N¹-(2,2-diethoxyethyl)thymine | 35016-79-6

• 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: N¹-(2,2-diethoxyethyl)thymine
• 英文别名: 1-(thymine-1-yl)-2,2-diethoxyethane；1,1-diethoxy-2-(thymin-1-yl)acetaldehyde；1-(2,2-Diethoxyethyl)-thymin；1-(2,2-diethoxy-ethyl)-5-methyl-1H-pyrimidine-2,4-dione；1-(2,2-diethoxyethyl)-5-methylpyrimidine-2,4-dione
• CAS: 35016-79-6
• 化学式: C₁₁H₁₈N₂O₄
• 分子量: 242.275
• InChiKey: NTEQMAGNJSCEDB-UHFFFAOYSA-N

物化性质

• 溶解度：
  >36.3 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 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：

  N¹-(2,2-diethoxyethyl)thymine 在 natural phosphate coated with HCl 作用下， 以 水 、 乙腈 为溶剂， 反应 2.0h， 生成 2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetaldehyde
  参考文献：
  名称：

  制备新型α-氨基膦酸酯和膦酸无环核苷的高效一锅三组分程序

  摘要：

  摘要 醛（无环核苷）、胺（或氨基酸）和亚磷酸三乙酯的高效一锅三组分 Kabachnik-Fields 反应用于合成氨基膦酸酯，使用碘包覆的天然磷酸盐 (I2@NP) 作为催化剂. 测试了新型 α-氨基膦酸酯和膦酸无环核苷的抗 HCV 和抗 HIV 活性。分子对接表明，这些化合物的非活性可能是由于不存在疏水性药效团。

  DOI：

  10.1080/15257770.2020.1826516
• 作为产物：
  描述：

  胸腺嘧啶 、 2-溴-1,1-二乙氧基乙烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以56%的产率得到N¹-(2,2-diethoxyethyl)thymine
  参考文献：
  名称：

  制备新型α-氨基膦酸酯和膦酸无环核苷的高效一锅三组分程序

  摘要：

  摘要 醛（无环核苷）、胺（或氨基酸）和亚磷酸三乙酯的高效一锅三组分 Kabachnik-Fields 反应用于合成氨基膦酸酯，使用碘包覆的天然磷酸盐 (I2@NP) 作为催化剂. 测试了新型 α-氨基膦酸酯和膦酸无环核苷的抗 HCV 和抗 HIV 活性。分子对接表明，这些化合物的非活性可能是由于不存在疏水性药效团。

  DOI：

  10.1080/15257770.2020.1826516

文献信息

• Sequence-defined vinyl sulfonamide click nucleic acids (VS-CNAs) and their assembly into dynamically responsive materials
  作者：Bryan P. Sutherland、Paige J. LeValley、Derek J. Bischoff、April M. Kloxin、Christopher J. Kloxin

  DOI：10.1039/d0cc04235h

  日期：——

  A scalable synthetic strategy was developed towards the creation of sequence-defined DNA analogues employing thiol-Michael click chemistry and a soluble polymer support.

  通过巯基-迈克尔点击化学和可溶性聚合物支持，开发了一种可扩展的合成策略，用于创造序列定义的DNA类似物。
• [EN] METHODS AND REAGENTS FOR SYNTHESIZING NUCLEOSIDES AND ANALOGUES THEREOF<br/>[FR] PROCÉDÉS ET RÉACTIFS POUR SYNTHÉTISER DES NUCLÉOSIDES ET DES ANALOGUES DE CEUX-CI
  申请人：UNIV FRASER SIMON

  公开号：WO2021191830A1

  公开（公告）日：2021-09-30

  The present invention relates to methods and intermediates for the synthesis of nucleosides and nucleoside analogues (NAs). More specifically, the present invention relates to methods of synthesizing nucleosides and NAs, using simple achiral materials by a 'one-pot' proline-catalyzed halogenation of a heteroaryl-substituted acetaldehyde together with a tandem enantioselective aldol reaction followed by a reduction or organometallic addition and cyclization (annulation) reaction involving halide displacement.

