Alkaloids Introduction

Alkaloids  meant 'alkali  like' which  was  applied to  all  the organic bases. it includes mainly the cyclic nitrogenous bases, which  occur in  plant.  Thus,  alkaloids  are  the  naturally occurring  organic  substances  having  a  cyclic  nitrogenous nucleus  exhibiting  basic  properties  and  a  pronounced physiological  action.  Alkaloids  are  found  distributed in various parts of the mature plants as in seeds (strychnos), in fruits  (piper), in  leaves  (belladonna), in  roots  (rauwolfia), in rhizomes and  roots (ipecac), in corms (colchicum) and in bark (cinchona). 

Utilizes from immemorial time

Rauwolfia – India

Ephedra – Indian text and Chinese 

Opium – Egyptian and European

Arrow poison - Aconitine and Tubocurarine

 

Definition (No Definite Definition)

Koings (1880) : “Naturally  occurring  organic  bases which contains a Pyridine ring”.

 Ladenburg : “Alkaloid are natural plant compound that have basic character & contains at least one nitrogen atom in heterocyclic ring”.

 Winsterstein and Trier‟s (1910): Basic compounds that contain heterocyclic nitrogen, and are synthesized in plants from amino acids or their immediate derivatives in either plant /animal origin.

Recent or New definition

Alkaloids  are  the  heterogeneous  organic products of  plant  and  animal  origin  containing basic  nitrogen  atoms  and  exhibits  specific physiological actions on humans or animal body, when used small quantities.

History

 First time name given alkaloid -coined by Messiner 

 German pharmacist (1819) – used as planzalkaline

 Latter became alkaloid

 First alkaloid isolated – morphine - Friedrich Sertürner

 The first complete synthesis of an alkaloid was achieved in 1886 by the German chemist Albert Ladenburg.

 Xanthine (1817), Atropine (1819), Strychnine (1818) and Quinine (1820). Several other alkaloids were discovered around that time, including  Caffeine (1820),nicotine (1828).

Occurrence and distribution

 Rare in lower plants. 

 Dicots are more rich in alkaloids than Monocots. 

Families rich in Alkaloids: Apocynaceae, Rubiaceae,   Solanaceae and Papaveracea.

Families free from Alkaloids: Rosaceae, Labiatae

Distribution in Plant

All Parts     e.g. Datura

Barks        e.g. Cinchona

Seeds        e.g. Nux vomica

Roots        e.g. Aconite

Fruits        e.g. Black pepper

Leaves       e.g. Tobacco

Latex        e.g. Opium

Forms of Alkaloids

Free bases

Salts with Organic acids   e.g. Oxalic, acetic acids

Salts with inorganic acids e.g. HCl, H2SO4.

Salts with special acids: e.g. Meconic acid in Opium

Quinic acid in Cinchona       

Glycosidal form  e.g. Solanine in Solanum.  

Function in Plants

They  may  act  as  protective  against  insects  and herbivores due to their bitterness and toxicity. They  are, in  certain  cases,  the  final  products  of detoxification (waste products). 

Source of nitrogen in case of nitrogen deficiency. They,  sometimes,  act as growth  regulators in  certain metabolic systems. They may be utilized as a source of energy in case of deficiency in carbon dioxide assimilation.

Nomenclature:

Trivial names should end by "ine". These names may refer to:  The genus of the plant, such as Atropine from A. belladona. The plant species, such as Cocaine from Erythroxylon coca. The common name of the drug, such as Ergotamine from ergot. The name of the discoverer, such as Pelletierine that was discovered by Pelletier.

The physiological action, such as Emetine that acts as emetic, Morphine acts as narcotic. A prominent physical character, such as Hygrine that is hygroscopic.

Prefixes and suffixes

Prefixes: 

"Nor-"  designates  N-demethylation or  N-demethoxylation,

e.g. nor-pseudo ephedrine and nor-nicotine.

"Apo-" designates dehydration e.g. apo-morphine.

"Iso- pseudo-, neo-, and epi-" indicate different types of isomers. 

Suffixes:

"-dine" designates isomerism as quinidine and cinchonidine.

"-ine"  indicates,  in  case  of  ergot  alkaloids,  a  lower pharmacological  activity  e.g.  ergotaminine is  less  potent than ergotamine.

Physical Properties

I- Condition:

Most alkaloids are crystalline solids.    

Few alkaloids are amorphous solids e.g. emetine.        

Some are liquids that are either:

                         Volatile e.g. nicotine and coniine, or

                        Non-volatile e.g. pilocarpine and hyoscine.

II- Color:

The majority of alkaloids are colorless but some are colored e.g.: Colchicine and berberine are yellow. 

Canadine is orange.

The salts of sanguinarine are copper-red.

III- Solubility:

Both alkaloidal bases and their salts are soluble in alcohol.

Generally, bases are soluble in organic solvents and insoluble in water  

Exceptions:

Bases  soluble  in  water:  caffeine,  ephedrine,  codeine,  colchicine, pilocarpine and quaternary ammonium bases.

Bases  insoluble  or  sparingly  soluble  in  certain  organic  solvents: morphine in ether, theobromine and theophylline in benzene.

Salts  are  usually soluble in water and, insoluble or sparingly soluble in organic solvents.

 Exceptions:

Salts insoluble in water: quinine monosulphate.

Salts soluble in organic solvents: lobeline and apoatropine hydrochlorides are soluble in chloroform.

IV- Isomerization:

Optically active isomers may show different physiological activities. 

l-ephedrine is 3.5 times more active than d-ephedrine.

l-ergotamine is 3-4 times more active than d-ergotamine.

d- Tubocurarine is more active than the corresponding  l- form. 

Quinine (l-form) is antimalarial and its d- isomer quinidine is anti-arrythmic. 

The racemic (optically inactive) dl-atropine is physiologically active.

Chemical Properties:

I- Nitrogen: Primary amines                R-NH2     e.g.   Norephedrine

Secondary amines                                R2-NH   e.g.   Ephedrine

Tertiary amines                                  R3-N     e.g.   Atropine

Quaternary ammonium salts              R4-N     e.g    d-Tubocurarine

 

II- Basicity:

R2-NH  >   R-NH2   >   R3-N

Saturated hexa-cyclic amines is more basic than aromatic amines.

According to basicity Alkaloids are classified into:

Weak bases         e.g. Caffeine

Strong bases        e.g. Atropine

Amphoteric             

  * Phenolic Alkaloids  e.g. Morphine            

  *Alkaloids with Carboxylic groups  e.g. Narceine

Neutral alkaloids   e.g. Colchicine

III- Oxygen:

Most alkaloids contain Oxygen and are solid in nature  e.g. Atropine.

Some alkaloids are free from Oxygen and are mostly liquids  e.g. Nicotine,  Coniine.

IV- Stability:

Effect of heat:  Alkaloids are decomposed by heat, except Strychnine and caffeine (sub-limable).

Reaction with acids:

 1- Salt formation.

 2- Dil acids hydrolyze Ester Alkaloids e.g. Atropine

3- Conc. acids may cause:

Dehydration:

Atropine    →    Apoatropine

Morphine  →    Apomorphine

Demethoxylation:    e.g. Codeine