2'-脱氧(5'-14C)-3,4-二氢胸苷 | 132376-92-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 中文名称: 2'-脱氧(5'-14C)-3,4-二氢胸苷
• 中文别名: [5'，5''-2H2]胸苷
• 英文名称: <5'-(2)H2>thymidine
• 英文别名: [5',5''-D,D]-thymidine；(5'-(2)H2)thymidine；Thymidine-5',5''-D2；1-[(2R,4S,5R)-5-[dideuterio(hydroxy)methyl]-4-hydroxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 132376-92-2
• 化学式: C₁₀H₁₄N₂O₅
• 分子量: 244.216
• InChiKey: IQFYYKKMVGJFEH-PQDUBQKDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 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：

  2'-脱氧(5'-14C)-3,4-二氢胸苷 在 吡啶 、 磷酸三乙酯 、 Ammonium hydroxide 、 溶剂黄146 作用下， 反应 19.17h， 生成
  参考文献：
  名称：

  Hydroxyl Ion Addition to One-Electron Oxidized Thymine: Unimolecular Interconversion of C5 to C6 OH-Adducts

  摘要：

  In this work, addition of OH- to one-electron oxidized thymidine (dThd) and thyinine nucleotides in basic aqueous glasses is investigated. At pHs ca. 9-10 where the thymine base is largely deprotonated at N3, one-electron oxidation of the thymine base by Cl-2(center dot-) at ca. 155 K results in formation of a neutral thyminyl radical, T(-H).. Assignment to T(-H). is confirmed by employing N-15 substituted S'TMP. At pH >= ca. 11.5, formation of the 5-hydroxythymin-6yl radical, T(5OH)., is identified as a metastable intermediate produced by OH- addition to T(-H). at CS at ca. 155 K. Upon further annealing to ca. 170 K, T(50H)" readily converts to the 6-hydroxythymin-S-yl radical, T(6OH). Oneelectron oxidation of N3-methyl-thymidine (N-3-Me-dThd) by Cl-2(center dot-) at ca. 155 K produces the cation radical (N3-Me-dThd(center dot+)) for which we find a pH dependent competition between deprotonation from the methyl group at CS and addition of OH- to CS. At pH 7, the 5-methyl deprotonated species is found; however, at pH ca. 9, N3-Me-dThd(center dot+) produces T(SOH). that on annealing up to 180 K forms T(6OH).. Through use of deuterium substitution at C5' and on the thymine base, that is, specifically employing [51,5 ''-D,D]-5'-dThd, [5',5 ''-D,D]-5'-TMP, [CD3]-dThd and [CD3,6131-dThd, we find unequivocal evidence for T(50H). formation and its conversion to T(6OH).. The addition of OH- to the CS position in T(-H). and N-3-Me-dThd" is governed by spin and charge localization. DFT calculations predict that the conversion of the "reducing" T(5OH). to the "oxidizing" T(60H). occurs by a unimolecular OH group transfer from CS to C6 in the thymine base. The T(5OH)" to T(6OH). conversion is found to occur more readily for deprotonated dThd and its nucleotides than for N3-Me-dThd. In agreement, calculations predict that the deprotonated thymine base has a lower energy barrier (ca. 6 kcal/mol) for OH transfer than its corresponding N3-protonated thymine base (14 kcal/mol).

  DOI：

  10.1021/ja310650n
• 作为产物：
  描述：

  胸腺嘧啶脱氧核苷-5-羧酸 在 borane-d3 作用下， 以 四氢呋喃 为溶剂， 反应 20.0h， 以71%的产率得到2'-脱氧(5'-14C)-3,4-二氢胸苷
  参考文献：
  名称：

  Isotope effects on the sequence-specific cleavage of DNA by neocarzinostatin: kinetic partitioning between 4'- and 5'-hydrogen abstraction at unique thymidine sites

  摘要：

  In this article it is shown that in certain sequences cleavage of DNA at thymidine residues by activated neocarzinostatin occurs via a rate-limiting abstraction of either a 4'- or 5'-hydrogen from the deoxyribose moiety and that this partitioning can be modulated by deuteriation at either position. An analysis by gel electrophoresis of the HindIII-BamHI restriction fragment (346 bp) of pBR322 revealed that in the first 45 nucleotides of the (+)-strand T14, T17, T27, and T44 are strongly sensitive to deuterium substitution at C-4' (k(H)/k(D) approximately 2.4-5.5) and are less sensitive to deuteriation at C-5' (k(H)/k(D) approximately 1.0-2.6). All four of these T sites are located in GT steps. Other T residues are cleaved and exhibit variable sensitivity to 5'-deuteriation; however, they show no evidence of 4'-chemistry. The 5'-radical intermediate yields 3'-phosphate termini. The 4'-radical intermediate is demonstrated to partition between a modified abasic carbohydrate terminus and a 3'-phosphoglycolate terminus. The relative ratio of these two termini is, in turn, modulated by the structure of the thiol activator/reductant.

  DOI：

  10.1021/ja00006a054