Journal of Medicinal Chemistry,
Год журнала:
2023,
Номер
66(24), С. 16939 - 16952
Опубликована: Дек. 14, 2023
In
this
study,
a
one-pot
synthesis
via
photoinduced
C(sp2)–C(sp3)
coupling
followed
by
amide
formation
to
access
proteolysis
targeting
chimeras
(PROTACs)
was
developed.
The
described
protocol
studied
on
cereblon
(CRBN)-based
E3-ligase
binders
and
(+)-JQ-1,
bromodomain
inhibitor,
generate
BET
(bromodomain
extra
terminal
domain)
protein
degraders.
generated
PROTACs
were
profiled
in
vitro
tested
for
their
degradation
ability
with
several
potent
candidates
identified.
Upfront,
the
individual
reactions
of
transformation
carefully
optimized
CRBN
binder
functionalization
multiple
heterobifunctional
linker
moieties
designed
synthesized.
Separate
scopes
detailing
PROTAC
are
report
as
well
library
miniaturization
study
showing
high-throughput
compatibility.
Overall,
developed
provides
rapid
single
process,
thereby
allowing
efficient
generation
CRBN-based
libraries.
Angewandte Chemie,
Год журнала:
2022,
Номер
134(22)
Опубликована: Март 16, 2022
Abstract
The
synthesis
of
sulfides
has
been
widely
studied
because
this
functional
subunit
is
prevalent
in
biomolecules
and
pharmaceuticals,
as
well
being
a
useful
synthetic
platform
for
further
elaboration.
Thus,
various
methods
to
build
C−S
bonds
have
developed,
but
typically
they
require
the
use
precious
metals
or
harsh
conditions.
Electron
donor–acceptor
(EDA)
complex
photoactivation
strategies
emerged
versatile
sustainable
ways
achieve
bond
formation,
avoiding
challenges
associated
with
previous
methods.
This
work
describes
an
open‐to‐air,
photoinduced,
site‐selective
C−H
thioetherification
from
readily
available
reagents
via
EDA
formation
that
tolerates
wide
range
different
groups.
Moreover,
C(sp
2
)−halogen
remain
intact
using
protocol,
allowing
late‐stage
installation
sulfide
motif
bioactive
scaffolds,
while
yet
modification
through
more
traditional
C−X
cleavage
protocols.
Additionally,
mechanistic
investigations
support
envisioned
scenario.
ACS Catalysis,
Год журнала:
2023,
Номер
13(13), С. 8624 - 8630
Опубликована: Июнь 14, 2023
CF3-containing
molecules
are
frequently
encountered
in
many
best-selling
pharmaceutical
drugs.
Consequently,
a
large
number
of
methods
have
been
developed
for
introducing
CF3
group
into
organic
compounds.
However,
innovative
protocols
enabling
direct
access
to
alkyl-CF3
moieties
still
sought
after.
In
this
context,
we
report
visible-light-induced
formal
trifluoropropanation
various
alkyl
and
aryl
halide
derivatives
using
the
2-Bromo-3,3,3-trifluoro-1-propene
(BTP)
as
readily
available
building
block.
Our
strategy
relies
on
use
catalytic
system
merging
amount
supersilane
NaBH4
an
additional
reductant.
These
mild
reaction
conditions
compatible
with
range
functional
groups.
Finally,
double
deuterium
incorporation
was
obtained
upon
replacement
NaBD4
under
these
conditions,
leading
formation
hitherto
unknown
α,α-d2-CF3
Organic Letters,
Год журнала:
2023,
Номер
25(32), С. 5995 - 6000
Опубликована: Авг. 8, 2023
A
Ni-catalyzed
reductive
dicarbofunctionalization
of
α-CF3
styrenes
with
benzyl
bromides
has
been
accomplished.
This
transformation
obviates
the
commonly
facile
β-F
elimination
effectively
and
enables
creation
CF3-substituted
all-carbon
quaternary
centers
pharmaceutical
interests.
Preliminary
mechanistic
studies
suggest
a
pathway
consisting
radical
addition
subsequent
nickel-mediated
benzylation
resulting
α-CF3-embedded
tertiary
C
radical.
Chemical Science,
Год журнала:
2023,
Номер
14(10), С. 2713 - 2720
Опубликована: Янв. 1, 2023
Diverse
DNA-encoded
libraries
of
complex
and
novel
sp
3
-rich
spirocycles
were
achieved
using
a
versatile
operationally
simple
visible
light-mediated
intermolecular
[2
+
2]
cycloaddition.
Journal of Medicinal Chemistry,
Год журнала:
2023,
Номер
66(24), С. 16939 - 16952
Опубликована: Дек. 14, 2023
In
this
study,
a
one-pot
synthesis
via
photoinduced
C(sp2)–C(sp3)
coupling
followed
by
amide
formation
to
access
proteolysis
targeting
chimeras
(PROTACs)
was
developed.
The
described
protocol
studied
on
cereblon
(CRBN)-based
E3-ligase
binders
and
(+)-JQ-1,
bromodomain
inhibitor,
generate
BET
(bromodomain
extra
terminal
domain)
protein
degraders.
generated
PROTACs
were
profiled
in
vitro
tested
for
their
degradation
ability
with
several
potent
candidates
identified.
Upfront,
the
individual
reactions
of
transformation
carefully
optimized
CRBN
binder
functionalization
multiple
heterobifunctional
linker
moieties
designed
synthesized.
Separate
scopes
detailing
PROTAC
are
report
as
well
library
miniaturization
study
showing
high-throughput
compatibility.
Overall,
developed
provides
rapid
single
process,
thereby
allowing
efficient
generation
CRBN-based
libraries.
