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Alkaloids
Definition:
the term alkaloid (alkalilike) is commonly used to designate basic heterocyclic nitrogenous compounds of plant origin that are physiologically active.
Classification:
True(Typical)alkaloids thatarederivedfrom aminoacidsandhavenitrogeninaheterocyclic ring.e.gAtropine Protoalkaloids thatarederivedfromaminoacids anddonothavenitrogeninaheterocyclicring. e.gEphedrine Pseudoalkaloids thatarenotderivedfrom aminoacidsbuthavenitrogeninaheterocyclic ring. e.gCaffeine Falsealkaloids arenonalkaloidsgivefalse positivereactionwithalkaloidalreagents.
Nomenclature: Trivialnames shouldendby"ine".Thesenamesmayrefer to: Thegenus oftheplant,suchasAtropinefromAtropa belladona. Theplantspecies,suchasCocainefromErythroxylon coca. Thecommonname ofthedrug,suchasErgotamine fromergot. Thenameofthediscoverer,suchasPelletierinethat wasdiscoveredbyPelletier. Thephysiologicalaction,suchasEmetinethatactsas emetic,Morphineactsasnarcotic. Aprominentphysicalcharacter,suchasHygrinethatis hygroscopic.
Physical Properties:
I Condition:
Most alkaloidsarecrystallinesolids. Fewalkaloidsareamorphoussolidse.g.emetine. Someare liquids thatareeither: Volatile e.g.nicotineandconiine,or Nonvolatile e.g.pilocarpineandhyoscine.
II Color:
Themajority ofalkaloidsarecolorless butsomeare colored e.g.: Colchicineandberberineareyellow. Canadineisorange. Thesaltsofsanguinarinearecopperred.
III- Isomerization:
Opticallyactiveisomersmayshowdifferentphysiological activities. lephedrineis3.5timesmoreactivethandephedrine. lergotamineis34timesmoreactivethandergotamine. d Tubocurarineismoreactivethanthecorrespondingl form. Quinine(lform)isantimalarialanditsd isomerquinidineis antiarrythmic. Theracemic(opticallyinactive)dlatropineisphysiologically active.
Chemical Properties:
I Nitrogen: PrimaryaminesRNH2e.g.Norephedrine SecondaryaminesR2NHe.g.Ephedrine TertiaryaminesR3Ne.g.Atropine QuaternaryammoniumsaltsR4Ne.gd Tubocurarine II Basicity: R2NH>RNH2 >R3N Saturatedhexacyclicaminesismorebasicthan aromaticamines.
*Alkaloids
Extraction,PurificationandIsolationof AlkaloidsfromPowderedplants
Extractionandpurification
MethodI: The powder is treated with alkalis to liberates the free bases that can then be extracted with water immiscible organic solvents. MethodII: The powdered material is extracted with water or aqueous alcohol containing dilute acid. Alkaloids are extracted as their salts together with accompanying soluble impurities. Method III: The powder is extracted with water soluble organic solvents such as MeOH or EtOH which are good solvents for both salts and free bases.
Liberationofthefreebases:
Alkalis are used to liberate free bases. Alkalis must be strong enough to liberate free bases. However, choice of strong alkalis must be avoided in some cases: 1 EsterAlkaloidse.g.SolanaceousAlkaloids 2 AmideAlkaloidse.g.Colchicine 3 PhenolicAlkaloidse.g.Morphine 4 LactoneAlkaloidse.g.Pilocarpine 5 FattyDrugsduetosaponificationandemulsionformation.
Preparation of Derivatives:
SeparationofPrimary,SecondaryandTertiaryAlkaloids.
O
Mixture + p-toluenesulphonyl chloride
Add HCl and filter
Cl
S O
Filtrate tertiary alkaloids as salt (no reaction with reagent 1ry alk derivative
O R-HN S O acidic hydrogen OH R-N S O
NaOH, filter
FractionalLiberation:
FractionalDistillation: e.g.SeparationofNicotineandAnabasine
ChromatographicSeparation.
Phenylalkylamines:
e.g.Ephedrine
CH2 CH NH2 CH3
Pyridineandpiperidine
e.g.lobeline,nicotine
N H
Tropane
e.g.Atropine.
NCH3 OH
Quinoline
e.g.quinine and quinidine
Isoquinoline
e.g. papaverine
Phenantheren
e.g. Morphine
Indole
e.g.ergometrine
N H
Imidazole
e.g. pilocarpine
Purine
e.g. caffeine
1 N 2
6 5
7 N
8 N 4 3 Purine N 9
Steroidal
e.g. Solanum and alkaloids Veratrum
Terpenoid
e.g. Taxol
Introduction: Asthemolecularstructureofalkaloidsisquite complex,verylittleprogresswasachievedinthe elucidationoftheirstructuresduring19th century. Butnowthenew methods fortheidentificationof unknownsubstancesareknown. Thefollowingpatternofprocedureisadoptedto establishthemolecularstructureofanalkaloid:
Forexample,thedifferencebetweenhexene (C6H12)
fromhexane (C6H14)istwohydrogen'sandthisdifferenceis calledadoublebondequivalent. Similarly,thedifferencebetweenbenzene (C6H6)and hexane (C6H14)iseighthydrogenswhichwillcorrespondto 8/2or4doublebondequivalents(accommodatedbythe threedoublebondsandonering). Theaboveprocedureisvalidforsimplercompoundsonly. However,forcomplexformulae,whereelementsotherthan hydrogenandcarbonarepresent,thesimplermethodis thatforanyformulaCaHbNcOd thenumberofdoublebond equivalentsisgivenbythefollowingexpression: a 1/2b+1/2c+1
Theabovemethodforthecalculationofdouble
bondequivalentsisusefultocalculatethenumberof ringsinagivencompound.Forexample,hygrine has themolecularformula,C8H15NOwhichcorrespondsto 8 15/2++1=2 doublebondequivalents.However,chemicaltests revealthathygrine containsonlyonecarbonylgroup (onedoublebondequivalent)anddoesnotshowother formofunsaturation.Thushygrine mustbemonocyclic toaccountfortheotherdoublebondequivalent. Thepresenceofunsaturation inanalkaloidmayalso beascertainedbytreatingthealkaloidwithbromine or halogen acid oralkalinepotassiumpermanganate whenaglycol isobtained
2) Functional Group Analysis: Applicationofclassicaltechniquesoforganic analysis(especiallyifthealkaloidisavailablein appreciableamounts)and/orinfraredexamination (especiallyifthealkaloidisavailableonlyinsmall amounts)canrevealthenatureofthefunctional groupspresent. Thiswillalsorevealthearomatic oraliphatic natureofthealkaloidandtheunsaturation,if present.