  本发明涉及合成核苷和核苷类似物（NAs）的方法和中间体。更具体地说，本发明涉及使用简单的无手性材料通过“一锅法”脯氨酸催化卤代异芳基乙醛的卤代反应，随后进行串联对映选择性Aldol反应，然后进行还原或有机金属加成和环化（环化）反应，涉及卤化物置换。
• Triostin A Derived Cyclopeptide as Architectural Template for the Alignment of Four Recognition Units
  作者：Ursula M. Kotyrba、Kevin Pröpper、Eike-F. Sachs、Anastasiya Myanovska、Tobias Joppe、Friederike Lissy、George M. Sheldrick、Konrad Koszinowski、Ulf Diederichsen

  DOI：10.1002/open.201400001

  日期：2014.8

  template, well suited for DNA double strand interactions. The new tetra‐nucleobase binders are synthesized as aza‐TANDEM derivatives lacking the N‐methylation of triostin A and based on a cyclopeptide backbone. Synthesis of two tetra‐nucleobase aza‐TANDEM derivatives is established, DNA interaction analyzed by microscale thermophoresis, cytotoxic activity studied and a nucleobase sequence dependent

  DNA双嵌入剂triostin A在结构上是基于二硫键桥联的二肽支架，可在10.5Å距离内对两个喹喔啉单元进行预组织。合成了Triostin A类似物，其核碱基识别单元取代了喹喔啉，并且在两者之间包含两个其他识别单元。因此，四个核碱基识别单元被组织在一个刚性模板上，非常适合DNA双链相互作用。新的四核碱基结合剂是作为aza-TANDEM衍生物合成的，缺乏Triostin A的N-甲基化，并基于环肽骨架。建立了两个四核碱基aza-TANDEM衍生物的合成，通过微尺度热泳分析了DNA相互作用，研究了细胞毒活性，并通过质谱研究了核碱基序列依赖性自聚集。
• Unsaturated Acyclic Analogs of 2'-Deoxyadenosine and Thymidine Containing Fluorine: Synthesis and Biological Activity
  作者：Ze-Qi Xu、Yao-Ling Qiu、Sudhichai Chokekijchai、Hiroaki Mitsuya、Jiri Zemlicka

  DOI：10.1021/jm00006a004

  日期：1995.3

  The syntheses and biological activities of fluorobutynol 11 and (E)- and (Z)-fluorobutenols 8a,d and 9a,d are described. Alkylation of adenine with bromofluorobutyne 13a afforded intermediate 14 which was converted to fluorobutynol 11. Aldehyde 16a and (carbothoxyfluoromethyl)triphenylphosphonium bromide furnished (E)- and (Z)-fluorobutenoates 19a and 20a accompanied by regioisomer 21a. A similar reaction of compound 16d afforded Z- and E-esters 19d and 20d. Reduction of the mixture of 19a and 20a with DIBALH gave (E)- and (Z)-fluoroalkenols 8a and 9a. Similarly, the Z-ester 19d gave (Z)-fluoroalkenol 9d. Both 19d and 20d were reduced with NaBH4 to give (Z)- and (E)-fluoroalkenols 9d and 8d. Hydrogenation of 19a and 20a afforded fluoro ester 23. A similar reduction of 8a and 9a led to fluoro alcohol 24 and the defluorinated product 25 which were separated by chromatography on a Bio-Rad AG 1-X2 (OH-) column. (Z)-Fluorobutenol 9a is a substrate for adenosine deaminase, whereas the E-isomer 8a is inert toward the enzyme. By contrast, analogue 8a inhibited the replication and cytopathic effect of HN-1 in ATH8 cells with an IC50 Of approximately 100 mu M, but the Z-isomer 9a was inactive. This effect was accompanied by 36% cytotoxicity at 100 mu M. Compounds 11 and 8d inhibited the growth of murine leukemia L1210 culture with IC50 = 89 and 60 mu M, respectively.
• Efficient one-pot, three-component procedure to prepare new α-aminophosphonate and phosphonic acid acyclic nucleosides
  作者：Laila Baddi、Driss Ouzebla、Az-Eddine El Mansouri、Michael Smietana、Jean-Jacques Vasseur、Hassan B. Lazrek

  DOI：10.1080/15257770.2020.1826516

  日期：2021.1.2

  efficient one-pot three-component Kabachnik–Fields reaction of aldehydes (acyclic nucleosides), amines (or amino acid), and triethyl phosphite proceeded for the synthesis of aminophosphonates using natural phosphate coated with iodine (I2@NP) as a catalyst. The novel α-aminophosphonate and phosphonic acid acyclic nucleosides were tested for their anti-HCV and anti-HIV activities. The molecular docking

  摘要 醛（无环核苷）、胺（或氨基酸）和亚磷酸三乙酯的高效一锅三组分 Kabachnik-Fields 反应用于合成氨基膦酸酯，使用碘包覆的天然磷酸盐 (I2@NP) 作为催化剂. 测试了新型 α-氨基膦酸酯和膦酸无环核苷的抗 HCV 和抗 HIV 活性。分子对接表明，这些化合物的非活性可能是由于不存在疏水性药效团。