5’-O-t-butyldimethylsilyl-2’,3’-O-isopropylidene-6-methoxycarbonyl uridine | 934014-52-5

• 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: 5’-O-t-butyldimethylsilyl-2’,3’-O-isopropylidene-6-methoxycarbonyl uridine
• 英文别名: 2',3'-O-isopropylidene-5'-O-(tert-butyldimethylsilyl)orotidine methyl ester；5'-O-(t-butyldimethylsilyl)-6-methoxycarbonyl-2',3'-O-isopropylidene-uridine；methyl 3-[(3aR,4R,6R,6aR)-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-2,6-dioxopyrimidine-4-carboxylate
• CAS: 934014-52-5
• 化学式: C₂₀H₃₂N₂O₈Si
• 分子量: 456.568
• InChiKey: GDPZOWOKGLBIHG-DTZQCDIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.76
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5’-O-t-butyldimethylsilyl-2’,3’-O-isopropylidene-6-methoxycarbonyl uridine 在 三氟乙酸 作用下， 以 水 为溶剂， 反应 2.0h， 以89%的产率得到6-methoxycarbonyl uridine
  参考文献：
  名称：

  Substrate Distortion Contributes to the Catalysis of Orotidine 5′-Monophosphate Decarboxylase

  摘要：

  Orotidine 5'-monophosphate decarboxylase (OD-Case) accelerates the decarboxylation of orotidine 5'-monophosphate (OMP) to uridine 5'-monophosphate (UMP) by 17 orders of magnitude. Eight new crystal structures with ligand analogues combined with computational analyses of the enzyme's short-lived intermediates and the intrinsic electronic energies to distort the substrate and other ligands improve our understanding of the still controversially discussed reaction mechanism. In their respective complexes, 6-methyl-UMP displays significant distortion of its methyl substituent bond, 6-amino-UMP shows the competition between the K72 and C6 substituents for a position close to D70, and the methyl and ethyl esters of OMP both induce rotation of the carboxylate group substituent out of the plane of the pyrimidine ring. Molecular dynamics and quantum mechanics/molecular mechanics computations of the enzyme-substrate complex also show the bond between the carboxylate group and the pyrimidine ring to be distorted, with the distortion contributing a 10-15% decrease of the Delta Delta G(double dagger) value. These results are consistent with ODCase using both substrate distortion and transition-state stabilization, primarily exerted by K72, in its catalysis of the OMP decarboxylation reaction.

  DOI：

  10.1021/ja408197k
• 作为产物：
  描述：

  尿嘧啶核苷 在 咪唑 、 硫酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 5’-O-t-butyldimethylsilyl-2’,3’-O-isopropylidene-6-methoxycarbonyl uridine
  参考文献：
  名称：

  Substrate Distortion Contributes to the Catalysis of Orotidine 5′-Monophosphate Decarboxylase

  摘要：

  Orotidine 5'-monophosphate decarboxylase (OD-Case) accelerates the decarboxylation of orotidine 5'-monophosphate (OMP) to uridine 5'-monophosphate (UMP) by 17 orders of magnitude. Eight new crystal structures with ligand analogues combined with computational analyses of the enzyme's short-lived intermediates and the intrinsic electronic energies to distort the substrate and other ligands improve our understanding of the still controversially discussed reaction mechanism. In their respective complexes, 6-methyl-UMP displays significant distortion of its methyl substituent bond, 6-amino-UMP shows the competition between the K72 and C6 substituents for a position close to D70, and the methyl and ethyl esters of OMP both induce rotation of the carboxylate group substituent out of the plane of the pyrimidine ring. Molecular dynamics and quantum mechanics/molecular mechanics computations of the enzyme-substrate complex also show the bond between the carboxylate group and the pyrimidine ring to be distorted, with the distortion contributing a 10-15% decrease of the Delta Delta G(double dagger) value. These results are consistent with ODCase using both substrate distortion and transition-state stabilization, primarily exerted by K72, in its catalysis of the OMP decarboxylation reaction.

  DOI：

  10.1021/ja408197k

文献信息

• WO2008/83465
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2007/38859
  申请人：——

  公开号：——

  公开（公告）日：——
• Hydrogen-Bonding Complexes of 5-Azauracil and Uracil Derivatives in Organic Medium
  作者：Alba Diez-Martinez、Eun-Kyong Kim、Ramanarayanan Krishnamurthy

  DOI：10.1021/acs.joc.5b00911

  日期：2015.7.17

  Uracil derivatives form strong complexes with complementary 2,4-diaminotriazine and adenine compounds, whereas derivatives of 5-azauracil (2,4-dioxotriazine) are known to form weak complexes in aqueous medium. However, herein we report that in organic medium (CDCl3), the 5-azauracil moiety forms hydrogen-bond-mediated complexes with complementary 2,4-diaminotriazine and adenine compounds, with strengths comparable to those formed by uracil compounds. Such dichotomous base-pairing behavior of the 5-azauracil moiety, in organic versus aqueous media, is found to be consistent with the ionization of the 5-azauracil moiety in aqueous medium leading to competitive interference from water molecules (via solvation), which is absent (lack of such ionization and solvent interference) in organic medium. This discriminating role of solvent (e.g., water) could have been an important factor in the selection of molecules, based on their physicochemical properties, and subsequently in the emergence of potential primordial informational oligomers that would have played a role in the origins of life.