Research Square (Research Square),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Dec. 13, 2023
Abstract
N-Glycosylated
heterocycles
play
important
roles
in
biological
systems
and
drug
development.
The
synthesis
of
these
compounds
heavily
relies
on
ionic
N-glycosylation,
which
is
usually
constrained
by
factors
like
labile
glycosyl
donors,
precious
metal
catalysts,
stringent
conditions.
Herein,
we
report
an
unprecedented
radical-based
method
for
synthesizing
N
-glycosides
leveraging
copper
metallaphotoredox
catalysis.
Complementing
with
the
well-established
approaches,
our
employs
inexpensive
photo-
copper-
catalysts
can
tolerate
some
extent
water.
Furthermore,
readily
available
stable
1-hydroxycarbohydrates
are
successfully
utilized
first
time
N-glycosylation.
reaction
exhibits
a
broad
substrate
scope,
encompassing
76
examples,
demonstrates
high
stereoselectivity,
favoring
1,2-trans
selectivity
furanoses
α-selectivity
pyranoses.
It
also
site-selectivity
substrates
containing
multiple
N-atoms.
synthetic
utility
was
showcased
through
late-stage
functionalization
bioactive
pharmaceuticals
Olaparib,
Axitinib,
Metaxalone.
Mechanistic
studies
proved
presence
intermediates
importance
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(12), P. 8768 - 8779
Published: March 14, 2024
2′-Deoxynucleosides
and
analogues
play
a
vital
role
in
drug
development,
but
their
preparation
remains
significant
challenge.
Previous
studies
have
focused
on
β-2′-deoxynucleosides
with
the
natural
β-configuration.
In
fact,
isomeric
α-2′-deoxynucleosides
also
exhibit
diverse
bioactivities
even
better
metabolic
stability.
Herein,
we
report
that
both
α-
can
be
prepared
high
yields
stereoselectivity
using
remote
directing
diphenylphosphinoyl
(DPP)
group.
It
is
particularly
efficient
to
prepare
an
easily
accessible
3,5-di-ODPP
donor.
Instead
of
acting
as
H-bond
acceptor
2-(diphenylphosphinoyl)acetyl
(DPPA)
group
our
previous
for
syn-facial
O-glycosylation,
phosphine
oxide
moiety
here
acts
participating
enable
highly
antifacial
N-glycosylation.
This
proposed
participation
mechanism
supported
by
first
characterization
important
1,5-briged
P-heterobicyclic
intermediate
via
variable-temperature
NMR
spectroscopy.
Interestingly,
antiproliferative
assays
led
α-2′-deoxynucleoside
IC50
values
low
micromole
range
against
central
nervous
system
tumor
cell
lines
SH-SY5Y
LN229,
whereas
its
β-anomer
exhibited
no
inhibition
at
100
μM.
Furthermore,
DPP
significantly
enhanced
antitumor
activities
10
times.
Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: July 7, 2023
Catalytic
glycosylation
is
a
vital
transformation
in
synthetic
carbohydrate
chemistry
due
to
its
ability
expediate
the
large-scale
oligosaccharide
synthesis
for
glycobiology
studies
with
consumption
of
minimal
amounts
promoters.
Herein
we
introduce
facile
and
efficient
catalytic
employing
glycosyl
ortho-2,2-dimethoxycarbonylcyclopropylbenzoates
(CCBz)
promoted
by
readily
accessible
non-toxic
Sc(III)
catalyst
system.
The
reaction
involves
novel
activation
mode
esters
driven
ring-strain
release
an
intramolecularly
incorporated
donor-acceptor
cyclopropane
(DAC).
versatile
CCBz
donor
enables
highly
construction
O-,
S-,
N-glycosidic
bonds
under
mild
conditions,
as
exemplified
convenient
preparation
synthetically
challenging
chitooligosaccharide
derivatives.
Of
note,
gram-scale
tetrasaccharide
corresponding
Lipid
IV
modifiable
handles
achieved
using
strain-release
glycosylation.
These
attractive
features
promise
this
be
prototype
developing
next
generation
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(7), P. 4973 - 4984
Published: Feb. 8, 2024
In
the
presence
of
an
arylboronic
acid
catalyst,
azole-type
heterocycles,
including
purines,
tetrazoles,
triazoles,
indazoles,
and
benzo-fused
congeners,
undergo
regio-
stereoselective
N-glycosylations
with
furanosyl
pyranosyl
trichloroacetimidate
donors.
The
protocol,
which
does
not
require
stoichiometric
activators,
specialized
leaving
groups,
or
drying
agents,
provides
access
to
nucleoside
analogues
enables
late-stage
N-glycosylation
azole-containing
pharmaceutical
agents.
A
mechanism
involving
simultaneous
activation
glycosyl
donor
acceptor
by
organoboron
catalyst
has
been
proposed,
supported
kinetic
analysis
computational
modeling.
ACS Central Science,
Journal Year:
2024,
Volume and Issue:
10(8), P. 1515 - 1523
Published: July 10, 2024
is
one
of
the
leading
causes
nosocomial
infections
and
has
become
increasingly
resistant
to
multiple
antibiotics.
However,
development
novel
classes
antibacterial
agents
against
multidrug-resistant
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
62(43)
Published: July 12, 2023
Cyclodextrins
are
widely
used
as
carriers
of
small
molecules
for
drug
delivery
owing
to
their
remarkable
host
properties
and
excellent
biocompatibility.
However,
cyclic
oligosaccharides
with
different
sizes
shapes
limited.
Cycloglycosylation
ultra-large
bifunctional
saccharide
precursors
is
challenging
due
the
constrained
conformational
spaces.
Herein
we
report
a
promoter-controlled
cycloglycosylation
approach
synthesis
α-(1→6)-linked
mannosides
up
32-mer.
thioglycosides
(Z)-ynenoates
was
found
be
highly
dependent
on
promoters.
In
particular,
sufficient
amount
gold(I)
complex
played
key
role
in
proper
preorganization
transition
state,
providing
32-mer
polymannoside,
which
represents
largest
synthetic
polysaccharide
date.
NMR
experiments
computational
study
revealed
that
2-mer,
4-mer,
8-mer,
16-mer,
adopted
states
shapes.
Chemistry - A European Journal,
Journal Year:
2024,
Volume and Issue:
30(43)
Published: April 30, 2024
Reported
herein
is
a
new
HPLC-based
automated
synthesizer
(HPLC-A)
capable
of
temperature-controlled
synthesis
and
purification
carbohydrates.
The
developed
platform
allows
to
perform
various
protecting
group
manipulations
as
well
the
O-
N-glycosides.
A
fully
was
showcased
in
application
different
carbohydrate
derivatives
including
glycosides,
oligosaccharides,
glycopeptides,
glycolipids,
nucleosides.
Organic Letters,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 10, 2025
We
herein
present
the
development
of
a
novel
glycosylation
protocol
using
glycosyl
o-N-(o-methoxybenzamidoyl)-propynyl
benzoates
as
donors,
activated
solely
by
catalytic
amount
In(OTf)3,
eliminating
need
for
Au(I)
catalyst.
This
approach
offers
mild
and
orthogonal
conditions,
enabling
across
broad
substrate
scope
facilitating
versatile
one-pot
strategies
glycan
assembly.
Mechanistic
insights
suggest
that
In(OTf)3
serves
dual
roles
being
recruited
to
auxiliary
group
through
σ-coordination
while
activating
alkyne
via
π-interaction.
