Alkaloids

Pooja H. Khanpara

Asst. professor

Pharmacognosy

Aksharpreet College of Pharmacy, Lakhabaval, Jamnagar

Definition

The term “alkaloid” (alkali-like) is commonly used todesignate basic heterocyclic nitrogenous compounds ofplant origin that are physiologically active. Derived fromamino acids.

DEVIATION FROM DEFINITION:Basicity: Some alkaloids are not basic e.g. Colchicine,

Piperine, Quaternary alkaloids.Nitrogen: The nitrogen in some alkaloids is not in a

heterocyclic ring e.g. Ephedrine, Colchicine, Mescaline.

Plant Origin: Some alkaloids are derived from Bacteria, Fungi, Insects, Frogs, Animals.

Biosynthesis: Some alkaloids are not derived from amino acids e.g purine, steroidal alkaloid .

History

NAMING OF ALKALOIDS

Numerous methods can be used to name alkaloids

1-Generic plant name –atropine from Atropa belladonna

2-Specific name of the plant –cocaine from Erythroxylum coca.

3-Common name of the herb –ergotamine from ergot (rye)

4-Physiological action of the plant –emetine producing emesis

5-Other –e.g. morphine derived from ancient Greek mythology –

Morpheus –god of dreams

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

antiarrythmic.

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

1. Stass otto method

Powdered plant material

Defatted with non-polar solvent

Defatted plant material

Moist with water and treated with NH3, Dil. Lime solution (Free Alkaloid)

Extracted with organic solvent like chloroform, ether

Extract, Concentrate it

Dissolved in Dil. Acid (Alkaloidal salt)

Aqueous phase Organic phase impurities

Basified with ammonia or sodium

Bi-carbonate or Dil. KOH

Aqueous phase Organic phase(Free Alkaloid)

Evaporate to dryness

Crude Alkaloids

2. Manske’s method

Powdered Crude material

Defatted with non-polar solvent

Defatted Crude material

Extract with methanol

Methanol Extract

Concentrate

Dissolve in water and Acidified it upto pH 2 (Alkaloidal salt)

Steam Distillation to remove traces of methanol

Stand for several days in refrigerator

OR boiled with paraffin

Filter

Filtrate

Shake with organic solvent like chloroform or ether

Aqueous phase (Alkaloidal salt) Organic phase

Basified with ammonia or sodium

Bi-carbonate or Dil. KOH

Aqueous phase Organic phase

Evaporate to dryness

Crude Alkaloids

Fractional crystallization

Ephedrine & Pseudoephedrine Oxalates

Crystallization from water

Ephedrine OxalateCrystals

Pseudoephedrine OxalateSolution

Atropine & Hyoscyamineine Oxalates

Crystallization from Acetone/Ether

Atropine OxalateCrystals

Hyoscyamine OxalateSolution

A) True alkaloids Sr. no. Type Structure Examples

1. Pyrrole and

pyrrolidine NH

NH

e.g. Hygrine, coca species

2. Pyiridine and

piperidine

N NH

e.g. Arecoline, anabasine, lobeline,

conine, trigonelline

3. Pyrrolizdine

N

e.g. Echimidine, senecionine,

seneciphylline

4. Tropane N

e.g. Atropine, hyoscine, hyoscyamine,

cocaine, pseudopelletirine

5. Quinoline

N

e.g. Quinine, quinidine, cinchonine,

cupreine, camptothecine

6. Isoquinoline

N

e.g.Morphine, codeine, emetine,

cephaline, narcotine, narceine, d-

tubocurarine

7

Indole

NH

e.g. Erotamine, ergotametriene,

reserpine, vincristine, vinblastine,

strychnine, brucine

8

Imidazole N

NH

e.g. Pilocrpine, isopilocarpine, pilosine

9 Norlupinane

N

e.g. Cystisine, laburinine

10 Piporphine

(reduced

isoquinoline

napthalene)

N

e.g. Boldine

B) PROTOALKALOID

1. Alkyalamine

HO

NH

Ephedrine, Pseudoephedrine

C) Pseudoalkaloid

1. Purine

N

NN

HN

e.g. Caffeine, thophylline, theobromine

2. Steroidal

e.g. Solanidine, conessine,

protoveratrine

3. Diterpene C20H32 e.g. Aconitine, aconine, hypoaconine

Pyridine - Piperidine

1. Tobacco

Chemical Test:

1) Aq. extract of tobacco treated with cyanogen-bromide give orange

color

2) Nicotine sulphate obtained as hexagonal tablets and soluble in

water and ethanol.

3) Nicotine HCl & Nicotine 2HCl obtained as deliquescence crystals.

Other Species: Nicotiana glauca (Tree tobacco),

Nicotiana rustica & Nicotiana glutinosa

USE: it is toxic (40mg) , stimulation leading to depression & then

paralysis.

