Chemoenzymatic Asymmetric Synthesis of Serotonin Receptor Agonist ( R)‐Frovatriptan

• Published in: European Journal of Organic Chemistry
• Main Authors: Busto, Eduardo, Martínez‐Montero, Lía, Gotor, Vicente, Gotor‐Fernández, Vicente
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2013
• Subjects: Antarc*; Antarctica
• Online Access: http://dx.doi.org/10.1002/ejoc.201300114; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fejoc.201300114; http://onlinelibrary.wiley.com/wol1/doi/10.1002/ejoc.201300114/fullpdf

Abstract A simple chemoenzymatic asymmetric route has been developed for the production of antimigraine agent ( R )‐Frovatriptan. Lipases and oxidoreductases have been identified as ideal biocatalysts for the production of enantiopure adequate synthetic intermediates under safe and environmentally friendly conditions. ( S )‐3‐Hydroxy‐2,3,4,9‐tetrahydro‐1 H ‐carbazole‐6‐carbonitrile, an optimal building block for the synthesis of the drug, has been efficiently prepared through Candida antarctica lipase type B catalyzed acylation of its corresponding racemic mixture or alcohol dehydrogenase A mediated bioreduction of the corresponding ketone. The inversion of the chiral center has been identified as a key step, optimizing the process to avoid partial racemization. Finally, amine functionalization and nitrile hydrolysis have allowed the production of ( R )‐Frovatriptan in enantiomerically pure form.