STK31003 Terrestrial Natural Product Chemistry PDF

STK31003 – Terrestrial Natural Product Chemistry SHIKIMATE PATHWAYS OR SHIKIMIC ACID PATHWAYS  Biosynthesis Pathways  Mevalonate Pathways – Involves the synthesis of terpenoids/steroids utilizing mevalonic acid: Examples limonene, camphor, pinene, farnesol, squalene, ch...

STK31003 – Terrestrial Natural Product Chemistry SHIKIMATE PATHWAYS OR SHIKIMIC ACID PATHWAYS  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  Phenylpropanoids Hydroxycinnamic acids and their derivatives Linammed Phenylpropene/phenylpropane and their derivatives -Gregg Monolighal Coumarin - Lignan Stilbenoids Coumanyl-acid Lignin  SHIKIMATE PATHWAYS Metabolic Derivatives From the Shikimate Pathway often referred to as the common aromatic biosynthetic pathway, the Shikimate pathway converts primary metabolites phosphoenolpyruvate and erythrose- 4-phosphate to chorismate.  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  SHIKIMATE PATHWAYS Chorismate is required for the biosynthesis of a wide variety of aromatic plant metabolites, including the aromatic amino acids – phenylalanine, tyrosine, and tryptophan (three of the essential twenty building blocks for protein synthesis) – as well as tetrahydrofolate, ubiquinone, and vitamin K.  SHIKIMATE PATHWAYS Phenylalanine is utilized in protein > - synthesis and as a substrate for the precusor phenylpropanoid pathway (via cinnamic acid), which produces numerous secondary plant products such as anthocyanins, lignin, growth promoters, growth inhibitors, and phenolics. Tyrosine and tryptophan also are required for protein synthesis.  SHIKIMATE PATHWAYS One of the plant hormones, indoleacetic acid, is derived from tryptophan and is absolutely necessary for cell expansion, maintenance of apical dominance, and well as other regulatory processes in the plant  Biosynthesis - Glucose  erythrose -4- phosphate + phosphoenolpyruvate    Shikimic acid Shikimic acid  chorismic acid  tryptophan Shikimic acid  chorismic acid  prephenic acid  Phenylalanine and tyrosine  cinnamic acid Cinnamic acid  various phenylpropanoids Enzyme Enzyme Enzyme DAPH-3-deoxy-D-arabino- heptulosonate 7-phosphate PAL, Phenylalanine ammonia-lyase; C4H, cinnamate 4-hydroxylase; 4CL, 4-coumaroyl CoA-ligase; TAL, Tyrosine Ammonia-lyase  Phenylpropanoids Phenylpropanoids are a class of plant- derived organic compounds that are biosynthesized from the amino acid phenylalanine. They have a wide variety of functions, including defense against herbivores, microbial attack, or other sources of injury; as structural components of cell walls; as protection from ultraviolet light; as pigments; and as signaling molecules.  Phenylpropanoids 1. Phenylpropanoids are a diverse group of natural products composed of thousands of different compounds, synthesized from phenylalanine or tyrosine amino acids, through a series of enzymatic reactions. 2. The aromatic amino acids are synthesized through the shikimate pathway, which is present in microorganisms, plants, and fungi, but is absent from animals.  Cinnamic Acid Phenylalanine is first converted to cinnamic acid by the action of the enzyme phenylalanine ammonia lysase (PAL). A series of enzymatic hydroxylations and methylations leads to coumaric acid, caffeic acid, ferulic acid, 5- hydroxyferulic acid, and sinapic acid. Conversion of these acids to their corresponding esters produces some of the volatile components of herb and flower fragrances which serve many functions such as attracting pollinators. Ethyl cinnamate is a common example.  Cinnamic Acid and Derivatives Cinnamic acid P-coumaric acid Caffeic acid Ethyl cinnmate Sinapic acid Ferulic acid  Cinnamic aldehydes and monolignols Reduction of the carboxylic acid functional groups in the cinnamic acids provides the corresponding aldehydes, such as cinnamaldehyde. Further reduction provides monolignols including coumaryl alcohol, coniferyl alcohol, and sinapyl alcohol. The monolignols are monomers that are polymerized to generate various forms of lignin and suberin, which are used as a structural component of plant cell walls.  Cinnamic aldehydes and monolignols Cinnamaldehyde P-coumaryl alcohol Coniferyl alcohol Sinapyl alcohol  Phenylpropene The phenylpropenes, including eugenol, chavicol, safrole and estragole, are also derived from the monolignols. The compounds are the primary constituents of various essential oils. Monolignols > - Phenylproper  Phenylpropene Chavicol Estragole Safrole Eugenol Sassafras albidum Eugenia aromaticum Cinnamomum spp. C. cassia C.camphora Cinnnamomum burminii p-coumarine acid > - Umbeliferne Coumarins Hydroxylation of cinnamic acid in the 4-position leads to p-coumaric acid, which can be further modified into hydroxylated derivatives such as umbelliferone. Another use of p-coumaric acid via its thioester with coenzyme A, i.e. 4- coumaroyl-CoA, is the production of chalcone. This is achieved with the addition of 3 malonyl- CoA molecules and their cyclization into a second phenyl group. Chalcone is the precursor of all flavonoids, a diverse class of phytochemicals.  