INTRODUCTION Two main source of medicine are, one is synthetic and another is naturally occurring.
Synthetic drugs show rapid onset of action but having more side effects in comparison to naturally occurring drugs. The modern trend re back to choose natural medicine against synthetic medicine. Natural source of drugs are plants, animals, or minerals. About 8000 plants are listed in medicinal uses. In this 1800 in Ayurveda, 1100 in Shiddha, 750 in Unani, 300 in Tibetan and 4700 plants are used as traditionally ethno medicinally. The world over the total trade of medicinal plants about 8800-lakh dollar, of which contribution of India in world trade less then 1%. Out of this majority of plants are yet to be study photochemical, estimated of such pants to the extent of 5000 to 6000. Phytochemistry is branch of Chemistry, which deals with the study of chemistry of plants. Where the term phytochemistry is comes out from phyta + chemistry (phyta⇒ plant). Pharmaphytochemistry The word pharmaphytochemistry is derived from pharmakon⇒drugs, phyta⇒ plants i.e. chemistry of medicinal substance inside the plants. Alkaloids Chemistry: Sertuerner in 1806 laid the foundation of Alkaloids Chemistry. It is the branch of Pharma Phyto Chemistry, which deals with the study of Alkaloids. He reported isolation of Morphine from opium. What is Alkaloids: Alkaloids means Alkali likes. The Pharmacist W.Meissner proposed the term Alkaloids in 1819. Acc. to him "Alkaloids (alkali = base, oid=like sub) are basic nitrogenous compd. of plant origin which have complex molecular structure & many pharmacological activity." Acc to Landenberg "Alkaloids are defined as natural plant compounds that have a basic character and contain at least one nitrogen atom in a heterocyclic ring and having biological activities." Acc to characteristic features Alkaloids are basic nitrogenous plant origin, mostly optically active & possessing nitrogen hetero cycles as there structural units with physiological action.
This definition not fully correct because not follow on all alkaloids for e.g. Colchicine: Colchicine is regarded as an alkaloid although it is not Heterocyclic and is scarcely basic. Thiamine: It is heterocyclic nitrogenous base but not as a alkaloid because it is universally distributed in living matter. Nitrogen as side chain: Some compound is classed as in alkaloids but they do not contain nitrogen in heterocyclic ring, but contain nitrogen inside the chain e.g. ephedrine, hordenine, betanine, choline, muscarine, strychnine & tryptamine etc. Naturally occurring open chain basic compound: These compounds have physiological activity but do not class in alkaloids e.g. Cholines, amino acid, phenylethylamines etc. Piperine: It is neither basic character nor possessing any physiological activity but include in alkaloids. Those compound, which fully satisfy the definitions, like physiological active, heterrocyclic basic nitrogenous ring but they do not classed in alkaloids e.g.- Thiamine, caffeine, purine, theobromine, and xanthenes. Acc. To Pelletier 1983 “an alkaloids is cyclic compounds containing nitrogen in negative of oxidation state. Which is of limited distribution in Living organisms”. "From above discussion, a conclusion can be drown quit safely that it is still difficult to define an Alkaloid"
-Apocynace.. Acc. e. According to their source: There are named according to the family in which they are found.. about15% of vascular plant & widely distributed in higher plant e. tannic. pelletierine group has been named its discoverer. 4. neo.OCCURRENCE OF ALKALOIDS Alkaloids are chemically nitrogenous heterocyclic basic compound occur in nature. few are with sugar e. papaveraceae. e. Glycyrrhizin. papavarine.g. According to there discover: There are named according to there discover. e. aconitic acid.g.
2. According to their Physiological response: There are named according to
their physiological response.. 3. tartaric. Punarnavine I & II NOMENCLATURE There was no systematic nomenclature. Nibidine. malic. Quinine. epi. oxalic acid. solenaceae. papilanaceae. pseudo. ephedrin.
