The Journal of Organic Chemistry,
Journal Year:
2024,
Volume and Issue:
89(15), P. 11078 - 11082
Published: July 17, 2024
This
study
describes
the
synthesis
of
4-azafluorenone
core
in
a
single
operation
using
readily
available
starting
materials.
Condensation
an
amidrazone
with
ninhydrin
intercepts
intermediate
1,2,4-triazine
derivative,
which
engages
norbornadiene
merged
[4
+
2]/bis-retro[4
2]
sequence
to
deliver
azafluorenone
core.
The
tricyclic
established
this
manner
was
elaborated
onychine,
simplest
natural
product
alkaloid
family.
Organic Letters,
Journal Year:
2022,
Volume and Issue:
24(19), P. 3544 - 3548
Published: May 9, 2022
Herein,
chiral
Brønsted
acid-catalyzed
intramolecular
asymmetric
allylic
alkylation
of
indoles
with
primary
alcohols
is
described.
The
allyl
were
directly
employed
as
the
precursors
in
this
metal-free
protocol,
without
preactivation
or
any
additional
activating
reagents.
This
method
provides
convenient
synthesis
a
broad
range
functionalized
tetrahydrocarbazoles
excellent
yields
(≤97%)
good
enantioselectivity
(≤93%
ee).
optimal
conditions
are
compatible
for
gram-scale
reaction.
Journal of the American Chemical Society,
Journal Year:
2021,
Volume and Issue:
143(21), P. 7935 - 7939
Published: May 21, 2021
Altemicidin
and
related
Streptomyces-derived
monoterpene
alkaloids
possess
dense,
highly
polar
azaindane
cores
as
well
potent
cytotoxic
tRNA
synthetase
inhibitory
properties.
The
congested
α-amino
acid
motif
decorating
their
presumed
iridoid-like
core
structure
has
proven
to
be
both
a
synthetic
challenge
biosynthetic
mystery
date.
Herein,
we
report
distinct,
abiotic
strategy
these
resulting
in
concise
synthesis
of
altemicidin
from
simple
chemical
feedstocks.
Key
findings
include
the
exploitation
dearomative
pyridinium
addition
dipolar
cycloaddition
sequence
stereospecifically
install
quaternary
amine
moiety,
chemoselective
molybdenum-mediated
double
reduction
establish
fully
functionalized
nucleus
with
minimal
redox
manipulations.
JACS Au,
Journal Year:
2023,
Volume and Issue:
3(10), P. 2883 - 2893
Published: Oct. 12, 2023
Monoterpene
alkaloids
encompass
distinct
chemical
diversity
and
wide-ranging
bioactivity.
Their
compact
complexity
has
made
them
popular
as
synthetic
targets
inspired
many
strategies
tactics
in
the
field
of
heterocyclic
chemistry.
This
article
documents
evolution
a
program
aimed
at
accessing
unusual
sulfonamide-containing
natural
product
altemicidin,
which
was
generally
believed
to
be
monoterpene
alkaloid
throughout
our
entire
investigations
but
recently
been
found
originate
through
an
unexpected
quite
disparate
biosynthetic
pathway.
By
leveraging
pyridine
dearomatization/cycloaddition
strategy,
we
developed
concise
pathway
5,6-fused
bicyclic
azaindane
core
and,
after
significant
experimentation,
ultimate
synthesis
altemicidin
itself.
Tactics
productively
manipulate
multiple
functional
groups
present
on
this
highly
polar
scaffold
proved
challenging
were
eventually
realized
via
several
carefully
orchestrated
chemoselective
transformations–investments
that
paid
dividends
form
significantly
shorter
synthesis.
Surprisingly,
bond-forming
logic
between
presumed
abiotic
strategy
class
its
subsequently
identified
is
eerily
similar.
The
undirected
functionalization
of
pyridines
at
positions
remote
to
the
N-atom
remains
an
outstanding
problem
in
organic
synthesis.
inherent
challenges
associated
with
overriding
strong
directing
influence
embedded
within
pyridine
was
overcome
through
use
n-butylsodium
which
provided
us
avenue
generate
4-sodiopyridine
over
traditionally
observed
2-metalated
products
when
organolithium
bases
are
utilized.
freshly
generated
4-
sodiopyrdine
found
undergo
transition
metal
free
alkylation
reactions
directly
a
variety
primary
halides
bearing
diverse
functional
groups.
In
addition,
after
transmetalation
zinc
chloride
simple
and
efficient
Negishi
cross-coupling
protocol
formulated
for
aromatic
heteroaromatic
halides.
robustness
this
demonstrated
late-stage
installation
4-pyridyl
fragments
into
complex
active
pharmaceutical
ingredients
including
loratadine
prochlorperazine.
This
not
only
unlocks
new
prepare
4-subsituted
but
highlights
preparative
advantages
differences
organosodium
their
lithium
counterparts.
The Journal of Organic Chemistry,
Journal Year:
2024,
Volume and Issue:
89(15), P. 11078 - 11082
Published: July 17, 2024
This
study
describes
the
synthesis
of
4-azafluorenone
core
in
a
single
operation
using
readily
available
starting
materials.
Condensation
an
amidrazone
with
ninhydrin
intercepts
intermediate
1,2,4-triazine
derivative,
which
engages
norbornadiene
merged
[4
+
2]/bis-retro[4
2]
sequence
to
deliver
azafluorenone
core.
The
tricyclic
established
this
manner
was
elaborated
onychine,
simplest
natural
product
alkaloid
family.