Coumarin Coumaric acid Cinnamic acid Umbeliferone  Umbelliferone Umbelliferone or 7-hydroxycoumarin is a widespread natural product of the coumarin family. It occurs in many familiar plants from the Apiaceae (Umbelliferae) family such as carrot and coriander. It is a yellowish-white crystalline solid which has a slight solubility in hot water, but high solubility in ethanol. It absorbs ultraviolet light strongly at several wavelengths, leading to its use in sunscreen creams and lotions.  Plants Rich in Coumarin Coriandrum sativum Daucus carota  Umbelliferone Synthesis Umbelliferone is traditionally synthesized using the Pechmann condensation, from resorcinol and formylacetic acid (generated from malic acid in situ). Umbelliferone Derivatives  Stilbenoids Stilbenoids, such as resveratrol, are hydroxylated derivatives of stilbene. They are formed through an alternative cyclization of cinammoyl- CoA or 4-coumaroyl-CoA  Stilbenoids Stilbenoids are secondary products of heartwood formation in trees that can act as phytoalexins. Chemically they are hydroxylated derivatives of stilbene. Biochemically they belong to the family of phenylpropanoids and share most of their biosynthesis pathway with chalcones. An example of stilbenoids is resveratrol which is found in grapes and which has been suggested to have many health benefits.  Stilbenoids Stilbenoids are a group of naturally occurring phenolic compounds found in various plant species. They share a common backbone structure known as stilbene, but differ in the nature and position of substituents. Stilbenoids are classified as phytoalexins, which are antimicrobial compounds produced de novo in plants to protect against fungal infection and toxins  Stilbenoids Stilbenoids exert various biological activities ranging from cardioprotection, neuroprotection, anti-diabetic properties, depigmentation, anti-inflammation, cancer prevention and treatment.  Phytoalexins 1. Phytoalexins are antimicrobial substances synthesized de novo by plants that accumulate rapidly at areas of incompatible pathogen infection. 2. They are broad spectrum inhibitors and are chemically diverse with different types characteristic of particular plant species. 3. Phytoalexins tend to fall into several classes including terpenoids, glycosteroids and alkaloids;  Phytoalexin properties Stilbenoids have been suggested by some studies to be responsible for resistance to some tree diseases, such as pine wilt.  Resveratrol 1. Resveratrol is a phytoalexin produced by several plants. It has also been produced by chemical synthesis. 2. Resveratrol is sold as a nutritional supplement. A number of beneficial health effects, such as anti-cancer, antiviral, neuroprotective, anti-aging, anti- inflammatory and life-prolonging effects have been reported. Resveratrol is found in the skin of red grapes.  Stilbene Resveratrol Pinosylvin Lignan – Dimer of phenylpropanoid 1. A lignan is a group of chemical compounds found in plants. 2. Lignans are one of the major classes of phytoestrogens, which are estrogen-like chemicals and also act as antioxidants. The other classes of phytoestrogens are the isoflavones, and coumestans. 3. Plant lignans are polyphenolic substances derived from phenylalanine via dimerization of substituted cinnamic alcohols.  Lignan Some examples of lignans are pinoresinol, podophyllotoxin and steganacin. When part of the human diet, lignans are converted into the mammalian lignans known as enterodiol and enterolactone by intestinal bacteria.  Lignan Dibenzyl butane Propyl benzene Neolignan Entrodiol Entrolactone  Lignan 7-hydroxymatairesinol matairesinol  Lignan Flax seed is among the highest sources of lignan (~301129 µg/100 g); the principal lignan precursor found in flaxseed is secoisolariciresinol diglucoside. Other sources of lignans include pumpkin seeds, sesame seeds, rye, soybeans, broccoli, beans, and some berries. Secoisolariciresinol and matairesinol were the first plant lignans identified in foods. Pinoresinol and laricresinol are more recently identified plant lignans contribute substantially to total dietary lignan intakes. Typically, Lariciresinol and pinoresinol contribute about 75% to the total lignan intake while secoisolariciresinol and matairesinol contributed only about 25%  Sources for Lignan Linum usitatissimum (Flax seed) Lignin