3'-叠氮基-3'-脱氧-5-甲基尿苷 | 215176-58-2

• 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'-叠氮基-3'-脱氧-5-甲基尿苷
• 英文名称: 1-(3'-azido-3'-deoxy-β-D-ribofuranosyl)thymine
• 英文别名: 1-(3-azido-3-deoxy-β-D-ribofuranosyl)thymine；3'-azido-3'-deoxy-β-ribosylthimine；3'-azido-3'-deoxy-5-methyluridine；3'-azido-3'-deoxythymidine；azidothymidine；zidovudine；1-[(2R,3R,4S,5S)-4-azido-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 215176-58-2
• 化学式: C₁₀H₁₃N₅O₅
• 分子量: 283.244
• InChiKey: DVRKESVZZVYJRB-JXOAFFINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  7

制备方法与用途

3'-叠氮基-3'-脱氧-5-甲基尿苷是一种嘌呤核苷类似物，具有广泛的抗肿瘤活性，尤其针对惰性淋巴系统恶性肿瘤。其抗癌机制主要通过抑制DNA合成和诱导细胞凋亡来实现。

反应信息

• 作为反应物：
  描述：

  3'-叠氮基-3'-脱氧-5-甲基尿苷 在 吡啶 、 4-二甲氨基吡啶 、 sodium hydroxide 、 三氟甲烷磺酰氯 、 溶剂黄146 、 4,4'-二氨基二苯乙烯-2,2'-二磺酸 作用下， 以 吡啶 、 乙醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 68.42h， 生成 1-(3-azido-2,3-dideoxy-2-fluoro-β-D-ribofuranosyl)thymine
  参考文献：
  名称：

  结核分枝杆菌胸苷单磷酸激酶抑制剂：2'-和3'-修饰胸苷类似物的生物学评价和构象分析

  摘要：

  结核分枝杆菌胸苷单磷酸激酶 (TMPKmt) 最近被引入作为抗结核药物基于结构设计的潜在目标。基于 TMPKmt X 射线结构和先前的 SAR 研究，我们合成了核苷类似物 3a-b、6a-b、7a-b 和 8a-b，在呋喃核糖环部分的 2'-和 3'-位置进行了修饰. 令我们惊讶的是，这些类似物仅表现出中等的结合亲和力（即 Ki 介于 118 和 1260 μM 之间）。这促使我们研究这些核苷的构象特征。我们得出结论，该系列的化合物，尤其是 8a-b，强烈偏向于“北方”呋喃糖环构象，而 X 射线晶体学显示 TMPKmt 偏爱相反的“南方”构象异构体。本文涵盖了合成，2'-和3'-修饰的dT类似物的生物学评价和构象特征（即优选的环褶皱）。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

  DOI：

  10.1002/ejoc.200300177
• 作为产物：
  描述：

  3-azido-5-O-benzoyl-3-deoxy-1,2-O-isopropylidene-α-D-ribofuranose 在 N,O-双三甲硅基乙酰胺 、 三氟甲磺酸三甲基硅酯 、 硫酸 、 potassium carbonate 、 溶剂黄146 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 19.0h， 生成 3'-叠氮基-3'-脱氧-5-甲基尿苷
  参考文献：
  名称：

  Chemoenzymatic Synthesis of 3′-Deoxy-3′-(4-Substituted-Triazol-1-YL)-5-Methyluridine

  摘要：

  An efficient protocol has been developed for the synthesis of a small library of 3-deoxy-3-(4-substituted-triazol-1-yl)-5-methyluridine using Cu(I)-catalyzed Huisgen-Sharpless-Meldal 1,3-dipolar cycloaddition reaction of 3-azido-3-deoxy-5-methyluridine with different alkynes under optimized condition in an overall yields of 76%-92%. Here, the azido precursor compound, i.e., 3-azido-3-deoxy-5-methyluridine was chemoenzymatically synthesized from D-xylose in good yield. Some of the alkynes used in cycloaddition reaction were synthesized by the reaction of hydroxycoumarins or naphthols with propargyl bromide in acetone using K(2)CO(3)in excellent yields. All synthesized compounds were unambiguously identified on the basis of their spectral (IR, H-1-, C-13 NMR spectra, and high-resolution mass spectra) data analysis.

  DOI：

  10.1080/15257770.2013.847957

文献信息

• Synthesis and Anti-HIV Activity of <i>β</i>-D-3′-Azido-2′,3′-unsaturated Nucleosides and <i>β</i>-D-3′-Azido-3′-deoxyribofuranosylnucleosides
  作者：Srinivas Gadthula、Chung K. Chu、Raymond F. Schinazi

  DOI：10.1080/15257770500267170

  日期：2005.9.1

  discovery of 3′-azido-3′-deoxythymidine (AZT) and 2′,3′-didehydro-2′,3′-dideoxythymidine (d4T) as potent and selective inhibitors of the replication of human immunodeficiency virus (HIV), there has been a growing interest for the synthesis of 2′,3′-didehydro-2′,3′-dideoxynucleosides with electron withdrawing groups on the sugar moiety. Here we described an efficient method for the synthesis of such nucleoside

