2-Isopropyl-5-octynoic acid

• 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: 2-Isopropyl-5-octynoic acid
• 英文别名: 2-Propan-2-yloct-5-ynoic acid
• 化学式: C₁₁H₁₈O₂
• 分子量: 182.263
• InChiKey: GEFCEXWUKDJIBL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  异戊酸乙酯 在 盐酸 、 N,N-二甲基丙烯基脲 、 氢氧化钾 、 正丁基锂 、 potassium tert-butylate 、 氨 、 水 、 溴 、 sodium amide 、 二异丙胺 、 lithium diisopropyl amide 作用下， 反应 10.0h， 生成 2-Isopropyl-5-octynoic acid
  参考文献：
  名称：

  New approaches to the synthesis of alkyl-substituted enol lactone systems, inhibitors of the serine protease elastase

  摘要：

  We have synthesized a series of alkyl-substituted enol lactones designed to act as mechanism-based inhibitors of human neutrophil elastase (HLE). General methods were developed for the preparation of alpha- and beta-alkyl-substituted 5-hexynoic acids by the bromoform reaction on the corresponding alkynoic methyl ketone, prepared by an Eschenmoser-Tanabe fragmentation sequence from a suitably substituted cyclohexenone. By this method, beta-methyl- and beta,beta-dimethyl-5-hexynoic acids were synthesized from commercially available isophorone and 3,5-dimethyl-2-cyclohexen-1-one, respectively. Alpha-Substituted 5-hexynoic acids were prepared from 3-ethoxy-2-cyclohexen-1-one, using a novel ZnCl2-mediated alkylation that we developed; this method gives high yields of alpha'-alkylation products, even with secondary halides. The most efficient method for the preparation of alpha-substituted 5-hexynoic acids involved a four-reaction sequence-alkylation of the alpha-substituted ester with 1,4-dibromobutane, elimination, bromination and bisdehydrobromination-that proceeded in high overall yield. Protio enol lactonizations were performed with mercury(II) catalysis in CH2Cl2 or CH2Cl2-H2O. Stereo-selective Z-bromo enol lactonization was carried out by Br+-induced lactonization in the presence of Ag+. E-Bromo enol lactonization with N-bromosuccinimide in CH2Cl2 in the presence of a small amount of water gave better yields and shorter reaction times than the traditional anhydrous conditions. In studies of the inhibitory activity of these lactones toward several proteases (reported in full elsewhere), we found that the alpha-alkyl-substituted protio and bromo enol lactones 1-3 were very good inhibitors of HLE, with k(a)/K(i) values ranging from 14 500 to 37 500 M-1 s-1; the beta-alkyl-substituted enol lactones 5-8 showed only moderate inhibition of HLE.

  DOI：

  10.1021/jo00059a049

文献信息

• New approaches to the synthesis of alkyl-substituted enol lactone systems, inhibitors of the serine protease elastase
  作者：Wei Dai、John A. Katzenellenbogen

  DOI：10.1021/jo00059a049

  日期：1993.3

  We have synthesized a series of alkyl-substituted enol lactones designed to act as mechanism-based inhibitors of human neutrophil elastase (HLE). General methods were developed for the preparation of alpha- and beta-alkyl-substituted 5-hexynoic acids by the bromoform reaction on the corresponding alkynoic methyl ketone, prepared by an Eschenmoser-Tanabe fragmentation sequence from a suitably substituted cyclohexenone. By this method, beta-methyl- and beta,beta-dimethyl-5-hexynoic acids were synthesized from commercially available isophorone and 3,5-dimethyl-2-cyclohexen-1-one, respectively. Alpha-Substituted 5-hexynoic acids were prepared from 3-ethoxy-2-cyclohexen-1-one, using a novel ZnCl2-mediated alkylation that we developed; this method gives high yields of alpha'-alkylation products, even with secondary halides. The most efficient method for the preparation of alpha-substituted 5-hexynoic acids involved a four-reaction sequence-alkylation of the alpha-substituted ester with 1,4-dibromobutane, elimination, bromination and bisdehydrobromination-that proceeded in high overall yield. Protio enol lactonizations were performed with mercury(II) catalysis in CH2Cl2 or CH2Cl2-H2O. Stereo-selective Z-bromo enol lactonization was carried out by Br+-induced lactonization in the presence of Ag+. E-Bromo enol lactonization with N-bromosuccinimide in CH2Cl2 in the presence of a small amount of water gave better yields and shorter reaction times than the traditional anhydrous conditions. In studies of the inhibitory activity of these lactones toward several proteases (reported in full elsewhere), we found that the alpha-alkyl-substituted protio and bromo enol lactones 1-3 were very good inhibitors of HLE, with k(a)/K(i) values ranging from 14 500 to 37 500 M-1 s-1; the beta-alkyl-substituted enol lactones 5-8 showed only moderate inhibition of HLE.