Group 1 3DPH Amican, Aegan Matthew Ares, Karen Gem Ballester, Ruvie Ann Barcelona, Mark Joseph Calleja

, Katherine Carmen Isabel Capuno, Christelle Venus

ALKALOIDS I. Characteristics and Properties These are the organic product of natural and synthetic origin which are basic in nature and contain one or more than one nitrogen compound normally in heterocyclic in nature, and posses specific physiological action on human and animal body, when use in small quantities A. Physical Property    Color - In general, Alkaloids are colorless but some may be colored. Physical Form - Most are crystalline solids - Few are amorphous Solubility Free alkaloid bases are invariably found to be fairly soluble in organic solvents, such as: either, chloroform, relatively non-polar solvents (hexane, benzene, petroleum ether), immiscible solvent, lower alcohols (methanol, ethanol); but they are either practically insoluble or very sparingly soluble in water.

Alkaloidal salts are almost freely soluble in water, relatively less soluble in alcohol and mostly either insoluble or sparingly soluble in organic solvents: Examples Atropine sulphate and morphine hydrochloride are much more soluble in water than their corresponding bases i.e., atropine and morphine.

There are a few exceptions to the above stated generalizations, namely: (i) Certain alkaloid bases are water soluble, but these may be solely regarded as exceptions rather than any specific rule, such as: ephedrine, colchicine, pilocarpine;the quaternary alkaloid-base like berberine and tubocurarine; caffeine-base readily extracted from tea with water. Narceine and pilocarpine are insoluble in organic solvents, whereas morphine is sparingly soluble in organic solvents viz., solubility in either 1:5000.

(ii)

g... quinine. Some alkaloidal salts are sparingly soluble in water whereas others are extremely watersoluble. such as: Quinine sulphate-soluble in 1:1000 parts of water.g. ephedrine. cocaine.(iii) (iv) Certain alkaloidal salts.vinblastinean d yohimbine . .. reserpine.... for instance: lobeline hydrochloride and apoatropine hydrochloride are found to be soluble in organic solvent like chloroform.g. ephedrine.morphine.The number of N-atoms vary from the bear minimum one in a molecule e. Quinine hydrochloride soluble in 1:1 part of water.g.whereas there are certain alkaloids that contain the N-atom in the aliphatic side chain o e.strychnine. mescaline.  lesser in the secondary-amine form (R2NH o e.reserpine.N-atom in the  tertiary-amine form (R3N) o e.g. to even five in a molecule e.ergotamine. .these N-atoms are normally present as a part of the heterocyclic ring in the alkaloid molecule  e. B.  and very rarely in the primary-amine form (RNH2) . Chemical Property  N-in the Molecule .g.

Furthermore. namely:  N-atom does not possess a H-atom. Classification  Chemical Classification This is a most accepted way of classification of alkaloids.- - o e.. the N-atom occurs in the quaternary ammonium form (R4N+ . nor-pseudo-ephedrine. and  Chemical properties are quite different. vinblastine. the tertiary N-atoms wherein only two of the bonds are involved in a ring.. In some very specific cases. for instance: N-methyl group in morphine. with a few exceptions where the oxygenated alkaloids usually occur as non-volatile liquids. dextro methorphan. whether the N-atom is located in the ring or in the sidechain. tert-. Hence.  O-in the Molecule Invariably. the quaternary ammonium compounds are logically and technically not regarded as alkaloids by virtue of the following two particular reasons. it essentially constitutes as an integral part of the ringsystem. or quaternary N-atom or atoms in it. Another vital factor. vindesine etc. o o True alkaloids(heterocyclic alkaloids) are divided into twelve group according to the nature of their heterocyclic ring Protoalkaloids or biological amine and pseudoalkaloids . They are eventually reflected by the different dissociation constant values (i.. by virtue of the presence of N-atom present in the molecule. sec-. methyl) to the N-atom etc.g.  Degree of Basicity: mostly depends upon the prevailing influence caused due to the electrostatic status of the N-atom present in the alkaloid molecule. these are prone to the formation of their respective salts with various acids.  Basicity (Alkalinity) In general. for instance. Hence. precisely the heterocyclic ring system. The alkaloidal drugs are broadly categorized into two divisions.e.. is the presence of pri-. codeine. methyl moiety seems to be the only alkyl group that has been found to be substituted on the N-atom. the number of Natom present in the alkaloid. these specific alkaloids are found in the solid state. The main criterion for chemical classification is the type of fundamental(normally heterocyclic) ring structure present in alkaloids. Noticeably. such as: pilocarpine. X–) e. pKa values) with regard to various alkaloids II. cocaine. physostigmine. the alkaloids are basic (alkaline) in reaction. the methyl moiety is usually found as the third component. colchicine. tubocurarine chloride Nevertheless. whenever N-atom occurs either in the tertiaryor secondary-form.g. the presence of alkyl group (e.g.

