(+/-)-2-[N-(2-fluoroacetyl)]amino-1-phenylethanol | 264881-21-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (+/-)-2-[N-(2-fluoroacetyl)]amino-1-phenylethanol
• 英文别名: 2-fluoro-N-(2-hydroxy-2-phenylethyl)acetamide
• CAS: 264881-21-2
• 化学式: C₁₀H₁₂FNO₂
• 分子量: 197.209
• InChiKey: KACUHHWEBHZJFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+/-)-2-[N-(2-fluoroacetyl)]amino-1-phenylethanol 在 四氮唑 作用下， 以 乙腈 为溶剂， 反应 3.25h， 生成 N-[1-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-[[(2S,5S)-3-(2-fluoroacetyl)-5-phenyl-1,3,2-oxazaphospholidin-2-yl]oxy]oxolan-2-yl]-2-oxopyrimidin-4-yl]benzamide
  参考文献：
  名称：

  Deoxyribonucleoside Cyclic N-Acylphosphoramidites as a New Class of Monomers for the Stereocontrolled Synthesis of Oligothymidylyl- and Oligodeoxycytidylyl- Phosphorothioates

  摘要：

  A simple and straightforward synthesis of the pyrimidine 2'-deoxyribonucleoside cyclic N-acylphosphoramidites R-P-1 and S-P-1 is described. Specifically, (+/-)-2-amino-1-phenylethanol 2 was chemoselectively N-acylated to 4 by treatment with ethyl fluoroacetate 3 followed by reaction with hexaethylphosphorus triamide to afford the cyclic N-acylphosphoramidite 5 as a mixture of diastereomeric rotamers (5a and 5b). Condensation of N-4-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2-deoxycytidine 8 with 5 in the presence of 1H-tetrazole gave, after silica gel chromatography, pure R-P-1 and S-P-1. P-31 NMR studies indicated that when Rp-l or Sp-l is reacted with 3'-O-acetylthymidine and N,N,N',N'-tetramethylguanidine in CD3CN, the dinucleoside phosphotriester S-P-9 or R-P-9 is formed in near quantitative yield with total P-stereospecificity (delta(P) 144.2 or 143.9 ppm, respectively). Sulfurization of Sp-9 or R-P-9 generated the P-stereodefined dinucleoside phosphorothioate R-P-11 or S-P-11 (delta(P) 71.0 or 71.2 ppm, respectively). The 2'-deoxycytidine cyclic N-acylphosphoramidite derivatives R-P-1 and S-P-1 were subsequently applied to the solid-phase synthesis of [R-P,R-P]- and [S-P,S-P] -trideoxycytidilyl diphosphorothioate d(CPSCPSC), and [R-P,S-P,R-P]-tetradeoxycytidilyl triphosphorothioate d(CPSCPSCPSC) Following deprotection, reversed-phase (RP) HPLC analysis of these oligonucleotide analogues showed a single peak for each oligomer. By comparison, RP-HPLC analysis of purified P-diastereomeric d(CPSCPSC) and d(CPSCPSCPSC) prepared from standard 2-cyanoethyl deoxyribonucleoside phosphoramidites exhibited 4 and 8 peaks, respectively, each peak corresponding to a specific P-diastereomer (see Figure 3A). The thymidine cyclic N-acylphosphoramidite derivatives R-P-14 and S-P-14 were also prepared, purified, and used successfully in the solid-phase synthesis of [R-P](11)-d[(T-PS)(11)T]. Thus, the application of deoxyribonucleoside cyclic N-acyl phosphoramidites to P-stereocontrolled synthesis of oligodeoxyribonucleoside phosphorothioates may offer a compelling alternative to the methods currently used for such syntheses.

  DOI：

  10.1021/ja991773u
• 作为产物：
  描述：

  氟乙酸乙酯 、 2-氨基-1-苯乙醇 反应 2.0h， 以72%的产率得到(+/-)-2-[N-(2-fluoroacetyl)]amino-1-phenylethanol
  参考文献：
  名称：

  Deoxyribonucleoside Cyclic N-Acylphosphoramidites as a New Class of Monomers for the Stereocontrolled Synthesis of Oligothymidylyl- and Oligodeoxycytidylyl- Phosphorothioates

