SAN

LORENZO RUIZ COLLEGE │COLLEGE OF PHARMACY

ALKALOIDS
OUTLINE:
• Biosynthesis of Alkaloids
• Classes of Alkaloids
• Extraction & Purifications
• Test for Alkaloids
• Sources and Uses of Alkaloids

CARBOHYDRATES AND RELATED

COMPOUNDS
• basic nitrogenous compounds of plant origin that are physiologically active
• most of them end in “-ine”

• Outstanding Alkaloid-yielding Plants;

-Leguminosae
-Papaveraceae
-Ranunculaceae
-Labiatae
-Rosaceae
• Alkaloids are named in various ways:

• from the generic name of the plant yielding them. (Hydrastine, Atropine)

• from the specific name of the plant yielding them. (Cocaine, Belladonine)

• from the common name of the drug yielding them (Ergatamine)

• from their physiologic activity (Emetine, Morphine)

• from their discoverer (Pelletierine)

• alkaloids usually contain one nitrogen atom (Ergotamine)
• insoluble or sparingly soluble in water
• salts formed on reaction with acids are usually formed soluble
• Free alkaloids are soluble in ether, chloroform or other relatively nonpolar,
immiscible solvents in which the alkaloidal salts are insoluble.
• Most alkaloids are;
-colorless crystalline solids (amourphous)
-possess bitter taste
• ALL alkaloids are SOLID except for; (CANS)
C - Coniine
A - Arecoline
N - Nicotine
S -Spartein
Naili, Mahboba & Alghazeer, Rabia & Saleh, Nabil & Al-Najjar, Asma. (2010). Evaluation of antibacterial and antioxidant activities of Artemisia campestris (
Astraceae) and Ziziphus lotus ( Rhamnacea). Arabian Journal of Chemistry. 3. 79-84. 10.1016/j.arabjc.2010.02.002.
• found as secondary metabolites in
plants, fungi and can be extracted from
their soruces by treatment with acids
(HCl, H2SO4)
• Alkaloids are derivatives from amino
acids.
HISTORY:
• 1803 - isolated narcotine by French aapothecary Derosne
• 1806-1816 - Serturner investigated opium and isolated morphine
• 1818 - strychnine was discovered by the French chemists Joseph-Bienaimé Caventou
and Pierre-Joseph Pelletier
• 1817- emetine
• 1819 - brucine
• 1819 - piperine
• 1819- caffeine
• 1820 - quinine ->first alkaloid to have structured established and to be synthesized
• 1820 - colchicine -> after a century
• 1826 - conine
OCCURENCE:
• abundant in higher plants
• Alkaloid plants contain more than 0.01% (Hegnauer)
• distribution of alkaloids in nature is restricted to some specific plants, animals or
lower plants.
• chiefly found in angiosperms
• Pseudomonas aeruginosa contains pyocyanine alkaloid
• Alkaloids are commonly found in these families;

• Chenopodiacea • Papaveraceae • Apocynaceae • Solanaceae

• Laureaceae • Fumaricaceae • Loganiaceae • Campanulaceae
• Berberidaceae • Leguminaseae • Rubiaceae • Compositae
• Menispermaceae • Papilionaceae • Boraginaceae
• Ranunculaceae • Rutaceae • Convolvulacea
EXTRACTION:
– based on their basic character and solubility profiles
TWO METHODS: NaHCO3
NH3
1. METHOD A CaOH 2. METHOD B
powdered material that contains powdered material is extracted w/ water
alkaloid is moistened w/ alkaline or alcoholc containing dil. acid.
substances which combines to
tannins, acids, phenolic
substances chloroform (other organic solvents) are
added & shaken to remove impurities
set free the alkaloids
free alkaloids are precipitated by addition of alkali solvents
extraction w/ organic solvents (ether or petrolerum spirit)
filtration or extraction w/ organic solvents
the concenttrated liquid is shaken
w/ acid and allowed to separate

