G
Synlett
K. Lauder, D. Castagnolo
Synpacts
yield the prochiral imine intermediate 21, a suitable sub-
strate for WGL. Then, the ketone reagent 22 reacts with 21
to yield indoles 23 with a stereodefined chiral quaternary
carbon centre.
Acknowledgment
We are grateful to Prozomix Ltd for providing the KRED biocatalysts
and to Johnson Matthey for providing ADH101 and ADH152.
Finally, Hönhe, Schmidt, and their co-workers exploited
photocatalysis to generate a range of prochiral ketones 25,
which were then transformed into a variety of derivatives
References and Notes
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J. Agric. Food Chem. 1998, 46, 1076.
34
26–30 by using various biocatalysts. Sodium anthraqui-
none-2-sulfonate (SAS) was used as photoinitiator to con-
vert a series of alkanes 24 into ketones 25. The latter were,
in turn, treated with an appropriate biocatalyst [lyase,
ERED, KRED, monooxygenase (CHMO or HAPMO), or amine
transaminase] to generate compounds 26–30 in good con-
versions and with high enantioselectivities.
Despite these initial successes in the development of
photo-biocatalysed cascades, a number of potential issues
will need to be addressed in the near future, such as the in-
terferences between the photocatalysed conditions and the
redox cofactors, the mutual deactivation of some enzymes
with the photocatalysts, and the occurrence of side reac-
tions due to the presence of radical intermediates in the re-
action media.
(
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(
(
(
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5
Conclusions
(
This Synpact article summarises the development of a
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novel photo-biocatalysed cascade for the synthesis of 1,3-
mercaptoalkanol derivatives from readily available building
blocks. The discovery of two new KRED enzymes able to ca-
talyse the reduction of mercapto ketones with high enantio-
selectivity is described. In particular, the development of
two screening approaches, a colorimetric and a spectro-
photometric assay, for the rapid selection of the most-ac-
tive KRED biocatalysts from a library of 384 enzymes is
highlighted. The work then focused on the development of
photo-biocatalytic cascade transformations that might per-
mit the direct synthesis of key chemical compounds
through a combination of photocatalytic and biocatalytic
reactions in a one-pot process. An overview of the most re-
cent and innovative photo-biocatalysed approaches for the
synthesis of chemical building blocks is also presented.
(
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1
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(
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K. E.; Janković, N. Z.; Tu, Q.; Pincus, L. N.; Falinski, M. M.; Shi, W.;
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Turner, N. J. Nat. Rev. Chem. 2018, 2, 409. (c) Sheldon, R. A.;
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Funding Information
This work was supported by Biotechnology and Biological Sciences
Research Council (BBSRC; iCASE Studentship to K.L.) as well as EPSRC
(19) (a) Hwang, K.-J.; Lee, J.; Chin, S.; Moon, C. J.; Lee, W.; Baek, C.-S.;
Kim, H. J. Arch. Pharmacal. Res. 2003, 26, 997. (b) Wakabayashi,
H.; Wakabayashi, M.; Eisenreich, W.; Engel, K.-H. J. Agric. Food
Chem. 2003, 51, 4349.
(King’s College London Strategic Fund).
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