CHAPTER – 10

ALKALOIDS

Today, more than 10,000 alkaloids are known to occur from more than 4000 species of Angiosperms. Ladenberg defined alkaloid as :

“It can be defined asthe naturally occurring basic, complex, nitrogenous organic, heterocyclic ring compound of plant origin with physiological and pharmacological properties.”

TWO BASIC PROPERTIES:

  1. Heterocyclic ring structure with N in the ring structure.
  2. Basic in nature.

COMPOSITION OF ALKALOIDS:

They are heterocyclic compounds having C,H,O and N in their structure ( exception : Nicotine without oxygen). They are mainly composed of pyrol, pyridine, quinoline, isoquinoline and tropane structure. Morphine contains phenanthrene without nitrogen.

GENERAL PROPERTIES:

They are colourless and non-volatile solids. They are slightly soluble in water (Coniine and nicotine are highly soluble in water) but soluble in most organic solvent. Some are colored substances (Barberine is yellow). Most alkaloids are optically active and are leavo rotatory but few are dextrorotatory too. While, some are optically inactive.

Almost all are bitter in taste. They are used in pharmacy. They are active at small concentration. At higher doses, they may cause death. They are basic in nature and form insoluble salts with picric acid, potassium mercuric iodine etc.

OCCURRENCE:

Alkaloids are found in vascular plants. They rarely occur in Cryptogram, gymnosperms or mono cotyledons. They occur abundantly in di-cotyledons, Apocynaceae, Papaveraceae, Papilonaceae, Rubiaceae, Solanaceae, etc. families. Papaveraceae is an unusual family that all its members contain alkaloids. They are isolated from roots, leaves, bark of the stem or seeds of the plants. In leaves of some plants, it constitutes 0.5 to 8.0 % of dry weight. They are stored in the vacuoles or in the cytoplasm in the solid form. Their quantity depends upon the age of plant, cultivation, type of growing, place of growing and climate.

Alkaloids are basic in character so they exist as salts of plant acids like oxalic, citric, malic, lactic, tannic, acetic acid etc. Most alkaloids occur in combined form with other compound however, glycolides, amides occur free.

NOMENCLATURE:

Although, their scientific nomenclature is not possible due to their complex structures. Nomenclature can be given according to following general criteria.

  1. According to their plant source. e.g. Papaverine, berberine
  1. According to their physiological actions e.g. Morphine, Narcotine, Emetine.
  1. According to the name of scientist who discovered it e.g. Palatrin which was discovered by P.J.Pelletior.
  1. By adding prefix or suffix in the name of plant source e.g. Cinchonine from Cinchona, quinine
  1. Same isomeric alkaloids have been designated by adding prefix iso, neo, epi, α and β.
  1. Some times Greek words are used in the nomenclature.

CLASSIFICATION: They are classified by two systems:

  1. Classification based on the genera of plants in which they occur. Cinchonine from Cinchona spp.
  1. Classification based on the nature (type) of the heterocyclic nucleus present in the structure which was given by Henry.
  1. PHENYL ETHYL AMINO GROUP OR PHENYLIALKYL AMINO GROUP

The examples of this group are:

Hordinine TyramineL-Ephedrine

  1. PYROLLIDINE GROUP. :

It was isolated Hygrine from Paruvian coke in 1814. It is extremely basic and boils at 194 0 C.

Hygrine ( C8 H15 O N ) Stachydrine ( C7 H14 O N )

  1. PYRIDINE GROUP : They are sub- classified in three groups.

a)Hemlock alkaloid (Dhatura) : Five alkaloids are included in this group. The main alkaloid of this group is Coniine was used to kill political prisoners in olden times. ( Socrates was given cup of Dhatura Alkaloid)CONIINE ( C8 H17 N )

b)Pepper Alkaloid: There are two members in this group. I) Piperine and II) Chavicine.It is found with isomer Chavicine in black and white peppers ( 5 to 8 % ) . Taste is pungent. It is less toxic than other alkaloid. They are solid, optically inactive, and soluble in water. Melting Point ( M.P.) = 128 0 C.PIPERINE ( C17 H19 O2 N )

C) Ricidine : They are isolated from castor oil. They are less toxic , contain cyanide group in its structure. It is present in castor seeds, optically inactive, weak base.

