Synthetic Study of Biologically Related Compounds Using Cellulose Derivatives as a Polymer-support

使用纤维素衍生物作为聚合物载体的生物相关化合物的合成研究

• 批准号: 02403011
• 负责人: ISHIDO Yoshiharu
• 金额: $ 15.36万
• 依托单位: Tokyo College of Pharmacy
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02403011/
• 关键词: A cellulose acetate as a polymer-support; A nucleoside with a modified base; 2'-omicron-(D-Ribofuranosyl)-adenosine; D-Ribofuranosylation; Glycosyl carbamate derivatives; Stable isotope labeled nucleosides; [2'-^2H]-2'-Deoxyribonucleosides; Nucleos

1.Synthetic Study of Oligonucleotides : (1)The cellulose acetate derivatives were found to be feasible for the syntheses of DNA-type8-mer and of RNA-type 13-mer. (2)Development of efficient methods for the protection of functional groups involved in pseudouridine (psi), 1-beta-D-ribofuranosylthymine(rT), 5, 6-dihydrouridine(D), and phosphate, led us to successful syntheses of RNA-type 12-mer involving psi and rT, 11-mer involving 5'-terminal phosphate through the polymer-support, and 8-mer involving D through the CPG-support.2.Synthetic Study of 2'-omicron-(alpha- and beta-D-ribofuranosyl)adenosines : The alpha-isomer, known as the key compound of poly(ADP-ribose), and the beta-isomer, found as the corresponding 5'-phosphate located at 64th position of Yeast initiator tRNA^<Met>, were synthesized with high stereoselectivity by the acid-catalyzed coupling reaction of an adenosine 2'-hydroxyl derivative with D-ribofuranosyl derivatives functionalized at their anomeric position.3.Synthetic Study of Oligosaccharides : Novel approaches to glycosylation in terms of acid-catalyzed coupling reaction of a glycosyl acceptor with glycosyl donors bearing 1-phenoxylcarbonate and 1-phenylcarbamate were developed. and the latter was found to be particularly feasible for the synthesis of oligosaccharides such as Le^Y antigenic tetrasaccharide.4.Synthetic Study of Nucleosides Specifically Labeled with Stable Isotopes : Highly diastereoselective syntheses of (2'R)- and (2'S)-[2'-^2H]-2'-deoxyribonucleosides, and efficient method for the syntheses of nucleosides bearing exocyclic amino groups, were labeled with ^<15>N atom, were realized. These products essentially contribute to the NMR spectroscopic study on delicate conformational analysis on interactions of nucleic acid-nucleic acid or nucleic acid-protein etc.

1.寡核苷酸的合成研究：（1）醋酸纤维素衍生物可用于DNA型8-mer和RNA型13-mer的合成。（2）开发了保护假尿苷（psi）、1-β-D-呋喃核糖基胸腺嘧啶（rT）、5，6-二氢尿苷（D）和磷酸基的有效方法，使我们成功地通过聚合物载体合成了涉及psi和rT的RNA型12-mer，涉及5 ′-末端磷酸基的11-mer，2.2 '-omicron-2的合成研究（α-和β-D-呋喃核糖基）腺苷：α-异构体，被称为聚乙烯的关键化合物（ADP-核糖）和β-异构体（被发现为位于酵母起始物tRNA α的第64位的相应5 ′-磷酸）<Met>通过腺苷2 ′-磷酸的酸催化偶联反应以高立体选择性合成。羟基衍生物与在其异头位置官能化的D-呋喃核糖基衍生物。3.寡聚体的合成研究：开发了根据糖基受体与带有1-苯基碳酸酯和1-苯基氨基甲酸酯的糖基供体的酸催化偶联反应的糖基化新方法。4.稳定同位素特异性标记核苷的合成研究：实现了（2 'R）-和（2'S）-[2'-^2H]-2 '-脱氧核苷的高非对映选择性合成，以及用^ N原子标记环外氨基核苷的高效合成方法<15>。这些产物为核磁共振波谱研究核酸-核酸、核酸-蛋白质等分子间相互作用的精细构象分析提供了基础。

项目成果

K.Kamaike, T.Ogawa, Y.Inoue, and Y.Ishido: "Further Improvement in Protecting Method for the Oligonucleotide Synthesis in Terms of a Cellulose Acetate Derivative as a Polymer-support" Nucleic Acids Res.Symposium Series. 24. 37-39 (1991)

K.Kamaike、T.Okawa、Y.Inoue 和 Y.Ishido：“以醋酸纤维素衍生物作为聚合物载体进一步改进寡核苷酸合成的保护方法”核酸研究研讨会系列。

K.Kamaike, T.Ogawa, and Y.Ishido: "Synthesis of an Oligonucleotide Bearing a Phosphate Function at the 5'-Terminus Using a Novel Protecting Group in Terms of a Cellulose Acetate Derivative as a Polymer-support" Nucleosides & nucleotides. 12. 1015-1032 (19

K.Kamaike、T.Okawa 和 Y.Ishido：“使用醋酸纤维素衍生物作为聚合物载体的新型保护基团合成 5 末端具有磷酸功能的寡核苷酸”

E.Kawashima: "Sonochemical and Triethylborane‐induced Tin Deuteride Reduction for the Highly Stereoselective Synthesis of(2′R)‐[2′‐^2H]‐2′‐Deoxyribonucleosides from 2′‐Functionalized Ribonucleosids" Tetrahedron Lett.34. 1317-1320 (1993)

E. Kawashima：“声化学和三乙基硼烷诱导的氘化锡还原，用于从 2′-功能化核糖核苷中高度立体选择性合成 (2′R)-[2′-^2H]-2′-脱氧核糖核苷”Tetrahedron Lett.34。 -1320 (1993)

S.Nishino,Y.Nagata,Y.Hasegawa,H.Yamamoto,K.Kamaike,and Y.Ishido: "Efficient Deanilidation of Phosphroanilidates by the Use of Nitrites and Acetic Anhydride" Heteroatom Chem.2. 187-196 (1991)

S.Nishino、Y.Nagata、Y.Hasekawa、H.Yamamoto、K.Kamaike 和 Y.Ishido：“通过使用亚硝酸盐和乙酸酐对 Phosphroanilidates 进行高效脱苯胺化”Heteroatom Chem.2。

K,Kamaike: "Oligonucleotide Synthesis in terms of a Novel Type of PolymerーSupport:a Cellulose Acetate Functionalized with 4ー(2ーHydroxyethylsulfonyl)ーdihydrocinnamate Substituent." Tetrahedron. 46. 163-184 (1990)

K, Kamaike：“新型聚合物的寡核苷酸合成 - 支持：用 4-(2-羟乙基磺酰基)-二氢肉桂酸酯取代基官能化的纤维素乙酸酯。” 46. 163-184 (1990)。