3',5'-二-氧-对甲苯磺酰基胸苷 | 63914-08-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 中文名称: 3',5'-二-氧-对甲苯磺酰基胸苷
• 英文名称: 3',5'-bis-O-(p-tolylsulfonyl)thymidine
• 英文别名: Tos(-3)[Tos(-5)]2-deoxy-D-eryPenf(b)-thymin-1-yl；[(2R,3S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-3-(4-methylphenyl)sulfonyloxyoxolan-2-yl]methyl 4-methylbenzenesulfonate
• CAS: 63914-08-9
• 化学式: C₂₄H₂₆N₂O₉S₂
• 分子量: 550.61
• InChiKey: VQRAMBPGTFRTIP-BHDDXSALSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  162
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  3',5'-二-氧-对甲苯磺酰基胸苷 在 potassium tert-butylate 、 potassium hydroxide 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 18.17h， 生成 司他夫定
  参考文献：
  名称：

  [EN] SYNTHESIS AND IMPROVEMENT OF A NUCLEOSIDE ANALOGUE AS AN ANTI-CANCER AND ANTI-VIRAL DRUG
  [FR] SYNTHÈSE ET AMÉLIORATION D'UN ANALOGUE NUCLÉOSIDIQUE EN TANT QUE MÉDICAMENT ANTICANCÉREUX ET ANTIVIRAL

  摘要：

  这项发明是一种用于抗癌和抗病毒疗法的药物，包括一种嘌呤类似物（7），其中包括一个与RNA/DNA合成链通过磷酸二酯键不可逆地结合的呋喃环，并具有SP3杂化，以及与包含呋喃环的嘌呤类似物（7）结合的叶酸（A）。所述嘌呤类似物的合成方法也包括在该发明的范围内。在这项研究中，通过将呋喃环的杂化从Sp2转变为Sp3，将嘌呤类似物转化为更具有不同酶选择性，并通过位点5与有效的叶酸连接，以便进入细胞内物质，并在控制DNA复制和繁殖过程后成为具有抗癌和抗病毒特性的最终化合物。

  公开号：

  WO2021101475A1
• 作为产物：
  描述：

  2-deoxy-D-ribose 在 吡啶 、 甲醇 、 硫酸 、 sodium methylate 、 溶剂黄146 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 反应 52.67h， 生成 3',5'-二-氧-对甲苯磺酰基胸苷
  参考文献：
  名称：

  [EN] SYNTHESIS AND IMPROVEMENT OF A NUCLEOSIDE ANALOGUE AS AN ANTI-CANCER AND ANTI-VIRAL DRUG
  [FR] SYNTHÈSE ET AMÉLIORATION D'UN ANALOGUE NUCLÉOSIDIQUE EN TANT QUE MÉDICAMENT ANTICANCÉREUX ET ANTIVIRAL

  摘要：

  这项发明是一种用于抗癌和抗病毒疗法的药物，包括一种嘌呤类似物（7），其中包括一个与RNA/DNA合成链通过磷酸二酯键不可逆地结合的呋喃环，并具有SP3杂化，以及与包含呋喃环的嘌呤类似物（7）结合的叶酸（A）。所述嘌呤类似物的合成方法也包括在该发明的范围内。在这项研究中，通过将呋喃环的杂化从Sp2转变为Sp3，将嘌呤类似物转化为更具有不同酶选择性，并通过位点5与有效的叶酸连接，以便进入细胞内物质，并在控制DNA复制和繁殖过程后成为具有抗癌和抗病毒特性的最终化合物。

  公开号：

  WO2021101475A1

文献信息

• 3′-Oxo-, amino-, thio- and sulfone-acetic acid modified thymidines: Effect of increased acidity on ribonuclease A inhibition
  作者：Dhrubajyoti Datta、Anirban Samanta、Swagata Dasgupta、Tanmaya Pathak

