2-羟基-4-氨基-5-羟甲基嘧啶 | 1123-95-1

• 物质功能分类: 医药中间体 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 2-羟基-4-氨基-5-羟甲基嘧啶
• 中文别名: 2-羟基-6=氨基-5-羟甲基嘧啶；4-氨基-2-羟基-5-羟甲基嘧啶；2-羟基-4-氨基-5-甲基吡啶；4-氨基-5-(羟甲基)嘧啶-2-醇；5-羟甲基胞间二氮苯；5-羟甲基胞嘧啶； 5-羟甲基胞嘧啶
• 英文名称: 5-hydroxymethylcytosine
• 英文别名: 5-Hydroxymethylcytosin；6-amino-5-(hydroxymethyl)-1H-pyrimidin-2-one
• CAS: 1123-95-1
• 化学式: C₅H₇N₃O₂
• mdl: MFCD00047369
• 分子量: 141.129
• InChiKey: RYVNIFSIEDRLSJ-UHFFFAOYSA-N

物化性质

• 熔点：
  >299.85°C
• 沸点：
  258.15°C (rough estimate)
• 密度：
  1.3818 (rough estimate)
• 溶解度：
  可溶于DMSO（少量）、甲醇（轻微、加热、超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S24/25
• WGK Germany：
  3
• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335

反应信息

• 作为反应物：
  描述：

  2-羟基-4-氨基-5-羟甲基嘧啶 在 Escherichia coli K₁₂ D₃₁₄A cytosine deaminase 作用下， 以 aq. buffer 为溶剂， 生成 5-羟甲基脲嘧啶
  参考文献：
  名称：

  Discovery of a Bacterial 5-Methylcytosine Deaminase

  摘要：

  5-Methylcytosine is found in all domains of life, but the bacterial cytosine deaminase from Escherichia coli (CodA) will not accept 5-methylcytosine as a substrate. Since significant amounts of 5-methylcytosine are produced in both prokaryotes and eukaryotes, this compound must eventually be catabolized and the fragments recycled by enzymes that have yet to be identified. We therefore initiated a comprehensive phylogenetic screen for enzymes that may be capable of deaminating 5-methylcytosine to thymine. From a systematic analysis of sequence homologues of CodA from thousands of bacterial species, we identified putative cytosine deaminases where a "discriminating" residue in the active site, corresponding to Asp-314 in CodA from E. coli, was no longer conserved. Representative examples from Klebsiella pneumoniae (locus tag: Kpn00632), Rhodobacter sphaeroides (locus tag: Rsp0341), and Corynebacterium glutamicum (locus tag: NCgl0075) were demonstrated to efficiently deaminate 5-methylcytosine to thymine with values of k(cat)/K-m of 1.4 x 10(5), 2.9 x 10(4), and 1.1 x 10(3) M-1 s(-1), respectively. These three enzymes also catalyze the deamination of 5-fluorocytosine to 5-fluorouracil with values of k(cat)/K-m of 1.2 x 10(5), 6.8 x 10(4), and 2.0 x 10(2) M-1 s(-1), respectively. The three-dimensional structure of Kpn00632 was determined by X-ray diffraction methods with 5-methylcytosine (PDB id: 4R85 ), 5-fluorocytosine (PDB id: 4R88 ), and phosphonocytosine (PDB id: 4R7W ) bound in the active site. When thymine auxotrophs of E. coli express these enzymes, they are capable of growth in media lacking thymine when supplemented with 5-methylcytosine. Expression of these enzymes in E. coli is toxic in the presence of 5-fluorocytosine, due to the efficient transformation to 5-fluorouracil.

  DOI：

  10.1021/bi5012767
• 作为产物：
  描述：

  2-甲基巯基-4-氨基嘧啶-5-甲酸乙酯 在 盐酸 、 lithium aluminium tetrahydride 、 乙醚 作用下， 生成 2-羟基-4-氨基-5-羟甲基嘧啶
  参考文献：
  名称：

  The Synthesis of Some Pyrimidine Metabolite Analogs¹

  摘要：

  DOI：

  10.1021/jo01111a021

文献信息

• Structure of mildiomycin, a new antifungal nucleoside antibiotic
  作者：Setsuo Harada、Eui Mizuta、Toyokazu Kishi

  DOI：10.1016/s0040-4020(01)92447-0

  日期：1981.1

  The chemical structure of mildiomycin (1) active against powdery mildews was determined by chemical degradations and physical analyses to be 2 - [(2R, 5S, 6S) - 2 - (4 - amino - 1,2 - dihydro - 5 - hydroxymethyl - 2 -oxopyrimidin -1 - yl) - 5,6 - dihydro - 5 - L - serylamino - 2H - pyran - 6 - yl] - 5 - (3H+ - guanidino) - 2,4 -dihydroxyvalerate as shown in Chart 1.1

  通过化学降解和物理分析，确定对白粉病具有活性的温和霉素（1）的化学结构为2-[（（2R，5S，6S）-2-（4-氨基-1,2-二氢-5-羟甲基- 2-氧嘧啶丁-1-基）-5,6-二氢-5-L-丝氨酰氨基-2H-吡喃-6-yl]-5-（3H + -胍基）-2,4-二羟基戊酸酯，如图1所示。1个
• Oxidation of Cytosine and 5-Methylcytosine Nucleosides and 5-Methyl-2′-deoxycytidine 5′-Monophosphate with Peroxosulfate Ions
  作者：Toshio Itahara

  DOI：10.1246/cl.1991.1591

  日期：1991.9

  Reaction of 5-methylcytosine nucleosides and nucleotide with Na2S2O8 resulted in an oxidation of the 5-methyl group, while treatment of them and cytosine nucleosides with KHSO5 gave the corresponding N3-oxides.

