Chemistry of Natural Products (PHG 322) Lecture Notes (MSA University) PDF

 Learning outcomes of this lecture Define and classify volatile oils Understand the physical characters of volatile oils Recognize the chemical composition of volatile oils Recognize the natural sources, chemical structures, pharmacological actions and therapeutic uses of volatile oil...

 Learning outcomes of this lecture Define and classify volatile oils Understand the physical characters of volatile oils Recognize the chemical composition of volatile oils Recognize the natural sources, chemical structures, pharmacological actions and therapeutic uses of volatile oil isolates belonging to the hydrocarbon class Scheme methods for isolation and determination of volatile oil isolates belonging to the hydrocarbon class Interactive teaching methods Socrative = easily evaporate on exposure to air at ordinary temperature. Latin word "essentia" * a liquid easily changed to a gas ** the "essences" or odoriferous constituents of the plants. VOLATILE OIL = ESSENTIAL OIL = ETHERIAL OIL DEFINITION Complex liquid mixtures of odoriferous principals obtained mainly from plant sources and rarely from animal sources of varying chemical composition. Easily evaporate when exposed to air at ordinary temperature. Used for either their specific therapeutic activity or their aroma. 1. Therapeutic & medicinal uses: local stimulants, carminatives, diuretics, mild antiseptics, local irritants, anthelmintics, parasiticides … 2. Spices & condiments: in food seasoning (to impart aroma & flavor) or as preservatives 3. Flavoring agents: in food (e.g. beverages, soups, bakery products, confectionery) & pharmaceutical industries 4. Aromatic agents: in all types of perfume industries (cosmetics, soaps, deodorizers, household cleaners, polishes & insecticides) 1. Colorless, pleasant smelling liquids, volatile at room temperature 2. Steam distillable 3. High refractive index 4. Mostly optically active 5. Density < water (i.e. lighter than water) except for few ones 6. Immiscible with water, but sufficiently soluble to impart a fragrance to water → aromatic waters [hydrosols] 7. Soluble in alcohol & common organic solvents 8. Darken in color if exposed to air & light (resinification)  Blue 1 Oils containing azulenes (oil of Chamomile) are colored. CH3CH2CH2CH2-- 2 Oil of Rose is turbid due to presence of paraffin hydrocarbons. 3 Oil of Anise and oil of rose solidify below room temperature (15 & 18oC, respectively) 4 Oil of Lemon is a non-volatile gummy residue. 5 Oil of Cinnamon, oil of Clove and winter green are heavier than water Chemical composition of volatile oils  Volatile oils Complex chemical mixtures Vary widely in chemical composition Many types of hydrocarbons and oxygenated compounds such as alcohols, ketones, aldehydes, ethers, oxides, phenols and esters N.B.: Few oils may consist of one main component e.g. volatile oil of mustard (93% allylisothiocyanate) and volatile oil of clove (85% eugenol).  Relationship between chemical structure and odour (Organoleptic Characteristics of Vol. Oils) 1. Compounds of different chemical constitution may sometimes give the same odour. 2. Some substances change their odour on dilution e.g. Indole in small concentrations is a pleasant component in perfumes of white flower of jasmine, but in larger concentrations gives an odour of putrefaction. 3. Aldehydes have characteristic strong odours. 4. Esters have fruity odours. 5. Ketones have pleasant odours. 6. Nitriles have a bitter almond odour. 7. Different isomers may produce different odours e.g. d- carvone has an odour of caraway, while l- carvone has spearmint odour.  Chemistry of Volatile Oils Constituents: Composition of Volatile oil ‫رخآال نم‬ The composition of volatile oils is quite complex. They include a great variability of constituents that belong mainly to the following groups: Not important!!!! 10 carbons Terpenoids Phenyl Aliphatic miscellaneous compounds (mainly mono- propanoids compounds mainly organo-nitrogen and Phenyl + Propane and organo-sulfur sesquiterpenoids). compounds. Mono = 10, Di = 20, Tri = 30 ▪ Each group includes both oxygenated and non-oxygenated (or hydrocarbons) members. ▪ The oxygenated compounds are, in most cases, those responsible for the characteristic odor of the oil.  