alkaloids.ppt

Alkaloids

1. Alkaloids
11/6/2023 1
Dr. Quazi Majaz A.,
Associate Professor & Head,
Department of Pharmacognosy,
Ali Allana College of Pharmacy,
Akkalkuwa

2. Theterm“alkaloid”(alkali-like)iscommonlyusedto
designatebasicheterocyclicnitrogenouscompoundsofplant
originthatarephysiologicallyactiveandshows
pharmacologicalactioninsmalldose.

3. Deviation from Definition
•Basicity:Somealkaloidsarenotbasice.g.Colchicine,
Piperine,Quaternaryalkaloids.
•Nitrogen:Thenitrogeninsomealkaloidsisnotina
heterocyclicringe.g.Ephedrine,Colchicine,Mescaline.
•PlantOrigin:SomealkaloidsarederivedfromBacteria,
Fungi,Insects,Frogs,Animals.
•Biosynthesis:Somealkaloidsarenotderivedfrom
aminoacidse.gpurine,steroidalalkaloid.

4. Thesearetheorganicproductsofnaturalorsynthetic
originwhicharebasicinnatureandcontainingoneor
morenitrogenatomnormallyofheterocyclicnatureand
possespharmacologicalactioninsmalldoseonhumanand
animals

6. Physical Properties:
I-State:
•Mostalkaloidsarecrystallinesolids.
•Fewalkaloidsareamorphoussolidse.g.emetine.
•Someareliquidsthatareeither:
Volatilee.g.nicotineandconiine,or
Non-volatilee.g.pilocarpineandhyoscine.
II-Color:
Themajorityofalkaloidsarecolorlessbutsomearecolored
e.g.:
•Colchicineandberberineareyellow.
•betanidineisorange.

7. III-Solubility:
Bothalkaloidalbasesandtheirsaltsaresolubleinalcohol.
Generally,thebasesaresolubleinorganicsolventsandinsolubleinwater
Exceptions:
Basessolubleinwater:caffeine,ephedrine,codeine,colchicine,pilocarpine
andquaternaryammoniumbases.
Basesinsolubleorsparinglysolubleincertainorganicsolvents:morphine
inether,theobromineandtheophyllineinbenzene.
Saltsareusuallysolubleinwaterand,insolubleorsparinglysolubleinorganic
solvents.
Exceptions:
Saltsinsolubleinwater:quininemonosulphate.
Saltssolubleinorganicsolvents:lobelineandapoatropinehydrochlorides
aresolubleinchloroform

8. IV-Isomerization
•Opticallyactiveisomersmayshowdifferentphysiologicalactivities.
l-ephedrineis3.5timesmoreactivethand-ephedrine.
l-ergotamineis3-4timesmoreactivethand-ergotamine.
d-Tubocurarineismoreactivethanthecorrespondingl-form.
•Quinine(l-form)isantimalarialanditsd-isomerquinidineis
antiarrythmic.
•Theracemic(opticallyinactive)dl-atropineisphysiologically
active.

9. 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

10. QUALITATIVECHEMICALTESTSFORALKALOIDS
1.Dragendorff’stest:To2–3mlofthesolutionaddfewdropsof
Dragendorff’sreagent(potassiumbismuthiodidesolution).Anorange
brownprecipitateisformed.
2.Mayer’stest:To2–3mlofthedrugaddfewdropsofMayer’sreagent
(potassiummercuriciodidesolution).Whitebrownprecipitateisformed.
3.Hager’stest:To2–3mlofthealkaloidsolutionaddfewdropsof
Hager’sreagent(saturatedsolutionofpicricacid).Yellowprecipitateis
formed.
4.Wagner’stest:To2–3mlofthealkaloidsolutionaddfewdropsof
Wagner’sreagent(iodine–potassiumiodidesolution).Reddishbrown
precipitateisformed.

11. 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 Extraction of alkaloids
1. Stass otto method

12. 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 Extraction of alkaloids
2. Manske’s method

13. Purification of Alkaloids
1. Direct crystallization from solvent
2. Repeated acid base treatment
3. Fractional crystallization
4. Chromatographic techniques
5. Gradient pH techniqueEphedrine & Pseudoephedrine Oxalates
Crystallization from water
Ephedrine Oxalate
Crystals
Pseudoephedrine Oxalate
Solution Atropine & Hyoscyamineine Oxalates
Crystallization from
Acetone/Ether
Atropine Oxalate
Crystals
Hyoscyamine Oxalate
Solution

14. A) True alkaloids
Sr. no. Type Structure Examples
1. Pyrrole and
pyrrolidine N
H
N
H

e.g. Hygrine, coca species
2. Pyiridine and
piperidine N N
H

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
Classification of alkaloids
Chemical classification

