A5009845282- Reproductive Biology and Fertility
- Catalytic Cross-Coupling Reactions
- X-ray Diffraction in Crystallography
- Asymmetric Hydrogenation and Catalysis
- Crystallization and Solubility Studies
- Synthetic Organic Chemistry Methods
- Legal and Labor Studies
- Catalytic C–H Functionalization Methods
- Microbial Natural Products and Biosynthesis
- Nanomaterials for catalytic reactions
- Animal Genetics and Reproduction
- HIV/AIDS drug development and treatment
- Innovative Microfluidic and Catalytic Techniques Innovation
- Viral Infections and Immunology Research
- Carbon dioxide utilization in catalysis
- Coordination Chemistry and Organometallics
- Viral gastroenteritis research and epidemiology
- HIV Research and Treatment
- SARS-CoV-2 and COVID-19 Research
- Organometallic Complex Synthesis and Catalysis
- Cancer Treatment and Pharmacology
- Finance, Taxation, and Governance
- Bioenergy crop production and management
- Synthesis and characterization of novel inorganic/organometallic compounds
- Political Philosophy and Ethics
Gilead Sciences (United States)
2021-2023
University of Illinois Urbana-Champaign
2014-2018
Urbana University
2015-2016
University of Milan
2010-2011
The transition metal-catalyzed cross-coupling of organometallic nucleophiles derived from tin, boron, and zinc with organic electrophiles enjoys a preeminent status among modern synthetic methods for the formation carbon–carbon bonds. In recent years, organosilanes have emerged as viable alternatives to conventional reagents, added benefits low cost, toxicity, high chemical stability. However, silicon-based reactions often require heating in presence fluoride source, which has significantly...
Remdesivir 1 is an phosphoramidate prodrug that releases the monophosphate of nucleoside GS-441524 (2) into lung cells, thereby forming bioactive triphosphate 2-NTP. 2-NTP, analog ATP, inhibits SARS-CoV-2 RNA-dependent RNA polymerase replication and transcription viral RNA. Strong clinical results for have prompted interest in oral approaches to generate Here, we describe discovery a 5′-isobutyryl ester 2 (GS-5245, Obeldesivir, 3) has low cellular cytotoxicity 3–7-fold improved delivery...
Through the combination of reaction kinetics (both stoichiometric and catalytic), solution- solid-state characterization arylpalladium(II) arylsilanolates, computational analysis, intermediacy covalent adducts containing Si–O–Pd linkages in cross-coupling reactions arylsilanolates has been unambiguously established. Two mechanistically distinct pathways have demonstrated: (1) transmetalation via a neutral 8-Si-4 intermediate that dominates absence free silanolate (i.e., arylsilanolate...
The rhodium-catalyzed water–gas shift reaction has been demonstrated to drive the reductive alkylation of several classes activated methylene compounds at room temperature. Under catalysis by rhodium trichloride (2–3 mol %), carbon monoxide (10 bar), water (2–50 equiv), and triethylamine (2.5–7 scope successfully expanded cover a wide range alkylating agents, including aliphatic aromatic aldehydes, as well cyclic ketones, in moderate high yields. This method is comparable to, for certain...
Through the combination of reaction kinetics (both catalytic and stoichiometric) solid-state characterization arylpalladium(II) alkenylsilanolate complexes, intermediacy covalent adducts containing Si-O-Pd linkages in cross-coupling reactions organosilanolates has been unambiguously established. Two mechanistically distinct pathways have demonstrated: (1) transmetalation via a neutral 8-Si-4 intermediate that dominates potassium alkenylsilanolates, (2) an anionic 10-Si-5 cesium...
Abstract Seit ihrer Entdeckung vor mehr als hundert Jahren hat die Wassergas‐Shift‐Reaktion (WGSR) entscheidende Bedeutung in der industriellen Chemie, indem sie den Wasserstoff zur Beschickung grundlegender großtechnischer Prozesse wie Haber‐Bosch‐Synthese von Ammoniak liefert. Obwohl Produktion immer noch Hauptanwendung WGSR ist, markierte Einführung homogenen Katalyse 1970er Beginn einer Synergie zwischen und organischen Chemie. Dabei wurde das Reduktionsvermögen des CO/H 2 O‐Paars...
Abstract The total syntheses of (+)‐9‐ epi ‐dictyostatin ( 1a ) and (–)‐12,13‐bis‐ 1b ), diastereomers the antimitotic marine sponge‐derived macrolide (–)‐dictyostatin 1 were achieved by creating 11 stereogenic centers 4stereogenic double bonds with a high level stereocontrol. yield for 29‐step longest linear sequence from Roche ester was 1.53 1.52 %, respectively. final key steps to these unnatural products addition vinylzincates C10‐C26 aldehyde C1–C9 (leading surprisingly complete...
Phosphonamidate 1 is a key fragment in the assembly of rovafovir etalafenamide, novel nucleotide reverse transcriptase inhibitor under development at Gilead Sciences for treatment HIV infection. An early manufacturing route, relying on simulated moving bed (SMB) chromatography separation phosphorus diastereomers, was executed scale to produce multiple batches 1. However, developing alternative synthetic conditions became desirable consideration high production cost, long lead time, and...
