Terpenoids PDF

NATURAL PRODUCTS FROM MEVALONATE & DEOXYXYLULOSE PHOSPHATE PATHWAY (TERPENOIDS) Assoc. Prof. Dr. Juriyati Jalil Faculty of Pharmacy Universiti Kebangsaan Malaysia  Natural products from mevalonate & deoxyxylulose phosphate pathway: o Terpenes o Terpenoids ...

NATURAL PRODUCTS FROM MEVALONATE & DEOXYXYLULOSE PHOSPHATE PATHWAY (TERPENOIDS) Assoc. Prof. Dr. Juriyati Jalil Faculty of Pharmacy Universiti Kebangsaan Malaysia  Natural products from mevalonate & deoxyxylulose phosphate pathway: o Terpenes o Terpenoids  INTRODUCTION Hydrocarbons known generally as terpenes and oxygen-containing compounds are called terpenoids. Terpenoids are the most important constituents of essential oils.  INTRODUCTION The terpenoids form a group of compounds the majority of which occur in the plant kingdom. A few terpenoids have been obtained from other sources.  INTRODUCTION Terpenoids are build up from two or more C5 units known as isoprene units. Isoprene is 2-methyl-1,3-butadiene (C5H8). Isoprene and the isoprene unit can be represented in various ways. INTRODUCTION  INTRODUCTION During the formation of terpenoids, the isoprene units are usually linked in a head to tail manner → known as the isoprene rule. The number of isoprene units is used as a basis for classification of these compounds. INTRODUCTION  Classification of terpenoids Class Carbon Isoprene Molecular atom units formula 1. Monoterpenoids 10 2 C10H16 2. Sesquiterpenoids 15 3 C15H24 3. Diterpenoids 20 4 C20H32 4. Sesterpenoids 25 5 C25H40 5. Triterpenoids 30 6 C30H48 6. Tetraterpenoids/Carotenes 40 8 C40H64 7. Polyterpenoids/Rubber >500 >100 (C5H8)n  Classification of terpenoids The terpenoids are further categorized as: ▪ Acyclic (open chain) ▪ Monocyclic (one ring) ▪ Bicyclic (two rings) etc ▪ Oxygenated derivatives such as alcohols, aldehydes, ketones, phenols, ethers and esters Representative terpenoids showing the isoprene units in each molecule  Nomenclature Terpenoids can be named systematically according to the general IUPAC rules of nomenclature → names derived are long and cumbersome. The trivial names are still used for common compounds.  Biosynthesis of terpenoids Terpenoids are synthesized in the plant by way of an important biochemical intermediate, isopentenyl pyrophosphate (IPP). Biosynthesis of terpenoids (IPP)  Biosynthesis of terpenoids IPP is derived from two pathways → mevalonic acid (MVA) → 1-deoxy-D-xylulose 5-phosphate (DOXP) General scheme of terpenoid biosynthesis (MVA pathway) MONOTERPENOIDS C10H16  Monoterpenoids Characteristic features → their volatility and intensely pungent odors. Responsible for fragrance and flavor. Hypothetic mechanism for biosynthetic formation of monoterpenoids Representative monoterpenoids  Monoterpenoids in Pharmacy Examples: ▪ Camphor ▪ Cineole ▪ Menthol  Camphor Ketone. Cinnamomum camphora (Lauraceae). Stems and roots. Crystalline. Dissolved in volatile oil. Topical antipruritic and anti- inflammatory, reducing cough when externally applied to the chest and throat, and local anesthetic by inhalation.  Cineole Or eucalyptol. Eucalyptus globus (Myrtaceae). Eucalyptus oil contains about 70- 85% cineole. Spicy taste → flavor. Nasal inhalers and sprays for antiseptic and mild anesthetic action to the nose and throat, and stimulating expectorants in bronchitis by steam inhalation. Menthol Menthan-3-ol → alcohol. Mentha arvensis. Colorless, needlelike crystals or cystalline powder. Peppermintlike odor. Tropical antipruritic, combined with camphor and eucalyptus oil (cineole) in ointments, cough drug, nasal sprays and inhalants to relieve bronchitis, sinusitis and nasal congestion. SESQUITERPENOIDS C15H24  Sesquiterpenoids The largest class of terpenoids. Among the first sesquiterpenoids isolated from nature → β-cadinene from oil of cade (juniper tar) and β-caryophyllene from clove oil. Sesquiterpenoid lactones → the presence of an -methylene--lactone system, also contain ,β-unsaturated carbonyls as well as epoxides.  