S-methylthiodeoxyinosine | 23526-11-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: S-methylthiodeoxyinosine
• 英文别名: 1-(6-methylsulfanyl-purin-9-yl)-β-D-erythro-1,2-dideoxy-pentofuranose；(2R,3S,5R)-2-(hydroxymethyl)-5-(6-methylsulfanylpurin-9-yl)oxolan-3-ol
• CAS: 23526-11-6
• 化学式: C₁₁H₁₄N₄O₃S
• 分子量: 282.323
• InChiKey: YRNDGOJOSCJYAI-XLPZGREQSA-N

物化性质

• 沸点：
  592.3±60.0 °C(Predicted)
• 密度：
  1.72±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  S-methylthiodeoxyinosine 在 吡啶 、 间氯过氧苯甲酸 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 9-(2-deoxy-3,5-di-O-acetyl-β-D-erythro-pentofuranosyl)purine-6-carbonitrile
  参考文献：
  名称：

  Synthesis and biological evaluation of certain 2'-deoxy-.beta.-D-ribo-and 2.beta.-D-arabinofuranosyl nucleosides of purine-6-carboxamide and 4,8-diaminopyrimido[5,4-d]pyrimidine

  摘要：

  The key intermediate 9-(2,3,5,-tri-O-acetyl-beta-D-arabinofuranosyl)purine-6-carbonitrile (7) was synthesized in four steps from 9-beta-D-arabinofuranosylpurine-6-thione (3) via 6-(methylsulfonyl)-9-(2,3,5-tri-O-acetyl-beta-D-arabinofuranosyl)purine (6). Reaction of compound 7 with methanolic ammonia provided the rearranged compound 4-amino-8-(beta-D-arabinofuranosylamino)pyrimido[5,4-d]pyrimidine (8). Treatment of 7 with ammonium hydroxide and hydrogen peroxide provided 9-beta-D-arabinofuranosylpurine-6-carboxamide (9). Compound 7 was also treated with sodium hydrosulfide to yield 9-beta-D-arabinofuranosylpurine-6-thiocarboxamide (10). Similarly, 9-(2-deoxy-3,5-di-O-acetyl-beta-D-erythro-pentofuranosyl)purine 6-carbonitrile (17) was prepared from 6-chloro-9-(2-deoxy-beta-D-erythro-pentofluranosyl)purine (11) via 9-(2-deoxy-beta-D-erythro-pentofuranosyl)purine-6-thione. Compound 17 was converted into 4-amino-8-[(2-deoxy-beta-D-erythro-pentofuranosyl)amino]pyrimido[5,4-d]pyrimidi ne (18) and 9-(2-deoxy-beta-D-erythro-pentofuranosyl)purine-6-carboxamide (20), respectively. Compound 2 showed immunosuppressive activity and also inhibited the growth of L-1210 leukemia in mice. Arabinonucleoside analogues 8-10 were inactive when tested against RNA and DNA viruses in cell culture.

  DOI：

  10.1021/jm00136a008
• 作为产物：
  描述：

  6-甲硫基嘌呤核苷 生成 S-methylthiodeoxyinosine
  参考文献：
  名称：

  含N 6，N 6-乙基去氧腺苷的脱氧寡核苷酸的合成与交联性能

  摘要：

  我们报告5'HO -dT 6（N 6，N 6- ethanonodeoxyadenosine）T 14的合成。该寡核苷酸在pH 7.5和20℃下与5'HO-dA 14 CA 6 T特异性交联，具有约一天的半衰期。

  DOI：

  10.1016/s0040-4039(00)95443-1

文献信息

• Synthesis of 2-Deoxy-β-D-ribonucleosides and 2,3-Dideoxy-β-D-pentofuranosides on Immobilized Bacterial Cells
  作者：Ivan Votruba、Antonín Holý、Hana Dvořáková、Jaroslav Günter、Dana Hocková、Hubert Hřebabecký、Tomas Cihlar、Milena Masojídková

  DOI：10.1135/cccc19942303

  日期：——

  Alginate gel-entrapped cells of auxotrophic thymine-dependent strain of E. coli catalyze the transfer of 2-deoxy-D-ribofuranosyl moiety of 2'-deoxyuridine to purine and pyrimidine bases as well as their aza and deaza analogs. All experiments invariably gave β-anomers; in most cases, the reaction was regiospecific, affording N⁹-isomers in the purine and N¹-isomers in the pyrimidine series. Also a 2,3-dideoxynucleoside can serve as donor of the glycosyl moiety. The acceptor activity of purine bases depends only little on substitution, the only condition being the presence of N⁷-nitrogen atom. On the other hand, in the pyrimidine series the activity is limited to only a narrow choice of mostly short 5-alkyl and 5-halogeno uracil derivatives. Heterocyclic bases containing amino groups are deaminated; this can be avoided by conversion of the base to the corresponding N-dimethylaminomethylene derivative which is then ammonolyzed. The method was verified by isolation of 9-(2-deoxy-β-D-ribofuranosyl) derivatives of adenine, guanine, 2-chloroadenine, 6-methylpurine, 8-azaadenine, 8-azaguanine, 1-deazaadenine, 3-deazaadenine, 1-(2-deoxy-β-D-ribofuranosyl) derivatives of 5-ethyluracil, 5-fluorouracil, and 9-(2,3-dideoxy-β-D-pentofuranosyl)hypoxanthine, 9-(2,3-dideoxy-β-D-pentofuranosyl)-6-methylpurine, and other nucleosides.

