ALKALOIDAL AMINES

ALKALOIDAL AMINES Subject name: PHARMACOGNOSY-4 Subject code: 250006 DR. HARISHKUMAR N. KAKRANI, PRICIPAL, C. V. M INSTITUTE OF DEGREE COURSE IN PHARMACY (institute code: 272), VALLABH VIDYANAGAR 388 121

ALKALOIDS Alkaloids are a group of naturally occurring organic organic substances, having nitrogen in their heterocyclic ring. o

Except

oto- and pseudo-alkaloids that do not have nitrogen in their structural rings. few i.e. pr oto-

Most alkaloids contain oxygen; those compounds are usually color less crystals at ambient conditions. o

Oxygen-free ygen-free alkaloids, such as as nicotine or coniine coniine are typically volatile, volatile, colorless, oily liquids.

o

Some alkaloi alkaloids ds are are colored, colored, like berberin berberine e (yellow (yellow)) and sanguinari sanguinarine ne (orange) (orange)..

Most alkaloid are

weak

bases, but some are amphoteri amphoteric, c, for example ample theobr theobromi omine ne and theoph theophyl yllin line. e.

Most alkaloids are poorly soluble in water water but readily dissolve in organic solvents, such as diethyl ether, ether, chloroform chloroform and 1,2-dichlo 1,2-dichloroeth roethane. ane. o

W

However, However, caffiene dissolves well in boiling boiling water. water.

ith acids, alkalo alkaloids ids f orm salts of various strengths. o

Those

salts are are usually soluble in water and alcohol and poorly soluble in most organic solvents.

o

Exceptions include scopolamine hydrobromide hydrobromide which is soluble soluble in organic organic solvents and and water-soluble water-soluble

quinine sulfate. Alkaloids occur as free bases, salts or N-oxides (NO).

W hen

the salt of an alkaloid is treated with

hydroxyl ion, nitrogen gives up a hydrogen ion and the free amine is liberated. Alkaloidal amines, Dr. Harish Kakrani, CDCP

2

ALKALOIDS May be of plant or animal origin Nitr ogen ogen of alkaloids: The Nitrogen Nitrogen atom can either be 1Û, 2Û, 3Û or 4Û (quaternary). (quaternary).

Alkaloids are usually bitter in taste. They o

are optically active. Generally the levo rotatory isomer l (-) (-) is pharmacologically pharmacologically more more active than the dextro rotato rotatory ry isomer d (+) of the same alkaloid.

o

Exception: d(+) pilocarpine, d(+) tubocurarine tubocurarine and d(+) quinidine are medically used.

Alkaloids are pharmacologically active even in microgram quantities. ±

Plant alkaloids alkaloids usually usually have profou profound nd physio physiologica logicall actions actions in human humans s even in in microgram microgramme me quantity with nervous system effects being the most prominent.

±

Examples

of some of the more dramatic actions of alkaloids are:

Analgesics/ narcotics²morphine

Mydriatics²atropine

Miotics²pilocarpine

Hypertensives²ephedrine

Hypotensives²reserpine

Bronchodilator²lobeline

Stimulants²strychnine

Antimicrobials²berberine

Antileukemic²vinblastine

BIOGENESIS OF ALKALOIDS: o

Alkaloids are produced in plants by basic substances and reactions well-known in organic chemistry. Alkaloidal amines, Dr. Harish Kakrani, CDCP

3

BIOGENESIS OFALKALOIDS True

alkaloids are based on an amino acid (pre-cursor). Only a few amino acids form the pre-

cursors for for all alkaloids: ornithine, lysine, lysine, phylalanine, phylalanine, tyrosine, tryptophan, tryptophan, histidine and anthranil anthranilic ic acid.

Alkaloidal amines, Dr. Harish Kakrani, CDCP

4

OCCURRENCE & DISTRIBUTION OF ALKALOIDS

Pseudomonas aeruginosa) and rarely Occur in bacteria (Pseudomonas rarely in fungi (pscilocin from hallucinogenic

mushrooms). Some alkaloids occur in several genera from different species (caffeine), but most occur in closely related species. Some occur in certain families (hyoscyamine), while others occur only in a specific species s pecies (morphine). Rarely do plants contain more than 1 type of alkaloid. All alkaloids of one plant will have a common biogenetic origin Alkaloids occur in all plant parts, but are usually localized in one organ (e.g. the bark or seeds). W

ithin the the plant, alkaloid can vary widely widely from part to part ± some parts may contain no alkaloids.

