A5050047134- Asymmetric Synthesis and Catalysis
- Hormonal and reproductive studies
- Estrogen and related hormone effects
- Chemical synthesis and alkaloids
- Sulfur-Based Synthesis Techniques
- Catalytic C–H Functionalization Methods
- Synthesis and Biological Evaluation
- Amyotrophic Lateral Sclerosis Research
- Diabetes Treatment and Management
- Prostate Cancer Treatment and Research
- Cyclopropane Reaction Mechanisms
- Catalytic Cross-Coupling Reactions
- Synthesis and Catalytic Reactions
- Synthesis of Organic Compounds
- Receptor Mechanisms and Signaling
- Pancreatic function and diabetes
- Oxidative Organic Chemistry Reactions
- Synthesis and Reactions of Organic Compounds
- Microbial Metabolites in Food Biotechnology
- Fibroblast Growth Factor Research
- Organic Chemistry Cycloaddition Reactions
- Chemical Synthesis and Analysis
- Cholinesterase and Neurodegenerative Diseases
- Pharmacology and Obesity Treatment
- Crystallization and Solubility Studies
Janssen (United States)
2012-2021
Springhouse
2012-2020
Analytical Services
2020
Johnson & Johnson (United States)
2002-2012
The Ohio State University
1996-2001
The first chemoselective direct dehydrative cross-coupling of tautomerizable heterocycles with alkynes has been achieved via C–H/C–OH bond activations C(sp2)–C(sp) formation, which is in line ideal synthesis using readily available materials.
A general approach to the synthesis of enantiomerically pure spirocyclic alpha,beta-butenolides is presented where fundamental framework rapidly elaborated by acid- or bromonium ion-induced rearrangement carbinol derived addition 2-lithio-4,5-dihydrofuran cyclobutanone. Subsequent resolution resulting ketones either sulfoximine mandelate acetal technology has been applied effectively. The availability these building blocks makes possible in turn acquisition enantiomers dihydrofurans typified...
[reaction: see text] An asymmetric intermolecular aza variant of the Mannich reaction is reported utilizing chiral sulfinimine anions as nucleophile and N-sulfonyl aldimines electrophilic component. A wide range nucleophiles electrophiles are tolerated by conditions, delivering condensation products in good to excellent yield with a high degree stereocontrol. Application this methodology total synthesis natural product reported.
The stereoselectivity of the acid-promoted rearrangement dihydrofuranyl and dihydropyranyl carbinols to spirocyclic ketones has been examined. These kinetically controlled isomerizations result in ring expansion hydroxyl-substituted with generation a newly stereogenic carbon atom. All adducts formed from several 4,5-dihydrofurans cyclobutanone, cyclopentanone, 2,2-dimethylcyclopentanone proved be reactive. Of 5,6-dihydropyrans examined, only cyclobutanone were sufficiently reactive warrant...
Inhibition of the serine protease enteropeptidase (EP) opens a new avenue to discovery chemotherapeutics for treatment metabolic diseases. Camostat has been used clinically treating chronic pancreatitis in Japan; however, mechanistic basis observed clinical efficacy not fully elucidated. We demonstrate that camostat is potent reversible covalent inhibitor EP, with an inhibition potency (k inact/KI) 1.5 × 104 M-1s-1 High-resolution liquid chromatography-mass spectrometry (LC-MS) showed...
GPR40 is a G-protein-coupled receptor which mediates fatty acid-induced glucose-stimulated insulin secretion from pancreatic beta cells and incretion release enteroendocrine of the small intestine. full agonists exhibit superior glucose lowering compared to partial in preclinical species due increased GLP-1 secretion, with added benefit promoting weight loss. In our search for potent agonists, we discovered superagonist displayed excellent vitro potency efficacy Gαs-mediated signaling...
The tetrahydro-pyrano[3,4-b]indoles 6 were synthesized from 2-(2-trimethylsilanyl-1H-indol-3-yl)-ethanols 5 and various ketones or aldehydes through silicon-directed oxa-Pictet-Spengler cyclizations. An unusual reaction led to the dimeric products 7 when some of was treated with acetone using BF(3) as catalyst.
The odoriferous principle of black tea has been produced from 2,2-dimethylcyclopentanone. reaction sequence begins with 1,2-addition 5-lithio-2-methyl-2,3-dihydrofuran to this ketone and immediate acid-catalyzed ring expansion the resulting carbinols a separable pair spiro ethers. Individual conversion these diastereomers α,β-unsaturated ketones is followed by tandem condensation methyllithium−lithium bromide complex oxidation pyridinium chlorochromate.
Synthesis of furoyl and benzofuroyl pyrroloquinolones as potent selective PDE5 inhibitors was reported. Their in vitro potencies inhibiting selectivity other PDE isozymes (PDE1-4 PDE6) were evaluated. Some these compounds are more than sildenafil with better toward PDE1 PDE6. Incorporation solublizing groups resulted bioavailable analogues. Selected showed vivo efficacy anesthetized dog model for penile erection.
Trypsin is the major serine protease responsible for intestinal protein digestion. An inhibitor, camostat (CS), reduced weight gain, hyperglycemia, and dyslipidemia in obese rats; however, mechanisms these are largely unknown. We reasoned that CS creates an apparent dietary restriction, which known to increase hepatic fibroblast growth factor 21 (FGF21). Therefore, metabolic responses a gut-restricted metabolite, FOY-251, were measured mice. Food intake, body weight, blood glucose,...
The discovery of the potent and selective PDE-5 inhibitory activity a pyrroloquinolone scaffold prompted us to explore SAR its acyl derivatives. During course these studies, three structural series were found with K(i) values for in subnanomolar range. Systematic modification one leads produced compound excellent selectivity over other phosphodiesterases oral bioavailability 15% male rats. This also displayed vivo efficacy an anesthetized canine model erection when dosed intravenously.
The preparation of a chemokine receptor type 2 (CCR-2) antagonist bearing cyclopenta[b]furan core is described on 600 g scale. Compared to our previously reported synthesis the all-carbon CCR-2 with similar peripheral 3-methoxypyran appendage, work required redesign original Discovery Chemistry route and took advantage side product seen in diastereoselective alkylation reaction. Elaboration by reduction oxy-cyclization eventually led N-Boc acid method. After amidation using traditional...