Slide 1: 1 MEDICINAL CHEMISTRY-II
STRUCTURE ELUCIDATION OF EMETINE
Mr. ABDUL RAZZAQ
Luqman College of Pharmacy
Gulbarga. Slide 2: Points going to discuss are,
FOR EMETINE Slide 3: 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. Slide 4: ISOLATION- Roots of iecacuanha & granadensis powder
Agited with Ethyl Alco. Or
Amyl alco. or Mix. Of Ben. & Lpetro.
Residue Organic solvent
Addition of ETHER
Aqueous Liquid Ether Layer
(Psychotrine alkaloids) (Remaining alkaloids containing EMETINE)
Concentrated & convert into HCl salt
EMETINE salts Remaining get converted
gets crystallized out into oxalates Slide 5: 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). Slide 7: (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) Slide 8: (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. : 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. Slide 12: The formation of ketone is also shown as; The structure of (6) can also be given as; Slide 13: From the structure (6) structures (7),(8),(9)and (10) were proposed .Based on (7) the structure of emetine was given. Slide 14: 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 Slide 19: REFERENCES
Organic chemistry of natural products,
by,Gurdeep Chatwal ,
Himalaya Publishing House,
page no :- 398 – 407. Slide 20: Thank you