Prepared By: Dr. Harminder singh
Alkaloids are the naturally occurring nitogeneous compounds which are isolated from plants. These are basic in nature and contain atleast one nitrogen atom in the form of heterocyclic ring which may be pyridine, pyrrole, quinoline etc. in nature. e.g. connine, quinine, nicotine, caffeine, atropine etc.
Alkaloid Natural Products Largest class of secondary metabolites, >6500 compds known Contains N, most compds basic (alkaline), often heterocyclic Often highly toxic Found in certain higher plants (seldom in bacteria) Little is known regarding why alkaloids are produced Biosynthesis from amino acids
Alkaloid: Difficult to define No definitive difference between an alkaloid and naturally occurring complex amines. Alkaloids: plant derived, are alkali and contain at least one N2-atom. They also normally have a significant physiological action on humans and animals.
Alkaloids are basic .usually derived from an amino acid.
. Bitter tasting. Most alkaloids are well-defined crystalline substances which unite with acids to form salts. does not precipitate like most alkaloids.they form water soluble salts.Contains nitrogen . generally white solids (exception nicotine is a brown liquid).
± Caffeine. ± as salts or ± as N-oxides. a purine derivative. they may exist
± in the free state. In plants. They give a precipitate with heavy metal iodides.
Occur in a limited number of plants. whereas. Nucleic acid exists in all plants. morphine exists in only one plant species.
All alkaloids of one plant will have a common biogenenetic origin
. but most occur in closely related species. Some occur in certain families (hyoscyamine). while others occur only in a specific species (morphine).Occurrence. Distribution & Location of Alkaloids
Occur in bacteria (Pseudomonas aeruginosa) and rarely in fungi (pscilocin from hallucinogenic mushrooms). Some alkaloids occur in several genera from different species (caffeine). Rarely do plants contain more than 1 type of alkaloid.
g. the bark or seeds). Alkaloid concentrations occur in wide ranges e.
.g. Within the plant. [alkaloid] can vary widely from part to part some parts may contain no alkaloids.Alkaloids occur in all plant parts. different alkaloids also form in different parts of the plant. but are usually localized in one organ (e. Occasionally. Madagascan periwinkle contains 3g per (anti-cancer) alkaloids per tonne of leaves.
. 3º or 4º (quaternary).The Nitrogen of Alkaloids
The N2 atom can either be 1º. This N2 feature affects the alkaloid derivatives which can be prepared and the isolation procedures. 2º.
Soluble in concentrated hydro-alcoholic solutions
. In rare cases they are coloured. Most solid bases rotate the plane of polarized light.Physical-Chemical Properties of Alkaloids
MW: 100 900 Most bases which do not contain O2 are liquid at room temperature (nicotine). have high melting points. Soluble in non-polar or slightly polar organic solvents. Normally are not soluble in water (occasionally slightly soluble). while those that do are solids.
i.Classification of Alkaloids
Alkaloids have a large variety in their botanical & biochemical origin. They can therefore be classified according to their Biological origin Chemical structure . in chemical structure and pharmaceutical action. A range of different classification systems exist for grouping alkaloids. Typical/hetrocyclic alkaloids (divided into 14 groups according to their ring structure)
. Atypical/non-hetrocyclic alkaloids (protoalkaloids or biological amines) ii.
terpenes.: on the solubility of bases and salts in water and organic solvents).g by forming emulsions) avoided by defatting the crushed herb (using petroleum ether and hexane)
. pigments and other lipophilic substances (e.Extraction of Alkaloids
Extraction is based on the basicity of alkaloids and on the fact that they normally occur in plants as salts (i. Herbs often contain other materials which can interfere with extraction such as large amounts of fat.e. waxes.
the purpose of extraction & the scale on which is to be performed. Alkaloid Extraction in basic medium. If larger amounts of alkaloids need to be extracted. one of the following methods can be used. 1. Alkaloid Extraction in acidified medium In both methods purification is needed
. For research purposes: chromatography allows for quick and reliable results. 2.Alkaloid Extraction
Extraction method normally depends on the raw material.
