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Issue 35, 2017
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Enantioselective bioreduction of benzo-fused cyclic ketones with engineered Candida glabrata ketoreductase 1 – a promising synthetic route to ladostigil (TV3326)

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Abstract

Biocatalysis has been recently emerging as a promising alternative to traditional chemical synthesis because of its “green” characteristics and comparable selectivities, which accord with the concept of sustainable development and demand for asymmetric synthesis. In this study, whole-cell biocatalysts containing glucose dehydrogenase (GDH) and Candida glabrata ketoreductase 1 (CgKR1) variants were constructed. These biocatalysts were applied to the reduction of benzo-fused cyclic ketones and showed good to high activities and enantioselectivities. Particularly, CgKR1 variants displayed high activities (90.6%–98.4% conversions) and enantioselectivities (>99.9% ee) towards 5a, a key intermediate of ladostigil (TV3326). Based on these results, a chemoenzymatic synthesis of (S)-5b was developed by using biocatalytic asymmetric reduction as a key step, giving the product with a total yield of 34.0% and 99.9% ee.

Graphical abstract: Enantioselective bioreduction of benzo-fused cyclic ketones with engineered Candida glabrata ketoreductase 1 – a promising synthetic route to ladostigil (TV3326)

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Publication details

The article was received on 21 Jul 2017, accepted on 11 Aug 2017 and first published on 14 Aug 2017


Article type: Paper
DOI: 10.1039/C7OB01803G
Org. Biomol. Chem., 2017,15, 7374-7379

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    Enantioselective bioreduction of benzo-fused cyclic ketones with engineered Candida glabrata ketoreductase 1 – a promising synthetic route to ladostigil (TV3326)

    J. Ou-yang, W. Zhang, F. Qin, W. Zuo, S. Xu, Y. Wang, B. Qin, S. You and X. Jia, Org. Biomol. Chem., 2017, 15, 7374
    DOI: 10.1039/C7OB01803G

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