[9.1] ALKALOIDS

ALKALOIDS

• Organic nitrogenous compounds with varied pharmacologic actions 

• Bitter taste; usually are crystalline or amorphous

• coniine

• asparteine

• nicotine

• sparteine

ALKALOIDS

• only liquids

ALKALOIDAL BASE

• Known as free alkaloids 

• Insoluble in water

• Soluble in organic solvents (non-polar)

ALKALOIDAL SALTS

Freely soluble in water

Derosne

Narcotine (1803)

Serturner

Morphine (1816)

Pelletier & Caventou

• Brucine 

• Emetine 

• Strychnine 

• Piperine 

• Quinine 

• Caffeine 

• Colchicine 

• Coniine

Schiff

coniine (first alkaloid with established structure)

• In fungi, the lysergic acid derivatives and sulfur-containing alkaloids are best known

• Also present in amphibians (many are antimicrobial) 

• Pteridophytes - Ephedra, Taxus

True alkaloids are rare occurrence in other organisms

Mayer’s reagent

Potassium mercuric iodide

Cream / yellowish ppt

Wagner’s reagent

Iodine in potassium iodide

Reddish brown ppt

Valser’s reagent

Mercuric iodide

White ppt

Dragendroff’s reagent

Potassium bismuth iodide

Orange ppt

Marme’s reagent

Cadmium in potassium iodide

Cream / yellowish ppt

Sonnechein’s reagent

Phosphomolybdic acid

Amorphous yellow white ppt

Scheiber’s reagent

Phosphotungstic acid

Reddish brown ppt

Picric acid

Mahogany red

Tannic acid

Buff color ppt

Gold salt test

ppt

Marquis

Codeine

Marquis reagent

Blue

Hasemann

Codeine

Ferric chloride

Blood red

Vitali

Atropine

Nitric acid

Gray ppt

Gulielmo

atropine

Sulfuric acid

Red with flower odor

Gerard’s

atropine

Ethanol, mercuric chloride

Yellow

Thalleioquin

Quinine

Acetic acid, Chlorine water, Ammonia

Fine Blue fluorescence, then green ppt with ammonia

Mandolin

Strychnine

Mandolin reagent

Violet

Murexide

Caffeine

Potassium chlorate, HCl

Purple color, Pink on paper chrom

true alkaloids

Almost all compounds considered to be alkaloids have their nitrogen atoms enclosed within a ring system, and are called

called pseudoalkaloids

Heterocyclic “alkaloids” that are not derived from amino acids are sometimes

protoalkaloids

Those which do not have nitrogenous alkaloids are called

NON-HETEROCYCLIC RING

• Sometimes called protoalkaloids 

  • Mescaline

  • Ephedrine

  • Colchicine (alkaloidal amine) 

• These group lacks one or more properties of alkaloids in that they are feeble bases. 

• They contain nitrogen in a side chain 

• These are alkaloids due to their physiological action rather than their chemical nature

• Coniine

• Arecoline

Pyridine and piperidine

• Hyoscyamine

• Atropine

Tropane

• Quinine

• Cinchonine

Quinoline

• Morphine

• Codeine

Isoquinoline

• Ergotamine

• Physostigmine

Indole

• Pilocarpine

Imidazole

• Caffeine

• Theobromine

Purine

• Hygrine

• Stachydrine

Pyrrole and pyrrolidine

Pyridine

- from ornithine or aspartate

Piperidine

- from lysine

Pyrrolidine

- from ornithine or aspartate

Pyrrolizidine

- from ornithine

• nicotine

• areca nut

• lobelia

• poison hemlock

examples of P alkaloids

Nicotiana tabaccum

NICOTINE

• source

Nicotine: Derivative of pyrrolidone

NICOTINE

• constituents

• Smoking deterrent

• CNS stimulant

• Cholinergic neurotransmitter

NICOTINE

• use

• betel nut

• nganga

• bunga

ARECA NUT

• other name

Areca catechu

ARECA NUT / BETEL NUT / NGANGA

• source

• Arecoline 

  • Strengthen teeth 

  • High tannin content: risk of mouth / esophageal cancer

ARECA NUT / BETEL NUT / NGANGA

• constituents

• Masticatory (betel chewing)

• Taenicide, anthelmintic (veterinary)

ARECA NUT / BETEL NUT / NGANGA

• use

indian tobacco

  LOBELIA

• other name

Lobelia inflata

LOBELIA / INDIAN TOBACCO

• source

Lobeline (less addictive than nicotine)v

  LOBELIA / INDIAN TOBACCO

• constituents

• Smoking deterrent (ingredient in tablets and lozenges) 

