17659-49-3

Basic information

• Product Name: ANISODAMINE
• Synonyms: ANISODAMINE;α-(Hydroxymethyl)benzeneacetic acid 6-hydroxy-8-methyl-8-azabicyclo[3.2.1]octan-3-yl ester;Tropic acid 6-hydroxy-3-tropanyl ester;LAnisodaMine;6-Hydroxy-8-methyl-8-azabicyclo[3.2.1]octan-3-yl 3-hydroxy-2-phenylpropanoate;Racanisodamine, 98%, from Anisodus tanguticus
• CAS NO: 17659-49-3
• Molecular Formula: C₁₇H₂₃NO₄
• Molecular Weight: 305.37
• Mol File: 17659-49-3.mol
• Article Data: 6

Chemical Properties

• Boiling Point: No Data Available
• Appearance: No Data Available
• Density: 1.27
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
• PKA: 14.12±0.10(Predicted)
• CAS DataBase Reference: ANISODAMINE(CAS DataBase Reference)
• NIST Chemistry Reference: ANISODAMINE(17659-49-3)
• EPA Substance Registry System: ANISODAMINE(17659-49-3)

Safety Data

• Hazardous Substances Data: 17659-49-3(Hazardous Substances Data)

Usage

Description

Different sources of media describe the Description of 17659-49-3 differently. You can refer to the following data:
1. Amisodamine is a kind of alkaloid which is mainly living in anisodus tanguticus, which is a M receptor just like Atropine. It is a kind of traditional Chinese medicine which comes from the “National assembly of Chinese Herbal medicine”, and it is the alias of zangjia registered in “Chines herbal medicine summary of shan gan ning qing”. It is a perennial root herb that lives in the bottom slope in the eastern Tibet, Qinghai Province, the Southern GanSu Province, the western SiChuan Province, the northwestward YunNan Province. Since the sources is scare, racemic form of raceanisodamine is the main drug in clinic.
2. Anisodamine is a natural tropane alkaloid shown to be a weak antagonist of α1-adrenoceptors, blocking WB-4101 and clonidine binding in brain membrane preparations with pKi values of 2.63 and 1.61, respectively. Anisodamine also has antioxidant effects that may protect against free radical-induced cellular damage. Anisodamine is predominantly found in the roots of A. tanguticus, which is used in traditional Chinese medicine for topical applications.

Physical properties

Appearance: raceanisodamine is a kind of white crystal and crystalline powder. It is odorless and bitter to the taste. Solubility: it is easy dissolubility in hydrochloric acid and ethyl alcohol and is soluble in water. Melting point: it’s melting point is from 103 to 113?°C.?The weld spacing is within 6°. Specific optical rotation: ?9° to +11°.

History

It is the traditional Chinese medicine and the rich folk herbs that create favorable conditions to look for and develop good medicine. Dated from ancient times, anisodus tanguticus used to the treatment of pain. Unfortunately, it can lead to atropine poisoning resulted from large dosage. When found the adverse effects, research made analysis and finally discovered six kinds of ramifications. Besides, they found two types alkaloid anisodamine and anisodine. Compared with atropine, anisodamen has one more hydroxy in tropic ring and named “654”.

Uses

Different sources of media describe the Uses of 17659-49-3 differently. You can refer to the following data:
1. anticholinergic, antispasmodic
2. Tropic Acid 6-Hydroxy-3-tropanyl Ester is a Hycosamine (H674300) derivative, which is a natural compound with inhibitory activity against cholinesterases.

Indications

Anisodamine is a kind of anticholinergic agent. The tablet and injection form are mainly used to relieve smooth muscle spasm, biliary spasm and AOIP in clinical practice. The eye drop is used to treat teenage pseudomyopia; raceanisodamine concomitant with other drugs to treat cluster headache syndrome, renal colic, infantile diarrhea, infantile jaundice hepatitis, infantile purpura, bronchopneumonia, etc.

Pharmacology

1. Cholinolytic effect. Anisodamine can block acetylcholine receptors. We always take it as a merely blocker of M receptor. In recent years, it turns out that anisodamine is also a blocker of N receptor. 2. Calcium antagonist effect. Anisodamine will put up Clacium antagonist effect when ischemia, oxygen deficit or other reasons result in irreversible damage and apoptosis. 3. Reduce the level of NO. 50 mg/L anisodamine can restrain lipopolysaccharide combined with vascular endothelial cells and promote the production of NO and over-dosage of NO is the pivotal pathologic mechanism of the toxic shock . Pretreatment with anisodamine can reduce the level of NO obviously when cells are damaged and remit toxicity resulted from over-dosage of NO. 4. Anti-oxygenation. anisodamine can restrain myocardial function damage resulted from pyrogallol obviously and can adjust the function of cardioid damaged by ROS .

