Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(44), P. 30242 - 30251
Published: Oct. 25, 2024
Dhilirane-type
meroterpenoids
(DMs)
featuring
a
6/6/6/5/5
ring
system
represent
rare
group
of
fungal
meroterpenoids.
To
date,
merely
11
DMs
have
been
isolated
or
derived,
leaving
their
chemical
diversity
predominantly
unexplored.
Herein,
we
leverage
an
understanding
biosynthesis
to
develop
workflow
for
discovery
by
genome
mining,
metabolite
analysis,
and
tailoring
enzyme
catalysis.
Twenty-three
new
DMs,
including
seven
unprecedented
scaffolds,
were
consequently
identified.
An
α-ketoglutarate
(α-KG)-dependent
oxygenase
DhiD
was
found
catalyze
the
stereodivergent
contraction
dhilirolide
D
form
dhilirane
skeleton;
while
cytochrome
P450
DhiH
reshaped
structural
establishing
diverse
C-C
bonds
oxidation.
Crystallographic
mutagenesis
experiments
provide
molecular
basis
reaction
its
products.
Notably,
exhibits
substrate-controlled
catalytic
versatility
in
expansion
through
contraction,
hydroxylation,
dehydrogenation,
epoxidation,
isomerization,
epimerization,
α-ketol
cleavage.
Bioassay
results
demonstrated
that
obtained
exhibited
anti-inflammatory
insecticidal
activities.
Our
work
provides
insight
into
nature's
arsenal
DM
functional
α-KG-dependent
P450,
which
can
be
applied
target
diversification
DM-type
natural
Organic & Biomolecular Chemistry,
Journal Year:
2020,
Volume and Issue:
19(8), P. 1644 - 1704
Published: Dec. 10, 2020
Fungal
meroterpenoids
are
secondary
metabolites
from
mixed
terpene-biosynthetic
origins.
Their
intriguing
chemical
structural
diversification
and
complexity,
potential
bioactivities,
pharmacological
significance
make
them
attractive
targets
in
natural
product
chemistry,
organic
synthesis,
biosynthesis.
This
review
provides
a
systematic
overview
of
the
isolation,
features,
biological
activities,
fungal
biodiversity
1585
novel
79
genera
terrestrial
marine-derived
fungi
including
macrofungi,
Basidiomycetes,
441
research
papers
2009-2019.
Based
on
nonterpenoid
starting
moiety
their
biosynthesis
pathway,
were
classified
into
four
categories
(polyketide-terpenoid,
indole-,
shikimate-,
miscellaneous-)
with
polyketide-terpenoids
(mainly
tetraketide-)
shikimate-terpenoids
as
primary
source.
Basidiomycota
produced
37.5%
meroterpenoids,
mostly
shikimate-terpenoids.
The
Ganoderma,
Penicillium,
Aspergillus,
Stachybotrys
dominant
producers.
Moreover,
about
56%
display
various
pronounced
cytotoxicity,
enzyme
inhibition,
antibacterial,
anti-inflammatory,
antiviral,
antifungal
activities.
It's
exciting
that
several
antroquinonol
4-acetyl
B
developed
phase
II
clinically
used
drugs.
We
assume
diversity
therapeutic
these
will
provide
biologists
medicinal
chemists
large
promising
sustainable
treasure-trove
for
drug
discovery.
Journal of the American Chemical Society,
Journal Year:
2023,
Volume and Issue:
145(33), P. 18161 - 18181
Published: Aug. 8, 2023
Bolstered
by
recent
advances
in
bioinformatics,
genetics,
and
enzyme
engineering,
the
field
of
chemoenzymatic
synthesis
has
enjoyed
a
rapid
increase
popularity
utility.
This
Perspective
explores
integration
enzymes
into
multistep
chemical
syntheses,
highlighting
unique
potential
biocatalytic
transformations
to
streamline
complex
natural
products.
In
particular,
we
identify
four
primary
conceptual
approaches
illustrate
each
with
number
landmark
case
studies.
Future
opportunities
challenges
are
also
discussed.
Natural Product Reports,
Journal Year:
2020,
Volume and Issue:
38(3), P. 566 - 585
Published: Oct. 1, 2020
Covering:
up
to
July
2020Fungal
meroterpenoid
cyclases
are
a
recently
discovered
emerging
family
of
membrane-integrated,
non-canonical
terpene
cyclases.
They
catalyze
the
conversion
hybrid
isoprenic
precursors
towards
complex
scaffolds
and
therefore
great
importance
in
structure
diversification
biosynthesis.
The
products
these
pathways
exhibit
intriguing
molecular
highly
potent
bioactivities,
making
them
privileged
structures
from
Nature
attractive
candidates
for
drug
development
or
industrial
applications.
This
review
will
provide
comprehensive
comparative
view
on
fungal
cyclases,
their
chemistries
scaffold
formation
step
polycyclic
natural
products.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
unknown
Published: April 11, 2024
Meroterpenoid
clavilactones
feature
a
unique
benzo-fused
ten-membered
carbocyclic
ring
unit
with
an
α,β-epoxy-γ-lactone
moiety,
forming
intriguing
10/5/3
tricyclic
nested
skeleton.
These
compounds
are
good
inhibitors
of
the
tyrosine
kinase,
attracting
lot
chemical
synthesis
studies.
However,
natural
enzymes
involved
in
formation
skeleton
remain
unexplored.
Here,
we
identified
gene
cluster
responsible
for
biosynthesis
clavilactone
A
basidiomycetous
fungus
Clitocybe
clavipes.
