3-C-allyl-1-[5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-β-D-erythro-pentofuranosyl]thymine | 146557-58-6

• 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: 3-C-allyl-1-[5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-β-D-erythro-pentofuranosyl]thymine
• 英文别名: 5'-O-(tert-butyldiphenylsilyl)-3'-C-allyl-3'-deoxythymidine；5'-O-tert-butyldiphenylsilyl-3'-C-allyl-2',3'-dideoxythymidine；3'-Deoxy-3'-Allyl-5'-O-Tert-Butyldiphenylsilylthymidine；1-[(2R,4S,5S)-5-[[tert-butyl(diphenyl)silyl]oxymethyl]-4-prop-2-enyloxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 146557-58-6
• 化学式: C₂₉H₃₆N₂O₄Si
• 分子量: 504.701
• InChiKey: SOSYPUAFWCNBRD-HDYLNDSGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 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：

  3-C-allyl-1-[5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-β-D-erythro-pentofuranosyl]thymine 在 sodium dihydrogenphosphate 、 四氧化锇 、 sodium perchlorate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N-甲基吗啉氧化物 、 triethylamine tris(hydrogen fluoride) 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 生成 2-((2S,3R,5R)-2-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3-yl)-N-(((2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl)acetamide
  参考文献：
  名称：

  [EN] LINKAGE MODIFIED OLIGOMERIC COMPOUNDS
  [FR] COMPOSÉS OLIGOMÈRES MODIFIÉS PAR LIAISON

  摘要：

  本发明提供了包含从1到大约3个核苷酸间连接的间隙寡聚合物化合物，其中所述核苷酸间连接具有I至XVI式中的一种。在某些实施例中，包含I至XVI式中的一种核苷酸间连接，可以提高与目标RNA相对于非靶RNA的选择性。在某些实施例中，提高的选择性还提供了改进的毒性概况。某些这样的寡聚合物化合物适用于与互补核酸杂交，包括但不限于细胞中的核酸。在某些实施例中，杂交导致细胞中目标核酸的活性或表达量的调节。

  公开号：

  WO2019245957A1
• 作为产物：
  描述：

  5'-O-tert-butyldiphenylsilylthymidine 在 吡啶 、 偶氮二异丁腈 作用下， 以 苯 为溶剂， 反应 72.0h， 生成 3-C-allyl-1-[5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-β-D-erythro-pentofuranosyl]thymine
  参考文献：
  名称：

  Synthesis of 3′-C-substituted thymidine derivatives by free-radical techniques: scope and limitations

  摘要：

  The scope and limitations of radical-mediated 3'-C-substitution of pyrimidine nucleosides was evaluated with 5'-O-(tertbutyldimethylsilyl)thymidine or its tert-butyldiphenylsilyl analogue having thionoester or thionoamide groups at O-3', including (methylthio)thiocarbonyl, (phenoxy)thiocarbonyl, (pentafluorophenoxy)thiocarbonyl, and (1-imidazoiyl)thiocarbonyl. Their reaction with acrylonitrile, methyl acrylate, and allyltributyltin under radical-generating conditions affords corresponding 3'-C-alkylated products, together with the product of simple deoxygenation at C-3'. The conditions for optimizing the yield of 3'-C-substituted product are presented. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2006.11.015

文献信息

• 3‘-<i>C</i>-Branched-Chain-Substituted Nucleosides and Nucleotides as Potent Inhibitors of <i>Mycobacterium </i><i>t</i><i>uberculosis </i>Thymidine Monophosphate Kinase
  作者：Veerle Vanheusden、Hélène Munier-Lehmann、Matheus Froeyen、Laurence Dugué、Arne Heyerick、Denis De Keukeleire、Sylvie Pochet、Roger Busson、Piet Herdewijn、Serge Van Calenbergh

  DOI：10.1021/jm021108n

  日期：2003.8.1

  3'-position was explored via the introduction of various substituents at the 3'-position of the thymidine monophosphate (dTMP) scaffold. Various 3'-C-branched chain substituted nucleotides in the 2'-deoxyribo (3-6) and ribo series (7, 8) were synthesized from one key intermediate (23). 2'-Deoxy analogues proved to be potent inhibitors of TMPKmt: 3'-CH(2)NH(2) (4), 3'-CH(2)N(3) (3), and 3'-CH(2)F (5) nucleotides

