Journal of the American Chemical Society,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 17, 2024
Many
terpene
glycosides
exhibit
contrasteric
patterns
of
1,2-diol
glycosylation
in
which
the
more
hindered
alcohol
bears
a
sugar;
protection
less
only
increases
steric
repulsion.
Here,
we
report
method
for
using
new
sugar-linker
that
forms
cleavable,
10-membered
ring
with
high
efficiency,
leading
to
syntheses
cotylenin
E,
J,
and
ISIR-050.
Linker
selection
was
aided
by
DFT
calculations
side
reactions
stereoselectivity,
as
well
conformational
analyses
autoDFT,
Python
script
converts
SMILES
strings
DFT-optimized
ensembles.
Journal of the American Chemical Society,
Год журнала:
2022,
Номер
144(8), С. 3314 - 3329
Опубликована: Фев. 21, 2022
Natural
products
are
the
result
of
Nature's
exploration
biologically
relevant
chemical
space
through
evolution
and
an
invaluable
source
bioactive
small
molecules
for
biology
medicinal
chemistry.
Novel
concepts
discovery
new
compound
classes
based
on
natural
product
structure
may
enable
wider
space.
The
pseudo-natural
concept
merges
relevance
with
efficient
by
means
fragment-based
development
to
inspire
matter
de
novo
combination
fragments
in
unprecedented
arrangements.
novel
scaffolds
retain
biological
but
not
obtainable
known
biosynthetic
pathways
which
can
lead
chemotypes
that
have
unexpected
or
bioactivities.
Herein,
we
cover
workflow
design
development,
highlight
recent
examples,
discuss
a
cheminformatic
analysis
significant
portion
active
synthetic
compounds
were
found
be
products.
We
compare
as
human-made
equivalent,
i.e.
structure.
Angewandte Chemie International Edition,
Год журнала:
2021,
Номер
60(29), С. 15705 - 15723
Опубликована: Март 1, 2021
Pseudo-natural
products
(PNPs)
combine
natural
product
(NP)
fragments
in
novel
arrangements
not
accessible
by
current
biosynthesis
pathways.
As
such
they
can
be
regarded
as
non-biogenic
fusions
of
NP-derived
fragments.
They
inherit
key
biological
characteristics
the
guiding
product,
chemical
and
physiological
properties,
yet
define
small
molecule
chemotypes
with
unprecedented
or
unexpected
bioactivity.
We
iterate
design
principles
underpinning
PNP
scaffolds
highlight
their
syntheses
investigations.
provide
a
cheminformatic
analysis
collections
assessing
molecular
properties
shape
diversity.
propose
discuss
how
iterative
NP
structure,
design,
synthesis,
evaluation
PNPs
human-driven
branch
evolution
products,
that
is,
structure.
Organic Chemistry Frontiers,
Год журнала:
2021,
Номер
8(24), С. 7050 - 7076
Опубликована: Янв. 1, 2021
Functionalization
of
olefins
has
been
an
important
transformation
in
synthetic
chemistry.
This
review
will
focus
on
the
natural
product
synthesis
employing
MHAT
reaction
as
key
strategy.
Current Research in Chemical Biology,
Год журнала:
2022,
Номер
2, С. 100028 - 100028
Опубликована: Янв. 1, 2022
Chirality
is
an
inherent
aspect
of
biology,
and
interactions
between
biomolecules
are
often
influenced
by
stereochemistry
topographic
complexity.
This
has
implications
for
how
small-molecule
libraries
assembled
screening
campaigns
in
chemical
biology
drug
discovery.
Here
we
review
the
state
field
context
harnessing
chirality
as
a
source
information
at
chemistry-biology
interface.
We
further
highlight
emergence
containing
stereoisomeric
sets
compounds
concept
using
stereoselectivity
phenotype
and/or
target
engagement
way
to
prioritize
actionable
targets
streamline
identification
selective
potent
modulators
disease-relevant
biomolecules.
The
density
FDA-approved
drugs
effect
on
molecular
complexity
reported.
