Organic Letters,
Год журнала:
2023,
Номер
25(43), С. 7868 - 7872
Опубликована: Окт. 19, 2023
A
cyclic
nucleoside
has
been
designed
and
synthesized
to
serve
as
a
conformationally
fixed
building
block
for
the
development
of
functional
oligonucleotides.
The
bridge
was
introduced
between
nucleobase
5'-position
fix
rotation
around
C4'-C5'
bond,
base
orientation,
sugar
puckering
all
at
once.
13-membered
structure
using
sulfonamide
linkage,
which
retains
an
N-H
group
that
can
be
used
attach
additional
moiety.
linkage
formed
through
end-to-end
cyclization
intermediate
contained
both
sulfonyltriazole
amino
groups.
Both
1H
NMR
computational
studies
revealed
conformation,
γ
torsion
angle
were
S-type,
anti,
trans,
respectively.
As
such,
nucleosides
show
promise
introducing
these
specific
distorted
conformations
into
nucleic
acids.
New Journal of Chemistry,
Год журнала:
2024,
Номер
48(11), С. 4645 - 4669
Опубликована: Янв. 1, 2024
This
review
summarized
the
progress
in
synthesizing
eight-membered
N-heterocycles
over
past
two
decades
(1995–2023),
inspiring
synthetic
chemists
to
develop
more
efficient
strategies
for
construction
of
these
skeletons.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(8), С. 5702 - 5711
Опубликована: Фев. 19, 2024
Macrocycles
and
medium-sized
rings
are
important
in
many
scientific
fields
technologies
but
hard
to
make
using
current
methods,
especially
on
a
large
scale.
Outlined
herein
is
strategy
by
which
functionalized
macrocycles
can
be
prepared
cyclization/ring
expansion
(CRE)
cascade
reactions,
without
resorting
high
dilution
conditions.
CRE
reactions
designed
operate
exclusively
via
kinetically
favorable
5–7-membered
ring
cyclization
steps;
this
means
that
the
problems
typically
associated
with
classical
end-to-end
macrocyclization
avoided.
A
modular
synthetic
approach
has
been
developed
facilitate
simple
assembly
of
requisite
linear
precursors,
then
converted
into
an
extremely
broad
range
one
nine
protocols.
Molecules,
Год журнала:
2024,
Номер
29(9), С. 1920 - 1920
Опубликована: Апрель 23, 2024
Skeleton
editing
has
rapidly
advanced
as
a
synthetic
methodology
in
recent
years,
significantly
streamlining
the
synthesis
process
and
gaining
widespread
acceptance
drug
development.
This
field
encompasses
diverse
ring
reactions,
many
of
which
exhibit
immense
potential
skeleton
editing,
facilitating
generation
novel
skeletons.
Notably,
reactions
that
involve
cleavage
two
distinct
rings
followed
by
reformation
new
through
insertion
play
pivotal
role
construction
article
aims
to
compile
systematize
this
category
emphasizing
primary
reaction
types
offering
thorough
exploration
their
associated
complexities
challenges.
Our
endeavor
is
furnish
readers
with
comprehensive
strategies,
igniting
research
interest
injecting
fresh
impetus
into
advancement
domain.
The Journal of Organic Chemistry,
Год журнала:
2023,
Номер
88(17), С. 12709 - 12715
Опубликована: Авг. 19, 2023
Macrocycles
fascinate
chemists
due
to
both
their
structure
and
applications.
However,
we
still
lack
efficient
sustainable
synthetic
methods,
giving
us
straightforward
access
them.
Herein,
a
rapid
macrocyclization
utilizing
two-step,
one-pot
approach
based
on
orthogonal
multicomponent
reaction
(MCR)
tactics
is
introduced.
This
protocol,
which
Ugi
Groebke-Blackburn-Bienaymé
reactions
with
isocyanides
tethered
alkyl
tosylates,
yields
medium
sized
macrocycles
that
are
otherwise
difficult
achieve.
Single
crystal
structures
reveal
conformational
reorganization
via
intramolecular
hydrogen
bonding,
modeling
studies
profile
the
synthesized
libraries.
Molecules,
Год журнала:
2024,
Номер
29(7), С. 1562 - 1562
Опубликована: Март 31, 2024
The
construction
of
a
small
molecule
library
that
includes
compounds
with
medium-sized
rings
is
increasingly
essential
in
drug
discovery.
