-chemistry behind the anti-malarial drug 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 Possesses 2 major ring systems: aromatic quinoline , bicyclic quinuclidine.

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

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

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.

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)

Types of bonds present in quinine All the bonds present in quinine are covalent bonds.

R and S forms

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

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.

(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.

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

Derivatives of quinine Quinine Trihydrate Quinine bisulphate heptahydrate Quinine dihydrochloride Quinine hydrochloride dehydrate Quinine sulphate dehydrate

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

Quinine bisulphate Heptahydrate It is obtained as bitter crystals Also known as Quinbisan, Dentojel.

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

Quinine Hydrochloride dihydrate Obtained as silky needles of bitter taste It effloresces on exposure to warm air. Forms anhydrous solution at 373 K.

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

Quinine isomer : quinidine (S)-(6-Methoxyquinolin-4-yl)((2R,4S,8R)-8-vinylquinuclidin-2-yl)methanol

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

uses It is an antiarrhythmic agent It helps in keeping the heart rate normal for the people with certain heart rhythm disorders.

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