10097-84-4

Basic information

• Product Name: Tetrahydropalmatine
• Synonyms: AKOS 208-04;L-TETRAHYDROPALMATINE;L-TETRAHYDROPALMATINE HCL;DL-TETRAHYDROPALMATINE;TETRAHYDROPALMATINE;ROTUNDINE;ROTUNDIN HYDRATE;ROTUNDINUM
• CAS NO: 10097-84-4
• Molecular Formula: C₂₁H₂₅NO₄
• Molecular Weight: 355.43
• EINECS: 1592732-453-0
• Product Categories: Alkaloids;Miscellaneous Natural Products;Pharmaceutical intermediate;Plant extracts;chemical reagent;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;Inhibitors
• Mol File: 10097-84-4.mol
• Article Data: 10

Chemical Properties

• Boiling Point: 482.9 °C at 760 mmHg
• Flash Point: 138.7 °C
• Appearance: light yellow powder crystal
• Density: 1.23 g/cm³
• Vapor Pressure: 1.76E-09mmHg at 25°C
• Refractive Index: 1.608
• Storage Temp.: Hygroscopic, Refrigerator, under inert atmosphere
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• CAS DataBase Reference: Tetrahydropalmatine(CAS DataBase Reference)
• NIST Chemistry Reference: Tetrahydropalmatine(10097-84-4)
• EPA Substance Registry System: Tetrahydropalmatine(10097-84-4)

Safety Data

• Safety Statements: 24/25
• Hazardous Substances Data: 10097-84-4(Hazardous Substances Data)

Usage

Description

Tetrahydropalmatine (THP) is an isoquinoline alkaloid derived from several plant species, predominantly in the Corydalis genus (Yan Hu Suo) and Stephania rotunda (Qian Jin Teng). It is an off-white solid, odorless, tasteless, and turns yellow when exposed to light and heat. THP exhibits analgesic, antinociceptive, anxiolytic, antidepressant, and anti-parasitic activities and has been traditionally used in Chinese herbal medicine. The levo isomer of THP (l-THP) is responsible for many of the therapeutic effects of these herbs, while the dextro isomer has distinct pharmacological actions, including depletion of monoamines and potential contribution to the toxicology profile of THP-containing preparations.

Uses

Used in Pharmaceutical Industry:
Tetrahydropalmatine is used as an analgesic drug for treating heart disease and liver damage. It is particularly effective due to its ability to alleviate pain and its presence in traditional Chinese herbal medicine.
Used in Traditional Chinese Medicine:
Tetrahydropalmatine is used as an active constituent in various herbal preparations, providing relief from pain and anxiety, as well as addressing depression and parasitic infections.
Used in Sedative Applications:
Tetrahydropalmatine, specifically the levo isomer (l-THP), is used as a sedative for more than 40 years in China, where it is available as Rotundine or Rotundin.
Physical Properties:
Appearance: Off-white solid, odorless, tasteless, turns yellow under light and heat
Solubility: Usually dissolved in chloroform, slightly soluble in ethanol or ether, insoluble in water, and soluble in dilute sulfuric acid
Melting Point: 141–144°C
Specific Optical Rotation: -290 to -300°

References

1. https://en.wikipedia.org/wiki/Tetrahydropalmatine 2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878639/ 3.https://www.worldseedsupply.com/product/corydalis-yanhusuo-tetrahydropalmatine-98-pure-thp-isolate/ 4. https://www.lktlabs.com/product/dl-tetrahydropalmatine/

References

Kondo, Matsuno., J. Pharm. Soc., Japan, 64, (9A), 28 (1944)

