Synthesis,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 5, 2024
Abstract
Discovery
Process
Chemistry
(DPC)
is
an
emerging
intersectoral
space
that
characterized
by
the
development
of
new
chemical
reactions
or
syntheses
enable
efficient
elucidation
structure-activity
relationships
(SARs)
and
structure-property
(SPRs)
as
well
a
rapid
transition
to
process
development.
Drug
discovery
are
accelerated
such
efforts
this
has
led
chemists
in
academia
industry
alike
place
increasing
importance
on
these
aims.
In
Short
Review,
we
explore
recent
advances
DPC
impact
it
can
have
SAR/SPR
interrogation
downstream
drug
efforts.
1
Introduction
2
Enabling
Interrogation
with
Bioisosteres
3
Couplings
Diversifiable
Reaction
Partners
4
Late-Stage
Functionalization
5
Conclusion
Outlook
ACS Medicinal Chemistry Letters,
Journal Year:
2023,
Volume and Issue:
14(5), P. 557 - 565
Published: April 24, 2023
Life
is
constructed
primarily
using
a
toolbox
of
20
canonical
amino
acids─relying
upon
these
building
blocks
for
the
assembly
proteins
and
peptides
that
regulate
nearly
every
cellular
task,
including
cell
structure,
function,
maintenance.
While
Nature
continues
to
be
source
inspiration
drug
discovery,
medicinal
chemists
are
not
beholden
only
acids
have
begun
explore
non-canonical
(ncAAs)
construction
designer
with
improved
drug-like
properties.
However,
as
our
ncAAs
expands,
hunters
encountering
new
challenges
in
approaching
iterative
peptide
design–make–test–analyze
cycle
seemingly
boundless
set
blocks.
This
Microperspective
focuses
on
technologies
accelerating
ncAA
interrogation
discovery
(including
HELM
notation,
late-stage
functionalization,
biocatalysis)
while
shedding
light
areas
where
further
investment
could
accelerate
medicines
but
also
improve
downstream
development.
Journal of the American Chemical Society,
Journal Year:
2023,
Volume and Issue:
145(20), P. 10930 - 10937
Published: May 15, 2023
Amines
and
carboxylic
acids
are
abundant
synthetic
building
blocks
that
classically
united
to
form
an
amide
bond.
To
access
new
pockets
of
chemical
space,
we
interested
in
the
development
amine-acid
coupling
reactions
complement
coupling.
In
particular,
formation
carbon-carbon
bonds
by
formal
deamination
decarboxylation
would
be
impactful
addition
synthesis
toolbox.
Here,
report
a
cross-coupling
alkyl
amines
aryl
C(sp
Chemical Reviews,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 26, 2024
Cross-electrophile
coupling
(XEC),
defined
by
us
as
the
cross-coupling
of
two
different
σ-electrophiles
that
is
driven
catalyst
reduction,
has
seen
rapid
progression
in
recent
years.
As
such,
this
review
aims
to
summarize
field
from
its
beginnings
up
until
mid-2023
and
provide
comprehensive
coverage
on
synthetic
methods
current
state
mechanistic
understanding.
Chapters
are
split
type
bond
formed,
which
include
C(sp
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(23), P. 16306 - 16313
Published: May 28, 2024
Transaminases
are
choice
biocatalysts
for
the
synthesis
of
chiral
primary
amines,
including
amino
acids
bearing
contiguous
stereocenters.
In
this
study,
we
employ
lysine
as
a
"smart"
amine
donor
in
transaminase-catalyzed
dynamic
kinetic
resolution
reactions
to
access
β-branched
noncanonical
arylalanines.
Our
mechanistic
investigation
demonstrates
that,
upon
transamination,
lysine-derived
ketone
byproduct
readily
cyclizes
six-membered
imine,
driving
equilibrium
desired
direction
and
thus
alleviating
need
load
superstoichiometric
quantities
or
deploy
multienzyme
cascade.
Lysine
also
shows
good
overall
compatibility
with
panel
wild-type
transaminases,
promising
hint
its
application
smart
more
broadly.
Indeed,
by
approach,
furnished
broad
scope
arylalanines,
some
hitherto
intractable
cyclopropyl
isopropyl
substituents,
high
yields
excellent
selectivities.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(40), P. 27583 - 27593
Published: Sept. 26, 2024
The
exploration
of
strong
chemical
bonds
as
synthetic
handles
offers
new
disconnection
strategies
for
the
synthesis
functionalized
molecules
via
transition
metal
catalysis.
However,
slow
oxidative
addition
rate
these
covalent
to
a
center
hampers
their
utility.
Here,
we
report
C(sp
From
a
retrosynthetic
standpoint,
functionalization
or
synthesis
of
heterocyclic
cores
are
fundamental
disconnections
that
chemists
make.
This
manuscript
highlights
heterocycle
as
the
strategic
bond
disconnection
by
leveraging
ubiquitous
building
blocks,
carboxylic
acids
and
amines,
for
preparation
in
library-friendly
format.
formation
strategy
allows
medicinal
to
access
much
wider
chemical
space,
especially
analogs
with
higher
Fsp3
vs
state-of-the-art
methods.
The
direct
impact
on
chemistry
programs
is
underscored
adapting
miniaturizing
N2-indazoles
C2-benzimidazoles
μ-scale
parallel
(PMC)
libraries,
affording
similar
success
rate
(80%)
venerable
Suzuki
Buchwald-Hartwig
libraries.
Nature Communications,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: Feb. 25, 2025
Cryptochiral
compounds
are
indispensable
in
biology
systems
and
medical
applications,
yet
the
development
of
high-performance
detection
method
remains
challenging.
Here,
we
report
a
hinge-like
dinuclear
Pt(II)
complex
as
stereodynamic
probe
for
cryptochirality
sensing.
This
features
constrained,
closed
conformation
achieved
through
synergistic
intramolecular
π
−
stacking
metal-metal
interactions
between
cyclometalated
wings.
The
shows
robust
chiroptical
response
to
center-to-axial
chiral
induction
during
rapid
condensation
with
cryptochiral
that
adopts
more
energetically
favorable
conformation.
resulting
intense
Cotton
effects
at
long
wavelengths
enable
in-situ
circular
dichroism
analysis
determinate
absolute
configuration
enantiometric
composition
molecules.
Furthermore,
near-infrared
phosphorescence
characteristics
hinge
have
been
explored
develop
it
an
optical
sensor
accurate
quantification
With
its
dual
CD
capabilities,
this
great
potential
high-throughput
screening
analysis.
authors
complexes
probes