  DOI：10.1016/j.bmc.2013.05.047

  日期：2013.8

  A family of 3'-functionalized thymidines carrying XCH2COOH (X = O, NH, S, SO2) groups has been designed as inhibitors of RNase A. This is because it is possible to manipulate the overall acidity of this new class of nucleic 'acids' by changing X from oxygen to the SO2 group in the series. It is also expected that the acyclic nature of the XCH2COOH group would provide enough flexibility to the -COOH group to have maximum interactions with the catalytic subsite P-1 of RNase A. As the -SO2CH2COOH substituted derivative showed better potency partially because of the increased acidity of the -COOH group, the inhibitory properties of both 5'-substituted and 3',5'-disubstituted sulfone acetic acid modified thymidines were investigated. Two -SO2CH2COOH groups were incorporated with the expectation of targeting two phosphate binding sites simultaneously. Thus, 3',5'-dideoxy-3',5'-bis-S-[(carboxymethyl)sulfonyl]thymidine emerged as the best inhibitor in this series with a K-i value of 25 +/- 2 mu M. (C) 2013 Elsevier Ltd. All rights reserved.
• Sehgal, Raj K.; Turcotte, Joseph G., Journal of Chemical Research, Miniprint, 1998, # 1, p. 301 - 326
  作者：Sehgal, Raj K.、Turcotte, Joseph G.

  DOI：——

  日期：——
• A novel two-step conversion of 3',5'-di-O-tosylthymidine to 5'-amino-5'-deoxythymidine analogs with inversion of the 3-hydroxyl group
  作者：Robert D. Elliott、John A. Montgomery、James M. Riordan

  DOI：10.1021/jo00389a043

  日期：1987.6
• A convenient method for the conversion of β-thymidine to α-thymidine based on TMSOTf-mediated C1′-epimerization
  作者：Yuichi Sato、Gohsuke Tateno、Kohji Seio、Mitsuo Sekine

  DOI：10.1016/s0040-4039(02)00411-2

  日期：2002.4

  A practically useful method for the synthesis of alpha-thymidine from beta-thymidine was developed by trimethylsilyl triflate-mediated C1'-epimerization. When 5'-O-diphenylacetyl-3'-O-toluoylthmidine was trimethylsilylated and successively treated with TMSOTf in acetonitrile, the resulting a-thymidine derivative was crystallized and isolated without silica-gel column chromatography. Deprotection gave unprotected alpha-thymidine in an overall yield of 50% from beta-thymidine. (C) 2002 Published by Elsevier Science Ltd.
• Synthesis of some 2′,3′-didehydro-2′,3′-dideoxynucleosides derived from modified pyrimidine bases
  作者：Colin B. Reese、Chamakura V. N. S. Varaprasad

  DOI：10.1039/p19940000189

  日期：——

  3'.5'-Bis-O-(4-tolylsulfonyl)-thymidine and -2'-deoxyuridine (13a and 13b) reacted with sodium ethoxide in boiling ethanol to give the corresponding ethoxy-oxetanes 12a and 12b in 67 and 66% overall yield for the two-step processes starting from thymidine 4a and 2'-deoxyuridine 4b; respectively. Treatment of the ethoxy-oxetanes 12a and 12b with hydrogen sulfide and N-1,N-1,N-3,N-3- tetramethylguanidine in dry pyridine solution gave the 2-thiothymine- and 2-thiouracil-derived oxetanes 19a and 19b in 62 and 68.5% yield, respectively. When the latter compounds were treated with potassium tert-butoxide in dimethyl sulfoxide, the corresponding 2',3'-didehydro-2',3'-dideoxynucleosides (d4 nucleosides) 10a and 10b were obtained in 66 and 60% yield. respectively. The 2-thiothymine-derived oxetane 19a was converted via the 5-methyl-2-thiocytosine-derived oxetane 21a into the 5-methyl-2-thiocytosine-derived d4 nucleoside 11a in 59.5% overall yield; the 2-thiouracil-derived oxetane 19b was similarly converted into the 2-thiocytosine- and 4-N-methyl-2-thiocytosine-derived d4 nucleosides 11b and 23 in 51 and 50% overall yield, respectively. Finally, the ethoxy-oxetane 12b was converted into the corresponding amino- and methylamino-oxetanes 25a and 25b in 74 and 83% yield, respectively. The latter compound. 25b, was successfully converted into the 2-N-methylisocytosine-derived d4 nucleoside 26b in 62% yield.