We
report
a
Cu-catalysed
oxidative
coupling
of
aliphatic
amines
with
alkylboronic
esters
to
give
high
value
alkyl
amines,
products
found
widely
in
applications
from
medicinal
chemistry
materials
science.
This
operationally
simple
reaction,
which
can
be
performed
on
gram
scale,
runs
under
mild
conditions
and
exhibits
excellent
functional
group
tolerance.
The
terminal
oxidant
the
reaction
is
O2
air,
avoiding
need
for
additional
chemical
oxidants.
Investigation
into
mechanism
suggests
intermediacy
an
radical,
generated
boronic
ester
upon
activation
through
amino
radical
transfer
process.
To
demonstrate
its
utility
potential
late-stage
functionalization,
we
showcase
method
as
final
step
total
synthesis
TRPV
1
antagonist.
Chemical Society Reviews,
Год журнала:
2023,
Номер
53(1), С. 227 - 262
Опубликована: Дек. 7, 2023
This
review
summarized
NAD(P)H-dependent
amine
dehydrogenases
and
imine
reductases
which
catalyzes
asymmetric
reductive
amination
to
produce
optically
active
amines.
ACS Catalysis,
Год журнала:
2022,
Номер
12(21), С. 13619 - 13629
Опубликована: Окт. 24, 2022
Noncanonical
amino
acids
are
attractive
molecules
in
synthetic
chemistry
as
important
building
blocks
for
pharmaceuticals
and
agrochemicals.
Asymmetric
reductive
amination
of
prochiral
keto
catalyzed
by
glutamate
dehydrogenase
(GluDH)
is
an
efficient
process
the
production
these
molecules.
However,
stringent
substrate
specificity
lack
engineering
strategy
hampered
its
wide
application
substrate-oriented
chiral
carbon–nitrogen
bond
formation.
To
address
this
issue,
first,
recognition
mechanism
GluDH
was
investigated
using
CdGluDH
(an
NADH-dependent
from
Clostridium
difficile)
four
including
natural
three
non-natural
substrates
models
through
computational
simulation
experimental
verification.
Second,
a
based
on
reducing
pocket
steric
hindrance
tuning
enzyme–substrate
electrostatic
interactions
and/or
X–H···π
developed
to
systematically
redesign
binding
with
mutations
10
sites
accept
distinct
substrates.
As
result,
tailor-made
variants
were
created
synthesize
corresponding
high-value
products,
l-norvaline,
l-phosphinothricin,
l-homophenylalanine,
specific
activities
improved
2.3-fold,
916.2-fold,
no
activity
66.64
U/mg,
respectively.
Finally,
efficiency
tested
simulated
industrial
catalytic
reaction,
demonstrating
that
enzyme
promising
enhancing
noncanonical
GluDHs.
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
62(48)
Опубликована: Авг. 28, 2023
Biocatalytic
cascades
are
a
powerful
tool
for
building
complex
molecules
containing
oxygen
and
nitrogen
functionalities.
Moreover,
the
combination
of
multiple
enzymes
in
one
pot
offers
possibility
to
minimize
downstream
processing
waste
production.
In
this
review,
we
illustrate
various
recent
efforts
development
multi-step
syntheses
involving
C-O
C-N
bond-forming
produce
high
value-added
compounds,
such
as
pharmaceuticals
polymer
precursors.
Both
vitro
vivo
examples
discussed,
revealing
respective
advantages
drawbacks.
The
use
engineered
boost
outcome
is
also
addressed
current
co-substrate
cofactor
recycling
strategies
presented,
highlighting
importance
atom
economy.
Finally,
tools
overcome
challenges
multi-enzymatic
oxy-
amino-functionalization
reactions
including
flow
systems
with
immobilized
biocatalysts
confined
nanomaterials.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(12)
Опубликована: Янв. 18, 2024
Abstract
Enzymes
and
peptide
catalysts
consist
of
the
same
building
blocks
but
require
vastly
different
environments
to
operate
best.
Herein,
we
show
that
an
enzyme
a
catalyst
can
work
together
in
single
reaction
vessel
catalyze
two‐step
cascade
with
high
chemo‐
stereoselectivity.
Abundant
linear
alcohols,
nitroolefins,
alcohol
oxidase,
tripeptide
provided
chiral
γ‐nitroaldehydes
aqueous
buffer.
High
yields
(up
92
%)
stereoselectivities
98
%
ee)
were
achieved
for
through
rational
design
identification
common
conditions.
C-H
oxyfunctionalisation
remains
a
distinct
challenge
for
synthetic
organic
chemists.
Oxygenases
and
peroxygenases
(grouped
here
as
"oxygenating
biocatalysts")
catalyse
the
oxidation
of
substrate
with
molecular
oxygen
or
hydrogen
peroxide
oxidant.
The
application
oxygenating
biocatalysts
in
synthesis
has
dramatically
increased
over
last
decade,
producing
complex
compounds
potential
uses
pharmaceutical
industry.
This
review
will
focus
on
hydroxyl
functionalisation
using
tool
drug
discovery
development.
Established
biocatalysts,
such
cytochrome
P450s
flavin-dependent
monooxygenases,
have
widely
been
adopted
this
purpose,
but
can
suffer
from
low
activity,
instability
limited
scope.
Therefore,
emerging
which
offer
an
alternative
also
be
covered,
well
considering
ways
these
hydroxylation
biotransformations
applied
development,
late-stage
(LSF)
biocatalytic
cascades.
European Journal of Organic Chemistry,
Год журнала:
2022,
Номер
2022(22)
Опубликована: Май 16, 2022
Abstract
Inspired
by
nature,
synthetic
chemists
try
to
mimic
the
efficient
metabolic
networks
in
living
organisms
build
complex
molecules
combining
different
types
of
catalysts
same
reaction
vessel.
These
multistep
cascade
processes
provide
many
advantages
procedures,
resulting
higher
productivities
with
lower
waste
generation
and
cost.
However,
chemo‐
biocatalysts
can
be
challenging
as
conditions
might
differ
greatly.
As
a
highly
multidisciplinary
field
that
benefits
from
advances
chemical
catalysis,
molecular
biology
engineering,
this
area
study
is
rapidly
progressing.
In
Review,
we
highlight
recent
trends
construction
chemoenzymatic
one‐pot
cascades
access
chiral
compounds
well
strategies
solve
current
challenges
field.
Chemistry - A European Journal,
Год журнала:
2024,
Номер
30(19)
Опубликована: Янв. 3, 2024
Abstract
We
report
a
Cu‐catalyzed
oxidative
coupling
of
aliphatic
amines
with
benzylic
and
boronic
esters
to
give
high
value
alkyl
amines,
products
found
widely
in
applications
from
medicinal
chemistry
materials
science.
This
operationally
simple
reaction,
which
can
be
performed
on
gram
scale,
runs
under
mild
conditions
exhibits
broad
functional
group
tolerance.
The
terminal
oxidant
the
reaction
is
O
2
air,
avoiding
need
for
additional
chemical
oxidants.
Investigation
into
mechanism
suggests
that
ester
activated
by
an
aminyl
radical,
formed
through
oxidation
amine
Cu
catalyst,
key
radical
intermediate.
To
demonstrate
its
utility
potential
late‐stage
functionalization,
we
showcase
method
as
final
step
total
synthesis
TRPV1
antagonist.
