5-O-(4,4-二甲氧基三苯基甲基)-胸苷-3-O-丁二酸 | 74405-40-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 中文名称: 5-O-(4,4-二甲氧基三苯基甲基)-胸苷-3-O-丁二酸
• 中文别名: 5'-O-(4,4'-二甲氧基三苯基甲基)-胸苷-3'-O-丁二酸；5'-O-(4,4'-二甲氧基三苯基甲基)-胸甙-3'-O-丁二酸
• 英文名称: 5'-dimethoxytritylthymidine-3'-O-succinyl hemiester
• 英文别名: 5'-O-(4,4'-dimethoxytrityl)thymidine hemisuccinic acid ester；5’-O-(4,4’-dimethoxytriphenylmethyl)thymidine-3’-O-succinate；5'-O-4,4'-dimethoxytrityl-thymidine-3'-O-succinate；5'-O-(4,4'-dimethoxytrityl)-3'-O-succinyl-thymidine；5'-O-(4,4'-Dimethoxytrityl)-thymidine-3'-O-succinic acid；4-[(2R,3S,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-4-oxobutanoic acid
• CAS: 74405-40-6
• 化学式: C₃₅H₃₆N₂O₁₀
• 分子量: 644.678
• InChiKey: ZGIVSINMMBIEBQ-FRXPANAUSA-N

物化性质

• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  47
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  150
• 氢给体数：
  2
• 氢受体数：
  10

安全信息

• 储存条件：
  存储条件：室温、密封、干燥

反应信息

• 作为反应物：
  描述：

  5-O-(4,4-二甲氧基三苯基甲基)-胸苷-3-O-丁二酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.47h， 生成 3'-O-succinyl-thymidine
  参考文献：
  名称：

  2-吡啶基-N-（2,4-二氟苄基）氨基乙基作为热控制工具，用于保护羧酸

  摘要：

  扩展了羧酸的热不稳定保护基策略。热敏酯易于使用已知方法制备，并且研究了它们在中性条件下的稳定性。证明了仅由温度引发的对不同羧酸的有效热解脱保护，并且还提出了在正交保护策略中热解保护基与酸性和碱性保护基的相容性。这项研究表明，在酸的pKa和其保护良好的部分的脱保护率之间存在有趣的相关性。

  DOI：

  10.1021/acs.orglett.6b01475
• 作为产物：
  描述：

  丁二酸 、 保护胸苷 在 三乙胺 作用下， 以 甲苯 、 二氯甲烷 为溶剂， 反应 5.0h， 以96%的产率得到5-O-(4,4-二甲氧基三苯基甲基)-胸苷-3-O-丁二酸
  参考文献：
  名称：

  Liquid-Phase RNA Synthesis by Using Alkyl-Chain-Soluble Support

  摘要：

  AbstractRecent progress in the RNA therapeutics has increased demand for the synthesis of large quantities of oligoribonucleotides. The assembly of RNA oligomers relies mainly on solid‐phase approaches. These allow rapid product purification and the ability to drive a target reaction to completion through the use of excess reagents. Despite the known advantages of solid‐phase synthesis, some issues in the process remain to be addressed, such as low and limited scale, reagent accessibility, and the use of a very large excess of reagents. Herein, we report a highly efficient and practical method of liquid‐phase synthesis of RNA oligomers by using alkyl‐chain‐soluble support. We demonstrate the utility of the liquid‐phase method through 21‐mer RNA synthesis on a gram scale.

  DOI：

  10.1002/chem.201300655

文献信息

• Solid Phase Synthesis of Oligodeoxyribonucleotides Utilizing the Phenylthio Group as a Phosphate Protecting Group
  作者：Jun-ichi Matsuzaki、Kyoko Kohno、Shin-ichiro Tahara、Mitsuo Sekine、Tsujiaki Hata

  DOI：10.1246/bcsj.60.1407

  日期：1987.4

  reaction from deoxyguanosine and used for preparation of the building blocks of deoxyguanosine required for the polymer support synthesis. Two kinds of polymer supports, i.e., 1% cross-linked polystyrene and controlled pore glass were chosen. The latter was employed for the synthesis of dodecadeoxyribonucleotides by using an automated DNA synthesizer.

