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Chemoenzymatic Asymmetric Synthesis of Serotonin Receptor Agonist ( R )‐Frovatriptan
Author(s) -
Busto Eduardo,
MartínezMontero Lía,
Gotor Vicente,
GotorFernández Vicente
Publication year - 2013
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201300114
Subject(s) - chemistry , enantiopure drug , racemization , candida antarctica , acylation , enantioselective synthesis , ketone , combinatorial chemistry , lipase , stereochemistry , organic chemistry , catalysis , enzyme
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.