The Journal of Organic Chemistry,
Journal Year:
2024,
Volume and Issue:
89(7), P. 4261 - 4282
Published: March 20, 2024
Small
molecule
therapeutics
represent
the
majority
of
FDA-approved
drugs.
Yet,
many
attractive
targets
are
poorly
tractable
by
small
molecules,
generating
a
need
for
new
therapeutic
modalities.
Due
to
their
biocompatibility
profile
and
structural
versatility,
peptide-based
possible
solution.
Additionally,
in
past
two
decades,
advances
peptide
design,
delivery,
formulation,
devices
have
occurred,
making
peptides
an
modality.
However,
manufacturing
is
often
limited
solid-phase
synthesis
(SPPS),
liquid
phase
(LPPS),
lesser
extent
hybrid
SPPS/LPPS,
with
SPPS
emerging
as
predominant
platform
technology
synthesis.
involves
use
excess
solvents
reagents
which
negatively
impact
environment,
thus
highlighting
newer
technologies
reduce
environmental
footprint.
Herein,
fourteen
American
Chemical
Society
Green
Chemistry
Institute
Pharmaceutical
Roundtable
(ACS
GCIPR)
member
companies
portfolio
compiled
Process
Mass
Intensity
(PMI)
metrics
help
inform
sustainability
efforts
This
includes
PMI
assessment
on
40
synthetic
processes
at
various
development
stages
pharma,
classified
according
phase.
most
comprehensive
date.
The
process
was
divided
into
(synthesis,
purification,
isolation)
determine
respective
PMI.
On
average,
(SPPS)
(PMI
≈
13,000)
does
not
compare
favorably
other
modalities
such
molecules
median
168–308)
biopharmaceuticals
8300).
Thus,
high
warrants
more
environmentally
friendly
manufacturing.
Bioconjugate Chemistry,
Journal Year:
2023,
Volume and Issue:
unknown
Published: March 9, 2023
The
site-directed
chemical
conjugation
of
antibodies
remains
an
area
great
interest
and
active
efforts
within
the
antibody-drug
conjugate
(ADC)
community.
We
previously
reported
a
unique
site
modification
using
class
immunoglobulin-G
(IgG)
Fc-affinity
reagents
to
establish
versatile,
streamlined,
site-selective
native
enhance
therapeutic
index
resultant
ADCs.
This
methodology,
termed
"AJICAP",
successfully
modified
Lys248
produce
site-specific
ADC
with
wider
than
Food
Drug
Administration-approved
ADC,
Kadcyla.
However,
long
reaction
sequences,
including
reduction-oxidation
(redox)
treatment,
increased
aggregation
level.
In
this
manuscript,
we
aimed
present
updated
Fc-affinity-mediated
technology
named
"AJICAP
second
generation"
without
redox
treatment
utilizing
"one-pot"
antibody
reaction.
stability
Fc
affinity
was
improved
owing
structural
optimization,
enabling
production
various
ADCs
aggregation.
addition
conjugation,
Lys288
conjugated
homogeneous
drug-to-antibody
ratio
2
were
produced
different
peptide
reagent
possessing
proper
spacer
linkage.
These
two
technologies
used
over
20
from
several
combinations
drug
linkers.
in
vivo
profile
also
compared.
Furthermore,
nontraditional
production,
such
as
antibody-protein
conjugates
antibody-oligonucleotide
conjugates,
achieved.
results
strongly
indicate
that
approach
is
promising
strategy
for
manufacturing
engineering.
Catalysts,
Journal Year:
2023,
Volume and Issue:
13(2), P. 366 - 366
Published: Feb. 7, 2023
The
prevalence
of
amides
in
biological
systems
and
chemical
fields
such
as
polymers,
materials
natural
products
drives
continuous
research
on
novel
procedures
to
obtain
these
ubiquitous
functional
groups.
Currently,
efforts
this
purpose
are
mainly
focused
around
the
discovery
direct
catalytic
methods
that
more
atom
economic,
safe
practical
for
diversified
applications
(e.g.,
organic,
medicinal
peptide
chemistries,
material
polymer
purposes,
etc.),
accordance
with
green
chemistry
principles.
field
amide
synthesis
has
attained
a
level
significance
number
reviews
articles
addressing
it
grown
exponentially
last
decade.
Rather
than
providing
general
overview
amidation
methods,
which
have
been
described
broadly
well
recent
literature,
review
is
highlight
formation
bonds
from
amines
carboxylic
acids
or
esters.
goal
emphasize
mechanistic
aspects,
but
also
discuss
substrate
tolerance
racemization
issues
(when
applicable).
Synthesis,
Journal Year:
2023,
Volume and Issue:
55(20), P. 3239 - 3250
Published: April 26, 2023
Abstract
The
ubiquity
of
carboxylic
acids
as
naturally
derived
or
man-made
chemical
feedstocks
has
spurred
the
development
powerful,
decarboxylative
C–C
bond-forming
transformations
for
organic
synthesis.