As insectiside in agriculture(40 %sol. of nicotine sulphate).

2. LOBELIA

Syn: Indian tobacco, Asthma weed, Emetic herb

B.S.: Consists of dried leaves and tops of Lobelia

inflata Linné

Fam. Campanulaceae

G.S.: Eastern & Central U.S., Canada, Holland, North

America.

Macroscopy:

Color: stem is green with purplish ting

Odour : none

Taste: extremely acrid, unplesent & irritating

Size: total plant abt. 2-3 mtr.

Cultivation & collection:

It is an annual herb abt 30 to 50 cm high. Latex vessels are present

in phloem stem.

Drug is obtained from both cultivated and wild plant.

For cultivation seeds are sawn in rich, moist, loamy soil usually in

autumn. Sometime march and april also.

After sawing seed cover with soil and pressure is applied on them

by placing wooden plank end on them.

Collection in Auguest & september.

Aerial part are collec.ted & dried in shade to minimum green color.

Limit of stems is kept up to 60%.

Chemical Constituents:

Contains 14 alkaloids which

LOBELINE is the major and most

important. It has a pungent, volatile

oil, resin, lipids, and gum.

This occurs as colorless

crystals which are

slightly soluble in water

but readily soluble in hot

alcohol.

Lobelanine

Lobelanidine

Uses:

• In tmt. of asthma, respiratory stimulant.

• Powder is used as inhalation.Anti-smoking preparations

Lobeline sulfate incorporated in tablets or lozenges are smoking

deterrents.

Lobeline had placebo effect on decreasing the physical craving for

cigarettes.

Chronic bronchitis, bronchial asthma.

Injection of lobeline hydrochloride is used in the resuscitation of

newborn infants (asphyxia)

Chemical test:

1. lobeline sol. + H2SO4 = red color with formaldehyde.

2. on boiling it form acetophenone which recognised by smell.

3. Pipper:

α & β pinene,

Phellandrene

Allied drug: Cubebs or tailed pepper

Morphology:

Shape: round or globular

Size: 3-6mm in dimeter

Color: greyish brown or black on outersurface, which is highly

reticulated.

Apex & base are easily distinguishable as apex shows remains of

stigmas & base shows scare points attachment to axis.

Taste: Strong Pungent ,

Odour: Aromatic

Cultivation & collection:

20-30 sessile flower develop sessile fruits.

Fruits are collected when their lower part turns red.

They are dried in open & artificial heat.

White pepper is prepare from black pepper by soaking in water

removing outer layer of black one then removing it by rubbing.then

washed & dried.

3A. Long Piper:

4. Areca

Syn.: Areca nut or Betel Nut , Pinag, Supari

B.S. : A dried, ripe seed of Areca catechu

Family: Palmae

G.S. : Philippines, India, East Africa, Sri Lanka,

Malasiya, Pinlang, Bangladesh

Areca- a Spanish and Portuguese term for betel nut

Catechu- East Indian name for an astringent extract or juice

Areca mixed with lime, the leaves of Piper bette Linné and

occasionally Gambier is known as “PUNSUPARI”. This mixture is

used as a stimulant masticator.

Consists of 0.45% alkaloids, 15% tannins, lipids, volatile oils and

gum.

Morphology:

Size & shape: Tall palm tree which bears fruit of nut type, each contain

single seed, thin seedcoat & large endosperm.

Color: testa brown

Taste: astringent

Chemical Constituent:

• These are reduced pyridine derivatives.

• Arecoline (arecaidine methyl ester)

• Arecaidine (N-methyl guvacine)

• Guvacine (Tetrahydronicotinic acid)

• Guvacoline (Guvacine methyl ester)

Uses:

• Psychoactive drug used as parasympathomimetic

• It contain sialogogue so used as masticatory .

• Anthelmintic drug used as vermicide & Taenifuge in veterinary

practice.

Indian ginseng

G.S.: South europe, india, africa, ajmer, manasa in M.P.

Cultivation & Collection:

Sandy loam soil, light red soil having PH 7.5 – 8 with good drainage.

It is perennial, branched, erect (verticle), under shrub.

Roots develop within 1-2 late winter rains received.

Seed propagation by broadcasting method during 2 week of july.

They are sawn in nursery, lightly covered with soil & germinating about

6-7 days after sowing.

When become 6 week old it transplant in open field in 60 cm wide. Area

Harvesting start from January to till march.

Roots are cut in to small pieces of 7-10 cm to facilitate drying.

Withhasomine,

Anaferine,

Anhygrine,

Hyggrine,

Withanolide,

isopellatierine.

