[5'-O-(4,4'-dimethoxytrityl)thymidine-3'-yl]-(N,N'-diisopropyl)methylphosphoramidite | 84416-85-3

• 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)thymidine-3'-yl]-(N,N'-diisopropyl)methylphosphoramidite
• 英文别名: 5'-O-(4,4'-dimethoxytrityl)thymidine 3'-(O-methyl-N,N-diisopropylphosphoramidite)；5'-dimethoxytritylthymidine(methoxydiisopropylamino)phosphite；5'-O-(dimethoxytrityl)thymidine 3'-O-(diisopropylaminomethoxyphosphine)；5'-O-(p,p'-Dimethoxytrityl)thymidine 3'-(methyl N,N-diisopropylphosphoroamidite)；N,N-diisopropylamino-3'-O<5'-O-(dimethoxytrityl)thimidine>methoxyphosphine；(R_P,S_P)-5'-O-(dimethoxytrityl)-3'-O-<(diisopropylamino)methoxyphosphino>-2'-deoxythymidine；5’-dimethoxytrityl 2’-deoxythymidine 3’-O-methyl-N,N-diisopropylphosphoramidite；5’-O-DMT-2’-deoxythymidine 3’-O-methyl N,N-diisopropylaminophosphoramidite；5'-O-dimethoxytritylthymidine 3'-methyl-N,N-diisopropylphosphoramidite；5'-O-DMT-thymidine-3'-methyl-N,N-diisopropylphosphoramide；1-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-[[di(propan-2-yl)amino]-methoxyphosphanyl]oxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 84416-85-3
• 化学式: C₃₈H₄₈N₃O₈P
• 分子量: 705.788
• InChiKey: VJITXURZFBABOD-BJFMWMJRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  50
• 可旋转键数：
  15
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  [5'-O-(4,4'-dimethoxytrityl)thymidine-3'-yl]-(N,N'-diisopropyl)methylphosphoramidite 在 四氮唑 、 2-过氧化丁酮 、 氨 、 溶剂黄146 作用下， 以 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 12.58h， 生成 胸苷酰(3'->5')胸苷铵盐
  参考文献：
  名称：

  Synthesis of novel cationic spermine-conjugated phosphotriester oligonucleotide for improvement of cell membrane permeability

  摘要：

  A spermine-conjugated ethyl phosphotriester oligonucleotide was obtained by solid-phase synthesis based on phosphoramidite chemistry. The ethyl phosphotriester linkage was robust to exonuclease digestion and stable in fetal bovine serum. Cell membrane permeability of the spermine-conjugated ethyl phosphotriester oligonucleotide was studied by fluorescence experiments. The effective cell penetrating potency of the spermine-conjugated ethyl phosphotriester oligonucleotide was determined by confocal laser scanning microscopy and measurement of intracellular fluorescence intensity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.06.071
• 作为产物：
  描述：

  保护胸苷 在 四氮唑 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 [5'-O-(4,4'-dimethoxytrityl)thymidine-3'-yl]-(N,N'-diisopropyl)methylphosphoramidite
  参考文献：
  名称：

  Synthesis of novel cationic spermine-conjugated phosphotriester oligonucleotide for improvement of cell membrane permeability

  摘要：

  A spermine-conjugated ethyl phosphotriester oligonucleotide was obtained by solid-phase synthesis based on phosphoramidite chemistry. The ethyl phosphotriester linkage was robust to exonuclease digestion and stable in fetal bovine serum. Cell membrane permeability of the spermine-conjugated ethyl phosphotriester oligonucleotide was studied by fluorescence experiments. The effective cell penetrating potency of the spermine-conjugated ethyl phosphotriester oligonucleotide was determined by confocal laser scanning microscopy and measurement of intracellular fluorescence intensity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.06.071

文献信息

• [EN] TRICYCLIC NUCLEIC ACID ANALOGS<br/>[FR] ANALOGUES TRICYCLIQUES D'ACIDE NUCLÉIQUE
  申请人：ISIS PHARMACEUTICALS INC

  公开号：WO2013154798A1

  公开（公告）日：2013-10-17

  The present disclosure provides tricyclic nucleosides and oligomeric compounds prepared therefrom. The tricyclic nucleosides each have a tricyclic ribosyl sugar moiety wherein a bridge between the 2' and 4' ribosyl ring carbon atoms further comprises a fused carbocyclic or heterocyclic ring. The tricyclic nucleosides are expected to be useful for enhancing properties of oligomeric compounds including for example binding affinity and nuclease resistance.

  本公开提供了由此制备的三环核苷和寡聚化合物。这些三环核苷每个都具有一个三环核糖糖基，其中2'和4'核糖环碳原子之间的桥进一步包括一个融合的碳环或杂环。预计这些三环核苷对增强寡聚化合物的性质将会有用，例如结合亲和力和核酸酶抗性。
• Oxidative Substitution of Boranephosphonate Diesters as a Route to Post-synthetically Modified DNA
  作者：Sibasish Paul、Subhadeep Roy、Luca Monfregola、Shiying Shang、Richard Shoemaker、Marvin H. Caruthers

  DOI：10.1021/ja511145h

  日期：2015.3.11

  and then treating these oligomers with iodine and various nucleophiles. In addition, we show that this reaction is an attractive method for preparing stereodefined phosphorus-modified oligonucleotides. We have also examined the mechanism of this reaction and show that it proceeds via an iodophosphate intermediate. Beyond nucleic acids synthesis, due to the ubiquity of phosphate derivatives in natural

