1
$\begingroup$

In many cases the L- or S- stereoisomer of organic compounds is vastly more bioactive than other enantiomers. So we see pharmaceutical companies producing escitalopram (i.e., S-citalopram), esomeprazole (S-omeprazole), esketamine (S-ketamine). (Granted some of this may be nothing more than a gambit to prolong patent protection on the underlying racemic drug, but leave that aside for now.)

What tricks enable such complex molecules to be produced or separated into a single, specific isomer in large quantities?

Improve this question
$\endgroup$
3
  • 1
    $\begingroup$ Asymmetric synthesis is quite a big deal. $\endgroup$
    – Ivan Neretin
    Commented Oct 27, 2022 at 1:30
  • $\begingroup$ Another way is applying separation techniques on racemic mixtures, using chiral counterparts. $\endgroup$
    – Poutnik
    Commented Nov 3, 2022 at 18:24
  • 1
    $\begingroup$ Of the naturally-occurring amino acids it may be said that they are both L-(Fischer) and at the same S-(CIP) stereoisomers. But this correlation is not true for all stereoisomers. While you have found several active S-stereoisomers, an active site knows nothing about the CIP rules. $\endgroup$
    – user55119
    Commented Nov 3, 2022 at 21:37

1 Answer 1

Reset to default
6
$\begingroup$

Small misconception: L is not S. Chirality is a part and parcel of life and there is no coincidence that a certain enantiomer is more biologically active than the other. You have already noted that. I don't think that patenting is the main driving force to develop chiral medicines. There is a very sad story, called the thalidomide tragedy which led to the birth of severely deformed babies who were crippled for life due to one of its enantiomers. Since 1992, chiral analysis of drugs is a must!

Approximately 63% of drugs approved by the Food and Drug Administration (FDA, USA) between 2015 and 2020 were chiral drugs, according to a survey conducted last year in J. Med. Chem. 2021, 64, 2339-2381). Coming to the main query, large scale preparation of a single enantiomer can come from:

(i) Asymmetric synthesis or enzymatic synthesis

(ii) Biological synthesis e.g., certain antibiotic are synthesized by microrganisms, whose complexity which can startle human minds. Nature is also a synthetic organic lab.

(iii) Chiral crystallization

(iv) Large scale (preparative) chiral chromatography (simulated moving bed etc.)

(v) Countercurrent chromatography, large scale isolation method.

Improve this answer
$\endgroup$
2
  • 4
    $\begingroup$ The thalidomide story as often told is simplistic. The enantiomers readily convert under biological conditions in the body so, had the manufacturer produce a single enantiomer product, there would still have been a tragedy. $\endgroup$
    – matt_black
    Commented Oct 27, 2022 at 13:45
  • $\begingroup$ @matt_black, This is correct. Thalidomide is still used for other medicinal purposes but not for pregnant women anymore. $\endgroup$
    – ACR
    Commented Oct 27, 2022 at 14:27

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service and acknowledge you have read our privacy policy.

Not the answer you're looking for? Browse other questions tagged or ask your own question.