Cocca

Morphology

morphology Bolivian peruvian

General appearance entire More or less broken

Size 4 – 8 cm long 2-5 cm long

Shape Oval Elliptical

Margine entire Entire

Apex acute Acute

Base tapering Tapering

Surface Glabrous, slight glossy Glabrous, not glossy

Color Brownish green Pale green

Odour faint Faint

taste bitter Bitter

texture Thin, firm (hard) Thin, fragile (weak)

venetion Prominent on lower side, midrib progecting slightly. 2 prominent ridges present

Similar but ridges not available

Cultivation & Collection

Planting by seed in rich, light & well drained soil at altitude 1500 – 6000 ft.

2nd year collect leaves in dry weather., usually 3 times in a year, dried in

shade.

G.S.: central & south europe, england, germany, america, india(kulu, kashmir, simla)

Atropa acuminata (indian)

Cultivation & collection:

Seed sawn in nursary, then seedling transplanted in deep well

drained, moist, calcareous soil & loamy soil in April.

Weeding & fertilizing are needed.

Leaves Collected in dry summer weather next 4 ft. hight, flowring

15th june to 15th july.

From 2nd cut plants harvesting are done in August & september and

sometime in october.

Root are dug out at 4th year

Drug dried at 40 – 60 °C in dark sheds.

Scopolia

• Synonym: Europian Scopolia, Russian Belladona

• B.S.: it consist dried root & rhizomes of Scopolia japonica

• Family: Solanaceae

• G.S.: india, england

• C.C: hyoscyamine, Scopolamine, Atroscine

• Morphology: ovate, smooth leaves, pale green

• Use: sedetive, arthritic pain, mydriatic

• Scopolamine

It has a depressant activity on the CNS.

It is used to treat motion sickness.

It is employed for preanesthetic sedation and for obstetric amnesia

in conjunction with analgesics and to calm delirium.

• Scopolamine or hyoscine

An alkaloid abundant in Datura fastuosa var. alba and in D. Metel.

It is an ester that, upon hydrolysis, yields tropic acid and scopoline.

It occurs as an almost colorless, syrupy liquid from its chloroformic

solution and colorless crystals from its ether solution.

• Scopolamine hydrobromide or hyoscine hydrobromide

It occurs as colorless or white crystals or as a white, granular powder

that is odourless and slightly efflorescent in dry air. It is extremely

poisonous.

It is classified as anticholinergic.

It is employed for preanesthetic sedation and for obstetric amnesia in

conjunction with analgesics and to calm delirium. It is administered SC or

IM in a single dose.

Quinoline & Isoquinoline

Tetrahydroxy-iso-quinoline monoterpenoid

Johore Ipecac, Ipecac Rio

Cephelis acuminata (panama)

Isoquinoline Alkaloid

Afim, Afin

G.S.: turkey, Yugoslavia(macedonia), india, pakistan, Iran, china, thiland, pakistan

Camptotheca

Syn: Cancer tree

B.S.: it is dried stem wood of Camptotheca acuminata Decane

Family: Nyssaceae

G.S.: Southern china, tibet

Cultivation & collection:

It is a desiduous tree, sawing seed, shading is require for increasing

alkaloidal content(leaves & root).

Fruits are collected late in autumn, others collected in year.

All part dried in sunlight.

morphology

Color: leaves are dark green with reddish ppetiole, flower are red

Odour: charecteristic

Taste: bitter

Size: 8-10 cm in length & 3-5 cm in width

Shape: leaves are entire, acuminate, ovate & lanceolate

Chemical Constituent:

Camptothecine

Use: Antitumer agent

Indole alkaloid

Physostigma

Syn: Calabar bean, Ordeal bean

B.S.: it consist dried ripe seeds of Physostigma venenosum.

Family: Leguminoceae

G.S.: West Africa, gulf of gunea

Macroscopy:

Shape: seed are flarrened, kideny

Size: 2-3 cm long and 1 to 1.5 cm wide, 1.5 cm thick

Color : Dark brown

C & C: Physostigmin(eserine), eseroline, isophysostigmine,

physovenine, geneserine, calabacine, calabatine.

Use: Cholinesterase inhibitors

Physostigmine salicylate is used for contracting the pupil eye

In glucoma

Imidazole alkaloid

Steroidal alkaloid

Veratrum

It contain 2 group of alkaloid jeveratrum & ceveratrum.

1) veretrum viride

Syn: American or green hellebore

B.S.: it consist of dried rizome & roots of veretrum viride Aiton.

Family: Lilliaceae

G.S.: New York, North carolina, Georgia, Tennessee.,canada

Macroscopy:

Color: brown

Odour: Unplesent

Taste: Acrid

Size: rhizomes 5-8 cm in length 2-3.5 cm wide.

Shape: Sub-cylindrical with numerous yellowish brown spot.

Use:

1) it lowers Blood pressure & decreases heart rate.

