Chemguide: Support for CIE A level Chemistry


Learning outcomes 23.1(a) and 23.1(b)

These statements are about chiral molecules in drugs.

Before you go on, you should find and read the statements in your copy of the syllabus.


Statement 23.1(a)

This just wants you to know that most chiral drugs extracted from natural sources often contain only a single optical isomer.

Well, now you know that and, if you take the syllabus literally, all you would ever need to do is to write down that statement. But that would always be dangerous with CIE! So we'll just add a little bit.

Chiral drug molecules

If you can't remember what chiral molecules are, then go back and look again at learning outcomes 14.4(b), 14.4(d) and 14.4(e).

Taxol

The anti-cancer drug Taxol was originally obtained from the bark of the Pacific yew tree. Unfortunately, it occurs in such small amounts that it was estimated that you would have to cut down six 100 year-old trees to get enough Taxol to treat just one patient.

Clearly that is impossible, and so a lot of work went into finding a way of synthesising the drug in the lab. Because Taxol is a seriously complicated molecule, that wasn't so easy. However, eventually it was done.

Here is the structure of Taxol shown as a skeletal formula. The Taxol molecule has a lot of chiral centres. These are carbon atoms which have four different groups attached to them. You can spot them very easily in this particular diagram of the structure of Taxol, because these are the ones which show the spatial arrangement of the atoms using either dotted or solid wedges.

Do NOT try to learn this - it is just an example that I already had from the previous syllabus!

There will be a very large number of possible optical isomers of Taxol, so why is only one of them likely to be present in the yew tree?

In any biological system, molecules are synthesised and broken down by reactions involving enzymes, but enzymes work by a lock-and-key mechanism. A molecule has to be exactly the right shape to fit the enzyme.

Different arrangements around a chiral centre will force an entirely different shape on the molecule, and it may well no longer fit the enzyme. So enzyme systems will tend to produce a single optical isomer because that is the only shape they can work with.


Statement 23.1(b)

So why is the presence of chiral centres important to drug design?

Each chiral centre will have two possible arrangements of bonds around it. A different arrangement of bonds will mean a differently shaped molecule. And differently shaped molecules won't necessarily fit the active site of an enzyme, or whatever else the drug needs to attach to.

A fairly simple example of a drug with a single chiral centre is thalidomide - a drug which was prescribed for morning sickness in pregnancy in the 1950s. The chiral centre is circled in red below:

This will have two optical isomers. One was the right shape and so did what it was supposed to, but the other one behaved completely differently, causing major birth defects. It is believed that the isomer responsible interfered with DNA.

These days, a lot of effort goes into producing a single isomer of a drug. Chemical reactions frequently produce mixtures of optical isomers. Trying to produce just one isomer is known as asymmetric synthesis.

Reasons for producing drugs consisting of a single active isomer:

  • It lowers the chances of undesirable side-effects due to the other isomers.

  • It is cheaper in the long-run, because it is a waste of money and materials producing a drug half of which (or more) is of no use.

  • The patient can be given smaller doses if all the drug is active.


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© Jim Clark 2011 (last modified July 2014)