Alkaloids

PharmacognosyII

•  Asignificantcontribu/ontothechemistryofalkaloidsintheearlyyearsofitsdevelopmentwasmadebytheFrenchresearchersPierreJosephPelle/erandJosephBienaimeCaventou,whodiscoveredquinine(1820)andstrychnine(1818).

•  Severalotheralkaloidswerediscoveredaroundthat/me,includingxanthine(1817),atropine(1819),caffeine(1820),coniine(1827),nico/ne(1828),andcocaine(1860).

Distribu/onandoccurrence

•  Rareinlowerplants.•  DicotsaremorerichinalkaloidsthanMonocots.

•  FamiliesrichinAlkaloids:Apocynaceae,Rubiaceae,SolanaceaeandPapaveracea.

•  FamiliesfreefromAlkaloids:Rosaceae,Labiatae

Distribu/oninPlant

•  AllPartse.g.Datura.•  Barkse.g.Cinchona•  Seedse.g.Nuxvomica•  Fruitse.g.Blackpepper•  Latexe.g.OpiumLeavese.g.Tobacco

PhysicalProper/es•  I-Condi/on:•  Mostalkaloidsarecrystallinesolids.•  Fewalkaloidsareamorphoussolidse.g.eme:ne.•  Someareliquidsthatareeither:•  Vola/lee.g.nico:neandconiine,orNon-vola/lee.g.

pilocarpineandhyoscine.•  II-Color:•  Themajorityofalkaloidsarecolorlessbutsomeare

colorede.g.:•  Colchicineandberberineareyellow.•  Canadineisorange.•  Thesaltsofsanguinarinearecopper-red.

PhysicalProper/es•  III-Solubility:•  Bothalkaloidalbasesandtheirsaltsaresolubleinalcohol.•  Generally,thebasesaresolubleinorganicsolventsand

insolubleinwater•  Excep/ons:

Basessolubleinwater:caffeine,ephedrine,codeine,•  colchicine,pilocarpineandquaternaryammoniumbases.•  Basesinsolubleorsparinglysolubleincertainorganic

solvents:morphineinether,theobromineandtheophyllineinbenzene.

•  Saltsareusuallysolubleinwaterand,insolubleorsparinglysolubleinorganicsolvents.

ChemicalProper/es

1-Nitrogen:•  Primaryamines(R-NH2)e.g.Norephedrine•  Secondaryamines(R2-NH)e.g.Ephedrine•  Ter/aryamines(R3-N)e.g.Atropine2-Basicity:R2-NH > R-NH2 > R3-N

•  AccordingtobasicityAlkaloidsareclassifiedinto:

•  Weakbases:e.g.Caffeine•  Strongbases:e.g.Atropine•  Neutralalkaloids:e.g.Colchicine

3-Oxygen:•  MostalkaloidscontainOxygenandaresolidinnaturee.g.Atropine.SomealkaloidsarefreefromOxygenandaremostlyliquidse.g.

•  Nico/ne,Coniine.4-Stability:•  Effectofheat:Alkaloidsaredecomposedbyheat,exceptStrychnineandcaffeine.

•  Reac/onwithacids:1-Saltforma/on.2-DiluteacidshydrolyzeEsterAlkaloidse.g.Atropine

Classifica:onofAlkaloids

N

N

NNH

NH

N

NH

MeN

Tropane

NH

N

N N

NH

Piperidine Pyridine Pyrrolidine Quinoline

Isoquinoline PurineImidazoleIndole

NH

Tetrahydro-isoquinoline

Classification of alkaloids depending on chemical structure

1)  derivatives of pyrrolidine (sthrahidrine, turicine) 2)  derivatives of tropane (atropine, cocaine) 3)  derivatives of pyperidine (lobeline, coniine) 4)  derivatives of pyridine (nicotine, anabasine) 5)  derivatives of pyrrolysidine (platyphylline) 6)  derivatives of quinolysidine (pahicarpine, lupinine) 7)  derivatives of quinoline (quinine) 8)  derivatives of isoquinoline (papaverine, morphine) 9)  derivatives of indol (reserpine, strychnine) 10)  derivatives of purine (caffeine, theobromine,

theophylline)

11)  derivatives of the different heterocycles (imidazol (pilocarpine), thiazol (agroheline), quinazoline (luotoline А), acridine (rutacridone), azenine (galantamine));

12) polypeptide alkaloids (13-, 14-, і 15-member) (buckthorn alkaloids);

13) alkaloids with exocyclic nitrogen atom (ephedrine, muscarine, spherophysine);

14)  terpenoid alkaloids (acronicyne, actinidine); 15)  steroid alkaloids (solasodine, cholophyllamine).

Dependingonbiosynthesispathways

•  (according to the substances from which they are obtained):

a)  true alkaloids (1-12 group) – which is synthezed from aminoacids and heterocycles are the base of their structure;

b)  protoalkaloids (13 group) – do not include heterocycles, also are the plant amines and formed from aminoacids;

c)  pseudoalkaloids (14, 15 group) – obtained by others ways different from aminoacids.

Methods of extraction from plant materials

•  extraction in the form of salts (water, alcohol, tartaric acid);

•  extraction in the form of basis (NH4OH, NaHCO3);

•  Distillation of alkaloids bases with aqueous steam (boiling point for which is less than 100 º C).

Extraction as salts: to raw material add water or ethanol with few drops of tartaric acid. All alkaloids forms salts with tartaric acid. For purification to this extract add base and all alkaloids form bases, which obtained by organic solutions. Operation of purification repeat few times. Then solvent separated from alkaloids. Sum of alkaloids is separated on individual compounds.

Extraction as bases: to raw material add alkali solution (ammonium, sodium hydrocarbonate or carbonate). Alkaloids bases are extracted by organic solutions. Purification realize by transferring alkaloids to salts and then to bases. Operation of purification repeat few times.

Themethodsofsepara/onoftheselectedamountofalkaloids:

•  Fractional distillation in vacuum; •  By the different solubility of alkaloids –

salts and bases; •  By the different power of basic properties of

alkaloids; •  based on the features of chemical properties; •  By the different ability to adsorption

(chromatography); •  Method of anticurrent separation.

 For identification of alkaloids use general, group and specific reaction.  The general reactions conduct with common alkaloid precipitation and special reagents.  General precipitate reactions based on the ability of alkaloids as bases to give simple or complex salt with different, more often complex acids, salts of heavy metals and others. These products are usually not soluble in water, so called precipitate.

Methodsofthequan/ta/vedetermina/onofalkaloids:

•  Acid-base titration in nonaqueous environment – for the quantitative determination of both salts and bases.

•  Acid-base titration: а) acid-base titration, direct titration of acids and bases; b) acid-base back-titration for determination of bases by reverse

titration; c) Alkalimetry – titration of alkaloids salts by alkali in water-

alcohol medium in the presence of phenolphthalein (with or without the usage of organic solvent that does not move with water for extraction of alkaloid bases)

d) Alkalimetry by the substituent •  Gravimetric method •  Methods based on individual chemical properties of

alkaloids. •  Physico-chemical methods.