EMETIN ELUCIDATION SEMINAR

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1 MEDICINAL CHEMISTRY-II (NATURAL PRODUTS) Seminar on STRUCTURE ELUCIDATION OF EMETINE Presented by: Mr. ABDUL RAZZAQ M. Pharm. Department -: Pharmaceutical Chemistry Luqman College of Pharmacy Gulbarga.

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Points going to discuss are, 1. Introduction 2. Isolation 3. Properties 4. Constitution 5. Synthesis FOR EMETINE

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INTRODUCTION Emetine being an alkaloid was first isolated by Pelletier and Magendie in the year 1817 from roots of Cephalis ipecacuanha belonging to the family Rubiaceae.

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ISOLATION- Roots of iecacuanha & granadensis powder Agited with Ethyl Alco. Or Amyl alco. or Mix. Of Ben. & Lpetro. Decantation Residue Organic solvent + dil.HCl + NH3 Addition of ETHER Aqueous Liquid Ether Layer (Psychotrine alkaloids) (Remaining alkaloids containing EMETINE) Concentrated & convert into HCl salt Fractional Extraction EMETINE salts Remaining get converted gets crystallized out into oxalates

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PROPERTIES- White amorphous powder melting point 70°C. sparingly soluble in Water completely miscible in organic solvents like Alcohol, Chloroform and Ether. Uses- Emetic, Expectorant & Amoebic dysentery

CONSTITUTION : 

CONSTITUTION Molecular formula- By analytical data it is found to be Emetine does not contain N-methyl groups but has a secondary and a tertiary nitrogen atoms. Presence of 4 methoxyl group- it is given by Zeisel Method where in on treating with hydroiodic acid this yields 4 molecules of methyl iodide showing presence of methoxyl groups. Presence of one unit of 6,7-dimethoxy isoquinoline- (a)oxidation with potassium permanganate in presence of acetone to give m-hemipinic acid(1) with small amounts of 6,7-dimethoxy,isoquinoline-1-carboxylic acid(2).

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(b) Oxidation with chromic acid- it yields 4,5-dimethoxy phthalonimide(3) Derivative of tetrahydro isoquinoline- this is shown by the UV-spectra of cephaline and emetine which resembles that of 1,2,3,4-tetrahydro isoquinoline Presence of o-dimethoxy benzene units- This is shown by the UV-spectra of emetine which closely resembles that of tetra hydro papaverine Further proof for 6,7-dimethoxy isoquinoline- (a)Gentle oxidation with alkaline potassium permanganate-this yields firstly Corydaldine(4) then when the remaining mother liquor is oxidized further with the permanganate it gives m-hemipinic acid(1)

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(b)Cephaeline another ipecac alkaloid on ethylation gives ethyl ether of cephaeline which yielded a mixture of corydaldine(4) and ethoxy methoxy isoquinoline (c) oxidation of emetine gives 96% yield of m-hemipinic acid which is higher when compared to papaverine this shows the presence of 2 isoquinoline units Partial structure of Emetine.

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The nature of fragment this is given by Hoffmann Degradation of Emetine which removes the nitrogen atoms completely. It is given in the following steps.

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The formation of ketone is also shown as; The structure of (6) can also be given as;

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From the structure (6) structures (7),(8),(9)and (10) were proposed .Based on (7) the structure of emetine was given.

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Emetine is found to contain only one C-alkyl group hence structures (9) and (10) are ruled out as they contain 2 alkyl groups. For biogenetic reasons structure (8) is said to be the structure of emetine.

SYNTHESIS Openshaw and Whittaker’s Synthesis : 

SYNTHESIS Openshaw and Whittaker’s Synthesis

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REFERENCES Organic chemistry of natural products, by,Gurdeep Chatwal , Himalaya Publishing House, page no :- 398 – 407.

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Thank you