  摘要：

  A simple and straightforward synthesis of the pyrimidine 2'-deoxyribonucleoside cyclic N-acylphosphoramidites R-P-1 and S-P-1 is described. Specifically, (+/-)-2-amino-1-phenylethanol 2 was chemoselectively N-acylated to 4 by treatment with ethyl fluoroacetate 3 followed by reaction with hexaethylphosphorus triamide to afford the cyclic N-acylphosphoramidite 5 as a mixture of diastereomeric rotamers (5a and 5b). Condensation of N-4-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2-deoxycytidine 8 with 5 in the presence of 1H-tetrazole gave, after silica gel chromatography, pure R-P-1 and S-P-1. P-31 NMR studies indicated that when Rp-l or Sp-l is reacted with 3'-O-acetylthymidine and N,N,N',N'-tetramethylguanidine in CD3CN, the dinucleoside phosphotriester S-P-9 or R-P-9 is formed in near quantitative yield with total P-stereospecificity (delta(P) 144.2 or 143.9 ppm, respectively). Sulfurization of Sp-9 or R-P-9 generated the P-stereodefined dinucleoside phosphorothioate R-P-11 or S-P-11 (delta(P) 71.0 or 71.2 ppm, respectively). The 2'-deoxycytidine cyclic N-acylphosphoramidite derivatives R-P-1 and S-P-1 were subsequently applied to the solid-phase synthesis of [R-P,R-P]- and [S-P,S-P] -trideoxycytidilyl diphosphorothioate d(CPSCPSC), and [R-P,S-P,R-P]-tetradeoxycytidilyl triphosphorothioate d(CPSCPSCPSC) Following deprotection, reversed-phase (RP) HPLC analysis of these oligonucleotide analogues showed a single peak for each oligomer. By comparison, RP-HPLC analysis of purified P-diastereomeric d(CPSCPSC) and d(CPSCPSCPSC) prepared from standard 2-cyanoethyl deoxyribonucleoside phosphoramidites exhibited 4 and 8 peaks, respectively, each peak corresponding to a specific P-diastereomer (see Figure 3A). The thymidine cyclic N-acylphosphoramidite derivatives R-P-14 and S-P-14 were also prepared, purified, and used successfully in the solid-phase synthesis of [R-P](11)-d[(T-PS)(11)T]. Thus, the application of deoxyribonucleoside cyclic N-acyl phosphoramidites to P-stereocontrolled synthesis of oligodeoxyribonucleoside phosphorothioates may offer a compelling alternative to the methods currently used for such syntheses.

  DOI：

  10.1021/ja991773u

文献信息

• Deoxyribonucleoside Cyclic <i>N</i>-Acylphosphoramidites as a New Class of Monomers for the Stereocontrolled Synthesis of Oligothymidylyl- and Oligodeoxycytidylyl- Phosphorothioates
  作者：Andrzej Wilk、Andrzej Grajkowski、Lawrence R. Phillips、Serge L. Beaucage

  DOI：10.1021/ja991773u

  日期：2000.3.1

  A simple and straightforward synthesis of the pyrimidine 2'-deoxyribonucleoside cyclic N-acylphosphoramidites R-P-1 and S-P-1 is described. Specifically, (+/-)-2-amino-1-phenylethanol 2 was chemoselectively N-acylated to 4 by treatment with ethyl fluoroacetate 3 followed by reaction with hexaethylphosphorus triamide to afford the cyclic N-acylphosphoramidite 5 as a mixture of diastereomeric rotamers (5a and 5b). Condensation of N-4-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2-deoxycytidine 8 with 5 in the presence of 1H-tetrazole gave, after silica gel chromatography, pure R-P-1 and S-P-1. P-31 NMR studies indicated that when Rp-l or Sp-l is reacted with 3'-O-acetylthymidine and N,N,N',N'-tetramethylguanidine in CD3CN, the dinucleoside phosphotriester S-P-9 or R-P-9 is formed in near quantitative yield with total P-stereospecificity (delta(P) 144.2 or 143.9 ppm, respectively). Sulfurization of Sp-9 or R-P-9 generated the P-stereodefined dinucleoside phosphorothioate R-P-11 or S-P-11 (delta(P) 71.0 or 71.2 ppm, respectively). The 2'-deoxycytidine cyclic N-acylphosphoramidite derivatives R-P-1 and S-P-1 were subsequently applied to the solid-phase synthesis of [R-P,R-P]- and [S-P,S-P] -trideoxycytidilyl diphosphorothioate d(CPSCPSC), and [R-P,S-P,R-P]-tetradeoxycytidilyl triphosphorothioate d(CPSCPSCPSC) Following deprotection, reversed-phase (RP) HPLC analysis of these oligonucleotide analogues showed a single peak for each oligomer. By comparison, RP-HPLC analysis of purified P-diastereomeric d(CPSCPSC) and d(CPSCPSCPSC) prepared from standard 2-cyanoethyl deoxyribonucleoside phosphoramidites exhibited 4 and 8 peaks, respectively, each peak corresponding to a specific P-diastereomer (see Figure 3A). The thymidine cyclic N-acylphosphoramidite derivatives R-P-14 and S-P-14 were also prepared, purified, and used successfully in the solid-phase synthesis of [R-P](11)-d[(T-PS)(11)T]. Thus, the application of deoxyribonucleoside cyclic N-acyl phosphoramidites to P-stereocontrolled synthesis of oligodeoxyribonucleoside phosphorothioates may offer a compelling alternative to the methods currently used for such syntheses.