4-[(R)-[(2S,4R,5R)-5-Vinyl-1-azabicyclo[2.2.2]octane-2-yl]hydroxymethyl]-6-methoxyquinoline

Base Information

• Chemical Name: 4-[(R)-[(2S,4R,5R)-5-Vinyl-1-azabicyclo[2.2.2]octane-2-yl]hydroxymethyl]-6-methoxyquinoline
• CAS No.: 130-95-0
• Molecular Formula: C20H24N2O2
• Molecular Weight: 324.423
• Hs Code.: 29392110
• European Community (EC) Number: 205-003-2
• Nikkaji Number: J3.440.050D
• Wikipedia: Quinine
• Wikidata: Q105154941
• NCI Thesaurus Code: C29399
• RXCUI: 9075
• Mol file: 130-95-0.mol

Synonyms:Biquinate;Bisulfate, Quinine;Hydrochloride, Quinine;Legatrim;Myoquin;Quinamm;Quinbisan;Quinbisul;Quindan;Quinimax;Quinine;Quinine Bisulfate;Quinine Hydrochloride;Quinine Lafran;Quinine Sulfate;Quinine Sulphate;Quinine-Odan;Quinoctal;Quinson;Quinsul;Strema;Sulfate, Quinine;Sulphate, Quinine;Surquina

Chemical Property of 4-[(R)-[(2S,4R,5R)-5-Vinyl-1-azabicyclo[2.2.2]octane-2-yl]hydroxymethyl]-6-methoxyquinoline

Chemical Property:

• Appearance/Colour: white to light yellow crystal powder
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 176-177 °C
• Refractive Index: 1.6250 (estimate)
• Boiling Point: 495.9 °C at 760 mmHg
• PKA: 8.52(at 25℃)
• Flash Point: 253.7 °C
• PSA: 45.59000
• Density: 1.21 g/cm³
• LogP: 3.11110
• Storage Temp.: Refrigerator
• Sensitive.: Light Sensitive
• Solubility.: H2O: soluble
• Water Solubility.: slightly soluble
• XLogP3: 2.9
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 4
• Exact Mass: 324.183778013
• Heavy Atom Count: 24
• Complexity: 457

Purity/Quality:

99% ^*data from raw suppliers

Quinine ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn,Xi
• Statements: 36/37/38-42/43-22-20/22-20/21/22-36/38
• Safety Statements: 22-26-36/37-45-37/39-36-7

