Chemistry of natural products

Classification of Natural product There is no rigid scheme for classifying natural products—their immense diversity in structure, function, and biosynthesis is too great to allow them to fit neatly into a few simple categories Five main classes of natural products: 4/5/2019 Chem-465

Terpenoids and Steroids, Fatty Acid–derived Substances and Polyketides, Alkaloids, Non Ribosomal Polypeptides, and Enzyme Cofactors. 4/5/2019 Chem-465

Natural Products (secondary metabolites) Terpenoids, Steroids Alkaloids Fatty acids, Polyketides Non ribosomal polypeptides Enzyme cofactors 4/5/2019 Chem-465

Terpenoids and steroids Are a vast group of substances—more than 35,000 are known—derived biosynthetically from Isopentenyl diphosphate. 4/5/2019 Chem-465

Alkaloids Are a large and diverse class of compounds, with more than 12,000 examples known at present. They contain a basic amine group in their structure and are derived biosynthetically from amino acids. 4/5/2019 Chem-465

Fatty acid Derived substances and polyketides, of which more than 10,000 are known, are biosynthesized from simple acyl precursors such as acetyl CoA, propionyl CoA, and methyl malonyl CoA. Natural products are derived from fatty acids, such as the eicosanoid prostaglandin E1,but polyketides, such as the antibiotic erythromycin A often have many oxygen substituents remaining. 4/5/2019 Chem-465

Nonribosomal polypeptides They are peptide like compounds that are biosynthesized from amino acids by a multifunctional enzyme complex without direct RNA transcription. The penicillins are good examples 4/5/2019 Chem-465

Enzyme cofactors Cofactors, mostly metal ions or coenzymes, are inorganic and organic chemicals that assist enzymes during the catalysis of reactions. Coenzymes are non-protein organic molecules that are mostly derivatives of vitamins soluble in water by phosphorylation; they bind apoenzyme to proteins to produce an active holoenzyme. 4/5/2019 Chem-465

Terpenoids Have an immense variety of apparently unrelated structures, while steroids have a common tetracyclic carbon skeleton and are modified terpenoids that are biosynthesized from the triterpene lanosterol 4/5/2019 Chem-465

Introduction to Natural Products Natural products are products from various natural sources, plants, microbes and animals. Natural products can be an entire organism (e.g. a plant, an animal or a micro-organism), a part of an organism (e.g. leaves or flowers of a plant, an isolated animal organ), an extract of an organism or part of an organism and an exudate, or pure compound (e.g. alkaloids, coumarins, flavonoids, lignans, steroids and terpenoids) isolated from plants, animals or micro-organisms. 4/5/2019 Chem-465

However, in practice, the term natural product refers to secondary metabolites, small molecules (molecular weight < 1500 amu), produced by an organism, but not strictly necessary for the survival of the organism. 4/5/2019 Chem-465

CHAPTER-1 CHEMISTRY OF NATURAL PRODUCTS, Prepared by Dr. Khalid Shadid 29/07/1440 The 18th century … At the end of the 18th century, crude drugs were still being used as powders, simple extracts, or tinctures. The era of pure compounds (In 1803, a new era in the history of medicine) Isolation of morphine from opium Strychnine (1817) Quinine and caffeine (1820) Nicotine (1828) Atropine (1833) Cocaine (1855) morphine Nicotine Strychnine caffeine Quinine Atropine Cocaine 4/5/2019 Chem-465

CHAPTER-1 CHEMISTRY OF NATURAL PRODUCTS, Prepared by Dr. Khalid Shadid 29/07/1440 In the 19th century, the chemical structures of many of the isolated compounds were determined In the 20th century, the discovery of important drugs from the animal kingdom, particularly hormones and vitamins. In addition, microorganisms have become a very important source of drugs Captopril Epibatidine Penicillin 4/5/2019 Chem-465

Epibatidine has a high analgesic potency Epibatidine is a putative  alkaloid that is secreted by the Ecuadoran frog Epipedobates Anthonyi  It was discovered by  John W. Daly in 1974, but its structure was not fully elucidated until 1992. Whether Epibatidine is the first observed example of a chlorinated alkaloid Epibatidine has a high analgesic potency   Captopril is used to treat high blood pressure (hypertension), congestive heart failure, kidney problems caused by diabetes, and to improve survival after a heart attack.  4/5/2019 Chem-465

CHAPTER-1 CHEMISTRY OF NATURAL PRODUCTS, Prepared by Dr. Khalid Shadid 29/07/1440 Compounds from natural sources play significant roles in modern medicine: They provide a number of extremely useful drugs that are difficult, if not impossible, to produce commercially by synthetic means Natural sources also supply basic compounds that may be modified slightly to render them more effective or less toxic Their utility as prototypes or models for synthetic drugs possessing physiologic activities similar to the originals 4/5/2019 Chem-465

Ibuprofen salicylic acid Aspirin Spirea 4/5/2019 Chem-465

Overview of a bioassay-guided traditional natural product drug discovery process Source materials (e.g. plant) Extract (s) Active extract (s) Extraction Chromatographic fractionation Bioassay Chromatographic fractions Active fraction (s) Isolation and purification Bioassay Isolated compounds Active compound (s) Identification by spectroscopic techniques, e.g. UV, IR, MS, NMR Bioassay Identified compounds Identified bioactive compound (s) 4/5/2019 Chem-465

Thank You 4/5/2019 Chem-465