Abstract
Indole‐pyrazole
hybrids
are
intriguing
due
to
their
potential
for
synergistic
pharmacological
effects,
unlike
molecules
with
only
one
pharmacophore.
This
study
presents
a
one‐pot
synthesis
of
fused
indole‐pyrazole
derivatives,
bis
4a
and
chromone
4b
using
an
aldehyde,
thiosemicarbizide,
indole,
as
anticancer
antidiabetic
agents.
The
synthesized
compounds
were
characterized
Fourier
transform
infrared
(FTIR),
nuclear
magnetic
resonance
(NMR),
time‐of‐flight
mass
spectrometry
(TOF‐MS).
Initially,
mutagenicity
test
was
performed,
the
showed
no
significant
increase
in
revertant
colonies
against
Salmonella
typhimurium
TA
98
100
strains.
In
MTT
assay
cytotoxicity
two
human
cancer
cell
lines,
A549
HepG‐2;
normal
line,
HEK
293.
Compound
high
potency
IC
50
values
18.70
50.07
µg/mL,
respectively,
whereas
both
low
inhibition
level
293
at
µg/mL.
vitro
α‐amylase
α‐glucosidase,
compound
demonstrated
excellent
3.9
µg/mL
12.1
respectively.
The Journal of Organic Chemistry,
Год журнала:
2023,
Номер
88(15), С. 10946 - 10959
Опубликована: Июль 14, 2023
Fluorinated
piperidines
find
wide
applications,
most
notably
in
the
development
of
novel
therapies
and
agrochemicals.
Cyclization
alkenyl
N-tosylamides
promoted
by
BF3-activated
aryliodine(III)
carboxylates
is
an
attractive
strategy
to
construct
3-fluoropiperidines,
but
it
suffers
from
selectivity
issues
arising
competitive
oxoaminations
inability
easily
modulate
reactions
diastereoselectivity.
Herein,
we
report
itemized
optimization
reaction
conditions
carried
out
on
both
cyclic
acyclic
substrates
outline
origins
substrate-
reagent-based
stereo-,
regio-,
chemoselectivity.
Extensive
mechanistic
studies
encompassing
multinuclear
NMR
spectroscopy,
deuterium
labeling,
rearrangements
stereodefined
substrates,
careful
structural
analyses
(NMR
X-ray)
products
are
performed.
This
revealed
processes
interactions
crucial
for
achieving
controlled
preparation
3-fluoropiperidines
using
I(III)
chemistry
has
provided
advanced
understanding
mechanism.
In
brief,
propose
that
BF3-coordinated
reagents
attack
C═C
produce
corresponding
iodiranium(III)
ion,
which
then
undergoes
diastereodetermining
5-exo-cyclization.
Transiently
formed
pyrrolidines
with
exocyclic
σ-alkyl-I(III)
moiety
can
further
undergo
aziridinium
ion
formation
or
reductive
ligand
coupling
processes,
dictate
not
only
final
product's
ring
size
also
Importantly,
depends
nature
bound
presence
electrolytes
such
as
TBABF4.
Reported
findings
will
facilitate
usage
ArI(III)-dicarboxylates
reliable
construction
fluorinated
azaheterocycles.
Abstract
Indole‐pyrazole
hybrids
are
intriguing
due
to
their
potential
for
synergistic
pharmacological
effects,
unlike
molecules
with
only
one
pharmacophore.
This
study
presents
a
one‐pot
synthesis
of
fused
indole‐pyrazole
derivatives,
bis
4a
and
chromone
4b
using
an
aldehyde,
thiosemicarbizide,
indole,
as
anticancer
antidiabetic
agents.
The
synthesized
compounds
were
characterized
Fourier
transform
infrared
(FTIR),
nuclear
magnetic
resonance
(NMR),
time‐of‐flight
mass
spectrometry
(TOF‐MS).
Initially,
mutagenicity
test
was
performed,
the
showed
no
significant
increase
in
revertant
colonies
against
Salmonella
typhimurium
TA
98
100
strains.
In
MTT
assay
cytotoxicity
two
human
cancer
cell
lines,
A549
HepG‐2;
normal
line,
HEK
293.
Compound
high
potency
IC
50
values
18.70
50.07
µg/mL,
respectively,
whereas
both
low
inhibition
level
293
at
µg/mL.
vitro
α‐amylase
α‐glucosidase,
compound
demonstrated
excellent
3.9
µg/mL
12.1
respectively.
