alpha-3'-azido-2',3'-dideoxythymidine | 66323-40-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: alpha-3'-azido-2',3'-dideoxythymidine
• 英文别名: 1-((2S,4S,5S)-4-azido-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione；1-(3-Azido-2,3-dideoxy-α-D-erythro-pentofuranosyl)-thymine；1(3-azido-2,3-dideoxy-α-D-erythro-pentofuranosyl)-thymine；1-(3-azido-2,3-deoxy-α-D-erythro-pentofuranosyl)thymine；3'α-azido-3'-desoxy-α-thymidine；3'-azido-2',3'-dideoxy-α-thymidine；1-[(2S,4S,5S)-4-azido-5-(hydroxymethyl)tetrahydrofuran-2-yl]-5-methyl-pyrimidine-2,4-dione；1-[(2S,4S,5S)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 66323-40-8
• 化学式: C₁₀H₁₃N₅O₄
• 分子量: 267.244
• InChiKey: HBOMLICNUCNMMY-RNJXMRFFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  19
• 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：
  93.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  alpha-3'-azido-2',3'-dideoxythymidine 在 水合三氯化钌 、 potassium persulfate 、 potassium hydroxide 作用下， 反应 5.0h， 以42%的产率得到(2S,3S,5S)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolane-2-carboxylic acid
  参考文献：
  名称：

  A new class of pyrimidine nucleosides: inhibitors of hepatitis B and C viruses

  摘要：

  Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are major health threats worldwide leading to liver cirrhosis, liver cancer and mortality. Herein, we report a new category of dideoxy pyrimidine nucleosides possessing a 4'-carboxyl (or carboxymethyl) function (7-9, 13, 16, 17), which are discovered as potential antiviral agents. For the first time, these nucleosides are recognized to be inhibitors of HBV and/or HCV replication. Among 4'-carboxy compounds, 3',4'-didehydrothymidine (16) was most effective against DHBV, HBV and HCV. Modification of the 4'-position in compound 7 from a carboxyl to carboxymethyl group (17) did not affect the anti-HBV activity but greatly increased the anti-HCV activity. Importantly, 17 yielded synergistic antiviral effect when combined with ribavirin without toxicity. The activity exhibited by a single agent towards both hepatitis viruses and no detectable in vitro cytotoxicity make this new class of compounds of interest. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.042
• 作为产物：
  描述：

  1-O-acetyl-3-azido-2,3-dideoxy-5-O-(tert-butyldimethylsilyl)-α,β-D-erythro-pentofuranose 在 四丁基氟化铵 、 四氯化锡 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 18.5h， 生成 alpha-3'-azido-2',3'-dideoxythymidine
  参考文献：
  名称：

  立体选择性合成3-azido-2,3-dideoxy-D-ribose衍生物及其在合成抗HIV核苷中的用途† ‡

  摘要：

  描述了使用3-叠氮基-2,3-二脱氧-D-核糖衍生物7作为关键中间体合成3'-叠氮基核苷的详细说明。从D-甘露糖醇以制备规模分8步合成关键中间体7。叠氮化物基团与α，β-不饱和-γ-丁内酯4的迈克尔反应受5-O位置取代基的空间体积的影响。在5-O处大体积的叔丁基二苯基甲硅烷基取代几乎仅产生α-叠氮基加合物5b，而在5-O处的不取代产生α-和β-加合物的1：1混合物。叠氮乙酸酯7a缩合反应中α与β异构体的比例所用溶剂和路易斯酸催化剂对制备AZT和AZDU的嘧啶碱有很大影响。在12（AZDU，CS-87）的合成中，二氯乙烷和三氟甲磺酸三甲基硅烷基酯的组合产生了最佳结果，而在14（AZT）的情况下，各种条件产生的α，β端基异构体比率相似。叠氮基中间体7b也用于合成3'-叠氮基嘌呤样核苷16-27。糖基化也受到路易斯酸催化剂的影响。三氟化硼醚化物可制得所需的N 1-糖基化化合物，其中α-端基异构体

  DOI：

  10.1002/jhet.5570300543

文献信息

• A Simple and Efficient Synthesis of 3′-Azido-3′-deoxythymidine (AZT) Employing a Convergent Route
  作者：Bhaskar Dhotare、Angshuman Chattopadhyay

  DOI：10.1055/s-2001-15234

  日期：——

  The syn-homoallyl alcohol 2a has been prepared with absolute stereoselectivity following PDC oxidation of the mixture of diastereomers 2a, 2b and subsequent K-selectride® reduction of the resulting ketone 3. Compound 2a has been efficiently utilized for a simple synthesis of AZT I in a convergent manner.