. e.g. like acetic acid. They are present in the form of salts of organic acid.CH3 group not attach to Nitrogen. punarnavin. Emetine means to vomit. Roots: Rawelfinine.g. veratrum groups.J. P. Solanum. to parts of plants: Leaves: Nicotine Bark: Cinchonine.g. Morphine means God of dreams. rananeulaceae. iso. But there are some methods for nomenclature are mention below.g. Prefixes: There are named by some prefixes are fix in nomenclature of alkaloids. Seeds: Strychnine. Pelletier. lactic. 1. nor.
. papilionaceous without reference their chemical type of alkaloids present & another according to genus.
1.g. Non-heterocyclic Alkaloids: In this group of alkaloid not has any one
Heterocyclic ring in their structure. D) Chemical classification: This classification is universally adopted & depends on the fundamental ring structure.g. Heterocyclic Alkaloids: According to heterocyclic ring the alkaloids are sub divide in following: 1) Pyrrole-Pyrrolidine: This type of alkaloids contains pyroll or
pyrrolidine ring in their structure e.g. Do not have chemical similarity in their group. papaverine.. e. B) Pharmacological based: Their pharmacological activity or response. Cardio active alkaloids etc. e.CLASSIFICATION Alkaloids are classified as: A) Taxonomic based: According to their family e. cinchona etc. narcotine.g.. 2.g.. According to these two main groups. 2) Pyrrolizidine: Alkaloids containing Pyrrolizidine Heterocyclic ring in their structure e. e. For example: 1.g. C) Bio Synthetic based: According to this alkaloids are classified on the basis of the type precursors or building block compounds used by plants to synthesise the complex structure.
. Ephedrine(Ephedra gerardiana) Genateceae. Analgesic alkaloids 2.. Morphine.seneciphylline Senecio sp. tubocurarine & calchicine in phenylalanine tyrosin derived base.. solanaceous.Hordinine (Hordeum vulgare). Hygrines Coca sp. ephedra.
Cinchonidine & cusparin -(cusparia bark 6) Iso Quinoline: Alkaloids containing iso quinoline ring in thier chemical structure e. (Peumus Baldus) (Manioniaceae) 8) Nor Lupinane: Alkaloids present in leguminoceae plants e.Solanceae Cocain.g..g. 1.. Following steps are involved in isolation process. Lobaline. lupanine.g.-
5) Quinoline : Those Alkaloids containing quinolin ring in their structure e.3) Pyridine & Piperidine: Alkaloids containing Pyridine Heterocyclic ring in their structure e.
.Coca sp.g. Piperidine. EXTRACTION AND ISOLATION Purification or isolation of alkaloids from a plant is always difficult process because an alkaloids bearing plant generally contains a complex mixture of several alkaloids with glycoside organic acid also complicate the process. Narceine Emetine & cephaline.. Baldine. Detection of presence of Alkaloids: First of all confirm the presence of alkaloids in raw material or crud drugs by various reagents called Alkaloids reagents e. Atropine Hyoscine. (Cinchona bark) Cinchonine.g. Hyoscyomine. Ricinine. Yohimbine. e. 4) Piperidine (Tropane): Alkaloid containing tropone ring. Papavarine.g. 7) Reduced isoquinoline (Aporphine): The alkaloid contain reduced isoquinoline ring in their structure e.g. Quinidine.g. e. (Cephalis sp Rubiaceae). Nicotine.Quinine. spartine. 9) Indole Alkaloids: Alkaloids containing indole ring. Aspidospermine (Apocynaceae) Vinblasine. vincristine (catheranthus roseus).
Crude Plant extract 1. Marquis (Conc. 4. Ether soluble Evaporate. The aqueous layer containing the salt of alkaloids and soluble plant impurities is made basic with NaOH. Mayer (Cream Co lour) Test II. extraction) 2. The solid man (ppt. Dissolve Water. HCHO) Test. Flow Chart of extraction Powdered Drug/ Macerated Plant Light Petroleum ether.) so obtained is then extracted with ether when alkaloid pass into solution and impurity left behind. when the bases (alkaloids) are extracted as their soluble salts. Filtrate Ether. Extraction: . Basic Material Aqueous residue Ether solution Evaporate. Filtrate Plant residue Evaporate. The solvent is distilled off and the residue treated with inorganic acids. Steam distillation. 1. then finally powdered and extracted with boiling methanol. 3. Filter. Erdmann (Conc. The insoluble alkaloids are set free precipitate out. Frohdes (Molybdic acid) Test 2. CH3OH (72 hrs. Filtration. Filtration. Fat 3.I. 2. (Crude Alkaloids)
Acid Solution Ether + NaOH
. Acidify to pH-2. Hager's (Yellow Colour) Test V. III.The plants is dried. Evaporate. HNO3) Test IV.
