1-[3-O-(tert-butyldimethylsilyl)-2,5-dideoxy-β-L-glycero-pent-4-enofuranosyl]thymine | 135911-57-8

• 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: 1-[3-O-(tert-butyldimethylsilyl)-2,5-dideoxy-β-L-glycero-pent-4-enofuranosyl]thymine
• 英文别名: 1-(3-O-tert-butyldimethylsilyl-2,5-dideoxy-β-L-glycero-pent-4-enofuranosyl)thymine；1-[3-O-(t-butyldimethylsilyl)-2,5-dideoxy-β-L-glycero-pent-4-enofuranosyl]thymine；1-[(2R,4R)-4-[tert-butyl(dimethyl)silyl]oxy-5-methylideneoxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 135911-57-8
• 化学式: C₁₆H₂₆N₂O₄Si
• 分子量: 338.479
• InChiKey: ZIESHTXGCMQNHU-CHWSQXEVSA-N

物化性质

• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.67
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[3-O-(tert-butyldimethylsilyl)-2,5-dideoxy-β-L-glycero-pent-4-enofuranosyl]thymine 在 吡啶 、 1,5-二氮杂双环[4.3.0]壬-5-烯 、 四丁基氟化铵 、 二甲基二环氧乙烷 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 、 乙腈 为溶剂， 反应 68.5h， 生成 festinavir
  参考文献：
  名称：

  Anti-viral nucleoside analogs and methods for treating viral infections, especially HIV infections

  摘要：

  本发明涉及根据一般式I、II、III、IV或V的新化合物： 其中B是根据以下结构的核苷酸碱基： 以及规范中定义的其余变量，以及包含这些化合物的药物组合物。这些化合物可用作抗病毒剂，用于病毒治疗。

  公开号：

  US09126971B2
• 作为产物：
  描述：

  3',4'-anhydrothymidine 在 咪唑 、 敌草腈 、 氨 、 sodium iodide 作用下， 以 吡啶 、 甲醇 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 50.5h， 生成 1-[3-O-(tert-butyldimethylsilyl)-2,5-dideoxy-β-L-glycero-pent-4-enofuranosyl]thymine
  参考文献：
  名称：

  Nucleophilic Substitution at the 4‘-Position of Nucleosides: New Access to a Promising Anti-HIV Agent 2‘,3‘-Didehydro-3‘-deoxy-4‘-ethynylthymidine

  摘要：

  For the synthesis of 2',3'-didehydro-3'-deoxy-4'-ethynylthymidine (8: 4'-Ed4T), a recently reported promising anti-HIV agent, a new approach was developed. Since treatment of 1-(2,5-dideoxy-beta-L-glyceropent4- enofuranosyl) thymine with Pb(OBz) 4 allowed the introduction of the 4'-benzoyloxy leaving group, nucleophilic substitution at the 4'-position became feasible for the first time. Thus, reaction between the 4'-benzoyloxy derivative (14) and Me3SiC CAl(Et) Cl as a nucleophile led to the isolation of the desired 4'-"down"-ethynyl derivative (18) stereoselectively in 62% yield. As an application of this approach, other 4'-substituted nucleosides, such as the 4'-allyl (24a) and 4'-cyano (26a) derivatives, were synthesized using organosilicon reagents. In these instances, pretreatment of 14 with MeAlCl2 was necessary.

