Chem 123 Lec - Module 6 Terpenoids PDF

Module 6 The TERPENOIDS Learning Outcomes: 1. Describe the terpenoid compounds: sources, importance; uses to plants and human wellness; physical and chemical properties 2.Trace the biosynthetic pathways in the synthesis of terpenoids 3.Identify the different classes of terpenoids 4.Discuss t...

Module 6 The TERPENOIDS Learning Outcomes: 1. Describe the terpenoid compounds: sources, importance; uses to plants and human wellness; physical and chemical properties 2.Trace the biosynthetic pathways in the synthesis of terpenoids 3.Identify the different classes of terpenoids 4.Discuss the extraction, isolation, structure elucidation of terpenoids What are isoprenoids, terpenes terpenoids? Used interchangeably to refer to class of natural products built two isoprene units, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DAMPP) one of the largest and structurally most diverse groups of natural products with more than 55,000 members play key metabolic, structural, and regulatory roles in all kingdoms of life. Biosynthetic pathways: MVA and MEP pathways  The Mevalonic Acid Pathway (in animals, plants (cytosol), fungi, and archaea) 3-hydroxy-3-methyl-glutaryl-CoA MVA acetylCoA acetoacetylCoA mevalonate-5-diphosphate mevalonate-5- phosphate In Methanocaldococcus jannaschii (enzyme phosphorylating isopentenyl phosphate (9) to IPP The Methylerythritol Phosphate Pathway (in eubacteria, green algae, and the plastids of higher plants methylerythritol cytidyl diphosphate pyruvate 1-Deoxy-D- xylulose 5- Glyceralde Reductively Methylerythritol phosphate hyde-3P isomerized by phosphate DXP reducto- isomerase 4-hydroxy-3-methyl- 2-C-methyl-D-erythritol-2,4- 4-diphosphocytidyl-2-C-methyl- butenyl 1-diphosphate cyclodiphosphate D-erythritol-2-phosphate What are terpenoids? ❑ Terpenes: belong to the biggest class of secondary metabolites and basically consist of five carbon isoprene units which are assembled to each other (many isoprene units) by thousands of ways. simple hydrocarbons, while ❑ terpenoids are modified class of terpenes with different functional groups and oxidized methyl group moved or removed at various positions. The Terpenes Most of the fragrance component of plant are terpenoids volatile and isolated by steam distillation is called as essential oil. The terpenoid essential oils comprise the volatile steam-distillable fraction responsible for the characteristic scent, odor or smell found in many plants. commercially important as the basis of natural perfumes and also of spices and flavorings in the food industry.  Examples of terpenoids beta-Citronellol Limonene, Citral  ISOPRENE RULE In 1887, Otto Wallach proposed the isoprene rule. “It states that the skeleton structures of all naturally occurring terpenoids can be built up of isoprene units or 2-methyl-1,3-butadiene”.  The isoprene rule derived from the following facts: The empirical formula of almost all terpenoids is C5H8. The thermal decomposition of all terpenoids gives isoprene as one of the products. The isoprene rule has been confirmed by the following facts: Isoprene, when heated to 280oC yield a dipentene Isoprene may be polymerized to yield a rubber like product  SPECIAL ISOPRENE RULE This rule was proposed by Ingold in 1925. According to this rule “the isoprene units in terpenoids are joined by head to tail linkage or 1,4- linkage (The branched end of isoprene unit was considered as head and other end as the tail). Violations of isoprene rule/Irregular isoprenoid structure. Carbon content of certain terpenoids are not a multiple of five. e.g: Cryptone, a naturally occurring ketonic terpenoid contains nine carbon atoms , it cannot be divided into two isoprene units. 4-(1-Methylethyl)-2- cyclohexen-1-one 4-(propan- 2-yl)cyclohex-2-en-1-one Violations of isoprene rule/Irregular isoprenoid structure. e.g: Lavandulol is composed of two isoprene units and are linked through C3 and C4. CLASSIFICATION OF TERPENOIDS Terpenoids are also subdivided into subclasses according to number of rings present in the molecule: 1.Acyclic terpenoid– open chain 2.Monocyclic terpenoid – one ring 3.Bicyclic terpenoid – two rings 4.Tricyclic terpenoid- three rings 5.Tetracyclic terpenoid – four rings 1. MONOTERPENOIDS consist of 10 carbon atoms with two isoprene units and molecular formula C10H16. naturally present in the essential and fixed oils of plants and related sources. structurally divided into the acyclic, monocyclic, and bicyclic type of compound. The compounds belong to this class usually have strong aroma and odor and are used in many pharmaceutical companies. MONOTERPENOIDS Mixture of different monoterpene-based oils is used as fragrances for making perfumes and in other cosmetics. Most of the monoterpenes are active biologically with strong antibacterial activities. Several studies have shown in vitro and in vivo antitumor activity of many essential oils obtained from plants. The antitumor activity of essential oils of many species has been related to the presence of monoterpenes in their composition. MONOTERPENOIDS ii) Monocyclic monoterpenoids iii) Bicyclic monoterpenoids The size of the first ring (six membered) in terpenoid is same in all these terpenoids but the size of second ring varies. On the basis of the size of second ring, bicyclic monoterpenoids are further divided into three classes. Structure of monoterpene Leaves of Perilla frutescens var. crispa The antitumor activity of essential oils of many species has been related to the presence of monoterpenes in their composition.  