Separation of Alkaloids: After detection of next step is separation of a
relatively small percentage of alkaloids from large amount of crude drugs. Belladona. Coniine.. Most of levo ratatory but few are -Dextro rotatory e. IV) Optically active. E.0. Chincona contains 5-8 % Quinine. crystalline solid. They are insoluble in water (exception liquid alkaloids soluble in water). Hager's Test: Specimen with Hager's reagent give yellow ppt. (Special Type)
5. PHYSICAL-PROPERTY I)
They are colorless.Berberin (Yellow).g.e.g. crystallization.g.papaverine. Nicotine Coniine (liquid). Wagners Test: Specimen with Wagner's Reagent give brown or reddish brown ppt.3. 2.. Dragendroff Reagent Test: Specimen with Dragendroff Reagent give orange ppt. Ethyl alcohol ether)
III) Taste: They are bitter in taste.
. 3.Opium contains 10% Morphine. soluble in organic solvent ( CHCl3.2% of Hyoscyamine. Mayer's Test: Specimen with Mayer's reagent give Cream or pale yellow ppt. chromatography and ion exchange method. 4. CHEMICAL TEST OF ALKALOIDS 1. some inactive. The required alkaloid is separated from the mixture from fractional. Exception . Amonium Rinker Test: Specimen with Ammonium Rinket solutions with
HCL give flocculent pink ppt.
2) Number of Double bond: .COOK (carboxylate).
Excess of Alkali is estimated by titration with standard HCl.OH + (CH3CO)2 O R. -COOH (Carboxylic). 1. Number of -OH group can be calculated from the volume of Alkali used for Hydrolysis. .GENERAL METHODS FOR STRUCTURE DETERMINATION OF ALKALOIDS Molecular formula of majority of Alkaloids is complex so very little achievement in their elucidation of structure. (1) Hydroxyl group: . Of double bond is determined by double bond equivalent method.OH (Phenolic/ Alcoholic).Oxygen presents in alkaloids as: .OH + C6H5COCl ROOCCH3 + CH3COOH ROOCCH3 + HCl ROOCC6H5 + HCl
If Primary amines are present in an alkaloids also give this test.OCOC6H5 ( Benzoxyl).It can be determined by infra red or organic analysis method.Formation of Acetate on treatment with Acetic anhydride /Acetyl chloride or benzoate on treatment with Benzyl chloride..OCOCH3 (Acetoxy).Ca Hb Nc Od Then number of double bond present in Ring= a-b/2 + C/2 + 1 3) Functional group Analysis: a) Functional Nature of Oxygen: . Grignard-method. Molecular formula molecular weight: A pure specimen of alkaloids its empirical formula and molecular weight by elemental or combustion analysis. . . Then Hydroxyl group is can be determined by zerewitinoff method.>C=O (Carbonyl).
NaOH R-OH +CH3COCl R-OCOCH3R. No.= C-O-O (Lactones Ring). Now general procedures for elucidation of structure of alkaloids are adopted.OCH3 Methoxy. During 19th Century.OH + CH3COCl R. R.Number of Rings present in an alkaloids can be determine by following formula.
Re precipitated by CO2 .
phenylhydrazide .semicarbazone phenyl Hydrazine >C=O + H2NOH >C=O +H2NNHCONH2 >C=N-OH >C=NNHCONH2
The distinction between aldehyde and ketone is done by oxidation or reduction.
(4) Methoxyle group: .
HI C2OH4OO4N 4MeI AgNO3 4AgI (estimated gravimetrically)
(5) Methylenedioxy group: .
