Towards a Systematic Understanding of the Influence of Temperature on Glycosylation Reactions
Angewandte Chemie International Edition,
Год журнала:
2022,
Номер
61(15)
Опубликована: Янв. 15, 2022
Glycosidic
bond
formation
is
a
continual
challenge
for
practitioners.
Aiming
to
enhance
the
reproducibility
and
efficiency
of
oligosaccharide
synthesis,
we
studied
relationship
between
glycosyl
donor
activation
reaction
temperature.
A
novel
semi-automated
assay
revealed
diverse
responses
members
panel
thioglycosides
at
various
temperatures.
The
patterns
protecting
groups
thiol
aglycon
combine
cause
remarkable
differences
in
temperature
sensitivity
among
building
blocks.
We
introduce
concept
capture
experimental
insights,
reasoning
that
glycosylations
performed
below
this
reference
evade
deleterious
side
reactions.
Activation
temperatures
enable
simplified
treatment
facilitate
optimization
usage.
Isothermal
glycosylation
halved
equivalents
block
required
comparison
standard
"ramp"
regime
used
solution-
solid-phase
synthesis
to-date.
Язык: Английский
More than a Leaving Group: N‐Phenyltrifluoroacetimidate as a Remote Directing Group for Highly α‐Selective 1,2‐cis Glycosylation
Angewandte Chemie International Edition,
Год журнала:
2022,
Номер
61(21)
Опубликована: Март 10, 2022
The
anomeric
configuration
can
greatly
affect
the
biological
functions
and
activities
of
carbohydrates.
Herein,
we
report
that
N-phenyltrifluoroacetimidoyl
(PTFAI),
a
well-known
leaving
group
for
catalytic
glycosylation,
act
as
stereodirecting
challenging
1,2-cis
α-glycosylation.
Utilizing
rapidly
accessible
1,6-di-OPTFAI
glycosyl
donors,
TMSOTf-catalyzed
glycosylation
occurred
with
excellent
α-selectivity
broad
substrate
scope,
remaining
6-OPTFAI
be
cleaved
chemoselectively.
remote
participation
is
supported
by
first
characterization
crucial
1,6-bridged
bicyclic
oxazepinium
ion
intermediates
low-temperature
NMR
spectroscopy.
These
cations
were
found
to
relatively
stable
mainly
responsible
present
stereoselectivities.
Further
application
highlighted
in
reactions
toward
trisaccharide
heparins
well
convergent
synthesis
chacotriose
derivatives
using
bulky
2,4-di-O-glycosylated
donor.
Язык: Английский
Direct Synthesis of 2,6‐Dideoxy‐β‐glycosides and β‐Rhamnosides with a Stereodirecting 2‐(Diphenylphosphinoyl)acetyl Group
Angewandte Chemie International Edition,
Год журнала:
2022,
Номер
61(33)
Опубликована: Июнь 13, 2022
Anomeric
stereocontrol
is
usually
one
of
the
major
issues
in
synthesis
complex
carbohydrates,
particularly
those
involving
β-configured
2,6-dideoxyglycoside
and
d/l-rhamnoside
moieties.
Herein,
we
report
that
2-(diphenylphosphinoyl)acetyl
highly
effective
as
a
remote
stereodirecting
group
direct
these
challenging
β-glycosides
under
mild
conditions.
A
deoxy-trisaccharide
mimic
sugar
chain
landomycin
E
was
prepared
stereospecifically
high
yield.
The
synthetic
potential
also
highlighted
Citrobacter
freundii
O-antigens
composed
[→4)-α-d-Manp-(1→3)-β-d-Rhap(1→4)-β-d-Rhap-(1→]
repeating
unit,
wherein
convergent
assembly
up
to
nonasaccharide
realized
with
strongly
β-directing
trisaccharide
donor.
Variable-temperature
NMR
studies
indicate
presence
intermolecular
H-bonding
between
donor
bulky
acceptor
spectral
evidence
support
concept
hydrogen-bond-mediated
aglycone
delivery.
Язык: Английский
Direct Experimental Characterization of a Bridged Bicyclic Glycosyl Dioxacarbenium Ion by 1H and 13C NMR Spectroscopy: Importance of Conformation on Participation by Distal Esters
Angewandte Chemie International Edition,
Год журнала:
2021,
Номер
60(48), С. 25397 - 25403
Опубликована: Сен. 20, 2021
Low-temperature
NMR
studies
with
a
4-C-methyl-4-O-benzoyl
galactopyranosyl
donor
enable
the
observation
and
characterization
of
bridged
bicyclic
dioxacarbenium
ion
arising
from
participation
by
distal
ester.
Variable-temperature
reveal
this
to
decompose
at
temperatures
above
≈-30
°C.
In
absence
methyl
group,
formation
is
not
observed.
It
concluded
that
typical
secondary
esters
in
glycosylation
reactions
disfavored
ground
state
conformation
ester
which
it
stereoelectronically
impossible.
Methylation
converts
conformationally
more
labile
tertiary
ester,
removes
barrier,
renders
favorable.
Nevertheless,
minor
changes
selectivity
model
on
going
both
low
room
temperature
argue
against
group
being
major
stereodirecting
factor
even
for
system.
Язык: Английский
Direct Experimental Characterization of a Bridged Bicyclic Glycosyl Dioxacarbenium Ion by 1H and 13C NMR Spectroscopy: Importance of Conformation on Participation by Distal Esters
Angewandte Chemie,
Год журнала:
2021,
Номер
133(48), С. 25601 - 25607
Опубликована: Сен. 20, 2021
Abstract
Low‐temperature
NMR
studies
with
a
4‐
C
‐methyl‐4‐
O
‐benzoyl
galactopyranosyl
donor
enable
the
observation
and
characterization
of
bridged
bicyclic
dioxacarbenium
ion
arising
from
participation
by
distal
ester.