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: COC1=CC2=C(C=CN=C2C=C1)C(C3CC4CCN3CC4C=C)O
• Isomeric SMILES: COC1=CC2=C(C=CN=C2C=C1)[C@H]([C@@H]3C[C@H]4CCN3C[C@@H]4C=C)O
• Recent ClinicalTrials: Effectiveness and Safety of Quinine Sulfate as add-on Therapy for COVID-19 in Hospitalized Adults in Indonesia ( DEAL-COVID19 )
• Indications: Quinine is the drug of choice in the treatment of severe and complicated chloroquine-resistant P. falciparum malaria. It is also useful for the treatment of non-severe chloroquineresistant cases. Quinine is one of several alkaloids derived from the bark of the cinchona tree. The mechanism by which it exerts its antimalarial activity is not known. It does not bind to DNA at antimalarial dosages. It may poison the parasite’s feeding mechanism, and it has been termed a general protoplasmic poison, since many organisms are affected by it. Quinine is rapidly absorbed following oral ingestion, with peak blood levels achieved in 1 to 4 hours. About 70 to 93% of the drug is bound to plasma proteins, depending on the severity of the infection. Quinine is extensively metabolized, with only about 20% of the parent compound eliminated in the urine. The primary present-day indication for quinine and its isomer, quinidine, is in the intravenous treatment of severe manifestations and complications of chloroquine- resistant malaria caused by P. falciparum. Aside from its use as an antimalarial compound, quinine is used for the prevention and treatment of nocturnal leg muscle cramps, especially those resulting from arthritis, diabetes, thrombophlebitis, arteriosclerosis, and varicose veins.
• description: Quinine, an alkaloid derived from the bark of the cinchona tree, is a blood schizontocidal agent that is more toxic than chloroquine.Quinine is used to treat malaria caused by Plasmodium falciparum. Plasmodium falciparum is a parasite that gets into the red blood cells in the body and causes malaria. Quinine works by killing the parasite or preventing it from growing. This medicine may be used alone or given together with one or more medicines for malaria. Quinine should not be used to treat or prevent night time leg cramps. This medicine may cause very serious unwanted effects and should only be used for patients with malaria.It is administered parenterally to patients with severe or complicated malaria who cannot take drugs by mouth because of coma, convulsions or vomiting. It is administered orally to less seriously ill patients with infections likely to be resistant to chloroquine or mefloquine, sometimes in combination with pyrimethamine/sulfadoxine or a tetracycline. Quinine is an extremely basic compound and is, therefore, always presented as a salt. Various preparations exist, including the hydrochloride, dihydrochloride, sulphate, bisulphate, and gluconate salts; of these the dihydrochloride is the most widely used. Quinine has rapid schizonticidal action against intra-erythrocytic malaria parasites. It is also gametocytocidal for Plasmodium vivax and Plasmodium malariae, but not for Plasmodium falciparum. Quinine also has analgesic, but not antipyretic properties. The anti-malarial mechanism of action of quinine is unknown.
• Uses: Quinine is one of the oldest antimalarial drugs. At as early as the 15th century, the quinine-containing cinchona bark has been used extensively in the treatment of malaria with its antimalarial effect being similar to that of chloroquine that is through interfering with DNA synthesis effect. It is capable of inhibiting the erythrocytic stage of a variety of Plasmodium, being able to control the malaria symptoms. It also has certain killing effect on the gametes of vivax malaria and quartan malaria. However, it has no effect on the exoerythrocytic stage. Its major advantage is not easy to produce drug resistance, possibly due to that quinine binds the plasmodium DNA in a different way from chloroquine, so having no cross-resistance and can be used for the treatment of the infection of anti-chloroquine strains (especially Plasmodium falciparum). In addition, quinine can also exciting the uterus, inhibit the myocardium and have antipyretic analgesic effect. In addition to medicinal application, in analytical chemistry it can be used as the detection agent of bismuth, platinum and other metal ions and also be used for the separation agent of racemic organic acid. Quinines use as an antimalarial agent spans several hundred years, but it has been replaced in recent years by other substances such as chloroquine. Because some Plasmodium strains have developed resistance to several malaria