STK 31003 Terrestrial Natural Product Chemistry PDF

STK 31003 Terrestrial Natural Product Chemistry  Primary Metabolites -Ubiquitous -Obvious function for growth and development e.g. lipids, nucleotides, amino acids, organic acids, sugars etc  Secondary Metabolite  Distributed among limited taxonomic groups  Divergent  Function no...

STK 31003 Terrestrial Natural Product Chemistry  Primary Metabolites -Ubiquitous -Obvious function for growth and development e.g. lipids, nucleotides, amino acids, organic acids, sugars etc  Secondary Metabolite  Distributed among limited taxonomic groups  Divergent  Function not clear e.g. saponins, flavonoids, steroids, alkaloids etc.  Why Do Plants Produce and Accumulate Natural Products?  Overflow of excess primary metabolism?  Natural selection?  Allelopathy?  Self defence? Phytoallexins ( and phytoanticipins The compounds are so diverse in order to adapt to diverse environment (e.g. pathogens).  Allelopathy is the biological process in which plants are able to suppress the growth of other plants near them. Some plants are able to do this by releasing chemicals in their leaves as they fall and decompose or by releasing allelopathic chemicals from their roots. Long pepper (Piper longum Sarmentine L.) Neem (Azadirachta indica Nimbolide B, Nimbic acid B A.Juss.) Sunflower (Helianthus Heliannuols annuus L.)  Phytoalexins are low molecular weight antimicrobial compounds that are produced by plants as a response to biotic and abiotic stresses. As such they take part in an intricate defense system which enables plants to control invading microorganisms.  Phytoanticipin are low molecular weight antimicrobial compound present in plants before challenge by microorganisms or produced after infection solely from preexisting constituents.  Why Study Secondary Metabolites/Natural Products?  Direct uses as drugs – The isolated secondary metabolites can be used direct as medicine for examples morphine as analgesic, codeine as antitussive, quinine as antimalarial, vinblastine and vincristine as antitumour etc.  As a starting materials in the synthesis of useful drugs. Examples steroid hormons such as adrenal cortex hormones are synthesized from steroidal sapogenin which can be found in various plants.  As a model for pharmacological active compounds – Limited sources or toxicity effect  Chemotaxonomy – Classification of plants based on chemical compounds. Chemical with rare distribution can be widely used for this purposes. For examples isoflavones in Leguminosea and Iridaceae; alkaloids in Rauwolfia and Catharanthus (Apocynaceae); cardenolides in Nerium, Thevetia and Strophantus (Apocynaceae) Classification of Natural Products  Classification based on chemical structures  Classification based on physiological activities  Classification based on taxonomy  Classification based on biogenesis  Classification based on chemical structures Formal classification based on molecular skeleton i. Open-chain aliphatic or fatty compounds – fatty acid, sugars, most amino acid ii. Alicyclic or cycloaliphatic compounds – terpenoids, steroids, alkaloids iii. Aromatic or benzenoid compounds – phenolics, quinones iv. Heterocyclic compounds – alkaloids, flavonoids, nucleic acid bases Many compounds will fall into more than one class. For example geraniol (1), farnesol (2) and squalene (3) belong to class I, and thymol (4) to class iii, but because of biogenetic consideration they are usually treated with other terpenoids and steroids under class ii Geraniol Farnesol Squalene Thymol Morphine Thebaine Codeine Narcotine 1-Benzylisoquinoline Classification based on physiological activities This classification is based on physiological activities. Although compounds belonging to each groups have diverse structures and biosynthetic origin, occasionally a close correlation is found between their activity. For examples: hormones, vitamins, antibiotics, mycotoxin etc. Examples: morphine (5), penicillin G (6), prostaglandin F (7), cardenolides (8) and bufadienolides (9). Although 8 and 9 differ in their structures but have similar cardiotonic activities. Prostaglandins :One of a number of hormone-like substances that participate in a wide range of body functions such as the contraction and relaxation of smooth muscle, the dilation and constriction of blood vessels, control of blood pressure, and modulation of inflammation. Prostaglandins are derived from a chemical called arachidonic acid. Classification based on taxonomy This is based on comparative morphological studies of plants or plants taxonomy. Compounds from certain family and genera are in general have limited distribution to that particular family or genera. For examples opium alkaloids (Papaver somniferum) such as morphine (5), thebaine (10), codeine (11) and narcotine (12) are all synthesized from 1- benzylisoquinoline precursor (13) by oxidative coupling. Similarly names representing genera and family such as ergot alkaloids, iboga alkaloids, Menispermaceae alkaloids etc always appears in the literature. Geraniol Farnesol Squalene Thymol Morphine Thebaine Codeine Narcotine 1-Benzylisoquinoline Tabernanthe iboga Papaver somniferum Ibogaine Morphine (Iboga alkaloids) (opium alkaloid)  Classification based on biogenesis  Biogenesis – Based on hypothesis  Biosynthesis – Experimentally proven route  Natural products can be produced by various pathways. Compounds produced by similar pathways are grouped together.  Isoprene rule proposed by Ruzicka stated that all terpenoids are built up from C5 isoprene units. Examples nerol (14), santonin (15), oleanolic acid (16), Geraniol Farnesol Squalene Thymol Morphine Thebaine Codeine Narcotine 1-Benzylisoquinoline  Robinson proposed polyketomethylene theory for phenolic compounds and was the first suggestion to acetogenin (polyketide) biosynthesis  Davis using Escherichia coli proposed Shikimic acid pathways and showed the biosynthesis of aromatic amino acids and related compounds by using shikimic acid as an intermediate  Biosynthesis Pathways  Mevalonate Pathways – Involves the synthesis of terpenoids/steroids utilizing mevalonic acid: Examples limonene, camphor, pinene, farnesol, squalene, cholesterol, cortisone etc  Shikimate Pathways – Involves the synthesis of aromatic amino acids and phenylpronoids/derivatives: examples tryptophan, phenylalanine, tyrosine, eugenol, lignan, lignin etc  Polyketide/acetogenin/acetate-malonate pathways – Involves in the synthesis of aromatic compounds such as quinone, depside/depsidone, coumarine, xanthone etc.  Alkaloids Pathways – Involves in the production of alkaloids utilizing amino acid, Mannich Reaction and phenol oxidation and coupling  Main Building Block for Carbon and Nitrogen in Natural Products i. Acetyl-CoA C2 unit Polyketides Malonyl-CoA (MeCO-) ii. Shikimic acid C6C3 Phenolics Amino acid (C6C1 or C6C2) iii. Mevalonic Acid Prenyl unit Isoprenoids (CH2CCH2CH2-) CH3 iv. Amino acid Alkaloids v. S-5’-deoxyadenylmethionine C1 Secondary metabolites can be formed by the mentioned pathways or combinations of this units  Starting Materials for Biosynthesis Photosynthesis Erythrose 4- Glucose Starch phosphate Glycolysis Shikimic acid Phosphoenol pyruvate Mevalonate Aromatic amino Acetyl CoA pathways acid and phenylpropanoid Amino acids Terpenoids  Phosphoenolpyruvic acid Shikimic acid Pyruvic acid Acetyl Aromatic Alkaloids coenzyme A amino acids Amino acids Mevalonic Cinnamic acids Malonyl acid coenzyme A Fatty Phenylpropanoid Flavonoid acids compounds compounds Polyketides Terpenoid Phenolic Steroids compounds Carotenoids Biosynthetic Pathways in Plants Acetyl CoA