2) it is used I hypertension(mainly in pregnancy, as liquid extract or

tincture.

2) Veratrum Album

• Syn: White hellebore, European hellebore

• B.S.: Dried rhizome of veratrum album Linn.

• Family: Liliaceae

• G.S.: native central & southern Europe, China & Japan.

• it is deciduous herb, flowering in June-July bears white flowers.

• Stem is hairy 50-125cm in height.

Macroscopical characteristic:

Color: Brown

Odour: Unpleasant characteristic

Taste: Burning, acrid & bitterish

Size: 5-15 cm in length & 2-3 cm in diameter

Shape: Tuberous, fleshy with number of long white fibres at end of

the roots.

Chemical Constituent:

Mainly veratrine , germidine, protoveratrine, cevadine,

pseudojervijne, veratrosine.

Use: in preeclampsia & eclampsia

Substitutes: Cevadilla seeds

Kantakari

Syn: Kateli, duhusparsh, Nidhigandhika, yellow-berried nightshade,

Indian Solannum

B.S.: it is obtained from plant of Solanum xanthocarpum

Family: Solanaceae

Macroscopy:

Size: 1.5 cm prickles,

Color: flower-purple, leaves- green, spines- light yellow

Shape: leaves- egg shaped, shiny prickles, hairy, round fruit.

Smooth seed

Chemical Constituent:

Carpesteral, 1.3% solanocarpine, solanine, solanidine.

Use:

Fruit as antianthelminitic & for indigestion.

Root as expectorant & diuretic.

In tmt of cough, asthma, chest pain.

Also used in flatulence, sour thought, toothache & constipation.

Adultrants & substituents:

Clepodendrum seeratum(Bharangi)

Alkaloidal Amine

Diterpene alkaloid

1) Aconite:

Syn: Monkshood, Friar cowl, Mouse-bane, Aconite root, Radix

aconiti.

B.S.: it consist of the dried root of Aconitum nepellus Linn.

Family: Ranunculaceae

G.S.: Europe, Alps, Carpathian, hills of Germany & Himalaya, Spain

Macroscopy:

It is varies from species to species.

Shape: Conical & tapering below

Surface: slightly twisted bearing longitudinal reading, some aconite

contain fibrous rootlets or their scars.

Color: dark brown

Size: root – 4-10 cm in length & 1-3 cm in diameter at crown.

Odour: Slight characteristic

Taste: sweet first then produce numbness

Chemical Constituent:

Aconitine, hypaconitine, sconine, napelline, neoline, acotinic acid

Uses:

Tincture as antipyretic in small doses

Local analgesic to treat neuralgia, rheumatism & inflammation.

2-3mg can lead respiratory failure, heart failure and end of the

death.

Commercial Verities:

1) Japanese Aconite: Aconitum Japonicum , roots are shorter, gray

or dark brown in color, its contain cardiotonic properties.

2) Chinese Aconite: A.carmichaelii, A. cusnezofii & A. brachypodum.

3) Indian Aconite: A. chasmanthum. 2.5-4.5 cm long. It contain

indaconitine. Others are A. deinorrhizum & A. balfourii,

A.spicatum & A.Lciniatum

Taxus

Syn: Pacific yew, western yew, American yew,

Oregon yew, bow plant, mountain mahogany

B.S.: it contain fruit of the tree of Taxus brevifolia

Family: Taxaceae

G.S.: western north america, south alaska to north california,&

pacific coast to Idaho, Montana, fransisco

Macroscopy: evergreen,

Height: 6-10 mtr. Dia.- 15-30 cm,

1.4 m also 25 m height( Washington)

Male tree: yellow flower

Female tree: seed enclosed in pulpy, red sweet, trunk is tapered &

fluted, covered by scaly, reddish-brown to purple-brown bark

C & C: terpenoids, n-alkanes, myrtenol, 3-hexenol, tricosane

Use: anticancer

Comercial varities:

T. canadensis

T.baccata

T. floridana

Tylophora

B.S.: leaves & root of Itylpphora indica

SYN: Antmul, antomul, Kharki-raena, pitakari, antamul

Family: Ascalepidaceae

G.S.: all over india

Macroscopy:

Leaves: 5-10 cm long ovate, oblong, acute, acuminate base cordate

Flower: yellow, purple witin

Fruit: Folicle, I pairs, ridged, 7.5-10 cm long, tapering the fine point

at apex

Roots: Fleshy, long

Latex: white

C & C: Tyloindicine – A,B,C,D,E,F

Chemical Test: Mayer’s, Dragendroff’s, Hager’s, Wagner’s tests

Use: Hepatoprotective, Anti-allergic, Diuretic, Anticancer, Anti-

asthamatic, cardiac activity, Imunomodulatory activity