Synthesis of Hypermodified Nucleosides Related to Phenylalanine Transfer Ribonucleic Acids.

与苯丙氨酸转移核糖核酸相关的超修饰核苷的合成。

• 批准号: 09672140
• 负责人: ITAYA Taisuke
• 金额: $ 2.05万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672140/
• 关键词: tRNA modified base; tRNA modified nucleoside; Wittig reaction; Osmium oxidation; Cyclic carbonic acid diester; Imidazolide linkage; Substituent effect; Hammett equation; キラル合成; 転移リボ核酸超修飾ヌクルオシド; 光学活性β,γ-不飽和アミノ酸; 高立体選択的ウィッテイッヒ反応; 環状炭酸ジエステル水素化分解

(1)An improved synthesis of the key intermediates for the synthesis of [R-(R*, S*)]- and [S-(R*, R*)]-beta-hydroxywybutines, the most probable structures for the minor base from rat liver tRNA^<Phe>, has been achieved by the Wittig reaction between 1-benzyl-7-formylwye and the phosphorane derived from (R)- 2-[(methoxycarbonyl)amino]-3-(triphenylphosphonio)- propanoate, followed by methylation, 0S0_4 oxidation, and cyclo-condensation with COCl_2 in the presence of pyridine. (R*, R*)-beta-Hydroxywybutine and its diastereomer, which were required for the determination of the optical purity of the chiral bases by means of chiral HPLC, were conveniently prepared through pyrolysis of the cyclic carbonate followed by NaBH_4 reduction and catalytic hydrogenolysis. The samples of [R-(R*, S*)]- and [S-(R*, R*)-beta-hydroxywybutines were thus shown to be optically pure.(2)The synthesis at the nucleoside level started with the Vilsmeier reaction of 3-[2,3,5-tris-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]wye and proceeded through the Wittig reaction with (R)-2-[(methoxycarbonyl)-amino]-3-(triphenylphosphonio)propanoate, methylation with trimethyl-silyldiazomethane, 0s04 oxidation, cyclocondensation with triphosgene, and catalytic hydrogenolysis. Chromatographic separation of the resulting diastereomeric mixture and subsequent deprotection afforded the two desired nucleosides for the first time.(3)it has been revealed that the rate of isomerization of l-benzyl-4-methyl-4,9-dihydro- 1H-imidazo[1 ; 2-alpha]purin-9-ones in 0.1 M MeONa-MeOH at .25*C increases with increasing electron-withdrawing nature of the 7-substituent and that the reactivity is further promoted by the intramolecular hydrogen bond between the carbonyl group at the 9-position and the 7-substituent.

(1)通过1-苄基-7-甲酰基与(R)- 2-[（甲氧羰基）氨基]-3-（三苯基膦）-丙酸衍生的磷烷进行Wittig反应，甲基化，0s_4氧化，并在吡啶存在下与COCl_2进行环缩合，得到了合成[R-(R*, S*)]-和[S-(R*, R*)]- β -羟基wybutin的关键中间体。（R*, R*）- β -羟基wybutine及其非对映体是通过手性高效液相色谱法测定手性碱光学纯度所必需的，通过环碳酸盐热解、NaBH_4还原和催化氢解制备得到。结果表明，[R-(R*, S*)]-和[S-(R*, R*)- β -羟基wybutine是光学纯的。(2)核苷水平的合成从3-[2,3,5-三- o -（叔丁基二甲基硅基）- β - d -核糖呋喃基]wye的Vilsmeier反应开始，然后与(R)-2-[（甲氧基羰基）-氨基]-3-（三苯基膦基）丙酸酯进行Wittig反应，与三甲基硅基重氮甲烷甲基化，004氧化，与三光气环缩合和催化氢解。色谱分离得到的非对映异构体混合物和随后的脱保护首次提供了两种所需的核苷。(3)揭示了l-苄基-4-甲基-4,9-二氢- 1h -咪唑的异构化速率[1；2- α]purin-9- 1在0.1 M MeONa-MeOH中。25*C随7取代基吸电子性质的增加而增加，9位羰基与7取代基之间的分子内氢键进一步促进了反应活性。

项目成果

Taisuke Itaya: "Studies towards the Synthesis of the Hypermodified Nucleoside of Rat Liver Phenylalanine Transfer Ribonucleic Acic: Improved Synthesis of the Based β-Hydroxywybutine" Chem.Phaim.Bull.46. 1220-1224 (1998)

Taisuke Itaya：“大鼠肝脏苯丙氨酸转移核糖核酸的超修饰核苷的合成研究：基于β-羟基维布汀的改进合成”Chem.Phaim.Bull.46 (1998)。

T.Itaya: "Studies towards the Synthesis of the Hypermodified Nucleoside of Rat Liver Phenylalanine Transfer Ribonucleic Acid : Improved Synthesis of the Base beta-Hydroxywybutine" Chem.Pharm.Bull.46. 1220-1224 (1998)

T.Itaya：“大鼠肝脏苯丙氨酸转移核糖核酸超修饰核苷的合成研究：基础β-羟基维布汀的改进合成”Chem.Pharm.Bull.46。

Taisuka Itaya: "Studies towards the Synthesis of the Hypermodified Nucleoside of Rat Liver Phenylalanine Transfer Ribonucleic Acid: Improved Synthesis of the Base β-Hydroxywybutine" Chem.Pharm.Bull.46(8). 1220-1224 (1998)

Taisuka Itaya：“大鼠肝苯丙氨酸转移核糖核酸的超修饰核苷的合成研究：基础β-羟基维布汀的改进合成”Chem.Pharm.Bull.46(8) (1998)。