harmaline. serotonin Ergolines: the ergot alkaloids (ergine.. based on the metabolic pathway used to construct the molecule. even some non-nitrogenous ones (since those molecules' structures appear in the finished product. Do not have chemical similarity in their group. For example: 1. the opium alkaloids are sometimes called "phenanthrenes". theobromine. Isopapa-dimethoxy-aniline. they were grouped under the names of known compounds. When not much was known about the biosynthesis of alkaloids.nicotine Tropane group: atropine. ecgonine.guvacine. cevadine Isoquinoline group: The opium alkaloids (morphine. strychnine. When more is learned about a certain alkaloid. berberine). narceine. catuabine Quinoline group: quinine. emetine.brucine.g. Pharmacological based: Their pharmacological activity or response. amphetamine Indole group: Tryptamines: DMT. all indole alkaloids from tryptophan are grouped together. quinidine. sparteine. the grouping is changed to reflect the new knowledge.arecaidine. berbamine. thebaine. or by the plants or animals they were isolated from. Cardio active alkaloids etc.oxyacanthin Phenethylamine group: mescaline. theophylline Terpenoid group: o Aconite alkaloids: aconitine o o o o . scopolamine. Analgesic alkaloids 2. phenylalanine.g.Papilionaceous without reference their chemical type of alkaloids present & another according to genus. dihydroquinidine. The alkaloidal drugs are catagorised on the fact whether are derived from amino acid procedure as ornithine. lysine. reserpine o Rauwolfia alkaloids: Reserpine Purine group: o Xanthines: caffeine. papaverine.pilocarpine. lysergic acid. tyrosine. dihydroquinine. for example).  Taxonomic Based in their Family e.According to this alkaloids are usually classified by their common molecular precursors. LSD etc. dopamine. ephedrine.pelletierine Pyrrolidine group: hygrine. sanguinarine. ephedra. ergotamine.trigonelline. Biosynthetic Classification This method gives significance to the precious from which the alkaloids are biosynthesized in the plant. o Beta-carbolines: harmine.g. usually taking the name of a biologically-important amine that stands out in the synthesis process. cinchona etc. N-methyltryptamine. veratrine.cytisine. hydrastine. Hence. cocaine. psilocybin. the varity of alkaloids with different taxonomic distribution and physiological activities can be brought under same group if they are derived from same procedure.cuscohygrine. tryptophen. yohimbine. narcotine. etc. E. o o o o o o o Pyridine group: piperine. codeine.coniine. e.nicotine. Solanaceous.

vincristine. Further divided into 14 groups based on ring structure containing nitrogen Heterocycle Example . choline. Structures 1. Miscellaneous: capsaicin. Heterocyclic Alkaloids or Typical Alkaloids . neurine Vinca alkaloids: vinblastine. Classifications of Alkaloids based on presence of nitrogen atom in a heterocyclic ring system 1. cynarin. They are antineoplastic and binds free tubulin dimers thereby disrupting balance between microtuble polymerization and delpolymerization resulting in arrest of cells in metaphase.o o Steroids: solanine. Show great diverse structure and origins as well as pharmacological actions 3. phytolaccotoxin o III. samandaris (quaternary ammonium compounds): muscarine. Non Heterocyclic Alkaloids or Atypical Alkaloids/ Proto-alkaloids . Are basic nitrogen containing compounds 2. phytolaccine.These have nitrogen as part of a cyclic ring system. The only common factor found is the presence of the Nitrogen atom R’ RNH CH CH2 R” Alkaloids are a group of nitrogen. while the majority of them are produced from amino acids .containing bases.These molecules have nitrogen atoms which are not a part of any ring system Examples : Ephedrine: Colchicine: 2. But few of them are derived from purines or pyrimidines.

Pyrrolizidine Tropane (Piperidine/ N-methyl-pyrrolidine) Quinoline Isoquinoline .

Aporphine(reduced isoquinoline/naphthalene) Quinolizidine Indole or Benzopyrole Indozolidine Imidazole or glyoxaline .

Purine (pyrimidine/imidazole) Steroidal (some combined as glycosides) Terpenoid IV. hence they are used as sedatives.Opium. which is extracted from the latex of the capsule of the poppy is the main ingredient of some sleeping pills . theobromine. .Scopolamine of henbane (Hyoscamus niger) have a calming role.Exert a stimulation role in the CNS (Caffeine.Aconitine.Strychnine causes violent and painful spasms . Those that most affect us are: 1. . strychnine) that in very small doses can be convulsive. Uses Some alkaloids focus their range in a particular part of the body. Nervous sytem . initially stimulating but later can be paralyzing .

