5'-O-(t-butyldimethylsilyl)-2,3'-anhydro-1-(2'-deoxy-β-D-threo-pentofuranosyl)thymine | 117383-85-4

• 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-(t-butyldimethylsilyl)-2,3'-anhydro-1-(2'-deoxy-β-D-threo-pentofuranosyl)thymine
• 英文别名: 10-({[1-(tert-butyl)-1,1-dimethylsilyl]oxy}methyl)-4-methyl-8,11-dioxa-2,6-diazatricyclo[7.2.1.0^2,7]dodeca-3,6-dien-5-one；5'-O-TBS-O(2),3'-anhydrothymidine；(1R,9R,10R)-10-[[tert-butyl(dimethyl)silyl]oxymethyl]-4-methyl-8,11-dioxa-2,6-diazatricyclo[7.2.1.02,7]dodeca-3,6-dien-5-one
• CAS: 117383-85-4
• 化学式: C₁₆H₂₆N₂O₄Si
• 分子量: 338.479
• InChiKey: NASMFRKQSZNTBI-JHJVBQTASA-N

物化性质

• 熔点：
  174-175 °C
• 沸点：
  384.2±52.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.62
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  60.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5'-O-(t-butyldimethylsilyl)-2,3'-anhydro-1-(2'-deoxy-β-D-threo-pentofuranosyl)thymine 在 sodium azide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 以58%的产率得到3'-azido-3'-deoxy-5'-O-(t-butyldimethylsilyl)-thymidine
  参考文献：
  名称：

  Synthesis, antiretrovirus effects and phosphorylation kinetics of 3'-isocyano-3'-deoxythymidine and 3'-isocyano-2',3'-dideoxyuridine

  摘要：

  The silylated AzddThd 5 and AzddUrd 6 prepared from 2,3'-anhydronucleoside derivatives 3 and 4 were transformed to formamides 7 and 8 by using the sequence RN3----RN = P(C6H5)----RNHCHO. Formamides 7 and 8 were dehydrated to the protected 3'-isocyano derivatives 9 and 10; deblocking gave 11 and 12. Neither 3'-isocyano-3'-deoxythymidine (11) nor 3'-isocyano-2',3'-dideoxyuridine (12) showed anti-HIV activity at noncytotoxic concentrations. ddThd derivative 11 was considerably more toxic to MT-4 cells than ddUrd derivative 12; it also had a much greater affinity (Ki) for MT-4 cell dThd kinase than ddUrd derivative 12. Both compounds appear to be linear mixed-type inhibitors of MT-4 cell dThd kinase.

  DOI：

  10.1021/jm00164a059
• 作为产物：
  描述：

  beta-胸苷 在 咪唑 、 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 5'-O-(t-butyldimethylsilyl)-2,3'-anhydro-1-(2'-deoxy-β-D-threo-pentofuranosyl)thymine
  参考文献：
  名称：

  Design and Synthesis of α-Carboxy Phosphononucleosides

  摘要：

  Rhodium catalyzed O-H insertion reactions employing alpha-diazophosphonate 20 with appropriately protected thymidine, uridine, cytosine, adenosine and guanosine derivatives leads to novel 5'-phosphononucleoside derivatives. Deprotection led to a novel series of phosphono derivatives bearing a carboxylic acid moiety adjacent to the phosphonate group with potential antiviral and/or anticancer activity. The phosphononucleosides bearing an alpha-carboxylic acid group are envisaged as potential diphosphate mimics. Conversion to mono- and diphosphorylated phosphononucleosides has been effected for evaluation as nucleoside triphosphate mimics. Most of the novel phosphononucleosides proved to be inactive against a variety of DNA and RNA viruses. Only the phosphono AZT derivatives 56-59 showed weak activity against HIV-1 and HIV-2.

  DOI：

  10.1021/jo101738e

文献信息

• Synthesis, structure, and biological evaluation of C-2 sulfonamido pyrimidine nucleosides
  作者：Irena Krizmanić、Aleksandar Višnjevac、Marija Luić、Ljubica Glavaš-Obrovac、Mladen Žinić、Biserka Žinić

  DOI：10.1016/s0040-4020(03)00589-1

  日期：2003.6

  The C-2 sulfonamido pyrimidine nucleosides were prepared by opening the 2,2′- or 2,3′-bond in anhydronucleosides under nucleophilic attack of sulfonamide anions. Reaction of the sodium salt of p-toluenesulfonamide or 2-(aminosulfonyl)-N,N-dimethylnicotinamide with 2,2′-anhydro-1-(β-d-arabinofuranosyl)cytosine gave the C-2 sulfonamido derivatives in excellent yields. Ring opening of the less reactive

