Alkaloids Morphine Opium Alkaloids First alkaloid to be
Alkaloids • Morphine (Opium Alkaloids) • First alkaloid to be isolated from serturner Plants. • It is present about 10: 23 % quantity in opium along with other substances like fats, resins, proteins, carbohydrates, mineral salts etc. and about 20 more alkaloids. • Morphin and other opium alkaloids are (codeine )are widely used as analgesic agents. • Morphin act as monoacid base& forms well defined salt with acids. • In medicine morphine is used as its chloride & it is also used as the diacetyl derivatives under the trade name heroin.
Opium poppy
Coniine Alkaloids The poisonous hemlock plants
Properties • • • It is colourless and poisonous oily liquid (B. P. 167 °C) It is optically active. It is soluble in water and having burning taste. It yields a crystalline hydrochloride and picrate` It is secondary amine , yields a crystalline 3, 5 -dinitrobenzoyl derivatives and an N-nitroso derivatives.
Synthesis of Coniine The first synthesis of coniine was carried out by Ladenburg in 1886. He heated methylpyridinium iodide at 300 o. C to obtain 2 -methyl pyidine. On treatment with acetaldehyde with a Lewis base 2 -propenylpyridine was obtained and this was reduced to (±)-coniine by reduction with sodium in alcohol. Enantiomeric separation was achieved by fractional crystallization of the diastereoisomers of the salt obtained with (+)-tartaric acid
Papaverine • Papaverine contains together nearly twenty four other alkaloids such as daudonosine, daudamine, narcotine, narceine, morphineetc. • PROPERTIES 1. It is colourless solid M. P. 147 ° C 2. It is an optically inactive tertiary base forming a any salts and tertiary iodides. 3. It is insoluble in water but soluble in hot alcohol and chloroform. 4. It acts as a pain killer but having weaker physiological action than Morphin. 5. It finds use of antispasmodics for the relaxation of cardiac muscles & in the remedy for cough. 6. In small dosage it causes light sleep (narcosis) , while in larger dosages it causes tetanus & respiratory paralysis.
Papaverine is a vasodilator that relaxes smooth muscles in your blood vessels to help them dilate (widen). This lowers blood pressure and allows blood to flow more easily through your veins and arteries. Papaverine is used to treat many conditions that cause spasm of smooth muscle. Structure:
Capsule of Papaver somniferum showing latex (opium) exuding from incision. Papaverine occurs naturally in opium.
Constitution / Structural determination • The structure of Papaverine is established as follows. 1. Mol. Formula – C 20 H 21 NO 4 2. Presence of tertiary base- Its adds to one mole of methyl iodide to gives quaternary methiodide derivative i. e. Nitrogen present in papaverine is tertiary. C 20 H 21 NO 4 + CH 3 I C 20 H 21 O 4 N+ CH 3 I- 3. Presence of 4 methoxy groups- When Papaverine is constant heated with HI it yields four equivalents of methyl iodide it indicates that Papaverine contains three(-OCH 3) methoxy groups. C 16 H 19 N(OCH 3)4 +4 HI C 16 H 19 N(OH)4 + 4 CH 3 I Papavaroline
• Presence of Methylene Group-(-CH 2) (C 19 H 19 NO 4)CH 2 + [O] (C 19 H 19 NO 4)CHOH + [O] (C 19 H 19 NO 4)CO C 16 H 13 NO 4 Papavarenic acid
Various fragments of Papaverine • When Papaverine is oxidised with Pott. permangnet it is broken down into small fragments. Like Veratric acid, Veratol, m-Hepanic acid, pyridine, 2, 3, 4 -tricarboxylic acid. • The structure of Veratric acid –C 9 H 10 O 4 Veratole is o-dimethoxy benzene its mean that veratric acid is must be dimethoxy benzoic acid. The position of the carbonyl group respect to the dimethoxy group is ortho is established by the synthesis of vatic acid as follows.
A. Synthesis of veratric acid Thus, Veratric acid must be 3, 4 - dimethoxybenzoic acid
B. Structure of m-Hemipinic acid C 10 H 10 O 4 • When m-hemipinic acid is heated with soda lime , this acid undergoes decarboxylation to yield veratrole. This reaction indicates that m-hemipinic acid contains two methoxy groups in the ortho positions. • m-hemipinic acid when heated with acetic anhydride yields anhydride , indicating that two carboxyl groups are ortho to each other in m-hemipinic acid.
Reactions
C. Structure of Pyridine 2, 3, 4 -tricarboxylic acid (C 8 H 5 O 6 N) • On decarboxylation it yields pyridine, indicating that it must be a tricarboxylic acid.
D. Structure of 6, 7 -dimethoxy isoquinoline -1 -carboxylic acid(C 12 H 11 NO 4)
From the above reactions & observations, we may now establish the structure of papaverine as follows • 1. The isolation of veratric acid reveals the presence of dimethoxy group in papaverine.
• The isolation of 6, 7 -dimethoxy isoquinoline-1 -carboxylic acid reveals the presence of group in the molecule. The presence of these two fragments also account for the isolation of other two fragments. (m-Hempinic acid and 2, 3, 4 -tricarbixylic acid)
The structure of veratric acid contains 9 carbon atoms whereas structure 6, 7 -dimethoxy isoquinoline-1 -carboxylic acid contains 12 C atoms, Therefore the total number of C atoms in these two structure is C 21 But Papaverine contains only 20 carbon atoms & it also contains a –CH 2 group. If it assumed that Cx and Cy are one and the same Carbon atom. i. e the carbon atom of the CH 2 group, then the structure of papaverine can be written as follows. Papaverine Papaverinol Papaverinic acid
The structure of papaverine has been confirmed by the following synthesis (Bide & Wilkinson) • Synthesis of homoveratroyl Chloride & homoveratroyl amine. 3, 4 -Dimethoxybenzyl nitrile Homovaratric acid Homovaratroyl chloride
Condensation of the amine and the chloride leading to the synthesis of papavarine Dihydropapavarine Papavarine
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