Occasionally, Occasionally, different alkaloids also form in different parts of the plant.


5

CLASSIFICATION OF ALKALOIDS

ALKALOIDS

Pr oto-alkaloids oto-alkaloids (AMINO (AMINO-- ALKALOIDS) LKALOIDS)

Tr ue ue Alkaloids

Nitrogen in its heterocyclic ring system

Have no nitrogen as a part of their heterocyclic ring

Derived from amino acids

Derived from amino acids


Pseudo-alkaloids

These

alkaloids have heterocyclic ring with nitrogen in it

But these are not derived from amino acids

6

CLASSIFICATION OF TRUE ALKALOIDS Sr . No.

1

2

3

4

Class

Pyridine/ piperidine

Tropane

Quinoline

Isoqinoline

Examples

Species

Pharmacological actions

Nicotine

icotiana tabacum N icotiana

Adrenergic, CNS stimulant

Lobeline

Lobelia inflata

Piperine

Piper nigrum P. longum

Arecoline

Areca catechu

Vermicide, Vermicide, taenifuge

Hyoscyamine

Atropa belladonna

Anticholinergic, Antisialagogue

Cocaine

Erythroxylon coca

CNS stimulant, anaesthetic, narcotic

Scopalamine

Datura metel

Anticholinergic, CNS depressant

Quinine

Cinchona spp.

Antimalarial, Antiarrhythmia Antiarrhythmia

Expectorant, bronchodilator

Stimulant hepatoprotective

Quinidine

-

Cardioactive

Berberine

Berberis spp.

Antimicrobial, antiprotozoal, cholagogue

Morphine

Papaver somniferu s omniferum m

Sedative, analgesic, Narcotic

Chelidonine

Chelidonium majus

Spasmolytic, cholagogue

Boldine

Pneumus boldo

Spasmolytic, choleretic

Emetine

Cephaelis Ipecacuanha

Emetic


7

CLASSIFICATION OF TRUE ALKALOIDS Sr . No.

Class

5

Quinolizidine

6

Pyrrolizidine

7

8

Indole

Imidazole

Examples

Species


Sparteine

arothamnus S arothamnus

Oxytocic, cardiotonic, diuretic

scoparius

Sececionine Symphytine

enecio jacobeae S enecio

Hepatotoxin

ymphytum spp. S ymphytum

Reserpine

Rauwolfia serpentina

Sedative, Antihypertensive

Ergotamine

Claviceps purpurea

Vasoconstrictor, hypertensive

Strychnine

trychnos nuxvomica S trychnos

CNS stimulant, deadly to xin

Yohimbine

Aspidosperma quebracho

Aphrodisiac, stimulant

Pilocarpine

Pilocarpus jaborandi

Miotic, cholinergic

CLASSIFICATION OF PROTOALKALOIDS Sr . No.

1

Class

Alkaloidal amines (protoalkaloids)

Examples

Species


Colchicine

Colchicum autumnale

Antimitotic, uric acid amines solvent

Ephedrine

Ephedra sinica

Sympathetic stimulant, bronchodilator

Mescaline

Lophophora williamsii

Hallucinogenic


8

CLASSIFICATION OF PSEUDO-ALKALOIDS

Sr . No.

1

2

3

Class

Purine alkaloids

Steroidal alkaloids Terpenoidal

Examples

Species


Caffeine

Coffea arabica

CNS and sympathetic stimulant

Theophylline

Thea sinensis

Bronchodilator, Bronchodilator, diuretic

Guaranine

Paullinia cupana

CNS and sympathetic stimulant

Solanine

olanum S olanum

Steroid precursors, antiinflammatory

Veratrine

Veratrum album

Cardiac depressants, antihypertensives

Aconitine

Aconitum spp.