Variable‐temperature
reveal
this
to
decompose
at
temperatures
above
≈−30
°C.
In
absence
methyl
group,
formation
is
not
observed.
It
concluded
that
typical
secondary
esters
in
glycosylation
reactions
disfavored
ground
state
conformation
ester
which
it
stereoelectronically
impossible.
Methylation
converts
conformationally
more
labile
tertiary
ester,
removes
barrier,
renders
favorable.
Nevertheless,
minor
changes
selectivity
model
on
going
both
low
room
temperature
argue
against
group
being
major
stereodirecting
factor
even
for
system.
Язык: Английский
More than a Leaving Group: N‐Phenyltrifluoroacetimidate as a Remote Directing Group for Highly α‐Selective 1,2‐cis Glycosylation
Angewandte Chemie,
Год журнала:
2022,
Номер
134(21)
Опубликована: Март 10, 2022
Abstract
The
anomeric
configuration
can
greatly
affect
the
biological
functions
and
activities
of
carbohydrates.
Herein,
we
report
that
N
‐phenyltrifluoroacetimidoyl
(PTFAI),
a
well‐known
leaving
group
for
catalytic
glycosylation,
act
as
stereodirecting
challenging
1,2‐
cis
α‐glycosylation.
Utilizing
rapidly
accessible
1,6‐di‐OPTFAI
glycosyl
donors,
TMSOTf‐catalyzed
glycosylation
occurred
with
excellent
α‐selectivity
broad
substrate
scope,
remaining
6‐OPTFAI
be
cleaved
chemoselectively.
remote
participation
is
supported
by
first
characterization
crucial
1,6‐bridged
bicyclic
oxazepinium
ion
intermediates
low‐temperature
NMR
spectroscopy.
These
cations
were
found
to
relatively
stable
mainly
responsible
present
stereoselectivities.
Further
application
highlighted
in
reactions
toward
trisaccharide
heparins
well
convergent
synthesis
chacotriose
derivatives
using
bulky
2,4‐di‐
O
‐glycosylated
donor.
Язык: Английский
Direct Synthesis of 2,6‐Dideoxy‐β‐glycosides and β‐Rhamnosides with a Stereodirecting 2‐(Diphenylphosphinoyl)acetyl Group
Angewandte Chemie,
Год журнала:
2022,
Номер
134(33)
Опубликована: Июнь 13, 2022
Abstract
Anomeric
stereocontrol
is
usually
one
of
the
major
issues
in
synthesis
complex
carbohydrates,
particularly
those
involving
β‐configured
2,6‐dideoxyglycoside
and
d
/
l
‐rhamnoside
moieties.
Herein,
we
report
that
2‐(diphenylphosphinoyl)acetyl
highly
effective
as
a
remote
stereodirecting
group
direct
these
challenging
β‐glycosides
under
mild
conditions.
A
deoxy‐trisaccharide
mimic
sugar
chain
landomycin
E
was
prepared
stereospecifically
high
yield.
The
synthetic
potential
also
highlighted
Citrobacter
freundii
O‐antigens
composed
[→4)‐α‐
‐Man
p
‐(1→3)‐β‐
‐Rha
(1→4)‐β‐
‐(1→]
repeating
unit,
wherein
convergent
assembly
up
to
nonasaccharide
realized
with
strongly
β‐directing
trisaccharide
donor.
Variable‐temperature
NMR
studies
indicate
presence
intermolecular
H‐bonding
between
donor
bulky
acceptor
spectral
evidence
support
concept
hydrogen‐bond‐mediated
aglycone
delivery.
Язык: Английский
Zu einem Systematischen Verständnis des Einflusses der Temperatur auf Glykosylierungsreaktionen
Angewandte Chemie,
Год журнала:
2022,
Номер
134(15)
Опубликована: Янв. 15, 2022
Abstract
Die
Bildung
von
glykosidischen
Bindungen
ist
eine
ständige
Herausforderung
in
der
Praxis.
Mit
dem
Ziel,
die
Reproduzierbarkeit
und
Effizienz
Synthese
Oligosacchariden
zu
verbessern,
wird
hier
Beziehung
zwischen
Aktivierung
des
Glykosyl‐Donors
Reaktionstemperatur
untersucht.
Ein
neues
semi‐automatisches
Assay
zeigt,
dass
Mitglieder
einer
Gruppe
Thioglykoside
unterschiedlich
auf
bei
verschiedenen
Temperaturen
reagieren.
Muster
Schutzgruppen
Thio‐Aglykons
führen
bemerkenswerten
Unterschieden
Temperaturempfindlichkeit
Glykosyl‐Donors.
Wir
das
Konzept
Donor‐Aktivierungstemperatur
ein,
um
experimentelle
Erkenntnisse
erfassen,
folgern
daraus,
Glykosylierungen,
unterhalb
dieser
Referenztemperatur
durchgeführt
werden,
schädlichen
Nebenreaktionen
entgehen.
Kentnisse
über
Aktivierungstemperaturen
ermöglichen
vereinfachte
Temperaturbehandlung
erleichtern
Optimierung
Verwendung
Bei
isothermen
Glykosylierung
Aktivierungstemperatur
halbierten
sich
benötigten
Bausteinäquivalente
im
Vergleich
bisher
Lösungs‐
Festphasen‐Oligosaccharidsynthese
verwendeten
Standard‐“Rampen”‐Verfahren.