Alkaloids: Definition amd Occurence ‘WAlkaloids (Alkali-like) Definition: Ocuurence: Basic ntogenous compounds, of plant origin have a marked (GA) At the level of kingdom physiological action on man or other animals, Nitrogen may be ‘ssn choice” (SSS RHR Major source of alkaloids. Deviation rom dfn: dso Basicity Lp aiealaar a) Dicotyledons families (major source) Sr Ct, prs yall 7 re Cane Fon eum” Nitrogen: The nitrogen in some alkaloids is notin a heterocyclic ing alata mene a hceee he eure Seung nos ‘are: Pap, amma kee al pe ‘eg. Ephedrine, Colchicine Mescaline Caines ‘amaryl nintr Sentech ic, es ” Ex, Rosaceae and Lamiaceae"Lablatae” Coes a ‘ise on inal oma of plat Darn) Ravinfomspremn Aiea of me Ose tomas goa ee no ons eoutin dem | Baer es Fe ‘Bs: Coto, Pmeponte (Cpt neni 3 ta: ont ed pep cron 3} Cnn Bl oer tote nie Scr ce it ten Somes Stans te Zoom Rar pres xn hd (6) Rhizomes and roots: /pecacuanha and oc alkaloids 7) Pericarp of fut opium alkaloid In some cases, there are also Fluctuation of alkaloids content in ‘various organs during the growing seasons or between day and nightte of formation and Storage ‘Some organs ofthe plant posses the function of forming alkaloids, which may be Stored in the same organ or translocated and stored in another organ Examples: [BNicotiana tabacum: Alkaloids are formed inthe root then translocated tothe leaves, ‘where they are accumulate and sored. B Papaver sommiferim: Alkaloids occur in the latex ofthe pericarp of he frit, while the seeds are fre Fim alkaloids, [WCinchona species: The alkaloids accumulate in the bark Nomenclature Forms of loids 1B Trivial names of alkaloids should terminate with the sufix ine". Aiajoids are base in teacton, due tothe prescence of nitrogen in the molecule They may exist as: |B Name may be derived from the following Genus name : eg arypine from atop. otal Species name (specifi epithe): eg. Cocaine from coca. Form salts with various acids: ‘Common name ofthe plant itself. © g.Ergoiamine from ergot. Physiological activity of the alkaloid itself imezne from Emesis. sme: eg Plletierin from pellet. 3 structure following IUPAC Organic acids eg, Oxalic, Acetic acids Salis with inorganic acids eg, HCL, H2SOS, Salts with special acids: eg. Meconie acid in opium, Quinic aed in cinchona © ASN-Oxide © Glycosidal form eg. Solanin in sotanum,Alkaloids: physical & Chemical Characters Physical Characters of alkaloids Er 1 = | onatee Peaeee eee aes ee liquids are either Betanine(red) Volatile e , nicotine and comine Non- Volatile eg, Pilocarpine and hyoscine. Decompose by heat but leaving Alkaloid free base: few sublimewithout decomposition soluble in organic solvents, | EXCEPTIONS. eg, cafe. Insoluble in water Some Pseudo- and proto-atkalods {fee bases) are soluble in water, e. cafene, Reaction with acids “ephedrine, codeine, Cofchicne,Pilocarpine and Onaternary ammonium bases 1- Salt fromation Alaoida sl: Alkaloids salts ex. Lobelin indrochlo le in chloroform) 2- Dilute acids hydrolyze eer ible in water, Some alkaloidal salts are sparingly soluble in water eg. Quinine sulphate alkaloid eg. atropine insl in organic solvent ‘Chemical Characters of alkaloids I. Nitrogen and Basi a ‘They are present in Alkaloids contain one or more Nitrogen atoms (1) Usually tertiary amine form (R,N) eg. Atropine in the molecule most commonly in heterocyclic ring (2) Less often in the secondary form (R,NH) e.g, Fphedrine. OR BG) Rarely in the primary form (RNH,) c.g. Norephedrine. Iman Aliphatic chain: eg, Ephedrine and colchicine, jy (4) Some alkaloids are in the Quaternary ammonium form [(R eg Tubocurarine chlorideAlkaloids: chemical Characters of alkaloids Basicity: R,-NH > R-NH,> R,-N Alkaloids are moiily basic, degree of basic strength depends on the availability of lone pair of Electrons on nitrogen presence of EWG adjacent to nitrogen Presence of EDGs adjacent to nitrogen eg