Stereoselective Chemoenzymatic Synthesis of Optically Active Aryl-Substituted Oxygen-Containing Heterocycles

• Main Authors: Paola Vitale, Antonia Digeo, Filippo Maria Perna, Gennaro Agrimi, Antonio Salomone, Antonio Scilimati, Cosimo Cardellicchio, Vito Capriati
• Format: Article
• Language: English
• Published: MDPI AG 2017-01-01
• Series: Catalysts
• Subjects: whole cell biocatalyst; baker’s yeast; enantioselective bioreduction; oxiranes; oxetanes; tetrahydrofurans; halohydrins; chloroketones; oxygen-containing heterocycles; chemoenzymatic synthesis
• Online Access: http://www.mdpi.com/2073-4344/7/2/37

A two-step stereoselective chemoenzymatic synthesis of optically active α-aryl-substituted oxygen heterocycles was developed, exploiting a whole-cell mediated asymmetric reduction of α-, β-, and γ-chloroalkyl arylketones followed by a stereospecific cyclization of the corresponding chlorohydrins into the target heterocycles. Among the various whole cells screened (baker’s yeast, Kluyveromyces marxianus CBS 6556, Saccharomyces cerevisiae CBS 7336, Lactobacillus reuteri DSM 20016), baker’s yeast was the one providing the best yields and the highest enantiomeric ratios (up to 95:5 er) in the bioreduction of the above ketones. The obtained optically active chlorohydrins could be almost quantitatively cyclized in a basic medium into the corresponding α-aryl-substituted cyclic ethers without any erosion of their enantiomeric integrity. In this respect, valuable, chiral non-racemic functionalized oxygen containing heterocycles (e.g., (S)-styrene oxide, (S)-2-phenyloxetane, (S)-2-phenyltetrahydrofuran), amenable to be further elaborated on, can be smoothly and successfully generated from their prochiral precursors.