A5037569609- Medieval Literature and History
- Historical and Archaeological Studies
- Linguistics and language evolution
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Folklore, Mythology, and Literature Studies
- Fashion and Cultural Textiles
- Linguistics and Cultural Studies
- Art, Politics, and Modernism
- Literature Analysis and Criticism
- Classical Antiquity Studies
- Historical Studies of British Isles
- Byzantine Studies and History
- Historical, Literary, and Cultural Studies
- Scottish History and National Identity
- Eurasian Exchange Networks
- Marine and fisheries research
- Asymmetric Synthesis and Catalysis
- Contemporary Literature and Criticism
- Chemical Synthesis and Analysis
- Maritime and Coastal Archaeology
- Historical and Architectural Studies
- Diverse Musicological Studies
- Marine and environmental studies
- Synthetic Organic Chemistry Methods
Merck & Co., Inc., Rahway, NJ, USA (United States)
2012-2024
Culham Science Centre
2022
University of Cambridge
2022
Northwestern University
2005-2020
ConocoPhillips (United States)
2018
University of British Columbia
2015
Vancouver Clinic
2014
University of California, Los Angeles
2013
City College of New York
2010-2012
University of North Carolina Wilmington
2011-2012
Molnupiravir (MK-4482) is an investigational antiviral agent that under development for the treatment of COVID-19. Given potential high demand and urgency this compound, it was critical to develop a short sustainable synthesis from simple raw materials would minimize time needed manufacture supply molnupiravir. The route reported here enabled through invention novel biocatalytic cascade featuring engineered ribosyl-1-kinase uridine phosphorylase. These enzymes were deployed with...
Biocatalytic oxidations are an emerging technology for selective C-H bond activation. While promising a range of oxidations, practical use enzymes catalyzing aerobic hydroxylation is presently limited by their substrate scope and stability under industrially relevant conditions. Here, we report the engineering application non-heme iron α-ketoglutarate-dependent dioxygenase direct stereo- regio-selective non-native fluoroindanone en route to oncology treatment belzutifan, replacing five-step...
An improved synthesis has been developed for belzutifan, a novel HIF-2α inhibitor the treatment of Von Hippel–Lindau (VHL) disease-associated renal cell carcinoma (RCC). The efficiency previous supply and commercial routes was encumbered by lengthy 5-step sequence, needed to install chiral benzylic alcohol traditional methods. Identification directed evolution FoPip4H, an iron/α-ketoglutarate dependent hydroxylase, enabled direct enantioselective C–H hydroxylation simple indanone starting...
Herein, we describe a strategy for converting catalytically inactive, highly crystalline nanoparticle superlattices embedded in silica into active, porous structures through superlattice assembly and calcination. First, body-centered cubic (bcc) is synthesized the of two sets 5 nm gold nanoparticles chemically modified with DNA bearing complementary sticky end sequences. These are calcined at 350 °C to provide access catalytic surface sites. The maintains its bcc ordering has area 210 m2/g....
Anomeric O-alkylation/arylation is applied to the synthesis of 2-deoxy-β-glycosides. Treatment lactols with NaH in dioxane followed by addition electrophiles leads formation 2-deoxy-β-glycosides high yield and selectivity. The β-selectivity observed here demonstrates a powerful stereoelectronic effect for stereoselective acetals under kinetic control.
Membranes are a compelling capture technology that has the advantages of no hazardous chemical use or emissions, steam usage, ability to co-capture water, simple operation, and benefits modular membrane skids. For more than dozen years, with support U.S. Department Energy (DOE), Membrane Technology Research, Inc. (MTR) been developing post-combustion carbon system based on our Polaris™ membrane. Prior research, development, field testing brought this readiness level (TRL) 6. This includes...
Using the HIV-1 protease binding mode of MK-8718 and PL-100 as inspiration, a novel aspartate bicyclic piperazine sulfonamide core was designed synthesized. The resulting inhibitor containing this showed an 60-fold increase in enzyme affinity 10-fold antiviral activity relative to MK-8718.
Theoretical and experimental field studies of 14 C uptake by marine phytoplankton were carried out to determine environmental conditions required for the technique measure net photosynthesis. Results theoretical indicate that rapidly metabolizing populations (rate constants gross photosynthesis respiration 0.1 h −1 0.007 respectively) may saturate with after about 30 continuous irradiation. a minimum 24 are be measured when daily irradiations exceed 20 cal cm −2 nutrient limitation does not...
Low-dose-rate brachytherapy is a radiation treatment method for localized prostate cancer. The standard of care this procedure to acquire transrectal ultrasound images the in order devise plan deliver sufficient dose cancerous tissue. Brachytherapy planning involves delineation contours these images, which closely follow boundary, i.e., clinical target volume. This process currently performed either manually or semi-automatically, requires user interaction landmark initialization. In paper,...
Molnupiravir (MK-4482) is an investigational direct-acting antiviral agent that under development for the treatment of COVID-19. Given potential high demand this compound, it was critical to develop a sustainable and efficient synthesis from commodity raw materials. The three-step route we report here embodies shortest possible molnupiravir, enabled through invention novel biocatalytic cascade final condensation step. Each step occurs in over 95% yield only utilizes widely available reagents...
A scandium triflate catalyzed, diastereoselective cyclization between aldehydes and β-hydroxy dioxinones has been discovered. This process capitalizes on the untapped nucleophilicity of embedded enol ether within dioxinone core. The bicyclic compounds from resulting can be isolated, or alternatively, alkoxide nucleophiles directly added. in situ addition fragments rings delivers 3-carboxy-substituted tetrahydropyran-4-ones good yields with high levels diastereoselectivity.
All things converge: A highly convergent synthesis of (−)-okilactomycin utilizes a Prins-type Maitland–Japp cyclization for the fragment assembly two complex intermediates (see scheme). The also employs diastereoselective Lewis acid promoted Diels–Alder reaction and an olefin ring-closing metathesis to close strained 11-membered macrocycle.
Aziridines are important synthetic intermediates which readily undergo ring-opening reactions. It is demonstrated that electron-rich phosphines efficient catalysts for the regioselective rearrangement of N-acylaziridines to oxazolines. The reactions occur in excellent yield under neutral conditions. Evidence provided an addition/elimination mechanism by generation a phosphonium intermediate. Similar may be useful development alternate aziridine processes and stereoselective synthesis with...
A common challenge when performing surface-based registration of images is ensuring that the surfaces accurately represent consistent anatomical boundaries. Image segmentation may be difficult in some regions due to either poor contrast, low slice resolution, or tissue ambiguities. To address this, we present a novel non-rigid surface method designed register two partial surfaces, capable ignoring where boundary unclear. Our probabilistic approach incorporates prior geometric information...
The development of a commercial manufacturing route to verubecestat (MK-8931) is described, highlights which include the application continuous processing step outcompete fast proton transfer in Mannich-type ketimine addition, copper-catalyzed amidation reaction, and an optimized guanidinylation procedure form key iminothiadiazine dioxide core.
An enantioselective arylation reaction catalyzed by palladium complexed with substituted phosphinooxazoline (PHOX) ligands is described. Aza-quaternary stereocenters are readily accessible through the between cyclic iminosulfates and a wide variety of arylboronic acids, including electron-poor ortho-substituted acids. This was applied to preparation verubecestat, which currently undergoing clinical evaluation for treatment Alzheimer's disease.