1-[(2R,4S,5R)-4-hydroxy-5-[[(2R,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxymethoxymethyl]oxolan-2-yl]-5-methylpyrimidine-2,4-dione | 130867-66-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 1-[(2R,4S,5R)-4-hydroxy-5-[[(2R,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxymethoxymethyl]oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 130867-66-2
• 化学式: C₂₁H₂₈N₄O₁₀
• 分子量: 496.474
• InChiKey: XYPFIEBNCKGKIL-ZDGDKENJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  176
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1-[(2R,4S,5R)-4-hydroxy-5-[[(2R,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxymethoxymethyl]oxolan-2-yl]-5-methylpyrimidine-2,4-dione 在 吡啶 、 N,N-二异丙基乙胺 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 2.0h， 生成 3-[[(2R,3S,5R)-2-[[(2R,3S,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxymethoxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-[di(propan-2-yl)amino]phosphanyl]oxypropanenitrile
  参考文献：
  名称：

  在预定位置包含（3'5'）-O-CH 2 -O-键的十核苷酸的合成和理化性质

  摘要：

  改性decadeoxynucleotides的合成16-20具有序列d（G 1 PC 2 PG）3的pT 4 X 1 Ť 5 X 2 Ť 6 X 3 Ť 7的pG 8 PC 9的pG 10）和含有一个（X2 = CH 2， X1 = X3 = p，即，16），两个（X1 = X3 = CH 2，X 2 = p，即，17，X2 = X3 = CH 2，X 1 = p，即，18并且x1 = x2 = CH 2，x3 = p。即，19）或三个（X1 = X2 = X3 = CH 2，即，20）-O-CH 2 -O-键可以使用相应的单- ，二-或三（-O-CH来完成2 -O ）3'-O-亚磷酰胺6、10和14作为进入的合成子。16-20与它们的天然互补链的杂交提供了稳定的双链体，通过1D和2D - 1 H-NMR和UV超色性技术对其进行了研究。

  DOI：

  10.1002/recl.19931120104
• 作为产物：
  描述：

  5'-O-dimethoxytrityl-N³-benzoyl-thymidine 在 N-碘代丁二酰亚胺 、 氨 、 水 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙醚 、 1,2-二氯乙烷 为溶剂， 反应 72.0h， 生成 1-[(2R,4S,5R)-4-hydroxy-5-[[(2R,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxymethoxymethyl]oxolan-2-yl]-5-methylpyrimidine-2,4-dione
  参考文献：
  名称：

  Veeneman, G. H.; Marel, G. A. van der; Elst, H. van den, Recueil des Travaux Chimiques des Pays-Bas, 1990, vol. 109, # 7/8, p. 449 - 451

  摘要：

  DOI：

文献信息

• Chemical Synthesis, Crystal Structure and Enzymatic Evaluation of a Dinucleotide Spore Photoproduct Analogue Containing a Formacetal Linker
  作者：Gengjie Lin、Chun-Hsing Chen、Maren Pink、Jingzhi Pu、Lei Li

  DOI：10.1002/chem.201101821

  日期：2011.8.22

  composes the unique SP biochemistry. Despite the fact that the SP was discovered almost 50 years ago, its crystal structure is still unknown and the lack of structural information greatly hinders the study of SP biochemistry. Employing a formacetal linker and organic synthesis, we successfully prepared a dinucleotide SP isostere 5R‐CH2SP, which contains a neutral CH2 moiety between the two thymine residues

  孢子光产物 (SP) 是在细菌内生孢子中发现的唯一 DNA 光损伤产物。它通过金属酶孢子光产物裂解酶 (SPL) 进行光形成和修复，构成了独特的 SP 生物化学。尽管SP已在近50年前被发现，但其晶体结构仍然未知，结构信息的缺乏极大地阻碍了SP生物化学的研究。使用甲缩醛连接剂和有机合成，我们成功地制备了二核苷酸 SP 等排体 5 R -CH 2 SP，其中包含一个中性 CH 2两个胸腺嘧啶残基之间的部分而不是磷酸盐。中性连接子极大地促进了结晶过程，使我们能够在发现半个世纪后获得这种有趣的胸腺嘧啶二聚体的晶体结构。对该 5 R -CH 2 SP 化合物的进一步 ROESY 光谱、DFT 计算和酶促研究证明它具有与 5 R -SP 物种相似的特性，表明所揭示的结构真正反映了自然界中产生的 SP 的结构。
• An efficient approach to the synthesis of thymidine derivatives containing phosphate-isosteric methylene acetal linkages
  作者：G.H. Veeneman、G.A. Van Der Marel、H. Van Den Elst、J.H. Van Boom