Antipyretic, analgesic, neurotoxin

spp.

alakaloids


9

AMINO-ALKALOIDS (PROTO-ALKALOIDS)


10

AMINO ALKALOIDS GENERAL CHARACTERISTIC FEATURES:

Protoalkaloids Have no nitrogen as the part of the heterocyclic ring. Derived from amino acid like l- phenyl alanine. Physiologically active compounds Ex

ample: Ephedrine (Ephedra species) species) and Colchicin Colchicine e (Colchicum autmnale)

BIOSYNTHESIS OF AMINO ALKALOIDS: acid pathway. Amino alkaloids are derived from amino acid l- phenyl alanine alanine through shikkimic acid The

pathway pathway finds its route from carbohydrates carbohydrates for the biosynthesis of C6- C3 units (i.e. phenyl

propane derivatives) derivatives) like phenyl phenyl alanine and tyrosine An important branching branching point arises at chorismic acid, which acts as a precursor for different amino amino acids.


11

BIOSYNTHESIS OF AMINO ALKALOIDS ALKALOIDS

Dehydration

3- dehydro Shikimic acid


12

BI

I

I

I

Shikimic acid

Prephenic acid Dehydration

Phenyl pyruvic acid Phosphoenol pyruvic acid

Shikimic acid3- phosphate

5- enolpyruvyl shikimate-3 phosphate


13

BIOSYNTHESIS OF AMINO ALKALOIDS ALKALOIDS

Phenyl

Ephedrine ( Ephedrine Ephedrine spp.)

alanine

Colchicine (Colchicum autumnale) autumnale) Alkaloidal amines, Dr. Harish Kakrani, CDCP

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GENERAL PHARMACOLOGICAL PHARMACOLOGICAL ACTION ACTION & USES OF AMINO- ALKALOIDS

Cause ±

Dila Dilati tion on of of the bro bronc nchi hi (as (asth thma ma), ),

±

Incr Increa ease se hear heartt rat rate e and and

±

Peri Periph pher eral al vaso vasoco cons nstr tric ictio tion n


15

EPHEDRA


16

EPHEDRA Synonym: Ma-Huang. Biological sour ce ce: It consists of dried young stems of Ephedra gerardiana (wall.) Stapf, and E. nebrodensis

(Tineo) Stapf. o

Family: Gneta Gnetacea ceae e (Ephedraceae).

o

Ephedra should

contain not not less than 1% of total alkaloids, calculated as ephedrine. ephedrine.

Geogr aphical sour ce ce: China, Pakistan, North-west parts of India, Australia, Kenya, Spain & Yugoslavia. Cultivation, Collection & pr epar ation ation: o

o

Cultivated at an altitude of 2500- 3000 m. Annual rainfall should not e xceed 50cm.

o

Propagated by by seeds or by layers or divisions of root stock.

o

Seeds sown sown early in spring at a distance of 5cm, keeping distance of 1 mt between 2 rows

o

Collected after attaining the age of 4 yrs for e xtraction of alkaloid

o

Alkaloid content varies from season to season. 

It is maximum in autumn

o

Twigs

dried in sun or even by artificial ways.

o

Stored in dry & well closed containers Alkaloidal amines, Dr. Harish Kakrani, CDCP

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EPHEDRA Macr osco oscopic Char acte acter s: o

Gener al al appear ance ance: Thin cylindrical or ellipsoidal ell ipsoidal cylinder, cylinder,

o

Size: 1±2 mm in diameter; 3.5±5.5cm in length of internode;

o

Color : Light green to yellow-green;

o

vertical furrows on the surface; scaly leaves at the node Sur f face ace: numerous parallel vertical portion;

o

Leaves: 2±4 mm in length, light brown to brown in colour, usually opposite at every

node, adhering at the base to form a tubular sheath around the stem. o

Tr ansve ansver se se section of the stem: appears as circle and ellipse, the outer portion

greyish green to yellow-green in colour, and the centre filled with a red-purple substance or hollow. o

Fr actu actur e at an inter node node: the outer part is fibrous and easily split vertically

o

Odou r : slight;

o

Taste: slightly bitter and astringent, giving a slight sensation of numbness on the

tongue .