(3) Oxo-group: .Soluble in NaOH .NMgI + CH4
1.4 liter of N2 STP
10. Papavarine. 20-OH. and UV techniques. which estimated gravimetrically..OH + MeMgI .. Semicanbezide. and then Alkaloid is . By oxidation or dehydration to unsaturated compound. also by NMR.BY Zeisel determination method.g.On heated with concentrated with HCL or
H2SO4 to form formaldehyde and further formation of dime done derivative.
dime done derivative (Estimated gravimetrically)
. When methoxy
group present in a alkaloids treated with HI at 1260C perform methyl iodide which can treated further with silver nitrites to perform silver iodide precipitate.On treatment with Hydroxylamine.OMgI + CH4 .oxime .soluble in aqueous solution sodium carbonate or
ammonia on treat with alcohol form ester. Ba(OH)2 solution by using phenolphthalein as an indicator. If OH group is phenolic. Which estimated gravimetrically e.Giving coloration with FeCl3
(2) Carboxylic group: .NH + MeMgI
.OH= 1>NH group= 22. Number of -COOH group can be determined by volumetrically by titration against a standard. 30 -OH group. IR.
. >CONH2 + NaOH >COOR + NaOH
-COONa + NH3 -COONa + ROH
c) Nature of Nitrogen
Majority of nitrogen presence in alkaloids are secondary and tertiary: If tertiary when treated with H2 O2 (50%) form. =N +H2O2 =N O +H2O
If alkaloids react with one molecule of methyl-iodide to form N-methyl derivative.g. and nitrous acid are often showing the nature of nitrogen If react with one molecule of methyl-iodide to form crystalline quaternary salt this indicates that nitrogen is tertiary e. it means secondary e. methyl-iodide. N= (C10H24)= N + 2CH3I IH3C+N= (C10H24)= N +CH3I-
N-methyl group: On distillation with soda lime if methylamine is produce show the presence of N-methyl group for e. which estimated gravimetrically.b) Ester Amide Lacton & Lactum group: These groups are identified
by the estimation of product.g. Soda-lime (C10H14N)=N-CH3 CH3NH2 Nicotine CaO Determination of Number of CH3-groups Attached to N-atom: By HerzigMayer’s method when a sample is treated with hydrogen iodide at 1500-3000C and than treated silver nitrate. which form silver iodide.g. (C8H16O4) NH + CH3I (C8H16O4) NCH3 + HI
General reaction of alkaloids with acetic-anhydride.
This is a composite reaction
of alkaloid (Heterocyclic amines). which estimated gravimetrically.N.methylamine + HI
>NH + MeI
d) Estimation of C-Me Group by Kuhn –Roth Oxidation: When
treated with K2Cr2O7 or H2SO4 an acid is produce.
. K2Cr2O7 or H2SO4 -C-Me MeCOOH Estimated gravimetrically
e) Degradation of Alkaloids: For discovering the structural system which
incorporate these substituents groups & is tackled by degradation of the molecules by following methods:
1) Hoffmann's exhaustive methylation: .
c) The step Ist and IInd are repeated when a second cleavage at the N-atom
given an unsaturated hydrocarbon which isomerase’s to conjugated derivative. The -OH of
hydroxide extracts hydrogen atom from beta position and eliminate a water molecule and also the ring is cleaved at the N-atom to give an open chain 30amine.
b) 40-ammonium iodide is converted to the hydroxide and heated. This involves following steps: a) The alkaloid is treated with excess of CH3I to form quartertionarey -ammoniumiodide.
g.This method is of two types:
A.g.Br -R . In such cases Emde degradation are applied. in this final step involve the reductive cleavage of quartertionarey ammonium salt either by Na-Hg or NaNH3 or by catalytic hydrogenation e. Secondary cyclic Amine is treated with Benzoyle chloride in presence of NaOH to yield the Benzoyle derivative which on treatment with phosphorus followed by distillation under reduced pressure yield di Halo compund. which contains at least one-alkyl substituents.
Na-Hg or NaNH3
RCH3 + NR3+ HX
2) Von Braun's Method: . – Cocaine B. is treated with cyanogen bromide.The exhaustive methylation of an alkaloid is an important method for the investigation of the nature of the C-skeleton in the heterocyclic system. The results in cleavage of an alkyls nitrogen bond to give an alkyl halide and a substituted Cyanamid.Br + R2N .
