Reserpine

Base Information

• Chemical Name: Reserpine
• CAS No.: 50-55-5
• Deprecated CAS: 1407-38-1,141099-49-2,8048-25-7,873409-80-4,909883-12-1,911481-85-1,141099-49-2,8048-25-7
• Molecular Formula: C33H40N2O9
• Molecular Weight: 608.689
• Hs Code.: 29399990
• European Community (EC) Number: 200-047-9
• NSC Number: 757309,237659,59272
• UN Number: 3077
• UNII: 8B1QWR724A
• DSSTox Substance ID: DTXSID7021237
• Nikkaji Number: J1.359E
• Wikipedia: Reserpine
• Wikidata: Q407841
• NCI Thesaurus Code: C803
• RXCUI: 9260
• Pharos Ligand ID: 39UGF3U8RS3T
• Metabolomics Workbench ID: 42610
• ChEMBL ID: CHEMBL772
• Mol file: 50-55-5.mol

Synonyms:3b,20a-Yohimban-16b-carboxylic acid, 18b-hydroxy-11,17a-dimethoxy- methyl ester 3,4,5-trimethoxybenzoate (ester)(8CI);11,17-Dimethoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]yohimban-16-carboxylic acidmethyl ester;3,4,5-Trimethoxybenzoyl methyl reserpate;Hiposerpil;Loweserp;Methylreserpate 3,4,5-trimethoxybenzoate (ester);Reserpic acid methyl ester 3,4,5-trimethoxybenzoate (ester);

Chemical Property of Reserpine

Chemical Property:

• Appearance/Colour: off-white crystalline powder
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: ~265 °C (dec.)
• Refractive Index: 177 ° (C=1, DMF)
• Boiling Point: 700.058 °C at 760 mmHg
• PKA: 6.6(at 25℃)
• Flash Point: 377.182 °C
• PSA: 117.78000
• Density: 1.329 g/cm³
• LogP: 4.10900
• Storage Temp.: 2-8°C
• Solubility.: Practically insoluble in water, very slightly soluble in ethanol (96 per cent).
• Water Solubility.: Soluble in water.
• XLogP3: 4
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 10
• Rotatable Bond Count: 10
• Exact Mass: 608.27338086
• Heavy Atom Count: 44
• Complexity: 1000
• Transport DOT Label: Class 9

Purity/Quality:

99%, ^*data from raw suppliers

Reserpine ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn,Xi
• Hazard Codes: Xn,Xi
• Statements: 22-67-36-10
• Safety Statements: 22-36/37/39-26