  利用苯硫基作为磷酸保护基团的寡聚脱氧核糖核苷酸合成应用于固相法。脱氧鸟苷和脱氧腺苷的碱基残基分别用双（异丁酰氧基）亚乙基（Bibe）和邻苯二甲酰基保护，以避免碱基修饰和脱嘌呤。N2-异丁酰-N1,N2-双(异丁酰氧基)亚乙基脱氧鸟苷的关键合成中间体通过脱氧鸟苷的四步反应以高收率制备，用于制备聚合物载体合成所需的脱氧鸟苷结构单元。选择了两种聚合物载体，即1%的交联聚苯乙烯和可控孔玻璃。后者用于通过使用自动 DNA 合成仪合成十二氧核糖核苷酸。
• Solid-Phase Synthesis of Oligonucleotide Glycoconjugates Bearing Three Different Glycosyl Groups:  Orthogonally Protected Bis(hydroxymethyl)-<i>N,N</i><i>‘</i>-bis(3-hydroxypropyl)malondiamide Phosphoramidite as Key Building Block
  作者：Johanna Katajisto、Petri Heinonen、Harri Lönnberg

  DOI：10.1021/jo048984o

  日期：2004.10.1

  O‘-(methoxymethylene)bis(hydroxymethyl)malonate (3) was observed to undergo a stepwise aminolysis when treated with 3-aminopropanol. This allowed convenient preparation of bis(hydroxymethyl)-N,N‘-bis(3-hydroxypropyl)malondiamide bearing orthogonal levulinyl (Lev) and tert-butyldiphenylsilyl (TBDPS) protections at the two N-hydroxypropyl groups (8). One of the hydroxylmethyl functions was then protected with a 4,4‘-dimethoxytrityl

  二ø，Ö “ - （甲氧基亚甲基）双（羟甲基）丙二酸二乙酯（3）中观察到当与3-氨基丙醇处理经过逐步氨解。这允许方便地制备在两个N-羟丙基上带有正交乙酰丙酰基（Lev）和叔丁基二苯基甲硅烷基（TBDPS）保护的双（羟甲基）-N，N'-双（3-羟丙基）丙二酰胺（8）。然后将一个羟甲基官能团用4,4'-二甲氧基三苯甲基（DMTr）基团进行保护，然后将另一个进行磷酸化以获得甲基N，N-二异丙基亚氨基膦酸酯（1）。该结构单元用于合成带有三个不同糖单元的寡核苷酸糖缀合物（25和26）。在含有1的序列的常规亚磷酰胺链组装后，除去5'-末端DMTr基团，并偶联合适的糖基6- O-亚磷酰胺基。按Lev和TBDPS的顺序除去支链单元的其余保护基，并使暴露的羟基官能团与所需的糖基6- O-亚磷酰胺基依次反应。通过常规的氨解作用实现了共轭物从载体上的整体脱保护和裂解。
• Solid-Phase Synthesis of (Poly)phosphorylated Nucleosides and Conjugates
  作者：Viktoria Caroline Tonn、Chris Meier

  DOI：10.1002/chem.201101291

  日期：2011.8.22

  Succinyl‐cycloSal‐phosphate triesters of ribo‐ and 2′‐deoxyribonucleosides were attached to aminomethyl polystyrene as an insoluble solid support and reacted with phosphate‐containing nucleophiles yielding nucleoside di‐ and triphosphates, nucleoside diphosphate sugars, and dinucleoside polyphosphates in high purity after cleavage from the solid support. Here, reactive cycloSal‐phosphate triesters were

