Nalpha-叔丁氧羰基-N-对甲苯磺酰基-L-组氨酸二环己胺盐 | 65057-34-3

• 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
• 中文名称: Nalpha-叔丁氧羰基-N-对甲苯磺酰基-L-组氨酸二环己胺盐
• 中文别名: N-BOC-1-(P-甲苯磺酰基)-L-组氨酸二环己基铵盐；N-叔丁氧羰基-N(咪唑)-(4-甲基苯磺酰基)-L-组氨酸二环己胺盐；N-BOC-1-(P-甲苯磺酰基)-L-组氨酸 二环己基铵盐
• 英文名称: dicyclohexylammpnoim salt of N-(tert-butoxycarbonyl)-N^im-tosyl-L-histidine
• 英文别名: N^α-t-butoxycarbonyl-N^im-tosyl-L-histidine dicyclohexylamine adduct；N^α-Boc-His(N^im-Tos)*Dcha；N-(tert-butoxycarbonyl)-1-(p-tosyl)-L-histidine, compound with dicyclohexylamine (1:1)；dicyclohexylazanium;(2S)-3-[1-(4-methylphenyl)sulfonylimidazol-4-yl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 65057-34-3
• 化学式: C₁₂H₂₃N*C₁₈H₂₃N₃O₆S
• mdl: MFCD00039005
• 分子量: 590.784
• InChiKey: RNRUVXUHYUOWJW-RSAXXLAASA-N

物化性质

• 熔点：
  ~165 °C (dec.)

计算性质

• 辛醇/水分配系数(LogP)：
  1.36
• 重原子数：
  41
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.633
• 拓扑面积：
  148
• 氢给体数：
  3
• 氢受体数：
  8

安全信息

• WGK Germany：
  3
• 储存条件：
  2-8°C

反应信息

• 作为反应物：
  描述：

  Nalpha-叔丁氧羰基-N-对甲苯磺酰基-L-组氨酸二环己胺盐 在 对甲苯磺酸 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 丙酮 、 苯 为溶剂， 反应 34.5h， 生成 N,N-ditetradecyl-N^α-(6-trimethylammoniohexanoyl)-L-histidinamide bromide
  参考文献：
  名称：

  功能化囊泡在 5'-磷酸吡哆醛与疏水性氨基酸转氨反应中的催化效率

  摘要：

  在 pH 7.0、μ 0.10 (KCl) 和 30.0±0.1 °C 的磷酸硼酸水溶液缓冲液中研究了 5'-磷酸吡哆醛 (PLP) 与 N-十二烷基-L-丙氨酰胺 (AlaC12) 的转氨反应。 N,N-二十四烷基-Nα-(6-三甲基羊离子己酰基)-L-组氨酰胺溴化物(N+C5His2C14)单壁囊泡的存在。在席夫碱形成过程中，囊泡和反应物之间的静电和疏水相互作用导致 PLP 和 AlaC12 分别掺入囊泡的极性和疏水域中。醛亚胺席夫碱异构化为相应的酮亚胺席夫碱被证实是转氨过程中的速率决定步骤。发现囊泡系统中的反应位点在极性上与二恶烷-水 (7:3 v/v) 相同。然而，相对于二恶烷-水 (7:3 v/v)，囊泡中的总体反应速率提高了 230 倍。疏水性和适当极性的微环境构建于...

  DOI：

  10.1246/bcsj.55.3004

文献信息

• Resin Selection Based on the Lability of Peptidyl-Resin Linkage towards HF and TFA Steps: Dependence on the C-Terminal Amino Acid and Peptide Length.
  作者：Guita N. JUBILUT、Maria Teresa MIRANDA、Mineko TOMINAGA、Yoshio OKADA、Antonio MIRANDA、Clovis R. NAKAIE

