ChemBioChem,
Journal Year:
2023,
Volume and Issue:
25(4)
Published: Dec. 5, 2023
Abstract
Amide
bond‐containing
biomolecules
are
functionally
significant
and
useful
compounds
with
diverse
applications.
For
example,
N‐acyl
amino
acids
(NAAAs)
an
important
class
of
lipoamino
acid
amides
extensive
use
in
food,
cosmetic
pharmaceutical
industries.
Their
conventional
chemical
synthesis
involves
the
toxic
chlorinating
agents
for
carboxylic
activation.
Enzyme‐catalyzed
biotransformation
green
these
is
therefore
highly
desirable.
Here,
we
review
a
range
enzymes
suitable
NAAA
their
strategies
adopted
Generally,
ATP‐dependent
biosynthesis
acyl‐adenylating
that
couple
hydrolysis
phosphoanhydride
bond
ATP
formation
acyl‐adenylate
intermediate.
In
contrast,
ATP‐independent
involve
hydrolases
such
as
lipases
or
aminoacylases,
which
rely
on
transient
activation
acid.
This
occurs
either
through
acyl‐enzyme
intermediate
by
favorable
interactions
surrounding
residues
to
anchor
acyl
donor
orientation
incoming
amine
nucleophile.
Recently,
development
alternative
pathway
involving
ester‐amide
interconversion
has
unraveled
another
possible
strategy
amide
esterification‐aminolysis
cascade
reactions,
potentially
expanding
substrate
scope
catalyze
amides.
Advanced Synthesis & Catalysis,
Journal Year:
2023,
Volume and Issue:
365(24), P. 4359 - 4391
Published: Nov. 7, 2023
Abstract
Amide
bond
construction
has
garnered
significant
interest
in
recent
decades
due
to
amides
being
one
of
the
most
prevalent
functional
groups
among
bioactive
molecules.
Out
thirty‐seven
new
drugs
approved
by
FDA
2022,
eleven
are
small
molecules
containing
at
least
amide
bond.
Additionally,
there
nineteen
large
as
drugs,
some
which
have
peptide
structures,
and
therefore,
also
bear
bonds.
In
years,
multiple
teams
embraced
challenge
developing
more
efficient
methods
for
formation.
This
dedication
led
numerous
publications
appearing
monthly
prestigious
journals,
showcasing
advancements
this
field.
The
primary
goal
review
is
present
viable
strategies
constructing
It
crucial
differentiate
between
formation
synthesis;
hence,
focus
on
describing
specific
forming
C(O)−N
particular,
concentrates
developed
within
last
six
years.
There
a
particular
emphasis
approaches
that
consider
thought
process
when
selecting
starting
materials
groups.
approach
ensures
coverage
all
common
chemical
transformations
yield
Nature Chemical Biology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: May 9, 2025
Abstract
E-64
is
an
irreversible
cysteine
protease
inhibitor
prominently
used
in
chemical
biology
and
drug
discovery.
Here
we
uncover
a
nonribosomal
peptide
synthetase-independent
biosynthetic
pathway
for
E-64,
which
widely
conserved
fungi.
The
starts
with
epoxidation
of
fumaric
acid
to
the
warhead
(2
S
,3
)-
trans
-epoxysuccinic
Fe(II)/α-ketoglutarate-dependent
oxygenase,
followed
by
successive
condensation
l
-amino
adenosine
triphosphate
grasp
enzyme
amine
fungal
example
amide
bond
synthetase.
Both
bond-forming
enzymes
display
notable
biocatalytic
potential,
including
scalability,
stereoselectivity
toward
broader
substrate
scopes
forming
bonds.
Biocatalytic
cascade
these
generated
library
inhibitors,
leading
more
potent
cathepsin
inhibitors.
Additionally,
one-pot
reactions
enabled
preparative
synthesis
clinically
relevant
Our
work
highlights
importance
investigation
discovery
potential
synthesizing
small-molecule
libraries.
ACS Catalysis,
Journal Year:
2023,
Volume and Issue:
13(17), P. 11771 - 11780
Published: Aug. 22, 2023
Despite
the
increasing
use
of
biocatalysis
for
organic
synthesis,
there
are
currently
no
databases
that
adequately
capture
synthetic
biotransformations.
The
lack
a
database
prevents
accelerating
biocatalyst
characterization
efforts
from
being
leveraged
to
quickly
identify
candidate
enzymes
reactions
or
cascades,
slowing
their
development.
RetroBioCat
Database
(available
at
retrobiocat.com)
addresses
this
gap
by
capturing
information
on
biotransformations
and
providing
an
analysis
platform
allows
data
be
searched
explored
through
range
highly
interactive
visualization
tools.
This
makes
it
simple
explore
available
enzymes,
substrate
scopes,
how
characterized
related
each
other
wider
sequence
space.
Data
entry
is
facilitated
openly
accessible
curation
platform,
featuring
automated
tools
accelerate
process.
democratizes
knowledge
has
potential
biocatalytic
reaction
development,
making
valuable
resource
community.
