5-trifluoromethyl-1-(2-deoxy-β-D-ribofuranosyl)-2,4-difluorobenzene | 333447-75-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-trifluoromethyl-1-(2-deoxy-β-D-ribofuranosyl)-2,4-difluorobenzene
• 英文别名: 1-(2-deoxy-β-D-ribofuranosyl)-2,4-difluoro-5-trifluoromethylbenzene；(2R,3S,5R)-5-[2,4-difluoro-5-(trifluoromethyl)phenyl]-2-(hydroxymethyl)tetrahydrofuran-3-ol；(2R,3S,5R)-5-[2,4-difluoro-5-(trifluoromethyl)phenyl]-2-(hydroxymethyl)oxolan-3-ol
• CAS: 333447-75-9
• 化学式: C₁₂H₁₁F₅O₃
• 分子量: 298.21
• InChiKey: XKWFGABVBAMTQC-HBNTYKKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  49.7
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-methylsalicylchlorophosphane 、 5-trifluoromethyl-1-(2-deoxy-β-D-ribofuranosyl)-2,4-difluorobenzene 在 N,N-二异丙基乙胺 、 叔丁基过氧化氢 作用下， 以 乙腈 为溶剂， 反应 1.33h， 以26%的产率得到cyclo-(3-methylsaligenyl)-5'-O-[1'-(2,4-difluoro-5-trifluoromethylphenyl)-2'-deoxy-β-D-ribofuranosyl]phosphate
  参考文献：
  名称：

  CycloSaligenyl Pronucleotides of 5-Iodo and 5-Trifluoromethyl-1-(2-deoxy-β-D-ribofuranosyl)-2,4-difluorobenzene Mimics of Thymidine: Synthesis and Evaluation of this Pronucleotide Monophosphate Delivery System for Compounds with Potential Anticancer Activity

  摘要：

  A group of unnatural 1-(2-deoxy-beta-D-ribofuranosyl)-2,4-difluorobenzenes possessing a 5-I or 5-CF3 substituent, that were originally designed as thymidine mimics, were coupled via their 5'-OH group to a cyclosaligenyl (cycloSal) ring system having a variety of C-3 substituents (Me, OMe, H). The 5'-O-cycloSal-pronucleotide concept was designed to effect a thymidine kinase-bypass, thereby providing a method for the intracellular delivery and generation of the 5'-O-monophosphate for nucleosides that are poorly phosphorylated. The 5'-O-cycloSal pronucleotide phosphotriesters synthesized in this study were obtained as a 1:1 mixture of two diastereomers that differ in configuration (S(P) or R(P)) at the asymmetric phosphorous center. The (S(P))- and (R(P))-diastereomers for the 5'-O-3-methylcycloSal- and 5'-O-3-methoxycycloSal derivatives of 1-(2-deoxy-beta-D-ribofuranosyl)-2,4-difluoro-5-iodobenzene were separated by silica gel flash column chromatography. This class of cycloSal pronucleotide compounds generally exhibited weak cytotoxic activities in a MTT assay (CC50 values in the 10(-3) to 10(-4) M range), against a number of cancer cell lines (143B, 143B-LTK, EMT-6, Hela, 293), except for cyclosaligenyl-5'-O-[1'-(2,4-difluoro-5-iodophenyl)-2'-deoxy-beta-D-ribofuranosyl]phosphate that was more potent (CC50 values in the 10(-5) to 10(-6) M range), than the reference drug 5-iodo-2'-deoxyuridine (IUDR) which showed CC50 values in the 10(-3) to 10(-5) M range.

  DOI：

  10.1081/ncn-120026634
• 作为产物：
  描述：

  1-氯-2-脱氧-3,5-二-O-对氯苯甲酰基-D-核糖 在 potassium fluoride 、 N-碘代丁二酰亚胺 、 copper(l) iodide 、 碘 、 sodium methylate 、 magnesium 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 三氟乙酸 为溶剂， 反应 54.17h， 生成 5-trifluoromethyl-1-(2-deoxy-β-D-ribofuranosyl)-2,4-difluorobenzene
  参考文献：
  名称：

  1-（2-脱氧-β-D-核呋喃核糖基）-2,4-二氟-5-取代的苯并嘧啶模拟物的合成*一些相关的α-阴离子，及其作为抗病毒和抗癌剂的评价

  摘要：

  一组具有各种C-5取代基（H，Me，F，Cl，Br，I，CF3，CN，NO2，合成了设计为胸苷模拟物的NH2）作为抗癌药和抗病毒药进行评估。3,5-双-O-（对氯苯甲酰基）-2-脱氧-α-D-呋喃呋喃糖基氯与有机镉试剂[（2,4-二氟苯基）2Cd]的偶联反应得到α-和-C的混合物β-异头物产物（α：β= 3：1至10：1的比例）。作为在主要的α-端基异构体上异构化成所需的β-端基异构体的有效方法，人们开发了在BF-​​110-C中在硝基乙烷中用BF3·Et2O处理α-端基异构体的方法。相对于胸腺嘧啶（CC50 = 10-3-10），在MTT分析（CC50 = 10−3–10−4 M范围）中，5取代的（H，Me，Cl，I，NH2）β-异头物显示出可忽略的细胞毒性。 -5 M范围），针对各种癌细胞系。相比之下，5-NO2衍生物具有更高的细胞毒性（CC50 = 10-5-6-10 M范围）。使用