15. 7

Indole N
H

e.g. Erotamine, ergotametriene,
reserpine, vincristine, vinblastine,
strychnine, brucine
8

Imidazole N
N
H

e.g. Pilocrpine, isopilocarpine, pilosine
9 Norlupinane N

e.g. Cystisine, laburinine
10 Piporphine
(reduced
isoquinoline
napthalene) N

e.g. Boldine

16. 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

17. Pharmacological classification
1.Narcotic analgesic e.g.Morphine
2.Antimaleriale.g. Quinine
3.Reflux excitability e.g.Strychnine
4.Respiratory stimulant e.g.Lobeline
5.Neuralgia e.g. Aconitine
6.Oxytocice.g. Erogotometrine
7.Bronchodilator e.g. Ephedrine, vasicine
8.Anticholinergice.g. Atropine
9.CNS stimulant e.g. Caffeine
10.Antitussivee.g. Codeine
11.Antiarrythmice.g.Quinidine
12.Antihypertensive e.g. Reserpine
13.Anticancer e.g. Vincristine
14.Antiglucomae.g. Pilocarpine

18. Catharanthus( Vinca)
Synonyms-Vincarosea, Catharanthus, periwinkle.
Biological Source-Vincais the dried entire plant of CatharanthusroseusLinn.,
belonging to family Apocynaceae.

19. Macroscopicalcharacters:
Type–Annularorperennialherb;
Size–0.5to1meterlength;
Leaves–Ovate,oblong,glossyaboveglaucousbelow;
Flowers–2to3incymes,axillaryandterminalclusters.Basesonflowercolour,
threevarietiesareknownnamely–alba-white,ocillata-whitewithpinkorcarmine
redeyesandroseus-withrosecolouredflowers.
Fruit-afollicle,cylindricalandmanyseeded.
Taste–Bitter;
Odour–slight

20. Microscopical characters

21. Chemical constituents:
Indole and indoline alkaloids:
Ajmalicine
Lochnerine
Serpentine and
Tetrahydro alstonine:
Dimeric Indole bases of monoterpene type
Vinblastin
Vincristin.

22. Uses
Vinblastinisanantitumouralkaloidusedinthetreatmentof
Hodgkin’sdisease.
Vincristineisacytotoxiccompoundandusedtotreat
leukaemiainchildren.
Vincaisusedinherbalpracticeforitsastringentandtonic
propertiesinmenorrhagiaandinhaemorrhages.
TheflowersofthePeriwinklearegentlypurgative,butlose
theireffectondrying.

23. Rauwolfia*
Synonyms-sarpagandha,
Biological source: Rauwolfia consists of the dried roots and rhizomes of
Rauwolfia serpentina Benth. It contains not less than 0.15% of reserpine belong
to Family Apocynaceae.

24. Cultivation:
•Itsgrowsspontaneousintropicalforests(temp,10°Cto40°C)whicharehumidin
summeratanaltitudeuptoabout1200metres.
•Rauwolfiaplantscannottoleratetemperaturebelow5°C.
•Forcultivationrainmustbeenoughandabundantinsummeroritshouldhavegood
irrigation.
•Propagationiscarriedoutbyplantingseeds,root-cultureorstem-cutting.Seed
propagationgivesbetteryieldofrootinspiteofthefactsomeseedsareweakin
germination.

25. Thereforecultivationofrauwolfiaisusuallycarriedoutbyseedpropagation.
Immersingtheminsalineeliminatessterileseeds.
Rauwolfiagrowswellinclays,acidic(pH-4to6)andwell-manuresoil.
Ploughingmustbedeepforfacilitatingthedevelopmentoftheroots.
Sterileseedsarelight,floatandareseparated.Fertileseedssinkandare
utilized.Freshseedsgerminatemoreandpreferablyfreshseedsareused.In
vegetativepropagationespeciallyinroot-cuttings,developmentofrootsis
betterifgrowthhormonesareused.

26. Collection:
They are collected in October-November after hot and dry period.
In Indian Pharmacopoeia collection of roots of 3 to 4 years old plants is
mentioned but in culture it is found that roots of 2 years old plants are
equally good.
For collection of roots plants are dug out, aerial parts are removed and
roots are separated.
Roots are washed and dried in air till moisture is about 10 to 12%. Roots
should be stored protected from light.

28. Microscopical characters (T.S.):
T. S. of the root presents a circular outline with typical stratified
cork and other secondary features. Following are the tissues
seen from the periphery to the center.