European Journal of Organic Chemistry,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Jan. 19, 2024
Abstract
N‐
Carboxyanhydrides
(NCAs)
are
compounds
derived
from
the
addition
of
a
carboxylic
acid
to
an
isocyanate,
and
known
form
amides
readily
with
release
CO
2
as
by‐product.
NCAs
have
been
for
over
120
years,
but
despite
their
lengthy
history,
remained
so
far
overshadowed
by
more
traditional
approaches
amide
bond
formation.
In
this
review,
potential
utility
in
context
formation
is
reviewed
preparation,
reactivity
practical
application
also
discussed.
ACS Catalysis,
Journal Year:
2024,
Volume and Issue:
14(11), P. 8913 - 8921
Published: May 25, 2024
The
amide
moiety
belongs
to
the
most
common
motives
in
pharmaceutical
chemistry,
present
many
prescribed
small-molecule
pharmaceuticals.
Methods
for
its
manufacture
are
still
high
demand,
especially
using
water/buffer
as
a
solvent
and
avoiding
stoichiometric
amounts
of
activation
reagents.
Herein,
we
identified
from
library
lipases/esterases/acyltransferases
variants
thereof
lipase
originating
Sphingomonas
sp.
HXN-200
(SpL)
able
form
amides
aqueous
solution
starting
broad
scope
sterically
demanding
heteroaromatic
ethyl
esters
well
aliphatic
amines,
reaching
isolated
yields
up
99%
on
preparative
scale
space
time
864
g
L–1
d–1;
thus,
selected
cases,
was
formed
within
minutes.
enzyme
features
an
aspartate
next
canonical
serine
catalytic
triad,
which
essential
formation.
Furthermore,
structure
revealed
two
tunnels
active
site,
presumably
one
ester
amine,
permit
bringing
together
amine
site.
This
work
shows
that
biocatalytic
formation
various
five-
six-membered
buffer
can
serve
platform
synthesis.
We
have
developed
an
efficient
solvent-free
protocol
for
amide
bond
formation
using
Boc
2
O/DMAP,
involving
the
in
situ
generation
of
a
mixed
anhydride
and
proceeding
via
sequential
mechanism.
ACS Catalysis,
Journal Year:
2024,
Volume and Issue:
14(2), P. 1021 - 1029
Published: Jan. 6, 2024
The
synthesis
of
amide
bonds
is
one
the
most
frequently
performed
reactions
in
pharmaceutical
synthesis,
but
requirement
for
stoichiometric
quantities
coupling
agents
and
activated
substrates
established
methods
has
prompted
interest
biocatalytic
alternatives.
Amide
Bond
Synthetases
(ABSs)
actively
catalyze
both
ATP-dependent
adenylation
carboxylic
acid
their
subsequent
amidation
using
an
amine
nucleophile,
within
active
site
enzyme,
enabling
use
only
a
small
excess
partner.
We
have
assessed
ability
ABS
from
Chinese Journal of Organic Chemistry,
Journal Year:
2024,
Volume and Issue:
44(2), P. 409 - 409
Published: Jan. 1, 2024
Amide
bond
constructions
are
crucial
in
peptide
synthesis
and
pharmaceutical
chemistry
research.The
traditional
methods
of
require
the
use
excessive
amounts
reagents
solvents,
posing
a
threat
to
environment
human
health.It
is
still
current
research
focus
develop
environmentally
friendly
novel
acylation
efficient,
green,
sustainable
amide
methods.From
green
chemistry's
principles,
this
paper
focused
on
efficient
formation
bonds
peptide,
including
catalysis
elemental
organic
chemicals,
some
solvents
reagents,
physical
strengthening
methods,
etc.The
application
these
technologies
was
also
discussed
chemistry.
Chemistry - A European Journal,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 6, 2024
Abstract
The
development
of
sustainable
chemistry
underlying
the
quest
to
minimize
and/or
valorize
waste
in
carbon‐neutral
manufacture
chemicals
is
followed
over
last
four
five
decades.
Both
chemo‐
and
biocatalysis
have
played
an
indispensable
role
this
odyssey.
particular
developments
protein
engineering,
metagenomics
bioinformatics
preceding
three
decades
a
crucial
supporting
facilitating
widespread
application
both
whole
cell
cell‐free
biocatalysis.
pressing
need,
driven
by
climate
change
mitigation,
for
drastic
reduction
greenhouse
gas
(GHG)
emissions,
has
precipitated
energy
transition
based
on
decarbonization
defossilization
organic
production.
latter
involves
biomass
CO
2
as
feedstock
green
electricity
generated
using
solar,
wind,
hydroelectric
or
nuclear
energy.
use
polysaccharides
feedstocks
will
underpin
renaissance
carbohydrate
with
pentoses
hexoses
base
bio‐based
solvents
polymers
environmentally
friendly
downstream
products.
availability
inexpensive
solar
led
increasing
attention
electro(bio)catalysis
photo(bio)catalysis
which
turn
leading
myriad
innovations
these
fields.