1-(2,3-Dideoxy-3,4-didehydro-β-D-erythro-pentofuranosyl)thymine | 37782-89-1

• 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: 1-(2,3-Dideoxy-3,4-didehydro-β-D-erythro-pentofuranosyl)thymine
• 英文别名: 1-(2,3-Dihydro-5-hydroxymethylfuran-2-yl)thymine；3',4'-didehydro-2',3'-dideoxythymidine；1-(5-hydroxymethyl-2,3-dihydro-furan-2-yl)-5-methyl-1H-pyrimidine-2,4-dione；3'-Deoxy-3',4'-didehydrothymidin；2'-Deoxy-3'-thymidinen；1-[(2R)-5-(Hydroxymethyl)-2,3-dihydrofuran-2-yl]-5-methylpyrimidine-2,4(1H,3H)-dione；1-[(2R)-5-(hydroxymethyl)-2,3-dihydrofuran-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 37782-89-1
• 化学式: C₁₀H₁₂N₂O₄
• 分子量: 224.216
• InChiKey: VJIJJLHYGOITDN-MRVPVSSYSA-N

物化性质

• 密度：
  1.391±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2,3-Dideoxy-3,4-didehydro-β-D-erythro-pentofuranosyl)thymine 在 吡啶 、 二甲基硫 、 臭氧 作用下， 反应 0.08h， 生成 1-<<<2-(Acetyloxy)acetyl>oxy>-3-oxopropyl>thymine
  参考文献：
  名称：

  Acyl migration in the production of thymine. Propenal from 3'-O-benzoyl-5'-deoxy-4'-(hydroperoxy)thymidine: a reinterpretation of a putative model for bleomycin-mediated DNA degradation

  摘要：

  Studies of Saito et al. (Saito, I.; Morii, T.; Matsuura, T. J. Org. Chem. 1987, 52, 1008) analyzing the decomposition of 3'-O-benzoyl-5'-deoxy-4'-hydroperoxythymidine (7) claimed to model the decomposition of the putative 4'-hydroperoxynucleotide intermediate in the bleomycin (BLM) mediated production of base propenal, 3'-phosphoglycolate, and 5'-phosphate termini from double-stranded DNA. A number of puzzling observations reported in this paper prompted a reinvestigation of this model system in detail. [4'-(HO2)-O-18]-7 and its 4' epimer 8 were prepared and their fate in aqueous solution as a function of pH was examined. Compound 7 decomposed in aqueous solution to produce thymine propenal accompanied by stoichiometric formation of benzoate containing 1 atom of O-18. In addition, thymine accompanied by stoichiometric amounts of malondialdehyde and [O-18]benzoate was also observed. Acetate containing 1 atom of O-18 accompanied production of both thymine and thymine propenal. The ratio of thymine propenal to thymine varied as a function of pH and temperature. Production of [O-18]benzoate and a detailed kinetic analysis of the decomposition of 7 unequivocally demonstrated that conversion of 7 to thymine propenal required the intermediacy of a 4'-perbenzoate ester. This perester produced by migration of the 3'-benzoyl blocking group of 7 to the terminal oxygen of its 4'-hydroperoxy moiety would then greatly facilitate heterolytic cleavage of the oxygen-oxygen bond. For stereochemical reasons a similar intramolecular benzoyl migration cannot occur with 8, explaining its lack of reactivity. These results call into question the relevance of the model proposed by Saito et al. to understanding the base propenal pathway in the BLM-catalyzed degradation of DNA. In addition, preparation of a second model of a putative intermediate in the base propenal pathway, [1-[[2-(acetyloxy)acetyl]oxy]-3-oxopropyl]thymine (12), is reported. The detailed kinetics of its decomposition as well as identification of the products accompanying its decomposition are reported. The relevance of these two model systems to the mechanism of degradation of DNA by BLM is discussed.

  DOI：

  10.1021/jo00001a011
• 作为产物：
  描述：

  O^3'-acetyl-5'-oxo-5'-deoxy-thymidine 在 sodium tetrahydroborate 、 三氟乙酸吡啶 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 3.75h， 生成 1-(2,3-Dideoxy-3,4-didehydro-β-D-erythro-pentofuranosyl)thymine
  参考文献：
  名称：

  Meggers, Eric; Dussy, Adrian; Schaefer, Thomas, Chemistry - A European Journal, 2000, vol. 6, # 3, p. 485 - 492

  摘要：

  DOI：

文献信息

• Identification of sugar degradation intermediates in a metalloporphyrin mediated DNA cleavage resulting from hydroxylation at C-5′
  作者：Geneviève Pratviel、Marguerite Pitié、Christian Périgaud、Gilles Gosselin、Jean Bernadou、Bernard Meunier

  DOI：10.1039/c39930000149

  日期：——

  Hydroxylation of poly(dA)·poly(dT) at the 5′ position of the deoxyribose units by the chemical nuclease Mn-TMPyP–KHSO5[Mn–TMPyP = manganese(III) complex of meso-tetrakis(4-N-methylpyridiniumyl)porphyrin] followed by an additional thermal step provides 5′-aldehyde-3′,4′-unsaturated nucleosides which can be reduced by sodium borohydride and then hydrogenated with palladium on charcoal giving 2′,3′-dideoxyribonucleosides having the natural β or the non-natural α configuration at 4′.

