Chemistry of Natural Products
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CHEMISTRY OF NATURAL PRODUCTS Prepared By Mr. Dilip Tayade (Associate Professor) Department of Chemistry Dhanaji Nana Mahavidyalaya, Faizpur Dist.-Jalgaon , Maharashtra, India- 425503 NATURAL PRODUCTS Terpenoids Terpenoids are naturally occurring compounds obtained from various parts of plants, microbes and animals. Terpene-Mixture of isomeric hydrocarbons of the molecular formula C10H16 occurring in terpentine and many other essential oils. All these compounds are composed of isoprene units C5H8 Terpene- It is defined as natural products which consist of one or more isoprene units. They are also called as terpenoids. Types:- Terpenoids are two types 1) Simple Terpenoids- obtained from sap and tissues of certain plants ,these are steam volatile ,occurred in essential oils 2) Complex Terpenoids – obtained from gum & resins of plants,these are not steam volatile. Isolation: Four Methods 1) Extraction 2) Steam Distillation 3) Solvent Extraction 4) Adsorption in purified fats ( enfleurage) Extraction Method- Barks, leaves, seeds and flowers are crushed & juice is screened to remove particles, centrifuged e.g.- Citrus , lemon and grass oil Steam Distillation- Volatile oil distill out along with steam when plant material is kept under steam distillation. An oil then collected by extracting with organic solvents such as petroleum ether . Oil under goes changes such as, Acid gets decarboxylated , ester gets hydrolyzed , some ring compounds may breaks and also affect on odor of essential oil. Solvent Extraction- crushed plant material is extracted with petroleum ether, diethyl ether and then distilled out Adsorption in purified fats ( enfleurage)- Classification of Terpenoids No. of Molecular Class of Terpenes Examples Isoprene Formula units 1 C5H8 Hemi-terpenoid Isoprene itself Citral,Limolene,α-terpenoids, 2 C10H16 Mono-terpenoid menthol,dipentone α-pineol,camphor 3 C15H24 Sequi-terpenoid Humulene,bisabolenes 4 C20H32 Di-terpenoid Sex hormons,testoteron, estradiol,vitamin-D 5 C30H48 Tri-terpenoid Steroids such as ( Steroid) choleterol, Ergosterol 6 C40H64 Tetra-terpenoid β-Carotene (Caretenoid) 7 (C6H8)n Poly-terpenoid Natural Rubber At the second level, each group of terpenoids is further classified into further groups on the basis of number of rings present in the molecule. Mono-terpenoids Acyclic Monocyclic Bicyclic Monoterpenoid Monoterpenoids Monoterpenoids CnH2n-2 CnH2n CnH2n-2 Citral α- Terpineol, C10H18O Camphor C H O C H O 10 16 Menthol C10H20O 10 16 α- Pinene C H Dipentene C10H16 10 16 Limolene C10H16 At the third level, each class is further subdivided according to functional groups present in the terpenes. Monocyclic Monoterpenoids Bicyclic monoterpenoids Hydrocarbons Alcohols Hydrocarbons Ketones Dipentene α- Terpineol α- pinene Camphor Menthol Isoprene Rule: The skeleton structure of all naturally occurring terpenoids is built up of two or more isoprene units called as isoprene rule Ingold pointed out that the isoprene unit in naturally occuring terpenoids were joined head to tail .This is known as special isoprene rule. Applications of rule: i) This rule helps in determining the framework of unknown terpenoids. ii)The framework in which the isoprene rule & special isoprene rules are noy followed are ruled out. The following frameworks are accepted . All these structure follows rules General Methods for Structure Determination of Terpenoids 1. Molecular Formula:-Presence of elements are determined from which empirical formula is determined. From empirical formula & mol.wt. the mol.formula is calculated. 2. Detection of unsaturation:- 3.Nature of Oxygen Function:- Oxygen atom may be (A)-OH, (B) –COOH, (C ) -C=O, (D) –CO-CH2- (E) –COCH3 can be detected as A) -OH ( Alcoholic )group:- It is detected by the action of acetic anhydride or phenyl isocyanate R-OH + Ac2O R-O-Ac + AcOH R-O-H + O=C=N-C6H5 R-O-CO-NH-C6H5 B ) -COOH ( Carboxylic ) group :- R-COOH +NaHCO3 R-COONa +CO2 + H2O C) >C=O ( Carbonyl ) group :- >C=O + H2N-OH >C=N-OH + H2O Oxime derivative R-CHO + 2Ag(NH3)2OH R-COOH +2Ag +2NH3 +H2O -CO-CH2- (Oxo) group :- C6H5CHO +HNO2 Oxime +Benzylidene deri. E) –CO-CH3 ( Acetyl ) group:-It forms haloform reaction or on strong oxidation with CrO3 gives acetic acid. 3 Br /NaOH Bromoform R-CH2-CO-CH3 2 R-CH2-COOH + CHBr3 CrO ( O ) Acetic acid R-CH2-CO-CH3 3 R-COOH + CH3COOH 4) Degradation Products: Oxidative oxidation is more imp in structure determination. Oxidizing agents such as alkaline KMnO4, H2O2,O3,CrO3,NaOBr etc. used for degradation. We can find out position of olefinic bond , primary, secondary & tertiary alcohol present in a terpenoid . a) Alkaline KMnO4 :- Olefinic bond gives dihydroxy compound ( glycol ) ii) Trisubstituted compound gives ketones & acid iii)Primary & secondary alcohols are stepwise oxidised to acids while tertiary alcohols are not oxidized by alkaline KMnO4 . R1-CHOH-R2 ( O ) R1-CO-R2 b)CrO3 – It also oxidizes alcohol stepwise. c) O3 ( Ozone )- Ozonolysis find out the position of olefinic double bond . i) Terminal alkenes after ozonolysis gives formaldehyde as one of the product. ii)Tetra-substituted alkene gives diketones:- d) OsO4 :- Alkenes react with OsO4 gives glycol e) Performic acid( H-COOOH):-Alkenes react with performic acid and forms epoxide which on hydrolysis gives glycols. 