5'-O-(4,4'-dimethoxytrityl)-3'-O-(2-thio-1,3,2-dithiaphospholan-2-yl)thymidine | 145498-71-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 5'-O-(4,4'-dimethoxytrityl)-3'-O-(2-thio-1,3,2-dithiaphospholan-2-yl)thymidine
• 英文别名: 1-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-[(2-sulfanylidene-1,3,2lambda5-dithiaphospholan-2-yl)oxy]oxolan-2-yl]-5-methylpyrimidine-2,4-dione；1-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-[(2-sulfanylidene-1,3,2λ5-dithiaphospholan-2-yl)oxy]oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 145498-71-1
• 化学式: C₃₃H₃₅N₂O₇PS₃
• 分子量: 698.822
• InChiKey: LOSVICICVRJIEC-FRXPANAUSA-N

物化性质

• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  46
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  178
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  5'-O-(4,4'-dimethoxytrityl)-3'-O-(2-thio-1,3,2-dithiaphospholan-2-yl)thymidine 在 1,2-环氧丁烷 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 胸苷酰(3'->5')胸苷铵盐
  参考文献：
  名称：

  Synthesis of Oligo(Deoxyribonucleoside Phosphorodithioate)s by the Dithiaphospholane Approach

  摘要：

  A novel method of synthesis of oligo(deoxyribonucleoside phosphorodithioate)s (S-2-ODNs), based on the ring-opening condensation of nucleoside 3'-0-(2-thiono-1,3,2-dithiaphospholane)s with 5'-O-deprotected nucleosi(ti)des in the presence of a strong organic base such as DBU, is presented. The process has been adapted to the requirements of automated solid-phase oligonucleotide synthesis with a relatively short condensation step (5 min) and reasonable step-yield(>95%). N-Methylpyrrolidin-2-ylidenyl (Pya) was found to be the group of choice for the protection of reactive aminofunctions of nucleobases in nucleotide substrates. Sarcosine-containing linker (LCA CPG SAR) was employed due to its known resistance to cleavage by DBU. Several medium-size S-2-ODNs were prepared by this approach. Their identity and purity was confirmed by means of P-31 NMR, gel electrophoresis, and mass spectrometry. It has been demonstrated that, contrary to a recent report, S-2-ODNs are not degraded by DNaseI.

  DOI：

  10.1021/jo00126a060
• 作为产物：
  描述：

  保护胸苷 在 三甲基氯硅烷 、 sulfur 作用下， 以 四氢呋喃 为溶剂， 生成 5'-O-(4,4'-dimethoxytrityl)-3'-O-(2-thio-1,3,2-dithiaphospholan-2-yl)thymidine
  参考文献：
  名称：

  Synthesis of P-Fluorodithioacids of Phosphorus and Their Synthetic Application

  摘要：

  Oligonucleotides containing 3'-S-P(S) and 5-S-P(S) fragments in the deoxy-series are available only by tedious multistep procedures. We have developed a novel and efficient methodology based on ring opening of anhydronucleosides by phosphorus dithioacids. This approach allows efficient synthesis of modified dinucleotides of the ribo-series.

  DOI：

  10.1080/10426500212294

文献信息

• The synthesis of di- and oligo-nucleotides containing a phosphorodithioate internucleotide linkage with one of the sulfur atoms in a 5′-bridging position
  作者：Magdalena Olesiak、Wojciech J. Stec、Andrzej Okruszek

  DOI：10.1039/b901791g

  日期：——

  phosphorodithioate linkage is described, wherein one of the sulfur atoms occupies a 5′-bridging position. Representative dinucleotides possessing such a bond were synthesized by S-alkylation of nucleoside-3′-O-phosphorodithioates with 5′-halogeno-5′-deoxy-nucleosides. A fully protected dithymidylate containing internucleotide 5′-S-phosphorodithioate linkage was converted into a 3′-O-phosphoramidite

