6
$\begingroup$

I've searched lots of free resources online but cannot find the answer. enter image description here

the top compound is Rosuvastatin. Some websites say it is metabolized by the enzyme CYP2C9, but I can't figure out how a CYP450 mediated reaction will produce Rosuvastatin 5 S-lactone. And I tried thinking about an intramolecular esterification, but it does not look like the answer. Perhaps I missed something?

$\endgroup$
  • $\begingroup$ It seems like you have drawn two excess double bonds. Maybe this is the source of your confusion. Besides this intramolecular esterification is ok. $\endgroup$ – aventurin Nov 25 '17 at 23:54
  • $\begingroup$ Oh I compared the picture of pubchem and drugbank, I found that they are different. If pubchem is right then it can be form through intramolecular esterification but I'm not sure. DB: drugbank.ca/reactions/2249 PC: pubchem.ncbi.nlm.nih.gov/compound/66631534#section=2D-Structure $\endgroup$ – ChemicalFool Nov 26 '17 at 20:55
4
$\begingroup$

Rosuvastatin is metabolized to a limited extent by CYP2C9 to form an N-desmethyl metabolite and the other metabolite is the rosuvastatin lactone.

enter image description here

The acid moeity (highlighted part) is likely to undergo glucuronidation first and subsequently lactonisation to form the rosuvastatin lactone

Unlike other statins, rosuvastatin undergoes relatively little metabolism by hepatic CYPs with no significant involvement of CYP3A4.

The metabolism of statins is complex, involving the inter-conversion of acid/lactone by various pathways. The acid forms are converted to the corresponding lactones via a glucuronide intermediate.

Here is the proposed, generalised metabolic pathway of statins. The acid forms of statins are converted to the corresponding lactones via a glucuronide intermediate via an elimination reaction.

enter image description here

Sidenote for some statins: (After metabolism by CYP3A4 some of the resulting lactone metabolites are converted to the corresponding acid forms:

References

  • Focus on Statin research. B. A. Wong: Drug Metabolism and Transporter profiles of Statins.

  • Foye’s Principles of Medicinal Chemistry 7th ed

$\endgroup$
  • $\begingroup$ Really appreciate your detailed answer! $\endgroup$ – ChemicalFool Nov 26 '17 at 20:43

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

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