1. Alkaloids

alkaloids

are naturally occurring, nitrogen-containing compounds (usually in heterocyclic rings) that often have physiological effects on humans and animals.

basic

alkakoids are typically (acidic/basic) in nature and primarily derived from plants

typical alkaloids

proto- alkaloids (amino- alkaloids)

synthetic alkaloids

types of alkaloids

typical alkaloids

are derived from plant sources, they are basic, they contain one or more nitrogen atoms (usually in a heterocyclic ring)

proto-alkaloids (amino- alkaloids)

Lack one or more properties of typical alkaloids (e.g., ephedrine, colchicine).

synthetic alkaloids

Not found in plants but closely resemble natural alkaloids (e.g., homatropine).

early isolations (19th century)

The first alkaloids were isolated in the __

early isolations (19th century)

Reintroduction of alkaloid-containing drugs into medicine.

early isolations (19th century)

Development of the percolation process for drug extraction.

Derosne

1803: isolated narcotine

Serturner (1806, 1816)

1806, 1816: isolated morphine from opium

Pelletier & Caventou

Isolated several alkaloids

Coniiine (Schiff, 1870)

First alkaloid with an established structure

20th Century Focus

Alkaloids became important in the search for plant- based anticancer drugs.

20th Century Focus

Investigating alkaloids for anticancer, antiaging, and antiviral properties.

crystalline solids

Most alkaloids are __ that can form salts with acids.

free bases, salts, or N-oxides

In plants, they can exist in different forms, including ___.

carbon, hydrogen, nitrogen, and often oxygen.

alkaloids are primarily made up of

liquids

Some alkaloids, like coniine (from hemlock) and nicotine (from tobacco), do not contain oxygen and exist as ___.

berberine (yellow) and sanguinarine salts (copper-red).

While most alkaloids are colorless, some have distinct colors, such as ___

sparingly soluble in water

soluble in organic solvents

alkaloids solubility in free bases

Soluble in water

Sparingly soluble in organic solvents

alkaloids solubility in free salts

low solubility

quinine sulfate solubility

highly soluble

alkaloids solubility in quinine hydrochloride

heterocyclic (typical)

non-heterocyclic (atypical)

classes of alkaloids

non-heterocyclic (atypical)

Also called "proto- alkaloids" or "biological amines"

heterocyclic (typical)

Contain a heterocyclic ring.

Divided into 14 groups based on ring structure

1.Pyrrole and Pyrrolidine

2. Pyridine and Piperidine

3. Pyrrolizidine

4. Tropane

5. Quinoline

6. Isoquinoline

7. Aporphine

8. Indole

9. Imidazole

10. Norlupinane

11. Purine

12. Steroidal

13. Diterpene

14. Alkylamine/ Amino

15. alkaloid

Heterocyclic (Typical) examples:

Phenylalanine, Tyrosine, Tryptophan, Ornithine, Lysine

Alkaloids are derived from the products of primary metabolism, with amino acids, such as ___ serving as their main precursors.

lysine

bioprecursor of alkaloids

Schiff bases and Mannich reaction.

Ways of alkaloid biosynthesis are too numerous and cannot be easily classified. However, there are a few typical reactions involved in the biosynthesis of various classes of alkaloids, including synthesis of ___

Schiff bases

can be obtained by reacting amines with ketones or aldehydes. These reactions are a common method of producing C-N bonds

Schiff bases

In the biosynthesis of alkaloids, such reactions may take place within a molecule

Mannich reaction

An integral component of the __, in addition to an amine and a carbonyl compound, is a carbanion, which plays the role of the nucleophile in the nucleophilic addition to the ion formed by the reaction of the amine and the carbonyl

intermolecularly and intramolecularly

The Mannich reaction can proceed both___

pyridine alkaloids

are nitrogen-containing chemical compounds that are found in plants and have a pyridine ring.

pyridine alkaloids

They perform a variety of functions in nature, such as defense mechanisms in insects and train pheromones

nicotine

is a naturally produced alkaloid in the nightshade family of plants (most predominantly in Nicotiana tabacum and Duboisia hopwoodii) and is widely used recreationally as a stimulant and anxiolytic.

areca alkaloids

are a group of pyridine alkaloids found in the seeds of the areca palm tree.

arecoline

a nicotinic acid-based mild parasympathomimetic stimulant alkaloid.

arecaidine

an alkaloid that can have a number of effects on the body, including increased heart rate, sweating, and facial flushing.

rove beetles ( family Staphylinidae)

particularly those in the genus Paederus, produce pyridine alkaloids.

pederin

One well-known example is ___, a potent toxin found in Paederus beetles.

arecha catechu

scientific name for betel nut

betel nut

mixed with lime and betel leaves then produce red color paste when chewed

pederin

is a complex pyridine-derived alkaloid responsible for the severe skin irritation caused by contact with these beetles. This chemical is primarily used as a defense mechanism against predators.

piperidine alkaloids

are chemical compounds found in plants, insects, amphibians, and marine animals. They are characterized by their saturated heterocyclic ring, or piperidine nucleus

piperine

a chemical compound that gives black pepper and long pepper their pungent flavor.

piperine

• It may help with digestion by increasing gastric juice production.

• It may help with blood sugar management by increasing the absorption of sugar from the blood into cells.