alkaloid salt is present in acqueous • Volatile liquid alkaloids (nicotine and

liquid coniine) are isolated by distillation
CHEMICAL TESTS FOR ALKALOIDS

Reagent Composition
Wagner’s Iodine in KI
Mayer’s Potassium Mercuric iodide
Valser’s Mercuric iodide
Dragendorff’s Potassium Bismuth iodide
Bouchdart’s Iodine in KI, *most sensitive
Marme’s Potassium Cadmium iodide
Sonnencheim’s Phosphomolybdic acid
Scheibler’s Phosphotungstic acid
Hagger’s Picric acid
 ALKALOIDAL TESTS
Most Alkaloids are precipitated from neutral or slightly acid solution by various reagent. Following colour
tests are used to detect the presence of alkaloid
Test for alkaloids
1. Dragendorff’s test
Reagent: potassium bismuth iodide solution
• Test: 1 ml of extract + 1 ml of Dragendorff’s reagent An orange-red precipitate indicates the
presence of alkaloids.

2.Mayer’s test
Reagent: potassium mercuric iodide solution
• Test: 1 ml of extract + 1 ml of Mayer’s reagent Whitish or cream colored precipitate indicates
the presence of alkaloids.

3.Hager’s test
• Reagent: saturated aqueous solution of picric acid
Test:1 ml of extract + 3 ml of Hager’s reagent Yellow colored precipitate indicates the presence
of alkaloids
4. Wagner’s test
Reagent: iodine in potassium iodide
Test: 1 ml of extract + 2 ml of Wagner’s reagent Reddish brown colored precipitate
indicates the presence of alkaloids.

5. Tannic acid test:

Reagent: Freshly prepared 5% saturated solution of tannic acid.
Test: Alkaloids give precipitate with tannic acid solution which is soluble in dilute acid or ammonia
solution.
Test: 1 ml of extract + 1 ml tannic acid reagent PPT Dilute acid Soluble
• Alkloids are generally classified by their commmon molecular precursors.

• Three Main Types of Alkaloids (accdg. to their shapes and origins in structure)
A. True Alkaloids
B. Protoalkaloids
C. Pseudoalkaloids
A. TRUE ALKALOIDS
-derive from amino acid and they share a heterocyclic ring with nitrogen
-highly reactive substances with biological activity even in low doses
-all have bitter taste and appear as white solid, with the exception of nicotine
which has a brown liquid.
-True Alkaloids may occur in plants
1. in free state
2. as salts
3. as N-oxides
-the primary precursors of true alkaloids are such amino acids
-L-ornithine, L-lysine, L-phenylalanine, L-tyrosine, L-Tryptophan,
L-histidine
B. PROTOALKALOIDS
-compounds in which the N atom derived from amino acid is not a part of
heterocyclic.
-those that are closed-ring being perfect but structurally simple alkaloids.
-they a minority of all alkaloids ex. Hordenine,Mescaline, Yohimbine
C. PSEUDOALKALOIDS
- are compounds in which the basic carbon skeletons are not derived from
amino acids.
-the N atom is insetedd into the molecule at a relatively late stage
ex. steroidal or terpenoid skeletons
-examples:
1. Coniine
2. Capsaicin
3. Ephedrine
4. Solanidine
5. Caffeine
6. Theobromine
Classification: ---> accdg. to the nature of basic chemical structures
1. Pyridine-Piperidine
2. Tropane/Solanaceous
3. Quinoline
4. Isoquinoline
5. Indole
6. Imidazole
7. Steroidal
8. Aklaloidal amine
9. Purine
Important Drugs:
1. Nicotine
2. Areca
2. Lobella
1. Nicotine (Nicorrete)
i. Biological Source: leaves of Nicotiana tabacum
ii. Uses: CNS stimulant, Smoking deterent
2. Areca/Areca Nut/Betel Nut
i. Biological Source: drief ripe seed of Areca catechu
ii. Family: Palmae
iii. Constituents: arecoline (arecaidine methyl ester),
arecaidine (N-methyl guvacine),
guvacine (tetrahydronicotinic acid), and
guvacoline (guvacine meth yl ester)