scopolamine from henbane leaf. Circulatory sytem .Digitalis acts on the heart muscle 2.Sparteine is used to increase metabolism and encourage the elimination of fluids in people with obesity 4. . Narcotics. Psychotropicsn. sedatives. altering perception a. lemon V.Resperine from (Rowulfa vomitoria) is used to lower blood pressure . to dilate .distorted illusion of reality -mescaline from peyote (Lophophora williamsii) -canabine from cannabis (Cannabis sativa) . 5.Among these are castor oil plant (Ricinus communis) that contain alkaloid ricinine which has been used as a purgative but extremely dangerous because a couple of chewed seeds can be fatal to a child. morphine from the latex of poppy (Papaver somniferum – main ingredient of sleeping pills) o Initially stimulating but paralyzing . Digestive System . Hallucinogens. tea. o Calming role..caffeine is present in coffee. 3.aconitine from the root of aconite ( Aconitum carmichaelii) o In muscles(pupil).scopolamine of henbane (Hyoscyamus Niger) .Eserin from calabar bean is used to contract the pupils of the eyes . Example of Plants a) Nervous system: o Stimulating role in CNS.harmaline from Syrian rue (Paganum harmala) . cacao. Respiratory system -scoparin contained in the flowers of common broom (Cytisis scoparuis) hass been used to combat respiratory diseases -ephedrine has been used as a decongestant as a treatment for bronchial asthma and has been later banned by the FDA because it possesses stimulant properties.cocaine is extracted form coca leaves (Erythroxylon coca) -nicotine is obtained from tobacco (Nicotiana tobacum) -solanaceae is an addictive stimulant and a dangerous poison even in low doses .induces a dreamy state -Opium -Morphine -Codeine c.affects the mind. theobromine (cacao) or strychnine(nux vomica).ergotoxine from ergot (Claviceps purpurea) -muscarine from mushroom amanita (Amanina muscarina) b. foliage. Stimulants-state of euphoria and well being . orange tree.caffeine (coffee and especially tea).Some are very toxic to the digestive system causing violent irritation to the gastric mucosa with typical manifestations such as diarrhea and vomiting. root and seed (Hyoscyamus Niger).Scopolamine is responsible for mydriasis or dilation of the pupil .

the alkaloidal salts are readily converted to the corresponding alkaloid bases. such as: seeds. such as oxalates and tannates. harmaline from Syrian rue (Peganum harmala). Liberation of Free Alkaloidal Base Alkaloids invariably occur as the salt of acids. foliage.b) c) d) e) Contracts muscles – eserine from calabar bean (Physostigma venenosum) – in pupil. Sample Preparation The plant material is reduced to a moderately coarse powder using grinders and sieves. colchicines of autumn crocus (Colchicum autumnale). Extraction Procedure 1. these non-alkaloidal chemical components need to be eliminated completely by extraction with a suitable non-polar solvent like n-hexane. NaOH or KOH should be avoided as far as possible by virtue of the fact that certain alkaloids undergo hydrolysis on prolonged contact with a strong base. when the plant substance is exposed to an alkaline medium. metabolism and elimination of fluids in people with obesity Respiratory System: o Dilating bronchial tubes – scoparin in the flowers of common broom (Cytisis scoparius). cannabine from cannabis ( Cannabis sativa). muscarine from mushroom Amanita ( Amanina muscarina) o Narcotics – morphine produced from opium extracted the latex of the poppy (Papaver somniferum).cocaine from coca leaves (Erythroxylon coca). sparteine of common broom Branch ends. which would not extract the alkaloids in question. In the case of plant substances that are rich in oils and fats. Leaf. the corresponding salt of a weakly basic alkaloid and a relatively weak organic acid shall require a rather weaker base for its cleavage. . Seed (Cytisis scoparius) has opposite effect useful to inc.the salt of a strongly basic alkaloid with a mineral acid usually tends to undergo cleavage under the influences of a stronger base. ergotoxine from ergot (Claviceps purpurea). (b) Chemical characteristics of the alkaloidal base: The usage of strong alkali e. digitalis (Digitalis sp) – on the heart Digestive system: o Poisonous – ricine in seeds of castor oil plant (Ricinus communis). Likewise. 2.. light petroleum ether. nicotine from tobacco leaf and foliage (Nicotiana tabacum) o VI. Therefore. cynoglossine from heliotrope (Heliotropium europaeum) Circulatory System: o Circulatory vessels – reserpine from Rauwolfia vomitoria ( lowers blood pressure). ephedrine from different species of the genus Ephedra (FDA in USA banned) Psychotropics: o Hallucinogens – strong poisonous drugs: mescaline from peyote (Lophophora williamsii). in a soxhlet apparatus.g. Factors Affecting the Choice of Alkali to be Used (a) Natural state of the alkaloids. to facilitate maximum effective contact of the solvent with the ruptured alkaloid bearing tissues and cells. codeine and heroin are derived from it(morphine) o Stimulants. kernels.

