A5005832983- Catalytic C–H Functionalization Methods
- Chemistry and Chemical Engineering
- Synthetic Organic Chemistry Methods
- Catalytic Cross-Coupling Reactions
- Asymmetric Hydrogenation and Catalysis
- Cyclopropane Reaction Mechanisms
- Crystallization and Solubility Studies
- Chemical Synthesis and Analysis
- RNA and protein synthesis mechanisms
- Synthesis and Catalytic Reactions
- Asymmetric Synthesis and Catalysis
- Nanomaterials for catalytic reactions
- Innovative Microfluidic and Catalytic Techniques Innovation
- Process Optimization and Integration
- Carbohydrate Chemistry and Synthesis
- X-ray Diffraction in Crystallography
- Catalytic Alkyne Reactions
- Sustainable Supply Chain Management
- RNA modifications and cancer
- Computational Drug Discovery Methods
- Chemical Synthesis and Reactions
- Microbial Natural Products and Biosynthesis
- Pharmacological Receptor Mechanisms and Effects
- Migraine and Headache Studies
- interferon and immune responses
Biohaven Pharmaceuticals (United States)
2023-2024
Takeda (United States)
2018-2022
Bristol-Myers Squibb (United States)
2005-2020
Takeda (Japan)
2018-2020
Bristol-Myers Squibb (Germany)
2016-2017
Indiana University Bloomington
2002-2004
University of Delaware
2000
As companies grow ever more mindful of the sustainability aspects their products and supply chains, an increasing focus on environmental impact pharmaceutical manufacture spurs innovation from chemists who support this industry. Metal catalysis has potential to greatly enhance products, leading shorter efficient synthetic routes direct access single stereoisomeric products. This perspective article seeks highlight a number important considerations for design new improved sustainable...
Green and sustainable drug manufacturing goes hand in with forward-looking visions seeking to balance the long-term sustainability of business, society, environment.
We report the catalytic stereocontrolled synthesis of dinucleotides. have demonstrated, for first time to our knowledge, that chiral phosphoric acid (CPA) catalysts control formation stereogenic phosphorous centers during phosphoramidite transfer. Unprecedented levels diastereodivergence also been enabling access either phosphite diastereomer. Two different CPA scaffolds proven be essential achieving stereodivergence: peptide-embedded phosphothreonine-derived CPAs, which reinforce and...
The transition metal-catalyzed allylic etherification represents a fundamentally important cross-coupling reaction for the construction of ethers. We have developed new regio- and enantiospecific rhodium-catalyzed acyclic unsymmetrical alcohol derivatives using copper(I) alkoxides derived from primary, secondary tertiary alcohols. This study demonstrates that choice halide salt is crucial obtaining excellent enantiospecificity, providing another example effect ions in asymmetric reactions....
The large and steadily growing demand for medicines combined with their inherent resource-intensive manufacturing necessitates a relentless push sustainable production. Pharmaceutical companies are constantly seeking to perform reliable life cycle assessments of medicinal products assess the true value development achievements; however, they find themselves impeded by lack universal metric system that allows objective quantification underlying core denominators. Guided unambivalent purpose...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTRegioselective and Enantiospecific Rhodium-Catalyzed Intermolecular Allylic Etherification with Ortho-Substituted PhenolsP. Andrew Evans David K. LeahyView Author Information Brown Laboratory Department of Chemistry Biochemistry University Delaware, Newark, Delaware 19716 Cite this: J. Am. Chem. Soc. 2000, 122, 20, 5012–5013Publication Date (Web):May 4, 2000Publication History Received1 February 2000Published online4 May inissue 1...
A scalable synthetic method is described for both the preparation of ultrasmall palladium nanoparticles and their subsequent use in catalyzing an α-arylation reaction nitriles aqueous micelles. This involves intermediacy carbanions or keteniminates, which are presumably stabilized by micellar environment rather than being quenched with water. These Pd thoroughly characterized. Mechanistic studies using 31P NMR spectroscopy revealed binding phosphine ligand surface control experiment...
Under the shielding effect of nanomicelles, a sustainable micellar technology for design and convenient synthesis ligand-free oxidizable ultrasmall Pd(0) nanoparticles (NPs) their subsequent catalytic exploration couplings water-sensitive acid chlorides in water is reported. A proline-derived amphiphile, PS-750-M, plays crucial role stabilizing these NPs, preventing aggregation oxidation state changes. These NPs were characterized using 13C nuclear magnetic resonance (NMR), infrared (IR),...