iv. Uses: antihelminthic (veterinary practice), substitute for tobacco

3. Lobeline ( (-)-lobeline/ alpha-lobeline)
i. Biological Source: Indian tobacco from Lobelia inflata
ii. Family: Palmae
iii. Constituents: Lobeline
iv. Uses: CNS stimulant and smoking deterent
Important Drugs:
1. belladonna lea
2. hyoscyamus
3. stramoniurn
4. atropine
5. hyoscyamine
6. scopolamine
7. coca
8. cocaine
1. Belladonna (Deadly nightshade)
i. Biological source: dried leaf and flowering or fruting top of
Atropa belladonna (Atropos = in Greek means inflexible )
*in Italian; Bella - beautiful and Donna - lady
ii. Family: Solanaceae
iii. Constituents: The leaves contain1% alkaloids.
3/4th Hyoscyamine and other one is Atropine.
Leaves also contain Scopoletin and calcium-oxalate.
iv. Uses:
• sedative, stop bronchial spasms in asthma and whooping cough, and as a cold and hay
fever remedy.
• used for Parkinson's disease, colic, motion sickness, and as a painkiller.
• used in ointments that are applied to the skin for joint pain (rheumatism), leg pain
caused by a disc in the backbone pushing on the sciatic nerve (sciatica), and nerve pain
(neuralgia).
1. Belladonna (Deadly nightshade)
– Belladonna is also used in plasters (medicine-filled gauze applied to the skin) for treating psychiatric
disorders, a behavior disorder called hyperkinesis, excessive sweating (hyperhidrosis), and bronchial
asthma.
– Rectally, belladonna is used in hemorrhoid suppositories.
2. Hyoscyamus (Henbane)
i. Biological source: Hyoscyamus niger (0.04%)
*toxic to swine
ii. Constituents: scopolamine, hyoscyamine
3. Egyptian hyoscyamus (1-5%)
i. Biological source: Hyoscyamus muticus
4. Duboisia
i. Source: Duboisa myoperoides
ii. Uses: commercial source of atropine
5. Withania
i. Source: Withania somnifera
ii. Uses; commercial source of atropine
6. Stramonium/Jameson weed/Jamestown weed
i. Source: Datura stramonium and Datura metel (used as antiasthma)

7. Mandragora / European Mandrake (Satan’s Apple)

i. Source: roots of mandragora
ii. constituent: mandragorin
iii, Use: emetic

8. Coca
i. Source: 1. Huanuco coca - Erythroxylon coca;
2. Truxillo coca - E. truxillense
ii. Constituent: 1. Cocaine (Crack/Coke)
-uses: psychomotor stimulant, local anesthetic
-Brompton’s Cocktail
 Atropine Scopolamine
Hyoscyamine
• treats cramps and irritable -antispasmodic -treatment of motion
bowel syndrome. sickness (Transderm/Trans-
• In cramping pain caused by -antisialogofue (naglalaway)
-antisialogogue (naglalaway)
kidney stones and gallstones, -mydriatic and cycloplegic scop)
• Parkinson’s disease.
• In addition, it is used to (paralysis of upper lids)
decrease side effects
of insecticides. -antidote for cholinesterase
• Decreases acid production in inhibitors
the stomach.
-(+) intotropic agent
-(+) intotropic agent
§ Alkaloids containing quinoline as their basic nucleous .

§ Cinchona and its alkaloids are only members of this group that are therapeutically important at
present.
§ Consist of alkaloids and alkaloid salts obtained from the bark of certain Cinchona species :
• Quinine and Quinidine,
• Cinchonine and Cinchonidine.
• Cinchona alkaloids are present as salts with Quinic and
Cinchotannic acids
Cinchona bark:
i. Biological source: Cinchona succirubra (Rubiaceae), and its varieties and hybrids
containing not less than 6.5% of total alkaloids. 30-60% of which consists of quinine-
type alkaloids.
*The former importance of cinchona bark and its alkaloids in the treatment of malaria has been
lessened by the introduction of synthetic drugs, but it remains of great economic importance.
ii. Constituents:
-stereoisomers quinine and quinidine and their respective demethoxy
derivatives, cinchonidine and cinchonine.