  DOI：10.1248/cpb.47.1560

  日期：——

  Ideally, the solid support used for tert-butyloxycarbonyl (Boc)-peptide synthesis method must allow sufficient stability of the peptide linkage towards TFA-α-amino deprotection but adequate lability to final HF cleavage. Due to these conflicting characteristics, the choice of the correct resin for peptide synthesis is complex and dependent upon many factors. Aiming to clarify this issue, a time-course study of the trifluoroacetic acid (TFA) and HF steps using model peptidyl-resins was developed. The peptidyl-resin bond stability was strongly dependent upon the resin and the carboxy-terminus residue. The decreasing order of acid stability for resins was : benzhydrylamine-resin (BHAR)>p-methylbenzhydrylamine-resin (MBHAR)≅4-(oxymethyl)-phenylacetamidomethyl-resin (PAMR)>chloromethyl-resin (CMR) and Phe>Gly≅His≅Asp for C-terminal amino acids. HF-cleavage times of near 6 h (BHAR) and 2-3 h (MBHAR and PAMR) were necessary for quantitative cleavage of hydrophobic Phe residue-containing sequence at its C-terminal portion. When premature chain loss in TFA and incomplete cleavage in HF values were both quantitatively considered, a significant decrease in the overall yield (up to 35%) was observed in some resins. Moreover, MBHAR was more suitable than BHAR only when the peptide C-terminal residue is hydrophobic. The data also allow the prediction that due to more significant chain loss in TFA when MBHAR is used, BHAR will be the resin of choice for much longer than 40-mer peptide sequences containing C-terminal hydrophilic residues. Otherwise PAMR is the best resin for the synthesis of free carboxyl peptides but significantly low HF cleavage was observed when the C-terminal amino acid is of the hydrophobic-type.

  理想情况下，用于叔丁氧羰基（Boc）多肽合成方法的固体载体必须确保多肽键对三氟乙酸（TFA）α-氨基脱保护有足够的稳定性，同时对最终氢氟酸（HF）裂解有足够的易变性。由于这些相互矛盾的特性，选择正确的用于多肽合成的树脂是复杂的，并取决于多种因素。为了阐明这一问题，我们开发了一项使用模型肽树脂进行三氟乙酸（TFA）和氢氟酸（HF）步骤的时间进程研究。肽树脂键的稳定性强烈依赖于树脂和羧基末端残基。树脂的酸稳定性递减顺序为：双苄胺树脂（BHAR）＞对甲基双苄胺树脂（MBHAR）≈4-（羟甲基）苯乙酰胺甲基树脂（PAMR）＞氯甲基树脂（CMR），以及对于C端氨基酸：Phe＞Gly≈His≈Asp。对于含有疏水性Phe残基的序列在其C端部分，需要接近6小时的HF裂解时间（BHAR）和2-3小时（MBHAR和PAMR）以实现定量裂解。当考虑TFA中的过早链损耗和HF中的不完全裂解时，某些树脂的整体产率显著下降（高达35%）。此外，只有当多肽C端残基是疏水性的时候，MBHAR才比BHAR更合适。数据还允许预测，由于使用MBHAR时TFA中链损耗更显著，对于含有C端亲水性残基的40-mer以上的多肽序列，BHAR将是首选树脂。否则，PAMR是合成游离羧基多肽的最佳树脂，但当C端氨基酸是疏水性类型时，观察到HF裂解显著降低。
• Design, structure-activity, and molecular modeling studies of potent renin inhibitory peptides having N-terminal Nin-For-Trp (Ftr): angiotensinogen congeners modified by P1-P1' Phe-Phe, Sta, Leu.psi.[CH(OH)CH2]Val or Leu.psi.[CH2NH]Val substitutions
  作者：Tomi K. Sawyer、Donald T. Pals、Boryeu Mao、Douglas J. Staples、Anne E. DeVaux、Linda L. Maggiora、Joseph A. Affholter、Warren Kati、David Duchamp