18

EPHEDRA

Macr osco oscopical ical char acte acter istics istics of Ephedr a Stem & Leaves


19

EPHEDRA Micr osco oscopic char acte acter istics istics: 1.

STEM: The

epidermal cells of the stem covered with a moderately thick granular cuticle; the cells are

polygonal or subrectangular, a xially elongated, elongated, having straight anticlinal walls. The

stomata are few and are are of the ranunculaceous type with lignified appendages. appendages.

Cortical parenchyma parenchyma and pith cells contain an amorphous reddish brown substance. Non-lignified or or lignified hypodermal hypodermal and pericyclic pericyclic fibres, which have thick walls, walls, bear slit-like pits and blunt, slightly tapering, occasionally forked ends. The

vessels of the secondary xylem of the stem are lignified with bordered pits, having rounded or

oval apertures. F

ew, ew, small, rounded, simple and compound starch granules granules with indistinct hilum are present in

cortical parenchyma, parenchyma, pith, and medullary medullary ray cells. F

2.

ew, ew, small prisms of calcium oxalate are present in the cortical parenchyma.

LEAF: The

epidermis of the scaly leaf is covered with smooth (upper) or warty (lower) cuticle and consists

of subrectangular subrectangular to polygonal polygonal cells, having straight straight or sometimes slightly beaded beaded anticlinal walls; few stomata are present resembling those of s tem. Alkaloidal amines, Dr. Harish Kakrani, CDCP

20

EPHEDRA The

epidermis of the apical and marginal regions of the scaly leaf shows short papillae-like

outgrowths. Chlorenchymatous Chlorenchymatous palisade-like cells form the outer zone of the corte x; rounded ordinary parenchymatous parenchymatous cells form the inner zone zone of the cortex. The

fibres of the scaly leaf are lignified.

Powder char acte acter istics istics: o

Powdered herb is greyish green.

o

The

characteristics observed are as follows: Thick

fragments of cutinized outer walls of epidermis

Sclerenchy Sclerenchyma ma fibres fibres with e xtremely thickened, non-lignified to lignified walls, narrow, narrow, frequently f requently indistinct lamina and sharp pointed ends. F

ragments of vascular tissue showing spiral and pitted tracheae.

F

ragments of epidermis with sunken elliptical stomata


21

EPHEDRA

Tr ansve ansver se se Section o f Ephedr a Stem

Powder char acte acter istics istics of Ephedr a stem


22

EPHEDRA Chemical constituents: constituents: o

o

Amino alkaloids:

Ephedrine, nor-ephedrine, n-methyl

ephedrine, pseudo-ephedrine. pseudo-ephedrine.

Chemically, Chemically, ephedrine is 1-phenyl-11-phenyl-1- hydroxy-2- methylamin methylaminopro opropane pane Soluble in water, water, alcohol, organic solvents and oil Odourless Odourless & colourless colourless Deliquescent Decomposes when e xposed to air.

o

Other constitutents: Macrocycl Macrocyclic ic alkaloidsalkaloids- ephedrad ephedradines ines present present in in roots. roots. Oxazolidone.

Ephedr ine

Nor -e -ephedr ine ine N-methyl ephedr ine ine Alkaloidal amines, Dr. Harish Kakrani, CDCP

23

EPHEDRA Chemical Tests: o

Ephedrine

dissol solved in water & dil. HCl

Violet col colored solution

treat individ vidually with Copper sulfate & NaOH if sha shaken ken with solvent ether, organic layer sh shows purple col color & aqueous

layer shows blue color. Uses: o

Sypathomimetic effects Bronchodilator in asthma In treatment of allergic conditions like hay fever As compared to adrenaline onset of action for ephedrine is slow, but effect is much prolonged, as it is not quickly hydrolysed by mono amine oxidase in the body body.

o

Causes peripheral contraction of arterioles, therefore used to correct the low blood pressure conditions.

Allied dr ugs ugs: o

o

Genus Ephedra phedra has about 45 species species About 25 species contain ephedrine.

o

Prominent species containing ephedrine are E. equisetina & E. sinica

o

Contain from 35- 87% of ephedrine in total alkaloids. E. intermedia, E. major , E. helryetica & E. alata: Contain

o

The

other plants plants containing ephedrine are Aconitum napelles (Ranunculaceae); S ida ida cordifolia; and S .

rhombifolia (Malvaceae); Roemeria refracta (Papaveraceae) and Taxus baccata (Taxaceae).


