Alkaloids with Exocyclic NitrogenAlkaloids with Exocyclic Nitrogen(Protoalkaloids- Phenylalkylamines- Biological amines)(Protoalkaloids- Phenylalkylamines- Biological amines)

1- Ephedra 1- Ephedra AlkaloidsAlkaloids

Source: Source: EphedraEphedra Herb (Ma Huang, Yellow Hemp). Herb (Ma Huang, Yellow Hemp).

EphedraEphedra used as remedy for Asthma in Chinese medicine. used as remedy for Asthma in Chinese medicine.

(-)-Ephedrine is the major Alkaloid in (-)-Ephedrine is the major Alkaloid in EphedraEphedra..

Ephedrine is a phenylalkylamine with N atom in the side Ephedrine is a phenylalkylamine with N atom in the side chainechaine

Ephedrine is similar to adrenaline in structures.Ephedrine is similar to adrenaline in structures. Advantages of Ephedrine over adrenaline:Advantages of Ephedrine over adrenaline:

1- Orally active.1- Orally active. 2- Prolonged action2- Prolonged action

CH CH CH3

NHOH CH3

Ephedrine

CH CH2

NHOH CH3

HO

HO

Adrenaline

* *

CH CH CH3

NHOH CH3

Ephedrine

* *

Isomers:Isomers: Two Chairal centers → 4 Isomres.Two Chairal centers → 4 Isomres. Most active is (-)-Ephedrine. (+)-Ephedrine have 1/3 the Most active is (-)-Ephedrine. (+)-Ephedrine have 1/3 the

activity.activity. Pseudoephedrine much less active.Pseudoephedrine much less active.

Properties:Properties:

Soluble in water and organic solventsSoluble in water and organic solvents Steam volatileSteam volatile Negative reaction with Mayer’s reagent.Negative reaction with Mayer’s reagent. React with Chloroform to produce React with Chloroform to produce

Ephedrine HCl and phosogenEphedrine HCl and phosogen Ephedrine HCl in 25% HCl isomerizes to Ephedrine HCl in 25% HCl isomerizes to

Pseudoephedrine. Pseudoephedrine.

Ephedrine & Pseudoephedrine Oxalates

Crystallization from water

Ephedrine OxalateCrystals

Pseudoephedrine OxalateSolution

Ephedrine & Pseudoephedrine HCl

Crystallization from Alcohol

Ephedrine HClCrystals

Pseudoephedrine HClSolution

Test for Identity:Test for Identity:

Chen’s test:Chen’s test:

Ephedrine HCl in water + 0.1 ml CuSOEphedrine HCl in water + 0.1 ml CuSO44 + 1ml NaOH → + 1ml NaOH →

Violet colour, shake with EtherViolet colour, shake with Ether →→

Ether layer → purpleEther layer → purple

Aqueous layer → blueAqueous layer → blue

Uses:Uses:1- Asthma.1- Asthma. 2- Hey fever. 3- Mydriatic. 2- Hey fever. 3- Mydriatic.

4- Nasal decongestant.4- Nasal decongestant.

5- Certain allergic conditions.5- Certain allergic conditions.

2- Cathe Alkaloids (Kat 2- Cathe Alkaloids (Kat القاطالقاط))

CNS stimulant activityCNS stimulant activity Abused drug.Abused drug.

CH CH CH3

NH2

OH

Cathine

C CH CH3

NH2

O

Cathinone

3- Peyote Alkaloids3- Peyote Alkaloids

Hallucinogenic AlkaloidHallucinogenic Alkaloid

NH2

H3CO

H3CO

OCH3

Mescaline

Tropolone AlkaloidsTropolone Alkaloids ColchicumColchicum Alkaloids Alkaloids Source: Colchicum Corm.Source: Colchicum Corm. Constituents: Colchicine.Constituents: Colchicine. Properties: Properties:

1- Neutral Alkaloid.1- Neutral Alkaloid.

2- Amid function.2- Amid function. Test:Test:

1- Red colour with FeCl1- Red colour with FeCl33..

2- Yellow colour with dil. Mineral acids.2- Yellow colour with dil. Mineral acids. Uses:Uses:

1- Treatment of Gout.1- Treatment of Gout. 2- Anticancer in vitro. 2- Anticancer in vitro.

3- Treatment of Mediterranean Sea fever.3- Treatment of Mediterranean Sea fever.

4- Polyploidy in Plants.4- Polyploidy in Plants.

H3CO

H3CO

OCH3

OCH3

O

NH-CO-CH3

Imidazole AlkaloidsImidazole Alkaloids PilocarpusPilocarpus Alkaloids Alkaloids

Source: Jaborandi leaves (Source: Jaborandi leaves (Pilocarpus jaborandiPilocarpus jaborandi).). Constituents: (+)-Pilocarpine.Constituents: (+)-Pilocarpine. Properties: Properties: 1- Oily liquid miscible with water.1- Oily liquid miscible with water.

2- Non-volatile liquid alkaloid.2- Non-volatile liquid alkaloid.3- Lactone function.3- Lactone function.

