4 Scope of the biocatalytic one-pot reaction
Having obtained a system capable of high productivity, we chose a
variety of aldehydes 1a -k , which were derived easily
from biomass (e.g., primary, aromatic, and furan aldehydes) (Wu, Moteki,
Gokhale, Flaherty, & Toste, 2016; Mahyari, Shaabani, & Bide, 2013;
Boruah & Das, 2018; Lee et al., 2018) and mated with α, β-unsaturated
carbonyl tandem reaction under optimized conditions. As shown in Table
2, the enzyme accepted a wide range of substrates. A high reaction rate
was obtained using primary aldehydes whose corresponding intermediates
may possess suitable sizes for adoption in the active center. The
appropriate length branch-chain was vital in fastening the hydrophobic
area in the active center of NerA(Peters, Frasson, Sievers, & Buller,
2019). Benzene (3f ) and furan (3h , 3i )
derivatives also achieved high yields (80%, 75%, and 70%
respectively), other ERs like DBVPG and OPRI had only 3% and 4% yields
after 24 hours (Reß, Hummel, Hanlon, Iding, & Gröger, 2015). Compared
to 3f , the substrate with an electron-withdrawing group
(3g ) showed a higher yield (85%). These results are probably
because benzene has electron donors with conjugating effects, which is
not conducive to hydrogen transfer. This can be further proven as furan,
a 5-center, 6-electron conjugate system with a higher electron cloud
density, caused a lower yield. We also noticed that although
enantioselectivity is a general property of most reductases including
NerA. However, e.e% of 3a -k are only around 10%
(data not shown), since the intermediates can be flipped at the active
center, and the keto-enol tautomerism of the ketone carbonyl in the
products may be the other reason for racemization under an aqueous
environment. Metal nanoparticles such as Ni and Pd were found to possess
the ability to drive the cascade reactions containing Knoevenagel
condensation and ene reduction as bifunctional catalysts similar to NerA
(Javad Kalbasi, Mesgarsaravi, & Gharibi, 2019; H. Wang et al., 2019).
Compared to our work, the reaction catalyzed by these metal
nanoparticles must be separated into two sub-steps. Meanwhile, as an
alternative to using metal catalysts, enzymes are coincident with the
concept of green chemistry.