HO HO 8
9
N N
H H H
H3CO H
H3CO

N N
Quinine Quinidine
 Test: Thalleioquin Test
-fine-blue flourescence then
green ppt.
Cinchona bark:
iii. Uses:
1. Galenicals of cinchona have long been used as bitter tonics and stomachics.
2. before World War II, quinine was the drug of choice for the treatment of
malaria but became largely superseded by the advent of synthetic
antimalarials developed during that period.
3. Quinine also has a use as a treatment for night cramps in the elderly .

* Quinine - anti-malarial drug

*Quinidine - antiarryhtmic drug
*Cinchonism - cinchona toxicity; temporary loss of hearing; Hallmark= tinnitus
*DOC for Malaria: Artemisinin Combination Therapy
*Wormwood (Artemisia annua)
-Artemether - lipid soluble
-Artesunate - water soluble
Cuprea
i. Source: Remijia pyridiena
ii. Family: Cupressaceae
iii. Extraction process: obtained by destructive
distillation
 The isoquinoline structure occurs in a considerable member of alkaloids, widely
distributed in plant families.

The important alkaloids in this group are:

1. Ipecac : emetine, cephaeline ,psychotrine

2. Curare: D. tubocurarine
3. Opium and its alkaloids.
Ipecac
i. Biological source: dried root or rhizome of Cephaelis ipecacuanha
ii. Family: Rubiaceae
iii. Constituents: Ipecacuanha contains the alkaloids :
§ emetine,
§ cephaeline ,
§ psychotrine,
§ psychotrine methylether
• emetamine.
iv. Uses:
1. Syrup is used in the treatment of drug over dose and in cases of poisonings.
2. Expectorant
3. Treatment of Amoebic Dysentery
Ipecac
i. Biological source: dried root or rhizome of Cephaelis ipecacuanha
ii. Family: Rubiaceae
iii. Constituents: Ipecacuanha contains the alkaloids :
§ emetine,
§ cephaeline ,
§ psychotrine,
§ psychotrine methylether
• emetamine.
iv. Uses:
1. Syrup is used in the treatment of drug over dose and in cases of poisonings.
2. Expectorant
3. Treatment of Amoebic Dysentery
*Ipecac syrup - emetic
*Ipecac fluidextract (14x more potent than syrup)
*Ipecac + Opium = “Dover’s powder” used as diaphoretic
Tubocurarine / Curare / Southamerican arrow poison
-Has a bisbenzylisoqinoline structure.
i. Biological source: obtained from the bark and stems of Chondrodendrum tomentosum
ii. Family: Menispermaceae
Tubocurarine chloride
iii. Constituent: Tubocurarine

*The term 'curare' is a generic one applied to various South American arrow poisons, because
crude extract prepared from different species was used by certain natives of the Amazon regions of South
America as arrow poison, which kills by paralysis of the muscles required to breathe.
*Assay: Head drop assay in rabbits

iv. Uses:
1.skeletal muscle relaxant
2. Used to control convulsions of strychnine poisoning and of tetanus.
3. after shock treatment (in mental diseases) as it reduces convulsion
Opium
i. Biological Source: the latex obtained by incision from the unripe capsules of
Papaver somniferum (Papaveraceae)
*Stone of immortality
ii. Constituents:
1. not less than 10% of morphine
2. not less than 2.0% of codeine.
3. thebaine content is limited to 3%.
Opium
OPIATES OPIOIDS
-naturally-occuring -derived, synthetic, direct affinity w/ opioid receptors
a. Morphine a. Diacetylmorphine/ Heroin
-most important -acetylation of morphine
-most abundant -increased danger of habit formation, very potent
-Use: Narcotic analgesic for cancer patients

