Direct Synthesis of α- and β-2′-Deoxynucleosides with Stereodirecting Phosphine Oxide via Remote Participation
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(12), С. 8768 - 8779
Опубликована: Март 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.
Язык: Английский
Recent Advance in the β‐Stereoselective Synthesis of 2‐Deoxy Glycosides
Asian Journal of Organic Chemistry,
Год журнала:
2024,
Номер
13(8)
Опубликована: Май 31, 2024
Abstract
Compounds
containing
a
2‐deoxy
β
‐glycoside
linkage
play
important
roles
in
carbohydrate
chemistry,
serving
as
potential
therapies
with
significant
biological
properties.
From
the
viewpoint
of
synthesis,
many
strategies
developed
recent
years
targeted
stereoselective
construction
glycosides.
This
review
aims
to
summarise
advances
synthetic
routes
toward
β‐
glycosides
over
last
decade.
Where
associated,
practical
applications
these
total
synthesis
natural
products
are
highlighted.
Язык: Английский