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It is known that although only the (S)-enantiomer of the infamous sedative thalidomide possesses teratogenic properties, it is not very useful to administer the pure (R)-enantiomer since it is racemized within the body. Are there other known examples of drugs that are stereoconverted in vivo? How does the body perform the conversion?

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""only the (S)-enantiomer of the infamous sedative thalidomide possesses teratogenic properties"" How was this fact estabished? You always have both enantiomers in vivo, right? – Georg Apr 28 '12 at 6:48
@Georg probably through study of the mechanism of interaction. – Kevin Apr 28 '12 at 19:07

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Although I can't think of any drug examples other than thalidomide, here's information on thalidomide's mechanism:

The chiral carbon of thalidomide can tautomerize in basic conditions into an enol, which is achiral. A reversal back to the ketone results in a mix of (R) and (S) enantiomers.

Chemical diagram for s-thalidomide

In the body, this tautomerization is generally catalyzed by basic amino acids. Specifically, albumin is the main catalyst in humans.

While this is beyond the scope of your question, the reason that only (S)-thalidomide causes birth defects is that it can insert itself into DNA and suppresses certain genes necessary for embryonic development.

  1. Reddy - Chirality in Drug Design and Development
  2. http://www.ncbi.nlm.nih.gov/pubmed/9860497
  3. http://www.ncbi.nlm.nih.gov/pubmed/9499573
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According to the relevant article, HSA does catalyze interconversion at pH 7.4, but once other components of blood plasma are added to the mixture, catalysis is inhibited. Don't forget that amines can themselves be chiral, as in this case, but that their interconversion barrier is low. The barrier is greater when the amine is cyclic, as in thalidomide, but it still can spontaneously interconvert. – CHM Apr 28 '12 at 18:01
I added that article to the list. Certain components do inhibit the reaction, although blood plasma on the whole is also a minor catalyst for the interconversion although not as good a catalyst as HSA. – Andrew Apr 28 '12 at 18:06

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