title: Exploitation of a Multienzymatic Stereoselective Cascade Process in the Synthesis of 2-Methyl-3-Substituted Tetrahydrofuran Precursors.
abstract: Enantiopure 2-methyl-3-substituted tetrahydrofurans are key precursors of several biologically active products (drugs, flavors, and agrochemicals). Thus, a stereocontrolled and efficient methodology for the obtainment of these synthons is highly desirable. We exploited a two-step multienzymatic stereoselective cascade reduction of α-bromo-α,β-unsaturated ketones to give the corresponding bromohydrins in good yields, with high ee and de values. The cascade process is catalyzed by an ene-reductase and an alcohol dehydrogenase. Further manipulations of these bromohydrins, by two diastereodivergent routes, allowed the preparation of the tetrahydrofuran synthons. One route is based on a lipase catalyzed cleavage of the protecting group. The second route is characterized by a camphor sulfonic acid mediated isomerization of a β-hydroxyepoxide to give the tetrahydrofuran-2-ol. Finally, the synthesis of the most odorous and pleasant stereoisomer of the roasted meat aroma, i.e., (2S,3R)-2-methyl-3-thioacetate tetrahydrofuran, is reported as well.
authors.affiliation: Dipartimento di Chimica, Materiali ed Ingegneria Chimica "G. Natta", Politecnico di Milano , P.zza Leonardo da Vinci 32, 20133 Milano, Italy.|The Protein Factory, Politecnico di Milano and Università degli Studi dell'Insubria , Via Mancinelli 7, 20131 Milano, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Brenna
authors.affiliation: Dipartimento di Chimica, Materiali ed Ingegneria Chimica "G. Natta", Politecnico di Milano , P.zza Leonardo da Vinci 32, 20133 Milano, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Crotti
authors.affiliation: Dipartimento di Chimica, Materiali ed Ingegneria Chimica "G. Natta", Politecnico di Milano , P.zza Leonardo da Vinci 32, 20133 Milano, Italy.|The Protein Factory, Politecnico di Milano and Università degli Studi dell'Insubria , Via Mancinelli 7, 20131 Milano, Italy.
authors.forename: Francesco G
authors.identifier: 0000-0003-0837-4616
authors.initials: FG
authors.lastname: Gatti
authors.affiliation: Dipartimento di Chimica, Materiali ed Ingegneria Chimica "G. Natta", Politecnico di Milano , P.zza Leonardo da Vinci 32, 20133 Milano, Italy.
authors.forename: Ludovico
authors.initials: L
authors.lastname: Marinoni
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare C.N.R. , Via Mario Bianco, 9, 20131, Milano, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Monti
authors.affiliation: Dipartimento di Chimica, Materiali ed Ingegneria Chimica "G. Natta", Politecnico di Milano , P.zza Leonardo da Vinci 32, 20133 Milano, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Quaiato