Clinical Use

Anisodamine is a new drug developed by Chinese scientists. It has been widely put into use in clinical practice such as slow reflow phenomenon of ST-elevation acute myocardial infarction patients with percutaneous coronary intervention, infusion leakage , neonatal sclerosis. At present, it is mainly used to dilate vessels, remove vasospasm, improve blood circulation, increase tolerance of ischemia hypoxia and reduce the probability of the surrounding tissue necrosis

references

[1] varma d r, yue t l. adrenoceptor blocking properties of atropine‐like agents anisodamine and anisodine on brain and cardiovascular tissues of rats[j]. british journal of pharmacology, 1986, 87(3): 587-594.[2] piascik m t, perez d m. α1-adrenergic receptors: new insights and directions[j]. journal of pharmacology and experimental therapeutics, 2001, 298(2): 403-410.[3] poupko j m, baskin s i, moore e. the pharmacological properties of anisodamine[j]. journal of applied toxicology, 2007, 27(2): 116-121.

Upstream product

• 51-34-3 scopolamine 
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• 4277-63-8 methyl 1H-pyrrole-1-carboxylate 
• 1083169-27-0 C₁₅H₂₉NO₄Si 
• 101-31-5 Hyoscyamine 

Downstream Products

• 4839-11-6 (3R,6R)-tropane-3α,6β-diol 
• 51-34-3 scopolamine 
• 16202-15-6 (S)-tropic acid 
• 126211-14-1 3α,6β-dihydroxytropane HCl 

Relevant articles and documents

Preparative separation of four isomers of synthetic anisodamine by HPLC and diastereomer crystallization

Anisodamine (654-1), a well-known cholinergic antagonist, is marketed as synthetic anisodamine (mixture of four isomers, 654-2) in China. To preparative resolution and comparison of the bioactivities of the four isomers of synthetic anisodamine, current work explores an economic and effective separation method by using preparative high performance liquid chromatography (HPLC) and diastereomer crystallization. Their absolute configurations were established by single-crystal X-ray diffraction and circular dichroism method. The purities of each isomer were more than 95%. Among them, 654-2-A2 (6R, 2′S configuration) exhibited better effect on cabachol preconditioned small intestine tension more than 654-2 and other isomers. The direct separation method without using HPLC was tried as well, which was still on progress. This is the first report of the method for preparative separation of four isomers of synthetic anisodamine which could be used for large-scale production in industry.

Evidence for Modulation of Oxygen Rebound Rate in Control of Outcome by Iron(II)- And 2-Oxoglutarate-Dependent Oxygenases

Iron(II)- and 2-oxoglutarate-dependent (Fe/2OG) oxygenases generate iron(IV)-oxo (ferryl) intermediates that can abstract hydrogen from aliphatic carbons (R-H). Hydroxylation proceeds by coupling of the resultant substrate radical (Ra€￠) and oxygen of the Fe(III)-OH complex ("oxygen rebound"). Nonhydroxylation outcomes result from different fates of the Fe(III)-OH/R?state; for example, halogenation results from R?coupling to a halogen ligand cis to the hydroxide. We previously suggested that halogenases control substrate-cofactor disposition to disfavor oxygen rebound and permit halogen coupling to prevail. Here, we explored the general implication that, when a ferryl intermediate can ambiguously target two substrate carbons for different outcomes, rebound to the site capable of the alternative outcome should be slower than to the adjacent, solely hydroxylated site. We evaluated this prediction for (i) the halogenase SyrB2, which exclusively hydroxylates C5 of norvaline appended to its carrier protein but can either chlorinate or hydroxylate C4 and (ii) two bifunctional enzymes that normally hydroxylate one carbon before coupling that oxygen to a second carbon (producing an oxacycle) but can, upon encountering deuterium at the first site, hydroxylate the second site instead. In all three cases, substrate hydroxylation incorporates a greater fraction of solvent-derived oxygen at the site that can also undergo the alternative outcome than at the other site, most likely reflecting an increased exchange of the initially O2-derived oxygen ligand in the longer-lived Fe(III)-OH/R?states. Suppression of rebound may thus be generally important for nonhydroxylation outcomes by these enzymes.

Molecular cloning, expression and characterization of hyoscyamine 6β-hydroxylase from hairy roots of Anisodus tanguticus

Anisodus tanguticus, one of the indigenous Chinese ethnological medicinal plants of the Solanaceae, produces anticholinergic alkaloids such as hyoscyamine, 6β-hydroxyhyoscyamine and scopolamine. Hyoscyamine 6β-hydroxylase (H6H), a key enzyme in the biosynthetic pathway of scopolamine, catalyzes the hydroxylation of hyoscyamine and epoxide formation from 6β-hydroxyhyoscyamine to generate scopolamine. A full-length cDNA of H6H has been isolated from A. tanguticus hairy roots. Nucleotide sequence analysis of the cloned cDNA revealed an open reading frame of 1035 bp encoding 344 amino acids with high homology to other known H6Hs. The equivalent amino acid sequence shows a typical motif of 2-oxoglutarate-dependent dioxygenase. The A. tanguticus H6H was expressed in Escherichia coli and purified for enzyme function analysis. This study characterized the recombinant AtH6H and showed it could generate scopolamine from hyoscyamine.