Finally,
axial
atroposelectivity
discussed
potential
expansions
aforementioned
concepts.
Journal of Medicinal Chemistry,
Год журнала:
2023,
Номер
66(18), С. 12739 - 12750
Опубликована: Авг. 31, 2023
The
fraction
of
sp3-hybridized
carbons
(Fsp3)
and
the
stereogenic
(FCstereo)
are
two
widely
employed
scores
molecular
complexity
with
strong
links
to
biologically
relevant
features.
However,
they
do
not
comprehensively
express
topology,
often
match
chemical
intuition
complexity.
We
propose
spacial
score
(SPS)
as
an
empirical
scoring
system
that
builds
upon
principle
underlying
Fsp3
FCstereo
expresses
a
compound
in
uniform
manner
on
highly
granular
scale.
size-normalized
SPS
(nSPS)
can
differentiate
distributions
natural
products
synthetic
compounds
is
applicable
analysis
biological
activity
data.
Analysis
ChEMBL
database
revealed
general
trends
increasing
selectivity
potency
nSPS.
also
be
used
advantageously
planning
synthesis
programs
for
direct
comparison
transformations
intermediates
reaction
sequences.
Chemical Communications,
Год журнала:
2023,
Номер
59(12), С. 1589 - 1604
Опубликована: Янв. 1, 2023
Although
alkynes
are
one
of
the
smallest
functional
groups,
they
among
most
versatile
building
blocks
for
organic
chemistry,
with
applications
ranging
from
biochemistry
to
material
sciences.
Alkynylation
reactions
have
traditionally
relied
on
use
acetylenes
as
nucleophiles.
The
discovery
and
development
ethynyl
hypervalent
iodine
reagents
allowed
greatly
expand
transfer
electrophilic
synthons.
In
this
feature
article
progress
in
field
since
2018
will
be
presented.
After
a
short
introduction
alkynylation
reagents,
developments
synthesis
alkynyl
discussed.
Their
recent
base-mediated
transition-metal
catalyzed
alkynylations
described.
Progress
radical-based
atom-economical
transformations
then
ACS Central Science,
Год журнала:
2024,
Номер
10(3), С. 519 - 528
Опубликована: Фев. 14, 2024
Research
into
natural
products
emerged
from
humanity's
curiosity
about
the
nature
of
matter
and
its
role
in
materia
medica
diverse
civilizations.
Plants
fungi,
particular,
supplied
materials
that
altered
behavior,
perception,
well-being
profoundly.
Many
active
principles
remain
well-known
today:
strychnine,
morphine,
psilocybin,
ephedrine.
The
potential
to
circumvent
constraints
supply
explore
properties
these
led
field
product
synthesis.
This
research
delivered
new
molecules
with
properties,
but
also
fundamental
insights
chemistry
nonmetal
elements
H,
C,
N,
O,
P,
S,
Se,
their
combinations,
i.e.,
organic
chemistry.
It
a
potent
culture
focused
on
bigger
races
finish
line,
perhaps
at
expense
actionable
next
steps.
About
20
years
ago,
began
contract
United
States.
solely
chemical
reaction
development,
especially
catalysis,
filled
void.
After
all,
reactions
mechanistic
insight
could
be
immediately
implemented
by
community,
so
it
became
hard
justify
lengthy
procurement
complex
molecule
sat
freezer
unused.
shift
coincided
divestment
portfolios
pharmaceutical
companies
an
emphasis
academic
applications-driven
research,
more
science.
However,
as
bioassays
tools
biology
become
widespread,
synthesis
finds
powerful
ally
allows
us
better
deliver
premise
field.
And
hard-won
can
encoded
digitally,
mined
data
science,
applied
challenges,
chemists
perturb
even
surpass
products.
21st
century
promises
developments,
both
interface
biology,
if
community
scientists
fosters
growth.
essay
tries
contextualize
for
broad
audience,
looks
ahead
transformation
coming
years,
expects
future
bright.
