talatisamine | 20501-56-8

• 物质功能分类: 天然产物 - 生物碱
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: talatisamine
• 英文别名: talatizamine；(1S,4S,5R,7S,8S,9R,10R, 11S,13S,14S,16S,17R)-N-methyl-8,14-dihydroxy-1,16-trimethoxy-4-(methoxymethylene)aconitane；(1S,2R,3R,4S,5S,6S,8S,9S,10R,13S,16S,17R)-11-ethyl-6,16-dimethoxy-13-(methoxymethyl)-11-azahexacyclo[7.7.2.12,5.01,10.03,8.013,17]nonadecane-4,8-diol
• CAS: 20501-56-8
• 化学式: C₂₄H₃₉NO₅
• 分子量: 421.577
• InChiKey: BDCURAWBZJMFIK-OGVVJMRYSA-N

物化性质

• 熔点：
  151-152℃
• 沸点：
  533.9±50.0 °C(Predicted)
• 密度：
  1.25
• 溶解度：
  DMF：1mg/mL；二甲基亚砜：2mg/mL；乙醇：10mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  71.4
• 氢给体数：
  2
• 氢受体数：
  6

制备方法与用途

生物活性

Talatisamine 是一种乌头生物碱，特异性地抑制 K+ 通道。研究显示，Talatisamine 能减弱 β- 淀粉样低聚物对培养皮层神经元的神经毒性。

靶点

Target	Value
IK channel	146 μM

上下游信息

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	cammaconine	——	C23H37NO5	407.55

反应信息

• 作为反应物：
  描述：

  talatisamine 在 potassium permanganate 作用下， 以 水 、 丙酮 为溶剂， 以55%的产率得到pengshenine B
  参考文献：
  名称：

  Gao, Liming; Zheng, Shangzhen; Hao, Xiaojiang, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1997, vol. 36, # 8, p. 682 - 684

  摘要：

  DOI：

文献信息

• Metabolite Profiling of Talatisamine in Heart Tissue After Oral Administration and Analysis of Cardiac Bioactivities
  作者：Shuai Huang、Yang Lv、Jian-Zhu Wang、Mei-Zhen Ye、Rui-Jie Lu、Lin Chen、Jiang Xie、Feng Gao、Xian-Li Zhou

  DOI：10.1055/a-1956-7542

  日期：——

  The lateral roots of the Aconitum carmichaelii (“Fuzi”) have been used for centuries as a cardiotonic in China. The diterpenoid alkaloid talatisamine (TA) is a major bioactive component of Fuzi, but the identity and bioactivities of the TA metabolites have not been examined in detail. In this study, metabolite profiling of TA was performed in rat heart by UPLC-MS following oral administration. Metabolites were identified by comparing protonated molecules, fragmentation patterns, and chromatographic behaviors with those of standard compounds. Metabolites of TA were then prepared and tested for cardiotonic activity on isolated frog hearts. The metabolite cammaconine, a C19 diterpenoid alkaloid with a hydroxyl group at C-18, exhibited substantial cardiotonic activity during frog heart perfusion. To further investigate the structure–cardiac effect relationships, a series of C19-diterpenoid alkaloids with 18-OH were prepared. Eight tested compounds (5–12) demonstrated measurable cardioactivity, of which compound 5 with an N-methyl group and compound 7 with a methoxy at C-16 showed stronger effects on ventricular contraction than the other compounds. Thus, 18-OH is a critical structural feature determining cardiotonic activity, and efficacy is improved by the presence of N-methyl or methoxy at C-16. Preliminary mechanistic studies suggested that the cardiotonic effect of compound 5 is mediated by enhanced cellular calcium influx. Metabolites of TA with these structural features may be useful therapeutics to prevent heart failure.

  摘要 附子（Aconitum carmichaelii，"Fuzi"）的侧根在中国被用作强心剂已有数百年的历史。二萜生物碱 Talatisamine（TA）是附子的主要生物活性成分。 但是，TA 代谢物的特性和生物活性尚未得到详细研究。本研究采用 UPLC-MS 对大鼠口服夫子后心脏中的 TA 代谢物进行了分析。 对大鼠口服 TA 后的心脏代谢物进行了分析。通过比较质子化分子、碎片模式以及色谱行为与标准化合物的差异，对代谢物进行了鉴定。 然后制备了 TA 的代谢物，并测试了其对离体蛙心的强心活性。代谢物樟脑碱是一种 C19 二萜生物碱，羟基位于 C-18 的二萜生物碱，在蛙心灌注过程中表现出很强的强心活性。为了进一步研究结构与心脏效应之间的关系，一系列带有 18-OH 生物碱。八个测试化合物（5-12）表现出了可测量的强心活性，其中带有 N-甲基的化合物 5 和在 C-16 位上带有甲氧基的化合物 7 7 对心室收缩的作用强于其他化合物。因此，18-OH 是决定强心活性的关键结构特征、 而 C-16 位上的 N-甲基或甲氧基可提高药效。初步机理研究表明，化合物 5 的强心作用是通过 细胞钙离子流入增强。具有这些结构特征的 TA 代谢物可能是预防心力衰竭的有用疗法。
• ——
  作者：E. G. Zinurova、N. N. Kabal"nova、V. V. Shereshovets、E. V. Ivanova、E. E. Shults、G. A. Tolstikov、M. S. Yunusov

  DOI：10.1023/a:1011385500970

  日期：——

  Oxidation of diterpene alkaloids by dimethyldioxirane was studied with eldeline, talatizamine, aconitine, and zongorine as examples. Nitrones and 19-oxo derivatives of bases were obtained. The results of the oxidation allow one to draw an analogy with the oxidation by KMnO4 and to suggest a mechanism of the reaction.
• Gao, Liming; Zheng, Shangzhen; Hao, Xiaojiang, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1997, vol. 36, # 8, p. 682 - 684
  作者：Gao, Liming、Zheng, Shangzhen、Hao, Xiaojiang、Wang, Xiaoxiong、Shen, Xuwei

  DOI：——

  日期：——