  立体选择性绝对的合成顺式同烯丙醇 2a，是通过对二对映体混合物 2a 和 2b 进行 PDC 氧化，然后对得到的酮 3 进行 K-selectride® 还原制备的。化合物 2a 被高效地用于以收敛方式进行 AZT I 的简单合成。
• Chemoselective Sequential Click Ligations Directed by Enhanced Reactivity of an Aromatic Ynamine
  作者：Marine Z. C. Hatit、Joanna C. Sadler、Liam A. McLean、Benjamin C. Whitehurst、Ciaran P. Seath、Luke D. Humphreys、Robert J. Young、Allan J. B. Watson、Glenn A. Burley

  DOI：10.1021/acs.orglett.6b00635

  日期：2016.4.1

  Aromatic ynamines or N-alkynylheteroarenes are highly reactive alkyne components in Cu-catalyzed Huisgen [3 + 2] cycloaddition (“click”) reactions. This enhanced reactivity enables the chemoselective formation of 1,4-triazoles using the representative aromatic ynamine N-ethynylbenzimidazole in the presence of a competing aliphatic alkyne substrate. The unique chemoselectivity profile of N-ethynylbenzimidazole

  在Cu催化的Huisgen [3 + 2]环加成（“点击”）反应中，芳族胺或N-炔基杂芳烃是高反应性炔烃组分。在竞争性脂族炔烃底物的存在下，这种增强的反应性使得能够使用代表性的芳族芳胺N-乙炔基苯并咪唑来化学选择性地形成1,4-三唑。N-乙炔基苯并咪唑的独特化学选择性特征通过使用杂双功能二炔的一系列高度官能化的叠氮化物的顺序点击连接得到了进一步证明，从而消除了对炔烃保护基的需求。
• Methyl 5-0--butyldiphenylsilyl-2-deoxy-α β -d--pentofuranoside as a divergent intermediate for the synthesis of 3'-substituted-2',3'-dideoxynucleosides: synthesis of 3'-azido-3'-deoxythymidine, 3'-deoxy-3'-fluorothymidine and 3'-cyano-3'-deoxythymidine.
  作者：George W.J. Fleet、Jong Chan Son、Andrew E. Derome

  DOI：10.1016/s0040-4020(01)85850-6

  日期：1988.1

  The use of methyl 5-0--butyldiphenylsilyl-2-deoxy-α , β -D--pentofuranoside, prepared from D-xylose,as a divergent intermediate for the synthesis of 3'-substituted-2',3'-dideoxynucleosides is illustrated by its conversion into 3'-azido-3'-deoxythymidine, 3'-deoxy-3'-fluorothymidine and 3'-cyano-3'-deoxythymidine.

  由D-木糖制得的甲基5-0-丁基二苯基甲硅烷基-2-脱氧-α，β-D-五呋喃糖苷作为合成3'-取代的2'，3'-二脱氧核苷的发散中间体的用途通过将其转化为3'-叠氮基-3'-脱氧胸苷，3'-脱氧-3'-氟胸苷和3'-氰基-3'-脱氧胸苷来举例说明。
• An efficient total synthesis of 3′-azido-3′-deoxythymidine (AZT) and 3′-azido-2′,3′-dideoxyuridine (AZDDU, CS-87) from D-mannitol
  作者：Chung K Chu、J.Warren Beach、Giliyar V Ullas、Yoshiyuki Kosugi

  DOI：10.1016/s0040-4039(00)82864-6

  日期：——

  An efficient stereoselective total synthesis of 3′-azido-3′-deoxythymidine (AZT) and 3′-azido-2′,3′-dideoxyuridine (AZDDU, CS-87) from readily available and inexpensive starting material, -mannitol has been achieved.

  3'-叠氮基-3'-脱氧胸苷，从容易获得和廉价的原料高效的立体选择性全合成（AZT）和3'-叠氮基-2'，3'-二脱氧尿苷（AZDDU，CS-87），-mannitol一直实现。
• Selective Deformylation of an α,β-Unsaturated Sugar Aldehyde in a Very Short Synthesis of 3′-Azido-3′-deoxythymidine (AZT) and its Stereoisomers
  作者：Jesper Wengel、Erik B. Pedersen

  DOI：10.1055/s-1991-26490

  日期：——

  (2E,4S)-5-Acetoxy-4-formyloxy-2-pentenal (2) prepared in one step from tri-O-acetyl-D-glucal was selectively deformylated to give the α,β-unsaturated aldehyde 3 with an unprotected hydroxy group at C-4. Michael-type addition reaction of hydrazoic acid to 3 followed by acylation at C-1 gave a 1:1 mixture of the erythro- and threo-isomers of 5-O-acetyl-3-azido-1 -O-(4-biphenylcarbonyl)-2,3-dideoxypentofuranoses 4 and 5. They were used as substrates for nucleoside coupling with silylated thymine to give all four D-isomers of 3′-azido-3′-deoxythymidine 6-9.

  (由三-O-乙酰基-D-葡萄糖醛一步制备的 (2E,4S)-5-乙酰氧基-4-甲酰氧基-2-戊烯醛（2）经选择性脱醛得到 C-4 位未受保护羟基的δ,δ-不饱和醛 3。将苯甲酸与 3 进行迈克尔型加成反应，然后在 C-1 处进行酰化，得到了 5-O- 乙酰基-3-叠氮-1-O-(4-联苯羰基)-2,3-二脱氧戊呋喃糖 4 和 5 的 1:1 红外异构体和 3-异构体混合物。它们被用作核苷与硅烷化胸腺嘧啶偶联的底物，从而得到 3′-叠氮-3′-脱氧胸苷 6-9 的所有四种 D-异构体。