(E)-4-(tert-Butyl-diphenyl-silanyloxymethyl)-6-hydroxy-hex-3-enoic acid methyl ester | 187871-93-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (E)-4-(tert-Butyl-diphenyl-silanyloxymethyl)-6-hydroxy-hex-3-enoic acid methyl ester
• 英文别名: methyl (E)-4-[[tert-butyl(diphenyl)silyl]oxymethyl]-6-hydroxyhex-3-enoate
• CAS: 187871-93-8
• 化学式: C₂₄H₃₂O₄Si
• 分子量: 412.601
• InChiKey: ZIWNJEDINZBWKV-HMMYKYKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.43
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-4-(tert-Butyl-diphenyl-silanyloxymethyl)-6-hydroxy-hex-3-enoic acid methyl ester 在 4-二甲氨基吡啶 、 sodium hydroxide 、 二苯基磷酸 、 四丁基氟化铵 、 sodium carbonate 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 205.0h， 生成 (2S,3S)-2-[3-(4-Benzyloxy-benzyl)-5-hydroxymethyl-2-oxo-2,3,6,7-tetrahydro-azepin-1-yl]-3-methyl-pentanoic acid tert-butyl ester
  参考文献：
  名称：

  Design, Synthesis, and Biological Activities of Four Angiotensin II Receptor Ligands with γ-Turn Mimetics Replacing Amino Acid Residues 3−5

  摘要：

  Disulfide cyclization is a powerful method for reducing the conformational space of a peptide. This in turn may enable the study of its bioactive conformation. Several analogues of angiotensin II (Ang II) containing a disulfide bridge between amino acids 3 and 5 have been reported. Among these the cyclic octapeptides c[Hcy(3,5)]-Ang II, c[Cys(3,5)]-Ang II, and c[Pen(3,5)]Ang II showed significant activity at Ang II receptors. We have performed conformational analysis studies using theoretical calculations and H-1-NMR spectroscopy on tripeptide model compounds of these cyclic octapeptides which show that the cyclic moieties of c[Cys(3,5)]-Ang II and c[Pen(3,5)]-Ang II preferentially assume an inverse gamma-turn conformation. On the basis of these results, we substituted amino acid residues 3-5 in Ang II with two different gamma-turn mimetics giving four diastereomeric Ang II analogues. Interestingly, two of these are equipotent to Ang II in binding to AT(1) receptors. In the contractile test using rabbit aorta rings, one of the analogues is an agonist with full contractile activity approximately equipotent to c[Pen(3,5)]-Ang II but 300-fold less potent than Ang II. This low potency may suggest that Ang II does not adopt a gamma-turn in the 3-5 region when interacting with the receptor.

  DOI：

  10.1021/jm960553d
• 作为产物：
  描述：

  tert-Butyl-(4-methoxy-cyclohexa-1,4-dienylmethoxy)-diphenyl-silane 在 sodium tetrahydroborate 、 二甲基硫 、 臭氧 作用下， 生成 (E)-4-(tert-Butyl-diphenyl-silanyloxymethyl)-6-hydroxy-hex-3-enoic acid methyl ester
  参考文献：
  名称：

  Design, Synthesis, and Biological Activities of Four Angiotensin II Receptor Ligands with γ-Turn Mimetics Replacing Amino Acid Residues 3−5

  摘要：

  Disulfide cyclization is a powerful method for reducing the conformational space of a peptide. This in turn may enable the study of its bioactive conformation. Several analogues of angiotensin II (Ang II) containing a disulfide bridge between amino acids 3 and 5 have been reported. Among these the cyclic octapeptides c[Hcy(3,5)]-Ang II, c[Cys(3,5)]-Ang II, and c[Pen(3,5)]Ang II showed significant activity at Ang II receptors. We have performed conformational analysis studies using theoretical calculations and H-1-NMR spectroscopy on tripeptide model compounds of these cyclic octapeptides which show that the cyclic moieties of c[Cys(3,5)]-Ang II and c[Pen(3,5)]-Ang II preferentially assume an inverse gamma-turn conformation. On the basis of these results, we substituted amino acid residues 3-5 in Ang II with two different gamma-turn mimetics giving four diastereomeric Ang II analogues. Interestingly, two of these are equipotent to Ang II in binding to AT(1) receptors. In the contractile test using rabbit aorta rings, one of the analogues is an agonist with full contractile activity approximately equipotent to c[Pen(3,5)]-Ang II but 300-fold less potent than Ang II. This low potency may suggest that Ang II does not adopt a gamma-turn in the 3-5 region when interacting with the receptor.

  DOI：

  10.1021/jm960553d

文献信息

• Design, Synthesis, and Biological Activities of Four Angiotensin II Receptor Ligands with γ-Turn Mimetics Replacing Amino Acid Residues 3−5
  作者：Boris Schmidt、Susanna Lindman、Weimin Tong、Gunnar Lindeberg、Adolf Gogoll、Zhennan Lai、Madeleine Thörnwall、Barbro Synnergren、Annika Nilsson、Christopher J. Welch、Morgan Sohtell、Christer Westerlund、Fred Nyberg、Anders Karlén、Anders Hallberg

  DOI：10.1021/jm960553d

  日期：1997.3.1

  Disulfide cyclization is a powerful method for reducing the conformational space of a peptide. This in turn may enable the study of its bioactive conformation. Several analogues of angiotensin II (Ang II) containing a disulfide bridge between amino acids 3 and 5 have been reported. Among these the cyclic octapeptides c[Hcy(3,5)]-Ang II, c[Cys(3,5)]-Ang II, and c[Pen(3,5)]Ang II showed significant activity at Ang II receptors. We have performed conformational analysis studies using theoretical calculations and H-1-NMR spectroscopy on tripeptide model compounds of these cyclic octapeptides which show that the cyclic moieties of c[Cys(3,5)]-Ang II and c[Pen(3,5)]-Ang II preferentially assume an inverse gamma-turn conformation. On the basis of these results, we substituted amino acid residues 3-5 in Ang II with two different gamma-turn mimetics giving four diastereomeric Ang II analogues. Interestingly, two of these are equipotent to Ang II in binding to AT(1) receptors. In the contractile test using rabbit aorta rings, one of the analogues is an agonist with full contractile activity approximately equipotent to c[Pen(3,5)]-Ang II but 300-fold less potent than Ang II. This low potency may suggest that Ang II does not adopt a gamma-turn in the 3-5 region when interacting with the receptor.