Regiodivergent and stereoselective hydroxyazidation of alkenes by biocatalytic cascades

Yong-Zheng Chen,Wen-Yong Han,Nan-Wei Wan,Qing-Ping Wang,Ying-Na Li,Bao-Dong Cui,Jing-Fei Wu

doi:10.1016/j.isci.2021.102883

Yong-Zheng Chen, Wen-Yong Han + Show 5 more

Open Access

https://doi.org/10.1016/j.isci.2021.102883

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Journal: iScience	Publication Date: Jul 17, 2021
Citations: 15	License type: cc-by

Affiliation: Zunyi Medical University

Abstract

SummaryAsymmetric functionalization of alkenes allows the direct synthesis of a wide range of chiral compounds. Vicinal hydroxyazidation of alkenes provides a desirable path to 1,2-azidoalcohols; however, existing methods are limited by the control of stereoselectivity and regioselectivity. Herein, we describe a dual-enzyme cascade strategy for regiodivergent and stereoselective hydroxyazidation of alkenes, affording various enantiomerically pure 1,2-azidoalcohols. The biocatalytic cascade process is designed by combining styrene monooxygenase-catalyzed asymmetric epoxidation of alkenes and halohydrin dehalogenase-catalyzed regioselective ring opening of epoxides with azide. Additionally, a one-pot chemo-enzymatic route to chiral β-hydroxytriazoles from alkenes is developed via combining the biocatalytic cascades and Cu-catalyzed azide-alkyne cycloaddition.

Highlights

The 1,2-azidoalcohols are useful building blocks for the synthesis of various pharmaceuticals, biologically active molecules, natural products and synthetic materials (Brase et al, 2005; Chiba et al, 2009; Meldal and Tornøe, 2008; Sletten and Bertozzi, 2011)
The HheG and HheCM were chosen as two regiocomplementary HHDHs for combining with SMO, constructing biocatalytic cascades SMO-HheG (BCa) and SMO-HheCM (BCb) for synthesizing (R)-3a and (S)-4a through asymmetric hydroxyazidation of 1a, respectively
In summary, we have developed an efficient method for regiodivergent and stereoselective hydroxyazidation of alkenes by two novel biocatalytic cascades, providing a direct and green approach to various enantiopure 1,2-azidoalcohols

Summary

Introduction

The 1,2-azidoalcohols are useful building blocks for the synthesis of various pharmaceuticals, biologically active molecules, natural products and synthetic materials (Brase et al, 2005; Chiba et al, 2009; Meldal and Tornøe, 2008; Sletten and Bertozzi, 2011). The biocatalytic cascade process is designed by combining styrene monooxygenase-catalyzed asymmetric epoxidation of alkenes and halohydrin dehalogenase-catalyzed regioselective ring opening of epoxides with azide. A one-pot chemo-enzymatic route to chiral b-hydroxytriazoles from alkenes is developed via combining the biocatalytic cascades and Cu-catalyzed azide-alkyne cycloaddition.

Results

Conclusion