module 2 tuts p8

ALKALOIDS

• Bitter, basic, nitrogenous substances that are physiologically active

• From the word ALKALINE that means BASIC

• Why BASIC? Chemically AMINES (R-NH2)

ALKALOIDS

1. End with -ine

2. All are SOLIDS except:

• Coniine

• Nicotine

• Sparteine

3. Free alkaloids are sparingly soluble in water

4. Forms salts or precipitates with these reagents:

• Mayers

• Wagners

• Dragendorffs

• Valsers

• Hagers

Coniine, Nicotine, Sparteine

All alkaloids are solid except:

Alkaloidal Salt

Alkaloidal Base + H₂SO₄ (acid)

Atropine Sulfate

Atropine + H₂SO₄ (acid) = ___

Ephedrine

Toxic alkaloid; A potent vasoconstrictor/vasopressor - it can cause an increase in blood pressure

Strychnine

Toxic alkaloid; when ingested can cayse tetanus-like effect (lock jaw)

Atropine

• Anti-cholinergic

• Antidote for organophosphate insecticide poisoning (malathion, parathion)

• Used as an antidiarrheal agent (lomotil® before: Atropine + Diphenoxylate)

Alkaloidal Precipitants

• Mayer’s Reagent → Mercury in Potassium Iodide

• Dragendorff’s Reagent → Iodine in Potassium Iodide

• Wagner’s Reagent → Potassium Bismuth Iodide

• Hager’s Reagent → Picric Acid Solution

Mayer’s Reagent

Mercury in Potassium Iodide (MaMeKi)

Wagner's Reagent

Iodine in Potassium Iodide (W-IKI)

Dragendorff’s Reagent

Potassium Bismuth Iodide (bismuth na dragon)

Hager’s Reagent

Picric Acid Solution

Valser’s Reagent

Red mercuric iodide

Pyridine-Piperidine Alkaloids

• Lobeline - Lobelia inflata

• Arecoline - Areca catechu

• Nicotine - Nicotiana tabacum

Lob ni Nico Pipy ni Coline

Tropane Alkaloids

✓ Solanaceous Alkaloids: Atropa belladona (nightshade family - solanaceae)

• Scopolamine

• Hyoscyamine

• Atropine

  ---

• Cocaine

SHAt na ng Coke

Isoquinoline Alkaloids

• Sanguinarine

• Emetine

• Hydrastine

• Morphine (opium representative)

• Tubocurarine

Iso inSan Em, nag Hy at sabi Mor Tubo sa business

Morphine

Most important and most abundant opium alkaloid (phenanthrene derivative)

Codeine

• METHYLMORPHINE - morphine’s OH → CH3

• Methylation of morphine

True

• Demethylation of codeine - product is morphine

• Methylation of morphine - product is codeine

• Acetylation of morphine - product is heroin

Heroin

• DIACETYLMORPHINE

• The two hydroxyl (OH) groups found on the morphine molecule are replaced by acetyl groups (COCH3).

Quinoline Alkaloids

Antimalarial agents

• Quinidine - also an antiarrhythmic

• Quinine

• Cinchonidine

• Cinchonine

Indole Alkaloids

• Catharantus

  • Vincristine, Vinblastine - antineoplastic agents

• Rauwolfia serpentina

  • Reserpine

• Physostigma / Calabar Bean

  • Physostigmine

• Ergot Alkaloids

  • Ergotamine, Ergonovine

• Nux vomica

  • Strychnine, Brucine

CaRPENter is INdole

Alkaloidal Amines

Phenylethylamine

• Ephedrine - vasoconstrictor/vasopressor

• Mescaline ⭐

• Colchicine

• Cathinone

Ephe Mes Col Cath

Steroidal Alkaloid

• Veratridine - cppp nucleus

Purines/Methylxanthines Alkaloids

• Caffeine

  • 1,3,7-trimethylxanthine

• Theophylline

  • 1,3-dimethylxanthine

• Theobromine

  • 3,7-dimethylxanthine

Imidazole Alkaloid

• Pilocarpine

Summary: Alkaloids

Refer to the picture

Ergonovine

• Classification: Ergot Alkaloid (INDOLE alkaloid)