RICIDINE ( C8 H8 O2 N2 )

  1. PYROLLIDINE- PYRIDINE GROUP:

It is known as TOBACCO ALKALOID. Important group is NICOTINE.

NICOTINE: It is found in the leaves of tobacco. They occur as malic and citric acid salts. Dry leaves contain around

4 %. They are strong basic. Optically active, found in leavo (L) form, water soluble, boiling point is 242 0 C. It is most toxic alkaloid at 40mg or more. It may cause death. It can also act as good insecticide. It is also used for the manufacturing of niacin and nicotinic acid. It does not have oxygen in its structure.

NICOTINE ( C10 H4 N2 )

5. TROPANE ALKALOID: There are two groups. A) Solanaceous alkaloid and B) Coca alkaloids.

a)Solanaceous alkaloids: They are obtained from Solanaceae family. ATROPINE is the main alkaloid in this group.

ATROPINE ( C17 H23N O3 )

They are isolated from Atropa belladonna. They are optically inactive, alkaline, bitter in taste, having Melting Point of 115 0 C. If it is taken orally, it can depress the Central Nervous System (CNS). It is used to dilate the pupils (widening of Iris) of eyes during the eye surgery.

Extraction of Atropine:

Juice of Atropa belladonna Spp. is treated with K2CO3 and extracted in chloroform. The chloroform is evaporated and alkaloid atropine is extracted with dilute H2SO4 . This is made alkaline by addition of K2CO3. The precipitated atropine is purified by washing and crystallization. Tropine and tropic acid can also be converted to atropine with heating in HCl.

b)Coca Alakloid: The important member of this group is COCAINE.

COCAINE: ( C17 H21 N O4 ) : Cocaine is extracted from leaves from cocawhich is grown in Java, Sri Lanka, Peru countries. It is colourless, alkaline and less soluble in H2O. Its Melting Point is 98 0 C. It is used as local anesthetic.

6.QUINOLINE GROUP:

It is also known as Cinchona alkaloid. Main alkaloids are Cinchonine and Quinine. These are isolated from the bark of Cinchona plant Spp. IN middle of 17th century; the barks of Cinchona were utilized to cure fever. It was later confirmed as Quinine (for malarial fever). More than 35 alkaloids have been extracted from Cinchona. Some of them are Strychnine, cinchonine, quinine, quinidine, cuperine, epiquinine, epiquinidine etc.

a) QUININE:

It is obtained from the bark of Cinchona plant. It is having bitter taste, crystalline, solid substance. Its Melting Point is 175 0C, semi soluble in ether and alcohol. It is used as quinine sulphate. The precursor for quinine synthesis is tryptophan.

Tryptophan → Corynanthrene → Cinchonamine → Quinine

IT IS USED AS ANTI-MALARIAL DRUG

QUININE ( C20 H24 N2 O2 )

b) CINCHONINE:

It is present in the bark of grey Cinchona plant. The precursor of its synthesis is tryptophan. It has bitter taste, less toxic than quinine, water soluble, optically active, dextro-rotatory, Melting Point is 265 0C.

Tryptophan → Corynanthrene → Cinchonamine → Cinchonine

CINCHONINE ( C19 H22 N O2 )

  1. ISOQUINOLINE ALKALOID AND PHENANTHRENE GROUP:

Isoquinoline contain several alkaloids including Morphine, Thebaine, Papaverine, Narcotine, Narceine etc. Almost all these alkaloids are obtained from Poppy Spp. (Papaver somaniferum).They are isolated from green capsules.

a)Papaverine : ( C20 H21 N O4) It is an important alkaloid of opium group.

b)MORPHINE: Opium contains 10-20 % morphine. It was isolated from Sertwener plants in 1806. It is insoluble in water having bitter taste, optically active, leavo –rotatory, Melting Point 255 0C. It is used as pain killer (analgesic) and sometimes as anaesthat, also used in medicine. The molecular formula is C17 H19 N O3.

c)Berberine: Isolated from the roots of Berberine plants. The molecular formula is C20 H9 O5 N .

