5'-O-acetyl-2',3'-didehydro-3'-deoxy-4'-C-methylthymidine | 160766-57-4

• 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: 5'-O-acetyl-2',3'-didehydro-3'-deoxy-4'-C-methylthymidine
• CAS: 160766-57-4
• 化学式: C₁₃H₁₆N₂O₅
• 分子量: 280.28
• InChiKey: UGLMAZNEGRYZGW-MFKMUULPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.25
• 重原子数：
  20.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  90.39
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  5'-O-acetyl-2',3'-didehydro-3'-deoxy-4'-C-methylthymidine 在 氨 作用下， 以 甲醇 为溶剂， 以98%的产率得到4′-methyl-d4T
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 4′-C-Methyl Nucleosides

  摘要：

  A series of 2'-deoxy, 2',3'-unsaturated and 2',3'-dideoxynucleoside analogues, which have an additional methyl group at the 4'-position, have been synthesized. When evaluated for their inhibitory activity against HIV in MT-4 cell, 2'-deoxy-4'-C-methyl nucleosides exhibited potent activity.

  DOI：

  10.1080/07328319608002385
• 作为产物：
  描述：

  Acetic acid (2R,3R,4R,5R)-2-acetoxymethyl-4-bromo-2-methyl-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl ester 在 铜 、 锌 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以28%的产率得到5'-O-acetyl-2',3'-didehydro-3'-deoxy-4'-C-methylthymidine
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 4′-C-Methyl Nucleosides

  摘要：

  A series of 2'-deoxy, 2',3'-unsaturated and 2',3'-dideoxynucleoside analogues, which have an additional methyl group at the 4'-position, have been synthesized. When evaluated for their inhibitory activity against HIV in MT-4 cell, 2'-deoxy-4'-C-methyl nucleosides exhibited potent activity.

  DOI：

  10.1080/07328319608002385

文献信息

• A NEW APPROACH TO THE SYNTHESIS OF 4′-CARBON-SUBSTITUTED NUCLEOSIDES: DEVELOPMENT OF A HIGHLY ACTIVE ANTI-HIV AGENT 2′, 3′-DIDEHYDRO-3′-DEOXY-4′-ETHYNYLTHYMIDINE
  作者：Kazuhiro Haraguchi、Shingo Takeda、Masanori Sumino、Hiromichi Tanaka、Ginger E. Dutschman、Yung-Chi Cheng、Takao Nitanda、Masanori Baba

  DOI：10.1081/ncn-200059774

  日期：2005.4.1

  Oxidation of 3'-O-TBDMS-4',5'-unsaturated thymidine 3 with dimethyldioxirane (DMDO) allowed the isolation of the epoxide 4. Upon reacting with organosilicon reagents in the Presence of SnCl4, 4 underwent stereoselective ring opening to give 4'-alpha-allyl (6), 4'-alpha-(2-bromoallyl) (7), 4'-alpha(cyclopenten-3-yl) (8), and 4'-alpha-cyano (9) derivatives of thymidine. Reactions of the 3'-epimer 12 with organoaluminum reagents gave 4-alpha-methyl (13), 4'-alpha-vinyl (14), and 4'-alpha-ethynyl (15) analogues. Compounds 13-15 were transformed into corresponding 2',3'-didehydro-3'-deoxy derivatives. Evaluation of their ability to inhibit the replication of HIV in cell culture showed that 4'-ethynyl-d4T (19) is more potent and less toxic than the parent compound d4T.
• Synthesis of a highly active new anti-HIV agent 2′,3′-Didehydro-3′-deoxy-4′-ethynylthymidine
  作者：Kazuhiro Haraguchi、Shingo Takeda、Hiromichi Tanaka、Takao Nitanda、Masanori Baba、G.E. Dutschman、Yung-Chi Cheng

  DOI：10.1016/j.bmcl.2003.07.009

  日期：2003.11

  Compounds having methyl, vinyl, and ethynyl groups at the 4'-position of stavudine (d4T: 2',3'-didehydro-3'-deoxythymidine) were synthesized. The compounds were assayed for their ability to inhibit the replication of HIV in cell culture. The 4'-ethynyl analogue (15) was found to be more potent and less toxic than the parent compound stavudine. (C) 2003 Elsevier Ltd. All rights reserved.