Pharmacognosy. 2 nd semester Lec:9. Alkaloids Derived from Phenylalanine and Tyrosine:-

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1 Third stage Dr. Enass Najem 2 nd semester Lec:9 Alkaloids Derived from Phenylalanine and Tyrosine:- A very large number of alkaloid structures arise from the metabolism of aromatic amino acids (phenylalanine, tyrosine), and at first approximation, these are always isoquinoline alkaloids. Isoquinolone alkaloids The isoquinolone structure occurs in considerable number of alkaloids in widely separated families. They represent the largest single group of plant alkaloids, and there is a great variation in their chemical structures. Some of the important isoquinlone subgroups are benzylisoquinolone represented by papaverine and tubocurarine, the benzophenanthridines represented by saguinarine, the pthalideisoquinolone that contain aγ- lactone ring and are represented by hydrastine, the morphinans represented by opium alkaloids, the protoberberines represented by by berberine, and those with emetine skeleton Tubocurare and d- tubocurarine:- Curare or south American arrow poison is a crude extract from the bark of Chondodendron tomentosum and C. platyphyllum (Menispermaceae), which grow wild in Brazil. The poisonous material is known as curare (which means poison in several local languages). The toxic principle is the biscoclaurinetype alkaloid d-tubocurarine an alkaloid derived from phenylalanine. The chemical structure of d-tubocurarine was first proposed as a bisbenzylisoquinoline with two quaternary ammonium moieties. 1

2 d-tubocurarine acts as an antagonist for the nicotinic acetylcholine receptor. The dominant pharmacological effect of curare is the paralysis of the whole skeletal muscle in animals. The sequence of the paralytic effects of the skeletal muscle is well defined. At first, the eyes, ears, and toes are affected, and next the muscles of the arms and legs. Paralysis of the muscles of the neck then occurs, and finally the respiratory muscles are affected, resulting in suffocation in animals. The muscle-relaxing activity of d-tubocurarine is useful during surgery and also to prevent the convulsions caused by strychnine poisoning. Curare is also used in the field of psychiatry to prevent convulsions during shock therapy. On the other hand, d-tubocurarine has also served as a pharmacophoric template for synthetic anticonvulsants, such as decamethonium and suxamethonium, and hypotensive drugs, such as hexamethonium. Phellodendron amurense AND Berberine:- Phellodendron amurense is a deciduous tree that grows wild in Japan, Korea, and the northern areas of China, and often grows to be 25 m high and 1 m in diameter. The dried bark of this tree is used as a tonic for the stomach, as a medicine for intestinal disorders, and as an antiinflammatory and antipyretic agent. The active constituent of Phellodendron amurense is berberine, and it is usually isolated as berberine chloride. Pills containing berberine chloride are marketed as a tonic for stomach and intestinal disorders in Japan. 2

3 Berberine is also obtained from Hydrastis canadensis (Berberidaceae), Coptis japonica (Ranunculaceae), and Hydrastis canadensis (Golden seal, berberine content 2-4.5%) which also contains Hydrastine, mirrors the choleretic and antibacterial properties of berberine containing plants and is excellent for any infectious condition of the mucus membranes. Regarding the many biological activities of berberine, other than antimicrobial activity against Staphylococcus aureus, dysentery bacillus, cholera vibrio, and gonococcus organisms,hypertensive, sedative, anti-inflammatory, and cytotoxic activities are reported. Cephaelis ipecacuanha and emetine:- Cepahelis species (Rubiaceae) are shrubs that grow wild in areas of Brazil, Colombia, and Malaysia. The roots of this plant (Ipecacuanhae Radix) are used as an emetic and to clear the throat of phlegm. Emetine (70% of the total alkaloids) and cephaeline were isolated as the main constituents of Ipecacuanhae Radix (C. ipecacuanha). Emetine shows an emetic effect by stimulating the gastric mucous membranes. It causes an increase of secretion in the trachea in a small dose and is used to clear throat of phlegm. Cephaeline shows stronger emetic activity and higher toxicity than emetine. Because emetine kills protozoa, even at a concentration of mg/ml, it is also used as hydrochloride as a specific medicine for amoebic dysentery. Amoebic dysentery is caused by the protozoan Endamoeba histolytica. 3

4 Opium and Morphine. Papaver somniferum (Papaveraceae) is a biennial originating in the southeastern area of Europe, and is cultivated as the material for opium and for morphine. Papaver somniferum is a typical narcotic plant, and is cultivated under strict control in a limited number of countries,including Pakistan, Bulgaria, Turkey, Australia, and Japan. Papaver somniferum flowers around May in Japan with red, white, partially colored, and double-petaled flowers. After flowering, it produces a large capsule, which, after ripening, contains many seeds. Opium is the dried latex (it is first white and becomes black subsequently) exuded by scratching the fruit slightly while it is immature. The milky fluid that seeps from cuts in the unripe poppy seed pod has been scraped off and air-dried to produce what is known as opium. This lets the opium gum ooze out. The semi-dried "gum" is harvested with a curved spatula and then dried in open wooden boxes. The dried opium resin is placed in bags or rolled into balls for sale. Opium contains 10 25% alkaloids, and the main constituent is morphine. Other than morphine, more than 25 alkaloids are known, and among them are other 4

5 morphinan-type alkaloids (codeine and thebaine), benzylisoquinoline- type alkaloids (papaverine and noscapine), and protopine-type alkaloids (protopine). The biosynthetic precursor of all of these alkaloids is phenylalanine. Semi synthetic opioids: created from the natural opiates, such as hydromorphone, hydrocodone, oxycodone, oxymorphone, desomorphine, diacetylmorphine (heroin), nicomorphine, benzylmorphine and ethylmorphine Morphine hydrochloride, purified from opium powder, is used as an analgesic and an anesthetic, and codeine phosphate and noscapine hydrochloride are used in cough medicines. Papaverine hydrochloride is used as a smooth muscle relaxant. Opioids bind to specific opioid receptors in the central nervous system and other tissues. There are three principal classes of opioid receptors, μ, κ, δ (mu, kappa, and delta). 5

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