(2S,3R,4S)-3-Hydroxy-4-((4E,6E,12E,14Z)-(2R,3S,9S,10S,11R)-10-hydroxy-3,15-dimethoxy-7,9,11,13-tetramethyl-16-oxo-oxacyclohexadeca-4,6,12,14-tetraen-2-yl)-2-methyl-pentanoic acid

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: (2S,3R,4S)-3-Hydroxy-4-((4E,6E,12E,14Z)-(2R,3S,9S,10S,11R)-10-hydroxy-3,15-dimethoxy-7,9,11,13-tetramethyl-16-oxo-oxacyclohexadeca-4,6,12,14-tetraen-2-yl)-2-methyl-pentanoic acid
• 英文别名: (2S,3R,4S)-3-hydroxy-4-[(2R,3S,4E,6E,9S,10S,11R,12E,14Z)-10-hydroxy-3,15-dimethoxy-7,9,11,13-tetramethyl-16-oxo-1-oxacyclohexadeca-4,6,12,14-tetraen-2-yl]-2-methylpentanoic acid
• 化学式: C₂₇H₄₂O₈
• 分子量: 494.626
• InChiKey: IJPJCRAUPZATAY-MQMGXAQVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (3Z,5E,7R,8S,9S,11E,13E,15S,16R)-8-hydroxy-16-[(2S,3R,4S)-3-hydroxy-4-[(2R,5R,6R)-2-hydroxy-5-methyl-4-oxo-6-propan-2-yloxan-2-yl]pentan-2-yl]-3,15-dimethoxy-5,7,9,11-tetramethyl-1-oxacyclohexadeca-3,5,11,13-tetraen-2-one 在 ammonium acetate 、 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 96.0h， 以29%的产率得到(2S,3R,4S)-3-Hydroxy-4-((4E,6E,12E,14Z)-(2R,3S,9S,10S,11R)-10-hydroxy-3,15-dimethoxy-7,9,11,13-tetramethyl-16-oxo-oxacyclohexadeca-4,6,12,14-tetraen-2-yl)-2-methyl-pentanoic acid
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Bafilomycin A₁ Derivatives as Inhibitors of Vacuolar H⁺-ATPase

  摘要：

  The macrolide antibiotic bafilomycin A(1) is a highly potent and selective inhibitor of all the vacuolar ATPases (V-ATPases). With the aim of obtaining novel analogues specific for the osteoclast subclass of vacuolar ATPase, 31 derivatives of bafilomycin A(1) were synthesized and tested for their ability to inhibit differentially the V-ATPase-driven proton transport in membrane vesicles derived from chicken osteoclasts (cOc) and bovine chromaffin granules (bCG). Although none of the new analogues were more potent than the parent compound, the obtained data provided a significant amount of information about the structural requirements for the inhibitory activity of bafilomycin A(1). The different effects of a few analogues on the two enzymes could also suggest the possibility of a selective modulation of the V-ATPases in different tissues.

  DOI：

  10.1021/jm9707838

文献信息

• Synthesis and Structure−Activity Relationships of Bafilomycin A₁ Derivatives as Inhibitors of Vacuolar H⁺-ATPase
  作者：Stefania Gagliardi、P. Andrea Gatti、Pietro Belfiore、Andrea Zocchetti、Geoffrey D. Clarke、Carlo Farina

  DOI：10.1021/jm9707838

  日期：1998.5.1

  The macrolide antibiotic bafilomycin A(1) is a highly potent and selective inhibitor of all the vacuolar ATPases (V-ATPases). With the aim of obtaining novel analogues specific for the osteoclast subclass of vacuolar ATPase, 31 derivatives of bafilomycin A(1) were synthesized and tested for their ability to inhibit differentially the V-ATPase-driven proton transport in membrane vesicles derived from chicken osteoclasts (cOc) and bovine chromaffin granules (bCG). Although none of the new analogues were more potent than the parent compound, the obtained data provided a significant amount of information about the structural requirements for the inhibitory activity of bafilomycin A(1). The different effects of a few analogues on the two enzymes could also suggest the possibility of a selective modulation of the V-ATPases in different tissues.