R3N + CN .
2) Emde Degradation Method: If alkaloids do not contain beta
Hydrogen atom then Hoffmann exhaustive degradation method is failed.
. Tertiary amine.CN
This method is often applicable to such compounds that do not respond to Hofmann's method e.
Papaverine. Cr2O3 (H2SO4). The nature of fragment. selenium or palladium dehydrogenation takes place to form relatively simple & easily recognizable product which provide the clue to gross skeleton. Moderate oxidation: KMnO4 (Alkali) Cr2O3 (Acetic Acid) C.H2O2. which will give information type of nucleus present in alkaloid molecule e. which is often employed to
break down the complex of complex alkaloids molecule to simpler fragment. Adrenaline.This method gives quite information about the structure of
alkaloids by varying the strength of the oxidizing agents it is possible to obtain a variety of product e. HI in ethanolic solution & alkaline potassium ferriccyanide. Coniine
Zn dust /Heat
+ 6H C3H7
4) Alkali fusion: This is very drastic method.g. HNO3. A. B. The final conformation of the structure must be done by the unambiguous synthesis.g. conc.
.The structure of the alkaloids arrived at by the exclusive
analytical evidence based on going method is only tentative. (H2SO4). MnO2 (H2SO4)
C10 H14N2 K2Cr2O7 (H2SO4) C6H5COOH
6) Dehydrogenation: .
7) Synthesis: .g. Vigorous oxidation: K2Cr2O7. Cinchonine
5) Oxidation: .When Alkaloid is distilled with catalyst such as
sulphur. Mild oxidation.NaOH
Br-RRBr + C6H5CN
3) Reductive degradation & Zinc dust distillation: In some case ring
may open by Heating up to 3000C with Hydroiogic acid e.
Because the great diversity of structure of alkaloids. it become increasingly probable that the precursor in the biosynthesis of many alkaloids were amino acids and amino-aldehyde or amines derived from them. Woodward 1948 proposed a biosynthesis of strychnine. it not possible to develop only one hypothesis of biosynthesis of alkaloids. Phenylalanine (R=H) RC6H5CH2CH(NH2)COOH iv.BIOSYNTHESIS OF ALKALOIDS As more and more structure of alkaloids were elucidated. Thus many pathways have been proposed. each one accounting for the biosynthesis of a number of alkaloids of related structure. Ornithine H2N (CH2) CHNH2COOH ii Lysine H2N (CH2)3 CHNH2COOH iii. The most common aminoacids that act as precursor in biosynthesis of alkaloids are: i. Methionine MeSCH2CH2CH(NH2)COOH vii Trytophen Some common reactions are: Decarboxylation : formation of amine RCH (NH2) COOH RCH2NH2 +CO2
Oxidation: formation of aldehyde RCH (NH2) COOH Shiff base formation: R1CHO +R2NH2 R1CH=NR2 RCOCOOH RCHO
. Tyrosine (R=OH) vi.
ATROPINE This is the most important alkaloid of tropane group and occurs in the roots of deadly nightshade (Atropa belladonna). In practice. The precipitated atropine is extracted with ether and purified by converting it in to an oxalate or a sulphate.C17H23NO3.V. thus atropine is ( ± )-hyoscyamine ISOLATION Atropine is extracted either by from belladonna root or from juice of datura plant. this atropine is extracted with chloroform.These following physical methods are applied to elucidate the structure of alkaloids: • • • • • • • U. Spectroscopy IR Spectroscopy Nuclear Magnetic resonance spectroscopy Mass spectroscopy Optical rotatory dispersion & circular dichroism. thron apple (Datura stamonium)n and many other member of solanaceous family together with lhyoscyamine which is optically active ( [<]D = -220 ). Structure15
. Melting point. Atropine is the racemic form of l-hyoscyamine which readily racemises to atropine when warmed in an ethanolic alkaline solution.118oC. Conformational Analysis X-Ray diffraction
1. The solution is made alkaline with potassium carbonate when atropine is precipitated out. the juice which contains hyoscyamine is heated with potassium carbonate solution when hyoscyamine is racemised to atropine. The chloroform is recovered by evaporation and the residue is then extracted from the residue with dilute sulphuric acid. STRUCTURAL ELUCIDATION Molecular formula. Then.
