1-<5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-3-C-styryl-β-D-erythro-pentofuranosyl>thymine | 161168-94-1

• 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)-2,3-dideoxy-3-C-styryl-β-D-erythro-pentofuranosyl>thymine
• 英文别名: 5'-O-tert-butyldiphenylsilyl-3'-deoxy-3'-((E)-2-phenylethenyl)thymidine；1-[(2R,4R,5S)-5-[[tert-butyl(diphenyl)silyl]oxymethyl]-4-[(E)-2-phenylethenyl]oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 161168-94-1
• 化学式: C₃₄H₃₈N₂O₄Si
• 分子量: 566.772
• InChiKey: AZVIFTOPTXAZLB-IAYLMWQJSA-N

物化性质

• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.04
• 重原子数：
  41
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 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-<5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-3-C-styryl-β-D-erythro-pentofuranosyl>thymine 在 吡啶 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 sodium periodate 、 四氧化锇 、 叠氮化锂 、 偶氮二异丁腈 、 三正丁基氢锡 、 sodium iodide 作用下， 以 1,4-二氧六环 、 甲醇 、 氯仿 、 水 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 生成 3'-(aminomethyl)-5'-O-tert-butyldimethylsilyl-3'-deoxythymidine
  参考文献：
  名称：

  Comparison of two amides as backbone replacement of the phosphodiester linkage in oligodeoxynucleotides

  摘要：

  The two isomeric amide modifications 1 and 2 show similar effects on the melting temperature of RNA/DNA duplexes, when they replace the natural phosphodiester linkage in the DNA strand. The synthesis of the amide dimer 1 is presented.

  DOI：

  10.1016/s0040-4039(00)77069-9
• 作为产物：
  描述：

  5'-O-tert-butyldiphenylsilylthymidine 在 偶氮二异丁腈 、 甲基三苯氧基碘磷 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 34.0h， 生成 1-<5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-3-C-styryl-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

• 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.
• Replacement of the phosphodiester linkage in oligonucleotides by heterocycles: the effect of triazole- and imidazole-modified backbones on DNA/RNA duplex stability
  作者：Peter von Matt、Karl-Heinz Altmann

  DOI：10.1016/s0960-894x(97)00270-9

  日期：1997.6

  Thymidine dinucleotide analogs with imidazole-derived backbones (III and IV) were synthesized. These modified dimeric building blocks were incorporated into oligodeoxyribonucleotides. The hybridization affinity of the modified oligonucleotides for RNA complements was determined and compared to the corresponding olefinic modifications I and II. (C) 1997 Elsevier Science Ltd.
• 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。
• Comparison of two amides as backbone replacement of the phosphodiester linkage in oligodeoxynucleotides
  作者：Jacques Lebreton、Adrian Waldner、Valérie Fritsch、Romain M. Wolf、Alain De Mesmaeker

  DOI：10.1016/s0040-4039(00)77069-9

  日期：1994.7

  The two isomeric amide modifications 1 and 2 show similar effects on the melting temperature of RNA/DNA duplexes, when they replace the natural phosphodiester linkage in the DNA strand. The synthesis of the amide dimer 1 is presented.