NFNF1813 Intro to Natural Products PDF

Introduction to Natural Products Chemistry ASSOC. PROF. DR. KHAIRANA HUSAIN NFNF1813  Medicinal Plants  Defined: as plants that contain properties or compounds that can be use for therapeutic purposes or those that synthesize metabolites to produce usef...

Introduction to Natural Products Chemistry ASSOC. PROF. DR. KHAIRANA HUSAIN NFNF1813  Medicinal Plants  Defined: as plants that contain properties or compounds that can be use for therapeutic purposes or those that synthesize metabolites to produce useful drugs (WHO 2008). Importance of medicinal plants:  80% of the world population uses only medicinal plants  In Western countries, about 35% of prescribed drugs are of natural origin  More than 50% of OTC drugs are derived from medicinal plants  The major killer diseases in the world AIDS: 3.1 m deaths per year, 5.5 m new cases Tuberculosis: 2 m deaths, 8 m new cases Diarrheal Diseases: 1.9 m deaths Malaria: 1 m deaths, 300-500 m new cases Hepatitis B Virus: 1 m deaths, 10-30 m new cases SARS: 04/04, 8,096 cases, 774 deaths (648 in HK/China) Tobacco-related: 3.5 m deaths (cancer, lung) Covid 19: ?? m deaths Some issues for drug discovery Major Global diseases have no effective therapy Drug Resistance (anti-infective, anticancer, antimalarial, etc) is increasing New Diseases are emerging (e.g. SARS, avian flu, Marburg virus, Covid 19 etc.) The Cost to market a new drug is now at least $800 million (not feasible for most of the world) The Role of natural products as pharmaceuticals is well- established  Medicinal plants are the richest bio-resource:  Drugs of traditional systems of medicine  Modern medicines  Nutraceuticals  Food supplements  Folk medicines  Pharmaceutical intermediates  Chemical entities for synthetic drugs  SHIKIMIC ACID DERIVED Phenylpropenes TERPENES Lignans Monoterpenes Coumarins Sesquiterpenes Flavonoids Diterpenes Tannins Triterpenes POLYKETIDES Tetraterpenes Fatty acids Glycerides NATURAL Tetracyclines PRODUCTS ALKALOIDS Griseofulvins CHEMISTRY Pyridine, piperidine Erythromycin A & pyrrolizidine Statins Phenylalkylamine Quinoline GLYCOSIDES Isoquinoline Cyanide glycosides Indole Glucosinolates Tropane Cardiac glycosides Xanthine Anthaquinone glycosides Imidazole Types of Phytochemical Oils & Fats Terpenoids Prostaglandins Alkaloids Vitamins Flavanoids Steroids Carbohydrates Lignins Lignans Proteins Nucleic acid Antibiotics Pigments Mycotoxins Pheromones etc Metabolic Pathways of Natural Products BIOSYNTHETIC PATHWAYS OF 2 METABOLITES Acetate Amino Acids Shikimate Aromatic Mevalonate Aliphatic Deoxyxylulose Phosphate  Natural products and Ecology Animals Antifeedant Toxins Toxins Scents Antipest Attractants Toxins Plants Insects Pheromones Communication Antifungals Symbiosis Symbiosis Antifungals Chemotaxis Fungi Bacteria Communication Antibacterials Cells of organisms - plants, fungi, bacteria, lichens, insects, animals - produce a large variety of organic compounds.  Some milestones in natural products chemistry: HO H 3 1 N H 4 N HO 12 10 O H 13 9 N H CH3O H H 5 15 N 10 6 CH3 O H O 7 16 N HO Morphine Strychnine Quinine (aromatic alkaloid from opium, (aromatic alkaloid from (quinoline alkaloid from Papaver somniferum) Strychnos nux-vomica) Cinchona species) Isolation: 1806, Sertürner Isolation: 1818, Pelletier & Isolation: 1820, Pelletier & Structure: 1925, Robinson Caventou Caventou Synthesis: 1954, Ginsberg Structure: 1946, Robinson Synthesis: 1944, Woodward Biogenesis: 1959, Leete Synthesis: 1954, Woodward 2001, Eichberg  Detection Methods  General chemical reagent ▪ Ferric chloride : dark blue to dark green colour  Semi-specific chemical reagents ▪ Bate-Smith reaction : tannins ▪ Cyanidine test : flavonoids ▪ Bornträger reaction : anthracenosides Extraction of phenolics in neutral medium General Extraction of Alkaloids from Powdered plants Plant material and solvent Organic solvent dissove Alkaloids Organic solvent dissove Impurities Extract Concentration Acidification Alkalinization Acidified Extract (Alk. as salts) Alkaline aqueous layer General isolation strategy of natural products: