5'-O-(4,4'-dimethoxytrityl)-α,α,α-trifluorothymidine | 133128-06-0

• 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)-α,α,α-trifluorothymidine
• 英文别名: 2'-deoxy-5'-O-(4,4′-dimethoxytrityl)-5-trifluoromethyluridine；5-trifluoromethyl-5'-(4,4'-dimethoxytrityl)-2'-deoxyuridine；5-trifluoromethyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxyuridine；1-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxyoxolan-2-yl]-5-(trifluoromethyl)pyrimidine-2,4-dione
• CAS: 133128-06-0
• 化学式: C₃₁H₂₉F₃N₂O₇
• 分子量: 598.576
• InChiKey: BVZXDHQWZFXCJZ-OYUWMTPXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  43
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  2-氰乙基N,N-二异丙基氯亚磷酰胺 、 5'-O-(4,4'-dimethoxytrityl)-α,α,α-trifluorothymidine 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以65%的产率得到3'-(2-cyanoethyl-N,N-diisopropyl)-2'-deoxy-5'-(4,4'-dimethoxytrityl)-5-(trifluoromethyl)uridine
  参考文献：
  名称：

  包含2'-脱氧-5-三氟甲基尿苷和2'-脱氧-5-三氟甲基胞苷的寡核苷酸的三链和双链形成能力。

  摘要：

  分别由市售的2'-脱氧尿苷和2'-脱氧胞苷容易地合成了2'-脱氧-5-三氟甲基尿苷和2'-脱氧-5-三氟甲基胞苷亚磷酰胺。将获得的亚磷酰胺掺入寡核苷酸中，并通过紫外熔融实验评估它们对双链DNA（dsDNA）和单链RNA（ssRNA）的结合亲和力。包括5-三氟甲基嘧啶核碱基和dsDNA的寡核苷酸的三链体形成能力降低。尤其是，包含三氟甲基胞嘧啶（CF3C）-GC碱三重态的三链体的稳定性很低，这可能是由于吸电子三氟甲基导致质子化CF3C的pKa低所致。

  DOI：

  10.1248/cpb.c17-00530
• 作为产物：
  描述：

  2-脱氧尿苷 在 吡啶 、 叔丁醇 作用下， 以 水 为溶剂， 反应 44.5h， 生成 5'-O-(4,4'-dimethoxytrityl)-α,α,α-trifluorothymidine
  参考文献：
  名称：

  包含2'-脱氧-5-三氟甲基尿苷和2'-脱氧-5-三氟甲基胞苷的寡核苷酸的三链和双链形成能力。

  摘要：

  分别由市售的2'-脱氧尿苷和2'-脱氧胞苷容易地合成了2'-脱氧-5-三氟甲基尿苷和2'-脱氧-5-三氟甲基胞苷亚磷酰胺。将获得的亚磷酰胺掺入寡核苷酸中，并通过紫外熔融实验评估它们对双链DNA（dsDNA）和单链RNA（ssRNA）的结合亲和力。包括5-三氟甲基嘧啶核碱基和dsDNA的寡核苷酸的三链体形成能力降低。尤其是，包含三氟甲基胞嘧啶（CF3C）-GC碱三重态的三链体的稳定性很低，这可能是由于吸电子三氟甲基导致质子化CF3C的pKa低所致。

  DOI：

  10.1248/cpb.c17-00530

文献信息

• Improved synthesis of 5-hydroxymethyl-2′-deoxycytidine phosphoramidite using a 2′-deoxyuridine to 2′-deoxycytidine conversion without temporary protecting groups
  作者：Anders S. Hansen、Armin Thalhammer、Afaf H. El-Sagheer、Tom Brown、Christopher J. Schofield

  DOI：10.1016/j.bmcl.2010.12.098

  日期：2011.2

  incorporation into oligonucleotides. To minimize manipulations we employed a temporary protecting group-free 2′-deoxyuridine to 2′-deoxycytidine conversion procedure that utilizes phase transfer catalysis. The desired 5-HOMedC phosphoramidite is obtained in six steps and 24% overall yield from 2′-deoxyuridine.