  藻酸盐凝胶包埋的辅助胸腺嘧啶依赖菌株大肠杆菌细胞催化2'-脱氧尿嘧啶的2-脱氧-D-核糖呋喃基团转移到嘌呤和嘧啶碱基以及它们的氮杂和去氮类似物。所有实验都不可避免地产生β-异构体；在大多数情况下，反应是区域特异性的，产生嘌呤中的N⁹-异构体和嘧啶系列中的N¹-异构体。此外，2,3-二脱氧核苷酸可以作为糖基团的供体。嘌呤碱基的受体活性仅在取代上有少许影响，唯一的条件是存在N⁷-氮原子。另一方面，在嘧啶系列中，活性仅限于大多数短链5-烷基和5-卤代尿嘧啶衍生物的狭窄选择。含氨基的杂环碱基会发生脱氨作用；可以通过将碱基转化为相应的N-二甲氨基甲烯基衍生物来避免这种情况，然后进行氨解作用。该方法通过分离腺嘌呤、鸟嘌呤、2-氯腺嘌呤、6-甲基嘌呤、8-氮杂腺嘌呤、8-氮杂鸟嘌呤、1-去氮腺嘌呤、3-去氮腺嘌呤的9-(2-脱氧-β-D-核糖呋喃基)衍生物，5-乙基尿嘧啶、5-氟尿嘧啶的1-(2-脱氧-β-D-核糖呋喃基)衍生物，以及9-(2,3-二脱氧-β-D-戊呋喃基)缺氧嘌呤、9-(2,3-二脱氧-β-D-戊呋喃基)-6-甲基嘌呤和其他核苷酸的验证。
• Preparation of Oligodeoxynucleotides Containing 6-Methylthiopurine Residues by Chemical Synthesis or Specific Methylation
  作者：Yao-Zhong Xu、Qinguo Zheng、Peter Swann

  DOI：10.1080/15257779508012504

  日期：1995.5.1

  Abstract Two methods (chemical synthesis and specific methylation) are described for the preparation of oligodeoxynucleotides containing 6-methylthiopurine residues. 6-Methylthiopurine phosphoramidite (6) is prepared and incorporated into oligomers. Methylation with methyl iodide of 6-thiopurine (or 6-thioguanine) in oligonucleotides also leads to exclusive production of 6-methylthiopurine (or 6-methylthioguanine)

  摘要描述了两种制备含有6-甲基硫代嘌呤残基的寡脱氧核苷酸的方法（化学合成法和特异性甲基化法）。制备6-甲基硫代嘌呤亚磷酰胺（6），并掺入低聚物中。寡核苷酸中的6-硫代嘌呤（或6-硫代鸟嘌呤）的甲基碘的甲基化还导致独家生产6-甲基硫代嘌呤（或6-甲基硫代鸟嘌呤）低聚物。
• Post-synthetic introduction of labile functionalities onto purine residues via 6-methylthiopurines in oligodeoxyribonucleotides
  作者：Yao-Zhong Xu

  DOI：10.1016/0040-4020(96)00596-0

  日期：1996.8

  oligodeoxynucleotides containing 6-methylthiopurine residues. 6-Methylthiopurine phosphoramidite (6) has been prepared and incorporated into oligomers. Methylation with methyl iodide of 6-thiopurine (or 6-thioguanine) in oligomers also exclusively produces oligomers containing 6-methylthiopurine (or 6-methylthioguanine). The methylthio group at defined purine residues in the deprotected oligomers can be oxidized

  描述了两种用于制备含有6-甲基硫代嘌呤残基的寡脱氧核苷酸的方法。已经制备了6-甲基硫代嘌呤亚磷酰胺（6），并将其掺入低聚物中。在低聚物中用6-硫代嘌呤（或6-硫代鸟嘌呤）的甲基碘进行甲基化还专门产生含有6-甲基硫代嘌呤（或6-甲基硫代鸟嘌呤）的低聚物。脱保护的低聚物中定义的嘌呤残基上的甲硫基可以被选择性氧化，并在最后一步转化为各种官能团，包括放射性35 S-硫基，这是进行交联研究的有用标签。
• Synthetic nucleosides and nucleotides. XXI. On the synthesis and biological evaluations of 2'-deoxy-.ALPHA.-D-ribofuranosyl nucleosides and nucleotides.
  作者：TOYOFUMI YAMAGUCHI、MINEO SANEYOSHI

