Theme 1 Drug History Lecture 1

Question 1

How does a beta lactam antibiotic function?

Answer 1

The main functional group the beta lactam, reacts with the hydroxy group on the serine residues thus covalently blocking it

Question 2

The 4 main parts of how drugs evolved

Answer 2

Plants, semi-pure extracts, isolation of molecules, and design/synthesis for a specific disease.

Question 3

First Pharmacopeia?

Answer 3

London 1618, feverfew parthenolide (anti-inflam and anti-hyperalgesic)

Question 4

Examples of medicinal plants

Answer 4

morphine (opium poppy), digoxin (foxglove),quinine (fever tree), cocaine (the divine plant of the Incas) and ephedrine (Mau Huang)

Question 5

Two structural features that are common to cocaine, amylocaine and procaine?

Answer 5

Tertiary Amine which is for stability of the structure and interacts with all of the biological receptors/ benzoate which is responsible for lipophilicity and interaction of receptors.

Question 6

Suggest a synthesis of procaine (3) using para-aminobenzoic acid and N,N-diethylethanolamine

Answer 6

PABA with HCL catalyst, to form the salt (which is a more reactive species) and then Para-aminobenzoic acid ethyl ester hydrochloride with N,N-diethylethanolamine to form Procaine.

Question 7

Explain the developments in late 1800s

Answer 7

Understanding of functional groups and semi-synthesis

(Morphine -> Diacetylmorphine = diamorphine (Heroin))

Question 8

What is semi synthesis

Answer 8

The formation of a different compound from a naturally occuring product.

Question 9

Nitrogen Containing plant Products

Answer 9

Many early medicines fell into the category of nitrogen-containing plant products

Morphine 1805
Friedrich Serturner ->

Colchicine 1820
Pelletier & Caventou ->

Cocaine 1855
Friedrich Gaedcke ->

Ephedrine 1885
Nagai Nagayoshi

Question 10

Isolation of Ephedrine (Ma Huang) and difference between morphine

Answer 10

The key difference is that morphine has the phenolic group and therefore interacts with water better and is more soluble in the aqueous phasetherefore making it easier for extraction

*Mechanism is in notes

Question 11

What is the organic solvent used in morphine

Answer 11

chloroform

Question 12

What is the usedto neutralise
in ephedrine

Answer 12

potassium permanganate, which neutralises HCL to make a more aq environment and chloroform

Question 13

Give two examples of semi-synthetic drugs?

Answer 13

Pacitaxel and Penicilin

Question 14

What are the structural differences between both and therapeutic indication?

Answer 14

Baccatin iii and major natural penicillin

Question 15

What is the most important thing to remember about morphine?

Answer 15

It has the acidic phenol and the others do not

Question 16

What happens to acidic molecules in the isolation of ephedrine

Answer 16

They would be ionised and partitioned into the aq layer.

Question 17

What form is ephedrine in?

Answer 17

Ephedrine is in the unionised basic form

Question 18

Adding dilute HCL would do what?

Answer 18

This would cause a separation of layers between aq and organic phase.

Question 19

What would happen to ephedrine due to the addition of HCL?

Answer 19

Ephedrine would become protonated.

Question 20

How is ephedrine converted back in comparison to morphine

Answer 20

Recrystallized as an oxalate salt after the free base step(potassium) which left pure epoherdrine, the precipitate of morphine is soaked in HOT ETHANOL and left to cool and then crystalised.

Question 21

Structural Identification

Answer 21

1902-1907: Four separate labs in Germany helped identify the empirical formula of morphine as well as some structural features