  DOI：10.1021/jm00396a006

  日期：1988.1

  A structure-conformation-activity investigation of several angiotensinogen (ANG) based inhibitors of human renin modified by either Phe-Phe, Sta, Leu psi[CH2NH]Val, or Leu psi[CH(OH)CH2]Val at the P1-P1' clevage site and P5 Trp(Nin-For) (Ftr) was performed. Specifically, Ac-Ftr-Pro-Phe-His-Phe-Phe-Val-Ftr-NH2 (1) provided a potent (KI = 2.7 X 10(-8) M) P1-P1' Phe-Phe substituted renin inhibitor to initiate these studies. Substitution of the P1-P1' Phe-Phe in compound 1 by Sta effected a 1,000-fold increase in biological potency for the resultant octapeptide Ac-Ftr-Pro-Phe-His-Sta-Val-Ftr-NH2 (10; KI = 6.7 X 10(-11) M). Kinetic analysis of compound 10 showed it to be a competitive inhibitor of human renin catalyzed proteolysis of human ANG. Chemical modifications of the compounds 1 and 10 were evaluated on the basis of comparative human plasma renin inhibitory activities (IC50 values) in vitro. Carboxy-terminal truncation studies on compound 10 showed that the P2' Val and P3' Ftr residues could both be eliminated without significant loss (ca. 10-fold) in renin inhibitory activity as exemplified by the pentapeptide Ac-Ftr-Pro-Phe-His-Sta-NH2 (12; IC50 = 3.8 X 10(-9) M). In addition, the corresponding P1-P1' Leu psi[CH(OH)CH2]Val and Leu psi[CH2NH]Val derivatives of compound 12 were potent renin inhibitors: Ac-Ftr-Pro-Phe-His-Leu psi[CH(OH)CH2]Val-NH2 (13; IC50 = 3.1 X 10(-10) M) and Ac-Ftr-Pro-Phe-His-Leu psi[CH2NH]Val-NH2 (14; IC50 = 2.1 X 10(-8) M). The structure-conformation-activity properties of the N-terminal Ftr substitution of these human renin inhibitors was examined by (1) comparative analysis of several analogues of 1 and Ac-Ftr-Pro-Phe-His-Sta-Ile-NH2 (17; IC50 = 1.0 X 10(-10) M) having P5 site modifications by Trp, His, D-Ftr, and D-His, (2) deletion of the N-terminal Ftr residue from compounds 12 and 17, to provide Ac-Pro-Phe-His-Sta-Ile-NH2 (16; IC50 = 3.1 X 10(-8) M) and Ac-Pro-Phe-His-Sta-NH2 (15; IC50 = 5.6 X 10(-6) M), and (3) computer modeling and dynamics studies of compounds 1 and 17 bound to CKH-RENIN, a simulated human renin model, which were focused on identifying potential intermolecular interactions of their common P5-P2 sequence, Ac-Ftr-Pro-Phe-His, at the enzyme active site.(ABSTRACT TRUNCATED AT 400 WORDS)
• General-base catalysis of the hydrolysis of p-nitrophenyl carboxylates by micellar surfactants involving a histidyl residue
  作者：Yukito Murakami、Akio Nakano、Akira Yoshimatsu、Kiyoshi Matsumoto

  DOI：10.1021/ja00400a044

  日期：1981.5
• SMITH, CLARK W.;SANEII, HOSSAIN H.;SAWYER, TOMI K.;PALS, DONALD T.;SCAHIL+, J. MED. CHEM., 31,(1988) N 7, 1377-1382
  作者：SMITH, CLARK W.、SANEII, HOSSAIN H.、SAWYER, TOMI K.、PALS, DONALD T.、SCAHIL+

  DOI：——

  日期：——
• Catalytic Efficiency of Functionalized Vesicles in the Transamination of Pyridoxal-5′-phosphate with a Hydrophobic Amino Acid
  作者：Yukito Murakami、Akio Nakano、Kazunari Akiyoshi

  DOI：10.1246/bcsj.55.3004

  日期：1982.9

  and AlaC12 into polar and hydrophobic domains of the vesicles, respectively, in the Schiff-base formation process. The isomerization of the aldimine Schiff-base to the corresponding ketimine Schiff-base was confirmed to be the rate-determining step in the transamination process. The reaction site in the vesicular system was found to be equivalent in polarity to dioxane–water (7:3 v/v). However, the

  在 pH 7.0、μ 0.10 (KCl) 和 30.0±0.1 °C 的磷酸硼酸水溶液缓冲液中研究了 5'-磷酸吡哆醛 (PLP) 与 N-十二烷基-L-丙氨酰胺 (AlaC12) 的转氨反应。 N,N-二十四烷基-Nα-(6-三甲基羊离子己酰基)-L-组氨酰胺溴化物(N+C5His2C14)单壁囊泡的存在。在席夫碱形成过程中，囊泡和反应物之间的静电和疏水相互作用导致 PLP 和 AlaC12 分别掺入囊泡的极性和疏水域中。醛亚胺席夫碱异构化为相应的酮亚胺席夫碱被证实是转氨过程中的速率决定步骤。发现囊泡系统中的反应位点在极性上与二恶烷-水 (7:3 v/v) 相同。然而，相对于二恶烷-水 (7:3 v/v)，囊泡中的总体反应速率提高了 230 倍。疏水性和适当极性的微环境构建于...