Chemo-enzymatic synthesis of optically pure rivastigmine intermediate using alcohol dehydrogenase from baker's yeast

An efficient and practical synthesis of (S)-rivastigmine intermediate was developed by employing a chemoenzymatic step toward the synthesis of chiral intermediate N-ethyl-N-methyl-carbamic acid-3-(1S-hydroxy-ethyl)-phenyl ester (2) using crude alcohol dehydrogenase from baker's yeast with reduced nucleotide adenosine dinucleotide (NADH) as proton donor has been demonstrated.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Biocatalytic reduction of rivastigmine intermediate by Baker's yeast is proposed. ► Several alcohol dehydrogenases from various strains have been screened. ► A cell free extract of Baker's yeast is used for reduction. ► A NADH recycling system has been adopted. ► The method has advantage of producing 95% yield with >99% ee S-alcohol.