8.PHENANTHRENE ALKALOID:

The morphine alkaloid constitute a separate sub-group of opium alkaloids. Phenanthrene nucleus is found in their structure. e.g. Morphine, Codeine, Thebaine (10-15 %)

9. INDOLE ALKALOIDS: There are three classes on the basis of occurrence and mode of action.

a)Ergot alkaloid: Their main source is ergot found on the grasses and rye isolated from fungi. There are more than 20 members.e.g. Ergotamine, Ergotaminine, Ergosine, Ergosinine. Ergot has been used is medicine as an activator in working of Uterus.

Strychnos alkaloid: e.g. Strychine, Bruchine: They are used as anti-helmentics (to kill Worms and insects). It affects respiration and CNS of animals.

10. RAUWOLFIA ALKALOID: e.g. raserpine which is used in the treatment of hypertension, tension, fevers, dizziness, and insomnia.

11. MISCELLANEOUS GROUPS: It is also called Tropolane alkaloids. Colchicine which is present in the seeds of Colchieum is used in artificial production of polyploidy. Molecular formula is C22 H25 N O6 .

USES AND IMPORTANCE OF ALKALOIDS:

(A)BIOLOGICAL SIGNIFICANCE:

  1. Protect the plants against fungi, insects and animals.
  1. Excretory products of plants.
  1. Some scientists proposed that alkaloids serve as reservoir of N and help the protein synthesis.
  1. They behave as growth regulators like hormones.
  1. Colchicine is used in the multiplication of chromosome by which new varieties of crops are developed.
  1. Helpful to neutralize the harmful effects of acids in plants.
  1. Morphine is essential in formation of poppy seeds.
  1. Alkaloids inhibit enzyme activity and seed germination. Some remove bad effects of tannins.
  1. Alkaloids are known as co-product in the metabolism of protein in plants.
  1. Alkaloids protect the plants from infection of plant disease.

MEDICINAL SIGNIFICANCE:

  1. Alkaloids are used as medicine in several diseases.
  1. Quinine is used as anti-malarial drug.
  1. Morphine is used as pain killer.
  1. Atropine is used to extend the size of Iris in the treatment of eye ailments.
  1. Ergotine is used to stimulate the function of uterus.
  1. Several alkaloids are used as insecticides and pesticides (Nicotine sulphate from tobacco and azadirachtin from neem).
  1. Several compounds of opium are useful in medicines.
  1. Colchicine is used to control rheumatic disease
  1. Some are used to control hypertension to improve Central Nervous System.
  1. Amitine is used as cough expectorant and prevent vomiting.

REMOVAL OF ALAKLOID TOXICITY:

If some one takes alkaloids orally in high concentrations, he should be directed for vomiting immediately and drink dilute tannic acid. The tannic acid precipitates out the alkaloid and thus acts as Antidote. This is the reason that tea or coffee 9containing tannin) act as antidote to alkaloid poisoning.

REFERENCE BOOKS:

  1. A TEXT BOOK OF BIOCHEMISTRY (1997) BY R.P.S. DHAKA AND NANAK SINGH , AMAN PUBLISHING HOUSE, MEERUT.

DEFINE:- Alkaloid

Classification of alkaloid (Only enlist)

What is biological significance of alkaloid ( any five)

QUININE IT IS USED AS ANTI-MALARIAL DRUG

NICOTINE: It is found in the leaves of tobacco.

MORPHINE: It is used as pain killer (analgesic) and sometimes as anaesthat, also used in medicine.

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