3 and 24. 2. 1. 1725 ( O-C=O ). Ar-H ). m. 2. 2810 ( N. H-5 ). Ar ). carbohydrates. t. 257. 770. meconic acid about 20 or more alkaloids. 1580 ( C=C. 1030 ( CC-O ). 1 H NMR ( CDCl3 ): δ 7.93 ( 2H. bs.8. ISOLATION Morphine is extracted from opium by involving the following steps :
.9 ( 1H.5. 2930 ( CH stretch ). 263. Codeine and thebaine are the other closely related alkaloids to morphine.6. proteins. 209. H-2. 3. it is present in a quantity of 10-23 percent along with other substances like fats. 143.1. In opium.66 ( 8H. 251. s.4.96 ( 1H.725 and 690 ( monosubs Ar ) cm-1. Theses three are commonly known as morphine alkaloids and from a sub-group of the opium alkaloids. resins. 271 nm ( c 147. mineral salts. H-3 ). 175.Hydrogen bonded). these are also known as phenanthrene alkaloids. m. The morphine alkaloids have been studied comparatively more due to the following reasons: (i) These are widely used as analgesic agents.6.UV ( Ethanol ): λmax 246.23 ( 5H. H10 ). and (ii) These undergo a wide variety of molecular rearrangements.CH3 stretch ). 4. Due to this.7 ). phenanthrene nucleus is present. 1595.6. MORPHINE Morphine was the first alkaloid to be isolated from serturner plant ( 1806 ).6 respectively ) IR ( KBr ): Vmax 3070 (OH. In all morphine alkaloids. 1155.
the raw opium is extracted with cold dichloromethane repeatedly. This results in precipitation of morphine.254-256oC. The filtrate still contains morphine.(i) First of all. Then the filtrate is neutralized with ammonia followed by the addition of alcohol. This is then treated with hot alcohol. (v) The benzene extract obtained from step (iii) is evaporated to yield a residue. Structure-
. When precipitate is shaken with hot alcohol. then treated with the charcoal and finally filtered. The filtrate when treated with sulphuric acid yields a precipitate of codeine sulphate which is filtered out. followed by cooling and filtration. codeine and thebaine are present in lime water which when extracted several times with benzene remove codeine and thebaine in a benzene layer. Then. (iv) The crude morphine obtained from step (iii) is dissolved in dilute HCl and filtered through alcohol. the papaverine goes into alcohol. From this. Papaverine. STRUCTURAL ELUCIDATION Molecular formula. when evaporated in vacuum and then extracted with amyl alcohol. This filtrate. The crude narcotine present in the residue from the alcohol extraction is similarly purified. (iii) The residue obtained from the dichloromethane extraction is agitated with lime water at temperature below 20oC. yields further amount of crude morphine. narcotine and gum go into the dichloromethane layer whereas morphine and other substances remain in the insoluble residue. (ii) The dichloromethane layer obtained from step (i) is evaporated to dryness to yield a residue which is extracted with hot dilute HCl. The precipitated morphine is dissolved in minimum quantity of dilute HCl and the resulting solution so obtained on concentration and cooling yields crystals of morphine hydrochloride. Dichloromethane layer is separated. The filtrate is neutralized with ammonia when papaverine and narcotine are precipitated out. the pH is raised to 8 when the crude morphine is precipitated out. To the resultant filtrate. Melting point.C17H19NO3. the two sample of crude morphine are mixed. tartaric acid is added to precipitate out thebaine as thebaine acid tartrate. morphine. papaverine is precipitated out as oxalate and then purified by recrystallisation.