Test:Test:Helche’s test: Helche’s test: Alkaloid + Dil acid + KAlkaloid + Dil acid + K22CrOCrO77 → violet colour → violet colour

(Pilocarpine dichromate)(Pilocarpine dichromate) Uses:Uses:

1- Miotic.1- Miotic. 2- Diaphoretic. 2- Diaphoretic.3- Hair preparations.3- Hair preparations.

N

N O

CH3

O

Pilocarpine & Isopilocarpine NO3

Crystallization from Ethanol

Pilocarpine NO3Crystals

Isopilocarpine NO3 Solution

Pyridine AlkaloidsPyridine Alkaloids TobaccoTobacco Alkaloids Alkaloids

Source: Tobacco leaves.Source: Tobacco leaves. Constituents: Constituents: 1- Nicotine (75%). 2- Nornicotine. 3- Anabasine.1- Nicotine (75%). 2- Nornicotine. 3- Anabasine.

Properties: Properties: 1- The 3 alkaloids are volatile liquids.1- The 3 alkaloids are volatile liquids.

2- Nicotine is tertiary alkaloid while the others are secondary.2- Nicotine is tertiary alkaloid while the others are secondary.3- Nicotine has some miscibility with water.3- Nicotine has some miscibility with water.

N

N

CH3

Nicotine

N

NH

Nornicotine

N

Anabasine

NH

Mixture + NaOH + NaNO2

Aqueous layerNicotine

(Tertiary Alkaloid)

Oily layerNitroso derivatives

of secondary alkaloids

Heat to librate free bases

Fractional Distillation to separate Nornicotine & Anabasine

Test for Nicotine:Test for Nicotine: 1- Aqueous Solution + p-dimethylaminobenzaldehyde in HCl →1- Aqueous Solution + p-dimethylaminobenzaldehyde in HCl →

Rose Red Colour → VioletRose Red Colour → Violet

2- Aqueous Solution + Vanillin HCl → Red Colour2- Aqueous Solution + Vanillin HCl → Red Colour

3- Solution in Ether + I3- Solution in Ether + I22 in Ether → deep red colourd needles in Ether → deep red colourd needles

of nicotine periodate of nicotine periodate

Uses:Uses:

1- Insecticide & Pesticide.1- Insecticide & Pesticide. 2- No medicinal use due to toxicity.2- No medicinal use due to toxicity.

Piperidine AlkaloidsPiperidine Alkaloids 1- 1- ConiumConium Alkaloids Alkaloids

Source: Hemlock fruits.Source: Hemlock fruits. Constituents: Coniine.Constituents: Coniine.

Properties: Properties:

1- Volatile liquid.1- Volatile liquid.

2- Free from Oxygen.2- Free from Oxygen.

3- CNS stimulant.3- CNS stimulant.

Uses:Uses:

1- Local analgesic so used for Hemorrhoids and anal 1- Local analgesic so used for Hemorrhoids and anal fissures.fissures.

NH

CH2 CH2 CH3

2- 2- LobeliaLobelia Alkaloids Alkaloids Source: Source: LobeliaLobelia Herb (Indian Tobacco). Herb (Indian Tobacco). Constituents: Constituents:

1- Lobeline (50%). 2- Lobelanine. 3- 1- Lobeline (50%). 2- Lobelanine. 3- Lobelanidine.Lobelanidine.

NH

CH2 CH2CC

O

NH

CH2 CH

OH

H2CC

O

O

Lobeline

Lobelaine

Properties: Properties:

1- Lobeline is sparingly soluble in water.1- Lobeline is sparingly soluble in water.

2- Lobeline HCl is soluble in CHCl2- Lobeline HCl is soluble in CHCl33..

Test:Test: 1- Lobeline + Marqui’s reagent → Red colour1- Lobeline + Marqui’s reagent → Red colour

2- Lobeline + Froehd’s reagent → Red colour → Blue2- Lobeline + Froehd’s reagent → Red colour → Blue

Uses:Uses:

1- Lobelia extract is used as expectorant.1- Lobelia extract is used as expectorant. 2- Lobeline is respiratory stimulant. 2- Lobeline is respiratory stimulant.

3- Lobeline is used to break tobacco habits in the form 3- Lobeline is used to break tobacco habits in the form of tablets or lozenges.of tablets or lozenges.

3-3- PomegranatePomegranate Alkaloids Alkaloids Source: Pomegranate barks.Source: Pomegranate barks. Constituents: Constituents: 1- Pelletierine. 2- Isopelletierine. 3- Methylpelletierine.1- Pelletierine. 2- Isopelletierine. 3- Methylpelletierine.

Properties: Properties: 1- Volatile liquid Alkaloids.1- Volatile liquid Alkaloids.

Uses:Uses:

1- Taeniafuge and Vermifuge.1- Taeniafuge and Vermifuge.

NH

CH2 C CH3

O

NH

CH2 CH2 CHO

Pelletierine Isopelletierine