3′-azido-3′-deoxy-2′-O,4′-C-methylene-5-methyluridine | 247025-17-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3′-azido-3′-deoxy-2′-O,4′-C-methylene-5-methyluridine
• 英文别名: 1-(3'-azido-3'-deoxy-2'-O,4'-C-methylene-β-D-ribofuranosyl)thymine；1-(3-Azido-3-deoxy-2-O,4-C-methylene-β-D-ribrofuranosyl)thymine；1-(3-azido-2-O,4-C-methylene-β-D-ribofuranosyl)thymine；3'-azido-3'-deoxy-2'-O,4'-C-methylene-5-methyluridine；3'-azido-3'-deoxy-2'-O,4'-C-methylenethymidine'；3'-azido-3'-deoxy-2'-O,4'-C-methylenethymidine；1-[(1R,4S,6R,7S)-7-azido-4-(hydroxymethyl)-2,5-dioxabicyclo[2.2.1]heptan-6-yl]-5-methyl-pyrimidine-2,4-dione；1-[(1S,3R,4R,7S)-7-azido-1-(hydroxymethyl)-2,5-dioxabicyclo[2.2.1]heptan-3-yl]-5-methylpyrimidine-2,4-dione
• CAS: 247025-17-8
• 化学式: C₁₁H₁₃N₅O₅
• 分子量: 295.255
• InChiKey: AOWRUWIBZOODMX-SZVQBCOZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3′-azido-3′-deoxy-2′-O,4′-C-methylene-5-methyluridine 在 吡啶 、 4-二甲氨基吡啶 、 三苯基膦 作用下， 生成 3'-amino-3'-deoxy-5'-O-DMT-2'-O-4'-C-methylenethymidine
  参考文献：
  名称：

  3′-Amino-2′,4′-BNA: novel bridged nucleic acids having an N3′→P5′ phosphoramidate linkage

  摘要：

  我们成功合成了含有 3â²-氨基-2â²,4â²-BNA 单元的新型寡核苷酸类似物，这些类似物与 BNA 本身一样，具有卓越的双链和三链形成能力，并且具有显著的酶稳定性。

  DOI：

  10.1039/b105640a
• 作为产物：
  描述：

  O,O-二(三甲基甲硅烷基)胸苷 在 四丁基氟化铵 、 四氯化锡 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 1,2-二氯乙烷 为溶剂， 生成 3′-azido-3′-deoxy-2′-O,4′-C-methylene-5-methyluridine
  参考文献：
  名称：

  构象锁定的AZT类似物3'-叠氮基-3'-脱氧-2'- O，4' - C-亚甲基-5-甲基尿苷的合成

  摘要：

  具有锁定N构象的双环3'-叠氮基3'-脱氧胸苷（AZT）类似物3'-叠氮基3'-脱氧-2'- O，4' - C-亚甲基-5-甲基尿苷（1a）由D-葡萄糖成功合成了其3'-氨基衍生物3'-氨基-3'-脱氧-2'- O，4' - C-亚甲基-5-甲基尿苷（1b）。还通过1 H NMR测量和分子模型（PM3）研究讨论了1a的构象。

  DOI：

  10.1016/s0040-4039(99)01324-6

文献信息

• Synthesis and antiviral evaluation of novel conformationally locked nucleosides and masked 5′-phosphate derivatives thereof
  作者：Torsten Bryld、Marianne H. Sørensen、Poul Nielsen、Troels Koch、Claus Nielsen、Jesper Wengel

  DOI：10.1039/b203484k

  日期：2002.7.11

  As part of a programme towards evaluating the potential of conformationally locked 3′-deoxy- and 3′-azido-3′-deoxy-nucleoside derivatives as prodrugs of potential 5′-O-triphosphorylated anti-HIV drugs, novel nucleoside derivatives with locked N-type (north-type, C3′-endo) furanose conformation were prepared using convergent synthetic strategies. In addition, masked 5′-monophosphate derivatives of these, and of a conformationally restricted 3′-azido-3′-deoxynucleoside with E-type (eastern-type, O4′-endo) furanose conformation, were prepared in order to potentially circumvent the first phosphorylation step. However, neither the free 5′-hydroxy derivatives nor the masked 5′-monophosphates showed anti-HIV activity in MT-4 cells.

  作为评估构象锁定的3′-脱氧和3′-叠氮-3′-脱氧核苷衍生物作为潜在5′-O-三磷酸化抗HIV药物的前药的程序的一部分，采用汇聚合成策略制备了具有锁定的N型（北型，C3′-内环）呋喃糖构象的新型核苷衍生物。此外，为了可能绕过第一步磷酸化反应，还合成了这些衍生物的掩蔽5′-单磷酸衍生物，以及具有E型（东型，O4′-内环）呋喃糖构象的构象受限的3′-叠氮-3′-脱氧核苷的掩蔽5′-单磷酸衍生物。然而，无论是游离的5′-羟基衍生物还是掩蔽的5′-单磷酸化合物在MT-4细胞中均未显示出抗HIV活性。
• Synthesis and Photophysical Studies on N1-(2′-O,4′-C-Methyleneribofurano-nucleoside-3′-yl)-C4-(coumarin-7-oxymethyl)-1,2,3-triazoles
  作者：Smriti Srivastava、Vipin K. Maikhuri、Rajesh Kumar、Kapil Bohra、Harbansh Singla、Jyotirmoy Maity、Ashok K. Prasad

