Lecture 7 - Volatile Oil Part 3-End - Phytochemistry PPC 303 - New Mansoura University PDF

New Mansoura University Faculty of Pharmacy Pharm D Program ___________________________________________________________________________ Phytochemistry (PPC 303) Volatile oil Dr. Mona Farouk El-Neketi...

New Mansoura University Faculty of Pharmacy Pharm D Program ___________________________________________________________________________ Phytochemistry (PPC 303) Volatile oil Dr. Mona Farouk El-Neketi Lecture 7 Phytochemistry PPC 303 (Volatile Oil) NMU 1 Phytochemistry PPC 303 (Volatile Oil) 3 NMU  Chemistry of Essential oils  Classification of Volatile oil constituents:  Oxygenated terpenoid Compounds 2- Phenols, Phenol ether 3- Aldehydes. 4- Ketones 5- Esters. 6- Acids. 7- Oxides. 8- Peroxides. Sulfur compounds. Sulfur and nitrogenous compounds. Phytochemistry PPC 303 (Volatile Oil) NMU 4  sources of volatile oils  Physical properties of volatile oil components  Chemistry of volatile oil components  the different classes of volatile oil constituents with emphasis on those having pharmaceutical applications.  The suitable methods for isolation, purification, identification, analysis of specific volatile oil constituents from their natural origin adapting the suitable laboratory rules Phytochemistry PPC 303 (Volatile Oil) NMU 5 Oxygenated Compounds ‫تابع‬ Phytochemistry PPC 303 (Volatile Oil) NMU 6 7  II. Phenols and Phenolic Ehthers Importance: Phenols are very important antiseptic and germicidal agents e.g. thymol, eugenol, …etc Isolation:  Formation of phenolates (= phenates) with alkali which is water soluble.  Fractional distillation  GC/MS and HPLC N.B. Phenolic ethers are neutral compounds and do not react with alkalis but generate phenols on heating.  Separation of phenols based on their acidic property (Formation of phenolates) Phenols are weak acids. They are acidic enough to form with dilute alkali water soluble salts (phenolates) This property is used to separate phenols from non-phenolic constituents. Oily layer Volatile oil with (dil.) KOH phenolic and H+ non-phenolic Aqueous layer Phenol constituents (water soluble salt) Distillation or Tests for identity: extraction Phenolics give highly colored compounds with FeCl3.  Estimation of Phenols: Principle: Phenol form water soluble salts with alkalis Method: In a cassia flask, add known volume of oil. Add aq. KOH solution and mix  Phenol forms phenolate soluble salt in water and the non phenolic part separates as oily layer which can be measured in the graduated neck of cassia flask. N.B. KOH is preferred than NaOH because the potassium salts of many phenols are more soluble than the corresponding sodium salts. 2. GC-MS and HPLC  Uses: All phenols and polyphenols antiseptic effect, antioxidant and free radical scavenger Hypocholesterolemic and Insect repellant  II- Phenols & Phenol Ethers B- Phenol ethers: A- Phenols: 1- Anethole. 1- Thymol. 2. Myristicin 2. Thymoquinone 3- Apiole 3- Eugenol. 4- Dillapiole OH  1-Thymol (3-hydroxy p-cymene ) OH Occurrence: oil of Thymus vulgaris ‫( الزعتر‬Fam. Labiatae) Isolation: cooling the oil, thymol crystallizes. Identification: b. Thymol + FeCl → no color (contrary Thymol 3 to carvacrol, that gives a green color) How can you prepare Thymol from Menthol ???  1-Thymol: Continue Synthesis of Thymol How can you prepare Thymol from Menthol ???  1-Thymol: Continue Uses: 1. Antiseptic, disinfectant, antifungal (e.g. gargles: mouth - Sore throat) 2. G.I.T. disinfectant in case of enteritis 3. Hepato-protective, 4. antioxidant, 5. free radical scavenger 6. Immune-stimulant which inhibits the synthesis of leukotrienes and thromboxane 7. Effective in treatment of productive cough  Occurrence: oil of Nigella sativa Uses: ‫حبة البركة‬ 1. Anti-inflammatory, 2. Antioxidant, 3. Hepatoprotective activity comparable with Silymarin 4. Inhibits leukotrienes and thromboxane synthesis which could help in treatment of productive cough.  2- Eugenol: Occurrence: in clove oil “Eugenia aromatica” Isolation: by 5% KOH method. Characters: Oily liquid with clove-like odour & burning spicy taste. Identification of eugenol: a) Colour test: with 2% alc. FeCl3 → blue colour Uses: 1. Local anaesthetic & antiseptic in toothache remedies 2. Eugenol is combined with zinc oxide to form zinc oxide eugenol, which is restorative in dentistry. 3. Spice & flavouring agent 4. Synthesis of vanillin (not practical)  1-Anethole: Occurrence: in oil of anise and fennel Isolation: By cooling the oil → anethole crystallizes  Characters: sweet odor & taste with Estrogenic effect Anethole is oxidized by light and air to give many products among which is photoanethole 1. In baby water Uses 2. Antioxidant 3. Flavouring agents in many pharmaceuticals, 4. Anethole has estrogenic and prolactin activity 5. Insecticidal activity 6. Precursor to illicit drugs: anethole is an inexpensive chemical precursor for paramethoxy amphetamine.  