European Journal of Organic Chemistry,
Год журнала:
2023,
Номер
27(3)
Опубликована: Ноя. 30, 2023
Abstract
Since
the
first
report
that
1,2,4,5‐tetrazines
undergo
a
bioorthogonal
reaction
with
dienophiles
in
form
of
an
inverse
electron‐demand
Diels‐Alder
reaction,
demand
for
high‐yielding
synthetic
approaches
towards
them
grew
steadily.
Despite
this
significant
interest,
tetrazines
were
predominantly
accessed
via
Pinner
synthesis
or
other
Pinner‐like
reactions,
significantly
limiting
available
substrates.
In
particular,
unsymmetrically
substituted
s‐tetrazines
selective
conjugation
to
another
species
presented
major
challenge.
To
tackle
these
challenges,
new
and
innovative
transformations
have
been
developed
widen
scope
accessible
symmetric
unsymmetric
tetrazines.
For
instance,
Ni(II),
Zn(II),
sulphur‐catalysed
reactions
between
two
nitriles
hydrazine
developed,
which
provide
access
wide
range
(un‐)symmetric
aryl
s‐tetrazines.
Also,
amidines
orthoesters
give
alkyl
substituents,
whereas
usage
CH
2
Cl
yields
valuable
H‐monosubstituted
Methods
using
thiocarbohydrazides,
terminal
fluoroolefins,
oxetane
esters,
tosyl
hydrazones
are
among
recent
additions.
Due
high
interest
tetrazine
click‐chemistry
approaches,
some
reach
beyond
we
expect
overview
routes
aid
exploration
further
applications
Ultimately,
hope
guide
chemists
chemical
biologists
accessing
functional
Abstract
This
contribution
aims
to
trace
the
origins
of
bioorthogonal
chemistry,
from
its
roots
in
early
alchemy
and
Scientific
Revolution,
development
as
a
response
quest
understand
fundamental
principles
life.
The
application
chemical
tools
study
manipulate
biological
processes
biomolecules
laid
foundation
for
modern
biology.
With
advent
first
reactions
that
proceed
selectively
efficiently
without
interfering
with
systems,
scientists
gained
unique
set
achieve
an
unprecedented
level
understanding
at
molecular
level.
New
techniques
such
strain-promoted
azide–alkyne
cycloaddition
(SPAAC),
tetrazine
ligation,
artificial
metalloenzymes
have
further
advanced
field.
These
chemistry
significantly
extended
potential
hold
promise
revolutionizing
healthcare
through
improved
drug
delivery
diagnostic
tools.
By
placing
these
achievements
context
history
science,
it
is
clear
this
field
has
bright
future.
As
our
deepens
technology
evolves,
we
can
anticipate
their
incorporation
into
wide
range
practices,
potentially
ushering
new
era
personalized
treatments.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(33), С. 23240 - 23251
Опубликована: Авг. 8, 2024
Selective
cleavage
of
amide
bonds
holds
prominent
significance
by
facilitating
precise
manipulation
biomolecules,
with
implications
spanning
from
basic
research
to
therapeutic
interventions.
However,
achieving
selective
via
mild
synthetic
chemistry
routes
poses
a
critical
challenge.
Here,
we
report
novel
bond-cleavage
reaction
triggered
Na[AuCl4]
in
aqueous
conditions,
where
crucial
cyclization
step
leads
the
formation
5-membered
ring
intermediate
that
rapidly
hydrolyses
release
free
amine
high
yields.
Notably,
exhibits
remarkable
site-specificity
cleave
peptide
at
C-terminus
allyl-glycine.
The
strategic
introduction
leaving
group
allyl
position
facilitated
dual-release
approach
through
π-acid
catalyzed
substitution.
This
was
employed
for
targeted
cytotoxic
drug
monomethyl
auristatin
E
combination
an
antibody-drug
conjugate
cancer
cells.
Finally,
Au-mediated
prodrug
activation
shown
colorectal
zebrafish
xenograft
model,
leading
significant
increase
apoptosis
and
tumor
shrinkage.
Our
findings
reveal
metal-based
cleavable
expanding
utility
Au
complexes
beyond
catalysis
encompass
reactions
therapy.
Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
67(21), С. 19905 - 19924
Опубликована: Ноя. 1, 2024
Bioorthogonal
cleavage
reactions
have
been
developed
as
an
intriguing
strategy
to
enhance
the
safety
of
chemotherapeutics.
Aiming
reduce
toxicity
and
improve
targeted
release
properties
colchicine
binding
site
inhibitors
(CBSIs)
based
on
previous
work,
a
series
biologically
inert
prodrugs
were
further
designed
synthesized
through
bioorthogonal
prodrug
strategy.
The
therapeutic
effects
could
be
"turned-on"
once
combined
with
palladium
resins.
Particularly,
2b
was
68.3-fold
less
cytotoxic
compared
parent
compound,
while
its
cytotoxicity
recovered
in
situ
presence
Mechanism
studies
confirmed
that
inhibited
cell
growth
same
manner
CBSIs.
More
importantly,
vivo
efficacy
demonstrated
efficient
activation
by
resins,
resulting
significant
inhibition
tumor
(63.2%).
These
results
suggest
improved
property
catalyzed
Pd-mediated
reaction
deserves
investigation.
European Journal of Organic Chemistry,
Год журнала:
2023,
Номер
27(3)
Опубликована: Ноя. 30, 2023
Abstract
Since
the
first
report
that
1,2,4,5‐tetrazines
undergo
a
bioorthogonal
reaction
with
dienophiles
in
form
of
an
inverse
electron‐demand
Diels‐Alder
reaction,
demand
for
high‐yielding
synthetic
approaches
towards
them
grew
steadily.
Despite
this
significant
interest,
tetrazines
were
predominantly
accessed
via
Pinner
synthesis
or
other
Pinner‐like
reactions,
significantly
limiting
available
substrates.
In
particular,
unsymmetrically
substituted
s‐tetrazines
selective
conjugation
to
another
species
presented
major
challenge.
To
tackle
these
challenges,
new
and
innovative
transformations
have
been
developed
widen
scope
accessible
symmetric
unsymmetric
tetrazines.
For
instance,
Ni(II),
Zn(II),
sulphur‐catalysed
reactions
between
two
nitriles
hydrazine
developed,
which
provide
access
wide
range
(un‐)symmetric
aryl
s‐tetrazines.
Also,
amidines
orthoesters
give
alkyl
substituents,
whereas
usage
CH
2
Cl
yields
valuable
H‐monosubstituted
Methods
using
thiocarbohydrazides,
terminal
fluoroolefins,
oxetane
esters,
tosyl
hydrazones
are
among
recent
additions.
Due
high
interest
tetrazine
click‐chemistry
approaches,
some
reach
beyond
we
expect
overview
routes
aid
exploration
further
applications
Ultimately,
hope
guide
chemists
chemical
biologists
accessing
functional
