2-<(9-fluorenylmethyl)oxy>-4-(S)-(1-(S)-methylpropyl)-5-(4H)-oxazolone | 142635-69-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 2-<(9-fluorenylmethyl)oxy>-4-(S)-(1-(S)-methylpropyl)-5-(4H)-oxazolone
• 英文别名: (4S)-4-[(2S)-butan-2-yl]-2-(9H-fluoren-9-ylmethoxy)-4H-1,3-oxazol-5-one
• CAS: 142635-69-6
• 化学式: C₂₁H₂₁NO₃
• 分子量: 335.403
• InChiKey: UYBVRAVCKBCMCF-DJJJIMSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  47.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  9H-芴-9-基甲基[(2S,3S)-1-氯-3-甲基-1-氧代-2-戊烷基]氨基甲酸酯 在 silver cyanide 作用下， 以 甲苯 为溶剂， 反应 0.5h， 生成 2-<(9-fluorenylmethyl)oxy>-4-(S)-(1-(S)-methylpropyl)-5-(4H)-oxazolone
  参考文献：
  名称：

  Use of N-Fmoc amino acid chlorides and activated 2-(fluorenylmethoxy)-5(4H)-oxazolones in solid-phase peptide synthesis. Efficient syntheses of highly N-alkylated cyclic hexapeptide oxytocin antagonists related to L-365,209

  摘要：

  Fmoc amino acid chlorides have been shown to be useful reagents in the solid-phase synthesis of hexapeptides containing up to four sequential secondary amino acids. The oxytocin antagonist cyclo-(D-Phe-Ile-D-Pip-Pip-D-(N-Me)Phe-Pro) (1) was prepared in 70% overall yield starting from Boc-L-Pro-O-(PAM)-resin. In the synthesis of 1, the high reactivity of Fmoc-L-pipecolic acid chloride used in the di- to tripeptide step averted diketopiperazine formation seen with active ester couplings. The use of Fmoc-amino acid chlorides in the subsequent couplings provided a rapid method for assembly of the linear hexapeptide. The two potent cyclic hexapeptide oxytocin antagonists L-366,682 and L-366,948 were prepared in 45-48% overall yield on a 20 mmol scale using the methodology developed for the synthesis of 1. A particularly difficult coupling was encountered that involved acylation of a sterically hindered N(delta)-Cbz-piperazic acid N-terminus with Fmoc-L-isoleucine. Excess Fmoc-L-isoleucine acid chloride in the presence of tertiary amine base gave only 30% conversion. The efficiency was improved to 76% by utilizing the acid chloride with AgCN in toluene. Further investigation revealed that this combination of reagents produces an activated form of the isoleucine 2-alkoxy-5(4H)-oxazolone derivative.

  DOI：

  10.1021/jo00042a016

文献信息

• Use of N-Fmoc amino acid chlorides and activated 2-(fluorenylmethoxy)-5(4H)-oxazolones in solid-phase peptide synthesis. Efficient syntheses of highly N-alkylated cyclic hexapeptide oxytocin antagonists related to L-365,209
  作者：Debra S. Perlow、Jill M. Erb、Norman P. Gould、Roger D. Tung、Roger M. Freidinger、Peter D. Williams、Daniel F. Veber

  DOI：10.1021/jo00042a016

  日期：1992.7

  Fmoc amino acid chlorides have been shown to be useful reagents in the solid-phase synthesis of hexapeptides containing up to four sequential secondary amino acids. The oxytocin antagonist cyclo-(D-Phe-Ile-D-Pip-Pip-D-(N-Me)Phe-Pro) (1) was prepared in 70% overall yield starting from Boc-L-Pro-O-(PAM)-resin. In the synthesis of 1, the high reactivity of Fmoc-L-pipecolic acid chloride used in the di- to tripeptide step averted diketopiperazine formation seen with active ester couplings. The use of Fmoc-amino acid chlorides in the subsequent couplings provided a rapid method for assembly of the linear hexapeptide. The two potent cyclic hexapeptide oxytocin antagonists L-366,682 and L-366,948 were prepared in 45-48% overall yield on a 20 mmol scale using the methodology developed for the synthesis of 1. A particularly difficult coupling was encountered that involved acylation of a sterically hindered N(delta)-Cbz-piperazic acid N-terminus with Fmoc-L-isoleucine. Excess Fmoc-L-isoleucine acid chloride in the presence of tertiary amine base gave only 30% conversion. The efficiency was improved to 76% by utilizing the acid chloride with AgCN in toluene. Further investigation revealed that this combination of reagents produces an activated form of the isoleucine 2-alkoxy-5(4H)-oxazolone derivative.