Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Июль 18, 2024
Abstract
Isotopic
labeling
is
at
the
core
of
health
and
life
science
applications
such
as
nuclear
imaging,
metabolomics
plays
a
central
role
in
drug
development.
The
rapid
access
to
isotopically
labeled
organic
molecules
sine
qua
non
condition
support
these
societally
vital
areas
research.
Based
on
rationally
driven
approach,
this
study
presents
an
innovative
solution
pyridines
by
nitrogen
isotope
exchange
reaction
based
Zincke
activation
strategy.
technology
conceptualizes
opportunity
field
labeling.
15
N-labeling
other
relevant
heterocycles
pyrimidines
isoquinolines
showcases
large
set
derivatives,
including
pharmaceuticals.
Finally,
we
explore
nitrogen-to-carbon
strategy
order
13
C-labeled
phenyl
derivatives
deuterium
mono-substituted
benzene
from
pyridine-
2
H
5
.
These
results
open
alternative
avenues
for
multiple
aromatic
cores.
Chemical Reviews,
Год журнала:
2023,
Номер
123(12), С. 7655 - 7691
Опубликована: Май 3, 2023
Azines,
such
as
pyridines,
quinolines,
pyrimidines,
and
pyridazines,
are
widespread
components
of
pharmaceuticals.
Their
occurrence
derives
from
a
suite
physiochemical
properties
that
match
key
criteria
in
drug
design
is
tunable
by
varying
their
substituents.
Developments
synthetic
chemistry,
therefore,
directly
impact
these
efforts,
methods
can
install
various
groups
azine
C–H
bonds
particularly
valuable.
Furthermore,
there
growing
interest
late-stage
functionalization
(LSF)
reactions
focus
on
advanced
candidate
compounds
often
complex
structures
with
multiple
heterocycles,
functional
groups,
reactive
sites.
Because
factors
electron-deficient
nature
the
effects
Lewis
basic
N
atom,
distinct
arene
counterparts,
application
LSF
contexts
difficult.
However,
have
been
many
significant
advances
reactions,
this
review
will
describe
progress,
much
which
has
occurred
over
past
decade.
It
possible
to
categorize
radical
addition
processes,
metal-catalyzed
activation
transformations
occurring
via
dearomatized
intermediates.
Substantial
variation
reaction
within
each
category
indicates
both
rich
reactivity
heterocycles
creativity
approaches
involved.
BioMed Research International,
Год журнала:
2023,
Номер
2023(1)
Опубликована: Янв. 1, 2023
Multidrug-resistant
(MDR)
pathogens
have
created
a
fatal
problem
for
human
health
and
antimicrobial
treatment.
Among
the
currently
available
antibiotics,
many
are
inactive
against
MDR
pathogens.
In
this
context,
heterocyclic
compounds/drugs
play
vital
role.
Thus,
it
is
very
much
essential
to
explore
new
research
combat
issue.
Of
nitrogen-bearing
compounds/drugs,
pyridine
derivatives
of
special
interest
due
their
solubility.
Encouragingly,
some
newly
synthesized
found
inhibit
multidrug-resistant
S.
aureus
(MRSA).
Pyridine
scaffold
bearing
poor
basicity
generally
improves
water
solubility
in
pharmaceutically
potential
molecules
has
led
discovery
numerous
broad-spectrum
therapeutic
agents.
Keeping
these
mind,
we
reviewed
chemistry,
recent
synthetic
techniques,
bacterial
preventative
activity
since
2015.
This
will
facilitate
development
pyridine-based
novel
antibiotic/drug
design
near
future
as
versatile
with
limited
side
effects
next-generation
therapeutics.
Nature Chemistry,
Год журнала:
2024,
Номер
16(5), С. 741 - 748
Опубликована: Янв. 18, 2024
Abstract
Skeletal
editing
is
a
straightforward
synthetic
strategy
for
precise
substitution
or
rearrangement
of
atoms
in
core
ring
structures
complex
molecules;
it
enables
quick
diversification
compounds
that
not
possible
by
applying
peripheral
strategies.
Previously
reported
skeletal
common
arenes
mainly
relies
on
carbene-
nitrene-type
insertion
reactions
rearrangements.
Although
powerful,
efficient
and
applicable
to
late-stage
heteroarene
structure
modification,
these
strategies
cannot
be
used
pyridines.
Here
we
report
the
direct
pyridines
through
atom-pair
swap
from
CN
CC
generate
benzenes
naphthalenes
modular
fashion.