  DOI：10.1248/cpb.32.1441

  日期：——

  N4-Benzoyl-2'-deoxycytidine (1) was converted to its 3', 5'-di-O-acetate (2). Compound 2 was smoothly anomerized to its α-counterpart (3) by reaction with trimethylsilyl trifluoromethanesul-fonate (TMS-triflate). Saponification of 3 afforded crystalline α-2'-deoxycytidine (4). Similarly, 3', 5'-di-O-p-toluoyl-2'-deoxythymidine (5) was anomerized to the α-anomer (6), which was then deblocked to give α-2'-deoxythymidine (7). α-2'-Deoxyadenosine (8) and 9-(2-deoxy-α-D-ribofuranosyl)-6-methylthiopurine (9a) were prepared by TMS-triflate-catalyzed trans-2-deoxyribosylation from compound 2 to N6-benzoyladenine and 6-methylthiopurine, respectively. α-5-Fluoro-2'-deoxycytidine (11a) and its β-anomer (11b) were synthesized by the reaction of the trimethylsilyl derivative of N4-p-toluoyl-5-fluorocytosine with 1-O-acetyl-3, 5-di-O-benzoyl-2-deoxy-D-ribofuranose followed by deblocking. Among the compounds related to α-2'-deoxyribonucleosides, compound 4 and 11a showed weak growth-inhibitory activity on mouse leukemic L5178Y cells in culture. Of the nucleoside 5'-triphosphates, α-deoxy ATP had some affinity with DNA polymerase α when activated DNA was used as a template-primer. α-Deoxythymidine 5'-triphosphate (TTP) showed a remarkable inhibitory effect on DNA polymerase β when poly [rA]-oligo dT was used as template-primer.

  将 N4-苯甲酰基-2'-脱氧胞苷（1）转化为其 3'，5'-二-O-乙酸酯（2）。通过与三氟甲磺酸三甲基硅酯（TMS-triflate）反应，化合物 2 顺利异构化成其 α-对应物（3）。3 的皂化反应得到了结晶α-2'-脱氧胞苷（4）。同样，3', 5'-di-O-p-toluoyl-2'-deoxythymidine (5) 被异构化为 α-异构体 (6)，然后脱锁得到 α-2'-deoxythymidine (7)。α-2'-脱氧腺苷（8）和 9-(2-脱氧-α-D-呋喃核糖基)-6-甲基硫嘌呤（9a）是通过 TMS-三late催化反式-2-脱氧核糖基化从化合物 2 分别制备成 N6-苯甲酰基腺嘌呤和 6-甲基硫嘌呤。α-5-氟-2'-脱氧胞苷（11a）及其 β-异构体（11b）是通过 N4-对甲苯甲酰基-5-氟胞嘧啶的三甲基硅烷衍生物与 1-O-乙酰基-3，5-二-O-苯甲酰基-2-脱氧-D-呋喃核糖反应，然后脱锁合成的。在与α-2'-脱氧核苷有关的化合物中，化合物 4 和 11a 对培养中的小鼠白血病 L5178Y 细胞表现出微弱的生长抑制活性。在核苷 5'-三磷酸酯中，α-脱氧 ATP 在以活化 DNA 为模板引物时与 DNA 聚合酶 α 有一定的亲和力；α-脱氧胸苷 5'- 三磷酸酯（TTP）在以聚[rA]-醇溶 dT 为模板引物时对 DNA 聚合酶 β 有显著的抑制作用。
• Deoxyadenosine Bisphosphate Derivatives as Potent Antagonists at P2Y₁ Receptors
  作者：Emidio Camaioni、José L. Boyer、Arvind Mohanram、T. Kendall Harden、Kenneth A. Jacobson

  DOI：10.1021/jm970433l

  日期：1998.1.1

  adenosine nucleoside precursors were carried out. The activity of each analogue at P2Y1 receptors was determined by measuring its capacity to stimulate phospholipase C in turkey erythrocyte membranes (agonist effect) and to inhibit phospholipase C stimulation elicited by 10 nM 2-MeSATP (antagonist effect). Both 2'- and 3'-deoxy modifications were well tolerated. The N6-methyl modification both enhanced

  腺苷3',5'-和2',5'-二磷酸先前被证明可作为P2Y1受体的竞争性拮抗剂(Boyer等人Mol.Pharmacol.1996, 50, 1323-1329)。已合成了 2'- 和 3'-脱氧腺苷二磷酸类似物，在腺嘌呤环的 2- 和 6- 位、核糖部分和磷酸基团上含有各种结构修饰，目的是开发更有效和选择性的 P2Y1对手。进行了腺苷核苷前体的一步磷酸化反应。通过测量其刺激火鸡红细胞膜中磷脂酶 C（激动剂作用）和抑制 10 nM 2-MeSATP 引起的磷脂酶 C 刺激（拮抗剂作用）的能力，确定每种类似物对 P2Y1 受体的活性。 2'-和3'-脱氧修饰均具有良好的耐受性。 N6-甲基修饰既增强​​了 2'-脱氧腺苷 3',5'-二磷酸的拮抗效力 (IC50 330 nM) 17 倍，又消除了先导化合物观察到的残留激动剂特性。 N6-乙基修饰提供了作为拮抗剂的中等效力，而N6-丙基完全消除了激动剂和拮抗剂特性。