3-Apiole: parsley seed oil 4-Dillapiole: dill oil ‫بقدونس‬ Use: 1. Anti-hyperlipidema 2. Have mild CNS activity.. 3. Have insect repellant activity 4. Apiole have diuretic effect facilitating passage of kidney calculi and even prevent its formation 5. Induces menstruation, effective for menstrual disorders, stimulates contractions of the uterus and may cause abortions in large doses 6. Dillapiole protect from gall bladder stones formation. Phytochemistry PPC 303 (Volatile Oil) NMU 20  III. Aldehydes and Ketone B. For Estimation of Aldehydes and ketones: Condensation reactions: Reaction with hydroxylamine HCl : the best of all Aldehyde + Hydroxylamine HCl → Oxime + HCl R-CHO+NH2OH.HCl RCH=N-OH(oxime)+HCl+H2O The produced HCl is titrated against standard KOH sol. Advantages: 1- It requires only little amount of oil (about 1-5 ml), 2- The reaction time about 20 minutes. 3- It is universal and valid for most aldehydes and ketones. However, determination of individual component in the mixture is impossible but the total carbonyl compounds will be determined.  III. Aldehydes and Ketones Examples : Occurrence: in Eucalyptus oi, Citronella oil Uses: 1. In perfumes, soaps,…to impart lemon-like odor. 2. In preparation of citronellol (rose-like odor) 3. Insect repellent.  2- Citral Occurrence: lemongrass oil as mixture of isomers Properties: lemon-like odor. Uses: in industry, perfuming, flavoring (7up) and insect repellant  Synthetic citral: can be obtained by oxidation of linalol or geraniol  Aromatic Aldehydes: 1- Benzaldehyde Source: Bitter almond oil as glycoside Use: employed to confer almond flavor to foods 2-Cinnamaldehyed Occurrence: in cassia and cinnamon bark oils. Uses: favoring, agent and manufacture of artificial cinnamon flavor.  3-Vanillin: Occurrence naturally: in vanilla pods as glycoside, By enzymatic hydrolysis these glucosides release Vanillin and purified by sod. bisulfite method. Properties It is considered to be phenol and can be estimated either as aldehydes using the bisulfite method or as phenol using alkali hydroxide method. Reaction: Vanillin gives blue color with FeCl3. Uses: 1. Flavoring agent in food, candies, perfumes & cosmetics 2. a general-purpose reagent for TLC plates  3-Vanillin:continue Syntheses: 2- From eugenol 1- Oxidation of lignin (lignin is a polymer of woody material and a by- product in manufacture of paper) commercially in large amount 3- From guaiacol: commercially in large amount application of Riemer Tiemann's reaction  Ketones Examples Occurrence: in oil of Mentha = peppermint oil Isolation: by fractional distillation Properties: colorless, oily liquid with menthe like odor O Uses: in compounding artificial essential oils, flavoring, antispasmodic, preventing biliary stasis and improve the digestive function of the liver (Rowachol® pills). Menthone  2- Carvone Occurrence: in oil of caraway Uses: Flavoring agent in many pharmaceutical preparations, Carvone gargles, and tooth pastes. 3- Diosphenol OH Occurrence: in Buchu leaf oil Isolation: By cooling at -20 ºC O Properties: camphor-like odor Diosphenol Has phenol-like character “enolic”, form soluble enolate salt with dil KOH: Identification: give a green color with FeCl3 test solution. Uses: Urinary tract antiseptic  Bicyclic terpene ketone  e.g. Fenchone  e.g. Camphor ☺ Synthesis From α-pinene ?! ‫اشجار الكافور‬ Occurrence: in oil of fennel Occurrence: oil of camphor tree and oils Isolation: of rosemary Fractional distillation (195ºC) Isolation: Crystallize on cooling Crystallization on cooling Uses: Uses: in room spray & bath Locally: Rubifacient & mild antiseptic preparations to mask the undesirable as cough suppressant and anti- odors inflammatory  Q: Synthetic camphor can be obtained from alpha- pinene: Explain? Most camphor of commerce is obtained synthetically from α-pinene How could you differentiate between natural and synthetic camphor? Test for Cl- Synthetic camphor usually gives a positive test for chloride ions due to the use of HCl in its preparation  How could you resolve a mixture of Camphor and borneol? Camphor and borneol are always together since borneol is the precursor of camphor. For resolving a mixture of borneol and camphor: Convert camphor to its oxime and oxime dissolves in sulphuric acid which is water soluble while borneol can be extracted by ether, camphor can be regenerated from its oxime by addition of alkali. Note: Borneol is alcohol while Camphor is ketone  a) Aliphatic b) Aromatic e.g. Geranyl acetate e.g. Linalyl acetate e.g. Benzyl benzoate e.g. Methyl salicylate Occurrence: oil of In lavender / In oil of wintergreen In balsams lemongrass bergamot oil (99%) as glycoside Isolation: By enzymatic by distillation under vacuum to avoid By cooling hydrolysis hydrolysis Main use is scabicidal Topical: Rubifacient, Uses: In perfume, cosmetic, & soap (Benzanil® Cream). analgesic & industry As diluent & fixative in antirheumatic perfumes  c) Esters Containing Nitrogen COOCH3 NH2 Occurrence: in leaf oil of lavender Identification: By physical examination of characteristic blue-violet fluorescence Uses: Antifungal 1- Methyl anthranilate is an ester containing Nitrogen isolated from Jasmine oil and can be used as…. 