Cyclic Deracemization of rac‐Sulfoxides via Alternating Biocatalytic Reduction and Light‐Dependent Oxidation Employing Eosin Y as Photocatalyst

A cyclic deracemization process that utilizes alternately a biocatalytic enantioselective reduction employing (S)-selective methionine sulfoxide reductase from Pseudomonas alcaliphila (paMsr) supplemented with DTT as external reducing equivalent, and a stereo-unselective photocatalytic oxidation reaction using the readily accessible Eosin Y as photocatalyst to achieve chiral sulfoxides is presented. Evaluation of the substrate scope demonstrates a general applicability of this modular system.

Abstract

The synergistic combination of biocatalysis and photocatalysis is emerging as powerful tool for the development of sustainable and atom-efficient synthetic concepts facilitating an enormous portfolio of possible reactions which even goes beyond the capabilities found in nature. Here, a cyclic deracemization process is presented tailored for the synthesis of optically pure sulfoxides which are versatile structural motifs in asymmetric synthesis as well as in bioactive compounds. Enantioselective enzyme-catalyzed reduction of rac-sulfoxides was combined with a stereo-unselective photocatalytic oxidation of the corresponding sulfide intermediate. The utilization of the readily accessible and rather inexpensive photocatalyst Eosin Y increases the usability of this synthetic method. To overcome the incompatibility between the photocatalyst Eosin Y and the biocatalytic step, the cyclic deracemization process was performed in a step-wise fashion via alternated reduction in the darkness and oxidation under illumination. This modular system allowed precise adjustments of reaction parameters yielding the desired sulfoxide targets with up to >99 % ee. Evaluation of the substrate scope including a range of structurally diverse molecules demonstrated its broad applicability.

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