These
are
for
identifying
novel
therapeutic
agents
capable
targeting
“undruggable”
targets
through
high-throughput
and
high-content
screening,
given
their
structural
complexity
diversity.
However,
synthesizing
presents
notable
challenges,
particularly
direct
cyclization
methods,
due
to
issues
such
as
transannular
strain
reduced
degrees
freedom.
This
review
an
overview
current
strategies
rings,
emphasizing
innovative
approaches
like
ring-expansion
reactions.
It
highlights
the
challenges
synthesis
potential
these
diversify
chemical
space
discovery,
underscoring
importance
developing
new
bioactive
compounds.
Accounts of Chemical Research,
Год журнала:
2024,
Номер
57(22), С. 3254 - 3265
Опубликована: Окт. 31, 2024
ConspectusProtein–protein
interactions
(PPIs)
are
essential
in
numerous
biological
processes
and
diseases,
making
them
attractive
yet
challenging
drug
targets.
While
many
advances
have
been
made
traditional
discovery,
targeting
PPIs
has
difficult
due
to
a
lack
of
specialized
chemical
libraries
designed
modulate
these
interactions.
Current
mainly
focus
on
conventional
target
proteins
like
enzymes
or
receptors
as
substrate
analogs
rather
than
small-molecule
modulators
PPIs.
These
targets
behave
differently
from
Conventional
druggable
relatively
small
surfaces
binding
pockets
that
allowed
be
targeted
with
current
libraries,
but
As
result,
there
is
an
urgent
need
for
innovative
approach
expand
the
space.To
address
this,
we
developed
privileged
substructure-based
diversity-oriented
synthesis
(pDOS)
strategy,
aimed
at
creating
maximal
skeletal
diversity
explore
broader
biochemical
space.
Pyrimidine
serves
substructure
our
approach,
which
employs
several
strategies:
(i)
silver-catalyzed
iodine-mediated
tandem
cyclizations
generate
pyrimidine-embedded
polyheterocycles;
(ii)
diverse
pairing
strategies
produce
pyrimidodiazepine-containing
polyheterocyclic
skeletons
enhanced
scaffold
saturation;
(iii)
transformation
develop
pyrimidine-fused
medium-sized
azacycles
via
chemoselective
cleavages
migrations
N–N
C–N
bond;
(iv)
design
peptidomimetics
systematically
mimic
three
pivotal
protein
secondary
structures
using
pyrimidodiazepine-based
scaffolds;
(v)
identification
small-molecules
allosterically
inhibits
interaction
between
human
ACE2
receptor-binding
domain
(RBD)
SARS-CoV-2
spike
block
viral
entry
into
host
cells.Through
approaches,
generated
39
distinct
frameworks,
demonstrating
significant
molecular
validated
by
chemoinformatic
analyses
such
Tanimoto
similarity
principal
moment
inertia
(PMI)
analysis.
This
extends
pyrimidine
beyond
linear
bicyclic
forms,
polyheterocycles
3D
structural
diversity.
novel
frameworks
overcome
limitation
simpler
scaffolds,
offering
promising
tools
modulating
PPIs.Our
pDOS
highlights
how
structure-embedded
polyheterocycles,
particularly
those
based
pyrimidine,
can
effectively
previously
undruggable
strategy
provides
new
direction
allowing
development
molecules
operate
drug-like
rules.
In
addition
expanding
space
PPI
modulation,
enables
creation
scaffolds
suited
complex
dynamic
interfaces.
innovation
could
significantly
impact
therapeutic
development,
solutions
intractable
By
scope
pyrimidine-based
opened
up
possibilities
advancing
biology.This
perspective
demonstrates
potential
outlines
structurally
platform
discovery
facilitating
exploration
untapped
spaces
potentially
transforming
way
Chemical Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
A
stereoselective
strategy
to
make
C–N
atropisomeric
amides
based
on
intramolecular
acyl
transfer
via
a
tethered
Lewis
basic
pyridine
or
tertiary
amine
group
is
reported.
The Journal of Organic Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 1, 2025
A
general
approach
is
described
for
the
synthesis
and
elaboration
of
medium-sized
ring
mono-
difunctionalized
8-
or
9-membered
lactone
building
blocks.
The
lactones
are
prepared
via
cascade
expansion
reactions
elaborated
Suzuki-Miyaura
cross
coupling
various
N-functionalization
reactions.
This
enables
efficient
access
to
diverse,
blocks
in
a
synthetically
challenging
under-represented
area
pharmaceutical
chemical
space.