  DOI：

  10.1021/jo060194m

文献信息

• Electrophile-promoted addition of hydroxymethylphosphonate to 4′,5′-didehydronucleosides: a way to novel isosteric analogues of 5′-nucleotides
  作者：Zdeněk Točík、Ivana Dvořáková、Radek Liboska、Miloš Buděšínský、Milena Masojídková、Ivan Rosenberg

  DOI：10.1016/j.tet.2007.03.059

  日期：2007.5

  addition of dialkyl-hydroxymethylphosphonate to the protected 4′,5′-didehydronucleosides resulted in an epimeric mixture of 4′-dialkylphosphonomethoxy derivatives of 2′,5′-dideoxynucleosides, novel analogues of 2′-deoxynucleoside 5′-monophosphates. Several types of electrophiles (pyridinium tosylate, NIS, NBS, MCPBA and others) were evaluated in addition reactions with 4′,5′-didehydrothymidine. Out

  亲电子促进的将二烷基羟甲基膦酸酯加到受保护的4'，5'-didehydronucleosides上，生成2'，5'-dideoxynucleosides的4'-di烷基膦酰基甲氧基衍生物的差向异构体混合物，这是2'-deoxynucleoside 5'-monophosphates的新类似物。在与4'，5'-二氢胸苷的加成反应中评估了几种类型的亲电试剂（甲苯磺酸吡啶鎓，NIS，NBS，MCPBA等）。从中发现，甲苯磺酸吡啶鎓在这些转化中具有实际用途。它的使用导致了一系列常见2'-脱氧核苷的4'-膦酰基甲氧基衍生物的制备。在生物学筛选中，这些游离膦酸没有发挥明显的细胞抑制或抗病毒活性。
• Selenoxide elimination for the synthesis of unsaturated-sugar uracil nucleosides
  作者：Kazuhiro Haraguchi、Hiromichi Tanaka、Hideaki Maeda、Yoshiharu Itoh、Shigeru Saito、Tadashi Miyasaka

  DOI：10.1021/jo00018a038

  日期：1991.8

  Introduction of a phenylseleno group to the sugar portion of uracil nucleosides and selenoxide elimination reactions of the resulting selenium-containing derivatives are described. A phenylselenide anion prepared by reducing (PhSe)2 with LialH4 was found to be highly reactive. By using this selenide as a nucleophile, ring openings of various types of cyclonucleosides and nucleosides having an anhydro structure in the sugar portion were accomplished. The products, which contain a phenylseleno group in the sugar portion, were oxidized with m-CPBA in CH2Cl2, and their susceptibility to the selenoxide elimination and regiochemistry of the reaction was investigated.
• An Alternative Synthetic Method for 4′-C-Ethynylstavudine by Means of Nucleophilic Substitution of 4′-Benzoyloxythymine Nucleoside
  作者：Kazuhiro Haraguchi、Masanori Sumino、Hiromichi Tanaka

  DOI：10.1080/15257770701503969

  日期：2007.11.26

  For the synthesis of 2,3'-didehydro-3'-deoxy-4'-C-ethynylthymidine (8: 4'-Ed4T), a recently reported promising anti-HIV agent, a new approach was developed. Since treatment of 1-(2,5-dideoxy-beta-L-glycero-pent-4-enofuranosyl)thymine with Pb(OBz)(4) allowed the introduction of a 4'-benzoyloxy leaving group, nucleophilic substitution at the 4'-position became feasible, for the first time. Thus, reaction between the 4'-benzoyloxy derivative (H) and Me3SiC CAl(Et)Cl as a nucleophile led to the isolation of the desired 4'-"down"-ethynyl derivative (15) stereoselectively in 62 % yield.
• 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.
• Anti-viral nucleoside analogs and methods for treating viral infections, especially HIV infections
  申请人：Cheng Yung-chi

  公开号：US09126971B2

  公开（公告）日：2015-09-08

  The present invention relates to novel compounds according to the general formulas I, II, III, IV or V: wherein B is nucleoside base according to the structure: and the remaining variables as defined in the specification, and pharmaceutical compositions comprising the compounds. The compounds are useful interalia as anti-viral agents in viral therapy.

  本发明涉及根据一般式I、II、III、IV或V的新化合物： 其中B是根据以下结构的核苷酸碱基： 以及规范中定义的其余变量，以及包含这些化合物的药物组合物。这些化合物可用作抗病毒剂，用于病毒治疗。