Terpenoids Terpenoids were proved to be synthesized from Isoprene. Isoprene is also known as isopentene or 2 methyl-buta-1: 3-diene The isoprene units arise from acetate, via mevalonate, and are branched five-carbon units containing two unsaturated bonds. 1 CH 2 h 4 t Abbreviated structure H2C 3 C 2 h=head, t=tail C CH3 - isoprene units arise from acetate (3 mol.) C5 H8 Isoprene, 2-methyl 1:3 butadiene,  isopentene 3 Acetyl CoA MVA+ (mevalonate) O-PP O-PP IPP DMAPP  Terpenoids - Biosynthesized from a variable number of isoprene units (via head-to-tail condensation) 1 h CH2 h= head t CH2 C t= tail 4 2 C CH3 3 Isoprene 2-methyl but-1:3-diene [1,3 isopentene] Each group of terpene arises from the head-to-tail condensation of a variable number of isoprene units  1 CH2 CH2 C 4 2 C CH3 3 Isoprene h h= head t t= tail  1 CH2 CH2 C 4 2 C CH3 3 Isoprene h h= head t t= tail Only for ideas!!! Bicyclic monoterpenes (C10) 1 Acyclic Paramenthane Metamenthane Isoprene monoterpenoid Monoclyclic!!! Monocyclic (C10) (C10) monoterpenoid Alicyclic: (No benzene) Thujane Carane Pinane Bornane Fenchane iso-Camphane (Camphane) Only for ideas!!! Sesquiterpenes (C15) Isoprene Isoprene Isoprene Acyclic sesquiterpene Monocyclic sesquiterpene  Terpenoids in essential oils Monoterpenoids (C10H16 ) - Volatile Sesquiterpenoids (C15H24 ) - Low Mol. Wt. They may be: - Acyclic (aliphatic) Carotene - Alicyclic (cyclic) - Hydrocarbons (90% of Citrus oil) - Oxygenated (alcohols, aldehydes, ketones, esters, ethers, oxides or peroxides) - They are optically active Compounds arising from terpenes degradation: → ionones (from auto-oxidation of carotenes) in fruit flavors → irones (from oxidation of bicyclic triterpenes)in the absolute of Iris florentina Irones Phenyl propanoids in essential oils Less common. Phenols (eugenol), Phenol ethers (anethole), Aldehydes (cinnamic ald.), Lactones (coumarins; but not V.O.)  The Isoprene Rule Classified according to the number of isoprene units involved in their molecules as follows: Class Empirical formula Isoprene units Examples Hemiterpenoids C5H8 1 Isoprene Myrcene, limonene, Monoterpenoids C10H16 2 -pinene Sesquiterpenoids 3 Santalene C15H24 Abietic acid, Taxol Diterpenoids C20H32 4 alkaloid Triterpenoids 6 Saponins C30H48 Tetraterpenoids C40H64 8 Carotenoids  Removal of Terpenoid Hydrocarbons (Preparation of Terpeneless Oil) Oils rich in terpenoid hydrocarbons are liable to rapid deterioration on storage through oxidation and polymerization to yield bad smelling (turpentine like odor) and resinified products. Also presence of high terpenoid content will cause: Decrease its aroma Decrease solubility of oil in low-strength alcohols Rapid resinification. Terpeneless oils are more expensive than natural oils and characterized by: More stable. More soluble in low strength alcohol. Smaller amount is used to give the same strength of aroma. Richer in oxygenated compounds.  Removal of Terpenoid Hydrocarbons (Preparation of Terpeneless Oil) Thus a considerable amount of the terpenoid hydrocarbons could be removed by: 1 Fractional distillation under reduced pressure; hydrocarbons have lower boiling points and therefore, distill first and are discarded. 2 Column chromatography on silica gel, by eluting hydrocarbons with n-hexane then oxygenated compounds with absolute alcohol. 3 Selective extraction of the oxygenated components by dilute alcohol followed by distillation.  Volatile oil isolates Is one definite chemical substance isolated from the oil Chemical Physical methods methods Formation of soluble salts , Cooling ,fractional distillation, derivatization (based on the preparative chromatography presence of functional groups) , adduct formation. Stearoptenes, oleoptenes → mix. of several components Volatile oil isolates: ⚫ 1-Hydrocarbons. ⚫ 2-Alcohols. ⚫ 3-Phenols and phenolic ethers. ⚫ 4-Aldehydes and ketones. ⚫ 5-Oxides and Peroxides. ⚫ 6-Esters. ⚫ 7-Organo-nitrogen and organo-sulphur compounds. Break