N-((S)-1-(1,1-dimethylethoxycarbonyl)-5-oxopyrrolidine-2-carbonyl)-L-valine pentafluorophenyl ester | 938075-92-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-((S)-1-(1,1-dimethylethoxycarbonyl)-5-oxopyrrolidine-2-carbonyl)-L-valine pentafluorophenyl ester
• CAS: 938075-92-4
• 化学式: C₂₁H₂₃F₅N₂O₆
• 分子量: 494.415
• InChiKey: VQNDVDGMJDNKFK-FVMDXXJSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.35
• 重原子数：
  34.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  102.01
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N-((S)-1-(1,1-dimethylethoxycarbonyl)-5-oxopyrrolidine-2-carbonyl)-L-valine pentafluorophenyl ester 在 吡啶 、 ammonium hydroxide 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.0h， 生成 (S)-3-(N-((S)-1-(1,1-dimethylethoxycarbonyl)-L-glutaminyl)-L-valyl)-2,2-dimethyltetrahydrothiazole-N-(2-(4-nitrophenyl)ethyl)-4-carboxamide
  参考文献：
  名称：

  Synthetic approaches to peptides containing the l-Gln-l-Val-D(S)-Dmt motif

  摘要：

  The pseudoprolines S-Dmo (5,5-dimethyl-4-oxaproline) and R-Dmt (5,5-dimethyl-4-thiaproline) have been used to study the effects of forcing a fully cis conformation in peptides. Synthesis of peptides containing these (which have the same configuration as L-Pro) is straightforward. However, synthesis of peptides containing S-Dmt is difficult, owing to the rapid cyclisation of L-Aaa-S-Dmt amides and esters to form the corresponding diketopiperazines (DKP); thus the intermediacy Of L-Aaa-S-Dmt amides and esters must be avoided in the synthetic sequence. Peptides containing the L-Gln-L-Val-D(S)-Dmt motif are particularly difficult, owing to the insolubility of coupling partners containing Gln. Introduction of Gln as N-Boc-pyroglutamate overcame the latter difficulty and the dipeptide active ester BocPygValOC(6)F(5) coupled in good yield with S-DmtOH. BocPygVal-SDmtNH(CH2)(2)C6H4NO2 was converted quantitatively to BocGlnVal-S-DmtNH(CH2)(2)C6H4NO2 with ammonia, demonstrating the utility of this approach. Two peptide derivatives (CbzSerLysLeuGInVal-S-DmtNH(CH2)(2)C6H4NO2 and CbzSerSerLysLeuGInVal-S- DmtNH(CH2)(2)C6H4NO2) were assembled, using these new methods of coupling a dipeptide acid active ester with S-DmtOH and introduction of Gin as Pyg, followed by conventional peptide couplings. The presence of the Val caused these peptides to be cleaved very slowly by prostate-specific antigen (PSA) at Len down arrow Gln, rather than the expected Gln down arrow Val. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.03.005
• 作为产物：
  描述：

  N-((S)-1-(1,1-dimethylethoxycarbonyl)-5-oxopyrrolidine-2-carbonyl)-L-valine phenylmethyl ester 在 palladium on activated charcoal 吡啶 、 氢气 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 N-((S)-1-(1,1-dimethylethoxycarbonyl)-5-oxopyrrolidine-2-carbonyl)-L-valine pentafluorophenyl ester
  参考文献：
  名称：

  Synthetic approaches to peptides containing the l-Gln-l-Val-D(S)-Dmt motif

  摘要：

  The pseudoprolines S-Dmo (5,5-dimethyl-4-oxaproline) and R-Dmt (5,5-dimethyl-4-thiaproline) have been used to study the effects of forcing a fully cis conformation in peptides. Synthesis of peptides containing these (which have the same configuration as L-Pro) is straightforward. However, synthesis of peptides containing S-Dmt is difficult, owing to the rapid cyclisation of L-Aaa-S-Dmt amides and esters to form the corresponding diketopiperazines (DKP); thus the intermediacy Of L-Aaa-S-Dmt amides and esters must be avoided in the synthetic sequence. Peptides containing the L-Gln-L-Val-D(S)-Dmt motif are particularly difficult, owing to the insolubility of coupling partners containing Gln. Introduction of Gln as N-Boc-pyroglutamate overcame the latter difficulty and the dipeptide active ester BocPygValOC(6)F(5) coupled in good yield with S-DmtOH. BocPygVal-SDmtNH(CH2)(2)C6H4NO2 was converted quantitatively to BocGlnVal-S-DmtNH(CH2)(2)C6H4NO2 with ammonia, demonstrating the utility of this approach. Two peptide derivatives (CbzSerLysLeuGInVal-S-DmtNH(CH2)(2)C6H4NO2 and CbzSerSerLysLeuGInVal-S- DmtNH(CH2)(2)C6H4NO2) were assembled, using these new methods of coupling a dipeptide acid active ester with S-DmtOH and introduction of Gin as Pyg, followed by conventional peptide couplings. The presence of the Val caused these peptides to be cleaved very slowly by prostate-specific antigen (PSA) at Len down arrow Gln, rather than the expected Gln down arrow Val. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.03.005