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Roque, Jason R. HUB 22

Organic Chemistry Lecture

ALKALOIDS
HISTORY: Alkaloid-containing plants were used by humans since ancient times for therapeutic and recreational purposes. For example, medicinal plants have been known in the Mesopotamia at least around 2000 BC. The Odyssey of Homer referred to a gift given to Helen by the Egyptian queen, a drug bringing oblivion. It is believed that the gift was an opium-containing drug. A Chinese book on houseplants written in 1st-3rd centuries BC mentioned a medical use of Ephedra and opium Friedrich Sertrner, the German chemist who poppies. Also, coca leaves were used by South first isolated morphine from opium. American Indians since ancient times. Extracts from plants containing toxic alkaloids, such as aconitine and tubocurarine, were used since antiquity for poisoning arrows.

Studies of alkaloids began in the 19th century. In 1804, the German chemist Friedrich Sertrner isolated from opium a "soporific principle" (Latin:principium somniferum), which he called "morphium" in honor of Morpheus, the Greek god of dreams; in German and some other Central-European languages, this is still the name of the drug. The term "morphine", used in English and French, was given by the French physicist Joseph Louis Gay-Lussac).

A significant contribution to the chemistry of alkaloids in the early years of its development was made by the French researchers Pierre Joseph Pelletier and Joseph Bienaim Caventou who discovered quinine (1820) and strychnine (1818). Several other alkaloids were discovered around that time, including xanthine (1817), atropine (1819), caffeine (1820), coniine (1827), nicotine (1828), colchicine (1833),sparteine (1851) and cocaine (1860).

The first complete synthesis of an alkaloid was achieved in 1886 by the German chemist Albert Ladenburg. He produced coniine by reacting 2-methylpyridine with acetaldehyde and reducing the resulting 2-propenyl pyridine with sodium. The development of the chemistry of alkaloids was accelerated by the emergence of spectroscopic and chromatographic methods in the 20th century, so that by 2008 more than 12,000 alkaloids had been identified.

GENERAL PROPERTIES:

1)

Most alkaloids are crystalline compound, odorless, colorless, non volatile. they contain C, H, N, O few oxygenated alkaloids, non Volatile liquid. e.g: Pilocarpine, pelletierine. Alkoids, Lack oxygen in their structure. Usually occur as volatile liquid. e.g: coniine, nicotine. Very rare colored alk. e.g: Berberine, Colchicine (yellow). Being basic, alkaloid Some alkaloids, Neutral or slight acidic reaction can not form salts. e.g: Ricinine, Theophylline. Amphoteric alkaloids contain-COOH group. A narceine or-OH gp. as morphine. Weak basic alkaloids. e.g: caffeine, narcotine, papaverine, piperine from salts are unstable.

2) 3) 4) 5.) 6) 7)

Solubility of alkaloids: In fact, the differences in solubility between alkaloids and their salts strongly facilitate the process of isolation and separation of the talks. From plant and from non-alkaloidal subst.

APPLICATION:

The role of alkaloids for living organisms which produce them is still unclear. Initially it was assumed that the alkaloids are the final products of nitrogen metabolism in plants, andurea in mammals. Later it was shown that alkaloid concentrations varies over time and this hypothesis was refuted. Most of the known functions of alkaloids are related to protection. For example, aporphine alkaloid liriodenine produced by the tulip tree protects it from parasitic mushrooms. In addition, presence of alkaloids in the plant prevents insects and chordate animals from eating it. However, some animals adapted to alkaloids and even use them in their own metabolism. Such alkaloid-related substances as serotonin, dopamine and histamine are important neurotransmitters in animals. Alkaloids are also known to regulate plant growth. Medicine Medical use of alkaloid plants has a long history, and thus when the first alkaloids were synthesized in the 19th century, they immediately found application in clinical practice. Many alkaloids are still used in medicine, usually in the form of salts, including the following: Alkaloid Ajmaline Atropine, scopolamine, hyoscyamine Vinblastine, vincristine Vincamine Codeine Cocaine Colchicine Morphine Reserpine Tubocurarine Physostigmine Quinidine Quinine Emetine Ergot alkaloids Action antiarrhythmic anticholinergic antitumor vasodilating, antihypertensive cough medicine anesthetic remedy for gout analgesic antihypertensive muscle relaxant inhibitor of acetylcholinesterase antiarrhythmic antipyretics, antimalarial antiprotozoal agent sympathomimetic, vasodilator, antihypertensive

Agriculture Prior to the development of a wide range of relatively low-toxic synthetic pesticides, some alkaloids, such as salts of nicotine and anabasine, were used as insecticides. Their use was limited by their high toxicity to humans.