1605 ( C=C. H-7 ). Ar ).68 ( d. 2940.6= 2Hz ). methylephedrine. 5. Ar ) cm-1. H-10 )
3. ( a Chinese drug ) which contains ephedrine and is said to have been used medicinally in china for 5000 years. 3.16 (d. H8 ). J5. 2840( N.4. N-Me ). 1250. 3. 1090( X-O stretch). 4.UV ( Ethanol ): λmax 286.20 (d. 250 and 298 nm ( log c 3. namely pseudoephedrine.H-5. It also increases blood pressure. 2920 ( CH stretch ). 5. 3210 (OH bonded). ISOLATION
. 1640 (C=C alkene ). 760 ( monosubs. 3.40 ( d. H-1 ).360 respectively ) IR ( KBr ): Vmax 3480.CH3 stretch ). Ephedrine has been used successfully in the treatment of bronchial asthma.76 (d.06 ( d. methylpseudoephedrine. America and Mediterranean. The Chinese have used the herb Ma Huang. It is a much stronger stimulant than caffeine. H-9 ). EPHEDRINE It is an important drug which occurs along with five other alkaloids. H-14 ).0 (s. ). 1 H NMR ( HCl ): δ 6. 6. norephedrine and norpseudoephedrine in the genus Ephedra. 3350 ( OH ). The base ephedrine was first isolated from the Ephedra in 1887 by Nagai and much later Gulland and Virden obtained a very small amount from the Yew ( Taxus baccata L. 5.37 ( m. 2.275.75 ( d. H-2 ).256. hey fever and other allergic conditions. a species which occurs in temperate and subtropical regions of Asia.
The salts prepared by fractional crystallization show no change in the melting point when recrystallized seven times. NH-CH3 ).60 (m.1 kilo of powdered Ma Huang was extracted with cold benzene in the presence of dilute Na2CO3 solution. and then with pure ether.C10H15NO.5° . In many of our experiments the salts were recrystallized twelve times. STRUCTURAL ELUCIDATION Molecular formula. and the benzene extract was shaken up with a sufficient quantity of dilute HCl to remove the basic substances. After filtering it was washed with a mixture of alcohol and ether.
. Nearly pure ephedrine hydrochloride crystallized out on standing. Structure-
UV (Methanol): λmax 250.9 ( s. 165 respectively) IR ( KBr ): Vmax 3330 ( -OH stretching ) 2480 ( NH + 2 stretching ). 256 and 262 nm (log c 170.28 ( d. Ephedrine hydrochloride crystallized out from alcohol in prismatic needles. CHNH2 ) 2. s. The acid solution was made alkaline with solid K2CO3 and the liberated base was then extracted with chloroform.38. and 1. 5. The final mother liquor was kept for the isolation of pseudoephedrine (see below).6 g of crude base. 1490. A further quantity of ephedrine hydrochloride may be got by concentrating the mother liquors and washings. and dried. 1 H NMR ( D2O ): δ 7.20 ( d. 3. The chloroform solution. Preparation of Ephedrine HCl by Fractional Crystallization The crude base obtained as above was taken up with about twice its weight of alcohol and neutralized with concentrated HCl diluted with twice its volume of alcohol.53 (5H. CH. Ar-H ).1oC. 1450 (ArH ) 750 and 699 ( C-H out of plane deformation ) cm-1. 20.CH3 ). OH ). Melting point. when dried over anhydrous Na2SO4 and distilled. gave 2. [α]D22 -32. mp 216°C.
A further quantity was obtained on longer standing. Other important alkaloids presents in these species are yohimbine. ISOLATION Mature root bark (264 g) was extracted with methanol in a Soxhlet for 30 hr. Any resinous material separating at this stage was dissolved in a little methanol and retreated in the same way. The combined acid extracts were then Basification with NH. this process being repeated thrice or until no more resin formation occurred.). the extract concentrated to remove the methanol.C33H40N2O9. STRUCTURAL ELUCIDATION Molecular formula. Reserpine is mainly used for the treatment of hypertension.
