Stereochemistry Importance of Chirality in Pharmacy

R/S notation E/Z notation

Enantiomers

(S)-(+)-Lactic acid (R)-(-)-Lactic acid

DiastereomersD-Threose D-Erythreose

Racemate/ Racemic mixture Enantiopure/ Enantiomerically pure

Racemate vs Enantiopure

In a survey of 1850 drugs: 1327 were synthetically obtained 528 contained one or more chiral centers 88.4% were used as a racemate

Racemate

Enantiomers in Biological Systems

Thalidomide

Thalidomide became an over the counter drug in Germany on October 1, 1957.

Shortly after the drug was sold, in Germany, between 5,000 and 7,000 infants were born with phocomelia (malformation of the limbs).

Throughout the world, about 10,000 cases were reported of infants with phocomelia due to thalidomide; only 50% of the 10,000 survived. 

Contergan

Today, thalidomide is being marketed by Celgene mainly as a treatment of certain cancers and of a complication of leprosy.

Contergan

To separate unwanted effects if they reside exclusively in one enantiomer

Less drug dosage Easier assessment of

drugs

Enantiopure

Escitalopram

Complexity of process Cost Thermodynamically unstable causing

racemization to occur◦ e.g. Thalidomide undergoes racemization in

aqueous media

Disadvantages

Enantiomerically pure drugs are genarally preferred over racemates

Disadvantage lies at the cost and the technology needed to separate the enantiomers

Conclusion