Chemical Science,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Jan. 1, 2024
The
previously
unreported
combination
of
nucleophilic
phosphine
catalysis
and
energy
transfer
allows
for
the
rapid
construction
structurally
distinct
2-oxabicyclo[2.1.1]hexanes
(2-oxa-BCH)
from
readily
available
building
blocks
with
high
atom
economy.
Previous
multistep
routes
to
these
important
phenyl
ring
bioisosteres
have
largely
depended
on
use
bespoke
strain-release
agents
or
multiple
post-functionalisation
reactions
access
structural
diversity
scaffold.
In
contrast,
this
cascade
reaction
medicinal
chemist
exploit
breadth
commercial
allyl
alcohols
synthesise
systematically
diverse
2-oxa-BCH
architectures.
Using
a
polar
radical
disconnections
in
same
flask,
every
position
scaffold
can
be
substituted
useful
functional
handles
such
as
protected
amines,
esters
alcohols,
well
arenes
alkyl
groups.
Cyclic
even
employed
yield
single
diastereomers
sp
Chemical Science,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 1, 2025
A
multiligand-involved
Cu
catalysis
offers
an
efficient
Hiyama
coupling
of
arylsilanes
with
unactivated
alkyl
halides,
where
copper
NHC
and
phenanthroline
ligands
were
account
for
C(sp
2
)–Si
activation
)–C(sp
3
)
formation,
respectively.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(27), P. 18682 - 18688
Published: June 27, 2024
The
incorporation
of
three-dimensional
structures
into
drug
molecules
has
demonstrated
significant
improvements
in
clinical
success.
Late-stage
saturation
provides
a
direct
pathway
for
this
transformation.
However,
achieving
selective
and
controllable
reduction
aromatic
rings
remains
challenging,
particularly
when
multiple
coexist.
Herein,
we
present
the
switchable
chemoselective
hydrogenation
benzene
pyridine
rings.
utility
protocol
been
comprehensively
investigated
diversified
substrates
with
assistance
fragment-screening
technique.
This
approach
convenient
access
to
diverse
array
cyclohexane
piperidine
compounds,
prevalent
various
bioactive
drugs.
Furthermore,
it
discloses
promising
avenues
applications
late-stage
drugs,
facilitating
an
increase
fraction
sp
ACS Catalysis,
Journal Year:
2025,
Volume and Issue:
15(3), P. 1596 - 1606
Published: Jan. 14, 2025
Transition
metal-catalyzed
reductive
coupling
chemistry
has
been
recognized
as
a
powerful
tool
for
the
synthesis
of
diverse
organic
molecules.
However,
despite
enormous
progress
in
this
field,
there
is
no
precedent
tandem
widely
accessible
nitriles
with
electrophiles
that
contain
σ-
and
π-type
(σ/π-type)
electrophilic
functional
groups
simultaneously.
Herein,
we
have
established
unique
cobalt
catalysis
system,
enabling
chemoselective
coupling/tandem
cyclization
reaction
aryl
halides
(Br,
Cl,
I)
bearing
carbonyl
moiety
variety
aryl,
alkenyl,
alkyl
via
carbocobaltation
unknown
yet.
The
protocol
allows
modular
structurally
isoquinolines
wide
substrate
scope
(>60
examples),
good
functionalities
tolerance,
chemoselectivity.
Journal of Medicinal Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 7, 2025
Heteroaromatics
are
the
basis
for
many
pharmaceuticals.
The
ability
to
modify
these
structures
through
selective
core-atom
transformations,
or
"skeletal
edits",
can
dramatically
expand
landscape
drug
discovery
and
development.
However,
despite
importance
of
modifications,
quantitative
impact
such
transformations
on
accessible
chemical
space
remains
undefined.
Here,
we
report
a
cheminformatic
platform
analyze
which
skeletal
edits
would
most
increase
access
novel
space.
This
study
underscores
significance
emerging
single
multiple
heteroaromatics
in
enhancing
diversity,
example,
at
late-stage
campaign.
Our
findings
provide
framework
prioritizing
modifications
heteroaromatic
structural
motifs,
calling
development
new
methods
achieve
types
transformations.
ACS Medicinal Chemistry Letters,
Journal Year:
2025,
Volume and Issue:
16(4), P. 583 - 587
Published: March 24, 2025
The
relatively
polar
4(1H)-pyridone
(4-pyridone)
heterocycle
is
found
in
many
drugs
and
drug
candidates.
In
a
comparison
of
the
hydrophobicity,
aqueous
solubility,
metabolic
stability
several
matched
sets
4-pyridones,
4(1H)-quinolones
(4-quinolones),
9(10H)-acridones
(9-acridones),
measured
chromatographic
log
D
7.4
values
show
that
9-acridones
are
more
hydrophobic
less
soluble
than
their
4-quinolone
4-pyridone
counterparts.
All
4-pyridone/4-quinolone
pairs
had
identical
or
very
similar
hydrophobicity
solubility
properties.
Metabolic
increased
steadily
from
to
4-quinolones
consistent
with
progressive
increase
Fsp3
D.
gain
was
not
as
great
for
those
featuring
additional
functional
groups/heterocycles.
RSC Medicinal Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 1, 2025
Despite
significant
progress
in
drug
discovery,
there
remains
an
urgent
need
to
identify
new
structures
capable
of
targeting
drug-resistant
diseases,
as
well
novel
pathogens,
address
the
growing
challenges
global
health.
This
work
highlights
underexplored
potential
twistane-like
promising
candidates
for
development,
particularly
antiviral
agents.
We
provide
first
comprehensive
study
their
activity,
particular
against
SARS-CoV-2.
report
synthesis
a
family
chiral
indolyl-twistenediones,
with
separation
and
characterization
both
enantiomers
via
semipreparative
HPLC.
The
absolute
configurations
were
determined
using
experimental
theoretical
ECD
techniques,
supported
by
DFT
calculations.
A
detailed
biological
activity
various
pathogenic
RNA
viruses
demonstrates
selective
efficacy
members
Coronaviridae
family,
specifically
post-entry
step
viral
replication
cycle.
Further
investigation
revealed
remarkable
distinction
between
two
enantiomers,
opening
avenues
research
3D
space
cage
compounds.
