1-<<2-hydroxy-1-(hydroxymethyl)ethoxy>methyl>thymine | 74554-16-8

• 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: 1-<<2-hydroxy-1-(hydroxymethyl)ethoxy>methyl>thymine
• 英文别名: 1-{[(1,3-dihydroxypropan-2-yl)oxy]-methyl}-5-methylpyrimidine-2,4(1H,3H)-dione；1-((1,3-dihydroxy-2-propyl)oxy)methyl-5-methyluracil；1-[(1',3'-dihydroxy-2'-propoxy)methyl]-5-methyluracil；1-[(1,3-dihydroxy-2-propoxy)methyl]-5-methyluracil；1-(1,3-dihydroxypropan-2-yloxymethyl)-5-methylpyrimidine-2,4-dione
• CAS: 74554-16-8
• 化学式: C₉H₁₄N₂O₅
• 分子量: 230.221
• InChiKey: BQFRWTWERQFADT-UHFFFAOYSA-N

物化性质

• 熔点：
  155-156 °C
• 密度：
  1.352±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-<<2-hydroxy-1-(hydroxymethyl)ethoxy>methyl>thymine 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 吡啶 为溶剂， 生成 1-<<2-dimethoxytrityl-hydroxy-1-(pentachlorophenylsuccinyl-hydroxy-methyl)ethoxy>-methyl>thymine
  参考文献：
  名称：

  Preparation of glyceronucleoside phosphoramidite synthons and their use in the solid phase synthesis of acyclic oligonucleotides

  摘要：

  DOI：

  10.1016/s0040-4039(00)80620-6
• 作为产物：
  描述：

  O,O-二(三甲基甲硅烷基)胸苷 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 48.0h， 生成 1-<<2-hydroxy-1-(hydroxymethyl)ethoxy>methyl>thymine
  参考文献：
  名称：

  与9-[（1,3-二羟基-2-丙氧基）甲基]鸟嘌呤有关的无环嘧啶对疱疹病毒的影响。

  摘要：

  已合成了一系列与有效的抗疱疹药9-[（（1,3-二羟基-2-丙氧基）甲基]鸟嘌呤（1，BW B759U）相关的嘧啶，它们均含有相同的无环链。其中一些化合物是天然存在的碱，胞嘧啶，尿嘧啶和胸腺嘧啶的衍生物。其他包括其中胞嘧啶和尿嘧啶部分的5-位被溴，碘，氟，甲基和氨基取代的化合物。胞嘧啶衍生物的其他变体是5-氮杂，2-巯基，4-甲基氨基，4-二甲基氨基和异胞嘧啶同源物。还制备了4-氨基嘧啶加合物。抗病毒测试表明，1-[（（1,3-二羟基-2-丙氧基）甲基]胞嘧啶（18，BW A1117U）在抵抗人巨细胞病毒和爱泼斯坦巴尔病毒的效力方面与鸟嘌呤类似物相当。

  DOI：

  10.1021/jm00396a021

文献信息

• Effect of Various Pyrimidines Possessing the 1-[(2-Hydroxy-1-(hydroxymethyl)ethoxy)methyl] Moiety, Able To Mimic Natural 2‘-Deoxyribose, on Wild-type and Mutant Hepatitis B Virus Replication
  作者：Rakesh Kumar、Wassila Semaine、Monika Johar、D. Lorne J. Tyrrell、Babita Agrawal

  DOI：10.1021/jm060102l

  日期：2006.6.1

  glycosyl moiety at the N-1 position, that have the ability to mimic the natural 2'-deoxyribosyl moiety. Some of these potential antiviral compounds included variations at both C-5 and C-6 positions of the uracil base. Other variations of the uracil derivatives were the 6-aza congeners. 4-Amino and 4-methoxy pyrimidine derivatives were also made. Compounds in which the base moiety was substituted by 5-chloro-

  乙型肝炎病毒（HBV）是全世界慢性肝病的最常见原因。由于长期使用和停止治疗后病毒DNA反弹，对临床抗HBV药物拉米夫定产生的耐药性已成为当前疗法的主要挫折。我们合成了一系列嘧啶核苷，它们在C-5位具有多个取代基，在N-1位具有1-[（（2-羟基-1-（羟甲基）乙氧基）甲基]柔性无环糖基部分，具有模仿天然2'-脱氧核糖基部分的能力。这些潜在的抗病毒化合物中的一些在尿嘧啶碱基的C-5和C-6位置均包含变异。尿嘧啶衍生物的其他变体是6-氮杂同源物。还制备了4-氨基和4-甲氧基嘧啶衍生物。碱基部分被5-氯-（25），5-（2-溴乙烯基）-（32）或5-溴-6-甲基-（37）基团取代的化合物对鸭HBV具有显着的活性，野生型人HBV（2.2.15个细胞）和抗拉米夫定的HBV，其中包含单突变和双突变。直至测试的最高浓度，在宿主HepG2和Vero细胞中均未见细胞毒性。与相应的嘌呤核苷更昔洛韦相比，化合物
• <i>Candida antarctica</i>lipase B catalyzed enantioselective acylation of pyrimidine acyclonucleoside
  作者：Renata Kołodziejska、Aleksandra Karczmarska-Wódzka、Andrzej Wolan、Marcin Dramiński