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antihypertensive Agent
• Canonical SMILES: COC1C(CC2CN3CCC4=C(C3CC2C1C(=O)OC)NC5=C4C=CC(=C5)OC)OC(=O)C6=CC(=C(C(=C6)OC)OC)OC
• Isomeric SMILES: CO[C@H]1[C@@H](C[C@@H]2CN3CCC4=C([C@H]3C[C@@H]2[C@@H]1C(=O)OC)NC5=C4C=CC(=C5)OC)OC(=O)C6=CC(=C(C(=C6)OC)OC)OC
• Recent ClinicalTrials: Mechanisms of Refractory Hypertension (Reserpine)
• Indications: Reserpine is a drug used for the treatment of hypertension[4, 5,7, 8] and schizophrenia[although rarely used nowadays][4, 6]. It can also be used as an anticholinergic drug to combat excessive cholinergic activity in many parts of the body as well as parkinsonism[9]. Reserpine can be used as sedative for horses in veterinary field. It is used as a long-acting tranquilizer to subdue excitable or difficult horses and has been used illicitly for the sedation of show horses, for-sale horses, and in other circumstances where a "quieter" horse might be desired[10]. In addition, it can be used frequently as a highly useful analytic reference standard in the field of mass spectrometry owing to its availability, ease of ionization under electrospray conditions and stability in solution[11].
• Description: Reserpine causes release of norepinephrine, dopamine, and serotonin at neuronal termini. It weakens the intracellular uptake of biogenic amines and decreases the ability to store them in vesicles. Reserpine is an alkaloid isolated from dried roots of R. serpentine, which is used in traditional Indian medicine. Reserpine irreversibly inhibits both human isoforms of vesicular monoamine transporter, VMAT1 and VMAT2 (Kis = 34 and 12 nM, respectively). As this leads to metabolism of monoamines, reserpine is used to experimentally deplete monoamines in animals. Reserpine also inhibits the multidrug resistance protein P-glycoprotein (IC50 = 0.5 μM).
• Physical properties: Appearance: crystalline powder, colorless to yellowish brown, darker in case of light. Solubility: soluble in chloroform, slightly soluble in acetone, and almost insoluble in water, methanol, ethanol, or ether. Melting point: 264–265 °C. Specific optical rotation: ?117.7°.
• Uses: Reserpine occurs in the roots of Rauwolfiaserpentina and other Rauwolfia species, suchas R. micrantha, R. canescens, and R. vomitoria Hook. It is used therapeutically as anantihypertensive agent and a tranquilizer. Itsuse has been reduced significantly because oftoxic side effects. An indole alkaloid found in Rauwolfia serpentina. Inhibits vesicular uptake of catecholamines and serotonin. Reserpine is reasonably anticipated to be a human carcinogen. Antihypertensive. An inhibitor of transport of biogenic amines into adrenal chromaffin granules
• Biological Functions: Reserpine (Serpasil) is the prototypical drug interfering with norepinephrine storage. Reserpine lowers blood pressure by reducing norepinephrine concentrations in the noradrenergic nerves in such a way that less norepinephrine is released during neuron activation. Reserpine does not interfere with the release process per se as does guanethidine. Reserpine also interferes with the neuronal storage of a variety of central transmitter amines such that significant depletion of norepinephrine, dopamine, and 5- hydroxytryptamine (serotonin) occurs. This central transmitter depletion is responsible for the sedation and other CNS side effects associated with reserpine therapy. The depletion of brain amines also may contribute to the antihypertensive effects of reserpine.
• Clinical Use: Reserpine is effective orally and parenterally for thetreatment of hypertension. After a single intravenous dose,the onset of antihypertensive action usually begins in about1 hour. After intramuscular injection, the maximumeffect occurs within approximately 4 hours and lasts about10 hours. When it is given orally, the maximum effectoccurs within about 2 weeks and may persist up to 4 weeksafter the final dose. When used in conjunction with otherhypotensive drugs in the treatment of severe hypertension,the daily dose varies from 100 to 250μg. When reserpine is given orally, its maximum effect is seenafter a couple of weeks. A sustained effect up to severalweeks is seen after the last dose has been given. This isbecause the tight binding of reserpine to storage vesicles continuesfor a prolonged time, and recovery of sympatheticfunction requires synthesis of new vesicles over a period ofdays to weeks after discontinuation of the drug. Most adverseeffects of reserpine (log P＝4.37) are caused by CNS effectsbecause it readily enters the CNS. Sedation and inability toconcentrate or perform complex tasks are the most commonadverse effects. More serious is the occasional psychoticdepression that can lead to suicide, which support monoaminetheory of pathology of depression. Agents with fewer sideeffects have largely replaced reserpine in clinical use.

