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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Stereodivergent Synthesis of Diversely Substituted Dibenzoxazepines Using Imine Reductases
Piyal Das1,2, Sandipan Mondal1,2, Manisha Bairwa1,2
1Department of Biological and Synthetic Chemistry, Centre of Biomedical Research, SGPGIMS Campus, Raebareli Road, Lucknow 226014, India.
Abstract:
The N-heterocycles containing a dibenzoxazepine framework have been found to display a variety of biological activities. Chiral dibenzoxazepines are usually synthesized through asymmetric hydrogenation using transition metal catalysts. Herein, we developed a biocatalytic method employing various imine reductases, where benzo-fused seven-membered cyclic imines containing oxygen are reduced using NADPH. This method gave access to a variety of substituted dibenzoxazepines (27 examples), with a high yield (up to 93%) and enantiomeric excess (up to >99%) in a stereo-divergent fashion. Insight into the stereochemical outcome of the reaction was gained through the docking of a model substrate with Cf-IR and IR-24. The kinetics of Cf-IR and IR-24 performed with seven-membered 1-benzazepine, benzoxazepine, and dibenzoxazepine revealed differences in their catalytic efficiency.
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