  通过在磺酰胺阴离子的亲核攻击下在脱水核苷中打开2,2'-或2,3'-键来制备C-2磺酰胺基嘧啶核苷。对甲苯磺酰胺或2-（氨基磺酰基）-N，N-二甲基烟酰胺的钠盐与2，2'-脱水-1-（β-d-阿拉伯呋喃糖基）胞嘧啶的反应以优异的产率得到C-2磺酰胺基衍生物。较低反应性的2,2'-脱水尿苷和2,3'-脱水胸苷的开环可以通过对甲苯磺酰胺的DBU / CH 3 CN活化来完成，从而得到适量的C-2磺酰胺基衍生物。乙酸或ZnBr 2 / CH 2 Cl 2对5-甲基-N 2-甲苯磺酰基-1-（2-脱氧-5- O-三苯甲基-β-d-苏-戊呋喃糖基）异胞嘧啶导致保护基和核苷键均裂解，产生5-甲基-N 2-甲苯磺酰基异胞嘧啶作为主要产品。通过1D和2D NMR实验以及4-亚氨基-N 2-甲苯磺酰基氨基-1-（β-d-阿拉伯呋喃糖基）嘧啶的X射线结构分析证实了所制备的C-2磺酰胺基核苷的结构。两种方法均证
• 5′-<i>O</i>-TBDMS-3′-<i>O-</i>-(1<i>H</i>-Imidazole-1-Thiocarbonyl)thymidine: A Novel Intermediate for the Synthesis of 2,3′-Anhydrothymidine
  作者：Zaesung No、Shi Yong Ryu、Seong-Kie Kim、Jong Woong Ahn、Bok Ju Song、Keun Jae Kim

  DOI：10.1080/00032719808006488

  日期：1998.3.1

  Abstract Thermal or base-promoted conversion of 5′-O-TBDMS-3′-O-(1H-imidazole-1-thiocarbonyl)thymidine (1) afforded 5′-O-TBDMS-2,3′-anhydro-thymidine (2), a pivotal intermediate for the transformation of the 3′-hydroxy group of 2′-deoxyribonucleosides, in high yield.

  摘要 5'-O-TBDMS-3'-O-(1H-咪唑-1-硫代羰基)胸苷 (1) 的热或碱促进转化得到 5'-O-TBDMS-2,3'-脱水胸苷 ( 2)，高产率转化 2'-脱氧核糖核苷的 3'-羟基的关键中间体。
• Stereoselective Preparation of 1-[5-<i>O</i>-(<i>tert</i>-Butyldimethylsilyl)-2,3-dideoxy-3-iodo-β-<scp>D</scp>-<i>threo</i>-pentofuranosyl]thymine from Thymidine: An Efficient Entry to 3′,4′-Unsaturated Nucleoside
  作者：Yutaka Kubota、Kohji Nakamura、Kazuhiro Haraguchi、Hiromichi Tanaka

  DOI：10.1080/00397910903161751

  日期：2010.5.19

  The title compound (13) has been synthesized from 5′-O-TBS-thymidine (8) through a highly stereoselective iodination of the 3′-hydroxyl group utilizing I2/PPh3/imidazole. This method provides an efficient entry to the 3′,4′-unsaturated derivative (7).

  标题化合物 (13) 是由 5'-O-TBS-胸苷 (8) 通过使用 I2/PPh3/咪唑对 3'-羟基进行高度立体选择性碘化而合成的。该方法提供了对 3',4'-不饱和衍生物 (7) 的有效入口。
• A Facile One-Pot Synthesis of 2,3'-Anhydro-2'-Deoxyuridines via 3'-O-Imidazolylsulfonates
  作者：No、Dong Seong Shin、Bok Ju Song、Ahn、Ha

  DOI：10.1080/00397910008086944

  日期：2000.11

  Continued interests in the novel synthetic methods of the pivotal compound, 2,3'-anhydro-2'-deoxyribonucleosides (7) uncovered a facile one-pot conversion of 5 with 1,1'-sulfonyldiimidazole in basic conditions to 7 with almost quantitative yields (91-99%).
• New nucleoside heteroanalogues: Desoxynucleoside selenocyanates
  作者：Anatoly M. Belostotskii、Jael Lexner、Alfred Hassner

  DOI：10.1016/s0040-4039(98)02559-3

  日期：1999.2

  Naw nucleoside heteroanalogues, 5'- and 9'-desoxynucleoside selenocyanates and primary desoxysugar selenocyanates, were synthesized from activated nucleoside and sugar derivatives and a new convenient seleno nucleophile, tetrabutylammonium selenocyanate. Tresylate-based activation of hydroxy functions turned out to be most successful for formation of these selenocyanates compared with mesylate- or triflate-based activation. (C) 1999 Elsevier Science Ltd. All rights reserved.