History

From the 1920s, many researchers have focused on the alkaloid compounds contained in the Yan Hu Suo and extracted more than 30 different kinds of alkaloids. Among them Rotundine is one of the most important active compounds and has been successfully applied in clinical practice.Tetrahydropalmatine (THP) was firstly discovered by Zhao Chenggu, a famous medicinal phytochemist in China. He isolated 13 kinds of alkaloids and identified the structure of 6 of them. In 1936, Huang Minglong, a famous organic chemist, proved THP is a racemate. From 1933, Wang Jingxi and Lu Zihui began to study the pharmacological effects of THP and found that THP could induce catalepsy in animals. Rotundine is a levo-THP and obtained from the resolution of DL-THP during 1959–1964. From 1956 to 1965, the famous Chinese neuropharmacologist, Jin Guozhang, identified Rotundine as the main effective component in Yan Hu Suo and further studied its underlying mechanisms. He also found that Stephania contains abundant L-THP, which could become the source of clinical medication.In 1965, Rotundine was recorded in the textbooks of pharmacology. After over 20?years of clinical practices, people have proved that Rotundine has reliable efficacy and low side effect. In 1977, Rotundine was recorded in the Chinese Pharmacopoeia. In 1979, THP achieved a full synthesis, and currently Rotundine is mainly produced by artificial synthesis. From 1980, the study on the mechanisms of Rotundine made great progress. The analgesic effect of Rotundine has nothing to do with opioid receptors or prostaglandins. Rotundine does not belong to narcotic analgesics and antipyretic analgesics. Further, Rotundine has been found to have no affinity with M-cholinergic receptor and GABA system in the brain. But it has affinity to dopamine receptors. The exact mechanisms and pharmacology effects of Rotundine still need more research.

Pharmacology

1. Effects on the central nervous system: Rotundine has significant analgesic, sedative, and hypnotic effects, and its mechanism has nothing to do with opioid receptors. It has no obvious addiction effect. Using Rotundine combined with pethidine can enhance the analgesic effect, reduce the amount of pethidine, and further reduce the occurrence of drug dependence. The present study suggests that Rotundine is a central dopamine receptor blocker that inhibits the transmission of peripheral pain information by blocking the D2 receptor of the striatum and nucleus accumbens and the PAG-RgpI-spinal dorsal horn nerve pathway. In addition, Rotundine also has a suppression of the strengthening of the motor response induced by drug abuse, that is, inhibition of behavioral sensitization.2. Effects on the cardio-cerebrovascular system: Rotundine has inhibitory effect on the injuries caused by cerebral ischemia and reperfusion and myocardial ischemia and reperfusion. It also could lower the blood pressure. The pharmacological mechanism of Rotundine on the cardiovascular and cerebrovascular aspects is quite complex and may relate to the regulation of inflammation and inhibition of apoptosis. It is also found that Rotundine acts on α-receptors and has a noncompetitive antagonistic effect on calcium.3. Rotundine can reverse the drug resistance of tumor cells; the mechanism may be through the downregulating of the expression of P-glycoprotein (P-gp) and the upregulating of the expression of topo II in tumor cells.4. Rotundine has an excitatory effect on the endocrine system, such as the pituitaryadrenal system, and also has a protective effect on the liver.5. Drug metabolisms: The absorption of Rotundine by oral administration is complete. At 15?min it can be absorbed by 40–50%. It begins to work at 10–30?min, and the effect can last 2–5?h. In vivo distribution is through fat and the lung, liver, and kidney. If administered by subcutaneous injection, after 12?h, Rotundine will be discharged by 80% with the urine.

Clinical Use

1. Pain induced by gastrointestinal and hepatobiliary disorders, menstrual pain, and pain after childbirth.2. Mild trauma and postoperative pain3. Headache insomnia and spasmodic cough.4. There is a report about the usage of Rotundine in arrhythmia caused by I–III hypertension and other diseases.5. The hypnotic effect of Rotundine happens in 15?min after administration and then appears after 2?h. Because the analgesic effect happens at the same time, Rotundine is particularly suitable for insomnia patients with pain.6. Side effects: drowsiness, dizziness, fatigue, and nausea. Large dose of Rotundine can inhibit the respiratory center and may cause extrapyramidal symptoms.

