Talatisamine
(Synonyms: 塔拉萨敏) 目录号 : GC45573
A diterpene alkaloid with diverse biological activities
Cas No.:20501-56-8
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Talatisamine is a diterpene alkaloid originally isolated from A. talassicum and has diverse biological activities.1,2,3,4,5 It blocks delayed rectifier potassium (IK) current in rat hippocampal neurons (IC50 = 146 μM).3 Talatisamine reduces increases in IK current and cytotoxicity in primary rat cortical neurons induced by amyloid-β (1-40) .4 It inhibits barium chloride-induced contractions in isolated rat intenstines (EC50 = 200 μM).2 Talatisamine exhibits feeding deterrent activity against red flour beetle (T. castaneum) adults (EC50 = 342.8 ppm).5
References
1. Konovalova, R.A., and Orekhov, A.P. Aconite alkaloids. I. Alkaloids of aconitum talassicum. B. Soc. Chim. Fr. 7, 95-105 (1940).
2. Dzhakhangirov, F.N., Tursunkhodzhaeva, F.M., Sultankhodzhaev, M.N., et al. Spasmolytic activity of diterpenoid alkaloids and their derivatives. Structure-activity relationship. Chem. Nat. Compd. 49(4), 702-706 (2013).
3. Song, M.K., Liu, H., Jiang, H.L., et al. Discovery of talatisamine as a novel specific blocker for the delayed rectifier K+ channels in rat hippocampal neurons. Neuroscience 155(2), 469-475 (2008).
4. Wang, Y., Song, M., Hou, L., et al. The newly identified K+ channel blocker talatisamine attenuates beta-amyloid oligomers induced neurotoxicity in cultured cortical neurons. Neurosci. Lett. 518(2), 122-127 (2012).
5. Liu, Z.L., Cao, J., Zhang, H.M., et al. Feeding deterrents from Aconitum episcopale roots against the red flour beetle, Tribolium castaneum. J. Agric. Food Chem. 59(8), 3701-3706 (2011).
| Cas No. | 20501-56-8 | SDF | |
| 别名 | 塔拉萨敏 | ||
| Canonical SMILES | [H][C@]1(C2)C([C@@H](OC)CC[C@]34COC)(C5N(CC)C4)[C@]3([H])CC5[C@]6(O)[C@@]1([H])[C@@H](O)[C@@]2([H])[C@@H](OC)C6 | ||
| 分子式 | C24H39NO5 | 分子量 | 421.6 |
| 溶解度 | DMF: 1mg/mL,DMSO: 2 mg/mL,Ethanol: 10mg/mL | 储存条件 | Store at -20°C,protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3719 mL | 11.8596 mL | 23.7192 mL |
| 5 mM | 0.4744 mL | 2.3719 mL | 4.7438 mL |
| 10 mM | 0.2372 mL | 1.186 mL | 2.3719 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Total Synthesis of Talatisamine
Angew Chem Int Ed Engl 2020 Jan 2;59(1):479-486.PMID:31677324DOI:10.1002/anie.201912737.
Talatisamine (1) is a member of the C19 -diterpenoid alkaloid family, and exhibits K+ channel inhibitory and antiarrhythmic activities. The formidable synthetic challenge that 1 presents is due to its highly oxidized and intricately fused hexacyclic 6/7/5/6/6/5-membered-ring structure (ABCDEF-ring) with 12 contiguous stereocenters. Here we report an efficient synthetic route to 1 by the assembly of two structurally simple fragments, chiral 6/6-membered AE-ring 7 and aromatic 6-membered D-ring 6. AE-ring 7 was constructed from 2-cyclohexenone (8) through fusing an N-ethylpiperidine ring by a double Mannich reaction. After coupling 6 with 7, an oxidative dearomatization/Diels-Alder reaction sequence generated fused pentacycle 4 b. The newly formed 6/6-membered ring system was then stereospecifically reorganized into the 7/5-membered BC-ring of 3 via a Wagner-Meerwein rearrangement. Finally, Hg(OAc)2 induced an oxidative aza-Prins cyclization of 2, thereby forging the remaining 5-membered F-ring. The total synthesis of 1 was thus accomplished by optimizing and orchestrating 33 transformations from 8.
Quantitative determination of Talatisamine and its pharmacokinetics and bioavailability in mouse plasma by UPLC-MS/MS
J Chromatogr B Analyt Technol Biomed Life Sci 2019 Aug 15;1124:180-187.PMID:31207562DOI:10.1016/j.jchromb.2019.06.015.