NO2, CN, SOSH, CHO, COR, COOH, eg. Alkyl gr, Amines (NH2, NHR, NR2), COOR, CONII2,CF3, CCB, Halogens Phenol (OH), Alkoxy, amide, eer groups Decreases the availabilty of electrons Increases availablity of electrons AF less basic} Neutral eg. Colchicine PMore basic eg ephedrine Even acid According to basicity, Alkaloids are classified into: Weak bases: Caffeine, Strong bases: Atropine , Neutral alkaloids: Colchicine. which is more basic / less acidic ? Taal aaa eee ee “im Activity Yio bic siceck 5 ae cosine Ephedtine is move basic due tothe presence of Electron donating group “CH,” ‘soup inthis case, which increases availabilty of electrons hence ineeases basic F Colchicine is less basic (in fact neutral) due othe presence of Electron ‘withdrawing group “OCH,” group which decreases availability of electrons hence decreases bast—— Alkaloids : chemical chrcters gf Precepating reagents 1. Alkaloid preciptating reagents & Alkaloids Coloring Agents: Alkaloids ean usually produce Amorphous or ryalline precipitates with certain reagents (Alkaloid ppt reagents). ‘B Certain colors with others (Alkaloid color reagen) (AP) atiatia preciptating rengents weight metals such as Hg, or, Reagent + Alkaloid > Ppt (Peta marcudetodde) (Aquos oition of nk) (Potassium bismuth odie) (potassium cadmium odie) Ges wit precgtates with ll Gres ron flocs pot wih Ges Ogee tin | Tannicacid reagent | tales except purine bares, al ili Prepared fom math nite Colehine ad rein. aoc pots idea ite Prepared fom Hg + Kin wate ic acd ‘Both Gold chloride and platinie chloride produce eralline ppt with definite shapes, ‘Which can Identify and differentiate chemically related alkaloid, e.g. Hyoscyamine, Hyoscine and atropineAlkaloids : chemical Cha ¥ General color reagents 1B Mandalin's reagent 1B Erdmann's reagent sulfuric acid containing a trace of nitric acid acid containing vanadie acid or ammonium vanadate sulphui 1B Frochd’s reagent |B Marquis reagent sulphuric acid containing molybdie acid or ammonium molybdate sulphuric acid containing formaldehyde 4 Special color reagents or reactions ‘Thaleoquin reaciton Murexide reaction _Vitali-Morin reagent __Acedified cerric ammonium sulphate for cinchona alkaloids for purine bases for ropane alkaloids. for indole alkaloids Yellow or orange-red color Erlich’s reagent (Acidified p-dimethylaminobenzaldehyde) for ergot alkaloids blue or grey-green color Nore Genel color reagents shouldbe added to the solid alkaloid in a lean porcelain evaporating dish ‘They may al produce certain colors with other constituents such as some Bitar principle and sme glycosides.Alkaloids : Classification of Alkaloids According to name ofthe family 7 Ex: Solanaceous alkaloids. Papaveraceous alkaloids. et ‘According to name ofthe genus Ex. : Cinchona alkaloids. Ipeca alkaloids, Ephedra alkaloids. et 1, Pharmacological ‘Action classification 1) CNS stimulants: strychnine, caffeine. 2) Narcotics and analgesics: morphine, codeine. 3) Mydriatics: amopine. 4) Mioties: pilocarpine, serine. 5) Expeetorants: Jobeline. 6) Anti-asthmaties: ephedrine, 7), Antitussive: codeine. 8) Skeletal muscle relaxants: d-tubocurarine. 9) Smooth muscles relaxants : papaverine. 10) Antiparasites: quinine, emetine. 11) Anthelmintie: pelleteirine, 12 Anticancer: Vincristine, Vinblastine, taxol. 13) Hypotensive: reserpine. Nitrogen atom in alkaloids originate from an amino acid. ‘The carbon skeleton ofthe amino-acid precursor is also largely fetaind inthe alkaloid rueture ‘The subdivision is based on the amino acid precursor used Few amino acid precursors are inolved in alkaloid biosynthesis (Ornithine, line, wosinc, ryptophan and histidine). Inadditon, other well known nitrozen containing organic acids, (Nicotinic acid and anthranilic acid), Therefore alkaloids may he clasiied according tothe amino acid used the plant in ther biosythesis: EL Alkaloids derived from Ornithine aa Simple