medications, quinine use is being revived. About 60% of quinine production is used for medicinal purposes, and the drug is available by prescription. In addition to its use as an antimalarial agent, quinine medications are used to treat leg cramps, muscle cramps associated with kidney failure, hemorrhoids, heart palpitations, and as an analgesic. At higher concentrations it is toxic and causes a condition known as cinchonism. Conditions associated with cinchonism include dizziness, hearing loss, visual impairment, nausea, and vomiting.Nonmedicinal use of quinine, accounting for about 40% of its use, is primarily as a fl avoringagent in condiments and liqueurs. The most common food use of quinine is tonic water. Tonicwater originated in India where English colonists drank carbonated water mixed with quinineto prevent malaria. The bitter taste of quinine was often masked by mixing it with alcoholicbeverages; one result of this practice was the drink gin and tonic. Current Food and DrugAdministration regulations in the United States limit the amount of quinine in tonic water to83 parts per million (83 mg per liter). This level is signifi cantly less than that required for therapeuticpurposes, so the use of commercial tonic waters to combat malaria is not practical. Primary alkaloid of various species of Cinchona (Rubiaceae). Optical isomer of Quinidine. Antimalarial; muscle relaxant (skeletal) Because of its relatively constant and well-known fluorescence quantum yield, quinine is also used in photochemistry as a common fluorescence standard. It has been used for imaging of oxygen evolution and oxide formation. Chloride and bromide have been sh antimalarial, skeletal muscle relaxant Quinine is a flavorant naturally obtained from the cinchona tree. it is used as a bitter flavoring in beverages such as quinine water, tonic water, and bitter lemon. quinine sulfate and quinine hydrochloride are cleared for use as a flavor in carbonated beverages at levels less than 83 ppm. Quinine occurs in the dried stems or rootbarks of cinchona (Cinchona ledgerianaMoens). It is used in the treatment of malaria.It is also used as an analgesic and antipyreticagent.
• Drug interactions: 1. It is not suitable to be used in combination with aminoglycoside antibiotics, furosemide and etacrynic acid 2. It is often used in combination with primaquine or pyrimethamine in order to achieve curing and enhance the effectiveness of the control of resistant strains. Potentially hazardous interactions with other drugs Anti-arrhythmics: flecainide levels increased; increased risk of ventricular arrhythmias with amiodarone - avoid. Antibacterials: increased risk of ventricular arrhythmias with moxifloxacin - avoid; concentration reduced by rifampicin. Antidepressants: possible increased risk of ventricular arrhythmias with citalopram and escitalopram. Antimalarials: increased risk of convulsions with mefloquine; avoid concomitant use with artemether/ lumefantrine. Antipsychotics: increased risk of ventricular arrhythmias with droperidol, pimozide, risperidone and possibly haloperidol - avoid. Antivirals: concentration possibly increased by atazanavir, darunavir, fosamprenavir, indinavir and tipranavir; concentration increased by ritonavir; increased risk of ventricular arrhythmias with saquinavir - avoid. Cardiac glycosides: levels of digoxin increased (halve maintenance dose). Ciclosporin: decreased ciclosporin levels reported. Cimetidine: may increase plasma levels of quinine.
• Description: Quinine, was the first known antimalarial. It is a 4-quinolinemethanol derivative bearing a substituted quinuclidine ring. The use of quinine in Europe began in the seventeenth century, after the Incas of Peru informed the Spanish Jesuits about the antimalarial properties of the bark of an evergreen mountain tree they called quinquina (later called cinchona, after Dona Franciscoa Henriquez de Ribera [1576–1639], Countess of Chinchon and wife of the Peruvian Viceroy).
• Physical properties: Appearance: white granular or microcrystalline powder. No smell, slightly bitter. Solubility: easily dissolved in ethanol, chloroform, and ethyl. Slightly soluble in water and glycerol. Melting point: 173–175 °C. Specific optical rotation: ?172° (ETOH, C = 1).
• Clinical Use: Falciparum malaria (alone or in combination with tetracycline, doxycycline, clindamycin or pyrimethamine–sulfadoxine) Babesiosis (in combination with clindamycin) It is particularly used in cerebral malaria if chloroquine resistance is suspected (Ch. 62). It is not recommended for treatment of uncomplicated falciparum malaria.