  核糖基和2'-脱氧核糖核苷的琥珀酰环Sal-磷酸三酯以不溶性固体支持物的形式连接到氨甲基聚苯乙烯上，并与含磷酸的亲核试剂反应，生成高纯度的核苷二和三磷酸核苷，核苷二磷酸糖和二核苷多磷酸。从固体支持物上裂解。在这里，反应性的环状Sal-磷酸盐三酯用作固定试剂，从而为有效合成磷酸化生物分子和磷酸盐桥联的生物共轭物提供了一种普遍适用的方法。
• High yield detritylation of surface-attached nucleosides with photoacid generated in an overlying solid film: roles of translational diffusion and scavenging
  作者：Peter B. Garland、Pawel J. Serafinowski

  DOI：10.1039/b813319k

  日期：——

  Conventional solid-phase oligonucleotide synthesis overcomes the reversibility of acid-dependent detritylation by washing away the released dimethoxytrityl cations (DMT+) with acid. This option is unavailable if the acid is photogenerated in an overlying solid film, as in the photolithographic fabrication of oligonucleotide arrays on planar surfaces. To overcome the resulting reversibility problem we developed methods of achieving ≥98% detritylation of glass-attached 5′-O-DMT-thymidine, a model for 5′-O-DMT-protected oligonucleotides, by the photogeneration of trichloroacetic acid in a solid film. Enhanced intrafilm diffusion, insufficient to degrade the photolithographic resolution but enabling DMT+ to move from its plane of release into the overlying photoacid-generating film, increased detritylation from ≤30% to ≥98%. Inclusion of an intrafilm carbocation scavenger such as a triarylsilane hydride converted the detritylation into a time-dependent irreversible process proceeding to ≥99% detritylation within 60 s following brief photoacid generation. Light sensitivity is high, exceeding direct photodeprotection methods by 15–100 fold.

  传统的固相寡核苷酸合成方法是用酸洗掉释放出的二甲氧基三苯甲基阳离子（DMT+），从而克服了酸依赖性脱苯作用的可逆性。如果酸是在上覆固体薄膜中光照生成的，就无法使用这种方法，例如在平面上光刻制造寡核苷酸阵列。为了克服由此产生的可逆性问题，我们开发了一种方法，通过在固体薄膜中光生成三氯乙酸，实现玻璃附着的 5′-O-DMT 胸苷（5′-O-DMT 保护寡核苷酸的模型）≥98% 的脱苯甲基化。膜内扩散的增强不足以降低光刻分辨率，但却能使 DMT+ 从其释放平面移动到上覆的光酸生成膜中，从而将脱盐率从≤30%提高到≥98%。加入膜内碳位清除剂（如三芳基硅烷氢化物）后，在短暂的光酸生成后 60 秒内，脱苯甲酰化转化为与时间相关的不可逆过程，脱苯甲酰化率≥99%。光敏感性很高，比直接光防护方法高出 15-100 倍。
• Linker phosphoramidite reagents for oligonucleotide synthesis on underivatized solid-phase supports
  作者：Richard T Pon、Shuyuan Yu

  DOI：10.1016/s0040-4039(01)01996-7

  日期：2001.12

  Linker phosphoramidite reagents containing a protected nucleoside with a cleavable 3′-ester linkage to either succinic acid, diglycolic acid, or hydroquinone-O,O′-diacetic acid (Q-Linker) allow the 3′-terminal nucleoside of an oligonucleotide sequence to be attached to underivatized ‘Universal’ amino or hydroxyl supports. After solid-phase oligonucleotide synthesis, treatment with NH4OH cleaves the

  含有具有可切割的3'-酯键要么琥珀酸，二甘醇酸，或hydroquinone-一个受保护的核苷连接体亚磷酰胺试剂ø，ö ' -二乙酸（Q-接头）允许的寡核苷酸序列与3'-末端核苷附着在未衍生的“通用”氨基或羟基载体上。固相寡核苷酸合成后，用NH 4 OH处理可裂解3'-酯与载体的连接，并产生仅具有3'-OH末端的寡核苷酸。无需更改现有的亚磷酰胺合成周期，裂解或脱保护方法。