  自从发现 3'-azido-3'-deoxythymidine (AZT) 和 2',3'-didehydro-2',3'-dideoxythymidine (d4T) 作为人类免疫缺陷病毒 (HIV) 复制的有效和选择性抑制剂以来，人们对合成在糖部分具有吸电子基团的 2',3'-didehydro-2',3'-dideoxynucleoside 越来越感兴趣。在这里，我们描述了一种合成具有 AZT 和 d4T 结构特征的核苷类似物的有效方法。关键中间体 3-azido-1,2-bis-O-acetyl-5-O-benzoyl-3-deoxy-D-ribofuranose, 5 由市售的 D-木糖分五步合成，其中一系列嘧啶和嘌呤核苷以高产率合成。使用适当的化学修饰将所得的受保护核苷转化为目标核苷。
• Biolabile constructs for pronucleotide design
  作者：Anne Jochum、Nathalie Schlienger、David Egron、Suzanne Peyrottes、Christian Périgaud

  DOI：10.1016/j.jorganchem.2004.11.015

  日期：2005.5

  After summarising the in vitro and in vivo results obtained with nucleotide prodrugs (pronucleotides) bearing two S-acyl-2-thioethyl (SATE) groups as esterase-labile phosphate protections, we will describe recent work on mononucleoside mixed phosphoester derivatives. These new series of biolabile constructs were designed to lead to the selective intracellular delivery of the corresponding 5'-mononucleotide through different enzyme-mediated activation steps. (c) 2004 Elsevier B.V. All rights reserved.
• Synthesis and evaluation of thymidine-5′-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase
  作者：Veerle Vanheusden、Hélène Munier-Lehmann、Sylvie Pochet、Piet Herdewijn、Serge Van Calenbergh

  DOI：10.1016/s0960-894x(02)00551-6

  日期：2002.10

  A number of 2'- and 3'-modified thymidine 5'-O-monophosphate analogues were synthesized as potential leads for new anti-mycobacterial drugs. Evaluation of their affinity for Mycobacterium tuberculosis thymidine monophosphate kinase showed that a 2'-halogeno substituent and a 3'-azido function are the most favorable leads for further development of potent inhibitors of this enzyme. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Chemoenzymatic Synthesis of 3′-Deoxy-3′-(4-Substituted-Triazol-1-YL)-5-Methyluridine
  作者：Anu Arya、Divya Mathur、Abhilash Tyagi、Rajesh Kumar、Vinod Kumar、Carl E. Olsen、Rajendra K. Saxena、Ashok K. Prasad

  DOI：10.1080/15257770.2013.847957

  日期：2013.12.2

  An efficient protocol has been developed for the synthesis of a small library of 3-deoxy-3-(4-substituted-triazol-1-yl)-5-methyluridine using Cu(I)-catalyzed Huisgen-Sharpless-Meldal 1,3-dipolar cycloaddition reaction of 3-azido-3-deoxy-5-methyluridine with different alkynes under optimized condition in an overall yields of 76%-92%. Here, the azido precursor compound, i.e., 3-azido-3-deoxy-5-methyluridine was chemoenzymatically synthesized from D-xylose in good yield. Some of the alkynes used in cycloaddition reaction were synthesized by the reaction of hydroxycoumarins or naphthols with propargyl bromide in acetone using K(2)CO(3)in excellent yields. All synthesized compounds were unambiguously identified on the basis of their spectral (IR, H-1-, C-13 NMR spectra, and high-resolution mass spectra) data analysis.
• Mycobacterium tuberculosis Thymidine Monophosphate Kinase Inhibitors: Biological Evaluation and Conformational Analysis of 2′- and 3′-Modified Thymidine Analogues
  作者：Philippe Van Rompaey、Koen Nauwelaerts、Veerle Vanheusden、Jef Rozenski、Hélène Munier-Lehmann、Piet Herdewijn、Serge Van Calenbergh

  DOI：10.1002/ejoc.200300177

  日期：2003.8

  Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt) has recently been introduced as a potential target for the structure-based design of anti-tuberculosis drugs. Based on the TMPKmt X-ray structure and previous S.A.R. studies, we synthesised the nucleoside analogues 3a−b, 6a−b, 7a−b, and 8a−b, modified in 2′- and 3′-position of the ribofuranose ring moiety. To our surprise, these analogues

  结核分枝杆菌胸苷单磷酸激酶 (TMPKmt) 最近被引入作为抗结核药物基于结构设计的潜在目标。基于 TMPKmt X 射线结构和先前的 SAR 研究，我们合成了核苷类似物 3a-b、6a-b、7a-b 和 8a-b，在呋喃核糖环部分的 2'-和 3'-位置进行了修饰. 令我们惊讶的是，这些类似物仅表现出中等的结合亲和力（即 Ki 介于 118 和 1260 μM 之间）。这促使我们研究这些核苷的构象特征。我们得出结论，该系列的化合物，尤其是 8a-b，强烈偏向于“北方”呋喃糖环构象，而 X 射线晶体学显示 TMPKmt 偏爱相反的“南方”构象异构体。本文涵盖了合成，2'-和3'-修饰的dT类似物的生物学评价和构象特征（即优选的环褶皱）。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)