A5005218140- Oxidative Organic Chemistry Reactions
- Radical Photochemical Reactions
- Crystallization and Solubility Studies
- Cyclopropane Reaction Mechanisms
- X-ray Diffraction in Crystallography
- Chemical synthesis and alkaloids
- Marine Sponges and Natural Products
- Thermal and Kinetic Analysis
- Synthetic Organic Chemistry Methods
- Chemistry and Chemical Engineering
- Chemical Synthesis and Analysis
- Edible Oils Quality and Analysis
- Fluorine in Organic Chemistry
- Cholesterol and Lipid Metabolism
- Click Chemistry and Applications
- Energetic Materials and Combustion
- Traditional and Medicinal Uses of Annonaceae
- Risk and Safety Analysis
- Synthesis and Catalytic Reactions
- Phytochemistry and Bioactivity Studies
- Carbohydrate Chemistry and Synthesis
- Chemical Synthesis and Reactions
- Chemical Safety and Risk Management
- Asymmetric Synthesis and Catalysis
- Catalytic Cross-Coupling Reactions
Vertex Pharmaceuticals (United States)
2020-2024
Pfizer (United States)
2003-2018
Pearl River Community College
2012
University of Pennsylvania
2007-2011
Philadelphia University
2007-2010
Monell Chemical Senses Center
2007-2010
Dartmouth College
2004-2007
University of Florida
2004
Tau is a microtubule-associated protein that promotes microtubule assembly and stability. In Alzheimer's disease related tauopathies, tau fibrillizes aggregates into neurofibrillary tangles. Recently, oleocanthal isolated from extra virgin olive oil was found to display non-steroidal anti-inflammatory activity similar ibuprofen. As our unpublished data indicates an inhibitory effect of on amyloid beta peptide fibrillization, we reasoned it might inhibit fibrillization as well. Herein,...
Oleocanthal, a major phenolic compound in extra-virgin olive oil with antiinflammatory properties, elicits an unusual oral pungency sensed almost exclusively the throat. This contrasts most other common irritants, such as cinnamaldehyde, capsaicin, and alcohol, which irritate mucus membranes throughout cavity. Here, we show that this rare irritation pattern is consequence of both specificity oleocanthal for single sensory receptor anatomical restriction to pharynx, within We demonstrate,...
The design, synthesis, and application of [4-(acetylamino)phenyl]imidodisulfuryl difluoride (AISF), a shelf-stable, crystalline reagent for the synthesis sulfur(VI) fluorides, is described. utility AISF demonstrated in diverse array aryl fluorosulfates sulfamoyl fluorides under mild conditions. Additionally, single-step preparation was developed that installed bis(fluorosulfonyl)imide group on acetanilide utilizing an oxidative C–H functionalization protocol.
Amide couplings are one of, if not the most common chemical reactions performed in pharmaceutical industry. Many amide bonds generated with help of highly active peptide coupling reagents. These reagents have garnered wide use industry, but many contain high-energy functional groups. As a result, significant time is spent assessing thermal stability these before scale-up commences. This paper assesses 45 by differential scanning calorimetry and accelerating rate calorimetry. Those compounds...
Abstract Objective In joint diseases, cartilage homeostasis is disrupted by mechanisms that are driven combinations of biologic factors vary according to the disease process. osteoarthritis (OA), biomechanical stimuli predominate, with up‐regulation both catabolic and anabolic factors. Likewise, OA progression characterized increased nitric oxide (NO) production, which has been associated degradation. Given relevance degenerative diseases in our society, development a novel pharmacologic...
Phenolic compounds extracted from extra virgin olive oil have attracted considerable recent attention. One of the components, (-)-oleocanthal (1), an inhibitor COX-1 and COX-2 enzymes, possesses similar potency as NSAID ibuprofen. In this, a full account, we disclose first- now second-generation syntheses both enantiomers oleocanthals, well first synthesis closely related (-)-deacetoxy-oleuropein aglycone series analogues for structure activity studies. To demonstrate utility synthesis,...
Process safety groups in the pharmaceutical industry are important components of active ingredient (API) development through its life cycle from discovery to commercial scale. The process laboratory staff conduct a series tests identify chemically unstable reagents, intermediates and solvents, mixtures ensure that proposed operating conditions provide sufficient margin onset undesired potentially catastrophic thermal decomposition. Across several companies, methods used for these assessments...