Purification Methods

Crystallise it from MeOH or EtOH by addition of water [see Kametani & Ihara J Chem Soc (C) 530 1967, Bradsher & Dutta J Org Chem 26 2231 1961]. When crystallised from Me2CO/Et2O, it has m 142o. The hydrate has m 115o(effervescence). The picrate has m 188o(dec) (from aqueous EtOH). [Bradsher & Datta J Org Chem 26 2231 1961, Beilstein 21 II 196, 21 III/IV 2769.]

InChI:InChI=1/C21H25NO4/c1-23-18-6-5-13-9-17-15-11-20(25-3)19(24-2)10-14(15)7-8-22(17)12-16(13)21(18)26-4/h5-6,10-11,17H,7-9,12H2,1-4H3/t17-/m0/s1

Upstream product

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• 102321-59-5 N-(2,3-dimethoxybenzyl)-2-(3,4-dimethoxyphenyl)ethan-1-aminium chloride 
• 47355-66-8 N-(2,3-dimethoxybenzyl)-2-(3,4-dimethoxyphenyl)ethan-1-amine 
• 120-20-7 2-(3,4-dimethoxyphenyl)-ethylamine 
• 86-51-1 2,3-dimethyoxybenzaldehyde 
• 26067-60-7 2,3,9,10-tetramethoxy-5,8-dihydro-6H-isoquinolino[3,2-α]isoquinoline 
• 1422431-15-9 (S)-6-((6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)methyl)-2,3-dimethoxylbenzyl acetate 
• 65495-21-8 N,N-dimethyl-3,4-dimethoxybenzylamine 
• 1356336-70-3 (S)-1,2-dimethoxy-4-methyl-3-(p-tolylsulfinyl)benzene 
• 1356336-72-5 (S)-1-(chloromethyl)-3,4-dimethoxy-2-(p-tolylsulfinyl)benzene 
• 1356336-71-4 (S)-1-[3,4-dimethoxy-2-(p-tolylsulfinyl)phenyl]-N,N-dimethylmethanamine 
• 1356336-74-7 (1S)-1-[3,4-dimethoxy-2-(S)-p-tolylsulfinyl]benzyl-6,7-dimethoxy-2-(S)-p-tolylsulfinyl-1,2,3,4-tetrahydroisoquinoline 
• 50-00-0 formaldehyd 
• 1356336-76-9 (1S)-1-[3,4-dimethoxy-2-(S)-p-tolylsulfinyl]benzyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 

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Relevant articles and documents

Studies on the alkaloids of Menispermaceous plants. 233. Alkaloids of Tinomiscium petiolare Miers

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Method for synthesizing tetrahydroberberine and derivatives thereof

The invention provides a method for synthesizing tetrahydroberberine and derivatives thereof. Specifically, in the presence of an iridium metal catalyst precursor, a chiral diphosphine ligand, an acid and a halogen-containing additive, in a hydrogen atmosphere, a compound (II) is subjected to an asymmetric catalytic hydrogenation reaction in an organic solvent so as to prepare the compound (I).

Asymmetric synthesis of (S)-(-)-tetrahydropalmatine and (S)-(-)-canadine via a sulfinyl-directed Pictet-Spengler cyclization

(S)-(-)-Tetrahydropalmatine 2 and (S)-(-)-canadine 4 were synthesized in three steps from (S)-6, in 33% and 34% overall yield, respectively. Thus, condensation of the (S)-(E)-sulfinylimines 10 and 11 with the carbanion derived from (S)-6 gave the tetrahydroisoquinolines 12 and 13, respectively, which upon TFA induced N-desulfinylation, and subsequent microwave assisted Pictet-Spengler cyclization effected both cyclization and C-desulfinylation producing (S)-(-)-tetrahydropalmatine 2 and (S)-(-)-canadine 4 in optically pure form.