  描述了一种新型的核苷酸间二硫代磷酸酯键，其中一个硫原子占据5'-桥接位置。具有这种键的代表性二核苷酸是通过将核苷-3'- O-二硫代磷酸酯与5'-卤素-5'-脱氧核苷进行S-烷基化而合成的。将含有核苷酸间5'- S-二硫代磷酸酯键的完全保护的二胸苷酸转化为3'- O-亚磷酰胺衍生物，并用于将修饰的二核苷酸引入寡核苷酸序列的预定位置。5'- S发现二核苷酸类似物中的β-二硫代磷酸酯键抗蛇毒PDE和核酸酶P1的核酸降解。然而，在小牛脾PDE处理下，观察到5'- S-二硫代磷酸二硫代二胸苷类似物的非对映异构体的P-立体选择性降解。在碘的存在下碘溶液容易降解新的5'- S-磷酸二硫酯键。水。还发现含有单个5'- S-磷酸二硫酯键的寡胸苷酸酯与其互补序列形成弱得多的双链体。
• The synthesis of Di- and oligo(deoxyribonucleoside phosphorodithioates) by dithiaphospholane method
  作者：Andrzej Okruszek、Agnieszka Sierzchala、Marek Sochacki、Wojciech J. Stec

  DOI：10.1016/s0040-4039(00)60831-6

  日期：——

  Four dinucleoside phosphorodithioates: TPS2T (1a), d(CPS2C) (1b), dAPS2A} and d(GPS2G) (1d) were synthesized by reacting solid support-bound nucleosides with nucleoside 5′-O-DMT-3′-O-(2-thio-1,3,2-dithiaphospholanes) (2a-d) in the presence of DBU. Pyrimidine pentamers, free from phosphorothioate contamination, were obtained by this method.

  通过使固相结合的核苷与核苷5'反应，合成了4种二核苷二硫代磷酸酯：T PS2 T（1a），d（C PS2 C）（1b），d A PS2 A}和d（G PS2 G）（1d）。在DBU存在下，-O-DMT-3'-O-（2-硫代-1,3,2-二硫代膦酸酯）（2a-d）。通过该方法获得了没有硫代磷酸酯污染的嘧啶五聚体。
• New efficient synthesis of phosphonofluorodithioates ROP(S)(S−)F and their structural analogues
  作者：Izabela Tworowska、Wojciech Dąbkowski

  DOI：10.1039/a807029f

  日期：——

  The title compounds 3 are formed in very high yield from a one-pot sequential reaction of 1,3,2-dithiaphospholane PIII derivatives 1, which are transformed into the corresponding PIV compounds 2 by addition of elemental sulfur and finally into fluoridodithioates 3 by TBAF.

  标题化合物3通过由1,3,2-二硫代膦烷PIII衍生物1进行的单锅连续反应，以非常高的产率形成，这些衍生物通过加成元素硫转化为相应的PIV化合物2，最终通过四丁基氟化铵（TBAF）转化为氟化二硫代盐3。
• Efficient One-Pot Synthesis of 2‘-Deoxyribonucleoside 3‘-<i>O</i>- and 5‘-<i>O</i>-Phosphorodithioates
  作者：Andrzej Okruszek、Magdalena Olesiak、Danuta Krajewska、Wojciech J. Stec

  DOI：10.1021/jo961801g

  日期：1997.4.1
• Synthesis of Oligo(Deoxyribonucleoside Phosphorodithioate)s by the Dithiaphospholane Approach
  作者：Andrzej Okruszek、Agnieszka Sierzcha-la、Karen L. Fearon、Wojciech J. Stec

  DOI：10.1021/jo00126a060

  日期：1995.10

  A novel method of synthesis of oligo(deoxyribonucleoside phosphorodithioate)s (S-2-ODNs), based on the ring-opening condensation of nucleoside 3'-0-(2-thiono-1,3,2-dithiaphospholane)s with 5'-O-deprotected nucleosi(ti)des in the presence of a strong organic base such as DBU, is presented. The process has been adapted to the requirements of automated solid-phase oligonucleotide synthesis with a relatively short condensation step (5 min) and reasonable step-yield(>95%). N-Methylpyrrolidin-2-ylidenyl (Pya) was found to be the group of choice for the protection of reactive aminofunctions of nucleobases in nucleotide substrates. Sarcosine-containing linker (LCA CPG SAR) was employed due to its known resistance to cleavage by DBU. Several medium-size S-2-ODNs were prepared by this approach. Their identity and purity was confirmed by means of P-31 NMR, gel electrophoresis, and mass spectrometry. It has been demonstrated that, contrary to a recent report, S-2-ODNs are not degraded by DNaseI.