Specifically,
use
sequential
dearomatization,
cycloaddition
rearomatizing
retrocycloaddition
one-pot
sequence
transform
parent
into
bearing
diversified
substituents
at
specific
sites,
as
defined
reaction
components.
Applications
pyridine
cores
several
drugs
are
demonstrated.
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
62(42)
Опубликована: Апрель 4, 2023
The
pyridine
moiety
is
an
important
core
structure
for
a
variety
of
drugs,
agrochemicals,
catalysts,
and
functional
materials.
Direct
functionalization
C-H
bonds
in
pyridines
straightforward
approach
to
access
valuable
substituted
pyridines.
Compared
the
direct
ortho-
para-functionalization,
meta-selective
far
more
challenging
due
inherent
electronic
properties
entity.
This
review
summarizes
currently
available
methods
meta-C-H
using
directing
group,
non-directed
metalation,
temporary
dearomatization
strategies.
Recent
advances
ligand
control
are
highlighted.
We
analyze
advantages
as
well
limitations
current
techniques
hope
inspire
further
developments
this
area.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(5), С. 2950 - 2958
Опубликована: Янв. 29, 2024
The
selective
modification
of
nitrogen
heteroaromatics
enables
the
development
new
chemical
tools
and
accelerates
drug
discovery.
While
methods
that
focus
on
expanding
or
contracting
skeletal
structures
are
emerging,
for
direct
exchange
single
core
atoms
remain
limited.
Here,
we
present
a
method
14N
→
15N
isotopic
several
aromatic
heterocycles.
This
isotope
transmutation
occurs
through
activation
heteroaromatic
substrate
by
triflylation
atom,
followed
ring-opening/ring-closure
sequence
mediated
15N-aspartate
to
effect
atom.
Key
success
this
transformation
is
formation
an
isolable
15N-succinyl
intermediate,
which
undergoes
elimination
give
isotopically
labeled
heterocycle.
These
transformations
occur
under
mild
conditions
in
high
yields.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(5), С. 2939 - 2943
Опубликована: Янв. 12, 2024
A
practical
method
for
the
synthesis
of
15N-labeled
azines
with
a
high
degree
isotopic
enrichment
is
described.
Activation
azine
heterocycles
an
electron-deficient
arene
allows
facile
substitution
nitrogen
atom
specifically
designed
reagent
that
undergoes
canonical
ANRORC-type
mechanism.
wide
range
can
be
converted
to
their
corresponding
15N
isotopologs
using
this
method,
and
it
also
dearomative
access
reduced
heterocyclic
congeners.
short
formal
15N-solifenacin
accomplished
as
well
demonstrate
application
generating
labeled
pharmaceuticals.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(5), С. 2944 - 2949
Опубликована: Янв. 16, 2024
Methods
to
incorporate
stable
radioisotopes
are
integral
pharmaceutical
and
agrochemical
development.
However,
despite
the
prevalence
of
pyridines
in
candidate
compounds,
methods
15N
atoms
within
their
structures
limited.
Here,
we
present
a
general
approach
pyridine
15N-labeling
that
proceeds
via
ring-opening
NTf-Zincke
imines
then
ring-closure
with
commercially
available
15NH4Cl
salts.
This
process
functions
on
range
substituted
pyridines,
from
simple
building
block-type
compounds
late-stage
labeling
complex
pharmaceuticals,
15N-incorporation
is
>95%
most
cases.
The
reactivity
Zincke
imine
intermediates
also
enables
deuteration
C3-
C5-positions,
resulting
higher
mass
isotopologs
required
for
LCMS
analysis
biological
fluids
during
drug
Journal of the American Chemical Society,
Год журнала:
2023,
Номер
unknown
Опубликована: Май 17, 2023
Asymmetric
intermolecular
C–H
functionalization
of
pyridines
at
C3
is
unprecedented.
Herein,
we
report
the
first
examples
such
transformations:
specifically,
C3-allylation
via
tandem
borane
and
iridium
catalysis.
First,
borane-catalyzed
pyridine
hydroboration
generates
nucleophilic
dihydropyridines;
then,
dihydropyridine
undergoes
enantioselective
iridium-catalyzed
allylation;
finally,
oxidative
aromatization
with
air
as
oxidant
gives
C3-allylated
pyridine.
This
protocol
provides
direct
access
to
excellent
enantioselectivity
(up
>99%
ee)
suitable
for
late-stage
pyridine-containing
drugs.