  • Sclerotium produced by a fungus

• Source: Ergot produced by Claviceps purpurea

• Use: Oxytocic agent

True

Ergotamine is for the treatment of migraine. Ergonovine is an oxytocic agent (induce labor)

Reserpine

• Classification: Indole Alkaloid

• Source: Rauvolfia serpentina

• Use: Hypotensive agent (can cause decrease in blood pressure)

Atropine

• Classification: Tropane Alkaloid

• Source: Atropa belladonna, Solanaceae

• Uses:

  • Anticholinergic

  • Antidote for organophosphate poisoning (Malathion, parathion)

  • Antidiarrheal

  • Anti-sialogogue (decrease secretion of saliva)

Hyoscyamine

• Classification: Tropane Alkaloid

• Source: Datura stramonium / Hyoscyamus niger

• Uses: Anti-cholinergic, spasmolytic (anti-spasmodic)

True

Datura metel is the source of scopolamine while Datura stramonium is the source of hyoscyamine

Lobeline

• Classification: Pyridine-Piperidine Alkaloid

• Source: Lobelia inflata

• Use: Smoking deterrent

True

Lobeline and nicotine are both used for smoking cessation

Cocaine

• Classification: Tropane Alkaloid

• Source: Erythroxylum coca

• Use: Local anesthetic

Nicotine

• Classification: Pyridine-Piperidine Alkaloid

• Source: Nicotiana tabacum

• Use: Smoking deterrent (more potent)

BIOSYNTHESIS OF TROPANE ALKALOIDS

Step 1:

• Ornithine → pyrrolidine ring of Tropine

Step 2:

• Phenylalanine → Tropic Acid

Step 3:

• Esterification of Tropine and Tropic Acid → (-) Hyoscyamine (a tropane alkaloid)

Step 4:

• Racemization of (-) Hyoscyamine → Atropine

Step 5:

• Scopolamine + Tropic Acid → Scopolamine or Hyoscine

Hyoscyamine: Biosynthesis

• Amino Acid: Ornithine

  • Plants need the amino acid Ornithine.

  • Ornithine is incorporated stereospecifically to form the pyrrolidine ring of tropine.

  • Tropine is synthesized from ornithine.

• Amino Acid: Phenylalanine

  • Phenylalanine is used by plants to synthesize tropic acid.

• Two products are formed: tropine and tropic acid.

• An esterification reaction occurs between tropine and tropic acid, producing levorotatory hyoscyamine.

  • Levorotatory means it can rotate plane-polarized light to the left.

Atropine: Biosynthesis

• L-hyoscyamine becomes racemic mixture - optically inactive

• Racemization of L-hyoscyamine is _____

Scopolamine: Biosynthesis

• Esterification of Scopoline + Tropic Acid = ______

• AKA Hyoscine

• Buscopan® - anti-spasmodic agent

Hyoscyamine: Biosynthesis

• Esterification of Tropine + Tropic Acid = _____ (levorotatory)

Hydrolysis in Solanaceous Alkaloids

Opposite of esterification

• Scopolamine → Scopoline + Tropic Acid

• L-hyoscyamine → Tropine + Tr

D. I and III

Select the statements that best describes the biosynthesis of hyoscyamine

I. Feeding studies with labeled ornithine have shown that this is incorporated stereospecifically to form the pyrrolidine ring of tropane

II. Tyrosine is the precursor of tropic acid (phenylalanine)

III. Esterification of tropic acid with tropine produces hyoscyamine

IV. Hyoscyamine is dextrorotatory (Levo)

A. II and III

B. II, III and IV

C. I, II and III

D. I and III

D. II and III

Select the statements that best describes the Solanaceous Alkaloids

I. The belladonna alkaloids are most abundant in plants after the fruits have ripened (fruits begin to form)

II. The principal solanaceous alkaloids are hyoscyamine, atropine and scopolamine

III. Atropine and scopolamine are competitive with acetylcholine at the post ganglionic synapse of the parasympathetic nervous system producing an antispasmodic effect