• Resuscitation of newborn infants 

• In toxic doses, paralytic

  LOBELIA / INDIAN TOBACCO

• use

Conium maculatum

POISON HEMLOCK

• source

• Coniine 

  • With KOH, develops strong, mouse-like odor due to the liberation of coniine

POISON HEMLOCK

• constituents

Used by Greeks for preparing draught by means of which criminals were put to death

POISON HEMLOCK

• use

• Hepatotoxic alkaloids

• Some are also carcinogenic, mutagenic

• Ecologic role in some species of butterflies

PYRROLIZIDINE ALKALOIDS

• comfrey

• coltsfoot

• indicine

• australine

PYRROLIZIDINE ALKALOIDS

• examples

breakdown to alkylating pyrrole esters

PYRROLIZIDINE ALKALOIDS

• Hepatotoxic properties are believed to arise by

Comfrey

was used to treat hypertension without extensive studies, causing people to have hepatic necrosis and problems

Indicine

- antitumor

Australine

- glycosidase inhibitory activity (reduce postprandial increase in blood sugar)

bicyclo structure

TROPANE ALKALOIDS

• ornithine

• putrescine

• acetate

TROPANE ALKALOIDS

• precursors

methionine

TROPANE ALKALOIDS

• n-methyl grp are from

phenylalanine

TROPANE ALKALOIDS

• tropic acid fragment is derived from

• belladonna

• hyscyamus

• egptian henbane

• stramonium

• talumpunay

• withania

• duboisia

• pituri

• mandragora

• coca

TROPANE ALKALOIDS

• examples

• deadly nightshade

BELLADONNA

• other name

Atropa belladonna

BELLADONNA / DEADLY NIGHTSHADE

• source

• Hyoscyamine

• Atropine  

Hyoscyamine → (racemize) → atropine

BELLADONNA / DEADLY NIGHTSHADE

• constituents

• Anticholinergic(mydriatic, antidiarrheal, spasmolytic/ antispasmodic)

• Antimuscarinic

• Sympathetic effect and antidote for organophosphate poisoning

BELLADONNA / DEADLY NIGHTSHADE

• use

• Atropine: physiologic antidote of organophosphate & carbamate poisoning (antimuscarinic) 

• Pralidoxime: chemical antidote (antinicotinic)

BELLADONNA / DEADLY NIGHTSHADE

• notes

Hyoscyamus niger

HYOSCYAMUS / HENBANE

• source

• Hyoscyamine

• Scopolamine

HYOSCYAMUS / HENBANE

• constituents

anticholinergic

HYOSCYAMUS / HENBANE

• use

Hyoscyamus muticus

EGYPTIAN HENBANE

• source

Hyoscyamine

EGYPTIAN HENBANE

• constituents

JIMSON WEED / JAMESTOWN WEED

STRAMONIUM

• other name

Datura stramonium

STRAMONIUM / JIMSON WEED / JAMESTOWN WEED

• source

• Hyoscyamine

• Scopolamine

STRAMONIUM / JIMSON WEED / JAMESTOWN WEED

• constituents

• Anticholinergic

• Vapor from burnt weed relieves asthma

STRAMONIUM / JIMSON WEED / JAMESTOWN WEED

• use

thornapple

TALUMPUNAY

• other name

• Datura metel 

• Datura fastuosa

TALUMPUNAY / THORNAPPLE

• source

Rich source of scopolamine (‘hyoscine’)

TALUMPUNAY / THORNAPPLE

• constituents

• Antimuscarinic 

• Motion sickness 

• Pre-anesthetic sedative depressant 

• CNS depressant, anticholinergic, calming delirium

TALUMPUNAY / THORNAPPLE

• use

ashwagandha

 WITHANIA

• other name

Withania somnifera

 WITHANIA / ASHWAGANDHA

• source

• Tropine

• Pseudotropine

• Hygrine

 WITHANIA / ASHWAGANDHA

• constituents

Sedative

 WITHANIA / ASHWAGANDHA

• use

Duboisia myoporoides

DUBOISIA

• source

• Chief source of atropine;

• also has hyoscyamine, scopolamine

DUBOISIA

• constituents

australian tobacco

PITURI

• other name

Duboisia hopwoodii

PITURI / AUSTRALIAN TOBACCO

• source

• nicotine

• nornicotine

PITURI / AUSTRALIAN TOBACCO

• constituents

used like tobacco

PITURI / AUSTRALIAN TOBACCO

• use

EUROPEAN MANDRAKE

MANDRAGORA

• other name

Mandragora officinarum

 MANDRAGORA / EUROPEAN MANDRAKE

• source

• Hyoscyamine

• Scopolamine

• Mandragorine (stimulant)

 MANDRAGORA / EUROPEAN MANDRAKE

• constituents