N-acetyl-L-phenylalanyl-L-histidine | 123580-40-5

• 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-acetyl-L-phenylalanyl-L-histidine
• 英文别名: (2S)-2-[[(2S)-2-acetamido-3-phenylpropanoyl]amino]-3-(1H-imidazol-5-yl)propanoic acid
• CAS: 123580-40-5
• 化学式: C₁₇H₂₀N₄O₄
• 分子量: 344.37
• InChiKey: XWIVXKIZCUAUAQ-GJZGRUSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  124
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  L-phenylalanyl-L-histidine methyl ester dihydrobromide 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 N-acetyl-L-phenylalanyl-L-histidine
  参考文献：
  名称：

  Mechanism of enantioselective ester cleavage by histidine containing dipeptides at a micellar interface

  摘要：

  Chiral p-nitrophenyl esters derived from the amino acid phenylalanine are cleaved by histidine-containing dipeptides at a micellar interface. High enantioselectivities (up to k(L)/k(D) = 30.4 at 0-degrees-C) are observed. Both the substrates and the catalysts contain an alternating sequence of hydrophobic and hydrophilic groups. Due to the need for hydration of the hydrophilic groups, the hydrophobic groups cannot dissolve completely into the micellar hydrocarbon phase. The kinetic data suggest that the micellar interface is capable of discriminating between transition states that have different hydrophilic and hydrophobic properties. One of the diastereomeric transition states is characterized by a hydrogen bond between the amide CO group of the ester and an NH group of the histidine-containing dipeptide. Upon formation of this hydrogen bond these polar CO and NH groups lose their hydrophilicity which allows the transfer of the adjacent apolar groups to the micellar hydrocarbon phase. The other diastereomeric transition state cannot form this hydrogen bond and the hydrophobic groups remain hydrated. Consequently, the latter transition state is of higher energy. The kinetic data reveal that it is important to prevent steric hinderance between the reactants in order to allow the unhindered formation of the hydrogen bond.

  DOI：

  10.1021/jo00012a019

文献信息

• Renin inhibiting dipeptides, their preparation and compositions containing them
  申请人：GLAXO GROUP LIMITED

  公开号：EP0320205A2

  公开（公告）日：1989-06-14

  There are described new compounds of formula (1) wherein R¹ represents an acyl group; X¹ represents phenylalanine or p-methoxyphenyl­alanine bonded N-terminally to R¹ and C-terminally to X²; X² represents histidine or N-methylhistidine bonded N-terminally to X¹ and C-terminally to the group -NH-; R² represents a C₄₋₆ cycloalkyl group; R³ represents a group CHR⁶R⁷ (where R⁶ is a hydrogen atom and R⁷ is a phenyl group, or R⁶ is a methyl group and R⁷ is a hydrogen atom or a methyl or ethyl group; X³ represents a C₂₋₆ alkylene chain optionally substituted by one or more C₁₋₄ alkyl groups; R⁴ and R⁵, which may be the same or different, each independently represent a hydrogen atom or a C₁₋₄ alkyl group, or NR⁴R⁵ may form a 5- or 6- membered polymethylenimine ring; and salts and solvates thereof. The new compounds have been found to exhibit activity as renin inhinitors, combining good duration of action with significant oral potency. Compositions containing the compounds of formula (1) and processes for preparing the compounds are also described.

  所述新化合物为式(1) 其中 R¹ 代表酰基 X¹ 代表苯丙氨酸或对甲氧基苯丙氨酸，N-端与 R¹ 键合，C-端与 X² 键合； X² 代表组氨酸或 N-甲基组氨酸，其 N 端与 X¹ 键合，C 端与基团 -NH- 键合； R² 代表 C₄₋₆环烷基； R³ 代表基团 CHR⁶R⁷（其中 R⁶ 是氢原子，R⁷ 是苯基，或 R⁶ 是甲基，R⁷ 是氢原子或甲基或乙基）； X³ 代表任选被一个或多个 C₁₋₄ 烷基取代的 C₂₋₆ 亚烷基链； R⁴和R⁵可以相同或不同，各自独立地代表一个氢原子或一个C₁₋₄烷基，或者NR⁴R⁵可以形成一个5-或6-成员的聚亚甲基亚胺环； 及其盐和溶剂。 研究发现，这些新化合物具有肾素抑制剂的活性，同时具有良好的作用持续时间和显著的口服效力。 此外，还描述了含有式（1）化合物的组合物以及制备这些化合物的工艺。
• CLEIJ, MARCO C.;DRENTH, WIENDELT;NOLTE, ROELAND J. M., J. ORG. CHEM., 56,(1991) N2, C. 3883-3891
  作者：CLEIJ, MARCO C.、DRENTH, WIENDELT、NOLTE, ROELAND J. M.

  DOI：——

  日期：——
• US4985407A
  申请人：——

  公开号：US4985407A

  公开（公告）日：1991-01-15
• Mechanism of enantioselective ester cleavage by histidine containing dipeptides at a micellar interface
  作者：Marco C. Cleij、Wiendelt Drenth、Roeland J. M. Nolte

  DOI：10.1021/jo00012a019

  日期：1991.6

  Chiral p-nitrophenyl esters derived from the amino acid phenylalanine are cleaved by histidine-containing dipeptides at a micellar interface. High enantioselectivities (up to k(L)/k(D) = 30.4 at 0-degrees-C) are observed. Both the substrates and the catalysts contain an alternating sequence of hydrophobic and hydrophilic groups. Due to the need for hydration of the hydrophilic groups, the hydrophobic groups cannot dissolve completely into the micellar hydrocarbon phase. The kinetic data suggest that the micellar interface is capable of discriminating between transition states that have different hydrophilic and hydrophobic properties. One of the diastereomeric transition states is characterized by a hydrogen bond between the amide CO group of the ester and an NH group of the histidine-containing dipeptide. Upon formation of this hydrogen bond these polar CO and NH groups lose their hydrophilicity which allows the transfer of the adjacent apolar groups to the micellar hydrocarbon phase. The other diastereomeric transition state cannot form this hydrogen bond and the hydrophobic groups remain hydrated. Consequently, the latter transition state is of higher energy. The kinetic data reveal that it is important to prevent steric hinderance between the reactants in order to allow the unhindered formation of the hydrogen bond.