10.1002/ejoc.202000096
European Journal of Organic Chemistry
COMMUNICATION
this purpose, both lunatin (14) and citreorosein (17) were
subjected to reduction using NaBH4 in presence of Na2S2O4 in
water under optimized conditions to obtain rac-16 and rac-19 in
51% and 42% yield, respectively (Figure 3A). The products
obtained are characterized by NMR spectroscopy and mass
spectrometry and analyzed using HPLC to confirm their
enantiomeric ratio, which was found to be nearly 50:50 (see
Supporting Information).
rugulosin (6) and (+)-2,2’-epi-cytoskyrin A (7) and related
metabolites
that
can
be
synthesized
using
such
dihydroanthracenones.
In summary, we have developed a general strategy for the
synthesis of racemic dihydroanthracenones by the regioselective
reduction of anthraquinones using NaBH4 in the presence of
Na2S2O4 in water. Under optimized conditions variously
substituted racemic dihydroanthracenones (9,16,19) were
obtained in 42–60% yields. Racemic dihydroanthracenones were
utilized for the determination of enantiomeric excess for the
chemoenzymatically reduced products. Both MdpC and PHAR
catalyzes the stereoselective reduction of hydroanthraquinones
with >99% ee. The results also suggest high enantiopurity for the
dimeric bisanthraquinones that have been reportedly synthesized
using (R)-configured dihydroanthracenones ((R)-9 and (R)-16).
Overall, the procedure is much simpler, greener and give access
to useful dihydroanthracenones in just a single step in moderate
yields.
Acknowledgements
Figure 3. Determination of enantiomeric excess for the enzymatically reduced
hydroanthraquinones (9,16,19).
We are grateful to Prof. Michael Müller, University of Freiburg for
providing the plasmids for enzymes, Science and Engineering
Board, New Delhi (CRG/2018/002682) and CSIR, New Delhi
(02(0258)/16/EMR-II) for funding, DBT for the fellowship of SKS
and Director, Centre of Biomedical Research, Lucknow for
research facilities.
In addition, we synthesized both (R)-16 and (R)-19 by
employing a chemoenzymatic procedure using MdpC of A.
nidulans as well as PHAR of C. lunatus.[5,9] The enzymatically
reduced products (R)-16 and (R)-19, were then analyzed for their
enantiopurity in comparison with rac-16 and rac-19 using chiral
HPLC. The data shows only single enantiomer, with >99% ee for
the enzymatically reduced products (Figure 3B).
Keywords: Dihydroanthracenones; chemoenzymatic synthesis;
sodium borohydride; enantiopurity; bisanthraquinones.
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of
new
enzymes
which
can
give
(S)-configured
dihydroanthracenones as well as the natural products such as (+)-
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