We
report
the
first
total
synthesis
of
monoterpene
indole
alkaloids
ophiorrhine
A
via
a
late
stage
bioinspired
intramolecular
Diels-Alder
cycloaddition
to
form
intricate
bridged
and
spirannic
polycyclic
system.
Several
strategies
were
investigated
construct
indolopyridone
moiety
ophiorrhiside
E,
postulated
biosynthetic
precursor
A.
Eventually,
Friedel-Crafts-type
coupling
indolyl-acetamide
with
secologanin-derived
acid
chloride
delivered
G.
Cyclode-hydratation
protected
latter
was
followed
by
desired
spontaneous
E
leading
Natural Product Reports,
Год журнала:
2021,
Номер
38(10), С. 1852 - 1886
Опубликована: Янв. 1, 2021
This
review
presents
the
chemistry
of
mavacuranes,
a
subfamily
monoterpene
indole
alkaloids,
from
their
isolation,
biosynthesis,
total
synthesis
to
tendency
assemble
with
other
partners
form
intricate
bis-indole
alkaloids.
Chemistry - A European Journal,
Год журнала:
2023,
Номер
29(18)
Опубликована: Янв. 21, 2023
Total
syntheses
of
geissoschizine-type
monoterpenoid
indole
alkaloids
(MTIAs)
are
reported.
An
intramolecular
Pictet-Spengler
cyclization
was
developed
for
the
selective
construction
3R
stereocenter.
The
first
total
synthesis
(+)-villocarine
A
then
achieved.
Furthermore,
highly
strained
(-)-apogeissoschizine
also
accomplished
in
an
aza-Michael
cyclization/E1cB
elimination/stereoselective
olefin
isomerization
sequence.
Finally,
(+)-geissoschizine,
a
common
biosynthetic
intermediate
MTIAs,
obtained
from
apogeissoschizine
through
ring-opening
along
with
release
ring
strain.
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
62(21)
Опубликована: Март 17, 2023
We
report
a
synthetic
endeavor
towards
the
highly
strained
pentacyclic
caged
framework
of
mavacuran
alkaloids
which
culminated
with
concise
total
synthesis
C-fluorocurine,
C-profluorocurine,
C-mavacurine,
normavacurine,
16-epi-pleiocarpamine
and
taberdivarine
H.
designed
strategy
involving
late-stage
construction
D
ring
by
Michael
addition
vinylic
nucleophile
to
2-indolyl
acrylate
moiety.
While
intramolecular
did
not
succeed,
we
were
able
perform
diastereoselective
unusual
intermolecular
1,4-addition
functionalized
vinyl
lithium
reagent
readily
accessible
acceptor
assistance
piperidine
nitrogen
atom
through
formation
complex
as
suggested
DFT
computations.
Final
cyclization
was
achieved
nucleophilic
substitution
form
an
ammonium
intermediate.
The
first
syntheses
C-profluorocurine
C-fluorocurine
finalized
dihydroxylation
C-mavacurine
pinacol
rearrangement,
respectively.
ACS Organic & Inorganic Au,
Год журнала:
2023,
Номер
3(6), С. 350 - 363
Опубликована: Окт. 9, 2023
Total
synthesis
is
a
field
in
constant
progress.
Its
practitioners
aim
to
develop
ideal
synthetic
strategies
build
complex
molecules.
As
such,
they
are
both
driving
force
and
showcase
of
the
progress
organic
synthesis.
In
this
Perspective,
we
discuss
recent
notable
total
syntheses.
The
syntheses
selected
herein
classified
according
key
strategic
considerations
for
each
approach.
Pharmaceutical Fronts,
Год журнала:
2023,
Номер
05(04), С. e227 - e242
Опубликована: Дек. 1, 2023
The
Pictet–Spengler
reaction
is
one
of
the
important
methodological
arsenals
in
synthetic
and
medicinal
chemistry,
acting
as
an
amenable
tool
for
preparing
tetrahydroisoquinoline,
tetrahydro-β-carbolines,
polycyclic
skeletons,
value-added
products.
