供筛选。

The overall objective of the program is the development of novel compounds that exhibit biological activity of interest in the treatment of AIDS. The specific aims of the program are: (i) The development of efficient and innovative chemistry for the synthesis of modified sugars related to ribose and deoxyribose. (ii) The utilization of these modified sugars in the synthesis of novel nucleoside analog as potential anti-AIDS drugs. (ii) To increase the understanding of the relationship between structure and biological activity in nucleoside analog which exhibit such activity by functioning as reverse transcriptase inhibitors and/or chain terminators during viral DNA synthesis. In some cases the syntheses will begin with common sugars or their derivatives such as diacetone glucose, in other cases the starting material will be cyclopentadiene and the syntheses will incorporate enzymatic asymmetrizations of meso derivatives. Many of the novel compounds proposed are derivatives of branched-chain sugars with methyl, trifluoroethyl and other alkyl groups strategically placed. Methods for the production of 4-C-alkyl ribose derivatives, especially 4-C-methyl and 4-C-trifluoroethyl derivatives are stressed. Application of trifluoroethyl-trimethylsilane for the introduction of trifluoroethyl groups in appropriate carbohydrate derivatives will be explored. Nucleoside derivatives of the ribo, 2-deoxyribo- and 2,3-dideoxyribo classes will be prepared and submitted for screening.