Evolution of a Green and Sustainable Manufacturing Process for Belzutifan: Part 3─Development of a Scalable Enzymatic Oxidation Process
Jungchul Kim,
No information about this author
Victoria Zhang,
No information about this author
Kotoe Abe
No information about this author
et al.
Organic Process Research & Development,
Journal Year:
2024,
Volume and Issue:
28(2), P. 422 - 431
Published: Feb. 1, 2024
Belzutifan
(MK-6482)
is
an
FDA-approved
hypoxia
inducible
factor
2α
inhibitor
for
the
treatment
of
Von
Hippel–Lindau
disease-associated
renal
cell
carcinoma.
One
key
synthetic
steps
enzymatic
benzylic
hydroxylation
indanone.
Prior
to
optimization,
reactions
required
dilute
conditions
(100
volumes
water)
and
high
enzyme
loading
(50
wt
%)
achieve
target
conversion,
which
was
unsuitable
a
long-term
manufacturing
process.
Reduction
reaction
introduced
additional
complexity
large-scale
operations
due
low
solubility
components.
In
addition
development,
it
also
necessary
find
optimal
method
protein
residue
removal
from
mixture
isolate
high-quality
product.
We
present
here
our
efforts
overcome
these
challenges
ultimately
successfully
developed,
optimized,
demonstrated
at
multikilogram
scale
process
with
improved
mass
intensity
using
only
7.5
%
enzyme,
25
water,
1-octanol
as
unique
additive.
Language: Английский
Scaling Up Pharmaceutical Cocrystals
Published: March 29, 2025
Language: Английский
Accelerating reaction optimization through data-rich experimentation and machine-assisted process development
Reaction Chemistry & Engineering,
Journal Year:
2024,
Volume and Issue:
9(8), P. 2160 - 2170
Published: Jan. 1, 2024
The
acceleration
of
drug
substance
process
development
is
realized
by
employing
data-rich
experimentation,
optimization
algorithms,
and
data-driven
modeling
techniques.
Language: Английский
Active learning enabled reactor characterization for mass transfer in aerobic oxidation reactions
Reaction Chemistry & Engineering,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 18, 2024
A
generalizable
active
learning
framework
enables
accurate
prediction
of
mass
transfer
coefficients
(
k
L
a
),
and
iterative
design
experiments
to
efficiently
characterize
new
reactor
configurations
with
minimal
experimental
trials.
Language: Английский
Overcoming Bottlenecks towards Complete Biocatalytic Conversions and Complete Product Recovery
Reaction Chemistry & Engineering,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 14, 2024
Sustainable
processes
by
completing
biocatalytic
conversions
and
recovering
products
completely.
Language: Английский