Free bases are then extracted with organic solvents. but a carbonate solution is used when alkaloids contain fragile elements such as a ester or lactone. dichloromethane or ethyl acetate depends on the toxicity. cost & ease of recovery and recycling of the solvent). a mixture of calcium hydroxide & sodium hydroxide should be used as the alkaloids are bound to tannins. Cinchona bark. Organic solvent: chloroform. safety. e. In some cases.Extraction in an Alkaline Medium
Step 1: Powdered.g. Normally aqueous ammonia is used. This displace alkaloids from their salt combinations.
. defatted herb is mixed with an alkaline aqueous solution.
Sulfuric. Many acids can be used (HCL. Solvent is stirred with an acidic aqueous solution: alkaloids go into the solution as salts. citric. Repeated until the organic phase no longer contains alkaloids.Extraction of Alkaloids: Step II
Organic solvent containing alkaloids (bases) is separated from residue & concentrated by distillation under pressure if needed. tartaric). but always in very dilute concentrations (1-5%)
. Impurities remain in the organic phase.
Alkaloids precipitate and dissolve in the organic phase.
.Alkaloid Extraction: Step III
Aqueous solution of alkaloid salts is washed with an non-polar solvent (hexane) Alkalinized with a base using an organic solvent not miscible with water. Extraction of aqueous phase continues till all alkaloids have moved into the organic phase (tested when Mayer s reaction on the aqueous phase becomes negative). This purification step may be carried out in a separation funnel or in centrifugal extractors.
freed from water traces (drying over anhydrous salt e.Final Step
Organic solvent containing alkaloid bases is decanted. sodium sulphate) and evaporated under reduced pressure. Kava Powder
.g. A dry residue remains: total basic alkaloids.
Nicotine is an important insecticide. and large amounts are prepared from the parts of the tobacco plant which is not used for tobacco manufacture
. Separation and final purification may be done using fractional precipitation or fractional crystallization of salts.Isolation of Alkaloids
Large-scale extractions may be sent to a factory for purification & separation (for cinchona and cocoa alkaloids). Chromatograpy is used for complex alkaloids and if only small amounts of alkaloids are needed. Volatile liquid alkaloids (nicotine) are isolated by distillation alkaloid is distilled off in steam.
ergot alkaloids). Also: local anesthetics (cocaine). ganglioplegics (nicotine). defibrillation (quinidine). antimalarial (quinine).Pharmacological Action & Uses
CNS Action: stimulants (caffeine) or depressants (morphine) ANS: sympathomimetics (ephedrine) or sympatholytics (yohimbine. and amoebicides (emetine). anticholinergics (choline). antitumour agents (ellipticine).
. anti-bacterials (berberine).
. and quinine from Cinchona bark. Although some are used as galenicals (belladonna. datura.These actions lead to the extensive use of alkaloid containing herbs and drugs. most are used as starting materials for industrial extraction (morphine from poppy straw or opium. and henbane).
Nicotine is a naturally occurring liquid alkaloid. many people enjoy the stimulating effects of another alkaloid. These chemicals have potent effects on the human body. hydrogen. An alkaloid is an organic compound made out of carbon. For example. nitrogen and sometimes oxygen. Nicotine (Nicotiana tabacum and other Nicotina spp) toxic used as an insecticide
It is extracted in an acidified medium
In the brain.
. nicotine is absorbed through the skin and mucosal lining of the mouth and nose or by inhalation in the lungs.When you smoke. The acute effects of nicotine subside within minutes. Once in the body. nicotine increases the level of the neurotransmitter dopamine. so people continue dosing themselves frequently throughout the day to maintain the pleasurable effects of nicotine and to prevent withdrawal symptoms. although to a lesser degree. which is a chemical in the brain responsible for feelings of pleasure. it activates the same reward system as do other drugs such as cocaine or amphetamine.
It's responsible for the death of one in ten adults worldwide. . a too long list to include it here.Smoking accounts for about 80-90% of all chronic obstructive pulmonary disease.
. tongue. larynx and esophagus.Some facts related with smoking: .Smoking has many other harmful effects in the body. . pharynx.Smoking is the major cause of cancer of the lips.Smoking is the second major cause of death in the world. mouth. .Smoking is involved in 85% of all lung cancer deaths. .
