Studies on the Synthesis of the Fluorescent Hypermodified Nucleoside.

荧光超修饰核苷的合成研究。

• 批准号: 63570988
• 负责人: ITAYA Taisuke
• 金额: $ 1.47万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570988/
• 关键词: Transfer ribonucleic acid; Hypermodified nucleoside; Fluorescent nucleoside; Optically active beta, gamma-unsaturated amino acid; Vinylglycine; Chiral synthesis; Heck reaction; High-performance liquid chromatography; 転移リボ核酸超修飾ヌクレオシド; 3環性ヌクレオシド

We had already achieved the synthesis of wybutine, the base of the title compound, wybutosine, by means of the Wittig or the, Heck reaction as a key step. Neither similar Wittig approach nor the modified procedure effected the synthesis of our target compound, 3-beta-D-ribofuranosylwye (1). On the other hand, the Heck reaction at the nucleoside level successfully afforded 1. This product, however, proved to be contaminated by its diastereomer. In order to develop a stereoselective synthesis of 1, we attempted several recent methods of C-C bond forming reactions as well as modification of the Heck reaction. Because none of them gave a positive result, we focused on separation of (S)-4,9-dihydro-alpha-[(methoxycarbonyl)amino]-4,6-dimethyl-9-oxo-3-(2,3,5-tri-omicron-acetyl-beta- D-ribofuranosyl)-3H-imidazo[1,2-alpha]purine-7-butanole acid (2), a precursor for the synthesis of 1, from its diastereomer by high-performance liquid chromatography. The separation was attained by use of a reversed-phase system [acetonitrile-0.02 M aqueous sodium dihydrogen phosphate (15:85, v/v)]. Compound 2 was treated with trimethyl- silyldiazomethane followed by deacetylation to afford stereochemically pure I for the first time. Compound 1 thus obtained underwent unusually fast hydrolysis at the N-glycosidic bond and the rate was of the same order of magnitude as that reported for wybutosine. Because 2',3',5'-tri-omicron-acetyl derivative of 1 proved much more stable than 1, isolation and identification of wybutosine should be done through its triacetate.

我们已经通过Wittig反应或Heck反应作为关键步骤合成了标题化合物怀布辛的基础物怀布汀。类似的Wittig方法和改进的方法都没有影响我们的目标化合物3-β-D-呋喃核糖基wye的合成（1）。另一方面，在核苷水平上的Heck反应成功地提供了1。然而，该产物被证明被其非对映异构体污染。为了发展1的立体选择性合成，我们尝试了几种最近的C-C键形成反应以及Heck反应的改进方法。因为它们都没有给出阳性结果，所以我们集中于通过高效液相色谱法从其非对映体中分离（S）-4，9-二氢-α-[（甲氧羰基）氨基]-4，6-二甲基-9-氧代-3-（2，3，5-三-三-甲基-乙酰基-β-D-呋喃核糖基）-3H-咪唑并[1，2-α]嘌呤-7-丁酸（2），其为1合成的前体。通过使用反相系统[乙腈-0.02 M磷酸二氢钠水溶液（15：85，v/v）]实现分离。化合物2用三甲基硅基重氮甲烷处理，然后脱乙酰化，首次得到立体化学纯的I。由此获得的化合物1在N-糖苷键处经历异常快速的水解，并且速率与所报道的异丁糖核苷的速率具有相同的数量级。由于1的2 '，3'，5 '-三乙酰基衍生物比1稳定得多，因此应通过其三乙酸酯进行分离和鉴定。

项目成果

T. Itaya: "Access to the Synthesis of Wybutosine, the First Tricyclic Fluorescent Nucleoside Isolated from Phenylalanine Transfer Ribonucleic Acids" Tetrahedron Lett., 29, 4129-4132 (1988).

T. Itaya：“获得威布托辛的合成，这是第一个从苯丙氨酸转移核糖核酸中分离出来的三环荧光核苷”Tetrahedron Lett.，29, 4129-4132 (1988)。

Taisuke Itaya: "Access to the Synthesis of Wybutosine,the First Tricyclic Fluorescent Nucleoside Isolated from Phenylalanine Transfer Ribonucleic Acids" Tetrahedron Lett.29. 4129-4132 (1988)

Taisuke Itaya：“获得威布托辛的合成，这是第一个从苯丙氨酸转移核糖核酸中分离出来的三环荧光核苷”四面体 Lett.29。

板谷泰助: 薬学雑誌. 108. 697-715 (1988)

Taisuke Itaya：制药杂志 108. 697-715 (1988)

板谷,泰助: "転移リボ核酸微量成分の合成化学的研究" 薬学雑誌. 108. 697-715 (1988)

Itaya, Yasuke：“转移核糖核酸微量成分的合成化学研究”制药杂志 108. 697-715 (1988)。

板谷泰助: "転移リボ核酸微量成分の合成化学的研究" 薬学雑誌. 108. 697-715 (1988)

Taisuke Itaya：“转移核糖核酸微量成分的合成化学研究”制药杂志 108. 697-715 (1988)。