b. Codeine (Methyl morphine) b. Hydromorphone

-discovered by Pierre Robiquet -more potent analgesic than morphine
-widely used opium alkaloid (cough syrup) -less frequent side effect
-obtained from methylation of morphine
-Use: Antitussive
c. Noscapine c. Apomorphine
-only non-narcotic-opium alkaloid -obtained by condensation of morphine + HCl
-Use: Antitussive -Use: emetic
-anarcotin/narcotine
d. Papaverine d. Hydrocodone
-smooth muscle relaxant; antitussive -antitussive
e. Thebane
-no particular use
Production of Opium
1. The plant is an annual herb with large solitary flowers, either white or pink in color
2. The incisions are made in the afternoon with an instrument bears narrow iron
spikes which are drawn down the capsule to produce several longitudinal cuts.
3. The incision must not penetrate into the interior of the capsule or latex will be
lost.
4. The latex, which is at first white, rapidly coagulates and turns brown.
5. Early in the morning of the day following the making of the incisions the
partly dried latex is scraped off.
6. Each capsule is cut several times at intervals of 2 or 3 days.
7. After collection the latex is placed in a tilted vessel so that the dark fluid
which is not required may drain off.
8. By exposure to air the opium acquires a suitable consistency for packing.
Opium Constituents
• Opium contain more than 40 alkaloids usually combined with a specific acid (Meconic acid) or with other
acids e.g. sulfuric and acetic acids.
• Opium alkaloids can be sub classified into 3 main groups with different basic nuclei:

1. Phenanthrene alkaloids e.g. morphine , thebaine and codeine.

2. Benzylisoquinoline alkaloids e.g. papaverine and noscapine (narcotine).

3. Phenylethylamine alkaloids e.g. narceine

Morphine

Narceine
Uses of Opium
• Opium and morphine are widely used to relieve pain and are particularly valuable as hypnotics, as, unlike
many other hypnotics, they act mainly on the sensory nerve cells of the cerebrum.

• Both morphine and codeine decrease metabolism, and the latter, particularly before the introduction of
insulin, was used for the treatment of diabetes.

• Opium, while closely resembling morphine, exerts its action more slowly and is therefore preferable in
many cases (e.g. in the treatment of diarrhea).

• Opium is also used as a diaphoretic.

Opium Adverse Effects:
1. constipation
2. sedation
3. nausea and vomiting
4. respiratory depression
5. Miosis
6. anticholinergic effect: dry mouth , urinary retention
7. tolerance: increase doses required to maintain analgesia.
8. dependence : addiction, if used for a long time
Rauwolfia
Synonyms: Rauwolfia Serpentina, Rauwolfia Root
Botanical source: Rauwolfia consists of the dried roots Rauvolfia serpentina Benth., a large shrub of the farnil,
Apocynaceae.
Geographical source: The Plant is indigenous to Bangladesh, India, Burma, Thailand, Malaysia and Indonesia.
Chemical constituents:
1. Rauwolfia contains 1.2 to 1.4 percent of total indole alkaloids , the most important of which are
reserpine, descrpidine and recinnamine.
2. also includes resinous matter, fatty acids, unsaturated alcohols, dextrose and sucrose.
Uses: hypotensive agent, sedative and tranquilizer property
Nux vomica
Synonyms: Strychni Semina, Crow Fig.
Botanical source: Nux-vomica consists of the dried seeds of Strychnos nux-vomica Linn., Family:
Loganiaceae.
Geographical source: plant grows wild in India, West Indies and Cameroon and sporadically in
Chittagong Hill Tracts of Bangladesh.
Chemical constituents:
The seed drug Nux-vomica contains the indole alkaloids, strychnine (about 1.24 %) and brucine
(about 1.5 %). It also contains caffeotannic acid, a glycoside, loganin and a fixed oil.
Uses:
It is used as a tonic and stomachic and is given in constipation.
It increases blood pressure. Thus, it is also useful in certain cases of heart failure
In large doses it causes convulsions and thus is used in pharmacological research.
Ergot
Biological source: Ergot is the dried sclertium of a fungus Claviceps purpurea that grows on the ears of rye plant
Secale cereal
Family: Gramineae
Ergotism: It is the danger of ergot that produces
Constituent:
various diseases. Before systemic cultivation of
1. Ergonovine -oxytocic agent for labor
ergot if the fungus invade the rye field then it is
2. Ergometrine - derivative of ergonovine
harvested with rye grain and rye flour is
3. Methylsergide - prophyltreatment for migraine; derivative of
contaminated with the fungus and when people
ergonovine
4. Ergotamine - DOC for migraine ingest this flour they become victim of some

