(2S,3S), 2-[4-methoxybenzylsulfanyl], 3-tertiobutyloxycarbonylamino-hexane-dioic acid 1-allyl ester, 6-tertiobutyl ester | 191401-96-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (2S,3S), 2-[4-methoxybenzylsulfanyl], 3-tertiobutyloxycarbonylamino-hexane-dioic acid 1-allyl ester, 6-tertiobutyl ester
• 英文别名: 6-O-tert-butyl 1-O-prop-2-enyl (2S,3S)-2-[(4-methoxyphenyl)methylsulfanyl]-3-[(2-methylpropan-2-yl)oxycarbonylamino]hexanedioate
• CAS: 191401-96-4
• 化学式: C₂₆H₃₉NO₇S
• 分子量: 509.664
• InChiKey: HUFHFKVZIFNNHU-UNMCSNQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  35
• 可旋转键数：
  17
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2S,3S), 2-[4-methoxybenzylsulfanyl], 3-tertiobutyloxycarbonylamino-hexane-dioic acid 1-allyl ester, 6-tertiobutyl ester 在 四氢吡咯 、 四(三苯基膦)钯 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以100%的产率得到(2S,3S), 2-[4-methoxybenzylsulfanyl], 3-tertiobutyloxycarbonylamino-hexane-dioic acid 6-tertiobutyl ester
  参考文献：
  名称：

  Investigation of Subsite Preferences in Aminopeptidase A (EC 3.4.11.7) Led to the Design of the First Highly Potent and Selective Inhibitors of This Enzyme

  摘要：

  The study of the physiological roles of the membrane-bound zinc-aminopeptidase A (glutamyl aminopeptidase, EC 3.4.11.7) needs the design of efficient and selective inhibitors of this enzyme. An acute exploration of aminopeptidase A active site was performed by a combinatorial approach using (3-amino-2-mercapto-acyl)dipeptides able to sc its S-1, S-1', and S-2' subsites. This analysis confirmed that the S-1 subsite is optimally blocked by a glutamate or isosteric residues and demonstrated that the S-1' subsite is hydrophobic whereas the S-2' subsite recognizes preferentially negatively charged residues derived from aspartic acid. The optimization of these structural parameters led to the synthesis of nanomolar and subnanomolar inhibitors of aminopeptidase A such as H3N+CH(CH2CH2SO3-)CH(SH)CO-Ile-(3-COOH)Pro that exhibits a K-i of 0.87 nM. The best compounds were synthesized by a stereochemically controlled route. These first described highly potent inhibitors could allow studies about the role of physiological substrates of APA such as angiotensin II- and cholecystokinin CCK8 in the central nervous system.

  DOI：

  10.1021/jm9903040
• 作为产物：
  描述：

  4-甲氧基苄硫醇 在 silver(I) acetate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 生成 (2S,3S), 2-[4-methoxybenzylsulfanyl], 3-tertiobutyloxycarbonylamino-hexane-dioic acid 1-allyl ester, 6-tertiobutyl ester
  参考文献：
  名称：

  2,4-Dinitrophenyl 4-Methoxybenzyl Disulfide:  A New Efficient Reagent for the Electrophilic Sulfenylation of β-Amino Ester Enolates

  摘要：

  DOI：

  10.1021/jo9623853

文献信息

• 2,4-Dinitrophenyl 4-Methoxybenzyl Disulfide:  A New Efficient Reagent for the Electrophilic Sulfenylation of β-Amino Ester Enolates
  作者：Laurent Bischoff、Christelle David、Loïc Martin、Hervé Meudal、Bernard-Pierre Roques、Marie-Claude Fournié-Zaluski

  DOI：10.1021/jo9623853

  日期：1997.7.1
• Investigation of Subsite Preferences in Aminopeptidase A (EC 3.4.11.7) Led to the Design of the First Highly Potent and Selective Inhibitors of This Enzyme
  作者：Christelle David、Laurent Bischoff、Hervé Meudal、Aurélie Mothé、Nadia De Mota、Sophie DaNascimento、Catherine Llorens-Cortes、Marie-Claude Fournié-Zaluski、Bernard P. Roques

  DOI：10.1021/jm9903040

  日期：1999.12.1

  The study of the physiological roles of the membrane-bound zinc-aminopeptidase A (glutamyl aminopeptidase, EC 3.4.11.7) needs the design of efficient and selective inhibitors of this enzyme. An acute exploration of aminopeptidase A active site was performed by a combinatorial approach using (3-amino-2-mercapto-acyl)dipeptides able to sc its S-1, S-1', and S-2' subsites. This analysis confirmed that the S-1 subsite is optimally blocked by a glutamate or isosteric residues and demonstrated that the S-1' subsite is hydrophobic whereas the S-2' subsite recognizes preferentially negatively charged residues derived from aspartic acid. The optimization of these structural parameters led to the synthesis of nanomolar and subnanomolar inhibitors of aminopeptidase A such as H3N+CH(CH2CH2SO3-)CH(SH)CO-Ile-(3-COOH)Pro that exhibits a K-i of 0.87 nM. The best compounds were synthesized by a stereochemically controlled route. These first described highly potent inhibitors could allow studies about the role of physiological substrates of APA such as angiotensin II- and cholecystokinin CCK8 in the central nervous system.