1-<5-O-(tert-butyldiphenylsilyl)-3-O-<(phenoxy)thiocarbonyl>-2-deoxy-β-D-erythro-pentofuranosyl>thymine | 161085-74-1

• 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: 1-<5-O-(tert-butyldiphenylsilyl)-3-O-<(phenoxy)thiocarbonyl>-2-deoxy-β-D-erythro-pentofuranosyl>thymine
• 英文别名: 1-[5-O-(tert-butyldiphenylsilyl)-2-deoxy-3-O-[(phenoxy)thiocarbonyl]-β-D-erythro-pentofuranosyl]thymine；1-[(2R,4S,5R)-5-[[tert-butyl(diphenyl)silyl]oxymethyl]-4-phenoxycarbothioyloxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 161085-74-1
• 化学式: C₃₃H₃₆N₂O₆SSi
• 分子量: 616.81
• InChiKey: ONOJQXQQDSPONJ-ZGIBFIJWSA-N

物化性质

• 熔点：
  82.5-84 °C
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.46
• 重原子数：
  43
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-<5-O-(tert-butyldiphenylsilyl)-3-O-<(phenoxy)thiocarbonyl>-2-deoxy-β-D-erythro-pentofuranosyl>thymine 在 Grubbs catalyst first generation 、 偶氮二异丁腈 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  Nucleoside homodimerisation by cross metathesis

  摘要：

  The cross metathesis of 3'-allylic analogues of thymidine, 2'-deoxyuridine and 2'-deoxycytidine is used to obtain nucleoside dimers, in which an unsaturated hydrocarbon chain links the 3' positions of the sugar moieties. The biological activity on HIV infected cells was also evaluated. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(00)02292-9
• 作为产物：
  描述：

  叔丁基二苯基氯硅烷 在 吡啶 、 4-二甲氨基吡啶 、 N-羟基丁二酰亚胺 作用下， 以 吡啶 、 苯 为溶剂， 反应 52.0h， 生成 1-<5-O-(tert-butyldiphenylsilyl)-3-O-<(phenoxy)thiocarbonyl>-2-deoxy-β-D-erythro-pentofuranosyl>thymine
  参考文献：
  名称：

  Efficient and Stereoselective Synthesis of 3′-Deoxy 3′ -C-Branched-Chain Substituted Thymidine

  摘要：

  在本报告中，我们首次利用分子间自由基 C-C 键形成反应，简便、高效、立体选择性地合成了 1-[5-O-(叔丁基二苯基硅烷基)-2,3-二脱氧-3-C-甲酰基-δ²-D-赤式戊呋喃糖基]胸腺嘧啶（12）。讨论了这种化合物在反义应用中的效用，作为延伸，12 被转化为 1-[2,3-二脱氧-3-C-(羟甲基)-δ-D-赤式戊呋喃糖基]胸腺嘧啶（14），这是一种有效的抗病毒和抗肿瘤药物。

  DOI：

  10.1055/s-1994-25664

文献信息

• 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。
• Rational Design of 5‘-Thiourea-Substituted α-Thymidine Analogues as Thymidine Monophosphate Kinase Inhibitors Capable of Inhibiting Mycobacterial Growth
  作者：Ineke Van Daele、Hélène Munier-Lehmann、Matheus Froeyen、Jan Balzarini、Serge Van Calenbergh

  DOI：10.1021/jm0706158

  日期：2007.11.1

  Recently, thymidine monophosphate kinase (TMPK) emerged as an attractive target for developing inhibitors of Mycobacterium tuberculosis growth. The elucidation of the X-ray structure of TMPK of M. tuberculosis (TMPKmt), as well as the structure of an earlier serendipitously discovered dimeric thymidine inhibitor, laid the foundation for the design of potent and selective TMPKmt inhibitors reported here. Several hits identified within a series of 3'-C-branched thiourea-substituted P-thymidine derivatives inspired us to construct a set of 5'-thiourea-substituted a-thymidine derivatives characterized by a similar relative orientation of the thymine and arylthiourea moieties. (x-Thymidine derivative 15, featuring a (3-trifluoromethyl-4-chlorophenyl)thiourea moiety, has a K-i of 0.6 mu M and a selectivity index of 600 versus human TMPK. Moreover, it represents the first TMPK inhibitor showing good inhibitory activity on growing M. bovis (MIC99 = 20 mu g/mL) and M. tuberculosis (MIC50 = 6.25 mu g/mL) strains.
• Synthesis of 3′-C-substituted thymidine derivatives by free-radical techniques: scope and limitations
  作者：Derek Horton、Kuangmin Chen、Zaesung No、Howard C. Lee

  DOI：10.1016/j.carres.2006.11.015

  日期：2007.2

  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.
• Efficient and Stereoselective Synthesis of 3′-Deoxy 3′ -<i>C</i>-Branched-Chain Substituted Thymidine
  作者：Yogesh S. Sanghvi、Ramesh Bharadwaj、Françoise Debart、Alain De Mesmaeker

  DOI：10.1055/s-1994-25664

  日期：——

  In this report, we provide for the first time a facile, efficient, and stereoselective synthesis of 1-[5-O-(tert-butyldiphenylsilyl)-2, 3-dideoxy-3-C-formyl-β-D-erythro-pentofuranosyl] thymine (12), using an intermolecular radical C-C bond formation reaction. The utility of this compound for antisense application is discussed and, as an extension, 12 was converted into 1-[2,3-dideoxy-3 -C-(hydroxymethyl)-β-D-erythro-pentofuranosyl]thymine (14), a potent antiviral and antitumor agent.

  在本报告中，我们首次利用分子间自由基 C-C 键形成反应，简便、高效、立体选择性地合成了 1-[5-O-(叔丁基二苯基硅烷基)-2,3-二脱氧-3-C-甲酰基-δ²-D-赤式戊呋喃糖基]胸腺嘧啶（12）。讨论了这种化合物在反义应用中的效用，作为延伸，12 被转化为 1-[2,3-二脱氧-3-C-(羟甲基)-δ-D-赤式戊呋喃糖基]胸腺嘧啶（14），这是一种有效的抗病毒和抗肿瘤药物。
• Nucleoside homodimerisation by cross metathesis
  作者：Nathalie Batoux、Rachida Benhaddou-Zerrouki、Philippe Bressolier、Robert Granet、Géraldine Laumont、Anne-Marie Aubertin、Pierre Krausz

  DOI：10.1016/s0040-4039(00)02292-9

  日期：2001.2

  The cross metathesis of 3'-allylic analogues of thymidine, 2'-deoxyuridine and 2'-deoxycytidine is used to obtain nucleoside dimers, in which an unsaturated hydrocarbon chain links the 3' positions of the sugar moieties. The biological activity on HIV infected cells was also evaluated. (C) 2001 Elsevier Science Ltd. All rights reserved.