1-(carboxymethyl)uracil (cis-syn)-cyclobutane dimer | 177019-55-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1-(carboxymethyl)uracil (cis-syn)-cyclobutane dimer
• 英文别名: 2-[(1R,2S,7S,8R)-12-(carboxymethyl)-4,6,9,11-tetraoxo-3,5,10,12-tetrazatricyclo[6.4.0.02,7]dodecan-3-yl]acetic acid
• CAS: 177019-55-5
• 化学式: C₁₂H₁₂N₄O₈
• 分子量: 340.249
• InChiKey: HOLKDBKDGSPVNR-KVFPUHGPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  173
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-ethyl-10-(2'-hydroxyethyl)-7,8-dimethyl-10H-benzo[g]pteridine-2,4-dione 、 1-(carboxymethyl)uracil (cis-syn)-cyclobutane dimer 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.17h， 以49%的产率得到2-(3-ethyl-7,8-dimethyl-2,4-dioxobenzo[g]pteridin-10-yl)ethyl 2-[(1R,2S,7S,8R)-12-[2-[2-(3-ethyl-7,8-dimethyl-2,4-dioxobenzo[g]pteridin-10-yl)ethoxy]-2-oxoethyl]-4,6,9,11-tetraoxo-3,5,10,12-tetrazatricyclo[6.4.0.02,7]dodecan-3-yl]acetate
  参考文献：
  名称：

  Investigation of Flavin-Containing DNA-Repair Model Compounds

  摘要：

  Irradiation of DNA with UV-B light causes the formation of mutagenic DNA lesions such as cis-syn and trans-syn cyclobutane pyrimidine dimers. DNA photolyases are flavin-dependent repair enzymes which directly revert the mutagenic cis-syn pyrimidine dimers into the corresponding monomers by a light-facilitated repair reaction. To gain deeper insight into the repair process, we recently prepared flavin-containing model compounds which are able to mimic the repair reaction (Carell, T.; Epple, R.; Gramlich, V. Angew. Chem., Int. Ed. Engl. 1996, 35, 620-623). This publication now contains a detailed description of the synthesis of a series of related model compounds and a comprehensive investigation of their cleavage properties. The results obtained help to unravel the requirements necessary for an efficient, flavin-mediated cleavage of pyrimidine dimers and provide insight into the factors on which the enzymatic repair process depends. The investigation of the cleavage reaction with cis-syn, trans-syn, and hans-anti cyclobutane pyrimidine dimer model compounds reveal an enhanced vulnerability for the cis-syn isomer. The trans-syn dimer is 10 times more stable, These results are comparable to those observed in a recent study on the E. coli enzyme. The excellent solubility of some of the model compounds has allowed a medium-dependent investigation of the flavin-initiated cleavage reaction. increased cleavage efficiencies are observed in polar solvents such as water (phi = 0.06) and acetonitrile (phi = 0.05). The quantum yields decrease by a factor of 4 in solvents with very low polarity such as dioxane (phi = 0.01). These results are not in agreement with earlier solvent-dependent evaluations performed with non-flavin-containing model compounds (Hartzfeld, D. G.; Rose, S. D. J. Am. Chem. Soc. 1993, 115,850-854). The results, however, suggest that the unusually polar flavin-binding pocket, observed in the X-ray crystal structure of the E, coli. photolyase, might be required to increase the catalytic repair efficiency. Investigations of the cleavage reaction in the presence of acid and base in organic solvents emphasize the strict requirement for a deprotonated reduced riboflavin chromophore. The determined pH values for half-maximal (pH = 6.5) and maximal (7 less than or equal to pH less than or equal to 9) cleavage efficiencies are in agreement with the pK(a) value (pK(a) = 6.3) of the reduced riboflavin and reveal that physiological conditions are required to reach maximum catalytic cleavage efficiency.

  DOI：

  10.1021/ja964097u
• 作为产物：
  描述：

  ((4aR,4bS,8aS,8bR)-8-Benzyloxycarbonylmethyl-2,4,5,7-tetraoxo-decahydro-1,3,6,8-tetraaza-biphenylen-1-yl)-acetic acid benzyl ester 在 palladium on activated charcoal 氢气 作用下， 以 溶剂黄146 为溶剂， 反应 2.0h， 以91%的产率得到1-(carboxymethyl)uracil (cis-syn)-cyclobutane dimer
  参考文献：
  名称：

  （羧甲基）-官能化的环丁缩合的尿嘧啶二聚体的合成和结构†

  摘要：

  在这里，我们报道了一种方便的方法，用于制备四个苄基酯保护的，（羧甲基）官能化的环丁缩合的尿嘧啶二聚体1-4，包括所需的顺式-顺式-顺式，顺式-异构体1，适用于制备催化性抗体，合成受体和模型化合物，这是研究DNA损伤，识别步骤和DNA修复机制所必需的。各异构体的全面结构测定通过1 H-NMR，并在的情况下，顺式cisoid -顺，顺和顺式traftsoid -顺，顺二聚体通过X射线晶体结构分析，本发明还提供。

  DOI：

  10.1002/hlca.19970800718

文献信息

• Flavin- and Deazaflavin-Containing Model Compounds Mimic the Energy Transfer Step in Type-II DNA-Photolyases
  作者：Robert Epple、Thomas Carell

  DOI：10.1002/(sici)1521-3773(19980420)37:7<938::aid-anie938>3.0.co;2-p

  日期：1998.4.20

  A distinct energy transfer between the deazaflavin and the flavin is observed in compounds that mimic the DNA repair function of DNA-photolase enzymes (see sketch). Studies on these models prove that the deazaflavin acts solely as photoantenna and suggest that the two cofactors have to be separated within the enzyme to suppress a competitive intercofactor electron transfer reaction.
• Carell, Thomas; Epple, Robert; Gramlich, Volker, Angewandte Chemie, 1996, vol. 108, # 6, p. 676 - 679
  作者：Carell, Thomas、Epple, Robert、Gramlich, Volker

  DOI：——

  日期：——