1,5-Anhydro-2,3-dideoxy2-(thymin-1-yl)-D-arabinohexitol | 149312-05-0

• 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: 1,5-Anhydro-2,3-dideoxy2-(thymin-1-yl)-D-arabinohexitol
• 英文别名: 1,5-anhydro-2,3-dideoxy-2-(thymin-1-yl)-D-arabino-hexitol；1-[(3S,5S,6R)-5-hydroxy-6-(hydroxymethyl)tetrahydropyran-3-yl]-5-methyl-pyrimidine-2,4-dione；1-[(3S,5S,6R)-5-hydroxy-6-(hydroxymethyl)oxan-3-yl]-5-methylpyrimidine-2,4-dione
• CAS: 149312-05-0
• 化学式: C₁₁H₁₆N₂O₅
• 分子量: 256.258
• InChiKey: GPMFEPCZMZRMRA-XHNCKOQMSA-N

物化性质

• 密度：
  1.388±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 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：

  1,5-Anhydro-2,3-dideoxy2-(thymin-1-yl)-D-arabinohexitol 在 吡啶 、 4-二甲氨基吡啶 作用下， 反应 48.0h， 生成 Succinic acid mono-[(2R,3S,5S)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-pyran-3-yl] ester
  参考文献：
  名称：

  1′, 5′ -Anhydrohexitol Oligonucleotides: Synthesis, Base Pairing and Recognition by Regular Oligodeoxyribonucleotides and Oligoribonucleotides

  摘要：

  AbstractOligonucleotides constructed of 1′, 5′‐anhydrohexitol nucleoside building blocks (hexitol nucleic acids, HNA) are completely stable towards 3′‐exonuclease and form very stable self‐complementary duplexes as well as sequence‐selective stable duplexes with the natural DNA and RNA. Triple‐helix formation has also been observed. These hybridisation characteristics are highly dependent on the base sequence and the experimental conditions. When using a phosphate buffer containing 0.1M NaCl, a homopurine HNA dodecamer gives a δTm of +3.0 °C/ base pair with RNA as complement. These oligomers may therefore be of considerable interest as antisense constructs.

  DOI：

  10.1002/chem.19970030118
• 作为产物：
  描述：

  N-3-benzoylthymine 在 palladium dihydroxide sodium hydroxide 、 sodium hydride 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 1,4-二氧六环 、 吡啶 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 环己烯 为溶剂， 反应 48.0h， 生成 1,5-Anhydro-2,3-dideoxy2-(thymin-1-yl)-D-arabinohexitol
  参考文献：
  名称：

  Synthesis and Antiviral Activity of the α-Analogues of 1,5-Anhydrohexitol Nucleosides (1,5-Anhydro-2,3-dideoxy-d-ribohexitol Nucleosides)

  摘要：

  1,5-Anhydro-2,3-dideoxy-D-ribohexitol nucleosides were synthesized starting from 4,6-di-O-benzyl-1,5-di-O-pivaloyl-3-deoxy-D-glucitol using a ring closure procedure. The target nucleoside adopts a C-4(1) conformation as also demonstrated for the corresponding 1,5-anhydrohexitol nucleosides with beta-configuration of the base-substituted carbon atom. The cytosine congener demonstrated a moderate but selective activity against Herpes simplex virus types I and 2.

  DOI：

  10.1021/jo961982m

文献信息

• Synthesis and antiherpes virus activity of 1,5-anhydrohexitol nucleosides
  作者：Ilse Verheggen、Arthur Van Aerschot、Suzanne Toppet、Robert Snoeck、Gerard Janssen、Jan Balzarini、Erik De Clercq、Piet Herdewijn

  DOI：10.1021/jm00066a013

  日期：1993.7

  of 1,5-anhydrohexitol nucleosides is described. These nucleoside analogues were obtained by alkylation of the heterocyclic bases with the tosylate 10 or by alkylation of the bases with the alcohol 12 under Mitsunobu conditions. The compounds were evaluated for antiviral and cytostatic activity. Highly selective activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) was noted for 1,5-anhydro-2

  描述了1，5-脱水己糖醇核苷的合成。这些核苷类似物是通过在甲苯磺酰脲（Mitsunobu）条件下用甲苯磺酸酯10使杂环碱烷基化或通过用醇12使碱烷基化而获得的。评价化合物的抗病毒和细胞抑制活性。对于1,5-脱水-2,3-二脱氧-2-（5-碘尿嘧啶-1-基）-D注意到对1型单纯疱疹病毒（HSV-1）和2型单纯疱疹病毒（HSV-2）具有高度选择性。 -阿拉伯糖基己糖醇4b的浓度为0.07微克/毫升。此活性必须取决于病毒编码的胸苷激酶（TK）的特定磷酸化作用，因为化合物4b对HSV-1的TK缺陷型突变体无活性。相应的胞嘧啶4c和鸟嘌呤4e类似物对HSV-1，HSV-2和其他疱疹病毒（例如巨细胞病毒，水痘-带状疱疹病毒）浓度远低于细胞毒性阈值（分别为2和20微克/ mL）。在这些浓度下，化合物4c和4e还被证明对人类T细胞（即MT-4，CEM，MOLT-4）的生长具有抑制作用。
• Antiviral tetrahydropyrans
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP0608809A1

  公开（公告）日：1994-08-03

  Compounds of the formula including pharmaceutically acceptable salts are useful as antiviral agents.

  式中的化合物包括药学上可接受的盐类可用作抗病毒剂。
• Hexitol Nucleic Acids (HNA): Synthesis and Properties
  作者：B. De Bouvere、L. Kerreinans、C. Hendrix、H. De Winter、G. Schepers、A. Van Aerschot、P. Herdewijn

  DOI：10.1080/07328319708006119

  日期：1997.7

  While improved alkylation procedures have been worked out for the coupling of purine bases to the anhydrohexitol ring using sulphonate activating groups on the anhydrohexitol ring, the Mitsunobu reaction seems to be the method of choice for synthesis of the pyrimidine analogues. In a mixed sequence context, the anhydrohexitol oligonucleotides still display strong and very selective basepairing properties, with a strong preference for RNA as the complement.
• Synthesis of 1,5-Anhydrohexitol Nucleosides as Mimics of AZT, D4T and DDC
  作者：Ilse Verheggen、Arthur Van Aerschot、Jef Rozenski、Gerard Janssen、Erik De Clercq、Piet Herdewijn

  DOI：10.1080/07328319608002387

  日期：1996.1

  1,5-Anhydrohexitol congeners of AZT, D4T and DDC were synthesized. These compounds did not show anti-HIV activity.
• 1,5-ANHYDROHEXITOL NUCLEOSIDE ANALOGUES AND PHARMACEUTICAL USE THEREOF
  申请人：Stichting REGA V.Z.W.

  公开号：EP0646125B1

  公开（公告）日：1998-05-27