We
showed
that
key
cytochrome
P450
monooxygenase
ClaR
catalyzes
diradical
coupling
reaction
between
intramolecular
hydroquinone
and
allyl
moieties
to
form
unit,
followed
by
ClaT
exquisitely
stereoselectively
assembles
moiety
biosynthesis.
unprecedentedly
acts
as
macrocyclase
catalyze
oxidative
cyclization
isopentenyl
nonterpenoid
macrocycle,
multifunctional
ten-electron
oxidation
accomplish
clavilactones.
Our
findings
establish
foundation
efficient
production
using
synthetic
biology
approaches
provide
mechanistic
insights
into
macrocycle
fungal
meroterpenoids.
Natural Product Reports,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 1, 2025
Four
cutting-edge
crystallography
strategies
for
structure
elucidation
of
natural
products
that
are
difficult
to
crystallize
or
in
nanocrystalline
form.
Journal of the American Chemical Society,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 4, 2025
The
synthesis
of
complex
natural
products
requires
efficient
control
over
chemoselectivity,
stereoselectivity,
and
regioselectivity.
Berkeleyacetals,
a
subfamily
3,5-dimethylorsellinic
acid
(DMOA)-derived
meroterpenoids,
pose
substantial
synthetic
challenges
due
to
their
densely
functionalized
highly
oxidized
architectures,
which
have
constrained
efforts.
Here,
we
present
the
first
total
this
class
DMOA-derived
specifically
(+)-berkeleyacetal
D
(+)-peniciacetal
I.
Our
approach
features
chemoselective
deprotonation
followed
by
an
intramolecular
single-electron
transfer
(SET)
from
enolate
alkyl
bromide,
enabling
construction
2,3-dihydrofuran
ring
in
berkeleyacetal
D.
Additional
selective
transformations
include
endo-selective
Diels–Alder
reaction,
methylations
semihydrogenation
[3]dendralene,
solvent-controlled
diastereoselective
epoxidation.
Beyond
providing
route
these
congested
products,
our
study
offers
mechanistic
insights
into
achieving
selectivity
assembly
architecturally
demanding
molecules.
Journal of the American Chemical Society,
Journal Year:
2021,
Volume and Issue:
143(43), P. 18280 - 18286
Published: Oct. 20, 2021
trans-syn-Fused
drimane
meroterpenoids
are
unique
natural
products
that
arise
from
contra-thermodynamic
polycyclizations
of
their
polyene
precursors.
Herein
we
report
the
first
total
syntheses
four
trans-syn-fused
meroterpenoids,
namely
polysin,
N-acetyl-polyveoline,
chrodrimanin
C,
and
verruculide
A,
in
7–18
steps
sclareolide.
The
unit
is
accessed
through
an
efficient
acid-mediated
C9
epimerization
Subsequent
applications
enzymatic
C–H
oxidation
contemporary
annulation
methodologies
install
requisite
C3
hydroxyl
group
enable
rapid
generation
structural
complexity
to
provide
concise
access
these
products.
Angewandte Chemie International Edition,
Journal Year:
2022,
Volume and Issue:
61(16)
Published: Feb. 7, 2022
Capitalizing
on
the
late-stage
diversification
of
an
essential
1,3-diene
intermediate,
we
describe
herein
a
9-step
enantioselective
total
synthesis
(+)-hyperforin
and
(+)-pyrohyperforin,
starting
from
commercially
available
allylacetone.
Our
convergent
features
series
critical
reactions:
1)
deconjugative
α-alkylation
α,β-unsaturated
acid
using
chiral
lithium
amides
as
noncovalent
stereodirecting
auxiliaries;
2)
HfCl4
-mediated
carbonyl
α-tert-alkylation
to
forge
intricate
bicyclo[3.3.1]nonane
framework;
3)
abiotic
cascade
pyran
formation;
4)
selective
1,4-semihydrogenation
polyenes.
During
course
our
synthesis,
also
identified
1,2-cyclopropanediol
overbred
intermediate
which
was
responsible
for
precursor
formation
through
controlled
fragmentation.
Journal of the American Chemical Society,
Journal Year:
2022,
Volume and Issue:
144(28), P. 12970 - 12978
Published: July 6, 2022
3,5-Dimethylorsellinic
acid
(DMOA)-derived
spiromeroterpenoids
are
a
unique
natural
product
family
with
attractive
structures,
unconventional
stereochemistry,
and
potent
biological
activities.
Herein,
we
report
the
first
asymmetric
total
syntheses
of
asnovolins,
DMOA-derived
spiromeroterpenoids.
The
spirocyclic
skeleton
was
efficiently
assembled
through
sterically
hindered
bis-neopentyl
1,2-addition
coupling/oxidative
Michael
addition
sequence.
unusual
axial
C12-methyl
stereochemistry
established
via
metal
hydrogen
atom
transfer
(MHAT)
reduction
involving
chair-to-boat
conformational
change.
mechanism
HAT
process
studied
both
deuterium
labeling
computational
studies.
Attempted
late-stage
alkene
isomerization
an
exocyclic
enone
proved
to
be
challenging
resulted
in
hetero-Diels–Alder
dimerization,
which
ultimately
led
development
alternative
desaturation/coupling
Endgame
core
modifications
including
orthogonal
desaturation,
Sc(III)-promoted
regioselective
Baeyer–Villiger
oxidation,
Meerwein–Ponndorf–Verley
enabled
collective
five
asnovolin-related
products.
This
study
demonstrates
utility
anionic
fragment
coupling
assemble
congested
molecular
framework
provides
foundation
for
synthesis
spiromeroterpenoid
congeners
higher
oxidation
states