Nucleosides. XVI. The synthesis of 2',3'-dideoxy-3',4'-didehydro nucleosides.
Nucleosides. XVI. The synthesis of 2',3'-dideoxy-3',4'-didehydro nucleosides.
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核苷。
DOI：
10.1021/jo00945a029
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发表时间：
1973
期刊：
影响因子：
--
通讯作者：
J. Horwitz
中科院分区：
文献类型：
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作者：
J. Žemlička;J. Freisler;R. Gasser;J. Horwitz
描述了制备3 ′，4 ′-不饱和核苷（15 a-d）的一般方法，该方法从2 ′-脱氧核苷糖醛酸酯（2a-d，3，8）出发，通过在DMF中的三乙胺或苯甲酸钠的作用，对相应的2 ′-脱氧-3 ′-O-甲磺酰基核糖核苷糖醛酸酯（4a-e）进行简单的消除反应。用双（甲氧基乙氧基）氢化铝钠完成中间体3 ′，4 ′-不饱和核苷糖醛酸酯（5a-d，11）的烷氧羰基官能团的选择性还原。5a在乙醇中的催化（Pd/C）氢化得到单一异构体，3 '-脱氧胸苷糖醛酸乙酯（17），其在氢化物还原时产生与3'-脱氧胸苷相同的产物。用叔丁醇钾处理时，4a降解为胸腺嘧啶和糠酸乙酯。在2a或5a与二甲基甲酰胺新戊基缩醛的反应中观察到相同的反应过程。尝试在4a与吡啶的情况下诱导消除反应，反而导致取代产物，乙基3 '-脱氧-3'-（-吡啶鎓）胸苷糖醛酸甲酯磺酸盐（6）。用苯甲酸钠的DMF溶液处理6，吡啶磺酸盐的元素很容易从6中消除。与吡啶不同，2，6-二甲基吡啶将4a转化为5a。2 ′，3 ′-二-O-甲磺酰基尿苷糖醛酸乙酯（4 e）与（C_2H_3）_3N在DMF中反应，高产率地得到5-（尿嘧啶-1-基）糠酸乙酯（13）。用碳酸二苯酯处理尿苷糖醛酸乙酯（2d）得到相同的产物（13）。本文讨论了这些消除反应与尿苷糖醛酸（Id）在无水乙酸酐中转化为O-（尿嘧啶-1-基）糠酸（13）的关系。此外，将后一条件应用于胸苷糖醛酸（Ia）导致3 '-脱氧-3'，4 '-二脱氢胸苷糖醛酸（14），其被表征为乙酯5a。本文讨论了5a-d，11和15 a-d的核磁共振谱。由于本实验室和其他实验室的研究结果，已经发展出了将内环和外环不饱和度引入各种核苷的糖部分的方法。2事实上，在四种可能的（单）烯属核苷（I-IV）中，仅在最近才描述了制备1-（2-脱氧-Df/reo-β-l-烯呋喃糖基）嘧啶（IV）的成功方法。28然而，迄今为止，只有I和II接受了详细的物理化学3和生物化学2k '2 r' 4研究。
A general approach to 3', 4'-unsaturated nucleosides (15a-d) is described which proceeds from a 2'-deoxy-nucleoside uronic acid ester (2a-d, 3, 8) via a facile elimination reaction effected on the corresponding 2'-deoxy-3'-O-methylsulfonylribonucleoside uronic acidester (4a-e), by the action ofeither triethylamine or sodium benzoate in DMF. Selective reduction of the carbalkoxy function of the intermediate 3', 4'-unsaturated nucleoside uronic esters (5a-d, 11) was accomplished with sodium bis (methoxyethoxy) aluminum hydride. Catalytic (Pd/C) hydrogenation of 5a in ethanol affords a single isomer, ethyl 3'-deoxythymidine uronate (17), which on hydride reduction yields a product identical with 3'-deoxythymidine. Degradation of4a to thymine and ethyl furoate was observed on treatment with potassium ferf-butoxide. The same course of reaction was observed in the reaction of either 2a or 5a with dimethylformamidedineopentyl acetal. Attempts to induce the elimination reaction in the case of 4a with pyridine led instead to thesubstitution product, ethyl 3'-deoxy-3'-(-pyridinium) thymidine uronate methyl sulfonate (6). The elements of pyridinium sulfonate are readily eliminated from 6 on treatment with sodiumbenzoate in DMF. Unlike pyridine, 2, 6-lutidineconverts 4a to 5a. Reaction of ethyl 2', 3'-di-O-methylsulfonyluridine uronate (4e) with (C2H3) 3N in DMF gave ethyl 5-(uracil-1-yl) furoate (13) in high yield. The same product (13) was obtained on treatment of ethyl uridine uronate (2d) with diphenyl carbonate. The relationship of these elimination reactions to the conversion of uridine uronic acid (Id) to o-(uracil-1-yl) furoic acid (13) in refluxing acetic anhydride is discussed. Moreover, the application of the latter conditions to thymidine uronic acid (la) leads to 3'-deoxy-3', 4'-didehydrothymidine uronic acid (14), which was characterized as the ethyl ester 5a. The nmr spectra of 5a-d, 11, and 15a-d are discussed.As a result of studies conducted in this laboratory and others, methods have been developed to introduce both endo-and exocyclicunsaturation into the sugar moiety of a wide spectrum of nucleosides. 2 In point of fact, of the four possible (mono-) olefinic nucleosides (I-IV), only recently has a successful approach to 1-(2-deoxy-Df/ireo-pent-l-enofuranosyl) pyrimidines (IV) been described. 28 However, only I and II have to date received detailed physicochemical3 and bio-chemical2k’2r’4 study.