5. Lysergic acid diethylamide (LSD) - most active and most specific diseases which are known as Ergotism.

psychomimetic drug; Hallucinogenic agent

Use:
1. Ergot is used as rich source of ergot alkaloid
2. Ergotamine and it’s semisynthetic derivatives are used in migraine
3. Ergometrine is oxytocic and is used in delivery
4. It stimulates the tone of uterine muscle
Pilocarpus
Common Names: Jaborandi, Pernambuco Jaborandi, Maranham Jaborandi.

Botanical Source :The dried leaflets of (1) Pilocarpus Jaborandi, Holmes; or (2) Pilocarpus microphyllus,

Family: Rutaceae

Chemical Composition.—The active principle of jaborandi leaves is the alkaloid pilocarpine, Several other active
principles were subsequently isolated from the mother liquors of pilocarpine-namely, the alkaloids jaborine,
pilocarpidine, jaboridine and volatile jabonine, as well as jaboric and pilocarpic acids;
Use:
1.it is helpful in renal disease
2. Increase the secretion of saliva
3. Is used to contract pupil

4. Tx for Glaucoma
Veratrum
Common Name(s):False hellebore, hellebore, Indian poke, American white hellebore
Biological source: It is the dried root and rhizome of Veratrum viride.
Family: Liliaceae
Constituents: There are more than 50 steroidal alkaloids found in American hellebore. Isolated chemical
constituents include: O-acetyljervine, cevadine, cryptenamine, cyclopamine (11-deoxojervine), cycloposine,
germitrine, germidine, jervine, muldamine, protoveratrine (A&B), veratramine, veratridine, and veriloid.
Use:
1. It is used in hypertension
2. It has been used in the treatment of pneumonia, peritonitis, and other sthenic fevers, but is chiefly useful
in chronic diseases, such as arterio-sclerosis and interstitial nephritis.
Ephedra / Ma Huang
Constituent: Ephedrine (from Ephedra sinica)
Use: Nasal decongestant, bronchodilator

Colchicine
Use: used in plant genetics because it can double the chromosomes; Gout
from Colchicum autumnale

Khat / Abyssynian Tea

Constituent: cathionone
-only alkaloid that can mimic methamphetamine

Peyote/ Mescal buttons

Constituent: mescaline (dried tops of Lophophora williamsii)
Use: Hallucinogenic agent and euphoric agent
Coffee
Synonym: Caffea
B.S.: Coffee bean or coffee seed is the dried ripe seed of Coffea arabica
Family: Rubiaceae Caffeine (1,3,7-trimethylxanthine)
Constituents: Beans contain Oil, wax, caffeine, aromatic oil, tannic acid, caffetannic acid, gum, sugar, protein.
Uses: People drink coffee to relieve mental and physical fatigue and to increase mental alertness.
Coffee is also used to prevent Parkinson's disease, gallstones, type 2 diabetes, gastrointestinal cancer, lung
cancer, and breast cancer.
Other uses include treatment of headache, low blood pressure, obesity, and attention deficit-hyperactivity
disorder

Decaffeinized coffee is prepared by extracting most of the

caffeine from the coffee bean yet retaining the pleasant
aroma of coffee. Such apreparation usually contains
0.085% caffein
Use: Acts as stimulant;diuretic; in CNS depressant
poisoning
Tea
Synonym: Cha
Theophylline (1,3-dimethylxanthine)
Biological source: It is consists of the prepared leaves and leaf buds of Camellia sinensis or
Camellia thea or Thea sinensis
Family:Theaceae
Constituent: Tea contains Tannin, caffeine, adenine, theophylline, theobromine, Xanthine and volatile oil.

Theophylline
-tx for bronchial asthma
-tocolytic
Aminophylline
-for pedia (bronchial asthma)
-semi-synthetic theophylline
Theobromine
-seed part is used
-diuretic and pulmonary edema