A5081725804- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Chemical Synthesis and Analysis
- Synthesis of heterocyclic compounds
- Sulfur-Based Synthesis Techniques
- Asymmetric Hydrogenation and Catalysis
- Catalytic C–H Functionalization Methods
- Asymmetric Synthesis and Catalysis
- HIV/AIDS drug development and treatment
- Chemical Synthesis and Reactions
- N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
- Coordination Chemistry and Organometallics
- Immune Response and Inflammation
- Neuroscience and Neuropharmacology Research
- Catalytic Cross-Coupling Reactions
- Pneumocystis jirovecii pneumonia detection and treatment
- Protein Degradation and Inhibitors
- Carbohydrate Chemistry and Synthesis
- Synthesis and pharmacology of benzodiazepine derivatives
- Fluorine in Organic Chemistry
- Analytical Chemistry and Chromatography
- Cancer therapeutics and mechanisms
- Synthesis and Characterization of Heterocyclic Compounds
- Marine Toxins and Detection Methods
- Chemokine receptors and signaling
Boehringer Ingelheim (United States)
1991-2024
University of Pittsburgh
1991-2013
Old Dominion University
2013
Centre Hospitalier de l’Université de Montréal
2011
Boehringer Ingelheim (Germany)
2004-2009
Harvard University
1996
By addressing the relative stereochemistry of four acyclic portions via organic synthesis, complete maitotoxin (MTX) has been established as 1B. The C.1−C.15 portion was elucidated a two-phase approach: (1) synthesis eight diastereomers possible for model C, representing C.1−C.11 portion, and D, C.11−C.15 comparison their proton carbon NMR characteristics with those MTX, concluding that 9 35 represent corresponding MTX; (2) two remote 51 52, represents MTX. C.35−C.39, C.63−C.68, C.134−C.142 ...
Abstract A practical and efficient synthesis of a complex chiral atropisomeric HIV integrase inhibitor has been accomplished. The combination copper‐catalyzed acylation along with the implementation BI‐DIME ligands for ligand‐controlled Suzuki cross‐coupling an unprecedented bis(trifluoromethane)sulfonamide‐catalyzed tert ‐butylation renders this molecule robust, safe, economical. Furthermore, overall was conducted in asymmetric diastereoselective fashion respect to imbedded atropisomer.
A scalable synthesis of the SMARCA2 degrading PROTAC 1 was developed. The linker fragment derived from (S)-citronellol by oxidative cleavage and diastereoselective aryl Grignard addition to a N-tert-butanesulfinyl aldimine for generation chiral amine stereocenter one-pot borylation/Suzuki reaction biaryl formation. dipeptide prepared T3P-mediated coupling hydroxyproline benzyl ester N-Boc tert-leucine followed capping with 1-fluorocyclopropancarboxylic acid hydrolysis. Unification binding...
Abstract The modular nature of the BIPI ligands allows for systematic optimization each ligand region. development optimized asymmetric hydrogenation challenging unfunctionalized olefin substrate class is described. naphthyl peri position, C‐8, has been identified as a critical stereocontrol element in design these ligands. Highly enantioselective suitable tri‐ and tetrasubstituted olefins are detailed.
[reaction: see text] Sulfinate alkylation is one of the conventional methods for sulfone synthesis. The magnesium sulfinates, which are easily accessible via reactions organomagnesium intermediates with sulfur dioxide, provides a convenient route preparation. In this communication, we report preliminary study arylmagnesium sulfinates. An application reaction to directly transform functionalized aromatic/heteroaromatic halides into sulfones also described.
A novel class of lymphocyte function-associated antigen-1 (LFA-1) inhibitors is described. Discovered during the process to improve physicochemical and metabolic properties BIRT377 (1, Figure 1), a previously reported hydantoin-based LFA-1 inhibitor, these compounds are characterized by an imidazole-based 5,5-bicyclic scaffold, 1,3,3-trisubstituted 1H-imidazo[1,2-α]imidazol-2-one (i.e. structure 3). The structure−activity relationship (SAR) shows that electron−withdrawing groups at C5 on...
