Efficient and Selective Synthesis of Biologically Active Compounds Related to Nucleic Acid by Uranyl Complex Catalyst

铀酰配合物催化剂高效选择性合成核酸相关生物活性化合物

• 批准号: 63470076
• 负责人: SAWAI Hiroaki
• 金额: $ 3.65万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 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/en/grant/KAKENHI-PROJECT-63470076/
• 关键词: Nucleic Acid; Biologically Active Compounds; Uranyl Complex; Oligonucleotide; 2'-5' Internucleotide Bond; Pyrophosphate Bond; Selective Synthesis; Metal Ion Catalyst; 核酸関連生理活性物質; 核酸-金属錯体; 2´- 5´結合

1. Various nucleoside-5-phosphorimidazolides were prepared from nucleotides such as adenylic acid uridylic acid, cytidylic acid, guanilic acid and 8-azide-adenylic acid, with imidazole and azole compounds such as benzimidazole and triazoles. 2. Using urany complex catalyst which was formed from uranyl nitrate and nucleoside-5'- phosphporimidazolide, the nucleoside-5'-phosphporimidazolide were polymerized.3. Analysis of the products by high performance liquid chromatography revealed that oligonucleotides from dimer to hexadecamer were formed in high yields. 4. The selectivity of 2'5'-internucleotide bond was 65 - 98%. The type, yield and the regioselectivity of the resulting oligonucleotides were greatly dependent on the pH of the medium, reaction temperature and the concentration of the catalyst. The polymerization took place most efficiently under neutral conditions. 5. Nucleoside-5'- phosphporimidazolides with any nucleic acid bases were polymerized by uranyl complex catalysts forming the corresponding oligonucleotides, though the type of the resulting oligonucleotides were different depending on the type of nucleic acid base used.6. Hg2+ or Ag+ ion coordinated to the base part exclusively and altered the selectivity of the oligocytidylate formation by uranyl complex catalyst. Use of azole compounds as a nucleotide activating group in the place of imidazole changed the rate, selectivity and yield of the uranyl-ion complex catalyzed oligonucleotide synthesis. 7. Further we have found that Mn2+ and Cd2+ facilitate the pyrophosphate bond formation of nucleotides through the different type of metal-nucleotide complex. 8. Applying the above reaction, we prepared some biologically active nucleotides such as 2-5A analogues, coenzymes and dinucleoside polyphosphates.

1.以腺苷酸、尿苷酸、胞苷酸、胍基酸、8-叠氮腺苷酸等核苷酸为原料，与苯并咪唑、三唑等咪唑类化合物反应，合成了各种核苷-5-磷酰咪唑。2.采用硝酸铀酰与核苷-5 '-磷酰咪唑形成的铀酰络合物催化剂，进行了核苷-5'-磷酰咪唑的聚合.通过高效液相色谱分析产物显示，以高产率形成从二聚体到十六聚体的寡核苷酸。4. 2 '5'-核苷酸间键的选择性为65 - 98%。寡核苷酸的种类、产率和区域选择性与反应介质的pH值、反应温度和催化剂浓度密切相关。聚合反应在中性条件下最有效地进行。5.通过铀酰络合物催化剂聚合具有任何核酸碱基的核苷-5 '-磷酸咪唑，形成相应的寡核苷酸，尽管所得寡核苷酸的类型取决于所使用的核酸碱基的类型而不同。Hg ~（2+）或Ag ~+离子仅与碱基部分配位，改变了铀酰络合物催化寡胞苷酸形成的选择性。使用唑类化合物代替咪唑作为核苷酸活化基团改变了铀酰离子络合物催化的寡核苷酸合成的速率、选择性和产率。7.此外，我们还发现Mn ~（2+）和Cd ~（2+）通过不同类型的金属-核苷酸络合物促进核苷酸的焦磷酸键形成。8.应用上述反应，我们制备了一些具有生物活性的核苷酸，如2-5A类似物、辅酶和二核苷多磷酸。

项目成果

H.Sawai: "Divalent Metal Ion-Mediated Phosphodiester Bond Formation from Adenosine-5'-phosphorimidazolide with Glycolic Acid or Lactic Acid.A Nonenzymatic Model Reaction for Nucleotidyl Transfer" Bull.Chem.Soc.Jpn(in press). 63. (1990)

H.Sawai：“二价金属离子介导的腺苷-5-磷咪唑与乙醇酸或乳酸形成磷酸二酯键。核苷酸转移的非酶模型反应”Bull.Chem.Soc.Jpn（正在印刷中）。

H.Sawai: Bull.Chem.Soc.Japan. 62. (1989)

H.Sawai：Bull.Chem.Soc.Japan。

H.Sawai,T.Shibusawa and K.Kuroda: "Uranyl Ion Catalyzed Oligonucleotide Synthesis from Adenosine-5'-Phosphorimidazolide.The Effect of Azoles as Nucleotide Activating Groups" Nucleic Acid Res.Sp.Ser.21. 91-92 (1989)

H.Sawai、T.Shibusawa 和 K.Kuroda：“铀酰离子催化的腺苷-5-磷酸咪唑化物合成寡核苷酸。唑类作为核苷酸激活基团的作用”核酸 Res.Sp.Ser.21。

H. Sawai: "Divalent Metal Ion-Mediated Phosphodiester Bond Formation from Adenosine-5'-phosphorimidazolide with Glycolic Acid or Lactic Acid. A Nonenzymatic Model Reaction for Nucleotidyl Transfer" Bull. Chem. Soc. Jpn, 63 (1990).

H. Sawai：“二价金属离子介导的腺苷-5-磷咪唑与乙醇酸或乳酸形成磷酸二酯键。核苷酸转移的非酶模型反应”公牛。

H. Sawai: "Efficient Oligoadenylate Synthesis Catalyzed by Uranyl Ion Complex in Aqueous Solution" Nucleic Acid Res. Sp. Ser., 19, 5-7 (1988).

H. Sawai：“水溶液中铀酰离子复合物催化的高效寡腺苷酸合成”核酸研究。