000 individual substances have been identified in tobacco smoke. which alters brain functioning. including carbon monoxide.Why smoking causes cancer? It's because tobacco and tobacco smoke contain more than 60 carcinogenic compounds. more than 4.000 toxic substances that can go inside your body when you smoke! Besides all the harmful effects of tobacco. it is addictive. more than 4. Yes. it's not a mistake. fewer than 7% succeed. And the main reason why tobacco becomes addictive is due to its content of nicotine.
. ammonia and other highly toxic irritants. In general. hydrogen cyanide. and this explains why although 70% of smokers want to quit and 35% attempt to quit each year.
tea leaves and guarana seeds). Beverages such as tea and coffee owe their stimulant action to the purine alkaloids.
Also known as non-alkaloids (xanthines) * Amphoteric Character * Peculiar solubility in warm water and in chlorinated solvents. Example is caffeine (seeds of coffee plants. kola plants.
Theobromine: opposite action.
.Caffeine: stimulates CNS and has a weak diuretic action. Theophylline: relaxes involuntary muscles more effectively than caffeine or theobromine Caffeine does not precipitate like most alkaloids.
causes tacchycardia. Very high doses: induces nervousness. increases CO. decreases the sensation of fatigue. facilitates thought formation.Pharmacological Activity of Caffeine
CNS activity. insomnia & tremors. slight peripheral dilation. mild diuretic action
. Stimulates respiratory centre of the brain (increasing sensitivity to CO2). Cardiovascular activity: Positive inotropic action. enhances alertness.
(increases the intestinal absorption of some of these drugs.Caffeine: Uses
In combinations with antipyretics and analgesics. Ingredient in nonalcoholic beverages and energizing beverages
. or to counteract drowsiness). cold and flu medication.
Caffeine Side Effects
Sinus tacchycardia Epigastric pain Nausea Vomiting Headaches Nervousness Insomnia tremors
. However. cocaine. it doesn't slow down the cell's activity like adenosine would. though with milder effects. caffeine looks like adenosine and it binds to the adenosine receptors. and that is one of the things that gives caffeine its addictive qualities.Caffeine operates using the same mechanisms of amphetamines. Then instead of slowing down because of the adenosine level. and heroin to stimulate the brain. To a nerve cell. that binds to certain receptors and slows down nerve cell activity when we are sleeping. There is a chemical in our brain called adenosine. It manipulates the same channels as the other drugs. as it's not really adenosine. the cells speed up. So the cell cannot "see" adenosine anymore because caffeine has taken up all the receptors adenosine binds to.
the breathing tubes to open up. as amphetamines. Because of this. Adrenaline is the "fight" hormone. so it releases hormones that tell the adrenal glands to produce adrenaline. caffeine also increases the levels of dopamine. and it makes your heart to beat faster. Moreover. you feel excited and you can feel your heart beat increasing.
. after consuming a big cup of coffee your muscles tense up. ready for action. which is associated with the pleasure system of the brain.The pituitary gland sees all of this activity and thinks some sort of emergency must be occurring. providing feelings of enjoyment and reinforcement. the liver to release sugar into the bloodstream for extra energy and your muscles to tighten up.
tropic or benzoic acid esters of tropine. Natural alkaloids include Hyoscyamine Hyoscine Atropine Cocaine The above mentioned alkaloids occur within the Solanaceae family (except cocaine from Erythroxylaceae family)
Derived from tropine and consist of mandelic. Are very closely related to each other All have pronounced physiological actions.
produces stomach acid and saliva & relaxes smooth muscle (asthma and colic). It is classified as an anticholinergic drug.Atropine
Atropine deadly nightshade. mandrake (Mandragora officinarum) and other plants of the family Solanaceae. Atropa belladonna: . jimsonweed(Datura stramonium). Treatment of bradycardia or Resuscitation
. decreases sweating. dilates eye pupils.
. nausea. loss of balance. dissociative hallucinations and excitation especially amongst the elderly. dizziness. photophobia. dilated pupils.Side Effects
tachycardia. dry mouth and potentially extreme confusion. blurred vision.