Angewandte Chemie,
Journal Year:
2024,
Volume and Issue:
136(42)
Published: July 15, 2024
Abstract
We
report
the
development
of
a
novel
synthetic
approach
for
highly
strained
atrop‐Tyr
C‐6‐to‐Trp
N‐1′
linkage,
which
can
be
executed
on
decagram
scale
using
modular
strategy
involving
palladium‐catalyzed
C−H
arylation
followed
by
Larock
macrocyclization.
The
first
total
synthesis
lapparbin
(
1
)
was
achieved
applying
this
strategy.
Furthermore,
utilizing
and
macrocyclization,
discovered
in
),
demonstrated
to
applicable
various
arbitrary
biaryl
linkages,
including
non‐natural
types.
ACS Chemical Biology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 2, 2025
Cross-link
containing
products
from
ribosomally
synthesized
and
post-translationally
modified
peptides
(RiPPs)
are
generated
by
radical
SAM
enzymes
(rSAM).
Here,
we
bioinformatically
expanded
rSAM
based
on
the
known
families
StrB,
NxxcB,
WgkB,
RrrB,
TqqB
GggB.
Through
in
vivo
functional
studies
E.
coli,
newly
identified
enzyme
WprB
Xenorhabdus
sp.
psl
was
found
to
catalyze
formation
of
a
cross-link
between
Trp-C5
Arg-Cγ
at
three
WPR
motifs
precursor
peptide
WprA.
This
represents
first
report
this
type
enzymes.
Journal of the American Chemical Society,
Journal Year:
2025,
Volume and Issue:
unknown
Published: May 12, 2025
Ribosomally
synthesized
and
post-translationally
modified
peptides
(RiPPs)
represent
a
valuable
class
of
natural
products,
often
featuring
macrocyclization,
which
enhances
stability
rigidity
to
achieve
specific
conformations,
frequently
underlying
antibiotic
activity.
ChlB
is
metalloenzyme
with
two
catalytic
domains─a
radical
S-adenosyl-l-methionine
(SAM)
domain
an
α-ketoglutarate-dependent
oxygenase─that
work
in
tandem
sequentially
form
three
cyclophanes
introduce
hydroxyl
groups
into
its
substrate
peptide,
ChlA.
Here,
we
present
the
crystal
structure
SAM
complex
ChlA,
revealing
mechanism
cyclophane
formation.
These
structures
also
elucidate
how
leader
sequence
ChlA
interacts
ChlB.
By
combining
structural,
vitro,
vivo
approaches,
determined
precise
formations,
interspersed
hydroxylation
events.
Our
findings
demonstrate
back-and-forth
movement
core
peptide
between
oxygenase
domain,
drives
stepwise
modification
process,
leading
fully
peptide.
A
modular,
atroposelective
total
synthesis
of
micitide
982
(1)
is
reported.
The
feature
this
report
the
gram-scale
C-H
biarylation
N-phthaloyl-L-alanine
followed
by
Larock
macrocyclization.
This
modular
approach
allowed
construction
a
highly
strained
atrop-Tyr-Trp
cross-linkage
with
unprecedented
atropisomerism,
as
well
first
(1).
RSC Chemical Biology,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Jan. 1, 2024
Radical
SAM
cyclophane
synthases
catalyze
C-C,
C-N,
and
C-O
crosslinking
reactions
in
the
biosynthesis
of
bioactive
peptide
natural
products.
Here,
we
studied
an
uncharacterized
rSAM
enzyme,
HtkB
from
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
unknown
Published: July 15, 2024
Abstract
We
report
the
development
of
a
novel
synthetic
approach
for
highly
strained
atrop‐Tyr
C‐6‐to‐Trp
N‐1′
linkage,
which
can
be
executed
on
decagram
scale
using
modular
strategy
involving
palladium‐catalyzed
C−H
arylation
followed
by
Larock
macrocyclization.
The
first
total
synthesis
lapparbin
(
1
)
was
achieved
applying
this
strategy.
Furthermore,
utilizing
and
macrocyclization,
discovered
in
),
demonstrated
to
applicable
various
arbitrary
biaryl
linkages,
including
non‐natural
types.
Chinese Journal of Chemistry,
Journal Year:
2024,
Volume and Issue:
42(23), P. 3023 - 3028
Published: Aug. 21, 2024
Comprehensive
Summary
The
first
total
synthesis
of
neopetromin,
featuring
the
highly
strained
Tyr
C‐6‐to‐Trp
N‐1’
linkage,
is
hereby
reported.
This
modular
synthetic
strategy,
employing
C—H
arylation
and
Larock
macrocyclization,
offers
a
novel
approach
to
various
RiPPs
natural
product
families.