  结核分枝杆菌（TMPKmt）的胸苷单磷酸激酶（TMPK）代表了一种阻断细菌DNA合成的有吸引力的靶标。为了找到TMPKmt的高亲和力抑制剂，通过在胸苷单磷酸（dTMP）支架的3'-位置引入各种取代基来探索酶在3'-位置的空腔。从一个关键的中间体（23）合成了2'-脱氧核糖（3-6）和核糖系列（7，8）中的各种3'-C支链取代的核苷酸。2'-脱氧类似物被证明是TMPKmt的有效抑制剂：3'-CH（2）NH（2）（4），3'-CH（2）N（3）（3）和3'-CH（2 F（5）个核苷酸在该系列中表现出最高亲和力，K（i）值分别为10.5、12和15 microM。这些结果表明，TMPKmt可耐受在3'-位引入空间上要求的取代基。核糖类似物经历了显着的亲和力降低，这可能是由于Tyr103在2'位置附近的空间位阻。尽管5'-O-磷酸化的化合物对酶具有更高的亲和力，但亲本核苷通常以相同的数量级显示出对
• SYNTHESIS AND PHOTOCHEMICAL BEHAVIOUR OF A T-T DIMER CONTAINING AN AMIDE LINKAGE
  作者：Martial Thomas、Pascale Clivio、Dominique Guillaume、Jean-Louis Fourrey

  DOI：10.1081/ncn-100002460

  日期：2001.3.31

  A T-T dimer characterized by an amide linkage to replace the phosphodiester backbone has been synthesized using a modified radical strategy. The new synthetic approach makes use of a thymidin-3'-yl phosphorodithioate derivative as a precursor of 3'-allyl-3'-deoxythymidine. Standard chemical transformations of this derivative led to the desired T-T dimer incorporating an amide bond. The latter was irradiated

  已使用改良的自由基策略合成了以酰胺键取代磷酸二酯主链为特征的TT二聚体。新的合成方法利用胸苷3'-基二硫代磷酸酯衍生物作为3'-烯丙基-3'-脱氧胸苷的前体。该衍生物的标准化学转化导致所需的掺入酰胺键的TT二聚体。后者用254 nm波长的光照射，主要生成环丁烷和[6-4]光加合物。
• Synthesis of Carbon E,E-Diene Chain-Linked Dinucleotide Analogues
  作者：Jacques Lebreton、Valérie Fargeas、Adjou Ané、Didier Dubreuil

  DOI：10.1055/s-0029-1218357

  日期：2009.12

  The synthesis of a dinucleotide thymidine-thymidine linked by a carbon E,E-diene chain is described. This dimer is synthesized by a coupling reaction between an (E)-vinylstannane and an (E)-iodovinyl partner prepared from acetylenic parents, which are both available from thymidine in six and five steps, respectively. In addition, a new efficient access to 3′-C-formyl thymidine is presented.

  描述了由碳E,E-二烯链连接的二核苷酸胸苷-胸苷的合成。该二聚体是通过 (E)-乙烯基锡烷和由炔属母体制备的 (E)-碘乙烯基配偶体之间的偶联反应合成的，这两种母体均可以分别通过六步和五步从胸苷中获得。此外，还提出了一种新的有效获取 3'-C-甲酰基胸苷的方法。
• Heteroatomic oligonucleoside linkages
  申请人：Isis Pharmaceuticals, Inc.

  公开号：US05677437A1

  公开（公告）日：1997-10-14

  Oligonucleotide-mimicking macromolecules that have improved nuclease resistance are provided. Replacement of the normal phosphorodiester inter-sugar linkages found in natural oligonucleotides with four atom linking groups provide unique compounds that are useful in regulating RNA expression and in therapeutics. Methods of synthesis and use also are disclosed.

  提供了具有改进核酸酶抵抗性的寡核苷酸仿效大分子。用四原子连接基替代自然寡核苷酸中的正常磷酸二酯间糖连接，提供了有用的调节RNA表达和治疗的独特化合物。还公开了合成和使用的方法。
• Nucleomimetic strategy for the inhibition of HIV-1 nucleocapsid protein NCp7 activities
  作者：Sabine Druillennec、Hervé Meudal、Bernard P. Roques、Marie-Claude Fournié-Zaluski

  DOI：10.1016/s0960-894x(99)00052-9

  日期：1999.2

  We report the synthesis and biological properties of three modified dinucleotides T*G, G*T and T*T in winch the natural phosphodiester linkage has been replaced by a methylene carboxamide unit. They have been designed to act as nucleomimetics of a sequence recognized by the HIV-1 nucleocapsid protein NCp7 and to inhibit this interaction. (C) 1999 Elsevier Science Ltd. All rights reserved.