pyrroidine:Hygrine(Coca), Nicotine. ‘Tropane alkaloids: Hyoseyamine(Hyoseyarms),cocaine/Coea) wow in —>O Bi Alkaloids derived from Aspartic acid vin nicotinic acid (aromatic) b v Pyridines: Nicotine (Nicotiana), Trigoneline( Trigonella), 9 Ricinine (Ricinus communis). Oo we 0-98 Neninini Aur n Nanaia)—— Alkaloids : biosynthetic classification 6 : GeO asaet inion * NH Alkaloids derived from Tyrosine Alkaloids derived from Zjyosine and phenyl alanine Tsoquinolines nucleas: morphine Codeine, Thebaine,Papverine “Modified phenglethylisoquinoline: Colchicine (Colchicum) Naseapine, Narceine, Fmetine, Cephaline Modified benzyltetrahydro-isoquinoline: morphine als (apa somnieram) | iL pene 1 Allis erted rom Tptphen CO enteaac Si tin: mine eon hay) moma wc Ny ya Ergoline "Terpencid indole": Ezgometrine (Cavceps) iw chenpaese “ony Paymaigna ont rc ‘Complex terpenoid indole: Reserpine (Rawlfa) Toephn + nontepse10C ZTapeten ee) Cchons ata a ee ae So cela, Quintin: Quiin(Cinchona) TB CO > 3 riwarnne ao at Y Quinozotine: Peganine/Pegamum) nen s+ Ate Histidine ImidazoleAlkaloids : source ofnitrogen + ret of alii Nitrogen atom or atoms originate from 2 or 3 sources: ’ Source of nitrogen and the rest of ae " , | 1) Mainly om amino the alkaloidal molecule 2) or containing organ acids nico acid, athranilc acid) 3) or Some alkaloids acquire nitrogen through transaminaton reactions. ‘The rest may originate from: Example . tpptenhen and its decarbaxyleted product; tryptamine, 1) Carbon skeleton of the particular amino-acid precursor. ‘sve rise othe indole elas of alkaloids 2) May be derived from other metabolic pathways such as + Mevalonic acid pathway (terpenes including Seroids) + Acetate or acrate-malonate pathway (polyketides) + Shikimic acid (pheny propane) pathways Remember pharmacological classification of alkaloids? Spatial considerations and pharmacological activity Most alkaloids must bind or interact with receptor sites and reactive sites of enzymes which have chareteristic surface Structural features, thus, Stereochemistry becomes important in understanding drug activity and in rationally desighing new agents Drug molecules that exis as optical isomers "=" —s do not fit the same receptor site and hence“ 5 isomers + Contatonl suc) 40-HOt have the same therapeutic properties x ss a ‘One may be useful while the other may be either eee ree hamnless (ibuprofen) or could have other properties Distewamers rations such as annoying or even dangerous side-effects cistansizomers— Conformers setctaemme eine Rotamers Lem waste AipsomersAlkaloids : Classitieation according to Nios Classification according to type of nitrogen and its biological or ©) rmeasase EB) maestro ats Derived from aminoacid [Nitrogen in heterocyclic Derived from aminoacid Nis NOT in heteoscyclic [NOT Derived from aa [Nitrogen in heteroeyelic ring ing ring Almost basie Basic weakly basie Ex. Meconic acid, Ex Ephedrine, Colchicine Ex. Caffeine uinic acd ete NOT: Tre Aas crn plan ete nd show we ragechphyslogactivty A) Non-Heterocycli alkaloids (protoalhaot) 1) Phenylalkylamine alkaloids I 1B Phenylpropylamine: Ephedrine, psudo-ephedrine, Cathie, __rewpentmne 1B Phenylethylamine: Narceine (opium alaloids) 1B Phenyimethylaine: Capsaicin 2) Diterpene pseudo-aalods: fax! 3) Tropoloe group: Colchicine vl 4 Serial atkaoid tne “ 5) Aminoglycosides: Actinomscins, Taracyelines, Srepromycin, BPyni \e Group: 1) Pyrolidine:Hygvine, 2) Pyridine: Tigoneline 4) Piperidine:Lobeline (Lobelia). 5) Pyridone: Recinine BW Tropane group: Solanaccous, Coca alkaloids NOTE: Tropa mick = Prone + Prine 3) Tetrahydropyridine: Arecoline (Areca) and ma chem 28S Classification according to main chemical nucleus 1) Heterocyclic alkaloids 1) Pyridine group 2) Tropane group 3) Quinoline groups 4)Iso-quiotine group 5) Terpenoid alkaloid 6) Phenanthrene alkaloid of Opium 7) Purine group 8) Imidazole 9) Indole group Bis Structures J eo 9 99 ee hie