University of Santo Tomas Faculty of Pharmacy

ALKALOIDS
3C-Pharmacy Group 7 Ong, Lexley Pobre, Kevin Quilaneta, Jane Remandaban, Ronald Joseph Reyes, Maria Veronica Rivera, Belle

Definition Alkaloids are naturally occurring, nitrogen-containing organic compounds with the exemption of amino acids, peptides, pterines and derivatives, purines and derivatives, amino sugars and antibiotics. Clearly, the division of naturally occurring, nitrogen-containing substances into alkaloids and nonalkaloids are somewhat arbitrary, and the boundary line is drawn in different positions by different authors. Classification/Types of Alkaloids:

Classification of alkaloids on the basis of origin: True Alkaloids: These are basic in nature, derivatives of amino acids having nitrogen inheterocyclic ring, occurs in plants as salts of organic acids. e.g.: Quinine, Morphine, Atropine.(b) Proto/amino-alkaloids: These are simple biological amines, basic in nature, derivatives of amino acids, dont have heterocyclic nitrogen atom in ring system (but in side chain). e.g.ephedrine, colchicine and mescaline(c) Pseudo alkaloids: These are weakly basic nitrogenous compounds, do not derived from aminoacid but have heterocyclic nitrogen atom. e.g. purine bases like caffeine and steroidal alkaloids like solasodine 1.)True and proto alkaloids (Amino acid derived alkaloids) a.)Ornithine and Lysine derived alkaloidsi. i. Pyrolidine alkaloids e.x. Nicotine17 ii. Tropane alkaloids e.x. Atropine, Hyoscine iii. Pyrolizidine alkaloids e.x. Alkaloids of Borage and Symphytum iv. Quinolizidine alkaloids e.x. Lupanine and sparteine v. Indolizidine alkaloids e.x. Castanospermine (Anti-HIV) vi. Piperidine alkaloids e.x. Lobeline, Piperine, pelleterine and coniine b.) Phenylalanine and tyrosine derived alkaloidsi. i. Phenyl ethyl amine alkaloids e.x. Ephedrine ii. Isoquinoline alkaloids e.x. Papaverine iii. Aporphine alkaloids e.x. Apomorphine iv. Morphinans e.x. Morphine, codine, thebain

c.) Tryptophan derived alkaloidsi. i. Tryptamine and carbolines e.x. Muscarine, serotonine, harmine andharmaline ii. Indolines e.x. Neostigmine and physiostigmine iii. Ergolines e.x. Lysergic acid derivative ergot alkaloids iv.Monoterpenoid indole e.x. vinca, cinchona, nux-vomica, rauwolfiaand camptotheca alkaloids d.)Histidine derived alkaloids e.x. Pilocarpine2. 2.) Pseudo alkaloids (non amino acid derived alkaloids) a.) Alkaloids derived from terpene metabolism i. Mono and sesque terpene alkaloids e.x. alkaloids of Nymphea sp. ii. Diterpene alkaloids e.x. alkaloids of Aconite sp. iii. Steroidal alkaloids e.x. alkaloids of Solanum and Veratrum sp. andkurchi alkaloids. b.) Purine bases e.x. caffeine and theine c.) Miscellaneous alkaloids like peptide alkaloids of Ziziphus sp. and maytansinoids. Chemical classification of alkaloids on the basis of heterocyclic ring: Alkaloids are mainly divided into two categories on the basis of their chemical structure i.e. heterocyclic rings. 1.) Atypical alkaloids: These are also known as non-heterocyclic alkaloids and contain nitrogen inaliphatic chain. 2.) Typical alkaloids: These are also known as heterocyclic alkaloids and contain nitrogen in heterocyclic ring system.

Uses: Role in Plants and Animals 1. For Protection Aporphine alkaloid liriodenine, protects the tulip plant from parasitic mushrooms. In addition, presence of alkaloids in the plant prevents insects and chordate animals from eating it. 2. Neurotransmitters Alkaloid-related substances as serotonin, dopamine and histamine are important neurotransmitters in animals. 3. Regulates plant growth Uses in Medicine Medical use of alkaloid-containing plants has a long history, and, thus, when the first alkaloids were isolated in the 19th century, they immediately found application in clinical practice. Many alkaloids are still used in medicine, usually in the form of salts, including the following: 1. Ajmaline anti-arrythmic 2. Atropine anticholinergic, antidote to gas poisoning 3. Scopalamine anticholinergic 4. Hyoscyamine anticholinergic 5. Vinblastine antitumor 6. Vincristine antitumor 7. Vincamine vasodilating, antihypertensive 8. Caffeine central nerve stimulant 9. Codeine antitussis 10. Coccaine Anaesthetics 11. Colchicine antigout 12. Morphine analgesic 13. Reserpine antihypertensive 14. Tubocurarine muscle relaxant 15. Physostigmine ACE inhibitor 16. Quinidine antiarrythmic