5) Dehydrogenation:- Dehydrogenation of terpenoids is carried out by heating them in S , Se , Pd & Zn. 6) Dehydration:- conc.H2SO4 ,KHSO4,P2O5, ZnCl2 are commonly used for dehydration of terpenoids , most of the terpenoids on dehydration gives p-cymene. 7) Physical Methods:- U.V., I.R., NMR,Mass spectroscopy are modern methods used for determining structure of terpenoids. 8) Synthetic Methods:- The final confirmation of structure is achieved by its synthesis in the laboratory. Monoterpenoids 1) Citral Class:- Citral belongs to acyclic ( open chain monoterpenoids) Occurrence:- Lemon grass oil ( 70-80 %) Isolation :- Isolated as sodium bisulphite addition product which on hydrolysis gives citral. Properties :- 1). It is a colourless oil,B.P .2280C 2). It is optically inactive. Uses:- 1). It is mostly used as perfume 2). It is the starting material for synthesis of vitamin A Structure determination of citral 1). Molecular Formula:- C10H16O 2). Detection of unsaturation:- 3)The formula for parent saturated hydrocarbon of citral becomes C10H22,which corresponds to a general formula CnH2n-2 suggesting that citral is a acyclic terpenoid. Nature of oxygen:- a) Citral forms an oxime withhydroxyl amine and bisulbhiteaddition productwith saturated NaHCO3. Therefore citral contains either aldehyde or ketonic group. b) Citral on reduction with Na/Hg in dil.acid forms a primary alcohol,geraniol (C10H19O ). Citral 0n mild oxidation with moist Ag2O gives geranic acid( C10H16O2) without loss of carbon atom. Geranic acid Citral Geraniol R-COOH R-CHO R-CH2-OH These reactions confirm the presence of aldehyde group. 5) Position of aldehyde group:- a)It shows λmax 238nm which is characteristic of conjugated aldehyde group. b) Citral on hydrolysis with aq.K2CO3 soln under high pressure gives acetaldehyde & a ketone i.e. methyl heptenone( 6-methyl-hep5-ene-2one) Both reaction proves that citral is a conjugated aldehyde. 6) Carbon skeleton in citral:- Citral when heated with KHSO4 undergoes cyclisation to form p-cymene. Formation of p-cymene proves that citral contains a C- CH3 and isopropylidenen gr. In 1:4position wrt each other By considering all above reactions,the possible carbon skeleton is Does not follow isoprene rule follow isoprene rule 7) Oxidative degradation:-a) b) Formation of acetone in both reaction shows the presence of gem dimethyl group in citral. From all above reactions following structure is assigned Reactions of Citral: Synthesis of Citral a)2,4 Dibromo2 methylbutane reacts with sodio acetyl acetone forms methyl heptenone b) Conversion of methyl heptenone into citral ALKALOIDS Alkaloids are naturally extracted which contain at least one nitrogen atom. These are similar to alkali hence called as alkaloids and having marked physiological,toxic and curative action on living organism. alkaloids are very poisonous but if taken into small quantity can act as medicine. E.g. -Nicotine stimulates the CNS, Morphine relieves pain Occurrence: - Alkaloids are naturally extracted from leaves roots , barks, seeds and fruits Isolation:- 1). The plant material containing alkaloids are dried , powdered & extracted with petroleum ether to remove soluble fats. 2). The residue is then extracted with methyl alcohol so that alkaloids get dissolved in methyl alcohol and residue containing cellulosic and other insoluble material is rejected. 3). The filtrate is distilled off & the crude plant extract is then treated with H dil.HCl or H2SO4 (P =2) when alkaloids converted into their soluble salts, which are then treated with ether or chloroform. 4). Ether layer contains non basic plant material & it is rejected . 5). The water soluble parts containig salt of alkaloids is treated with Na2CO3 or NaOH when alkaloids precipitate out which are then extracted with ether or chloroform. 6). The ether layer is distilled off & the residue obtained contains a mixture of alkaloids . The individual alkaloids are separated by using techniques like fractional distillation, steam distillation and chromatography. Powered Plant Material Extracted with Petroleum Ether Residue Ether Part Extracted with Methyl alcohol (Soluble fats rejected) Methyl Alcohol Part contain Alkaloids Residue Distilled off to remove methyl alcohol ( Cellulosic material rejected) Crude Plant Extract