Lecture â„–24 Alkaloids derivatives of tropane, ecgonine and isoquinoline. Social significance of the research which help to find the morphine-type analgesics

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  • Lecture 24 Alkaloids derivatives of tropane, ecgonine and isoquinoline. Social significance of the research which help to find the morphine-type analgesics As. Kozachok S.S.
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  • ropane bicyclic condensed system, which contains the piperidine and pirrolidine cycles. PyrrolidinePiperidineTropane
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  • ropane is a base of the alkaloids row and their structural analogs. According to the chemical structure these compounds are divided into two groups: derivatives of tropane alcohol (1) and derivatives of tropane-2- carboxylicecgonine (2):
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  • Tropanes alkaloids are in the plants of Solanaceae family (belladonna, datura, hioscyamus niger).
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  • The maine representatives of topanes alkaloids are racemic atropine, its left rotation isomer hyoscyamine and the analogue of hyoscyamine - scopolamine. Atropine was first isolated from belladonna in 1833. In the plants it is contained in very small quantities with hyoscyamine and scopolamine together. Atropine was first isolated from belladonna in 1833. In the plants it is contained in very small quantities with hyoscyamine and scopolamine together. Obtaining the atropine and hyoscyamine from plant materials in the form of bases (after treatment with ammonia), organic solvents (dichloromethane, benzene). Atropine is formed from hyoscyamine by racemization at 114-116 C, at a higher temperature is formed apoatropin having no pharmacological activity of atropine. After hyoscyamine separation from solution, scopolamine is released.
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  • Synthetically extracted from amber aldehyde, methylamine, acetone and d, l-tropic acid.
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  • Atropine sulphate (Atropini sulfas) (SPhU) bis(1R,R,5S)-3-[(RS)-(3-hydroxy-2-phenylpropanoate) oxy]-8-methyl-8-azabicyclo[3.2.1] octane sulfate monohydrate Bis[(1R,3r,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (2RS)-3- hydroxy-2-phenylpropano] sulphate monohydrate. Tropine ester d,l-tropic acid sulfate monohydrate
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  • Scopolamine hydrobromide (Scopolamini hydrobromidum) Scopolamine ester (-)-tropic acid hydrobromide, trihydrate IUPAC ()-(S)-3-hydroxy-2-phenylpropionic acid(1R,2R,4S,7S,9S)-9-methyl-3-oxa-9- azatricyclo[3.3.1.02,4]non-7-yl ester
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  • Physical properties Atropine sulphate White or almost white, crystalline powder or colourless crystals. Very soluble in water, freely soluble in ethanol (96 per cent). Melting at 190 and decomposing. Scopolamine hydrobromide. in water in ethanol, very slightly soluble in chloroform. White or almost white, crystalline powder or colourless crystals. Freely soluble in water soluble in ethanol, very slightly soluble in chloroform.
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  • Identification Atropine sulphate 1. According to the physical- chemical constants: infrared spectroscopy and o (-0,5 -+0,05 ). 1. According to the physical- chemical constants: infrared spectroscopy and optical rotation (-0,5 -+0,05 ). 2. Melting point of atropine picrate. 3. Vitali's-Morena reaction ( on tropic acid). 4.. 4. It gives the reactions of sulphates. 5. : 5. It gives the reaction of alkaloids Non pharmacopoeia reaction: ) Melting point of atropine base (115-117 ) after settled down by ammonia solutiobn; b) formation of benzaldehyde (small of bitter almond) at the heating atropine with sulfuric concentrated acid and crystalline potassium dichromate: Scopolamine hydrobromide 1. (three reaction according to SPhU). 1. It gives the reactions of bromides (three reaction according to SPhU). 2. Vitali's-Morena reaction ( on tropic acid). 3. Melting point (192-196 ) and o : -22 till -26 (5 %-water solution). 3. Melting point (192-196 ) and optical rotation : -22 till -26 (5 %-water solution). 4. 4. It gives the reaction of alkaloids
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  • Formation of benzaldehyde
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  • Vitali's-Morena reaction Vitali's-Morena reaction To about 1 mg add 0.2 ml of fuming nitric acid R and evaporate to dryness in a waterbath, formation a polynitrocompound of a yellow colour. Dissolve the residue in 2 ml of acetone R and add 0.1 ml of a 30 g/l solution of potassium hydroxide R in methanol R. A violet colour develops.
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  • Purity test Atropine sulphate 1. 1. Apoatropine(