1-(But-3-enyl-methyl-phenylsilyl)-3-methylbutan-1-amine | 202743-86-0

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: 1-(But-3-enyl-methyl-phenylsilyl)-3-methylbutan-1-amine
• CAS: 202743-86-0
• 化学式: C₁₆H₂₇NSi
• 分子量: 261.483
• InChiKey: NLPZDIKZWOEVGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.46
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  苯甲酰氯 、 1-(But-3-enyl-methyl-phenylsilyl)-3-methylbutan-1-amine 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以2.6 g的产率得到N-[1-(3-butenyl(methyl)phenylsilyl)-3-methylbutyl] benzamide
  参考文献：
  名称：

  Silicon-Based Metalloprotease Inhibitors:  Synthesis and Evaluation of Silanol and Silanediol Peptide Analogues as Inhibitors of Angiotensin-Converting Enzyme¹

  摘要：

  Silanols are best known as unstable precursors of siloxane (silicone) polymers, substances generally considered stable and inert, but have the potential to mimic a hydrated carbonyl and inhibit protease enzymes. While previous testing of simple silanediol and silanetriol species as inhibitors of hydrolase enzymes found them ineffective, this study reports polypeptide mimics with a central methylsilanol [SiMeOH] or silanediol [Si(OH)(2)] group and their assessment as effective transition state analogue inhibitors of the well-studied metalloprotease angiotensin-converting enzyme (ACE). Central to the synthesis strategy, phenylsilanes were employed as acid-hydrolyzable precursors of the silanol group. The N-benzoyl Leu[SiMeOH]-Gly benzyl amides proved to be stable and readily characterized. In contrast, the Leu-[Si(OH)(2)]Gly structure was difficult to characterize, possibly because of self-association. Capping the silanediol with chlorotrimethylsilane gave a well-defined trisiloxane, demonstrating that the silanediol was monomeric. The Leu-[Si]-Gly structures were converted to Leu-[Si]-Ala analogues by enolate alkylation. Coupling of the silanol precursors with proline tert-butyl ester gave N-benzoyl Leu-[Si]-Gly-Pro and N-benzoyl Leu[Si]-Ala-Pro tripeptide analogues. Treatment of these with triflic acid formed the corresponding methylsilanols and silanediols, all of which were monomeric. The silanediol tripeptide mimics inhibited ACE with IC50 values as low as 14 nM. Methylsilanols, in contrast, were poor inhibitors, with IC50 values above 3000 nM. These data, including comparisons with inhibition data from carbon analogues, are consistent with binding of the silanediols by chelation of the ACE active site zinc, whereas the methylsilanols ligate poorly.

  DOI：

  10.1021/ja026158w
• 作为产物：
  描述：

  methyldifluorophenylsilane 在 lithium aluminium tetrahydride 、 正丁基锂 、 sodium azide 、 三乙胺 、 mercury dichloride 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 5.92h， 生成 1-(But-3-enyl-methyl-phenylsilyl)-3-methylbutan-1-amine
  参考文献：
  名称：

  Silicon-Based Metalloprotease Inhibitors:  Synthesis and Evaluation of Silanol and Silanediol Peptide Analogues as Inhibitors of Angiotensin-Converting Enzyme¹

  摘要：

  Silanols are best known as unstable precursors of siloxane (silicone) polymers, substances generally considered stable and inert, but have the potential to mimic a hydrated carbonyl and inhibit protease enzymes. While previous testing of simple silanediol and silanetriol species as inhibitors of hydrolase enzymes found them ineffective, this study reports polypeptide mimics with a central methylsilanol [SiMeOH] or silanediol [Si(OH)(2)] group and their assessment as effective transition state analogue inhibitors of the well-studied metalloprotease angiotensin-converting enzyme (ACE). Central to the synthesis strategy, phenylsilanes were employed as acid-hydrolyzable precursors of the silanol group. The N-benzoyl Leu[SiMeOH]-Gly benzyl amides proved to be stable and readily characterized. In contrast, the Leu-[Si(OH)(2)]Gly structure was difficult to characterize, possibly because of self-association. Capping the silanediol with chlorotrimethylsilane gave a well-defined trisiloxane, demonstrating that the silanediol was monomeric. The Leu-[Si]-Gly structures were converted to Leu-[Si]-Ala analogues by enolate alkylation. Coupling of the silanol precursors with proline tert-butyl ester gave N-benzoyl Leu-[Si]-Gly-Pro and N-benzoyl Leu[Si]-Ala-Pro tripeptide analogues. Treatment of these with triflic acid formed the corresponding methylsilanols and silanediols, all of which were monomeric. The silanediol tripeptide mimics inhibited ACE with IC50 values as low as 14 nM. Methylsilanols, in contrast, were poor inhibitors, with IC50 values above 3000 nM. These data, including comparisons with inhibition data from carbon analogues, are consistent with binding of the silanediols by chelation of the ACE active site zinc, whereas the methylsilanols ligate poorly.

  DOI：

  10.1021/ja026158w

文献信息

• Silicon-Based Metalloprotease Inhibitors:  Synthesis and Evaluation of Silanol and Silanediol Peptide Analogues as Inhibitors of Angiotensin-Converting Enzyme¹
  作者：Mwangi wa Mutahi、Thomas Nittoli、Luxuan Guo、Scott McN. Sieburth

  DOI：10.1021/ja026158w

  日期：2002.6.1

  Silanols are best known as unstable precursors of siloxane (silicone) polymers, substances generally considered stable and inert, but have the potential to mimic a hydrated carbonyl and inhibit protease enzymes. While previous testing of simple silanediol and silanetriol species as inhibitors of hydrolase enzymes found them ineffective, this study reports polypeptide mimics with a central methylsilanol [SiMeOH] or silanediol [Si(OH)(2)] group and their assessment as effective transition state analogue inhibitors of the well-studied metalloprotease angiotensin-converting enzyme (ACE). Central to the synthesis strategy, phenylsilanes were employed as acid-hydrolyzable precursors of the silanol group. The N-benzoyl Leu[SiMeOH]-Gly benzyl amides proved to be stable and readily characterized. In contrast, the Leu-[Si(OH)(2)]Gly structure was difficult to characterize, possibly because of self-association. Capping the silanediol with chlorotrimethylsilane gave a well-defined trisiloxane, demonstrating that the silanediol was monomeric. The Leu-[Si]-Gly structures were converted to Leu-[Si]-Ala analogues by enolate alkylation. Coupling of the silanol precursors with proline tert-butyl ester gave N-benzoyl Leu-[Si]-Gly-Pro and N-benzoyl Leu[Si]-Ala-Pro tripeptide analogues. Treatment of these with triflic acid formed the corresponding methylsilanols and silanediols, all of which were monomeric. The silanediol tripeptide mimics inhibited ACE with IC50 values as low as 14 nM. Methylsilanols, in contrast, were poor inhibitors, with IC50 values above 3000 nM. These data, including comparisons with inhibition data from carbon analogues, are consistent with binding of the silanediols by chelation of the ACE active site zinc, whereas the methylsilanols ligate poorly.