A5055181050- Carbohydrate Chemistry and Synthesis
- Synthetic Organic Chemistry Methods
- Chemical Synthesis and Analysis
- Innovative Microfluidic and Catalytic Techniques Innovation
- Fluorine in Organic Chemistry
- Radical Photochemical Reactions
- Computational Drug Discovery Methods
- Enzyme Catalysis and Immobilization
- Chemistry and Chemical Engineering
- Glycosylation and Glycoproteins Research
- Catalytic C–H Functionalization Methods
- Synthesis of Organic Compounds
- Crystallization and Solubility Studies
- Physics and Engineering Research Articles
- Synthesis and biological activity
- Catalytic Cross-Coupling Reactions
- Asymmetric Hydrogenation and Catalysis
- Sulfur-Based Synthesis Techniques
- Inorganic Fluorides and Related Compounds
- Bioactive Compounds and Antitumor Agents
- Hemoglobinopathies and Related Disorders
- Hemoglobin structure and function
- Microbial Metabolites in Food Biotechnology
- X-ray Diffraction in Crystallography
- Chemical Synthesis and Reactions
Pfizer (United States)
2019-2024
Eli Lilly (United States)
2016-2020
University of California, San Diego
2005-2007
Scripps Research Institute
2005-2007
Wayne State University
2002-2005
Henry Ford Health System
2005
The application of abundant and inexpensive fluorine feedstock sources to synthesize fluorinated compounds is an appealing yet underexplored strategy. Here, we report a photocatalytic radical hydrodifluoromethylation unactivated alkenes with industrial chemical, chlorodifluoromethane (ClCF2H, Freon-22). This protocol realized by merging tertiary amine-ligated boryl radical-induced halogen atom transfer (XAT) organophotoredox catalysis under blue light irradiation. A broad scope readily...
Abstract While aldehydes represent a classic class of electrophilic synthons, the corresponding acyl radicals are inherently nucleophilic, which exhibits umpolung reactivity. Generation typically requires noble metal catalysts or excess oxidants to be added. Herein, we report convenient and green approach access radicals, capitalizing on neutral eosin Y-enabled hydrogen atom transfer (HAT) photocatalysis with aldehydes. The generated underwent SOMOphilic substitutions various functionalized...
Nirmatrelvir (PF-07321332, 1) is a selective, orally bioavailable inhibitor of SARS-CoV-2 2 Mpro. Development an efficient synthesis this molecule was critical for the rapid advancement compound from first to successful emergency use authorization in just 17 months. This paper provides overview development commercial synthesis, with focus on supply chains three starting materials, which leveraged key synthetic studies earlier protease research programs and/or products.
The introduction of difluoromethylene moieties into organic molecules has garnered significant attention due to their profound influence on the physicochemical and biological properties compounds. Nonetheless, existing approaches for accessing difluoroalkanes from readily available feedstock chemicals remain limited. In this study, we present an efficient modular protocol synthesis difluorinated compounds alkenes, employing accessible reagent, ClCF2SO2Na, as a versatile "difluoromethylene"...
The G protein-coupled receptor 40 (GPR40) also known as free fatty acid 1 (FFAR1) is highly expressed in pancreatic, islet β-cells and responds to endogenous acids, resulting amplification of insulin secretion only the presence elevated glucose levels. Hypothesis driven structural modifications FFAs, focused on breaking planarity reducing lipophilicity, led identification spiropiperidine tetrahydroquinoline derivatives GPR40 agonists with unique pharmacology, selectivity, pharmacokinetic...
The total syntheses of 2,2'-epi-cytoskyrin A, rugulosin, and the alleged structure rugulin are described. These naturally occurring bisanthraquinones their relatives characterized by novel molecular architectures at core, which lies a more or less complete, cage-like structural motif termed "skyrane". strategies developed for synthesis feature cascade sequence called "cytoskyrin cascade" deliver these molecules in short order stereoselective manner.
Nirmatrelvir is a potent, selective, and orally bioavailable inhibitor of SARS-CoV-2 Mpro. Herein, we report scalable cyclopropanation to produce the bicyclic [3.1.0]proline derivative, which one key starting materials for synthesis nirmatrelvir. To ensure robust supply chain this building block meet significant API demand, needed develop synthetic process that was complementary existing strategies. achieve goal, used widely available inexpensive raw material...
Development of a scalable route for the synthesis nirmatrelvir, novel SARS-CoV-2 3C-like protease inhibitor discovered in 2020 by Pfizer scientists, was initiated shortly thereafter to supply material first clinical studies. This optimized commercial manufacture nirmatrelvir high yield and acceptable quality with consideration efficiency sustainability. Herein, we report evolution final steps (3–5) used synthesize (steps 3–5), from initial regulatory lot design implementation process.
