ALKALOIDS Valenzuela Joseph, Valero Michael, Vega Francesca, Vergara Ina Marie, Victoria Jaxon 3F-Pharmacy Group 9

Alkaloids Alkaloids are a group of naturally occurring chemical compounds, which mostly contain basic nitrogen. These are cyclic organic compounds containing such nitrogen that is in a negative state of oxidation with limited distribution among living organisms. Alkaloids usually contain one or two nitrogen atoms although some like ergotamine may contain up to five nitrogen atoms. The boundary between alkaloids and other nitrogen-containing natural compounds is uncertain. In 1819,pharmacist Wilhelm Meissner first used the term alkaloid, meaning alkali-like molecules. True alkaloids are defined as follows: 1. The nitrogen atom is part of the heterocyclic system 2. The compound has complex molecular structure. 3. The compound manifest significant pharmacological activity. 4. The compound is restricted to the plant kingdom. Characteristics of Alkaloids Usually derived from Amino Acids Basic- Forming H2O soluble salts Bitter Tasting Soluble in Hydroalcoholic solutions occur naturally in seed bearing plants and are found in berries, bark, fruit, roots and leaves. Basicity of alkaloids depends on the availability of lone pairs or e- on the N2 atoms. Basicity of alkaloids allow it to form salts from mineral acids and (hydrochlorides, nitrites, and Sulfates) and inorganic acids (tartrates and Sulfamates) 3 Types of Alkaloids True Alkaloid - Contains a Heterocyclic ring with Nitrogen (derived from amino acids) Protoalkaloid - Do not contain a Heterocyclic ring With nitrogen (derived from amino acids) Pseudoalkaloid - Contains a Heterocyclic ring with Nitrogen (not derived from amino acids) Classification of Alkaloids (based on chemical structures) Alkaloids have large variety in botanical and biochemical origin as well as in chemical structure and pharmaceutical action. Therefore, a range of different classification systems exists for alkaloids. I. Phenylethylamine Derivatives II. Pyridine and Piperidine Alkaloids a. Pyridine Alkaloids b. Dihydro- and Tetrahydropyridine c. Piperidine Alkaloids d. Tropane Alkaloids III. Quinoline Alkaloids a. Cinchona Alkaloids IV. Isoquinoline Alkaloids

a. Benzylisoquinoline Alkaloids b. Morphine (Phenanthrenisoquinoline) Alkaloids c. Other Isoquinoline Alkaloids V. Alkaloids derived from miscellaneous heterocyclic systems a. Senecio Alkaloids b. Lupine Alkaloids c. Amaryllidaceae Alkaloids d. Purine Bases VI. Indole Alkaloids a. Simple Indole Alkaloids b. Yohimbine Alkaloids and Related Bases c. Rauwolfia Alkaloids d. Strychnos Alkaloids e. Ergot Alkaloids VII. Imidazole Alkaloids VIII. Diterpine and Steroid Alkaloids a. Diterpine b. Steroid Alkaloids V. Alkaloids derived from miscellaneous heterocyclic systems - May include an pyrrole or acridine ring

V. a. Senecio Alkaloids - Occur as ester of pyrolizidine hydroxy derivatives

Retronicine

Indicine N-oxide

v. b. Lupine Alkaloids - Contains quinolozidine more exactly as octahydroquinolozidine

Lupinine V. c. Amaryllidaceae Alkaloids - Based on hydrogenated phenanthridine ring

Sparteine

V. D. Purine Bases - Sometimes not regarded as alkaloid because they are not related biogenetically to the amino acids

Caffeine VI.

Theophylline

Theobromine

Indole Alkaloids - alkaloid that contains indole group

VI.A. Simple Indole Alkaloids - biosynthetically derived from tryptophan

Gramine

Bufotenine

Harman

Harmine

VI. b. Yohimbine Alkaloids and Related Bases - contains five asymmetric carbon atoms

Yohimbine

Corynantheine

Alstonine

Aricine - Methoxy derivatives of Alstonine VI. c. Rauwolfia Alkaloids - Contain a large number of bases: Yohimbine alkaloids, Isoquinoline and ajmaline alkaloids

Ajmalicine

Reserpine

Ajmaline

VI. d. Strychnos Alkaloids - all of them are toxic, strychnine illustrates structural complexity of this alkaloid.

Strychnine

Brucine - Dimethoxy derivative of strychnine

Strychnospermine

Spermostrychnine

VI.E. Ergot Alkaloids - Derived from lysergic acids, Exhibit action on smooth muscle

Lysergic Acid

Ergonovine

Ergotamine

Ergosine

Ergocristine

Ergocryptine VII. Imidazole Alkaloids - derived from histidine

Ergocornine

Ergothioneine

Pilocarpine

VIII. Diterpine and Steroid Alkaloids - are sometimes classified as pseudo-alkaloids because they are not related biogenetically to the amino acids VIII. a. Diterpine

Posses diterpine skeletal structure

VIII. B. Steroid Alkaloids - Contains a nitrogenous cholesterol backbone

Solanidine USES:

Tomatidine

Traditional: Human recognition of alkaloid is as old as civilization, since this substance have been used as drugs, in potions, teas, medicines, poultices and poisons, and antidotes for 4000 years. It is likely that in the hunt for food and in dealing with enemies, particularly used was of plants containing alkaloids for arrow poisons Example: 1. Traditional medicinal uses of Rauwolfia(Rauwolfiaserpentina) vary from treating poisonous snake bites and insomnia. 2. Strychnine was one prescribe as a remedy for heart and repiratorycompliants and as a stimulant. It is no longer used today because the size of an effective dose would be toxic. 3. Yohimbine is a plant that is native to areas in West Africa. It has been used in folk remedies for weight control and aphrodisiac purposes for thousands of years. Pharmacological:

INDUSTRIAL: - Chocolate (theobromine) - Coffee ( caffeine) - Tea (caffeine and theophylline) - Dye (Indole alkaloids) - Poison EXTRACTION: main procedure that prepares a sample for the determination of alkaloids in a plant material. Before extraction, the plant material should be reduced to a fine powder as possible. Using Basic Medium:

Plants Containing alkaloid Coffea arabica L.(coffee)- caffeine Theobroma cacao L.(cocoa)- Theobromine Lycopersicum esculentum(tomato)- tomatidine Solanum tuberosum(potato)- solanidine Claviceps purpurea (ergot fungi)- ergot Pausinystalia yohimbe (Yohimbe)- yohimbine

References: Websites:

http://www.discoveriesinmedicine.com/Ra-Thy/Strychnine.html#b (Aug 03,2012) http://www.ehow.com/how_4740204_use-yohimbe-bark.html (Aug 03, 2012) http://www.uni-heidelberg.de/institute/fak14/ipmb/phazb/pdffiles/1998%20Pdf.Pubwink/14.%201998.pdf (Aug 03, 2012) http://www.wisegeek.com/what-are-the-medical-uses-of-rauvolfia.htm (Aug 03, 2012) Books: Cordell.G.A. (1981). Introduction to Alkaloids, a Biogenetic Approach. John Wiley, new jersey, New York.