Alkaloids 1y1v2k

Alkaloids Dr Mohsina Zubair

Content of the Chapter • • • • •

Nomenclature Classification Occurrance Function of alkaloids Isolation, properties of alkaloid, detection of alkaloids • Quinine • Therapeutic uses of quinine • Morphine

introduction of alkaloids

• The term alkaloids a alkali–like was defined by a pharmacist Meissnei in 1819, as the basic, nitrogenous organic compounds of plant origin. • The alkaloids are now generally defined now as physiologically active basic compounds of plant origin, having one or more basic nitro atoms in heterocyclic system, which induce pronounced physiological activity in animals and man.

Nomenclature •

• i.

A large no: of alkaloids are known and consist of such a variety of molecular structure that their rational classification is very difficult. Alkaloids are often classified according to plant from which they are isolated. e.g. cinchona, opium etc. Nowadays they are classified according to the heterocyclic ring system, which is common group of alkaloids. They are classified as follows: Phenylethylamine alkaloids

ii. iii. iv. v. vi. vii. viii. ix. x.

Pyrrolidine alkaloids e.g. hygrine etc. Piperidine e.g. conine Pyridine ..pyrrolidine e.g. Nicotine Quinoline e.g. Quinine Tropane e.g. atropine Isoquinoline e.g. papaverine Phenantherene isoquinoline e.g. Morphine Indale e.g. strychnine Tropolone

Occurrence of alkaloids

• Alkaloids are cheifly found in plants of dicotyledons families and occur in leaves, roots, seeds and bark etc. • The alkaloid content of the plant varies with season, age and its locality, closely related alkaloids generally occur together in the same plant e.g. nearly twenty alkaloids have been isolated from opium. • Some alkaloids are found to occur as free amides e.g. piperine, as esters e.g. tropine, and as cocaine or organic acids.

Functions of alkaloids • •

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The function of alkaloids in plant are uncertain and they are regarded as by products of plant metabolism. they may act as reservoir of protein synthesis. alkaloids are also believed to act as protective substance against the animal or insect attack. They may function as plant stimulant or regulator’s like hormones and regulates activities like growth, metabolism and reproduction. Alkaloids may function as detoxicating agents by methylating, condensing and cyslising the compounds.

Isolation • alkaloids are isolated by a general procedure, recommended by Manske, is described here. The general scheme for the extraction of alkaloids is as follows.

Properties of alkaloids 1.

2. 3. 4.

5. 6. 7.

Alkaloids are generally colourless, crystalline, nonvolatile solids through a few exceptions are there which occurs as liquids e.g. coniine etc. Alkaloids are insoluble in water but are soluble in most of the organic solvents like ethanol, ether, chloroform. Alkaloids are optically active compounds are a majority of them are laevo rotatory. Most of them posses marked physiological activity and are of great value in medicine e.g. morphine, atropine, quinine etc. Alkaloids are bitter in taste. They are poisonous in nature. Alkaloids are precipitated by common alkaloid reagent e.g. tannic acid, picric acid, perchloric acid.

Detection of alkaloids • Alkaloids are detected by physical methods as well as by chemical methods. • Physical methods 1. Infra red spectroscopy 2. Ultra violet spectroscopy 3. X-ray analysis 4. NMR spectroscopy 5. Mass spectrometry 6. Optical rotatory dispersion (ORD) and circular dichroism.

Detection of alkaloids • Infra red spectroscopy studies used to identifying the several functional group like methylene groups, N-methyl group, on C-methyl group, heterocyclic ring such as pyridine, pyrrole etc. • UV spectroscopy are used to indicate the probable structure of the alkaloids molecule. • X-ray analysis has been used for distinguishing the various possible alternative structures. • Mass spectrometry has been recently used for determining the types of nuclues (aromatic and heterocyclic) and the size and structure of side chains in the various groups. • The stereochemistry of alkaloids is determined by X-ray analysis, ORD and circular dichroism.

Detection of alkaloids •

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1. 2. 3. 4.

Chemical methods several important colour reaction are used for detection of alkaloids. They following general reagents may be used to detect the presence of alkaloids. The reagent should be added to a cold solution of the substance in the minimum quantity of dilute mineral acid. These reagents precipitate the alkaloid from aqueous solution. In many cases the presence of the trace of alkaloids can be detected by adding a suitable reagent to its solution. Mayer’s Reagent. Dragendorff’s Reagent Wagner’s Reagent Hager’s Reagents. It is a saturated solution of picric acid in cold water.