Nirmatrelvir is a potent, selective, and orally bioavailable inhibitor of SARS-CoV-2 Mpro. In this paper, we report the development magnesium sulfate (MgSO4)-mediated aminolysis for synthesis (S)-2-amino-3-[(S)-2-oxopyrrolidin-3-yl]propenamide hydrogen chloride, eastern fragment nirmatrelvir. Previous building block required protecting group, high equivalents ammonia, long reaction time generated materials with moderate potency levels residual solvents. We determined that MgSO4, widely...
Nirmatrelvir (1), a novel and specific inhibitor of the SARS-CoV-2 3C-like protease, was developed by Pfizer scientists in mid 2020. Efforts to develop scalable process manufacture nirmatrelvir were undertaken with great sense urgency, as there no effective treatments available for worldwide patient population at that time. We used convergent approach generate this molecule. The first two steps western fragment from l-tert-leucine, ethyl trifluoroacetate, [3.1.0] bicyclic proline derivative...
The cytoskyrin cascade: total syntheses of the bisanthraquinones 2 (+)-2,2′-epi-cytoskyrin A (R2=OMe) and (+)-rugulosin (R2=Me) has been achieved through a cascade sequence from anthradihydroquinone monomeric units 1.
We report a photoredox platform for constructing styrenyl polyfluoro (hetero)arenes with branch selectivity by taking advantage of sulfinate as both radical-relay precursor and sacrificial nucleofuge. This protocol merges catalysis radical–radical coupling an elimination process in one-pot operation features good functional group tolerance, mild conditions, facile method to access (hetero)aryl derivatives natural products drugs.
Models revealed: A series of model systems, for example, cytoskyrin and rugulin, were prepared from an anthraquinone (see scheme). The cascade sequence features Michael additions oxidation reactions.
The synthesis of a variety stable carbohydrate mimetics using RCM approach is discussed. An esterification-RCM has been utilized for the preparation alkyl, aryl β-C-glycosides as well number β-C-saccharides.
Radical fluoroalkylation is a powerful synthetic tool for the late-stage incorporation of fluorinated moieties into organic molecules, which widely used in development pharmaceuticals and agrochemicals. Here, we report an efficient radical chlorodifluoromethylation protocol with sodium chlorodifluoromethanesulfinate, complementary to existing difluoromethylation strategies. CF2Cl suitable surrogate accessing CF2H group while possessing completely different electronic properties compared...
The synthesis of a small library differentially-linked β-C-disaccharides has been carried out through the use radical allylation-RCM strategy. Acids 6 were prepared by Keck allylation suitable carbohydrate-based precursor, followed oxidative cleavage formed alkene. Dehydrative coupling these acids with known olefin alcohol 5 then gave precursor esters 7 in excellent yield. Methylenation was RCM and situ hydroboration−oxidation glycals to furnish protected 10 good overall Five examples...
Good things come in threes: A variety of β-C-trisaccharides have been successfully synthesized by double ring-closing metathesis, which provides the products excellent overall yield after functionalization newly formed bonds (see scheme). The precursor olefin–enol ethers were prepared Takai methylenation appropriate diesters. Supporting information for this article is available on WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z53478_s.pdf or from author. Please note: publisher not...
The synthesis of a number biologically relevant C-glycosides has been carried out through the use an esterification−ring-closing metathesis (RCM) strategy. required acid precursors were readily prepared via standard chemical transformations followed by dehydrative coupling these acids with several olefin alcohols 1 to yield precursor esters 3 in excellent yield. Methylenation was RCM and situ hydroboration−oxidation formed glycals furnish protected β-C-glycosides 6 good overall Several...
The first synthesis of a branched β-C-tetrasaccharide has been carried out through the use an esterification−ring closing metathesis (RCM) strategy. precursor triacid 2a was readily prepared via standard chemical methods from known starting material, and dehydrative coupling with excess olefin alcohol 1a gave triester 3a in excellent yield. Methylenation subsequent triple RCM reaction followed by situ hydroboration−oxidation to furnish 6a good overall
An esterification−RCM approach to a variety of biologically relevant β-C-glycoconjugates is reported herein. A range carboxylic acids were coupled with several different olefin alcohols 1 provide esters 3. The then converted the final ring-closed product 6 in three steps 49−60% overall yield. formed compounds are and serve as stable carbohydrate mimics corresponding O-glycosides.
Die Cytoskyrin-Kaskade: Totalsynthesen der Bisanthrachinone 2 (+)-2,2′-epi-Cytoskyrin A (R2=OMe) und (+)-Rugulosin (R2=Me) gelang mithilfe einer Kaskadensequenz ausgehend von monomeren Anthradihydrochinoneinheiten 1.