  5-甲基胞嘧啶核苷和核苷酸与 Na2S2O8 反应导致 5-甲基基团氧化，而用 KHSO5 处理它们和胞嘧啶核苷产生相应的 N3-氧化物。
• Single-Molecule Detection of 5-Hydroxymethylcytosine in DNA through Chemical Modification and Nanopore Analysis
  作者：Wen-Wu Li、Lingzhi Gong、Hagan Bayley

  DOI：10.1002/anie.201300413

  日期：2013.4.15

  DNA threading the needle: A new method of single‐molecule detection of 5‐hydroxymethylcytosine (5hmC) in DNA has been developed. Selective thiol substitution of 5hmC (giving SMC) in a single‐step, bisulfite‐mediated reaction (see scheme) allows the incorporation of a peptide (yellow sphere) or biotin into DNA. Modified 5hmC bases can be readily distinguished at the single‐molecule level using protein

  DNA穿刺针：开发了一种单分子检测DNA中5-羟甲基胞嘧啶（5hMC）的新方法。在亚硫酸氢盐介导的单步反应中（参见方案），将5hMC选择性硫醇取代（产生SMC）可将肽（黄色球体）或生物素掺入DNA中。修饰的5hMC碱基可以使用蛋白质纳米孔分析在单分子水平上轻松区分。
• Hydrophilic modifications in peptide nucleic acid — Synthesis and properties of PNA possessing 5-hydroxymethyluracil and 5-hydroxymethylcytosine
  作者：Robert HE Hudson、Yuhong Liu、Filip Wojciechowski

  DOI：10.1139/v07-030

  日期：2007.4.1

  precedent, we prepared a peptide nucleic acid monomer, possessing 5-hydroxymethyuracil, which was compatible with Fmoc-based oligopeptide synthesis. An improved, large-scale synthesis of 5-hydroxymethylcytosine was developed, as a starting point for the synthesis of a monomer containing this nucleobase. In each case, the hydroxyl group was blocked as a t-butyldiphenylsilyl ether, and the exocyclic amino

  我们研究了在肽核酸 (PNA) 中掺入 C5-羟甲基-尿嘧啶和 -胞嘧啶的化学过程以及这种修饰对 PNA 杂交行为的后续影响。很大程度上基于文献先例，我们制备了一种肽核酸单体，具有 5-羟基甲氧嘧啶，与基于 Fmoc 的寡肽合成兼容。开发了一种改进的、大规模的 5-羟甲基胞嘧啶合成方法，作为合成含有该核碱基的单体的起点。在每种情况下，羟基被封闭为叔丁基二苯基甲硅烷基醚，胞嘧啶的环外氨基另外被苯甲酰基封闭。使用标准方案将修饰的单体并入寡聚体序列中的分离位置。
• Synthesis of modified pyrimidine bases and positive impact of chemically reactive substituents on their in vitro antiproliferative activity
  作者：Steffi Noll、Marijeta Kralj、Lidija Šuman、Holger Stephan、Ivo Piantanida

  DOI：10.1016/j.ejmech.2008.06.002

  日期：2009.3

  The antiproliferative activity screening on human tumor cell lines of a series of modified uracil and cytosine bases as well as some corresponding acyclonucleosides, and comparison of structure–activity relationship revealed the importance of chemical reactivity of the substituent attached to the C5-position of uracil for the activity of studied compounds. Namely, the results obtained for the most

  一系列修饰的尿嘧啶和胞嘧啶碱基以及一些相应的无环核苷在人肿瘤细胞系中的抗增殖活性筛选，以及结构-活性关系的比较表明，尿嘧啶C5位上取代基的化学反应活性对于研究化合物的活性。即，对于活性最高的化合物5-（氯乙酰氨基）尿嘧啶（2）及其无环糖类似物18所获得的结果表明，反应性取代基与胸苷酸合酶机制内若干可能的靶标之间形成了共价键（半胱氨酸残基，酶的基本部分，N，N-亚甲基四氢叶酸或其反应性亚胺形式）是最可能的作用方式。另外，新型的C 5-取代的尿嘧啶衍生物6（5- [双-（2-对-甲氧基苄基硫乙基）胺]乙酰氨基尿嘧啶）通过未知的机制对HeLa和MiaPaCa-2细胞系表现出高的抗增殖活性。