Carboxylic
benefit
not
only
from
extensive
commercial
availability,
but
are
stable
surrogates
organohalides
organometallic
reagents
in
transition-metal-catalysed
cross-coupling.
Open
shell
reactivity
(or
derivatives
thereof)
to
furnish
carbon-centred
radicals
is
proving
transformative
synthetic
chemistry,
enabling
novel
and
strategy-level
C(sp3)–C
bond
disconnections
with
exquisite
chemoselectivity.
This
short
review
will
summarise
several
latest
advances
this
ever-expanding
area.
1
Introduction
2
Improved
Decarboxylative
Arylations
3
sp3–sp3
Cross-Coupling
Acids
Aliphatic
Bromides
4
Alcohols
Amines
5
Doubly
6
Bond
Formation
(Hetero)aryl
7
Conclusions
Chemical Science,
Journal Year:
2023,
Volume and Issue:
14(13), P. 3462 - 3469
Published: Jan. 1, 2023
Technology
for
generating
especially
important
amide
and
peptide
bonds
from
carboxylic
acids
amines
that
avoids
traditional
coupling
reagents
is
described.
The
1-pot
processes
developed
rely
on
thioester
formation,
neat,
using
a
simple
dithiocarbamate,
are
safe
green,
Nature-inspired
thioesters
then
converted
to
the
targeted
functionality.
Advanced Functional Materials,
Journal Year:
2024,
Volume and Issue:
34(22)
Published: Jan. 6, 2024
Abstract
Flexible
wearable
and
implantable
devices
are
contributing
to
the
healthcare
field
by
enabling
intuitive
interfaces
with
tissues
of
human
body
through
their
thin
form
factors,
which
enable
more
accurate
monitoring
signals
effective
delivery
therapy.
The
development
such
is
accompanied
an
increasing
interest
in
strategies
technologies
for
conformally
fixing
adhering
flexible
biomedical
place
acquire
high‐quality
biosignals
over
a
long
period,
even
subtle
movements
target.
Owing
various
mechanical
properties
wet
or
dynamic
environments
tissues,
it
necessary
use
different
adhesion
that
consider
biocompatibility
cohesive
each
case.
This
paper
provides
in‐depth
analysis
recent
bio‐adhesives
practical
applications
classifying
them
into:
1)
Conventional
Fixation,
2)
Mechanical
3)
Chemical
Adhesion,
based
on
mechanism,
4)
Functional
Adhesion
5)
Biomimetic
unique
properties.
Furthermore,
principles
detailed
mechanisms
strategy
design
characteristics
bioadhesives
thoroughly
reviewed
provide
valuable
insights
overall
summary
prospects
challenges
future
technology.
Chemical Communications,
Journal Year:
2023,
Volume and Issue:
59(23), P. 3439 - 3442
Published: Jan. 1, 2023
The
solventless
synthesis
of
an
amide
was
performed
in
a
twin-screw
extruder
the
presence
coupling
agent,
providing
high
yielding
and
productive
method.
reaction
conditions
were
optimized
to
prepare
APIs,
teriflunomide
moclobemide.
Deleted Journal,
Journal Year:
2023,
Volume and Issue:
2(1), P. 288 - 306
Published: July 26, 2023
Polysaccharides
are
inspiring
and
valuable
molecules
to
the
development
of
novel
drug
delivery
systems
owing
their
natural
availability,
non-toxicity,
biocompatibility,
good
biological
performance,
chemical
similarity
physiological
environment,
besides
noticeable
use
for
tailored-materials
assembly.
Biodegradable
hydrogels
based
on
polysaccharides
have
been
widely
studied
as
potential
pharmaceutical
forms
due
controlled
release
properties,
which
improve
bioavailability,
therapeutic
efficacy,
patient
compliance.
Despite
these
advantages,
polysaccharide
materials
present
insufficient
mechanical
properties
or
processability,
thus,
overcome
drawbacks,
feasible
suitable
crosslinking
methods
employed
strength
stability.
Therefore,
this
review
presents
recent
advances
in
hydrogels,
including
chitosan,
cellulose,
hyaluronic
acid,
alginate,
providing
examples
manufacturing
processes
with
emphasis
carriers
delivery.
Polysaccharide-based
represent
a
sustainable,
biocompatible,
appreciable
alternative
obtain
systems.
Organic Letters,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 16, 2025
Reported
herein
is
a
visible-light-promoted
strategy
for
the
α-C(sp3)–H
amidation
of
cyclic
ethers
using
N-acyloxyamide
as
an
oxidative
amidating
reagent.
This
transformation
provides
straightforward
approach
to
various
α-amidated
under
metal-
and
additive-free
conditions.
The
synthetic
utility
products
was
demonstrated
through
facile
transformations,
including
reduction,
allylation,
acylation,
sulfonamidation,
gram-scale
reactions.
Preliminary
mechanistic
studies
suggest
radical/radical
cross-coupling
process,
with
C(sp3)–H
bond
cleavage
identified
rate-determining
step.