N-(N-(N-(Nε-(1,1-dimethylethoxycarbonyl)-L-lysyl)-L-leucyl)-L-glutaminyl)-L-valine methyl ester | 938076-30-3

• 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-(N-(N-(Nε-(1,1-dimethylethoxycarbonyl)-L-lysyl)-L-leucyl)-L-glutaminyl)-L-valine methyl ester
• 英文别名: N-(N-(N-(N^ε-(1,1-dimethylethoxycarbonyl)-L-lysyl)-L-leucyl)-L-glutaminyl)-L-valine methyl ester
• CAS: 938076-30-3
• 化学式: C₂₈H₅₂N₆O₈
• 分子量: 600.756
• InChiKey: XWXXESUOTNHDJK-XWUOBKMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  42.0
• 可旋转键数：
  18.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  221.04
• 氢给体数：
  6.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  N-(N-(N-(Nε-(1,1-dimethylethoxycarbonyl)-L-lysyl)-L-leucyl)-L-glutaminyl)-L-valine methyl ester 在 4-二甲氨基吡啶 、 三乙胺 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 76.0h， 生成 N-(N-(N-(N^α-(N-(phenylmethoxycarbonyl)-L-seryl)-L-lysyl)-L-leucyl)-L-glutaminyl)-L-valine methyl ester trifluoroacetic acid salt
  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-芴甲氧羰基-N'-叔丁氧羰基-L-赖氨酸五氟苯酯 在 4-二甲氨基吡啶 、 二乙胺 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 生成 N-(N-(N-(Nε-(1,1-dimethylethoxycarbonyl)-L-lysyl)-L-leucyl)-L-glutaminyl)-L-valine methyl 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