  化学核酸酶 Mn-TMPyPâKHSO5[MnâTMPyP=中-四(4-N-甲基吡啶鎓)卟啉的锰(III)络合物]在脱氧核糖单元的 5â²位对聚(dA)Â-聚(dT)进行羟基化，然后再经过一个热步骤，得到 5â²-醛-3â²、4â²-不饱和核苷，这种核苷可以用硼氢化钠还原，然后在炭上用钯氢化，得到 2â²,3â²-二脱氧核苷，这种核苷在 4â² 处具有天然的 β 或非天然的 α 构型。
• 3′-Modified oligodeoxyribonucleotides for the study of 2-deoxyribose damage in DNA
  作者：Buthina Al-Oudat、Alex Salyer、Kevin Trabbic、Amanda Bryant-Friedrich

  DOI：10.1016/j.bmcl.2012.11.050

  日期：2013.2

  Well-defined substrates for the study of oxidative processes are important for the elucidation of the role of DNA damage in the etiology of diseases such as cancer. We have synthesized 3'-modified oligodeoxyribonucleotides (ODNs) using 5' -> 3' 'reverse' DNA synthesis for the study of 2-deoxyribose oxidative damage to DNA. The modified monomers designed for these studies all share a common feature, they lack the naturally occurring 3'-hydroxyl group found in 2-deoxyribonucleosides. Modified H-phosphonates containing 3'-phenyl selenides as well as saturated and unsaturated sugars were obtained and incorporated in ODNs. These ODNs were used to investigate the fate of C3'-dideoxyribonucleotide radicals in DNA. (c) 2012 Elsevier Ltd. All rights reserved.
• MCGALL, GLENN H.;STUBBE, JOANNE;KOZARICH, JOHN W., J. ORG. CHEM., 56,(1991) N, C. 48-55
  作者：MCGALL, GLENN H.、STUBBE, JOANNE、KOZARICH, JOHN W.

  DOI：——

  日期：——
• Acyl migration in the production of thymine. Propenal from 3'-O-benzoyl-5'-deoxy-4'-(hydroperoxy)thymidine: a reinterpretation of a putative model for bleomycin-mediated DNA degradation
  作者：Glenn H. McGall、JoAnne Stubbe、John W. Kozarich

  DOI：10.1021/jo00001a011

  日期：1991.1

  Studies of Saito et al. (Saito, I.; Morii, T.; Matsuura, T. J. Org. Chem. 1987, 52, 1008) analyzing the decomposition of 3'-O-benzoyl-5'-deoxy-4'-hydroperoxythymidine (7) claimed to model the decomposition of the putative 4'-hydroperoxynucleotide intermediate in the bleomycin (BLM) mediated production of base propenal, 3'-phosphoglycolate, and 5'-phosphate termini from double-stranded DNA. A number of puzzling observations reported in this paper prompted a reinvestigation of this model system in detail. [4'-(HO2)-O-18]-7 and its 4' epimer 8 were prepared and their fate in aqueous solution as a function of pH was examined. Compound 7 decomposed in aqueous solution to produce thymine propenal accompanied by stoichiometric formation of benzoate containing 1 atom of O-18. In addition, thymine accompanied by stoichiometric amounts of malondialdehyde and [O-18]benzoate was also observed. Acetate containing 1 atom of O-18 accompanied production of both thymine and thymine propenal. The ratio of thymine propenal to thymine varied as a function of pH and temperature. Production of [O-18]benzoate and a detailed kinetic analysis of the decomposition of 7 unequivocally demonstrated that conversion of 7 to thymine propenal required the intermediacy of a 4'-perbenzoate ester. This perester produced by migration of the 3'-benzoyl blocking group of 7 to the terminal oxygen of its 4'-hydroperoxy moiety would then greatly facilitate heterolytic cleavage of the oxygen-oxygen bond. For stereochemical reasons a similar intramolecular benzoyl migration cannot occur with 8, explaining its lack of reactivity. These results call into question the relevance of the model proposed by Saito et al. to understanding the base propenal pathway in the BLM-catalyzed degradation of DNA. In addition, preparation of a second model of a putative intermediate in the base propenal pathway, [1-[[2-(acetyloxy)acetyl]oxy]-3-oxopropyl]thymine (12), is reported. The detailed kinetics of its decomposition as well as identification of the products accompanying its decomposition are reported. The relevance of these two model systems to the mechanism of degradation of DNA by BLM is discussed.
• Meggers, Eric; Dussy, Adrian; Schaefer, Thomas, Chemistry - A European Journal, 2000, vol. 6, # 3, p. 485 - 492
  作者：Meggers, Eric、Dussy, Adrian、Schaefer, Thomas、Giese, Bernd

  DOI：——

  日期：——