Thioacetic acid S-[(1S,2R)-2-tert-butoxycarbonylamino-1-(3-methyl-butylcarbamoyl)-3-phenyl-propyl] ester | 114886-67-8

• 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: Thioacetic acid S-[(1S,2R)-2-tert-butoxycarbonylamino-1-(3-methyl-butylcarbamoyl)-3-phenyl-propyl] ester
• 英文别名: S-[(2S,3R)-1-(3-methylbutylamino)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-1-oxo-4-phenylbutan-2-yl] ethanethioate
• CAS: 114886-67-8
• 化学式: C₂₂H₃₄N₂O₄S
• 分子量: 422.589
• InChiKey: IAWZXXBWTKLFQY-MOPGFXCFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  29
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Thioacetic acid S-[(1S,2R)-2-tert-butoxycarbonylamino-1-(3-methyl-butylcarbamoyl)-3-phenyl-propyl] ester 在 sodium hydroxide 作用下， 以85%的产率得到[(1R,2S)-1-Benzyl-2-[(1S,2R)-2-tert-butoxycarbonylamino-1-(3-methyl-butylcarbamoyl)-3-phenyl-propyldisulfanyl]-2-(3-methyl-butylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis of sulfur-containing analogs of bestatin. Inhibition of aminopeptidases by .alpha.-thiolbestatin analogs

  摘要：

  Sulfur-containing amino acid and peptide analogues of bestatin [((2S,3R)-3-amino-2-hydroxy-4-phenyl-butanoyl)-L-leucine] (1) have been synthesized and evaluated as inhibitors of aminopeptidase M (AP-M), leucine aminopeptidase (LAP), and aminopeptidase B (AP-B). The 2-thiolbestatin analogue (6) was found to be a potent inhibitor of all three aminopeptidases (AP-M, Ki = 4.4 microM; LAP, Ki = 0.55 microM; AP-B, Ki = 4.6 nM) but only a slightly better inhibitor of these aminopeptidases than the parent hydroxy-containing compound 1. Synthetic analogues of L-leucinethiol(4), a strong inhibitor of aminopeptidases, were prepared in which the carbon alpha to the thiol groups was substituted with methyl, methyl carboxylate, and carboxamide derivatives and found to be much weaker inhibitors of all aminopeptidases. A thioamide analogue of bestatin (49) is a modest inhibitor of AP-M (Ki = 40 microM), LAP (Ki = 0.33 microM), and AP-B (Ki = 2.4 microM). These results suggest that the sulfur atoms in 2-thiolbestatin and bestatin thioamide do not interact strongly with the active-site zinc atom of these aminopeptidases when the inhibitors are bound to the enzyme. These results are not consistent with proposed models for the inhibition of aminopeptidases by bestatin and related analogues.

  DOI：

  10.1021/jm00119a022
• 作为产物：
  描述：

  [(1R,2R)-1-Benzyl-2-hydroxy-2-(3-methyl-butylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester 在 TEA 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 Thioacetic acid S-[(1S,2R)-2-tert-butoxycarbonylamino-1-(3-methyl-butylcarbamoyl)-3-phenyl-propyl] ester
  参考文献：
  名称：

  Synthesis of sulfur-containing analogs of bestatin. Inhibition of aminopeptidases by .alpha.-thiolbestatin analogs

  摘要：

  Sulfur-containing amino acid and peptide analogues of bestatin [((2S,3R)-3-amino-2-hydroxy-4-phenyl-butanoyl)-L-leucine] (1) have been synthesized and evaluated as inhibitors of aminopeptidase M (AP-M), leucine aminopeptidase (LAP), and aminopeptidase B (AP-B). The 2-thiolbestatin analogue (6) was found to be a potent inhibitor of all three aminopeptidases (AP-M, Ki = 4.4 microM; LAP, Ki = 0.55 microM; AP-B, Ki = 4.6 nM) but only a slightly better inhibitor of these aminopeptidases than the parent hydroxy-containing compound 1. Synthetic analogues of L-leucinethiol(4), a strong inhibitor of aminopeptidases, were prepared in which the carbon alpha to the thiol groups was substituted with methyl, methyl carboxylate, and carboxamide derivatives and found to be much weaker inhibitors of all aminopeptidases. A thioamide analogue of bestatin (49) is a modest inhibitor of AP-M (Ki = 40 microM), LAP (Ki = 0.33 microM), and AP-B (Ki = 2.4 microM). These results suggest that the sulfur atoms in 2-thiolbestatin and bestatin thioamide do not interact strongly with the active-site zinc atom of these aminopeptidases when the inhibitors are bound to the enzyme. These results are not consistent with proposed models for the inhibition of aminopeptidases by bestatin and related analogues.

  DOI：

  10.1021/jm00119a022