24

COLCHICUM


25

COLCHICUM Synonyms: Meadow saffron seeds, autumn crocus Botanical sour ce ce : It consists of dried ripe seeds and fresh or dried sliced corms of Colchicum autumnale o

Family: Liliaceae.

Geogr aphical sour ces: ces: o

Indigenous to Britain

o

Grows in Central and Southern Europe

Cultivation & Collection: o

Colchicum propagates by repeating the life cycle with the corm, which is present as a swollen underground stem with sheathing leaves.

o

Towards

the end of summer, the fully grown corm develops daughter corms in the axil of scaly scaly leaf leaf

near the base. o

These

daughter corms develop parasitically on parent corm & su bsequently parent corm withers aw ay. ay.

o

The

o

May also be propagated by seeds, sown 1/8 inch deep in a bed of fine soil outdoors in August or

daughter corms develop into new corms.

September; transplanting seedlings 3 inches apart when two years old; or by division of bulbs in August. Seedling bulbs do not flower till four or five years old. Alkaloidal amines, Dr. Harish Kakrani, CDCP

26

COLCHICUM Macr osco oscopic char acte acter istics istics: 1. Colchicum seeds: o

Very hard in nature

o

Have a projection projection at hilum & from there

o

develops strophiole, which which is an outgrowth of testa.

o

Size: 2-3mm in diameter

o

Taste:

o

Odour: Odourless

bitter & acrid

2. Colchicum corm: o

Size: 2-3cm in diameter, 2-5mm thickness

o

Fracture: Short

o

Shape: sub-reniform sub-reniform or ovate in outline

o

Color: yellowish brown

o

Taste:

o

Odour: Odourless

bitter


27

COLCHICUM Micr osco oscopic char acte acter s: 1.

2.

T.S of Seed: o

Shows parenchyma & endosperm

o

Parenchymatous Parenchymatous cells are reddish brown with thick walls walls

o

Endospermic

o

Strophiole portion of the seeds contain starch

cells show show pitted walls & contain aleurone grains and fi xed oils

T.S of corm: o

Corm has epidermis, parenchyma & vascular tissue

o

Parenchymatous Parenchymatous cells have abundant abundant starch grains

o

Epidermis

o

In vascular part, the xylem vessels are spiral or annular. annular.

has circular stomata

Chemical Constituents: Constituents: o

SEED: 0.2-1% amino alkaloid , of which which Colchicine is 0.8%

o

CORMS: 0.6% Colchicine. Also contains demecolcine

o

Both the alkaloids contain tropolone or cycloheptatrien-ol-one cycloheptatrien-ol-one ring structure.

o

Colchicine Colchicine is a toxic, yellowish-white yellowish-white amorphour or crystalline substance that darkens on exposure to light. It is soluble in alcohol & chloroform, sparingly soluble in water. water. Alkaloidal amines, Dr. Harish Kakrani, CDCP

28

COLCHICUM

Powder char acte acter istics istics of Colchicum seed powder Alkaloidal amines, Dr. Harish Kakrani, CDCP

29

COLCHICUM

Demecolcine

Colchicine


30

COLCHICUM Chemical tests: o

o

Colchicine + 60 60 - 70% su sulphuric acid or or co conc. HC HCl

yellow co colour is pr produced.

Alcoholic solution of colchicine + ferric chloride

red color

Uses: o

o

o

Gout & rheumatism Also possesses anti-tumor activity Used in horticulture as a chemical c hemical agent for bringing polyploidy

Allied dr ugs ugs: o

Plants bearing chemical chemical contents similar to colchicine type of alkaloids belong to different different genera such as, Dipida x, Gloriosa, Androcybium, Camptorrhiza, etc.

o

Other genera genera of same family liliaceae which contain colchicine- Androcybium, Bulbocodium, Bulbocodium, Dipidax, Littonia, Fritillaria, Ornithoglossum, etc.


31

ALKALOIDAL AMINES

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