  DOI：10.3109/10242422.2012.715637

  日期：2012.8

  Abstract The influence of solvent and acyl group donor on selectivity of the transesterification reaction of 1-[1′,3′-dihydroxy-2′-propoxymethyl]-5-methyluracil, a structural analogue of ganciclovir was examined. Lipase (EC 3.1.1.3) B from Candida antarctica (CALB) enabled desymmetrization of prochiral hydroxyl groups when 1-butyl-3-methylimidazolium hexafluorophosphate ([Bmim][PF6]) was used as a

  摘要 研究了溶剂和酰基供体对更昔洛韦结构类似物1-[1',3'-二羟基-2'-丙氧基甲基]-5-甲基尿嘧啶酯交换反应选择性的影响。当 1-丁基-3-甲基咪唑鎓六氟磷酸盐 ([Bmim][PF6]) 用作反应介质时，来自南极念珠菌 (CALB) 的脂肪酶 (EC 3.1.1.3) B 能够使前手性羟基去对称化。据观察，CALB 在离子液体 [Bmim][PF6] 中的对映选择性是传统有机溶剂的 2.7-4 倍。
• ANTIVIRAL NUCLEOSIDES
  申请人：Kumar Rakesh

  公开号：US20100130440A1

  公开（公告）日：2010-05-27

  Disclosed are nucleosides which are useful in diagnosing and treating viral infections, for example, infections caused by hepatitis B virus (HBV), and herpes viruses including Epstein Barr virus.

  本发明涉及一种核苷，其在诊断和治疗病毒感染中有用，例如由乙型肝炎病毒（HBV）和包括Epstein-Barr病毒在内的疱疹病毒引起的感染。
• Prevention and Treatment of Cancer and Other Diseases
  申请人：Bondarev Igor E.

  公开号：US20090203636A1

  公开（公告）日：2009-08-13

  Nucleoside chemical compounds, which interact with specific structures of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) are disclosed. The compounds interfere with the activities of telomerase and reverse transcriptase, and are useful as antivirals, antibacterials and anticancer agents. Methods of treating or preventing cancers in patients involving administration of a therapeutically effective amount of a composition having an inhibitor or antagonist of the reverse transcriptases (RTs) expressed in cells of the patients are also disclosed. Method of using nucleoside analogs and other inhibitors of RTs in conjunction with DNA damaging agents such as genotoxic agents or radiation or photodynamic therapy or combinations these for the treatment of various cancers are also disclosed.

  本文披露了与脱氧核糖核酸（DNA）或核糖核酸（RNA）的特定结构相互作用的核苷类化合物。这些化合物干扰端粒酶和反转录酶的活性，并且可用作抗病毒、抗菌和抗癌剂。本文还披露了一种治疗或预防患者癌症的方法，包括向患者细胞中表达的反转录酶（RTs）的抑制剂或拮抗剂的组合物的治疗有效量的给药。本文还披露了使用核苷类类似物和其他RTs抑制剂与DNA损伤剂（如基因毒性剂、辐射或光动力疗法）或这些剂的组合物相结合治疗各种癌症的方法。
• Enantioselective enzymatic desymmetrization of the prochiral pyrimidine acyclonucleoside
  作者：Renata Kołodziejska、Marcin Górecki、Jadwiga Frelek、Marcin Dramiński

  DOI：10.1016/j.tetasy.2012.05.003

  日期：2012.5

  The effect of the solvent and the acyl group donor on the selectivity of the transesterification reaction of [(1,3-dihydroxypropan-2-yl)oxy]methyl}-5-methylpyrimidine-2.4(1H,3H)-dione was examined. Lipase (EC 3.1.1.3) Amano PS from Burkholderia cepacia (BCL) enabled desymmetrization of prochiral hydroxyl groups and gave the (R)-monoester in high enantiomeric excess (ee 88-99%). The best selectivity was obtained for the transesterification reaction with vinyl benzoate as the acylating agent (only monoester, 99% ee). The absolute configuration of the newly formed stereogenic center was determined with a high degree of confidence on the basis of the combined experimental and theoretical electronic circular dichroic (ECD) studies. The hydrolysis of prochiral diesters formed during the transesterification reaction in the presence of BCL provided the opposite enantiomer, that is, the (S)-monoester. (C) 2012 Elsevier Ltd. All rights reserved.