Fractionation of Crude Alkaloids (a) Fractional crystallization (b) Fractional distillation (c) Derivatization with low solubility products Latest methods employed: High performance liquid chromatography (HPLC)\ High performance thin-layer chromatography (HPTLC) Chromatotron Counter-current distribution Column chromatography Ion-exchange chromatography Methods of Extraction (a) Soxhlet Extraction Process -generally suitable for the extraction of alkaloids from powdered plant materials with the help of organic solvents -the powdered drug is usually moistened with dilute ammonia solution and then packed loosely in the thimble of the Soxhlet apparatus.partition. Purification of Alkaloidal Extract (a) Extraction with Acid Solution-dilute H2SO4 is always preferred over HCl for general use in the extraction of alkaloids. perchloric. The acid solution is rendered alkaline with dilute NH4OH solution to liberate the alkaloids which is then extracted with an organic solvent. (b) Precipitation of Alkaloid with Precipitating Reagent -accomplished by the addition of a suitable precipitating reagent. such as: hydrochloric. sulphuric. oxalic and tartaric acids. recrystallization and ultimately decomposed to obtain the desired free alkaloid(s).by addition of an appropriate mineral or organic acid. hydrobromic. -and the organic solvent affords a deep penetration of the moist drug thereby allowing the greatest possible extraction of the alkaloids from the exposed surfaces of the cells and tissues of the crude drug. ion-exchange and column chromatography are invariably used for the purification of a host of alkaloids. (c) Formation of Crystallized Alkaloidal Salt.3. The solvent is removed under reduced pressure and the traces of moisture are removed with anhydrous sodium sulphate. 5. -the solvent is filtered and evaporated in a Rotary Thin-Film Evaporator and the residue is treated further for the isolation of individual alkaloids. (d) Various separation techniques. It is further purified by filtration. Extraction of Alkaloidal Base The extraction of alkaloidal base may be accomplished by three different types of solvents: (a) Extraction with Water-Miscible Solvents (b) Extraction with Water-Immiscible (c) Extraction with Water 4. .

successively to remove the bulk of the alkaloids.com/Minor/UK/IN0001. nicotine.il/plants/aharoni/PlantMetabolomeCourse/June192007.pdf http://www. the third alkaloid. -resulting filtrate is thoroughly shaken with petroleum ether to get rid of faulty materials. -proportion of crude drug to solvent should be maintained as 1 Kg to 1 L.authorstream.us. cooled to ambient temperature and finally filtered. -the resulting residual extract may still contain narceine.(b) Stas-Otto Process -treating the powdered and sieved drug substance with 90–95% (v/v) ethanol. References http://www. -residue is extracted with absolute ethanol thereby dissolving the total alkaloids.erowid. curarine and morphine.htm http://www.html http://www.org/archive/rhodium/chemistry/alkastract. narcotine. -the fat-free crude plant extract is subsequently acidified and shaken with chloroform.pdf . -alcohol is distilled off under vacuum and the resulting aqueous residue is treated with petroleum-ether (60-80°C) to remove the fatty components completely.elsevierhealth.com/archive/opiates___opioids__morphine__codeine____other_ medications http://www.com/2012/07/classification-of-alkaloids. codeine.ac.com/media/us/samplechapters/9780702029332/9780702029332_2 .com/english/alkaloids.com/Presentation/prem07-1580026-complete-info-alkaloids-ppt/ http://www. and the last traces of petroleum ether is removed from the extract by heating either on a water-bath or exposure to Infra-Red Lamp.epharmacognosy. may be extracted by agitation with a mixture of equal volumes of ether and chloroform. curarine. (c) Kippenberger’s Process -powdered and sieved plant substance is digested with solution of tannin (100 g) in glycerol (500 g) at a constant temperature of 40°C for a duration of 48 hours.com/2012/07/general-characteristics-of-alkaloids.html http://www.epharmacognosy. However. Finally. previously acidified with tartaric acid. VII. -combination of Kippenberger’s process and Stas-Otto process by its application to the final alcoholic extract obtained by the latter process is found to give better separation of alkaloids. which is then ultimately subjected to solvent extraction using a mixture of alcohol and chloroform.html http://www.html http://www. narceine and morphine may be isolated by passing freshly generated CO 2 directly into extract so as to convert the alkali hydroxide into their corresponding carbonate. spartenine and thebaine. colchicine.liberherbarum. namely.htm http://www. -the combined aqueous extract is filtered and evaporated to dryness preferably in a Rotary Thin-Film Evaporator under vacuum. -resulting mixture is further heated to 50°C so as to help in the complete coagulation of proteinous substances.weizmann.botanical-online.epharmacognosy. papaverine. atropine.com/2012/07/general-characteristics-of-alkaloids.thecabinchiangmai.

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