10.1002/anie.201902761
Angewandte Chemie International Edition
COMMUNICATION
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In conclusion, two new enzymes, a tyrosinase CnTYR and
tyrosine decarboxylase EfTyrDC were cloned and used with a
range of substrates to highlight their use with non-natural
analogues. When combined together in different combinations
with 4, 8, 9, 30, CvTAm and TfNCS, artificial cascades were
successfully constructed, giving BIAs in 23-66% isolated yields
(35-99% yields by HPLC) and high stereoselectivities in up to 4
enzyme steps. Moreover, selected reactions were scaled up
successfully to 1 g. Overall, this work highlights the versatility of
the ‘mix and match’ strategy with enzymes in vitro to generate two
natural and six non-natural BIAs. Interestingly, in parallel with this
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produced or what the stereoselectivity was. Here, the one-pot in
vitro cascades demonstrate an extremely powerful strategy for
introducing molecular diversity using sustainable catalysts.
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Acknowledgements
We gratefully acknowledge UCL (Dean’s Prize) for funding to Y.W.
We also thank the BBSRC (BB/N01877X/1) for funding D.M.S.,
and EPSRC (EP/K014897/1) for funding M.B. We thank K. Karu
(UCL Mass Spectrometry Facility) and A. E. Aliev (UCL NMR
Facility) in the Department of Chemistry.
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Keywords: benzylisoquinoline alkaloids • Cascade reactions •
biocatalysis • tyrosinase • tyrosine decarboxylase • transaminase
• norcoclaurine synthase
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