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

该计划的总体目标是发展小说 在治疗中表现出感兴趣的生物活性的化合物 艾滋病 该方案的具体目标是：（一）发展 用于合成改性糖的高效和创新化学 与核糖和脱氧核糖有关。 (ii)利用这些 修饰糖在合成新型核苷类似物中的应用 抗艾滋病药物。 (ii)增进对关系的了解 核苷类似物的结构和生物活性之间的关系， 通过作为逆转录酶抑制剂发挥作用而显示出这种活性 和/或病毒DNA合成过程中的链终止子。 在某些情况下 合成开始于普通糖或其衍生物， 二丙酮葡萄糖，在其他情况下，起始材料将是 环戊二烯和合成将纳入酶 meso衍生物的不对称化。 许多新的化合物 提出了支链糖与甲基的衍生物， 三氟乙基和其它烷基策略性地放置。 方法 4-C-烷基核糖衍生物，特别是4-C-甲基和 强调4-C-三氟乙基衍生物。 的应用 用于引入三氟乙基的三氟乙基-三甲基硅烷 将探索适当的碳水化合物衍生物中的基团。 核糖、2-脱氧核糖和2，3-二脱氧核糖的核苷衍生物 课程将准备好并提交筛选。

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.