Iridoids - a type of monoterpenoids in the general form of cyclopentanopyran, found in a wide variety of plants and some animals. - biosynthetically derived from 8-oxogeranial. - Iridoids are typically found in plants as glycosides, most often bound to glucose. - - derivatives of monoterpenes - - occur usually, but not invariably, as glycosides. - - Structurally, these are cyclopentano [c] pyran monoterpenoids - - provide a biogenetical and chemotaxonomical link between terpenes and alkaloids. - - The cleavage of the cyclopentane ring of iridoids produces secoiridoids. 2) SESQUITERPENOIDS - the class of secondary metabolites consisting of three isoprene units (C15H24) and found in linear, cyclic, bicyclic, and tricyclic forms. - also found in the form of lactone ring. Many of the latex in latex-producing plants contain sesquiterpene, these are potent antimicrobial and anti- insecticidal agent. SESQUITERPENOIDS Structures of sesquiterpenes Chrysanthemum indicum Canelo tree Drimys winteri Mechanistic study Studies show the potency revealed the potential anti- for drimenin is several folds inflammatory activity of higher than that for other Chrysanthemulide A. clinically used antidepressants. 3) DITERPENOIDS belong to a versatile class of chemical constituents found in different natural sources having C20H32 molecular formula and four isoprene units. This class of compounds showed significant biological activities including anti-inflammatory, antimicrobial, anticancer, and antifungal activities. Some of the diterpenes also have cardiovascular activity. DITERPENOIDS DITERPENOIDS Source and biological activities of some diterpenes. -Buds of Wikstroemia chamaedaphne - Compounds exhibited potential antihepatitis B.  Source and biological activities of some Ciphinoids H demonstrated an anti- diterpenes inflammatory activities. Cephalotaxus fortunei var. alpina C. lanceolata 4. SESTERTERPENES consist of 25 carbon atoms with 5 isoprene units and molecular formula C25H40. naturally present in the fungus, marine organism, insects, sponges, lichens, and protective waxes of insects. These types of compounds are biologically active having anti-inflammatory, anticancer, antimicrobial, and antifungal activities Source and biological activities of some sesterpenes Nostoc sp. Cyanobacterium A and B showed moderate in vitro antibiotic activities. Sesterterpenes are rare among microbial secondary metabolites, with only one report of a previous alkaloid— sesterterpene found in cyanobacteria. This discovery represents a significant addition to the novel chemical structures active against resistant bacterial strains. Source and biological activities of some sesterpenes. Pleurotus ostreatus Mushroom species: Pleurotus ostreatus and Scleroderma areolatum (Earth Ball)  5) TRITERPENOID - A major class of secondary metabolites - usually contains 30 carbon atoms consisting of 6 isoprene units. - derived from the squalene biosynthetic pathway. - Triterpenes have many methyl groups; - can be oxidized into alcohols, aldehydes, and carboxylic acids, which make it complex and differentiate it biologically. - Triterpenes have many active sites for the glycosylation which converts it into other big class of compounds, namely: saponins, steroids, cardiac glycosides, etc. TRITERPENOIDS Structure of triterpenes Tubers of Hemsleya penxianensis Xuedanencins G and H were evaluated for cytotoxic activity against the Hela human cancer cell line and compounds showed significant cytotoxicity. Structure of triterpenes Leaves of Cyclocarya paliurus Cyclocariol A, B, and H were tested against human colon tumor (HCT-116) cell lines, exhibited good activities.  Meroterpenes the secondary metabolites with partial terpenoid skeleton. Meroterpenoids were partially derived from mevalonic acid pathways and widely derived from animals, plants, bacteria, and fungi. The classification of meroterpenoids is mainly based on their biosynthetic origin and two main groups can be observed: polyketide-terpenoids and nonpolyketide- terpenoids.  Structures of meroterpenes Ganoderma applanatum Liverwort Radula sumatrana This compound showed activity against the human cancer cell lines MCF-7, PC-3, and SMMC- 7721.  Structures of meroterpenes Mangrove endophytic fungus Talaromyces amestolkiae YX1 Amestolkolide B showed strong anti-inflammatory activity.  ISOLATION OF TERPENOIDS a)Steam distillation method b)Solvent extraction c)Maceration Isolation of essential oils from plants a) Steam Distillation b) Solvent Extraction c) Maceration  Structure Elucidation UV spectroscopy: It is used for the detection of conjugation in terpenoids IR spectroscopy: Used for detecting the presence of a hydroxyl group, an oxo group. Used for distinguish between cis and trans isomer. NMR spectroscopy: Proton NMR for the type of hydrogen Carbon NMR for the type of carbon Mass spectroscopy: Molecular weight of the compound  Uses: Many terpenoids inhibited different human cancer cells are used as anticancer drugs such as Taxol and its derivatives. Many flavorings and nice fragrances are consisting on terpenes because of its nice aroma. Terpenes and its derivatives are used as antimalarial drugs such as artemisinin and related compounds.  PHYSICAL PROPERTIES Soluble in organic Most of the Terpenoids are solvents and terpenoids are colourless liquid insoluble in water. optically active. Boiling point 150o Volatile in nature. – 180o C CHEMICAL PROPERTIES unsaturated compounds. undergo addition reaction with hydrogen, halogen, halogen acids to form addition products like NOCl, NOBr and hydrates. undergo polymerization and dehydrogenation in the ring. 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