The preparation of annulated furan systems as key synthetic intermediates through the application a two-step annulation involving an electrochemical ring closure between and silyl enol ether has been studied. reaction was shown to be quite general for formation six-membered rings in good yields tolerant variety different functional groups. highly stereoselective, leading cis-fused systems. Cyclic voltammetry probe molecules were used gain mechanistic insight into reaction. These studies...
In a quest to develop an effective, scalable synthesis of (+)-spongistatin 1 (1), we devised concise, third-generation (+)-7, the requisite F-ring tetrahydropyran aldehyde, employing proline-catalyzed cross-aldol reaction. Subsequent elaboration (+)-EF Wittig salt (+)-3, followed by union with advanced ABCD aldehyde (−)-4, macrolactonization and global deprotection permitted access >1.0 g totally synthetic (1).
This work describes the optimization and scale-up of a Buchwald–Hartwig amination reaction for preparation pharmaceutical intermediate. C–N bond formation is challenged by use chiral primary amine, which both adds cost favors biaryl byproducts. In order to develop scalable process, number factors had be investigated including catalyst selection stoichiometry amine. These all needed optimized while maintaining low palladium levels in isolated product. The was found most effective using...
Process safety groups in the pharmaceutical industry are important components of active ingredient development through its life cycle, from discovery to commercial manufacturing. The process laboratory staff conduct a series tests identify chemically unstable reagents, intermediates, solvents, reaction mixtures, and high-energy reactions ensure that proposed operating conditions provide sufficient margin onset undesired potentially catastrophic thermal decomposition. Across several...
The difluoromethylation of methyl 4-hydroxy-3-iodobenzoate has been demonstrated on multikilogram scale. Prior to execution, several issues had be addressed. First, the difluorocarbene source explored avoid using highly toxic gases such as chlorodifluoromethane. After choosing sodium chlorodifluoroacetate difluororcarbene precursor and potassium carbonate base, a safety evaluation performed ensure this transformation could carried out safely Herein, we report safe practical protocol...
The development of the potent and selective mGluR5 negative allosteric modulator (NAM) 1 is described. Key features in process, which has been implemented on a multikilogram scale, include high-temperature difluoromethylation reaction, Sonogashira coupling, careful control residual Pd Cu final API. Due to relative nonpolar nature intermediates, water-miscible solvents were employed all four steps allow for direct crystallizations upon reaction completion. In addition, several crystalline...
When a material is identified as potentially capable of explosive propagation by the Yoshida correlation, process safety scientists have few options for semiquantitatively assessing hazards associated with use that material. Oxygen balance calculations, Rule 6, and United Nations (U.N.) functional group list are commonly employed qualitative/semiquantitative methods to assess explosivity without requiring additional experimental data. In contrast, full Transportation Dangerous Goods testing...
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at glance that was extracted from about 200 leading journals. To access Abstract, please click on HTML or PDF.
An electrochemical furan annulation strategy has been developed for the synthesis of seven-membered rings. Key to success is placement a gem-dialkyl group in tether. Voltammetric studies indicate that this effect lowers oxidation potential by approximately 110 mV.
A new methodology for the annulation of five-membered carbocyclic rings onto enones through dearomatizing electrochemical cyclization furans and thiophenes has been developed.
Hint is a universally conserved, dimeric AMP-lysine hydrolase encoded on the avian Z chromosome. Tandemly repeated female-specific W chromosome, Asw encodes potentially sex-determining, dominant-negative dimerization partner whose substrate-interacting residues were specifically altered in evolution. To test hypothesis that Gln127 of responsible for depression and/or alteration enzyme activity, corresponding mutant was created chicken homodimer, and novel substrate developed links reversal...
Mammalian cells synthesize significant amounts of precursor sterols, in addition to cholesterol, at the endoplasmic reticulum (ER). The newly synthesized sterols rapidly move plasma membrane (PM). mechanism by which back ER for their enzymatic processing cholesterol is essentially unknown. Here we performed pulse-chase experiments and showed that C29/C30 from PM are converted cholesterol. retrograde sterol transport largely independent Niemann-Pick type C proteins, play important roles late...