17. Quinine antipyretics, anitmalarial 18. Emetine antiprotozoal 19. Ergot alkaloids sympathomimetic vasodilator, antihypertensive 20. Sanguinarine antiplaque activity In agriculture Prior to the development of a wide range of relatively low-toxic synthetic pesticides, some alkaloids, such as salts of nicotine and anabasine, were used as insecticides. Their use was limited by their high toxicity to human. Plants that contain alkaloids Common Name Tobacco Coffee opium poppy Scientific Name Nicotiana tabacum Coffea arabica Papaver somniferum Plant part Leaf, foliage seed Latex Exudate, Plant juice, Sap Areca nut Datura/ Jimson Weed Areca catechu Datura stramonium Fruit, Seed Fruit, Herb/ Grass, Leaf, Foliage, Plant, Root, seed, stem Belladonna Purple betony Ergot Angel's trumpet Atropa belladonna Betonica officinalis Claviceps purpurea Datura metel Leaf, foliage, root Aerial parts Whole plant Flower / Blossom, Fruit, Leaf, foliage, Plant, Root, Seed, Sprout Seedling, Stem Common Honey-Locust Apricot vine Locust tree/ False acacia Pomegranate Gleditsia triacanthos Passiflora Incarnata Robinia pseudacacia Punica granatum Flower / Blossom Plant, Shoot Bark Rind / Bark / Cortex, Root bark Bitter gourd Mormordica charantia Unripe fruit

African Cucumber

Momordica charantia

Fruit

http://waynesword.palomar.edu/ww0703.htm http://medical-dictionary.thefreedictionary.com/Coffee+(drink) http://www.henriettesherbal.com/eclectic/usdisp/robinia.html http://www.nhmrc.gov.au/publications/synopses/withdrawn/n23.pdf

Extraction Procedure Extraction is based on the basicity of alkaloids and on the fact that they normally occur in plants as salts (i.e.: on the solubility of bases and salts in water and organic solvents). Herbs often contain other materials which can interfere with extraction such as large amounts of fat, waxes, terpenes, pigments and other lipophilic substances (e.g by forming emulsions) avoided by defatting the crushed herb (using petroleum ether and hexane). Extraction method normally depends on the raw material, the purpose of extraction & the scale on which is to be performed. For research purposes: chromatography allows for quick and reliable results. If larger amounts of alkaloids need to be extracted, one of the following methods can be used. GENERAL METHOD Step 1: Powdered, defatted herb is mixed with an alkaline aqueous solution. Free bases are then extracted with organic solvents. Normally aqueous ammonia is used, but a carbonate solution is used when alkaloids contain fragile elements such as a ester or lactone. In some cases, e.g. Cinchona bark, a mixture of calcium hydroxide & sodium hydroxide should be used as the alkaloids are bound to tannins. Organic solvent: chloroform, dichloromethane or ethyl acetate depends on the toxicity, safety, cost & ease of recovery and recycling of the solvent).

Step 2: Organic solvent containing alkaloids (bases) is separated from residue & concentrated by distillation under pressure if needed. Solvent is stirred with an acidic aqueous solution: alkaloids go into the solution as salts. Impurities remain in the organic phase. Aqueous solution of alkaloid salts is washed with an apolar solvent (hexane) Alkalinized with a base using an organic solvent not miscible with water. Alkaloids precipitate and dissolve in the organic phase. Extraction of aqueous phase continues till all alkaloids have moved into the organic phase (tested when Mayers reaction on the aqueous phase becomes negative). This purification step may be carried out in a separation funnel or in centrifugal extractors Step 3: Organic solvent containing alkaloid bases is decanted, freed from water traces (drying over anhydrous salt e.g. sodium sulphate) and evaporated under reduced pressure. A dry residue remains: total basic alkaloids. Extraction of Liquid Alkaloids 2 Methods possible: Plant powder is extracted directly with acidified water Plant powder is extracted with acidified alcoholic or a hydroalcoholic solution. This is then followed by distillation under vacuum (eliminates that alcohol, leaving behind and acidic aqueous solution of alkaloid salts)