• It may help with cholesterol levels.

• It may have anti-inflammatory and antibacterial properties.

• It may help with arthritis

lobeline

a chemical compound found in plants such as Indian tobacco and Devil's tobacco. It's a white, amorphous powder that dissolves easily in water.

lobelanidine

is a chemical analog of lobeline.

lobelia

herbal remedy for respiratory conditions such as asthma, bronchitis, pneumonia, and cough

coniine

is a poisonous alkaloid found in poison hemlock and other plants. It's toxic to humans and animals

nicotinic acetylcholine receptor antagonist

Coniine is a __. It inhibits the nervous system

Conium maculatum

scientific name for poison hemlock

Poison Hemlock (Conium maculatum)

One of the most poisonous plants in the world

sedamine

A natural product found in plants and used as a tablet that contains medications for stomach and intestinal cramping and anxiety.

Hylotelephium telephium or Orpine

Sedamine is most commonly found in__

buttercups

and other plants in the family (Ranunculaceae) contain a variety of alkaloids, some of which are poisonous

aconitine

a dangerous poison found in Buttercups that can cause vomiting, paralysis, and death

lupine

The piperidine alkaloids ammodendrine and N- methylammodendrine are found in ___ which is considered a teratogen, meaning it can cause birth defects in livestock if ingested by pregnant animals

ammodendrine and N- methylammodendrine

teratogen, meaning it can cause birth defects in livestock if ingested by pregnant animals

lupinus

looks like lavander but carries a deadly secret

tropane alkaloids

are a class of naturally occurring alkaloids that contain a tropane ring in their chemical structure.

cocaine

is a tropane alkaloid that acts as a powerful CNS stimulant derived from the leaves of the Erythroxylum coca plant.

cocaine

While it was traditionally used as a form of pain relief by locals, it is commonly known today as an illegal drug that induces euphoria but has severe long term effects.

Erythroxylum coca

scientific name of coca plant

Hyoscyamine

is a tropane alkaloid that acts as a muscarinic antagonist, which blocks acetylcholine at muscarinic receptors.

Hyoscyamine

It is used to treat spasms and excessive secretions.

Atropa belladonna, Datura stramonium and Hyoscyamus niger

Hyoscyamuine: It is typically found in plants of the Solanaceae family, including

scopolamine

Also known as hyoscine, ___ is a tropane alkaloid that acts as a muscarinic antagonist, which blocks acetylcholine at muscarinic receptors.

scopolamine

It is similar in structure and function to hyoscyamine. However, it contains an additional epoxide bridge, and iS generally more sedative and amnesic.

Atropa belladonna, Datura stramonium and Hyoscyamus niger

plant for the Solanacease family

Atropa belladonna

scientific name of deadly night shade

Datura stramonium

scientific name of Jimsonweed

Hyoscyamus niger

scientific name of henbane

calystegine

are tropane alkaloids that act as glycosidase inhibitors,which are primarily used for potentially treating metabolic disorders and diabetes by modulating carbohydrate metabolism. It is derived from plants in the Solanaceae and Convolvulaceae (e.g., Calystegia sepium) families

Calystegia sepium

scientific name of hedge bindweed

solanaceous alkaloids

are naturally occurring nitrogen- containing compounds found in plants of the Solanaceae family. They exhibit a wide range of pharmacological effects, such as anticholinergic activity, neurotoxicity, and enzyme inhibition.

atropine, scopolamine, hyoscyamine

examples of tropane alkaloids

tropane alkaloids

Can block muscarinic acetylcholine receptors, causing pupil dilation, decreased secretions, and CNS effects

1) Atropa belladonna (Deadly nightshade)

2) Datura stramonium (Jimsonweed)

3) Hyoscyamus niger (Henbane)

tropane alkaloid sources

Solanine, Chaconine, Tomatine

examples of steroids alkaloids

steroidal alkaloids

Can disrupt cell membranes

Toxic to humans

Can gastrointestinal and neurological symptoms

1) Solanum tuberosum (Potato, especially any green bits)

2) Solanum lycopersicum (Tomato)

3) Solanum nigrum (Black nightshade)

sources of steroidal alkaloids

Solanum lycopersicum

scientific name for tomato

Solanum nigrum

scientific name for black nightshade

Calystegines

examples of nortropane alkaloids

nortropane alkaloids

Inhibits glycosidase enzymes, potentially treating metabolic disorder

1) Atropa

2) Datura

3) Solanum

4) Calystegia

5) Ipomoea

sources of nortropane alkaloids

quinoline alkaloids

are a class of naturally occurring organic compounds that contain a quinoline core structure. These alkaloids are found in various plants species and are known for their diverse biological activities, including antimalarial, antimicrobial, anti- inflammatory, and anticancer properties.

quinoline alkaloids

First isolated from Cinchona bark in the 19th century.

quinine

was the first alkaloid used to treat malaria

quinine

Played a crucial role in the development of modern pharmacology.

quinine, quinidine, cinchonine

TYPES OF QUINOLINE ALKALOIDS

quinine

Antimalarial drug

quinidine

Antiarrhythmic agent.

cinchochine

Used in traditional medicine for fever and malaria

Cinchona officinalis

scientific name of cinchona tree

shikimate pathway

Biosynthesis of Quinoline Alkaloids

⟡ Derived from the ___