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Synthetic Research Work of Compounds Related to Carbohydrates and Nucleic Acids

碳水化合物和核酸相关化合物的合成研究工作

基本信息

批准号：
59430006
负责人：
ISHIDO Yoshiharu
金额：
$ 18.37万
依托单位：
Tokyo Institute of Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1984
资助国家：
日本
起止时间：
1984 至 1986
项目状态：
已结题

项目摘要

The excellent utility of glycosyl fluorides in glycosylation reaction (Mukaiyama et al.) led us to develop their efficient preparative methods involving reaction of hexafluoropropene - <NHR_2> with 1-OH sugar derivatives. Lewis acid-catalyzed coupling reactions of the fluorides with an enol trimethylsilyl ether, cyanotrimethylsilane, and allyltrimethylsilane were effectively induced to give the corresponding C -glycosyl compounds. Based on the results obtained by a series of reactions, steresochemistry and mechanism of the reaction were rationalized.2'-Deoxyribonucleosides were aroylated with high regioselectivity to give their 5'-aroates in a high yield on treatment with an aroyl chloride through dilution - drop-by-drop - addition procedure, The 5'-aroates were efficiently converted into the corresponding 2',3'-dideoxyribonucleosides in a usual manner. The acylation procedure was also useful for ribonucleosides to give their 5'-acylates and/or 2',5'-diacylates depending on the amount of the acyl chlorides, and the latter were derived into 3',5'-diacylates by treating with Wakogel C-300. In a usual manner, they were converted to 3'- and 2'-THP derivatives which have been known as the key-intermediates for the synthesis of oligoribonucleotides, and, thus, we conducted a series of oligoribonucleotide syntheses bearing both 2'-5' and 3'-5 phosphodiester linkages up to an undecamer, It is noteworthy that a novel polymer support approach with a cellulose acetate which is functionalized with 4-(2-hydroxyethylsulfonyl)dihydrocinnamate made up possible to perform coupling reactions of oligonucleotide-fragments efficiently due to its properties in solubility, demonstrating the excellence of both liquid- and solid-phase approaches. In addition, highly regioselective phenylcarbamoylation, methoxymethylation, and triisopropylsilylation of hydroxyl groups of carbohydrates involving nucleosides, and protection of nucleic acid base moieties of ribonucleosides were developed.

糖基氟化物在糖基化反应中的优异效用（Mukaiyama等人）使我们开发了他们的有效制备方法，包括六氟丙烯-<NHR_2>与1-OH糖衍生物的反应。在刘易斯酸催化下，氟化物与烯醇三甲基硅醚、氰基三甲基硅烷和烯丙基三甲基硅烷发生偶联反应，得到相应的C -糖基化合物。在此基础上，对反应的立体化学和反应机理进行了合理的解释。2 ′-脱氧核苷经芳酰氯稀释-逐滴加成反应，高区域选择性地芳酰化得到5 ′-芳酸酯。5 ′-芳酸酯按常规方法有效地转化为相应的2 ′，3 ′-二脱氧核苷。酰化过程也适用于核糖核苷，根据酰氯的量，得到它们的5 ′-酰化物和/或2 ′，5 ′-二酰化物，后者通过用Wakogel C-300处理而衍生成3 ′，5 ′-二酰化物。以通常的方式，它们被转化为3 ′-和2 ′-THP衍生物，这些衍生物已知是合成寡核糖核苷酸的关键中间体，因此，我们进行了一系列带有2 ′-5 ′和3 ′-5磷酸二酯键的寡核糖核苷酸合成，直到十一聚体，值得注意的是，使用用4-羟基乙酸官能化的乙酸纤维素的新型聚合物载体方法是可行的。（2-羟乙基磺酰基）二氢肉桂酸酯，由于其溶解性，证明了液相和固相方法的优越性。此外，开发了涉及核苷的碳水化合物的羟基的高度区域选择性苯基氨基甲酰基化、甲氧基甲基化和三异丙基甲硅烷基化，以及核糖核苷的核酸碱基部分的保护。