Quinine •

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Quinine is a cinchona alkaloids. It occurs a along with other cinchona akaloids like quinidine, cinchoninie, cinchonidine etc., in the cinchona bark. Among these alkaloids quinine is the most important. All the alkaloids are present in the bark in combination with various complex organic acids such as quinic acids, cinchotannic acid etc. Quinine is widely used as an antimalarial drug. Malaria is a protozoan infection caused by plasmodium faiciprun, plasmodium vivax, plasmodium malaria and plasmodium ovale.

Quinine • Sources. It is obtained from cinchona ledgeriana and its hybrids. • Extraction. The bark is powdered and mixed with sodium hydroxide solution and slaked lime and the librated alkaloids are extracted with hot petroleum. The separated extract is shaken with hot dilute sulphuric acid. The alkaloids es into the aqueous layer as sulphate. The solution is then cooled and the sparingly soluble quinine sulphate crystallizes.

Structure

Properties of Quinine 1.

2. 3.

4. 5. 6.

Quinine crystallizes as colourless needles containing 3HO. It is sparingly soluble in water but readily soluble in most organic solvents. It is better in taste and is laevo-rotatory. It is derivative of quinoline. It is a di-acid tertiary base and forms salts with two equivalents of an acid. The dihydrochloride is more soluble than monohydrochloride. on oxidation quinine gives quininic acid. A dilute solution of quinine or quinine salt in dilute sulphuric acid shows a characteristic blue fluorescence. Another characteristic test is thalloquin reaction which is as follows: then 2 ml of dilute ammonia solution is added to it when it gives bright green colouration.

Structure and activity of quinine and related Antimalarials 1.

2. 3.

The antimalarial activity of the cinchona alkaloids has been studied. Depending on the infection the biological activity of quinine, quinidine, cinchonidine , cinchonine differ both qualitatively and quantitatively. Quinidine is more active than quinine against plasmodium falciperum plasmodium vivex. Quinine has many adverse side effects such as blurred vision, deafness etc. it requires dosing and quinine sulphate is poorly absorbed from the gastro intestinal tract.

Therapeutic activity of cinchona alkaloids • Until the early 1930 quinine and the related alkaloids were the sole chemotherapeutic agents available for the treatment of malaria. Despite its limitation it is still frequently used because of its low cost. • It is effective as a suppressive and in the control of acute attacks of malaria due to P. falciperum, P. vivax etc.

Therapeutic uses of Quinine • It is mainly used in the treatment of malaria. Quinine is termed as general protoplasmic poison. It can depress a large no: of enzymatic processes. Quinine has local anaesthetic activity. It can also depress the myocardium by reducing its conductivity, excitability. • Quinine is also used in hereditary myopathy ( disease of a muscle). • Chloroquine is effective against malaria due to P. vivax and P. falcipurum. These are also useful in the treatment of an acute attack of malaria. • Intravenous injection of quinine has a relaxant effect on vascular smooth muscle causing a fall in blood pressure.

Morphine •

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Morphine is one of the narcotic analgesic. it is obtained opium there are three important opium alkaloids namely morphine, codeine and thebaine which contain phenanthrene nucleus. Morphine is the chief alkaloid obtained from opium which is the dried sap of the unripe fruit capsules of papaver somniferum. Structure of morphine morphine is C17H19NO3 and contains a phenanthrene nuclues and has a tertiary nitrogen. it has a secondary hydroxyl group position 6 and a phenolic group at position 3.

Properties of Morphine i. ii. iii. iv. v.

vi.

It is a solid having m.p at 254°C and natural morphine is levo rotatory, has a specific rotation of - 131°C. Morphine forms a diactetate salt showing the presence of two hydroxylic group on alcoholic and on phenolic. It gives ferric chloride test for phenols due to the presence of phenolic hydroxylic group. It dissolves in aqueous NaOH to give mono Na Salts. On treatment with halogen acids morphine forms monohalogen product indicating that an alcoholic hydroxyl group is present in morphine. Morphine has stimulant and depressant effects on central nervous system and procedures a sense of euphoria, and is a valuable analgesic.

Question Q1. explain the nomenclature and classification of alkaloids ? Q2. Describe the function and isolation of alkaloids? Q3. Quinine structure and properties? Q4. Describe Morphine structure and properties ? Q5. Define the detection method of alkaloids?