2- Benzyl benzoate is an aromatic ester that can be used as ……….. 3- Methyl salicylate can be obtained from oil of wintergreen and can be used as ………….. 7- Uses of 1,4 cineol include…… 9- Uses of Thymol include ……………  V - Oxide Occurrence: In all species of Eucalyptus and sage Preparation: By fractional distillation ‫المرمرية‬ Isolation and estimation: 1,4-Cineol H3PO4-Cineol Uses: ‫الكافور‬  Cineole is expectorant, in case of bronchitis  Diuretic  Prevent calculus formation in kidney or even help in dissolving the already formed calculus either in kidney or gall bladder.  Locally: antiseptic and inflammatory disorders  Isolation and Estimation 3ml phosphoric acid 10 ml Eucalyptus oil 10 min. Oil converted Ice to solid mass Transfer the solid mass into piece of cloth  wrap it  pressing by test tube till give no stain Transfer the dry solid mass to cassia flask  mix well with boiling water. Add on W.B. till decomposition is complete & give oily layer then raise the oily layer into graduated neck of the flask by addition of hot water.  VIII- Sulfur Containing Compounds 1- (Allicin) SO enzymatic action SO COOH S Allicin Allin NH2 Allicin is occurring in garlic (Allium sativum) in a combined form (allin) and is freed by enzymatic action. Allin is converted to allicin by air oxidation or under alkaline condition. Garlic yield 0.3 -0.5% of allicin which possess the characteristic taste and odor of garlic. Allicin and garlic possess pronounced immunostimulant, bacteriostatic, antiviral and antioxidant properties and used in treatment of hypercholesterolemia. Resin and Resin combinations  Definition: The term "resin" is applied to indicate a group of solid or semisolid substances of very complex chemical nature and variable chemical composition. These substances are brittle secretions or exudation of plant tissue, either produced normally Or as the result of pathogenic condition as colophony.  PHYSICAL PROPERTIES : Resins, as a class, are:  hard, transparent or translucent brittle substances.  On heating at a comparatively low temperature, resins often soften and finally melt forming sticky or adhesive fluids, without volatilization or decomposition. On heating (direct flame) in the air, resins burn readily with a smoky flame owing to the large amount aromatic compounds.  Resin Combinations 1-Oleoresins: Resins associated with volatile oils (turpentine) 2-Gum-resins: Resins with gum, similar in composition to gum acacia. 3-Oleo-gum-resin: Resin in association with volatile oil and gum.(Myrrh and Olibanum) Classification of Resins i. Resins: Colophony, cannabis ii. Oleoresins: copaiba. iii. Oleo-gum resins: Myrrh and Olibanum  Distillation to separate resin from oil Resins Method of preparation of Colophony resin from pine tree oleoresin  Turpentine Oil -Turpentine oil consists mainly of α-pinene & β-pinene. Pharmaceutical uses: - Mild antiseptic action. - As insecticide. - In production of synthetic camphor Non-pharmaceutical uses: - As solvent for waxes & furniture polishes.  4- Cannabis Resin  Origin: Cannabis (Indian hemp or cannabis indica) consists of the dried- flowering tops of Cannabis sativa (Fam. Cannabinaceae). Constituents: Resin Alcohol  Mastic: is resin Mastic is a resin obtained from the mastic tree. It is also known as tears Chemical Composition: Resin phenol Uses Anti-Inflammatory Anti-Oxidant Properties Antibacterial Properties: spectrum of antimicrobial activity, which extends beyond the H. Pylori eradication  Oleo-Gum-Resins 1- Myrrh ‫مر البطارخ‬ Is an oleo-gum-resin obtained from stems and branches of Commiphora molmol and other species of Commiphora (Fam. Burseraceae) Oleo-gum resin is formed in: schizogenous secretion in the bark and pith. Active Constituents 7-17% yellowish-green thick volatile oil. 20-40% resin 57-61% gum of acacia type. - - Recent studies: revealed that Myrrh is a new schistosomicidal drug.‫لعالج البلهارسيا‬  Olibanum: Oleo-Gum-Resin ‫اللبان الدكر‬ Origin: Olibanum is the oleo-gum-resin obtained from Boswellia carterii Uses: Constituents:  boswellic acid  Immunostimulant  volatile oil  Olibanum, in the form of a  and bitter principal decoction; is used as expectorant and cough sedative. ‫مهم‬  It is also used in the manufacture of incense ‫البخور‬. Phytochemistry PPC 303 (Volatile Oil) NMU 49  End of Lecture 7 Volatile oil part 3- end Phytochemistry PPC 303 (Volatile Oil) NMU 50