quinine

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QUININE -CHEMISTRY BEHIND THE ANTI-MALARIAL DRUG

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QUININE. -chemistry behind the anti-malarial drug. WHAT IS QUININE?. Natural, white crystalline alkaloid Possesses antipyretic, antimalarial , analgesic and anti-inflammatory properties Bitter taste Stereoisomer of quinidine - PowerPoint PPT Presentation

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Page 1: QUININE

QUININE-CHEMISTRY BEHIND THE ANTI-MALARIAL

DRUG

Page 2: QUININE

WHAT IS QUININE?

• Natural, white crystalline alkaloid• Possesses antipyretic, antimalarial , analgesic

and anti-inflammatory properties• Bitter taste • Stereoisomer of quinidine• Possesses 2 major ring systems: aromatic

quinoline , bicyclic quinuclidine.

Page 3: QUININE

BIOLOGICAL SOURCES AND HISTORY

• Cinchona species (Rubiaceae)• Obtained from cinchona or peruvian bark• First discovered by Quechua of Peru and

Bolivia• First used antimalarial drug

Page 4: QUININE

CHEMICAL STRUCTURE

(R)-(6-Methoxyquinolin-4-yl)((2S,4S,8R)-8-vinylquinuclidin-2-yl)methanol

Page 5: QUININE

CHARACTERISTICS• Fluoresces in direct sunlight• Sublimes in vacuum at 443-453k.• Dissociation constants Pk1=5.07 and

pK2=9.7• pH of saturated solution=8.8• Fluoresces with a blue colour especially in

sulphuric acid.

Page 6: QUININE

FUNCTIONAL GROUPS • It's functional groups are:

* alkene* tertiary amine (the quinuclidine bicyclic system)* secondary alcohol* quinoline (an aromatic system, specifically 1- azanaphthalene)* phenolic ether (or perhaps simply an aromatic ether)

Page 7: QUININE

TYPES OF BONDS PRESENT IN QUININE

• All the bonds present in quinine are covalent bonds.

Page 8: QUININE

R AND S FORMS

Page 9: QUININE

Powdered Bark- Alk. CaO + NaOH + H2O- Reflux with benzene &- Filtration while hot

Benzene filtrate (Alkaloidal bases)dilute H2SO4

Acidic aqueous layer(Alkaloidal bisulphates)

pH to 6.5 with Na2CO3

PrecipitateQuinine quinidine,

cinchonine & cinchonidine Hot water, Na2CO3

Quinine NaOH, ether

Aqueous layerEther layerCinchonineQuinidine & Cinchonidine

-HCl PH=7, Na, K Tart. salt- filter

Precipitate Filtrate

Cinchonidine tartrate Quinidine tartrate

Aqueous solution (Monosulphates)(monosulphate)

Page 10: QUININE

RABE AND KINDLER PROCESS

• In 1918 Paul Rabe and Karl Kindler obtained a three step preparation of quinine from d- quinotoxine

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IDENTIFICATION TESTS(a)Colour Tests:1.Oxygenated Acids : Strong, blue fluorescence

in sulphuric acid, acetic acid,etc.2. Herpathite Test: boiling mixture of

quinine(0.3g)+ 7.5ml glacial acetic acid+ 5 drops of conc. H2SO4 in 3ml ethanol(0.9v/v)+3.5 ml of I2 solution(0.01w/v) in ethanol—dark crystals of sulphate of iodoquinine (herpathite) obtained.

Page 13: QUININE

(c) Thalleioquin Test: Br2 water+2-3 ml of weakly acidic solution of quinine salt+0.5-1 ml of strong ammonia solution—distinct emerald green colouration.

(d) Erythroquinine Test(Rosequin Test): Quinine+ dil. Acetic acid+ freshly prepared Br2 water+ 10% solution of [K4Fe(CN)6]+ conc. NH4OH soln—red colouration.

Page 14: QUININE

USES

• Flavour in carbonated beverages.• Antimalarial agent.• Skeletal muscle relaxant.• Used to treat hemorrhoids and varicose veins• Oxytocic agent.• Prophylactic for flu.

Page 15: QUININE

DERIVATIVES OF QUININE

1)Quinine Trihydrate2)Quinine bisulphate heptahydrate3)Quinine dihydrochloride4)Quinine hydrochloride dehydrate5)Quinine sulphate dehydrate

Page 16: QUININE

QUININE TRIHYDRATE

• It has a melting point of 330 K • It becomes anhydrous at 398 K

Page 17: QUININE

QUININE BISULPHATE HEPTAHYDRATE

• It is obtained as bitter crystals• Also known as Quinbisan, Dentojel.

Page 18: QUININE

QUININE DIHYDROCHLORIDE

• Also known as quinine dichloride, Quinine bimuriate• Slightly soluble in chloroform and very

slightly soluble in ether• Aqueous solutions are found to be higly

acidic with a pH of 2.6

Page 19: QUININE

QUININE HYDROCHLORIDE DIHYDRATE

• Obtained as silky needles of bitter taste• It effloresces on exposure to warm

air.• Forms anhydrous solution at 373 K.

Page 20: QUININE

QUININE SULPHATE DIHYDRATE

• Also known as Quinsan, Quine and Quinate• Its is obtained as dull needles or rods

making a light and readily compressible mass.• Losses water of crystallization at 383 K.• Slightly soluble in ether and chloroform

Page 21: QUININE
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QUININE ISOMER : QUINIDINE

(S)-(6-Methoxyquinolin-4-yl)((2R,4S,8R)-8-vinylquinuclidin-2-yl)methanol

Page 23: QUININE

Powdered Bark- Alk. CaO + NaOH + H2O- Reflux with benzene &- Filtration while hot

Benzene filtrate (Alkaloidal bases)dilute H2SO4

Acidic aqueous layer(Alkaloidal bisulphates)

pH to 6.5 with Na2CO3

PrecipitateQuinine quinidine,

cinchonine & cinchonidine Hot water, Na2CO3

Quinine NaOH, ether

Aqueous layerEther layerCinchonineQuinidine & Cinchonidine

-HCl PH=7, Na, K Tart. salt- filter

Precipitate Filtrate

Cinchonidine tartrate Quinidine tartrate

Aqueous solution (Monosulphates)(monosulphate)

Page 24: QUININE

PROPERTIES• It is optical isomer of quinine• It is a diastereomer of quinidine• It is found as white powder or crystals• Insoluble in water• It melts at 441 K

Page 25: QUININE

USES

• It is an antiarrhythmic agent • It helps in keeping the heart rate normal

for the people with certain heart rhythm disorders.

Page 26: QUININE

….THANK YOU….DONE BY DHRUVI, RUTVI, SIDDHARTH