Sesquiterpenoids Sesquiterpenoid lactones can be classified according to their carbocyclic skeleton: ▪ Germacranolides: a ten-membered ring. ▪ Eudesmanolides: two fused six-membered rings. ▪ Guaianolides: a five-membered ring fused to a seven-membered ring. Sesquiterpenoids  Sesquiterpenoids in Pharmacy Examples: ▪ Artemisinin ▪ Parthenolide Artemisinin Or qinghaosu. Sesquiterpenoid lactones. Artemisia annua (Asteraceae). Leaves and flowers. Traditionally used to treat malaria. More potent derivatives → artemether and sodium artesunate. Active against Plasmodium vivax and P. falciparum. Artemisinin Discovered by a pharmaceutical chemist, Tu Youyou from China. Based on the use of Artemisia annua in traditional Chinese herbal medicine to treat malaria. She received Nobel Prize in medicine in December 2015.  Parthenolide Sesquiterpenoid lactones → germacranolide type. Tanacetum parthenium (Asteraceae) →known as feverfew. Leaves. Anti-pyretic or febrifuge. DITERPENOIDS C20H32  Diterpenoids Non-volatile. Plants, fungus, marine organisms and insects. Usually isolated as optically active solids. Rarely combined with sugars to form glycosides.  Diterpenoids in Pharmacy Examples: ▪ Forskolin ▪ Ginkgolide ▪ Taxol  Forskolin Or colforsin. Labdane diterpenoids. Coleus forskohlii (Lamiaceae) → Indian herb. Roots. Congestive cardiomyopathy, bronchial asthma, glaucoma and hypertension.  Ginkgolide Diterpenoids lactone. Ginkgo biloba (Ginkgoaceae) Leaves. Ginkgolides A, B, C and M. Inhibit platelet-activating factor (PAF).  Taxol Or paclitaxel. Complex diterpenoid with a taxane ring system, a four- membered oxetane ring and an ester side chain at C-13. Taxus brevifolia (Taxaceae) → Pacific yew. Bark. Treatment of ovary and breast cancer. TRITERPENOIDS C30H48  Triterpenoids Can be divided into two main classes: ▪ Tetracyclic triterpenoids ▪ Pentacyclic triterpenoids  Triterpenoids Tetracyclic triterpenoids ▪ Contain steroid carbon skeleton. ▪ Comprised mainly of two groups → lanosterol and euphol.  Triterpenoids 17 17 9 8 3 HO HO Lanosterol Euphol  Triterpenoids Pentacyclic triterpenoids ▪ Comprised of various subgroups → ursane (-amyrin), oleanane (-amyrin), lupane (lupeol), etc.  Triterpenoids 20 20 19 -Amyrin 12 13 3 HO HO -Amyrin 29 30 20 21 19 11 25 26 1 28 10 15 3 27 HO Lupeol 23 24  Triterpenoids Most triterpenoids are alcohols and can combine with sugars to form glycosides → saponins. ▪ Steroidal saponins (tetracyclic triterpenoid saponins) ▪ Triterpenic saponins (pentacyclic triterpenoid saponins) Free triterpenoids are often components of resins, latex or cuticle of plants.  Triterpenoids Steroidal saponin Pentacyclic triterpenoid saponin Dioscin Glycyrrhizic acid (Dioscorea spp.) (Glycyrrhiza spp.) TETRATERPENOIDS/CAROTENOIDS C40H64  Tetraterpenoids/Carotenoids Yellow, orange, red and purple colors seen in living organisms are due to the presence of these compounds. Functions: ▪ Plants and microorganisms → as photoprotective agents, as photosynthetic accessory pigments and as a membrane stabilization components. ▪ Animals → as a source of vitamin A, as photoprotective and cancer prevention agents. Tetraterpenoids/Carotenoids in Pharmacy Examples: ▪ Vitamin A ▪ -Carotene  Vitamin A Common dietary sources → animal organs (heart, kidney, liver), eggs, dairy products and fish. Involved in vision, growth and tissue differentiation. Retinol is the major form of the vitamin.  -Carotene Colours of the red tomato and the orange carrot. Non-toxic, used as colorants in the formulation of tablets and in the food industry. Reducing photosensitivity in individuals with erythropoietic protoporphyria.