(S)-4-[(Z)-3-(3-Amino-2-bromo-phenoxy)-propenyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester | 168335-72-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (S)-4-[(Z)-3-(3-Amino-2-bromo-phenoxy)-propenyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester
• CAS: 168335-72-6
• 化学式: C₁₉H₂₇BrN₂O₄
• 分子量: 427.338
• InChiKey: HEUANNYZCLFGJQ-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.34
• 重原子数：
  26.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  74.02
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (S)-4-[(Z)-3-(3-Amino-2-bromo-phenoxy)-propenyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 在 四丁基氯化铵 、 sodium formate 、 palladium diacetate 、 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 以79%的产率得到(S)-4-(4-Amino-benzofuran-3-ylmethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Effect of Alteration of the Heterocyclic Nucleus of Indolactam V on Its Isoform Selectivity for PKC. Palladium-Catalyzed Route to Benzofuran Analogs of ILV

  摘要：

  The discovery of isoform-selective modulators of protein kinase C (PKC) appears worthwhile in further defining the roles of the individual PKC isoforms in cell type-specific processes. In comparison with the phorbol esters, little information is available regarding the isoform selectivity of the teleocidin family. Blumberg has reported recently that 7-n-octylindolactam V exhibits little if any selectivity for the isoforms tested. In order to probe the possibility of developing isotype-selective agents based on the indolactam V (ILV) structure, we sought to explore replacement of the indole nucleus by a benzofuran ring. Herein we describe a novel palladium-catalyzed route to four benzofuran analogues 11a-d of ILV together with details of their isoform selectivity. Of considerable interest is the unexpected finding that this subtle N to O structural change leads to a compound (11b) that is modestly more like 12,13-dibutyrate phorbol and less like n-octyl-ILV in its pattern of activity. Moreover, the effect of introducing an additional stereocenter at C-14 into these benzofurans was explored, and a clear preference for R-stereochemistry at the C-14 center of the teleocidin family was found, thus providing additional verification of previously published structural correlations between the families of PKC activators. Overall, the present findings provide an important new direction in the quest for isoform-selective activators of PKC.

  DOI：

  10.1021/ja00130a003
• 作为产物：
  描述：

  Hexanoic acid 2-bromo-3-(2,2-dimethyl-propionylamino)-phenyl ester 在 盐酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 生成 (S)-4-[(Z)-3-(3-Amino-2-bromo-phenoxy)-propenyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Effect of Alteration of the Heterocyclic Nucleus of Indolactam V on Its Isoform Selectivity for PKC. Palladium-Catalyzed Route to Benzofuran Analogs of ILV

  摘要：

  The discovery of isoform-selective modulators of protein kinase C (PKC) appears worthwhile in further defining the roles of the individual PKC isoforms in cell type-specific processes. In comparison with the phorbol esters, little information is available regarding the isoform selectivity of the teleocidin family. Blumberg has reported recently that 7-n-octylindolactam V exhibits little if any selectivity for the isoforms tested. In order to probe the possibility of developing isotype-selective agents based on the indolactam V (ILV) structure, we sought to explore replacement of the indole nucleus by a benzofuran ring. Herein we describe a novel palladium-catalyzed route to four benzofuran analogues 11a-d of ILV together with details of their isoform selectivity. Of considerable interest is the unexpected finding that this subtle N to O structural change leads to a compound (11b) that is modestly more like 12,13-dibutyrate phorbol and less like n-octyl-ILV in its pattern of activity. Moreover, the effect of introducing an additional stereocenter at C-14 into these benzofurans was explored, and a clear preference for R-stereochemistry at the C-14 center of the teleocidin family was found, thus providing additional verification of previously published structural correlations between the families of PKC activators. Overall, the present findings provide an important new direction in the quest for isoform-selective activators of PKC.

  DOI：

  10.1021/ja00130a003