Technology Process of Reserpine

There total 95 articles about Reserpine which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield:

(1S,2R,3S,4S,7S)-7-Benzyloxymethyl-3-(fluoro-dimethyl-silanyl)-5-oxo-bicyclo[2.2.2]octane-2-carboxylic acid methyl ester → reserpine (50-55-5)

Guidance literature:

Multi-step reaction with 8 steps

1: H₂ / Pd/C / ethyl acetate / 30 h / 760 Torr

2: pyridine; 4-dimethylaminopyridine / CH₂Cl₂ / 10 h / Heating

3: m-chloroperbenzoic acid; Na₂PO₄ / CH₂Cl₂ / 15 h / 20 °C

4: Ag₂O; CaSO₄ / 20 h

5: diisobutylaluminum hydride / diethyl ether; tetrahydrofuran / 0.5 h / -78 °C

6: MgSO₄ / acetonitrile / 1 h

7: aq. HCl / tetrahydrofuran / 30 h / 20 °C

8: pyridine / 96 h / 20 °C

With pyridine; hydrogenchloride; dmap; calcium sulfate; hydrogen; diisobutylaluminium hydride; magnesium sulfate; 3-chloro-benzenecarboperoxoic acid; silver(l) oxide; palladium on activated charcoal; In tetrahydrofuran; diethyl ether; dichloromethane; ethyl acetate; acetonitrile; 6: Strecker reaction;

DOI:10.1021/ja055744x

Reference yield:

(1S,2R,3S,4S,7S)-7-Benzyloxymethyl-3-(furan-2-yl-dimethyl-silanyl)-5-oxo-bicyclo[2.2.2]octane-2-carboxylic acid methyl ester (871938-43-1) → reserpine (50-55-5)

Guidance literature:

Multi-step reaction with 9 steps

1: tetrabutylammonium fluoride / tetrahydrofuran / 0.03 h / 20 °C

2: H₂ / Pd/C / ethyl acetate / 30 h / 760 Torr

3: pyridine; 4-dimethylaminopyridine / CH₂Cl₂ / 10 h / Heating

4: m-chloroperbenzoic acid; Na₂PO₄ / CH₂Cl₂ / 15 h / 20 °C

5: Ag₂O; CaSO₄ / 20 h

6: diisobutylaluminum hydride / diethyl ether; tetrahydrofuran / 0.5 h / -78 °C

7: MgSO₄ / acetonitrile / 1 h

8: aq. HCl / tetrahydrofuran / 30 h / 20 °C

9: pyridine / 96 h / 20 °C

With pyridine; hydrogenchloride; dmap; calcium sulfate; tetrabutyl ammonium fluoride; hydrogen; diisobutylaluminium hydride; magnesium sulfate; 3-chloro-benzenecarboperoxoic acid; silver(l) oxide; palladium on activated charcoal; In tetrahydrofuran; diethyl ether; dichloromethane; ethyl acetate; acetonitrile; 7: Strecker reaction;

DOI:10.1021/ja055744x

Reference yield:

3,4,5-Trimethoxybenzoyl chloride (4521-61-3) + methyl reserpate (2901-66-8) → reserpine (50-55-5)

Guidance literature:

With dmap; triethylamine; In dichloromethane; Yield given; Ambient temperature;

DOI:10.1021/jo961713w

upstream raw materials:

Isoreserpin

3,4,5-Trimethoxybenzoyl chloride

methyl reserpate

(1S,2R,3S,4S,7S)-3-(Fluoro-dimethyl-silanyl)-7-hydroxymethyl-5-oxo-bicyclo[2.2.2]octane-2-carboxylic acid methyl ester

Downstream raw materials:

<3-²H>reserpine

7-hydroperoxy-7H-reserpine

dioxyreserpine

3,4-dehydroreserpine

Refernces

• 1、 Shamma,Shine. "-". . p. 2277. Retrieved 1964.
• 2、 Park, Jisook,Chen, David Y.-K.. "A Desymmetrization-Based Total Synthesis of Reserpine". . p. 16152 - 16156. Retrieved 2018/11/23.
• 3、 Stork, Gilbert,Tang, Peng Cho,Casey, Michael,Goodman, Burton,Toyota, Masahiro. "Regiospecific and stereoselective syntheses of (±)-reserpine and (-)-reserpine". . p. 16255 - 16262. Retrieved 2007/10/03.