  DOI：

  10.1081/ncn-100001435

文献信息

• SYNTHESIS OF 1-(2-DEOXY-β-<scp>D</scp>- RIBOFURANOSYL)-2,4-DIFLUORO-5-SUBSTITUTED-BENZENE THYMIDINE MIMICS,^*SOME RELATED α-ANOMERS, AND THEIR EVALUATION AS ANTIVIRAL AND ANTICANCER AGENTS
  作者：Zhi-Xian Wang、Weili Duan、Leonard I. Wiebe、Jan Balzarini、Erik De Clercq、Edward E. Knaus

  DOI：10.1081/ncn-100001435

  日期：2001.2.26

  Me, F, Cl, Br, I, CF3, CN, NO2, NH2), designed as thymidine mimics, were synthesized for evaluation as anticancer and antiviral agents. The coupling reaction of 3,5-bis-O-(p-chlorobenzoyl)-2-deoxy-α-D-ribofuranosyl chloride with an organocadmium reagent [(2,4-difluorophenyl)2Cd] afforded a mixture of the α- and β-anomeric products (α:β = 3:1 to 10:1 ratio). Treatment of the α-anomer with BF3·Et2O in

  一组具有各种C-5取代基（H，Me，F，Cl，Br，I，CF3，CN，NO2，合成了设计为胸苷模拟物的NH2）作为抗癌药和抗病毒药进行评估。3,5-双-O-（对氯苯甲酰基）-2-脱氧-α-D-呋喃呋喃糖基氯与有机镉试剂[（2,4-二氟苯基）2Cd]的偶联反应得到α-和-C的混合物β-异头物产物（α：β= 3：1至10：1的比例）。作为在主要的α-端基异构体上异构化成所需的β-端基异构体的有效方法，人们开发了在BF-​​110-C中在硝基乙烷中用BF3·Et2O处理α-端基异构体的方法。相对于胸腺嘧啶（CC50 = 10-3-10），在MTT分析（CC50 = 10−3–10−4 M范围）中，5取代的（H，Me，Cl，I，NH2）β-异头物显示出可忽略的细胞毒性。 -5 M范围），针对各种癌细胞系。相比之下，5-NO2衍生物具有更高的细胞毒性（CC50 = 10-5-6-10 M范围）。使用
• <i>Cyclo</i>Saligenyl Pronucleotides of 5-Iodo and 5-Trifluoromethyl-1-(2-deoxy-β-<scp>D</scp>-ribofuranosyl)-2,4-difluorobenzene Mimics of Thymidine: Synthesis and Evaluation of this Pronucleotide Monophosphate Delivery System for Compounds with Potential Anticancer Activity
  作者：Wei Yan Sun、Aihua Zhou、Leonard I. Wiebe、Edward E. Knaus

  DOI：10.1081/ncn-120026634

  日期：2003.12.31

  A group of unnatural 1-(2-deoxy-beta-D-ribofuranosyl)-2,4-difluorobenzenes possessing a 5-I or 5-CF3 substituent, that were originally designed as thymidine mimics, were coupled via their 5'-OH group to a cyclosaligenyl (cycloSal) ring system having a variety of C-3 substituents (Me, OMe, H). The 5'-O-cycloSal-pronucleotide concept was designed to effect a thymidine kinase-bypass, thereby providing a method for the intracellular delivery and generation of the 5'-O-monophosphate for nucleosides that are poorly phosphorylated. The 5'-O-cycloSal pronucleotide phosphotriesters synthesized in this study were obtained as a 1:1 mixture of two diastereomers that differ in configuration (S(P) or R(P)) at the asymmetric phosphorous center. The (S(P))- and (R(P))-diastereomers for the 5'-O-3-methylcycloSal- and 5'-O-3-methoxycycloSal derivatives of 1-(2-deoxy-beta-D-ribofuranosyl)-2,4-difluoro-5-iodobenzene were separated by silica gel flash column chromatography. This class of cycloSal pronucleotide compounds generally exhibited weak cytotoxic activities in a MTT assay (CC50 values in the 10(-3) to 10(-4) M range), against a number of cancer cell lines (143B, 143B-LTK, EMT-6, Hela, 293), except for cyclosaligenyl-5'-O-[1'-(2,4-difluoro-5-iodophenyl)-2'-deoxy-beta-D-ribofuranosyl]phosphate that was more potent (CC50 values in the 10(-5) to 10(-6) M range), than the reference drug 5-iodo-2'-deoxyuridine (IUDR) which showed CC50 values in the 10(-3) to 10(-5) M range.