This manuscript describes the chemical process development and multi-kilogram synthesis of rovafovir etalafenamide (GS-9131), a phosphonamidate prodrug nucleotide reverse transcriptase inhibitor under investigation for treatment HIV-1 infection. Rovafovir is assembled in four-step sequence beginning from nucleoside core an elaborated alcohol. The assembly starts with decarboxylative elimination β-hydroxyacid to yield corresponding cyclic enol ether, which subsequently coupled functionalized...
Abstract Remdesivir 1 is an amidate prodrug that releases the monophosphate of nucleoside GS-441524 ( 2 ) into lung cells thereby forming bioactive triphosphate 2-NTP . , analog ATP, inhibits SARS-CoV-2 RNA-dependent RNA polymerase replication and transcription viral RNA. Strong clinical results for have prompted interest in oral approaches to generate Here we describe discovery a 5’-isobutyryl ester GS-5245, Obeldesivir, 3 has low cellular cytotoxicity three seven-fold improved delivery...
Abstract The total synthesis of (+)‐9‐ epi ‐dictyostatin ( 1b ), a diastereomer the antimitotic marine‐sponge‐derived macrolide (–)‐dictyostatin 1a was achieved by creating 11 stereogenic centers and 4 double bonds with high level stereocontrol. yield for 29‐step longest linear sequence from Roche ester 1.53 %. final key steps to this unnatural product were vinylzincate C10–C26 addition aldehyde C1–C9 (leading surprisingly complete stereoselectivity 9 R ‐epimer), followed Yamaguchi...
The reaction of organometallic reagents with vinylogous esters (Stork–Danheiser transposition) provides direct access to 3-substituted cyclic enones. However, the typically fails sterically hindered aryl or alkyl nucleophiles due competing enolization. Cerium(III) chloride and other lanthanide salts have traditionally been used mitigate basicity enhance nucleophilic behavior challenging nucleophiles. Yet, in our experience, using CeCl3 as a mediator Stork–Danheiser transposition resulted...
The ability to identify embryos that have the highest developmental potential from a cohort would significantly increase chances of achieving pregnancy. Metabolic analysis is well-established analytical approach in biological systems. Starting this idea, we chose use high-resolution nuclear magnetic resonance (<sup>1</sup>H-NMR) spectroscopy. aim study was determine if it possible select viable after 48 h culture using metabolic activity as parameter. We evaluated embryo metabolism first and...
Abstract ( Z )‐Vinyl iodides 6a – d were synthesized in high yield with good diastereo‐ and enantioselectivity using a Marshall–Tamaru, Pd‐catalyzed allenylzinc reaction as the key step. The addition of to dictyostatin C1–C9 β‐silyloxy aldehyde 5 was carried out through vinyllithium lithium vinylzincate routes. additions always proceeded higher yields gave fewer side products than corresponding additions. configuration newly created C9 stereocenter assigned Rychnovsky's acetonide 13 C NMR...
Abstract A six‐step, stereoselective synthesis of cyclin‐dependent kinase 2 (CDK2) inhibitor GNE‐140 was developed. The key bonds were assembled through palladium‐catalyzed Negishi cross‐coupling and Buchwald–Hartwig C−N coupling steps. stereodiad established a single‐step, CuH‐catalyzed enone reduction proceeding in >99 : 1 er 89 11 dr. obtained 25 % overall yield with 98.6 A% HPLC purity.
Allenylsilanolates can undergo cross-coupling at the α- or γ-terminus, and site selectivity appears to be determined by intrinsic transmetalation mechanism. Fine-tuning of concentration, nucleophilicity, steric bulk silanolate moiety allows for selective formation one isomer over other. Whereas α-isomer obtained in synthetically useful yield, γ-isomer is favored only when employing reaction conditions that are inevitably associated with diminished reactivity.
It has been previously shown that during the pre-implantation phase of embryo development, pentose phosphate energy pathway is 4 times more active in female embryos when compared with male (Tiffin et al. 1991 J. Reprod. Fertil. 93, 125–132). The different metabolic and growth rates can be attributed to expression X-linked genes between sexes early stages which both X chromosomes are still (Okamoto 2004 Science 303, 644–649). aim this study was evaluate, by proton magnetic resonance (H1-NMR)...
Wide-spread use of IVF has significantly increased the number multiple births (Janvier et al. 2011 J. Pediatr. 159, 409–413). A potential solution to this problem is develop improved methods for embryo selection permit single-embryo transfer. Identification a noninvasive technique assess implantation in assisted reproduction would greatly increase success rates and lead more efficient The aim study was whether there are metabolic differences among embryos produced by obtained parthenogenetic...
Despite the presence of glycogen and triglycerides as energy reserves in bovine embryos, viability embryonic cells culture is maintained primarily by energetic substrates present medium. The aim this experiment was evaluate embryo metabolism during three important stages development: Days 1 to 3, 3 5, 5 7; before formation Barr body, differentiation into ICM trophectoderm, blastocyst formation, respectively. In study, we evaluated some (Krebs cycle intermediates). For these analyses chose...
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