The transition metal-catalyzed allylic alkylation represents a fundamentally important cross-coupling reaction for the construction of ternary carbon stereogenic centers. We have developed regioselective and enantiospecific rhodium-catalyzed acyclic unsymmetrical alcohol derivatives using copper(I) enolates to prepare beta-substituted ketones. This protocol convenient asymmetric Claisen rearrangement surrogate in which alpha-substituted permit introduction an additional center. synthetic...
A dramatic enhancement of the stereospecificity title reaction was observed with trimethylphosphite-modified copper(I) alkoxide reagents. The combination this ring-closing metathesis provides a direct approach to cis- and trans-disubstituted cyclic ethers (see scheme). seven-step total synthesis natural product gaur acid highlighted potential methodology. LG=leaving group. transition-metal-catalyzed intermolecular allylic etherification is fundamentally important cross-coupling strategy for...
The authors of this concept article are members the IQ Green Chemistry working group, one many subgroups International Consortium for Innovation and Quality in Pharmaceutical Development (IQ Consortium) which has been officially chartered April 2010. Working Group seeks to drive innovation awareness green chemistry pharmaceutical development through establishment adoption best practices, sharing information within peer networks, collaboration with regulatory agencies other key stakeholders.
Starting in 2007, the ACS Green Chemistry Institute Pharmaceutical Roundtable (GCIPR) has invested sustainable chemical reactions and technologies order to positively impact pharmaceutical manufacturing routes processes of future. It done so by committing over $2 million support a grant program focused on spurring innovative solutions industrially relevant problems with significant unmet need. This resulted funding 28 research programs from academic groups across globe, spanning wide range...
The amphiphile PS-750-M generates stable, phosphine ligand-free, and catalytically active ultrasmall Pd(II) nanoparticles (NPs) from Pd(OAc)2, preventing their precipitation, polymerization, oxidation state changes. directly interacts with NP surfaces, as confirmed by high-resolution mass spectrometry IR spectroscopy, resulting in high stability. Pd cations NPs are most likely held together hydroxides acetate ions. were characterized HRTEM, revealing morphology particle size distribution,...
A manufacturing process conducted almost entirely in water has been developed to produce <bold>TAK-954</bold>, an investigational 5-HT<sub>4</sub> receptor agonist.
While suppressing the decomposition of trichloromethyl carbanions (generated from CHCl3 using LiOH base) to carbon monoxide and their participation in transmetallation reductive elimination steps cross-coupling's catalytic cycle, a micelle-enabled carboxylation (hetero)aryl halides is developed. The aqueous micelles play crucial role stabilizing both highly reactive carbanion single-metal atom catalyst facilitate desired reaction pathway efficiently. Comprehensive mechanistic analyses,...
An enantioselective synthesis of the CGRP antagonist BMS-846372, amenable to large scale preparation, is presented. This new showcases a chemo- and reduction cyclohepta[b]pyridine-5,9-dione as well Pd-catalyzed alpha-arylation reaction form key carbon-carbon bond set absolute relative stereochemistry.
The cobalt-catalyzed asymmetric hydrogenation of indazole-containing enamides relevant to the synthesis calcitonin gene-related peptide (CGRP) receptor antagonist, zavegepant (1), approved for treatment migraines, is described. Both neutral bis(phosphine)cobalt(II) and cationic bis(phosphine)cobalt(I) complexes served as efficient precatalysts enamide reactions, providing excellent yield enantioselectivities (up >99.9%) a range related substrates, though key reactivity differences were...
A process greenness scorecard has been developed that provides a comprehensive assessment of aspects not encompassed by mass-based metrics, including environmental, health and safety impacts, in order to facilitate the design greener, more benign inherently safer processes.
1-(Piperidin-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one (1) is a privileged substructure found in >1000 unique CGRP receptor antagonists. Two practical and efficient syntheses of 1 are described from complementary starting materials. One route features chemoselective reductive amination, while the second utilizes Pd-catalyzed amination using an ammonia surrogate to overcome issue poor selectivity.
Macrocyclic peptides containing N-alkylated amino acids have emerged as a promising therapeutic modality, capable of modulating protein-protein interactions and an intracellular delivery hydrophilic payloads. While multichannel automated solid-phase peptide synthesis (SPPS) is practical approach for synthesis, the requirement slow inefficient chromatographic purification product significant limitation to exploring these novel compounds. Herein, we invent "catch-release" strategy...
We report a new catalytic method for alcohol sulfamoylation that deploys electron-deficient aryl sulfamates as activated group transfer reagents. The reaction utilizes the simple organic base N-methylimidazole, proceeds under mild conditions, and provides intrinsic selectivity 1° over 2° alcohols (up to >40:1 certain nucleosides). requisite sulfamate donors are stable crystalline solids can be readily prepared on large scale. Mechanistic considerations support intermediacy of HNSO2...