Technology Process of 4-[(R)-[(2S,4R,5R)-5-Vinyl-1-azabicyclo[2.2.2]octane-2-yl]hydroxymethyl]-6-methoxyquinoline

There total 183 articles about 4-[(R)-[(2S,4R,5R)-5-Vinyl-1-azabicyclo[2.2.2]octane-2-yl]hydroxymethyl]-6-methoxyquinoline 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: 95.0%

quinidine acetate (56652-53-0) → quinindine (56-54-2,130-95-0,572-59-8,572-60-1,42151-59-7,47342-58-5,72402-50-7,72402-51-8,72402-52-9,72402-53-0,101143-86-6,101143-87-7,101143-88-8,146925-10-2)

Guidance literature:

With methanol; potassium carbonate; at 20 ℃; for 1.5h; Inert atmosphere;

DOI:10.1016/j.tetlet.2010.12.066

Reference yield: 75.0%

(3R,4S)-4-[(2S,3S)-3-(6-Methoxy-quinolin-4-yl)-oxiranylmethyl]-3-vinyl-piperidine-1-carboxylic acid 2-trimethylsilanyl-ethyl ester (865853-19-6) → quinindine (56-54-2,130-95-0,572-59-8,572-60-1,42151-59-7,47342-58-5,72402-50-7,72402-51-8,72402-52-9,72402-53-0,101143-86-6,101143-87-7,101143-88-8,146925-10-2)

Guidance literature:

With cesium fluoride;

DOI:10.1016/j.tetlet.2005.06.171

Reference yield:

6-Methoxy-4-[(2S,3S)-3-((3R,4S)-3-vinyl-piperidin-4-ylmethyl)-oxiranyl]-quinoline → quinindine (56-54-2,130-95-0,572-59-8,572-60-1,42151-59-7,47342-58-5,72402-50-7,72402-51-8,72402-52-9,72402-53-0,101143-86-6,101143-87-7,101143-88-8,146925-10-2)

Guidance literature:

In acetonitrile; at 185 ℃; for 0.333333h; Microwave irradiation;

DOI:10.1021/ja039550y

upstream raw materials:

quinidine

O-tosylquinine

water

pentan-1-ol

Downstream raw materials:

(S)-(6-Methoxy-quinolin-4-yl)-((1S,2S,4S,5R)-5-vinyl-1-aza-bicyclo[2.2.2]oct-2-yl)-methanol; compound with [benzyl-(2-oxo-2H-quinolin-1-yl)-amino]-acetic acid

6'-methoxycinchonidone

6'-methoxycinchoninone

viquidil

Refernces

Early and Late Steps of Quinine Biosynthesis

10.1021/acs.orglett.1c00206

The study investigates the enzymatic basis for quinine biosynthesis, focusing on the early and late steps of the pathway. Quinine, an alkaloid produced by Cinchona trees, is historically used as an antimalarial drug and as a flavor ingredient in beverages. The researchers combined metabolomics and transcriptomics data from different tissues of Cinchona pubescens to identify genes involved in quinine biosynthesis. They discovered three key enzymes: a medium-chain alcohol dehydrogenase (CpDCS), an esterase (CpDCE), and an O-methyltransferase (CpOMT1). CpDCS and CpDCE were involved in converting strictosidine aglycone to dihydrocorynantheal, an intermediate in quinine biosynthesis, through reduction and esterase-triggered decarboxylation. CpOMT1 was found to specifically act on 6′-hydroxycinchoninone, suggesting a preferred order for the late steps of quinine biosynthesis. The chemicals used in the study included strictosidine, corynantheine aldehyde, dihydrocorynantheine aldehyde, and cinchoninone, among others, which served as substrates, intermediates, and products in the biosynthetic pathway of quinine. The purpose of these chemicals was to elucidate the enzymatic steps and intermediates involved in the biosynthesis of quinine, providing insights into the metabolic pathways and potential for synthetic biology applications in quinine production.

Metal-Free-Visible Light C-H Alkylation of Heteroaromatics via Hypervalent Iodine-Promoted Decarboxylation

10.1021/acs.orglett.8b01085

The study presents a metal-free photoredox C?H alkylation of heteroaromatics using hypervalent iodine dicarboxylates and an organic photocatalyst, 9-mesityl-10-methyl acridinium (MesAcr), under blue LED light. The method leverages readily available carboxylic acids as coupling partners and operates under mild conditions at room temperature. Key chemicals include bis(trifluoroacetoxy)iodobenzene (PIFA) as the oxidant, which helps avoid complications from forming undesired alkylated products and eliminates the need for additional trifluoroacetic acid. The study explores the scope of various carboxylic acids, which generate different alkyl radicals (primary, secondary, tertiary) under the reaction conditions, and tests a range of heteroaromatics and complex molecules, including drugs like voriconazole, varenicline, and quinine, demonstrating good functional group tolerance. Mechanistic investigations, including control experiments, photophysical studies, and DFT calculations, suggest a distinct reaction mechanism involving a chain reaction with a low quantum yield, likely due to an inefficient initiation step.