Ornithine and Lysine Alkaloids & Drugs • Ornithine.. a. Tropane Alkaloids • -Folia Stramonii • -Folia Hyoscyami • -Herba ve Radix Belladonnae • -Duboisia myoporoides • -Withania Somnifera • -Atropinum • -Folia Cocae • -Pyridine and Piperidine Alkaloids • -Folia Nicotianae • -Nicotine and derivatives • • -Lysine....... b. Pyrolizidine Alkaloids • -Herba Lobeliae • -Cortex Radicis granatii • c. Phenyl alanine, Tyrosine and dihydroalanine derivatives • -Herba Ephedrae • -Catha • -Anona scuomosa • -Radix Sanguniaria Tropane alkaloids TROPANE NORTROPANE N-methyl pyrolidine+ piperidine Pyrolidine+Piperidine N CH3 H N piperidine pyrolidine Tropane alkaloids *Tropane or nortropanol ring carries 1,2/3 –OH groups and esterifies with acids. *Also some of them carry epoxy group. 1-Monohydroxy Alkamine and esthers 2-Dihydroxy Alkamine and esthers 3-Trihydroxy Alkamine and esthers 4-Epoxytropanole esthers Tropane alkaloids 1-Monohydroxy Alkamine and esthers Contain Tropanol (trans), Pseudotropanol (cis) and Nor- tropanol rings. CH3 N H OH a-Tropanol esthers •Tropanol + atropic acid Atropamin •Tropanol + veratric acid Konvolamin •Tropanol + 2-OH-3-Phenyl Propionic acid Littorin •Tropanol + vanillic acid Fillabin •Tropanol + asetic acid •Tropanol + propionic acid •Tropanol + butyric acid •Tropanol + benzoic acid •Tropanol + izobutyric acid •Tropanol + izovalerianic acid Tropic acid esthers Optically active structures (l) tropic acid + tropanol Hyoscyamine (l) (dl) tropic acid + tropanol ->> Atropine (dl) Tropanol esthers; parasympatholyticCH3 and midriatic activity. N H HOOC C CH2OH H OH b-Pseudotropanol and Ecgonine Esthers • Pseudo-Tropanol + benzoic acid Tropacocaine • Pseudo-Tropanol + tiglic acid Tigloidine • Ecgonine + Methanol + benzoic acid Cocaine Ecgonine-metyl esther +sinnamic A. Sinnamyl Cocaine Ecgonine-metyl esther +truxillic A. -Truxilline Ecgonine-metyl esther +isotruxillic A. -Truxilline CH3 N COOH OH H c-Nortropanol Esthers • Nor-Tropanol + l-tropic acid norhyoscyamine • Nor-Tropanol + 3-metyl butyric acid poroidine H • Nor-Tropanol + 2-metyl butyric acid isoporoidineN • Nor-Tropanol + veratric acid convolvine 2-Dihydroxy Alkamine Esthers • Dihydroxytropan + 3-methylbutyric acid Valeroidine • Duboisia myoporoides • Datura sanguinea N CH3 HO OH 3-Trihydroxy Alkamine Esthers • Trihydroxytropan (Teloidin) + Tiglic acid Meteloidine • Datura ferox • Datura innoxia N CH3 HO HO OH 4-Epoxytropanol Esthers • Scopanole + l-tropic acid Hyoscine • Scopanole + dl-tropic asid Scopolamine N CH3 O H OH General features of tropan alkaloids • Tropan alkaloitlerinin genel özellikleri • Interacts with general alkaloid reagents such as Mayer, Dragendorff. • Atropine, hyoscyamine and scopolamine have strong mydriatic activity. • Cocaine (pseudo-tropanol) has short mydriasis time. • Vitali-Morin Reaction: The Vitali Morin is a specific example of the well known colour reaction between acetone and aromatic nitro compounds in the presence of sodium hydroxide. In this reaction dinitro compounds generally give a purplish-red colour, whereas trinitro compounds give a blood-red colour. • Powdered drug + base Organic solvent (Evaporate) residue+ conc. Nitric acid acetone+ KOH in methanol Red-Blue • Cocaine does not give Vitali Morin reaction. It can be tested by Rathenasinkam’s Reaction. • To add nitro groups you can use conc. nitric acid + sulphuric acid Identification of Tropan Alkaloids -Paper chromatography -TLC Quantification; Titrimetric: Alkaloids are taken to the ether in NH3 media, then ether evaporated titrate with 0.1 N HCl. Colorimetric: -Vitali-Morin Reaction -Using some colour materials (Bromcresole purple) Tropan Alkaloids • Many physiological activity. • Relaxes the smooth muscles • Dilates pupil • Dilates blood vessels • Increases the body temperature • Stops pain, gives some sleep • First stimulates nervous system, then inhibits • Some of them induces halusinogenic activity The usage of tropane alkaloids -To dilate the pupil -As an antidote especially for morphine and lead poisining -Prepare for anestesia -Antiemetic -Asthma crisis -Pseudo-tropanol esthers (cocaine) local anesthetic Drugs containing tropan alkaloids • Herba ve Radix Belladonnae • Folia Hyoscyami-Folia Stramoni • Duboisia myoporoides • Radix Mandragorae • Withania somnifera • Folia Cocae Duboisia myoporpides • Grows naturally in Australia, 2-12 m tree. • Solanaceae family plant. • To obtain scopolamine from the leaves. Also poroidine, isoporoidine, norhyoscyamine. • 3 species growing in Australia. • D. leichardtii is a source plant for tropan alkaloids. • D. hopwoodii carries nicotine and similars. • D. myoporoides and D. leichardtii grows in the east coasts of Australia; D. hopwoodii grows in the West and Inner Australia. • Mainly used for obtaining hyoscyamine and scopolamine. 