IV. Scopolamine is also known as hyoscyamine, and atropine is also known as hyoscine

A. I and II

B. III and IV

C. I, II and III

D. II and III

B. I, II, III and IV

Select the statements that best describes the following alkaloids

I. Atropine is racemic hyoscyamine

II. Hyoscyamine is the ester of tropic acid and tropine

III. Scopolamine is particularly abundant in Datura metel

IV. On hydrolysis, Scopolamine yields tropic acid and scopoline

A. I, II and III

B. I, II, III and IV

C. II and III

D. I and IV

Reserpine

Determine the names of these alkaloids: Refer to the picture (Indole Ring)

A. Cocaine - Tropane

B. Reserpine - Indole

C. Quinine - Quinoline

D. Morphine - Isoquinoline

C. Caffeine - Xanthine/Purine

Determine the names of these alkaloids: Refer to the picture: (1,3,7-trimethylxanthine)

A. Morphine - Isoquinoline

B. Cocaine - Tropane

C. Caffeine - Xanthine/Purine

D. Quinine - Quinoline

A. Quinine - Quinoline

Determine the names of these alkaloids: Refer to the picture

A. Quinine - Quinoline

B. Morphine - Isoquinoline

C. Caffeine - Purine/Xanthine

D. Reserpine - Indole

D. Morphine - Isoquinoline

Determine the names of these alkaloids: Refer to the picture

A. Caffeine - Purine

B. Cocaine - Tropane

C. Reserpine - Indole

D. Morphine - Isoquinoline

True

Isoquinoline Alkaloids

• Codeine - antitussive CNS depressant

• Heroin - hallucinogen CNS depressant

• Morphine - most useful and abundant

---

Tropane Alkaloid

• Cocaine - local anesthetic CNS stimulant

C. Cocaine - Tropane

Determine the names of these alkaloids: Refer to the picture

A. Morphine - Isoquinoline

B. Caffeine - Xanthine/Purine

C. Cocaine - Tropane

D. Reserpine - Indole

A. Dragendorff’s

The Alkaloidal test reagent is a solution of potassium bismuth iodide and gives an orange colored precipitate.

A. Dragendorff’s - Beastmode

B. Mayer’s - MaMeKi

C. Wagner’s - W-IKI

D. Hager’s - Picric Acid

D. Indole

Classify Ergonovine and Reserpine.

A. Imidazole

B. Purine

C. Steroidal

D. Indole

C. Solanaceae

Family name of Atropa belladonna

A. Papaveraceae

B. Fabaceae

C. Solanaceae

D. Berberidaceae

A. Lobelia inflata – hyoscine (lobeline)

Find the pairs that are NOT correctly matched.

A. Lobelia inflata – hyoscine (lobeline)

B. Hyoscyamus niger – hyoscyamine

C. Erythroxylum coca – cocaine

D. Datura stramonium – hyoscyamine

D. Coca- local analgesic (local anesthetic)

Select the pair that is NOT correctly matched.

A. Tobacco – nicotine for smoking cessation

B. Belladonna – spasmolytic agent

C. Datura – anticholinergic agent

D. Coca- local analgesic

D. P. bracteatum

The source of the alkaloid thebaine

A. P. somniferum

B. P. mirabilis

C. P. aeruginosa

D. P. bracteatum

A. Rubiaceae

Quinine is from a plant from the family

A. Rubiaceae

B. Apocynaceae

C. Berberidaceae

D. Labiatae

Isoquinoline

Morphine

Indole

Ergotamine

Quinoline

Quinine

Purine

Caffeine

Tropane

Atropine

Tropane Alkaloids

A condensation product of pyrrolidine and piperidine

Isoquinoline Alkaloids

The class to which opium alkaloids belong

Indole Alkaloids

The class to which ergonovine, reserpine and strychnine belong

Quinoline Alkaloids

The class to which quinine, quinidine, cinchonine and cinchonidine belong

Purine Alkaloids

The class to which caffeine and theobromine belong