An efficient asymmetric synthesis of 11-β-HSD inhibitor 1 has been accomplished in five linear steps and 53% overall yield, starting from the readily available 3-chloro-1-phenylpropan-1-one. The key feature includes an methallylation 3-chloro-1-phenylpropan-1-one catalyzed by highly effective organocatalyst (S)-3,3'-F2-BINOL under solvent-free metal-free conditions.
The first uncatalyzed hydrophosphinations of propargylic amines and alcohols with phosphine- borane complexes are described. reactions proceed at ambient temperature or below without the use protecting groups need to handle pyrophoric secondary phosphines, furnishing air-stable phosphineborane-amines in good yields. Utilization chiral substrates unsymmetrical phosphineboranes leads diastereomeric P-chiral products that can be separated by fractional crystallization chromatography. Initial...
Abstract A simple N‐heterocyclic carbene (NHC) derived from 1‐methyl‐3‐ethylimidazolium tetrafluoroborate was found to be an efficient ligand for a range of copper‐catalyzed cross‐coupling reactions, leading the formation aromatic ethers and thioethers. magnified image
An enantioselective approach to analogues of the pseudopterosin family structures, which entails Diels-Alder reaction a ß-nitroacrylate derivative (dimethyl (E)-3-nitro-2-pentenedioate) with an (S)-carvone-derived silyloxydiene [(3S,6S)-3 - (1,2- isopropylidenedioxy-1-methylethyl) 6 methyl -1- (1- trimethylsilyloxyethenyl)-1-cyclohexene], is described.
Hydrophosphination of secondary propargylic alcohols generates phosphine-containing allylic that undergo facile [2,3]-sigmatropic rearrangements with chlorophosphines, furnishing highly enantioenriched, crystalline diphosphine monoxides. The configuration at the newly formed stereocenter is opposite to expected based on prior studies, and an ab initio computational evaluation possible transition states was performed help explain stereochemical course reaction.
The route design and process development for the synthesis of BI 1702135 are described. synthetic centers around an amide involving a 2-amino benzimidazole analog 4 that has two competing acylation sites. A highly selective protocol at desired N-2′ site was identified. Robust convenient processes were developed each step in this five-step 1702135.
Compound 1 ((4-amino-3,5-dichlorophenyl)-1-(4-methylpiperidin-1-yl)-4-(2-nitroimidazol-1-yl)-1-oxobutane-2-sulfonamido) was discovered to be a 690 nM antagonist of human CCR10 Ca2+ flux. Optimization delivered (2R)-4-(2-cyanopyrrol-1-yl)-S-(1H-indol-4-yl)-1-(4-methylpiperidin-1-yl)-1-oxobutane-2-sulfonamido (eut-22) that is 300 fold more potent than and eliminates potential toxicity, mutagenicity, drug–drug-interaction liabilities often associated with nitroaryls anilines. eut-22 highly...
Due to their unique properties, dihydroazaindoles are important fragments of active pharmaceutical ingredients and great interest in the industry. In this manuscript, a scalable economical process for synthesis complex (R)-2-(4-fluorophenyl)-2-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid (R)-1 on multikilogram scale is described. The was advanced through second-generation synthetic strategy that did not rely chiral Supercritical Fluid Chromatography separation, which...
Abstract IL-7 plays vital roles in thymocyte development, T cell homeostasis and the survival of these cells. receptor alpha (IL-7R-alpha) on thymocytes cells is rapidly internalized upon ligation. Ephrins (EFN) are surface molecules ligands largest family kinases, Eph kinases. We discovered that cell-specific double deletion EFNB1 EFNB2 (double KO) mice led to reduced IL-7R-alpha expression cells, downregulation KO CD4 treatment was accelerated. On other hand, overexpression line EL4...
Abstract A simple N‐heterocyclic carbene derived from imidazolium salt [enim]BF 4 is found to be an efficient ligand in a range of Cu‐catalyzed cross‐coupling reactions furnishing aromatic ethers and thioethers.