A5080892892- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Cyclopropane Reaction Mechanisms
- Chemical Synthesis and Analysis
- Catalytic C–H Functionalization Methods
- Carbohydrate Chemistry and Synthesis
- Click Chemistry and Applications
- Catalytic Alkyne Reactions
- Microbial Natural Products and Biosynthesis
- Chemical Synthesis and Reactions
- Synthesis and Catalytic Reactions
- Glycosylation and Glycoproteins Research
- Oxidative Organic Chemistry Reactions
- Chemical Reactions and Isotopes
- Computational Drug Discovery Methods
- Synthesis of Organic Compounds
- Crystallography and molecular interactions
- Asymmetric Synthesis and Catalysis
- Asymmetric Hydrogenation and Catalysis
- Legume Nitrogen Fixing Symbiosis
- Bioactive Compounds and Antitumor Agents
- Fluorine in Organic Chemistry
- Catalytic Cross-Coupling Reactions
- Chemical synthesis and alkaloids
- Chemical Reaction Mechanisms
University of Oklahoma
2016-2025
Norman Regional Hospital
2017-2020
Memorial Sloan Kettering Cancer Center
2011-2017
Kettering University
2014
Tri-Institutional PhD Program in Chemical Biology
2014
Sarojini Naidu Medical College
2013
Wayne State University
2008-2012
University of Illinois Chicago
2008
Indian Institute of Technology Kharagpur
2007
Central Drug Research Institute
1989
Given the prevalence of nitrogen-containing heterocycles in commercial drugs, selectively incorporating a single nitrogen atom is promising scaffold hopping approach to enhance chemical diversity drug discovery libraries. We harness distinct reactivity sulfenylnitrenes, which insert transform readily available pyrroles, indoles, and imidazoles into synthetically challenging pyrimidines, quinazolines, triazines, respectively. Our additive-free method for skeletal editing employs easily...
Highly activated thioesters formed by the rapid reaction of C-terminal thioacids derived from protected amino acids and peptides with Sanger reagent other electron-deficient aryl halides in presence a free amine immediately form peptide bond amine. This essentially epimerization-free method was used for 4+4 block synthesis hindered octapeptide (see scheme; Boc, Pbf, Trt are protecting groups).
Given its earth abundance, cost-effectiveness, and ecofriendly qualities, iron serves as a promising alternative to precious metals in catalysis. This article presents an carbene-initiated cascade approach for synthesizing highly substituted tetrahydrofurans at the gram scale. reaction utilizes readily accessible β-hydroxyketones diazo compounds works with catalyst loading low 5 mol %. proceeds through O–H insertion into diazo-derived carbenes, followed by intramolecular aldol access...
The Gram-negative bacterial pathogen Pseudomonas aeruginosa uses three interconnected intercellular signaling systems regulated by the transcription factors LasR, RhlR, and MvfR (PqsR), which mediate cell–cell communication via small-molecule natural products control production of a variety virulence factors. system is activated controls biosynthesis quinolone quorum sensing HHQ PQS. A key step in these quinolones catalyzed anthranilyl-CoA synthetase PqsA. To develop inhibitors PqsA as novel...
Abstract MenE, the o ‐succinylbenzoate (OSB)‐CoA synthetase from bacterial menaquinone biosynthesis, is a promising new antibacterial target. Sulfonyladenosine analogues of cognate reaction intermediate, OSB‐AMP, have been developed as inhibitors MenE enzymes Mycobacterium tuberculosis (mtMenE), Staphylococcus aureus (saMenE) and Escherichia coli (ecMenE). Both free carboxylate ketone moiety on OSB side chain are required for potent inhibitory activity. OSB‐AMS ( 4 ) competitive inhibitor...
A convergent approach for the stereoselective synthesis of diverse spiroethers is described. The reaction involves trapping diazo-derived rhodium carbenoids with gold-activated alkynols installation spiro cores. has proven general a range readily accessible homopropargylic alcohols and diazo carbonyls to provide functionalized spiroether cores bioactive scaffolds such as spirobarbiturates, spirooxindoles, pseurotin natural products.
Abstract Rh 2 (esp) has been identified as a highly efficient catalyst for O–H insertion of carboxylic acids into acceptor/acceptor diazo compounds. The reaction proceeds in CH Cl within minutes at room temperature excellent yields and accommodates having varying functionalities including amino acids, free alcoholic phenolic O–H, indole N–H, alkenes, alkynes, substituted aromatics. In addition, the tolerates broad range stable compounds carrying diverse functional groups.
Among the opioid receptors, κ-opioid receptor (κOR) has been gaining considerable attention as a potential therapeutic target for treatment of complex CNS disorders including depression, visceral pain, and cocaine addiction. With an interest in discovering novel ligands targeting κOR, we searched natural products unusual scaffolds identified collybolide (Colly), nonnitrogenous sesquiterpene from mushroom Collybia maculata. This compound furyl-δ-lactone core similar to that Salvinorin A (Sal...
1,2-cis-Furanosides are present in various biomedically relevant glycosides, and their stereoselective synthesis remains a significant challenge. In this vein, we have developed approach to 1,2-cis-furanosylations using earth-abundant copper catalysis. This protocol proceeds under mild conditions at room temperature employs readily accessible benchtop stable enynal-derived furanose donors. chemistry accommodates variety of alcohols, including primary, secondary, tertiary, as well mannosyl...
