3-[3-[(2R,4S,5R)-4-羟基-5-(羟基甲基)四氢呋喃-2-基]-5-甲基-2,6-二氧代嘧啶-1-基]丙腈 | 72718-33-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 中文名称: 3-[3-[(2R,4S,5R)-4-羟基-5-(羟基甲基)四氢呋喃-2-基]-5-甲基-2,6-二氧代嘧啶-1-基]丙腈
• 中文别名: 2-癸基-1,4,7,10,13-五氧杂环十五烷
• 英文名称: N³-(2-cyanoethyl)thymidine
• 英文别名: 3-(2-cyanoethyl)thymidine；3-[3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-2,6-dioxopyrimidin-1-yl]propanenitrile
• CAS: 72718-33-3
• 化学式: C₁₃H₁₇N₃O₅
• 分子量: 295.295
• InChiKey: JQUAFYUNOCCDRA-HBNTYKKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  21
• 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：
  114
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-[3-[(2R,4S,5R)-4-羟基-5-(羟基甲基)四氢呋喃-2-基]-5-甲基-2,6-二氧代嘧啶-1-基]丙腈 在 钾硼氢 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以82%的产率得到3-(3-aminopropyl)thymidine
  参考文献：
  名称：

  胸腺嘧啶激酶1-靶向的硼烷嘧啶核苷核苷类似物的合成及评估，用于硼中子俘获疗法的癌症

  摘要：

  合成了十六个第二代氨基和酰胺基取代的碳硼烷基嘧啶核苷类似物的文库，并设计为可用于癌症的硼中子捕获疗法（BNCT）的胸苷激酶1（TK1）的底物和抑制剂，并通过酶动力学进行了评估-，酶抑制-，代谢组学和生物分布研究。这些第二代碳硼烷基嘧啶核苷类似物（YB18A [ 3 ]）中的一个，氨基直接与通过乙烯间隔基束缚在胸腺嘧啶3位上的间甲碳氢化合物笼相连，具有约3-4倍的底物hTK1和抑制剂比N5 - 2OH（2-），是第一代碳硼烷基嘧啶核苷类似物。既2和3似乎是5'-单磷酸化在TK1（+）细胞RG2，无论在体外和体内。对携带脑内RG2神经胶质瘤的大鼠进行生物分布研究后，选择性摄取了3种肿瘤，瘤内浓度大约是2种的4倍。获得的结果大大提高了对TK1和碳硼烷基嘧啶核苷类似物之间结合相互作用的理解，并将深刻影响这些试剂的未来设计策略。

  DOI：

  10.1016/j.ejmech.2015.05.042
• 作为产物：
  描述：

  5'-O-(4,4'-dimethoxytrityl)-N3-(2-cyanoethyl)thymidine 在 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以90%的产率得到3-[3-[(2R,4S,5R)-4-羟基-5-(羟基甲基)四氢呋喃-2-基]-5-甲基-2,6-二氧代嘧啶-1-基]丙腈
  参考文献：
  名称：

  Synthesis of High-Quality Antisense Drugs. Addition of Acrylonitrile to Phosphorothioate Oligonucleotides:  Adduct Characterization and Avoidance

  摘要：

  It is demonstrated that the acrylonitrile (AN) generated during the ammonolysis step of oligonucleotide manufacture selectively adds to thymine residue present in ISIS 2302 to give a full-length oligonucleotide in which thymine is replaced by an N-3-cyanoethylthymine residue. Treatment of support-bound ISIS 2302 with a solution of triethylamine in CH3CN before ammonolysis is sufficient to prevent formation of this class of impurity.

  DOI：

  10.1021/op020090n

文献信息

• The 4-[<i>N</i>-Methyl-<i>N</i>-(2,2,2-trifluoroacetyl)amino]butyl Group as an Alternative to the 2-Cyanoethyl Group for Phosphate Protection in the Synthesis of Oligodeoxyribonucleotides
  作者：Andrzej Wilk、Andrzej Grajkowski、Lawrence R. Phillips、Serge L. Beaucage

  DOI：10.1021/jo990835w

  日期：1999.10.1

  The 4-[N-methyl-N-(2,2,2-trifluoroacetyl)amino]butyl group for phosphate protection in the synthesis of oligodeoxyribonucleotides has been developed to completely prevent nucleobase alkylation by acrylonitrile that could potentially occur upon deprotection of the traditional 2-cyanoethyl phosphate protecting group. The properties of this new phosphate protecting group were evaluated using the model phosphotriester 9. The mechanism of phosphate deprotection was studied by treating 9 with concentrated NH4OH. NMR analysis,of the deprotection reaction demonstrated that cleavage of the N-trifluoroacetyl group is rate-limiting. The resulting phosphotriester intermediate 13 was also shown to undergo rapid cyclodeesterification to produce O,O-diethyl phosphate 15 and N-methylpyrrolidine -16 (Scheme 2). Given the facile removal of the 4-[N-methyl-N-(2,2,2-trifluoroacetyl)amino]butyl phosphate protecting group under mild basic conditions, its utilization in oligonucleotide synthesis began with the preparation of the deoxyribonucleoside phosphoramidites 4a-d (Scheme 3). The coupling efficiency of 4a-d and conventional a-cyanoethyl deoxyribonucleoside phosphoramidites 24a-d was then compared in the solid-phase synthesis of the 20-mer d(ATCCGTAGCTAAGGTCATGC). As previously observed in the deprotection of 9, the 4-[N-methyl,N-(2,2,2-trifluoroacetyl)amino]butyl phosphate protecting groups were easily and completely removed from the oligonucleotide by using either concentrated NH4OH or pressurized ammonia gas. Analysis of the deprotected oligomer by polyacrylamide gel electrophoresis (Figure 3) indicated that the phosphoramidites 4a-d are as efficient as the 2-cyanoethyl phosphoramidites 24a-d in the synthesis of the 20-mer. Furthermore, following digestion of the crude 20-mer by snake venom phosphodiesterase and bacterial alkaline phosphatase, HPLC analysis showed complete hydrolysis to individual nucleosides and no detectable nucleobase modification.
• Nitromethane as a scavenger of acrylonitrile in the deprotection of synthetic oligonucleotides
  作者：Tadashi Umemoto、Takeshi Wada

  DOI：10.1016/j.tetlet.2005.04.066

  日期：2005.6

  A novel deprotection procedure for synthetic oligonucleotides was developed to prevent nucleobase alkylation. Acrylonitrile, a side product of the deprotection of a 2-cyanoethyl phosphate protecting group and which causes nucleobase alkylation, was found to be trapped by the addition of some acidic compounds, which generate a carbanion species under the conventional deprotection conditions using aqueous NH3. The 2-cyanoethylation of thymidine was inhibited effectively in the presence of nitromethane. (c) 2005 Elsevier Ltd. All rights reserved.
• Cell culture medium
  申请人：Genetix Limited

  公开号：EP1818392B1

  公开（公告）日：2010-08-25
• CELL CULTURE MEDIUM
  申请人：Bramke Irene

  公开号：US20110104754A1

  公开（公告）日：2011-05-05

  We describe a method of growing an animal cell in a culture medium, in which the culture medium comprises an elevated concentration of a thymidine family member, in which the growth or viability of the animal cell is increased as a result of the elevated concentration of the thymidine family member in the cell culture medium. Preferably, the cell culture medium comprises a semi-solid medium, which is a serum free or chemically defined medium.