Talatisamine, as the efficacy ingredient of Aconitum, was known as a novel specific blocker for the delayed rectifier K+ channels in rat hippocampal neurons. In this study, a rapid, selective and reproducible UPLC-MS/MS separation method was established and fully validated for the quantitative determination of Talatisamine levels in ICR (Institute of Cancer Research) mouse blood. A total of 24 healthy male ICR mice were divided into four groups that was administered Talatisamine via intravenous at a dose of 1 mg/kg and oral administration of three doses (2, 4, 8 mg/kg). All blood samples were protein precipitate by using acetonitrile with an internal standard (IS) deltaline. The effective chromatographic separation was carried out through an UPLC BEH C18 analytical column (2.1 mm × 50 mm, 1.7 μm) with an initial mobile phase that consisted of acetonitrile and 10 mmol/L ammonium acetate aqueous solution (containing 0.1% formic acid) with a gradient elution pumped at a flow rate of 0.4 mL/min. Also, an electrospray ionization (ESI) was applied to quantify the Talatisamine in the positive ions mode. The method validation demonstrated good linearity over the range of 1-1000 ng/mL (r2 ≥ 0.9993) for Talatisamine in mouse blood with a lower limit of quantification (LLOQ) at 1 ng/mL. The accuracy values of the method were within 89.4% to 113.3%, and the matrix effects were between 103.2% and 106.3%. The mean extraction recoveries for Talatisamine obtained from four concentrations of QC blood samples were exceeded 71.7%, and the relative standard deviation (RSD) both of intra- and inter-day precision values for replicate quality control samples did not exceed 15% respectively for all analytes during the assay validation. This method was successfully applied to the evaluation of the pharmacokinetic of Talatisamine, regardless of intragastric or intravenous administration in mice. Based on the pharmacokinetics data, the bioavailability of Talatisamine in mice was >65.0% after oral administration, exhibiting an excellent oral absorption.
Talatisamine, a C(19)-diterpenoid alkaloid from Chinese traditional herbal 'Chuanwu'
Acta Crystallogr Sect E Struct Rep Online 2011 Dec 1;67(Pt 12):o3145-6.PMID:22199672DOI:10.1107/S1600536811044242.
THE TITLE COMPOUND [SYSTEMATIC NAME: (1S,4S,5R,7S,8S,9R,10R,11S,13S,14S,16S,17R)-N-methyl-8,14-dihy-droxy-1,16-tri-meth-oxy-4-(meth-oxy-methyl-ene)aconitane], C(24)H(39)NO(5), was isolated from the roots of Aconitum carmichaelii Debx., which is known as 'Chuanwu' in Chinese traditional herbal medicine. The mol-ecule has an aconitane carbon skeleton with four six-membered rings and two five-membered rings, including a six-membered N-containing heterocyclic ring. Both five-membered rings adopt envelope conformations. The four six-membered adopt chair conformations. Two intra-molecular O-H⋯O hydrogen bonds occur.
Investigation of the potential anticancer effects of napelline and Talatisamine dirterpenes on experimental brain tumor models
Cytotechnology 2020 Aug;72(4):569-578.PMID:32529352DOI:10.1007/s10616-020-00405-8.
Brain cancers are one of the most aggressive tumours in humans. Especially, gliomas are among the deadliest of human cancers and show high resistance to chemotherapeutic agents. On the other hand, discovery of biologically effective non-synthetic biomaterials in treatments of different diseases, especially cancer, has continued to be one of the most popular research topics today. Therefore, we aimed to investigate biochemical, cytological and molecular genetic effects of napelline and Talatisamine diterpenes in human U-87 MG glioma cells by using total antioxidant status and total oxidative status, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxphenyl)-2-(4-sulfophenyl)-2H-tetrozolium, inner salt and lactate dehydrogenase release assay and RT2 Prolifer PCR Arrays. Our results revealed that napelline and Talatisamine exhibited cytotoxic effects at high doses. Napelline and Talatisamine diterpenes increased apoptosis compared to control in U-87 MG cells. While napelline induced up-regulation of 50 and down-regulation of 13 genes, Talatisamine induced up-regulation of 32 and down-regulation of 18 genes in U-87 MG cells. Napelline was shown to have a higher anticancer activity than Talatisamine. We think that, napelline and Talatisamine might be evaluated as potential chemotherapeutic agents for treatment of glioblastoma.
Construction of the Fused Pentacycle of Talatisamine via a Combination of Radical and Cationic Cyclizations
J Org Chem 2016 Nov 4;81(21):10204-10213.PMID:27266504DOI:10.1021/acs.joc.6b01011.
The fused 6/7/5/6/6-membered (ABCDE) ring system of Talatisamine was synthesized in 22 steps. After preparation of the AE-ring structure from 2-(ethoxycarbonyl)cyclohexanone, elaboration of the carboskeleton was realized by sequential additions of allyl magnesium bromide and the lithiated C-ring. The C11-bridgehead radical derived from the ACE-ring underwent the 7-endo cyclization with the enone moiety to form the B-ring in C10-stereoselective and C11-stereospecific manners. The 6-endo cyclization of the remaining D-ring was in turn attained by using the silyl enol ether as the nucleophile and the PhSeCl-activated olefin as the electrophile. These radical and cationic cyclizations were demonstrated to be highly chemoselective, and they significantly contributed to streamlining the route to the intricately fused pentacycle of Talatisamine.