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SYNTHETIC COMMUNICATIONS
3
Knoevenagel–Michael reaction is also involved in the synthesis of various biologically
[
17–19]
active scaffolds.
prepare biscoumarin derivatives.
marin derivatives using methyl iodide and heating the complex with HCl.
several researchers have developed various synthetic methodologies for the synthesis of
In the past reports, several methodologies have been designed to
[
20,21]
Abramovitch et al. synthesized a series of biscou-
[
22]
Thereafter,
[
23]
biscoumarins using heterogeneous catalysts like W-doped ZnO nanocomposites,
methyl pyrrolidonium zinc chloride,
N-
[
24]
[25]
ionic liquid [Dabco-H][AcO],
ethylene gly-
[
26]
[27]
[28]
col,
zwitterionic liquid (ZIL) coated CuO,
o-benzenedisulfonimide,
ceric ammonium nitrate,
FeNi -ILs
3
[
29]
[30]
[31]
[32]
nanoparticles,
Fe O @SiO @VB1-Ni(II),
3
[34]
taurine,
4
2
[
33]
[35]
HY-Zeolite,
VB1,
choline hydroxide,
etc. Several acid catalysts like glacial acetic
[
36]
[37]
[38]
acid,
acid,
phosphotungstic acid,
succinimide-N-sulfonic acid
pentafluropropanoic acid,
phosphor-sulfonic
[
39]
[40]
[41]
[42]
other lewis acids like RuCl3,
ZnCl2,
etc.
were also used to improve the selectivity, yield and atom economy. These synthetic
pathways have their own merits but include harsh reaction conditions. To overcome
these restrictive causes, solid acid catalysts have gained enormous attention due to their
surface properties and good acidic characters. In lieu of this, different solid acid cata-
[
43]
lysts have also been used for biscoumarin synthesis such as sulfonated rice husk,
[
44]
[45]
starch–sulfuric acid,
silica-bonded n-propyldiethylenetriamine sulfamic acid,
melamine trisulphonic acid,
cellu-
Pistachio peels based sulfonic
However, the literature-reported pathways have provided efficient access to bis-
[
46]
[47]
lose sulfonic acid,
[
48]
acid.
coumarins but include harsh reaction conditions, tedious workup, long reaction time,
expensive catalyst, high catalyst loading, limited substrate scope, and use of hazardous
solvents. To beat such circumstances and to find a more beneficial protocol, a new eco-
friendly method needs to be developed to combat several environmental issues. An
[
49]
exhaustive literature study has been done by our research group
and it was found
that no work has been done using glycerol-based carbon-SO H for the synthesis of bis-
3
coumarins to date. Keeping all these points into consideration; we have developed a
robust carbon-SO H catalyst for the synthesis of biscoumarin derivatives. Carbon-SO H
3
3
[
50–52]
has been used earlier to catalyze diverse organic transformations
and also fruitful
for the multi-component reactions to synthesize 4-thiazolidinones, thiazepinones,
[
53,54]
etc.
Taking all the points into mind, we have designed a novel approach for the
generation of biologically potent biscoumarin derivatives (3a–j) using carbon-SO H as a
3
robust catalyst. (Scheme 1).
For the molecular docking studies of synthesized compounds (3a–j), we have selected
cytochrome P450 3A4 (CYP3A4) and methylenetetrahydrohyrofolate reductase
(
1
MTHFR) enzyme predicted by PASS online program (PASS online-Way2Drug) (Table
[
55]
[56]
) and literature studies.
PDB IDs pertaining to CYP3A4 and MTHFR are 4D75
[
57]
and 6FCX,
respectively. The PASS computer program allows estimating the probable
profile of the biological activity of a drug-like organic compound. CYP3A4 catalyzes
various oxidative reactions and is recognized as a xenobiotic-metabolizing enzyme in
[
56]
humans.
HIV infection.
reduction of 5,10-methylenetetrahydrofolate to 5-methyl-tetrahydrofolate which is indir-
The inhibition of this enzyme is considered beneficial in the treatment of
[
58]
Again, in humans, MTHFR is involved in catalyzing the irreversible
[
57]
ectly involved in the biosynthesis of purines and monophosphates.
sidered essential for the exploration of anti-cancer drugs.
This target is con-
[
59]