Late-stage functionalization (LSF) is a crucial strategy in drug discovery, allowing the modification of complex molecules, including pharmaceuticals, to enhance chemical diversity libraries. We harness chemoselectivity sulfenylcarbenes, which selectively react with alkenes even presence more reactive functional groups such as alcohols, carboxylic acids, and amines. This reactivity allows sulfenylcarbenes insert single carbon atom bearing diverse groups, transforming pyrroles, indoles,...
Conventional methods for thioglycoside activation often rely on precious and toxic platinum group metals. Here, we report a catalytic glycosylation strategy employing diazo-thioglycoside donors activated by earth-abundant iron or photosensitizer-free blue light conditions. It confers orthogonal reactivity relative to most glycosyl donors, including widely used thioglycosides alkyne-based thereby enabling one-pot synthesis of glycans. The Thorpe-Ingold-like effect drives the proximity iron-...
One after the other: Triblock peptide synthesis was achieved at ambient temperature by sequential reaction of sulfonamide-protected peptidyl thioacids first with highly reactive 2,4-dinitrobenzenesulfonamides and second more moderately sulfonamides to produce oligopeptides in good yields. The method is compatible C-terminal thioesters thus presents a new approach for native chemical ligation strategies. Detailed facts importance specialist readers are published as "Supporting Information"....
Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving previously isolated or synthesized compounds largely completely untested. To address this issue, the Canvass library natural was assembled, in collaboration with academic industry researchers, quantitative high-throughput screening (qHTS) across a diverse set cell-based biochemical assays. Characterization...
2,3-Di-O-benzyl-4,6-O-benzylidene-thiohexopyranosides, on activation with 1-benzenesulfinyl piperidine and triflic anhydride, react allyl silanes stannanes, silyl enolethers to give C-glycosides. In the mannose series beta-isomers are formed selectively whereas glucose provides alpha-anomers. This selectivity pattern parallels that of O-glycoside formation eliminates need consider donor-acceptor hydrogen bonding in O-glycosides.
α-C-Glucopyranosides and mannopyranosides are obtained in 65−85% yields from 4,6-O-benzylidene-protected glucosyl mannosyl thioglycosides bearing ester functionality at the 3-O-position by a coupling reaction with C-nucleophiles on activation diphenyl sulfoxide, 2,4,6-tri-tert-butylpyrimidine, trifluoromethanesulfonic anhydride.
MenE is an o-succinylbenzoyl-CoA (OSB-CoA) synthetase in the bacterial menaquinone biosynthesis pathway and a promising target for development of novel antibacterial agents. The enzyme catalyzes CoA ligation via acyl-adenylate intermediate, we have previously reported tight-binding inhibitors based on stable acyl-sulfonyladenosine analogues this including OSB-AMS (1), which has IC50 value ≤25 nM Escherichia coli MenE. Herein, show that reduces levels Staphylococcus aureus, consistent with...
Attachment of a growing peptide chain to glycylaminomethyl resin via thioglycinamide bond is compatible with Fmoc-chemistry solid-phase synthesis. Subsequent S-alkylation the thioamide gives thioimide that, on treatment aqueous trifluoroacetic acid, releases from in form C-terminal thioester.
A stereocontrolled synthesis of benzannulated spiroketals has been developed using solvent-dependent Sc(OTf)3-mediated spirocyclizations exo-glycal epoxides having alcohol side chains. In THF, the reaction proceeds via Lewis acid catalysis under kinetic control with inversion configuration at anomeric carbon. contrast, in CH2Cl2, Brønsted thermodynamic leads to retention configuration. The reactions accommodate a variety aryl substituents and ring sizes provide stereochemically diverse spiroketals.
A convergent 5-step cascade approach for the stereoselective synthesis of functionalized quinolines.
A novel and highly efficient diazo-OH insertion/Conia-ene cascade reaction of readily available homopropargylic acids alcohols with diazo carbonyl compounds is described. The involves a synergistic Rh/Ag/Au catalyst cocktail proceeds instantly variety substituted acids/alcohols to provide functionalized γ-butyrolactones tetrahydrofurans complete regio- stereoselectivity. unprecedented rate-enhancement, stereoselectivity, the enabling new Conia-ene cyclizations suggest concerted...
A convergent cascade approach for the stereoselective synthesis of diverse lactones is described. The Rh2(TFA)4-catalyzed reaction proceeds via a carboxylic acid O–H insertion/aldol cyclization with high chemo-, regio-, and diastereoselectivity. provides quick access to highly functionalized γ-butyro- δ-valerolactones from readily accessible ketoacid diazo synthons. To demonstrate utility this approach, thermally induced oxy-Cope ring-expansion strategy has been incorporated in sequence...
A novel diazo-cascade approach has been developed for the synthesis of nine-membered oxacycles utilizing readily accessible β-hydroxy vinyl ketones and diazo esters. The Rh(II)-catalyzed cascade reaction begins with carbene O–H insertion followed by an intramolecular aldol cyclization to provide a substituted tetrahydrofuran intermediate that undergoes oxy-Cope rearrangement functionalized complete stereoselectivity.
In this study, we harness the distinct reactivity of sulfenylnitrenes, which insert a single nitrogen atom to transform readily available pyrroles, indoles, and imidazoles into synthetically challenging pyrimidines, quinazolines, triazines, respectively. Our additive-free method for skeletal editing employs easily accessible, benchtop-stable sulfenylnitrene precursors as source atom. This chemical approach is compatible with free diverse functional groups, including oxidation-sensitive...