. A solution of this material in a little methanol gradually deposited a crystalline precipitate which after several recrystallizations from methanol (Yield 0.0.) then 2% HC1 (2 x 100 c.4. ajmalicine and ajmaline. tension states.c. headache. asthma and dermatological disorders.07 g). vomitoria.264-265oC. particularly R. and the residue treated with NaHCO. RESERPINE Reserpine is the main constituent of Rauwolfia species. All these alkaloids are hypertensive and sedative reagents. All the aqueous solutions were extracted four times with ether and the combined ether extracts washed with 2% acetic acid (3~100c. solution and ether. Melting point. gave a resin which would not dissolve in ether. serpentina and R.
and then distill out the methanol from it . 1 H-NMR (CDCl3 ): δ 7.3 ( indole Ar-H ).05 ( H-18.OMe X 2 ). 5. Dissolve the residue by mixing it with dilute tartaric acid and hot methanol. C16.43 ( H-3. STRUCTURAL ELUCIDATION Molecular formula. m ). VINCRISTINE Vincristine is an indole alkaloid obtained along with the Vinblastine from the catharanthus roseus family. Chloroform and Chloroform + Methanol mixture. Apocynaceae. s. t ).7-7.29 ( 3H. CH-OMe ). The concentrated extract is then steam distillated to obtain insoluble residue. reticulum sarcoma. 15700 and 55700 respectively ) IR: Vmax 3480 ( N-H stretching ). breast and lung. 6. C17 OMe ) 5. 2840-3030 ( C-H stretching ).85 ( s.273-281oC.79 ( 3H. Melting point. NH ). Collect benzene extract and evaporate till concentrate. 216 nm (c 9660. trimethoxybenzene Ar-H ). 267. benzene + Chloroform. 3.46 ( s. ISOLATION The mixture of dried ground plant of Vinca rosea and dilute tartaric acid is extracted with benzene. The dried powder of Vincristine is dissolved in benzene and chromatographic separation is carried out on alumina column using eluting solvents as benzene. s. 3.UV: λmax 296.34 ( 2H. 4. Collect the extract. s. evaporate and dry. 3. 1732 and 1713 ( C=O stretching ) cm-1. Vincristine is one of the cytotoxic drugs and used in treatment of acute leukemias particularly in children and in other cases such as lymphosarcoma. 3.OMe ). This plant was previously known as Vinca roseae L. s. Structure21
.Carryout the extraction of the bottom product using dilute solution of ammonia.C46H56N4O10. 7.92 ( 6H. neuroblastoma wilms tumor and tumors of the brain.
255. negligible ). 14000.
Alkaloids functions • As reservoir of nitrogen • As reservoir for protein synthesis • As detoxicating agents • As toxicating agents • As harm one for many activity of plant. 11400. MS : m/z 824 ( M +. 221 nm (c 15600. 275. 806 ( M+ . 290.
.18 ).UV: λmax 296. 15400 and 47100 respectively ).
Alkaloids are naturally occurring heterocyclic complex compounds.
. B. Shah and Query’s Pharmacognosy. Alkaloids have mainly nitrogen in heteroatom. 3) Handa S.
1) Qadry J. 3. 5. A Text Book of Pharmacognosy.S (Twelth Edition). B. 2. S. Shah Parkashan. 11th edition. 4. J. &.. Alkaloids have indefinite definition.S. S. A Text Book of Pharmacognosy. New Delhi. Vallabh Parkashan. S. Alkaloids are bio & physiologically and pharmacologically active. Shah Parkashan. Alkaloids have complex molecular structure. 2) Shah C.S Qadry.Alkaloids have many physiologically biological and pharmacological properties
It can be concluded that: 1.
. Pharmacognosy Phytochemistry of Medicinal Plants. L. 6) Agarwal. 9) Brunton Jean.4) Gupta A.B.. Alkaloids (Biochemistry. York. 7) Finar I. 5) Evans W. Organic Chemistry (Stereochemistry & Chemistry of Natural Products) ELBS. Levoisier Paris. ICMR. M Wink. Vol-2. O.K. Page 193-311. New Delhi. 2nd edition. . (Fifteenth edition) Trees & Evans Pharmacognosy. Chemistry of Natural Product. Quality Standards of Indian Medicinal Plants. Saunders. Goel Publication Meerut.C. W. Vol-II Vth edition. Medicine application) Plenum Press. Page 783-799. P.. Ecology.. Vol-1. N. Page 696702 8) Robert MF.