Alkaloids: Definition, Function, Extraction, Classification, and Biosynthesis, Lecture notes of Pharmacognosy

Download Alkaloids: Definition, Function, Extraction, Classification, and Biosynthesis and more Lecture notes Pharmacognosy in PDF only on Docsity!

Alkaloids

Definition

 Alkaloids (Alkali-like): ‘are naturally occurring

compounds having a basic character and containing at

least one nitrogen in a heterocyclic ring.’ with

( a ) Complex molecular structure, and

( b ) Significant pharmacological activity.

 Atypical alkaloids or protoalkaloids

• Compounds that lack one or more of the properties of typical

alkaloids

For example:

1. Choline alkaloid : The N-atom in the side chain and not in a

heterocylic ring [HOCH 2 CH 2 N +(CH 3 ) 3 ]…………… ‘biological-amines’ or

‘protoalkaloids’.

2. Ephedrine: It has the N-atom only

in the side chain and not embedded in the heterocylic ring

And others……….^2

Site and Distribution in Different Plant Organs:

May be

1. In the roots of the plant and then translocated to the leaves: alkaloids of tobacco
2. Fruit fresh latex: Opium
3. Seeds and the Corm: colchicum
4. Bark: Cinchona  The source and biosynthesis route can be studied by radio-labelling and feeding study

Alkaloid Occurrence

1. Mainly as Salts of organic acid such as nicotine
2. Rarely salts with inorganic acids such as Morphine
3. Gluco-Alkaloids: in glucosidal combination

Ex. Solanidine (aglycone) obtained from the hydrolysis of the toxic glycoside solanine  Found in the sprouts of potato tubers

Function of Alkaloids in Plants

( a ) They are poisonous agents in plants thereby protecting them either against herbivorous animals or insects ( b ) As by-products of various detoxification reactions ( c ) As regulatory growth factors ( d ) As reserve substances in plant capable of supplying nitrogen or other necessary elements.

Isomerism

 Most alkaloids contain one or more asymmetric carbon atoms in the molecule, and hence exhibit optical activity.  It has been observed that the (–)- isomer ( i.e. , the levorotatory component) has distinct pharmacological activity than the corresponding (+)-isomer ( i.e. , the dextrorotatory , component) of the same alkaloidal species.

D- ; For steric configuration But (+) and (-) are for optical rotation

Chemical properties

• The substitution on the nitrogen atom
• The state of the alkaloid

R

NH 2

R

H

N

R 2 R

N

R 3

R 2

R

N

R 4

R 2

• R 3

Cl - 1ry 2ry (^) 3ry quaternary

R

NH 2

R

N R 3

R 2

R

NH 3

Cl -

O

Free base Salt form N- oxide

Few typical pharmacological actions of some alkaloids

The separation as well as isolation of the hundreds of

alkaloids from the natural plant sources, adapt the following

five steps

( i ) Sample preparation: grinding

( ii ) Liberation of free alkaloidal base

( iii ) Extraction of alkaloidal base with organic solvent

( iv ) Purification of crude alkaloidal extract

( v ) Fractionation of crude alkaloids

Liberation of free alkaloidal base

1. Salt/ Base rule: The alkaloids invariably occur in the plant sources as the salt of acids, such as: oxalates, tannates etc………exposure to alkali…….liberate alkaloid base 2. Choice of base: Strong alkali such as KOH and NaOH is avoided because - possible hydrolysis in case of alkaloidal ester - possible saponification (emulsion) in case of the presence of fatty acid - phenolic alkaloid may tend to soluble - possible cleavage

******* Best choice is ammonia** (NH 4 OH)………………..Diluted

powder Water and lime

Extraction with organic solvent ether

Lime combines with acids, tannins and other phenolic substances

Organic extract

• concentration
  • Aqueous acid

Organic liquid Aqueous liquid

Alkaloid salts impurities

Extraction procedure 1

powder

• Water or aqueous alcohol containing dilute acid
  • chloroform

organic

aqueous

Pigments and other unwanted materials

Alkaloid salts

Sod. Bicarbonate or ammonia solution

Ppt. of alkaloid free base

Extract with organic solvent

Extraction procedure 2

( b ) Chemical Classification

1. Non-heterocyclic

2. Heterocyclic

Based on the basic heterocyclic nucleus ( i.e. , the chemical entity ) it is divided into several groups Examples ( i ) Pyrrolidine alkaloids e.g. , Hygrine; ( ii ) Piperidine alkaloids e.g. , Lobeline; ( iii ) Pyrrolizidine alkaloids e.g. , Senecionine; ( iv ) Tropane alkaloids e.g. , Atropine; ( v ) Quinoline alkaloids e.g. , Quinine; ( vi ) Isoquinoline alkaloids e.g. , Morphine; ( vii ) Aporphine alkaloids e.g. , Boldine; ( viii ) Indole alkaloids e.g. , Ergometrine; ( ix ) Imidazole alkaloids e.g. , Pilocarpine; ( x ) Diazocin alkaloids e.g. , Lupanine; ( xi ) Purine alkaloids e.g. , Caffeine; ( xii ) Steroidal alkaloids e.g. , Solanidine; ( xiii ) Amino alkaloids e.g. , Ephedrine; ( xiv ) Diterpene alkaloids e.g. , Aconitine.

H 3 CO

H 3 CO OCH 3

CH (^2) CH 2

NH 2

Mescaline

N

H

N

H

N

N

pyrrole pyrrolidine^ pyrrolizidine^ pyridine H N NMe

N

N

piperidine tropane^ quinoline^ isoquinoline

N H NH

N

N H

NMe

indole (^) indolizidine imidazole

aporphine

Heterocyclic

17

( d ) Taxonomic Classification

Based on Plant Families

( i ) Cannabinaceous Alkaloids: e.g. , Cannabis sativa Linn., ( Hemp, Marijuana ).

( ii ) Rubiaceous Alkaloids: e.g. , Cinchona Sp. ( Quinine ); Mitragyna speciosa

Korth ( Katum, Kratum, Kutum ); Pausinystalia johimbe (K. Schum) ( Yohimbe ).

( iii ) Solanaceous Alkaloids

Biosynthesis

• A large group of alkaloids are found to acquire their nitrogen atoms via

1. Transamination reactions, incorporating only the nitrogen from an

amino acid

2. Whilst the rest of the molecule may be derived from acetate or

shikimate

3. Others may be terpenoid or steroid in origin or methylerythritol

phosphate pathways