More
than
100
years
after
its
initial
discovery,
reaction's
response
has
not
withdrawn
from
stage,
but
it
once
again
become
focus
attention
with
new
features.
review
summarizes
recent
advances
Pictet–Spengler-based
multicomponent
reactions
2007
to
2022,
including
three-component
four-component
cyclization
presence
metal
catalysts,
organocatalysts,
biological
enzyme
so
on.
These
protocols
provide
atom-/step
economic
approach
synthesis
a
library
chemical
entities.
Chemistry - A European Journal,
Год журнала:
2020,
Номер
26(71), С. 17190 - 17194
Опубликована: Сен. 2, 2020
Abstract
The
second‐generation
synthesis
of
(−)‐cymoside
as
well
the
formation
a
new
hexacyclic‐fused
furo[3,2‐
b
]indoline
framework
is
reported.
After
Pictet–Spengler
condensation
between
secologanin
tetraacetate
and
tryptamine,
course
cyclization
7‐hydroxyindolenine
intermediate,
generated
by
oxidation
with
an
oxaziridine,
depended
on
stereochemistry
3‐position.
3
‐
(
S
)‐strictosidine
delivered
efficiently
scaffold
cymoside
via
intramolecular
coupling
C16–C17
enol
ether,
while
R
)‐vincoside
directed
towards
reaction
C18–C19
terminal
alkene
unexpected
caged
compound.
Organic Letters,
Год журнала:
2021,
Номер
23(4), С. 1355 - 1360
Опубликована: Фев. 1, 2021
Toward
the
mavacurane
and
akuammilane
monoterpene
indole
alkaloids,
we
developed
divergent
oxidative
couplings
between
nucleus
(at
N1
or
C7)
C16-malonate
of
a
common
tricyclic
model
related
to
strictosidine
according
biosynthetic
hypothesis
postulated
by
Hesse
Schmid.
These
cyclizations
led
selectively
formation
N1-C16
bond
pleiocarpamine
C7-C16
strictamine.
We
were
then
able
obtain
scaffold
talbotine.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 25, 2024
Abstract
Plants
can
generate
structural
diversity
by
enzymatic
rearrangement
of
a
central
intermediate.
19
E
-geisssochizine
is
one
such
chemically
versatile
intermediate
that
plays
role
in
the
biosynthesis
monoterpene
indole
alkaloids
as
strychnine,
ibogaine
and
vinblastine.
Here
we
report
how
-geissoschizine
undergoes
oxidative
transformations
to
four
distinct
alkaloid
scaffolds
through
action
three
biosynthetic
enzymes.
Using
vitro
assays
gene
silencing,
demonstrate
these
cytochrome
P450
enzymes
medicinal
plant
Catharanthus
roseus
transform
-geisssochzine
into
strychnos,
sarpagan,
akuammiline
-type,
mavacurane-
type
alkaloids.
We
use
mutational
analysis
show
minimal
changes
active
site
similar
modulate
product
specificity.
This
work
highlights
substrate
reactivity
enzyme
mutations
synergistically
chemical
diversity.
Advanced Synthesis & Catalysis,
Год журнала:
2023,
Номер
365(8), С. 1224 - 1237
Опубликована: Март 29, 2023
Abstract
We
report
a
convenient
two‐step
approach
to
α‐amino
ketones
involving
cross‐coupling
and
oxidative
cleavage
sequence.
The
reaction
creates
divergent
functionalization
of
the
molecular
platform,
e.
g.,
N
‐(2‐bromoallyl)amine,
whereas
establishes
carbonyl
functionality.
This
strategy
allows
for
an
introduction
aryl/heteroaryl
alkyl
groups,
either
through
Suzuki
with
arylboronic
acids
or
via
dual
photoredox/Ni‐catalysis
install
groups.
provide
target
can
be
realized
by
treating
ozone
employing
milder
photochemical
protocols
oxygen
photoexcited
nitroarenes
as
oxidants.
successfully
demonstrate
scalability
this
protocol,
which,
together
its
simplicity,
generality,
ability
access
amino
that
are
inaccessible
other
strategies,
highlights
suitability
wide
range
applications
across
different
chemical
sciences.
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