Use as psychoactive drugs Preparations of plants containing alkaloids and their extracts, and later pure alkaloids have long been used as psychoactive substances. Cocaine and cathinone are stimulants of the central nervous system. Mescaline and many of indole alkaloids (such as psilocybin, dimethyltryptamine and ibogaine) have hallucinogenic effect. Morphine and codeineare strong narcotic pain killers. There are alkaloids that do not have strong psychoactive effect themselves, but are precursors for semi-synthetic psychoactive drugs. For example, ephedrine and pseudoephedrine are used to produce methcathinone (ephedrine) and methamphetamine.

*Atropine: 1. In general, atropine lowers the parasympathetic activity of all muscles and glands regulated by the parasympathetic nervous system. This occurs because atropine is a competitive antagonist of the muscarinic acetylcholine receptors (acetylcholine being the mainneurotransmitter used by the parasympathetic nervous system). Therefore, it may cause swallowing difficulties and reduced secretions. 2. Topical atropine is used as a cycloplegic, to temporarily paralyze the accommodation reflex, and as a mydriatic, to dilate the pupils. Atropine degrades slowly, typically wearing off in 7 to 14 days, so it is generally used as a therapeutic mydriatic, whereas tropicamide (a shorter-acting cholinergic antagonist) or phenylephrine (an adrenergic agonist) is preferred as an aid to ophthalmic examination. Atropine induces mydriasis by blocking contraction of the circular pupillary sphincter muscle, which is normally stimulated by acetylcholine release, thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil. Atropine induces cycloplegia by paralyzing the ciliary muscles, whose action inhibits accommodation to allow accurate refraction in children, helps to relieve pain associated

with iridocyclitis, and treats ciliary block (malignant) glaucoma. is contraindicated in patients pre-disposed to narrow angle glaucoma. Atropine can be given to patients who have direct globe trauma.

Atropine

3. Injections of atropine are used in the treatment of bradycardia (an extremely low heart rate), asystole and pulseless electrical activity(PEA) in cardiac arrest. This works because the main action of the vagus nerve of the parasympathetic system on the heart is to decrease heart rate. Atropine blocks this action and, therefore, may speed up the heart rate. 4. Atropine's actions on the parasympathetic nervous system inhibits salivary, sweat, and mucus glands. This can be useful in treating hyperhidrosis, and can prevent the death rattle of dying patients. 5. Atropine is not an actual antidote for organophosphate poisoning. However, by blocking the action of acetylcholine at muscarinic receptors, atropine also serves as a treatment for poisoning by organophosphate insecticides and nerve gases, such as Tabun (GA), Sarin (GB), Soman (GD) and VX. Troops that are likely to be attacked with chemical weapons often carry autoinjectors with atropine and obidoxime, which can be quickly injected into the thigh. Atropine is often used in conjunction with Pralidoxime chloride. *Vinblastine: 1. Antimicrotubule drug used to treat certain kinds of cancer, including Hodgkin's lymphoma, non-small cell lung cancer,breast cancer, head and neck cancer, and testicular cancer. It is also used to treat Langerhan cell histiocytosis. 2. Relieve severe or agonizing pain andsuffering. Like other opioids, such as oxycodone (OxyContin, Percocet, Percodan), hydromorphone (Dilaudid, Palladone), and diacetylmorphine (heroin), morphine acts directly on the central nervous system (CNS) to relieve pain. Unlike the opioids, morphine is an opiate and a natural product. Morphine has a high potential for addiction; tolerance and psychological dependence develop rapidly, althoughPhysiological dependence may take several months to develop.