  5-羟甲基胞嘧啶最近被定性为人类 DNA 中的“第六个碱基”。为了能够对这种 DNA 修饰进行研究，我们报告了一种合成 5-羟甲基-2'-脱氧胞苷 ( 5-HOMe dC) 亚磷酰胺的改进方法，用于位点特异性掺入寡核苷酸中。为了最大限度地减少操作，我们采用了一种利用相转移催化的临时无保护基团 2'-脱氧尿苷到 2'-脱氧胞苷的转化过程。所需的5-HOMe dC 亚磷酰胺通过 6 个步骤从 2'-脱氧尿苷中获得，总产率为 24%。
• Modified Oligonucleotides and Applications Thereof
  申请人：Mullah Khairuzzaman Bashar

  公开号：US20110144319A1

  公开（公告）日：2011-06-16

  Disclosed, among other things, are primers containing certain modified nucleobases in the 3′ terminal region of the primers that provide reduced formation of primer-dimers during amplification reactions, and various methods of use thereof.

  披露了包含在引物的3'端区域中的某些修饰核苷酸碱基的引物，这些引物在扩增反应过程中减少引物二聚体形成，并且披露了各种使用方法。
• Incorporation of 2′-deoxy-5-(trifluoromethyl)uridine and 5-Cyano-2′-deoxyuridine into DNA
  作者：John C. Markley、Panadda Chirakul、Dina Sologub、Snorri Th. Sigurdsson

  DOI：10.1016/s0960-894x(01)00461-9

  日期：2001.9

  In an attempt to synthesize DNA containing 2'-deoxy-5-(trifluoromethyl)uridine (1) using previously published protocols, we found that the trifluoromethyl group converted into a cyano group, resulting in DNA containing 5-cyano-2'-deoxyuridine (3). We show that nucleoside 1 can be incorporated into DNA using phosphoramidite 2 in combination with acetyl-protected deoxycytidine and phenoxyacetyl-protected

  在尝试使用先前公开的方案合成包含2'-脱氧-5-（三氟甲基）尿苷（1）的DNA时，我们发现三氟甲基基团转化为氰基，从而导致包含5-氰基-2'-脱氧尿苷的DNA （3）。我们表明，可以使用亚磷酰胺2与乙酰基保护的脱氧胞苷和苯氧乙酰基保护的嘌呤亚磷酰胺结合将核苷1掺入DNA中。用1代替DNA中的胸苷导致pH 6.9时DNA双链体稳定性略有下降。
• Synthesis, annealing properties, fluorine-19 NMR characterization, and detection limits of a trifluorothymidine-labeled antisense oligodeoxyribonucleotide 21 mer'
  作者：William H. Gmeiner、Richard T. Pon、J. William Lown

  DOI：10.1021/jo00011a028

  日期：1991.5

  The synthesis and characterization are described of trifluorothymidine groups incorporated into an antisense 21 mer designed to target gene sequences that encode serine proteases in T-lymphocytes. H-1 NMR titration studies on 3',5'-O-TPDS-trifluorothymidine (3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)trifluorothymidine) with 3',5'-O-TPDS-2'-deoxyadenosine provided clear evidence of normal Watson-Crick base pairing via detection of the imino proton signals. The chemical shift of the imino proton is moved ca. 0.5 ppm upfield relative to the position with the natural nucleoside. H-1 NMR also confirmed normal annealing in the 21 mer with its complement in the imino proton detection with the most notable difference being that six AT signals move upfield into the region characteristic of Watson-Crick GC base pairs. 1D-NMR experiments confirm that a single species exists in solution and CD studies indicate that the duplex formed with its complement adopts B-form geometry. The 1D-NMR experiments show that two of three ordinary methyl groups in the hybrid duplex exist in a single conformation while the third methyl group is predominantly in a single conformation. Molecular modeling of the duplex formed between the trifluorothymidine antisense sequence and complementary mRNA indicates a stable A-type helix in which the CF3 groups cause the thymidine base pairs to be displaced somewhat compared with the natural structure. The limits of F-19 NMR detection of the trifluorothymidine labeled 21 mer were determined to be ca. 10-mu-M at a 10:1 signal to noise ratio, i.e., satisfactory for projected in vivo NMR imaging studies.