1-3% alkaloid. Leaves can be picked up easily twice in a year. Approximately 1200 tones of leaves are exported to European countries like Germany, Switzerland and also to Japan. • There are some patent studies on obtaining hyoscyamine and scopolamine from Duboisia leaves using cell culture methods. Radix Mandragorae, Mandrake Mandragora officinarum var. vernalis (green-white flowers) (Solanaceae) M. officinarum var. autumnalis (pale purple flower) Mediterranean plant. Fruits are yellow-orange, sometimes mixed with some edible fruits so that some toxication events reported. Unique radix which looks like man. Roots carries 0.4% alkaloids. (Atropine, scopolamine, hyoscyamine, cuscohygrine) Drug; sedative, narcotic and analgesic. Mystic plant, in thge past used in religious anniversaries. The only anesthetic material used in the operations in the middle age. • Ecballium elatarium or Tamus communis roots are sold as Radix Mandragorae in Turkey, but they do not contain alkaloids. Folia Cocae • Small trees or shrubs. Grows aproximately to 2m. Native to South America. • Cultivated for long years, and leaves are picked up three times in a year (March, June and November). Erythroxylum; red tree. E. coca (Bolivian Coca) E. truxillense (Peru / Truksillo Coca) Different type of E. truxillense (Java Coca) Coca; tree is called as Coca in Spain. Truksillo is a harbour city in Peru. Peru and Bolivya produce Coca leaves for medicine industry legally with international pacts. In the same time these two countries are the illegal source of Coca leaves and Cocain. Plant is cultivated at an altitude of 500- 2000m. 25% of the cultivated plant was used by native public. 2% is used for medicine industry. The rest is for illegal purposes. The Europeans meet with the Coca leaves in 1688, and cocain was isolated in 1860. Bolivian Coca leaves: Short stalk, oval, 2.5-7.5 height; 1.5-4 cm width; leaf leathery, greenish brown, margins entire. Peru/Truksillo Coca leaves: E. truxillense Pale green colour, easily fragile, lamina 1.6-5 cm length Anatomic features • F. Cocae; simple crystals near veins in the mesophyll of leaf. • Wide spaces between cells in spongy parenchyma. Stoma and papil exist in lower epiderm. • Stoma has two neighbour cells, and the common wall is not significant, stoma is in the middle of two cells. • Leaves contain 0.7- 1.5% alkaloid. • Cocaine, cinnamyl cocaine and truxilline are the main alkaloids. • Methyl salisilate is the volatile constituent and composes the 13.6 of the essential oil. Before obtaining Cociane from the leaves, Coca pasta is prepared in Columbia. 100-200 kg leaves produce 1 kg pasta. 1 kg cocaine is obtained from 2.5 kg pasta. • Cocaine was isolated in 1860. • Coca is Inka’s holy plant. • Koller determied the local anesthetic effect. • Coca leaves contain 3 types of alkaloids. Ecgonine derivatives (cocaine, cinnamyl cocaine, and - truxilline) • Tropine derivatives (Tropa-cocaine, Valerine) • Hygrine derivatives (Hygrine ve cuscohygrine) • Only the ecgonine type is commercially important. • 30-50% of Coca leaf is cocaine. • Native South Americans chew this leaf to stop hunger and thirst. This effect is due to the local anesthetic activity on the stomach mucosa. Also used for toothache. COCAINUM Obtained from leaves of Erythroxylum coca varieties. Also semisynthetically obtained from ecgonine derivatives. Cocaine is a methyl esther of benzoyl ecgonine. Hydrolization products are ecgonine + benzoic acid and methanol. Cinnamyl cocaine; Ecgonine + cinnamic acid and methanol Cocaine is obtained by different patented techniques in large scale. Cocaine is a strong stimulant, and has a strong addiction potential. Decreases eating and sleeping activities. Cocaine HCl HCL salt of Cocaine. White or clourless crystals or in powder form. Used to stop strong pains of cancer patients together with morphine and methadone. (Brompton Coctail) Nearly 6,5 million people are using Cocaine in USA. (i.v. or subcutaneus injection or base cocaine). Base Cocaine is volatile at 98 C, while HCl salt is volatile at 195 C. Cocaine inhalation starts quickly stimulation and euphoria. «Crack»is the version addition with water and Na bicarbonate or amonium bicarbonate. Effective afer 10 secons of consumption. In operative sciences cocaine was used as local anesthetic as 10% solutions in ear nose operations. Addiction Cocaine addiction is similar to amphetamine addiction. Euphoric effect is stronger than the other psycoactive drugs like eroin. Paranoid symptoms, agressive behaviour, antisocial behaviour. Very strong psycological addiction occurs. No tolerence or physically addition occur. No deficienct syndrome. Folia Stramoni; Stramonium Leaf Dried leaves or sometimes leaves with flowers of