  将修饰引入寡核苷酸对于核酸领域的大量应用很重要。然而，固相 DNA 合成方法对掺入许多对制备合成 DNA 的条件不稳定的有用修饰提出了重大挑战。在这里我们报告硼烷膦酸二酯在被碘激活后以立体特异性方式进行容易的亲核取代。我们随后利用这种反应性将包括叠氮化物和荧光团在内的修饰后合成引入 DNA，方法是首先合成硼烷膦酸酯连接的 2'-脱氧寡核苷酸，然后用碘和各种亲核试剂处理这些寡聚物。此外，我们表明该反应是制备立体定义的磷修饰寡核苷酸的一种有吸引力的方法。我们还研究了该反应的机理，并表明它是通过碘磷酸盐中间体进行的。除了核酸合成之外，由于磷酸盐衍生物在天然化合物和治疗剂中的普遍存在，这种立体特异性反应在有机磷化学中有许多潜在的应用。
• Cytotoxic and mutagenic properties of alkyl phosphotriester lesions in Escherichia coli cells
  作者：Jiabin Wu、Pengcheng Wang、Yinsheng Wang

  DOI：10.1093/nar/gky140

  日期：2018.5.4

  translesion synthesis DNA polymerases. In this study, we synthesized oligodeoxyribonucleotides containing four pairs (Sp and Rp) of alkyl phosphotriester lesions at a defined site, and examined how these lesions are recognized by DNA replication machinery in Escherichia coli cells. We found that the Sp diastereomer of the alkyl phosphotriester lesions could be efficiently bypassed, whereas the Rp counterparts

  暴露于许多内源性和外源性物质会引起DNA烷基化，这是DNA损伤的主要类型。在DNA烷基化产物中，烷基磷酸三酯的出现频率较高，并且对哺乳动物组织的修复具有抵抗力。但是，关于这些损伤如何影响细胞中DNA复制的效率和保真度或如何通过跨病变合成DNA聚合酶调节这些损伤的复制旁路知之甚少。在这项研究中，我们合成了在定义的位点包含四对（S p和R p）烷基磷酸三酯病变的寡脱氧核糖核苷酸，并研究了这些病变如何被大肠杆菌中的DNA复制机制识别细胞。我们发现，烷基磷酸三酯病变的S p非对映异构体可以被有效地绕过，而R p对应物适度地阻断了DNA复制。而且，S p-甲基磷酸三酯在侧翼的TT二核苷酸位点诱导TT→GT和TT→GC突变，并且这些突变的诱导需要Ada蛋白，已知该蛋白可有效地从S p-甲基磷酸三酯中除去甲基。 。总之，我们的研究提供了对细胞中DNA复制机制对烷基磷酸三酯损伤识别的全面理解，并首次揭示了
• Synthesis of the TT pyrimidine (6–4) pyrimidone photoproduct–thio analogue phosphoramidite building block
  作者：Sandra Karina Angulo Matus、Jean-Louis Fourrey、Pascale Clivio

  DOI：10.1039/b305067j

  日期：——

  The phosphoramidite building block synthesis of the thio analogue at the 5,6-dihydropyrimidine C5 position of the thymidylyl(3′–5′)thymidine (6–4) photoproduct 1 is presented. This compound was readily obtained from the appropriately protected dinucleotide P-methyl-5′-O-dimethoxytritylthymidilyl(3′→5′)-4-thiothymidine 2 after irradiation at 366 nm, then S-sulfenylmethylation of the thiol function of the resulting (6–4) adduct, and phosphitylation of the 3′-hydroxyl group.

  介绍了在胸苷（3′–5′）胸苷（6–4）光产物1的5,6-二氢嘧啶C5位置合成硫类似物的磷氨基酸分子构建块的合成。这种化合物可以通过对保护好的二核苷酸P-甲基-5′-O-二甲氧基三苯甲基胸苷（3′–5′）-4-硫胸苷2进行366 nm的照射后容易获得，然后对所得（6–4）加合物的巯基功能进行S-硫酰基甲基化，并对3′-羟基进行磷酸化。
• A cyclobutane thymine–N4-methylcytosine dimer is resistant to hydrolysis but strongly blocks DNA synthesis
  作者：Junpei Yamamoto、Tomoko Oyama、Tomohiro Kunishi、Chikahide Masutani、Fumio Hanaoka、Shigenori Iwai

  DOI：10.1093/nar/gkt1039

  日期：2014.2

  Exposure of DNA to ultraviolet light produces harmful crosslinks between adjacent pyrimidine bases, to form cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6–4)pyrimidone photoproducts. The CPD is frequently formed, and its repair mechanisms have been exclusively studied by using a CPD formed at a TT site. On the other hand, biochemical analyses using CPDs formed within cytosine-containing sequence

  DNA 暴露在紫外线下会在相邻的嘧啶碱基之间产生有害的交联，形成环丁烷嘧啶二聚体 (CPD) 和嘧啶 (6-4) 嘧啶酮光产物。CPD 经常形成，并且已经通过使用在 TT 站点形成的 CPD 专门研究了其修复机制。另一方面，使用在含胞嘧啶序列上下文中形成的 CPD 进行生化分析实际上很困难，因为饱和胞嘧啶很容易发生水解脱氨。在这里，我们发现2'-脱氧胞苷的环外氨基的N-烷基化阻止了 CPD 形成中的水解，并且N含-甲基化胞嘧啶的 CPD 足够稳定，可以衍生为亚磷酰胺结构单元并掺入寡核苷酸中。含 CPD 的寡核苷酸的动力学研究表明，其在生理条件下的寿命相对较长（~7 天）。在使用人类 DNA 聚合酶 η 的生化分析中，除了 dGMP 掺入之外，还清楚地检测到了与 CPD的N-甲基胞嘧啶部分相反的 TMP掺入，并且不正确的 TMP 掺入会阻止 DNA 合成。热力学参数证实了这种不寻常的碱基对的形成。