29. Periderm:
a.Cork(Phellum):Stratified,consistsofalternatingbands-ofsmaller,
suberizedandun-lignifiedcellupto8to10rawinradialdepth-larger,
suberizedbutlignifiedcellupto5to7rawinradialdepth.
b.Phellogen:Indistinctbutisseenasanarrowlayerofthinwalled
cells,
c.Phelloderm:5to7layers,immediatelybelowthephloem,cellis
arrangedintheradialrowswhereasawayfromphloem,cellisovaland
hasintercullarspaces.Phellodermcontainsabundantstarchgrains
(withtriradiatehilum)andtypicaltwinprismsofcalciumoxalate.

30. Secondaryphloem:
Istransversebyconspicuousmedullaryrays.Phloemconsistsofsieve
tubes,companioncellsandphloemparenchyma.
Starchgrainsandcalciumoxalateprismoccursthroughoutthephloem
tissue.
Secondaryxylem:
Itisalsotransversebywelldevelopmedullaryrays.Xylemconsistsof
vessels,woodfibresandlignifiedparenchyma.

31. Medullaryrays:
Itrunsradiallyfromthecentertothecortexthroughthephloem.Raysinthe
xylemregionarelignified,pittedandare1to5cellswidealthoughuniseriate
raysareprominent.Inthephloemregiontheraycellsarenotlignified.Starch
andtypicaloxalateprismsareinthemedullaryraycells.

32. Chemical constituents:
Alkaloids-Indole alkaloids (1.5 or 3%) present.
Weakly basic Indole type (pH 7 to 7.5)
Reserpine group –Reserpine, Rescinnamine, deserpidine.
Tertiary indoline alkaloids (pH-8). Ajmaline group-Ajmaline and Ajmalicine.
Strongly basic anhydronium bases (pH-11).
Serpentine group –Serpentine, Serpentinine and Alsotonine.

34. Uses:
1.Rauwolfiaisusedashypotensiveandtranquillizer.
2.Reserpinebeingthemainalkaloidisresponsiblefortheactivityand
isusedinanxietyconditionandotherneuropsychoiatricdiseases.
3.Sedative–calmdownactivitiesandexcitement(reserpinegroup).
4.Stimulatesthecentralofperipheralnervoussystems(Ajmaline
group).
5.Thedecoctionofrootisusedtoincreaseuterinecontractionin
difficultcases.
6.Theextractisusedforintestinaldisordersandasanthelminticbitter
tonicandfebrifuge.

35. Belladonna
Synonym-Belladonna leaf
Biologicalsource-
Itconsistofdriedleavesofortheleavesandthearialpartof
theplantAtropabeladona,belongtofamilySolanaceae
Morphological characters-
Color-leaves-green to brownish green
flower-purple to yellowish brown
Fruits-green to brown

36. Odour-slight and characterists
Taste-bitter and acrid
Size-leaves-5 to 25 cm long and 2.5 to 12 cm widw
Shape-leaves are ovate
Chemical const-
The active agents in belladonna,atropine,hyoscine(scopolamine), and
hyoscyamine

37. Uses-
Belladonna has been used inherbal
medicinefor centuries as a pain reliever,
muscle relaxer, and anti-inflammatory, and
to treat menstrual problems, peptic ulcer
disease, histaminic reaction, and motion
sickness

38. Chemical test-
Vitali-Morin reaction-
1.Tropanealkaloidtreatedwithfumingnitricacidfollowedbyevaporation
todrynessandadditionofmethanolicpotassiumhydroxidesolutionto
anacetonesolutionofnitratedresidue.Violetcolorationtakeplace.
Tr.Alk.+FumingNitricacid------Evap.Todry+met.KOH+acetone-----
violetcolouration.
2.Onadditionofsilvernitratetosolutionofhyoscinehydrobromide,
yellowishwhitepptisformed,whichisinsolubleinnitricacid,butsoluble
indil.Ammonia.
Hyoscine+Silvernitrate----------yellowwhiteppt

39. OPIUM
•Synonyms: Raw Opium, Crude Opium
•Biological Source:
Opium is the dried milky latex obtained by
incision fromthe unripe capsules of
Papaver somniferum, belonging to
family Papaveraceae.
Characteristics
Opium occurs in rounded or flattened mass
which is 8–15 cm in diameter and weighing
from 300 g to 2 kg each. The external
surface is pale or chocolate-brown, texture
is uniform and slightly granularand odour is
characteristic; taste is bitter and distinct.

49. •Chemical Constituents
•Opium contains about 19 alkaloids among
which morphine is the most important base.
The alkaloids are combined with meconic acid.
The other alkaloids isolated from the drug are
codeine, narcotine, thebaine. noscapine,
narceine and papaverine.

52. Uses
•Opium and morphine have narcotic,
analgesic and sedative action and used to
relieve pain, diarrhoea dysentery and
cough. Poppy capsules are astringent,
somniferous, soporific, sedative and
narcotic.