*Morphine: 1. Regarded as the gold standard, or benchmark, of analgesics used to relieve severe or agonizing pain andsuffering. Like other opioids, such as oxycodone (OxyContin, Percocet, Percodan), hydromorphone (Dilaudid, Palladone), and diacetylmorphine (heroin), morphine acts directly on the central nervous system (CNS) to relieve pain. Unlike the opioids, morphine is an opiate and a natural product. Morphine has a high potential for addiction; tolerance and psychological dependence develop rapidly, althoughPhysiological dependence may take several months to develop. 2. Morphine can be used as an analgesic to relieve: Pain associated with Chronic Pancreatitis pain in myocardial infarction pain in sickle cell crisis pain associated with surgical conditions, pre- and postoperatively pain associated with trauma severe chronic pain, e.g., cancer[15] pain from kidney stones (renal colic, ureterolithiasis) severe back pain

3. Morphine can also be used: as an adjunct to general anesthesia in epidural anesthesia or intrathecal analgesia for palliative care (i.e., to alleviate pain without curing the underlying reason for it, usually because the latter is found impossible) as an antitussive for severe cough in nebulized form, for treatment of dyspnea, although the evidence for efficacy is slim.[16] Evidence is better for other routes.[17] as an antidiarrheal in chronic conditions (e.g., for diarrhea associated with AIDS, although loperamide (a non-absorbed opioid acting only on the gut) is the most commonly used opioid for diarrhea). for relief of acute pulmonary edema through an unknown mechanism for lowering and stabilising blood glucose in diabetics and combating other diabetic effects including diabetic neuropathy. Morphine and whole opium preparations were used for this purpose well into the 1960s in North America and Europe and in much

curtailed fashion now and in other countries. Morphine will also impact hypertension, levels of lipids like cholesterol in blood, and improve laboratory indices in certain types of anaemia, although whole opium preparations are preferred for these purposes if allowed. Most often, chronic pain patients with one or more of the four above conditions are treated with morphine rather than synthetics like pethidine. experimentally for refractory depression. Morphine, hydromorphone, opium products and the like were used on-label for depression from antiquity or prehistoric time up into the middle 1950s. Even today, some doctors prescribe morphine and other opiates off label for depression, anxiety, and other mental illness. The dilemma is that a lifetime of treatment, sometimes with increasing doses, is required in these cases.

*Quinine: 1. Quinine is a flavor component of tonic water and bitter lemon. According to tradition, the bitter taste of anti-malarial quinine tonic led British colonials in India to mix it with gin, thus creating the gin and tonic cocktail. 2. Quinine is also used in photochemistry as a common fluorescence standard. 3. Quinine is used as a treatment for Cryptocaryon irritans (commonly referred to as white spot, crypto or marine itch) infection of marine aquariumfish.

REFERENCE: 1. Andreas Luch (2009). Molecular, clinical and environmental toxicology. Springer. p. 20. ISBN 3764383356. 2. IUPAC. Compendium of Chemical Terminology, 2nd ed. (The "Gold Book"). Compiled by A. D. McNaught and A. Wilkinson. Blackwell Scientific Publications, Oxford (1997) ISBN 0-9678550-9-8 doi:10.1351/goldbook 3. R. H. F. Manske. The Alkaloids. Chemistry and Physiology. Volume VIII. - New York:Academic Press, 1965, p. 673

4. Robert Alan Lewis. Lewis' dictionary of toxicology. CRC Press, 1998, p. 51 ISBN 156670-223-2 5. Chemical Encyclopedia: alkaloids 6. Rhoades, David F (1979). "Evolution of Plant Chemical Defense against Herbivores". In Rosenthal, Gerald A., and Janzen, Daniel H. Herbivores: Their Interaction with Secondary Plant Metabolites. New York: Academic Press. p. 41. ISBN 0-12-597180-X. 7. Robert A. Meyers Encyclopedia of Physical Science and Technology, Eighteen-Volume Set, Third Edition. - Alkaloids ISBN 0-12-227411-3 8. Leland J. Cseke Natural Products from Plants Second Edition. - CRC, 2006, p. 30ISBN 0-8493-2976-0 9. A. William Johnson Invitation to Organic Chemistry, Jones and Bartlett, 1999, p. 433ISBN 0-7637-0432-6 10. Raj K Bansal A Text Book of Organic Chemistry. 4th Edition, New Age International, 2004, p. 644 ISBN 81-224-1459-1