3',5'-di-O-acetyl-α-thymidine | 153737-54-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 3',5'-di-O-acetyl-α-thymidine
• 英文别名: 3'-5'-di-O-acetyl-α-D-thymidine；1-(O³,O⁵-diacetyl-α-D-erythro-2-deoxy-pentofuranosyl)-5-methyl-1H-pyrimidine-2,4-dione；((2R,3S,5S)-3-acetoxy-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl acetate；[(2R,3S,5S)-3-acetyloxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl acetate
• CAS: 153737-54-3
• 化学式: C₁₄H₁₈N₂O₇
• 分子量: 326.306
• InChiKey: RGVBNBFNSBMXID-TUAOUCFPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3',5'-di-O-acetyl-α-thymidine 在 劳森试剂 、 吡啶 、 甲醇 、 sodium azide 、 氨 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.17h， 生成 5'-amino-5'-deoxy-4-thio-α-D-thymidine
  参考文献：
  名称：

  Synthesis and inhibitory activity of thymidine analogues targeting Mycobacterium tuberculosis thymidine monophosphate kinase

  摘要：

  We report on Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt) inhibitory activities of a series of new 3'- and 5'-modified thymidine analogues including alpha- and beta-derivatives. In addition, several analogues were synthesized in which the 4-oxygen was replaced by a more lipophilic sulfur atom to probe the influence of this modification on TMPKmt inhibitory activity. Several compounds showed an inhibitory potency in the low micromolar range, with the 5'-arylthiourea 4-thio-alpha-thymidine analogue being the most active one (K(i) = 0.17 mu M). This compound was capable of inhibiting mycobacteria growth at a concentration of 25 mu g/mL. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.021
• 作为产物：
  描述：

  3,5-双-O-乙酰胸苷 在 硫酸 、 乙酸酐 作用下， 以 乙腈 为溶剂， 反应 0.67h， 生成 3',5'-di-O-acetyl-α-thymidine
  参考文献：
  名称：

  A mild procedure for the anomerization of 2′-deoxynucleosides

  摘要：

  Addition of a catalyst containing sulfuric acid and acetic anhydride to a solution of 3',5'-di-O-acetylthymidine in acetonitrile at room temperature, results in the almost instantaneous production of an equilibrium mixture of alpha- and beta-anomers. Under certain conditions with increasing time, substantial quantities of a diasterioisomeric mixture of fully acetylated open-chain nucleosides are formed.

  DOI：

  10.1016/s0040-4039(00)61700-8

文献信息

• Rational Design of 5‘-Thiourea-Substituted α-Thymidine Analogues as Thymidine Monophosphate Kinase Inhibitors Capable of Inhibiting Mycobacterial Growth
  作者：Ineke Van Daele、Hélène Munier-Lehmann、Matheus Froeyen、Jan Balzarini、Serge Van Calenbergh

  DOI：10.1021/jm0706158

  日期：2007.11.1

  Recently, thymidine monophosphate kinase (TMPK) emerged as an attractive target for developing inhibitors of Mycobacterium tuberculosis growth. The elucidation of the X-ray structure of TMPK of M. tuberculosis (TMPKmt), as well as the structure of an earlier serendipitously discovered dimeric thymidine inhibitor, laid the foundation for the design of potent and selective TMPKmt inhibitors reported here. Several hits identified within a series of 3'-C-branched thiourea-substituted P-thymidine derivatives inspired us to construct a set of 5'-thiourea-substituted a-thymidine derivatives characterized by a similar relative orientation of the thymine and arylthiourea moieties. (x-Thymidine derivative 15, featuring a (3-trifluoromethyl-4-chlorophenyl)thiourea moiety, has a K-i of 0.6 mu M and a selectivity index of 600 versus human TMPK. Moreover, it represents the first TMPK inhibitor showing good inhibitory activity on growing M. bovis (MIC99 = 20 mu g/mL) and M. tuberculosis (MIC50 = 6.25 mu g/mL) strains.
• Targeting Chimeric alpha,beta-Oligonucleotides to the Flanks of a Stem in DNA. The Enhanced Effect of an Intercalator.
  作者：Ahmed F. Khattab、Erik B. Pedersen、Hans Vallberg

  DOI：10.3891/acta.chem.scand.51-1245

  日期：——

  3'-O-(4,4'-Dimethoxytrityl)-5-methyl-N-4-(1-pyrenylmethyl)-alpha-cytidine (7) was prepared from alpha-thymidine by the reaction of 1-pyrenylmethylamine with an appropriate protected 4-(1,2,4-triazolyl)-alpha-thymidine derivative 5. 3'-O-(4,4'-Dimethoxytrityl-alpha-thymidine (9) was synthesized by successive, 5'-O-acetylation, 3'-O-tritylation and 5'-O-deacetylation of alpha-thymidine. Phosphitylation of the 5'-hydroxy group of 7 and 9 afforded the amidites 8 and 10. These amidites and commercial beta-2'-deoxyribonucleoside-3'-phosphoramidites were used in the synthesis of chimeric ODNs with 3'-3' and 5'-5' internucleotidic phosphodiester linkages. The stability of a DNA three way junction (TWJ) was studied by observing the thermal melting when a DNA was targeted to the flanks of a hairpin. The TWJ was considerably stabilized when 7 and 9 were inserted into the junction region. The corresponding duplex obtained by deleting the hairpin, however, was destabilized on insertion of 7 and 9.
• Synthesis and inhibitory activity of thymidine analogues targeting Mycobacterium tuberculosis thymidine monophosphate kinase
  作者：Sara Van Poecke、Hélène Munier-Lehmann、Olivier Helynck、Matheus Froeyen、Serge Van Calenbergh

  DOI：10.1016/j.bmc.2011.10.021

  日期：2011.12

  We report on Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt) inhibitory activities of a series of new 3'- and 5'-modified thymidine analogues including alpha- and beta-derivatives. In addition, several analogues were synthesized in which the 4-oxygen was replaced by a more lipophilic sulfur atom to probe the influence of this modification on TMPKmt inhibitory activity. Several compounds showed an inhibitory potency in the low micromolar range, with the 5'-arylthiourea 4-thio-alpha-thymidine analogue being the most active one (K(i) = 0.17 mu M). This compound was capable of inhibiting mycobacteria growth at a concentration of 25 mu g/mL. (C) 2011 Elsevier Ltd. All rights reserved.
• A mild procedure for the anomerization of 2′-deoxynucleosides
  作者：David I. Ward、Steven M. Jeffs、Paul L. Coe、Richard T. Walker

  DOI：10.1016/s0040-4039(00)61700-8

  日期：1993.10

  Addition of a catalyst containing sulfuric acid and acetic anhydride to a solution of 3',5'-di-O-acetylthymidine in acetonitrile at room temperature, results in the almost instantaneous production of an equilibrium mixture of alpha- and beta-anomers. Under certain conditions with increasing time, substantial quantities of a diasterioisomeric mixture of fully acetylated open-chain nucleosides are formed.