  DOI：10.1016/j.carres.2018.09.007

  日期：2018.12

  A series of eight N1-(2'-O,4'-C-methylene-β-D-ribofuranonucleoside-3'-yl)-C4-(coumarin-7-oxymethyl)-1,2,3-triazoles have been synthesized by Cu(I)-catalyzed azide-alkyne cycloaddition reaction of 3'-azido-3'-deoxy-2'-O,4'-C-methyleneuridine and 3'-azido-3'-deoxy-2'-O,4'-C-methylene-5-methyluridine with 7-propargyloxy coumarins in 82-88% yields. The synthesized coumarintriazolyl-bicyclonucleoside conjugates

  一系列的八个N1-（2'-O，4'-C-亚甲基-β-D-呋喃核糖核苷-3'-基）-C4-（香豆素-7-氧甲基）-1,2,3-三唑由Cu（I）催化的3'-叠氮基-3'-脱氧-2'-O，4'-C-亚甲基尿苷和3'-叠氮基-3'-脱氧-2'-O的叠氮化物-炔烃环加成反应合成带有7-炔丙氧基香豆素的4，-C-亚甲基-5-甲基尿苷，产率为82-88％。合成的香豆素三唑基-双环核苷共轭物在核苷部分的2'-O和4'-C之间具有一个额外的桥，这有利于其预组织为N型糖折叠。通过对一种共轭物，即在N1-（3'-脱氧-2'-O，4'-C-亚甲基-5-甲基尿素-3'-基）-C4-上的X射线晶体结构研究证实了这一点。 （4-苯基香豆素-7-氧甲基）-1，2，3-三唑。
• Chemo-enzymatic synthesis of bicyclic 3′-azido- and 3′-amino-nucleosides
  作者：Manish Kumar、Vivek K. Sharma、Carl E. Olsen、Ashok K. Prasad

  DOI：10.1039/c4ra06805j

  日期：——

  Conformationally locked 3′-azido-3′-deoxythymidine analogues of T, U, A and C containing a 2′-O,4′-C-methylene linked bicyclic furanose moiety has been efficiently synthesized following a greener chemo-enzymatic convergent route. Thus, one of the two diastereotopic hydroxyl groups of 3-azido-3-deoxy-4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-ribofuranose has been regioselectively acetylated using Novozyme®-435 in quantitative yield. The selective enzymatic acetylation can be carried out with the same efficiency using Novozyme®-435 for 10 cycles of reaction. The monoacetylated sugar derivative was converted to bicyclic 3′-azidonucleosides in four steps in overall yields of 60 to 68%. It has been demonstrated that 3′-azido-3′-deoxy-2′-O,4′-C-methylenethymidine can easily be converted into 3′-amino-3′-deoxy-2′-O,4′-C-methylenethymidine in 95% yield, which is an important monomer for the synthesis of therapeutically useful sugar-modified oligonucleotides.

  顺式锁定的3′-叠氮-3′-脱氧胸苷类似物，含有2′-O, 4′-C-亚甲基连结的双环呋喃糖部分，已通过一种更绿色的化学-酶促收敛路线高效合成。因此，3-叠氮-3-脱氧-4-C-羟甲基-1,2-O-异丙基腈-α-D-核糖的两个非对映体羟基中的一个已使用Novozyme®-435进行区域选择性乙酰化，量产率达到定量。选择性的酶促乙酰化在10次反应循环中使用Novozyme®-435也能以相同的效率进行。单乙酰化的糖衍生物在四个步骤中转化为双环3′-叠氮核苷，整体产率为60%到68%。已证明3′-叠氮-3′-脱氧-2′-O, 4′-C-亚甲基胸苷可以轻松转化为3′-氨基-3′-脱氧-2′-O, 4′-C-亚甲基胸苷，产率为95%，这是一种合成具有治疗用途的糖修饰寡核苷酸的重要单体。
• Synthesis and evaluation of anti-HIV-1 activity of 3′-azido-3′-deoxy-2′-O,4′-C-methylene-linked bicyclic thymine nucleosides
  作者：Anne G. Olsen、Vivek K. Rajwanshi、Claus Nielsen、Jesper Wengel

  DOI：10.1039/b005469k

  日期：——

  4′-C-methylene-linked bicyclic furanose moiety, are synthesized via the 3′-azido-3′-deoxy-4′-C-hydroxymethyl nucleoside 16. The β-D-ribo-configured derivative 4 is shown by NOE experiments to exist in a north-type (3E, C3′-endo) conformation and the α-L-xylo-configured derivative 5 in a south-type (3E, C3′-exo) conformation. Both nucleosides were devoid of anti-HIV activity in MT-4 cells.

  通过3'-叠氮基-3'-脱氧-4'- C-羟甲基合成两个构象锁定的AZT类似物4和5，每个类似物均含有2'- O，4' - C-亚甲基连接的双环呋喃糖部分。核苷16。所述β- d -核糖-构型衍生物4由NOE实验示于北-型存在（3 é，C3'-内）构象，并且α-大号-木糖-构型衍生物5在南型（3 E，C3'-外切）的构象。两个都核苷 在MT-4细胞中没有抗HIV活性。
• 3′-Amino-2′,4′-BNA: novel bridged nucleic acids having an N3′→P5′ phosphoramidate linkage
  作者：Satoshi Obika、Mayumi Onoda、Jun-ichi Andoh、Takeshi Imanishi、Koji Morita、Makoto Koizumi

  DOI：10.1039/b105640a

  日期：——

  Novel oligonucleotide analogues, containing a 3′-amino-2′,4′-BNA unit, were successfully synthesized, and they showed superior duplex and triplex forming ability as well as BNA itself, along with remarkable enzymatic stability.

  我们成功合成了含有 3â²-氨基-2â²,4â²-BNA 单元的新型寡核苷酸类似物，这些类似物与 BNA 本身一样，具有卓越的双链和三链形成能力，并且具有显著的酶稳定性。