title: A chemoenzymatic dynamic kinetic resolution approach to enantiomerically pure (R)- and (S)-duloxetine.
abstract: The synthesis of (R)-duloxetine is described. Dynamic kinetic resolution of β-hydroxynitrile rac-1 using Candida antarctica lipase B (CALB, N435) and ruthenium catalyst 6 afforded β-cyano acetate (R)-2 in high yield and in excellent enantioselectivity (98% ee). The subsequent synthetic steps were straightforward and (R)-duloxetine was isolated in 37% overall yield over 6 steps. The synthetic route also constitute a formal total synthesis of (S)-duloxetine.
authors: Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden.
authors: Annika
authors: A
authors: Träff
authors: Richard
authors: R
authors: Lihammar
authors: Jan-E
authors: JE
authors: Bäckvall
mesh_terms: D000068736:Duloxetine Hydrochloride; D005656:Fungal Proteins; D007700:Kinetics; D008049:Lipase / Q000378:metabolism*; D012428:Ruthenium / Q000737:chemistry; D013237:Stereoisomerism; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D005656:Fungal Proteins; D013876:Thiophenes; D012428:Ruthenium; D000068736:Duloxetine Hydrochloride; D008049:Lipase; C431349:lipase B, Candida antarctica