10 - Chirality in Pharmaceutical Synthesis Flashcards
What determines the pharmacological activity of a molecule?
Biological molecules 3D structure determines the pharmacological activity of a molecule. This determines if it will have the desired therapeutic effect.
Why is single isomer production advantageous to pharmaceutical companies?
The risk from undesirable side effects are reduced. Also drug doses are reduced if there’s two isomers only one of them will be active and effective. Therefore 50% will be wasted - if this could be cut it would reduce the desired drug dosage by 50%.
How do chiral compounds in nature differ to those artificially made?
When a chiral compound is synthesised in nature only a single isomer is produced. When a chiral compound is synthesised in a laboratory a mixture of both isomers are formed.
Why is it hard to isolate pharmacologically active isomers?
Complicated separation techniques are needed to isolate pharmacologically active isomers. Separation is very difficult as optical isomers have the same physical properties - melting/boiling points and solubilities are the same.
How can you isolate pharmacologically active isomers?
Separation techniques involve enzymes, electrophoresis and chromatography. These methods are time consuming and costly.
What are the current methods used to prepare single chiral isomers?
Using enzymes as biological catalysts: If a synthetic route can be designed using enzymes, then a single isomer can be produced. Chiral pool synthesis: Makes use of naturally occurring chiral molecules within the synthetic route. The chirality of the molecule can lead to a product that is a single pure isomer. Common starting materials are natural alpha-amino acids and sugars. Use of transition element complexes: transition metal complexes produce chiral catalysts. These could then transfer chirality to synthesise a single isomer product.
What happens with Ibruprofen in the body?
Ibruprofen has 1 chiral carbon - one isomer relives pain more readily than the other isomer. In the body the less active form is converted to the pharmacologically active isomer - so the whole dose is active. This minimises side effects.