  DOI：10.1016/s0040-4020(01)86429-2

  日期：1991.1

  judicious choice of the iodoinium source and protecting groups led to an efficient preparation of thymidine dimers having internucleosidic-3′5′)-methylene bonds. The latter procedure was utilized towards the synthesis, in solution and on a solid support, of DNA-fragments containing one or more T-CH2-T dimers. Further, 5′-O-methylthiomethyl-3′-O-methoxyacetyl-N3-benzoyl-thymidine proved to be a suitable

  探索了碘鎓离子促进了适当保护的3'- O-甲硫基甲基或3' - O-（4-戊烯-1-氧甲基）-胸苷与3' - O-甲氧基乙酰基胸苷的缩合。对碘鎓源和保护基的明智选择导致有效制备具有核苷间3'5'）-亚甲基键的胸苷二聚体。后一种方法用于在溶液中和在固体支持物上合成含有一个或多个T- CH 2 -T二聚体的DNA片段。此外，事实证明5'- O-甲硫基甲基-3'- O-甲氧基乙酰基-N 3-苯甲酰基胸苷是引入5'- O的合适供体。在2,3,4,6-四-O-苄基-D-葡萄糖，苄基N-苄氧羰基-L-丝氨酸和磷酸二苄酯之间的-亚甲基缩醛键。
• Mechanism of UV-Induced Formation of Dewar Lesions in DNA
  作者：Karin Haiser、Benjamin P. Fingerhut、Korbinian Heil、Andreas Glas、Teja T. Herzog、Bert M. Pilles、Wolfgang J. Schreier、Wolfgang Zinth、Regina de Vivie-Riedle、Thomas Carell

  DOI：10.1002/anie.201106231

  日期：2012.1.9

  The importance of a backbone: The mechanism of formation of Dewar lesions (see scheme) has been investigated by using femtosecond IR spectroscopy and ab initio calculations of the exited state. The 4π electrocyclization is rather slow, occurs with an unusual high quantum yield, and—surprisingly—is controlled by the phosphate backbone.

  骨干的重要性：通过使用飞秒红外光谱法和从头算出退出状态，研究了杜瓦损伤的形成机理（参见方案）。4π电环化相当缓慢，发生时具有异常高的量子产率，而且-令人惊讶的是-是受磷酸盐骨架控制的。
• Synthesis and binding properties of pyrimidine oligodeoxynucleoside analogs containing neutral phosphodiester replacements: the formacetal and 3'-thioformacetal internucleoside linkages
  作者：Robert J. Jones、Kuei Ying Lin、John F. Milligan、Shalini Wadwani、Mark D. Matteucci

  DOI：10.1021/jo00063a014

  日期：1993.5

  The replacement of the phosphodiester linkage with neutral, achiral, nuclease resistant entities is desirable for the development of oligodeoxynucleotide (ODN) analogs as therapeutic agents in either the antisense or antigene modes. Described herein is the use of the formacetal and 3'-thioformacetal connections as phosphodiester backbone analogs. Pyrimidine dimer blocks containing these moieties were synthesized and incorporated into ODNs in an alternating array with phosphodiester bonds, such that the ODNs had seven acetal and seven phosphodiester linkages. The binding properties of the resulting chimeric ODNs to single-stranded (ss) RNA and double-stranded (ds) DNA were then determined. ssRNA binding properties were determined by thermal denaturation (Tm) analysis, and the 3'-thioformacetal ODN/ssRNA duplex showed a 5.5-degrees-C enhancement in Tm relative to the control phosphodiester ODN. The triple helix formation properties of the 3'-thioformacetal and formacetal ODNs were determined by footprint and restriction enzyme inhibition assays. The 3'-thioformacetal ODN binds to dsDNA with an affinity slightly less than the control ODN. The high affinity and specificity of an ODN containing the 3'-thioformacetal for the ssRNA target and dsDNA target suggest that this linkage is a promising analog for both antisense and triple helix therapeutic applications.
• Veeneman, G. H.; Marel, G. A. van der; Elst, H. van den, Recueil des Travaux Chimiques des Pays-Bas, 1990, vol. 109, # 7/8, p. 449 - 451
  作者：Veeneman, G. H.、Marel, G. A. van der、Elst, H. van den、Boom, J. H. van

  DOI：——

  日期：——