erythro pumiliotoxin PTX-B | 112455-73-9

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 普米里奥毒素、同普米里奥毒素和别普米里奥毒素
• 英文名称: erythro pumiliotoxin PTX-B
• 英文别名: (8S,8aS)-8-hydroxy-8-methyl-6(Z)-<6'-(R),7(S)-dihydroxy-2'(R),5'-dimethyl-4'(E)-octenylidene>octahydroindolizidine；(E,2S,3R,7R,8Z)-8-[(8S,8aS)-8-hydroxy-8-methyl-1,2,3,5,7,8a-hexahydroindolizin-6-ylidene]-4,7-dimethyloct-4-ene-2,3-diol
• CAS: 112455-73-9
• 化学式: C₁₉H₃₃NO₃
• 分子量: 323.476
• InChiKey: WDSCDQQQRGGVPJ-YJFWMCLUSA-N

物化性质

• 沸点：
  481.5±45.0 °C(predicted)
• 密度：
  1.10±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  63.9
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  乙酸酐 、 erythro pumiliotoxin PTX-B 在 吡啶 作用下， 反应 2.0h， 生成 Acetic acid (E)-(1R,5R)-1-((S)-1-acetoxy-ethyl)-6-[(8S,8aS)-8-hydroxy-8-methyl-hexahydro-indolizin-(6Z)-ylidene]-2,5-dimethyl-hex-2-enyl ester
  参考文献：
  名称：

  A naturally occurring erythro diastereomer of pumiliotoxin b

  摘要：

  DOI：

  10.1016/s0040-4020(01)86205-0
• 作为产物：
  描述：

  (8S,8aS)-8-hydroxy-8-methyl-6(Z)-<4-oxo-2(R)-methylbutylidene>octahydroindolizidine 在 lithium aluminium tetrahydride 、 氨 、 lithium 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 68.0h， 生成 erythro pumiliotoxin PTX-B
  参考文献：
  名称：

  Pumiliotoxin alkaloids: relationship of cardiotonic activity to sodium channel activity and phosphatidylinositol turnover

  摘要：

  The cardiotonic activity of pumiliotoxin B (PTX-B, 6-(6',7'-dihydroxy-2',5'-dimethyl-(E)-4'-octenylidene)-8-hydroxy-8 -methyl-1- azabicyclo[4.3.0]nonane) as assessed in guinea pig atrial preparations is markedly dependent on the nature of the 6-alkylidene side chain. Pumiliotoxin A (PTX-A), which differs from PTX-B only in lacking the 7'-hydroxy moiety, is much less active than PTX-B. Alteration in the configuration of the 6'- and/or 7'-hydroxy side chain moieties in synthetic isomers of PTX-B reduces activity, while the lack of such moieties or replacement with methoxy or ketone moieties in PTX-B or PTX-A analogues yields cardiodepressant compounds. PTX-B markedly stimulates phosphoinositide turnover in atrial and brain preparations and sodium influx in brain preparations, while analogues that are cardiac depressant or have low cardiotonic activity have no or minimal effects on such parameters. It is suggested that activation of sodium channels and resultant stimulation of phosphoinositide breakdown play a role in the cardiotonic activity of pumiliotoxin alkaloids.

  DOI：

  10.1021/jm00397a036

文献信息

• DALY, J. W.;MCNEAL, E.;GUSOVSKY, F.;ITO, F.;OVERMAN, L. E., J. MED. CHEM., 31,(1988) N 2, 477-480
  作者：DALY, J. W.、MCNEAL, E.、GUSOVSKY, F.、ITO, F.、OVERMAN, L. E.

  DOI：——

  日期：——
• GARRAFFO, H. M.;EDWARDS, M. W.;SPANDE, T. F.;DALY, J. W.;OVERMAN, LARRY E+, TETRAHEDRON, 44,(1988) N 22, C. 6795-6800
  作者：GARRAFFO, H. M.、EDWARDS, M. W.、SPANDE, T. F.、DALY, J. W.、OVERMAN, LARRY E+

  DOI：——

  日期：——
• A naturally occurring erythro diastereomer of pumiliotoxin b
  作者：H.M. Garraffo、M.W. Edwards、T.F. Spande、J.W. Daly、Larry E. Overman、C. Severini、V. Erspamer

  DOI：10.1016/s0040-4020(01)86205-0

  日期：1988.1
• Pumiliotoxin alkaloids: relationship of cardiotonic activity to sodium channel activity and phosphatidylinositol turnover
  作者：J. W. Daly、E. McNeal、F. Gusovsky、F. Ito、L. E. Overman

  DOI：10.1021/jm00397a036

  日期：1988.2

  The cardiotonic activity of pumiliotoxin B (PTX-B, 6-(6',7'-dihydroxy-2',5'-dimethyl-(E)-4'-octenylidene)-8-hydroxy-8 -methyl-1- azabicyclo[4.3.0]nonane) as assessed in guinea pig atrial preparations is markedly dependent on the nature of the 6-alkylidene side chain. Pumiliotoxin A (PTX-A), which differs from PTX-B only in lacking the 7'-hydroxy moiety, is much less active than PTX-B. Alteration in the configuration of the 6'- and/or 7'-hydroxy side chain moieties in synthetic isomers of PTX-B reduces activity, while the lack of such moieties or replacement with methoxy or ketone moieties in PTX-B or PTX-A analogues yields cardiodepressant compounds. PTX-B markedly stimulates phosphoinositide turnover in atrial and brain preparations and sodium influx in brain preparations, while analogues that are cardiac depressant or have low cardiotonic activity have no or minimal effects on such parameters. It is suggested that activation of sodium channels and resultant stimulation of phosphoinositide breakdown play a role in the cardiotonic activity of pumiliotoxin alkaloids.