A5081178355- Synthetic Organic Chemistry Methods
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Chemical synthesis and alkaloids
- Alkaloids: synthesis and pharmacology
- Pharmacological Effects and Toxicity Studies
- Chemical Synthesis and Analysis
- Electroconvulsive Therapy Studies
- Microbial Natural Products and Biosynthesis
- Carbohydrate Chemistry and Synthesis
- Metabolism and Genetic Disorders
- Neurological and metabolic disorders
- Asymmetric Synthesis and Catalysis
- Epilepsy research and treatment
- Advanced Synthetic Organic Chemistry
- Diet and metabolism studies
- Schizophrenia research and treatment
- Cancer Treatment and Pharmacology
- Forensic Toxicology and Drug Analysis
- Marine Sponges and Natural Products
- Poisoning and overdose treatments
- Glycosylation and Glycoproteins Research
- Treatment of Major Depression
- Cannabis and Cannabinoid Research
- Receptor Mechanisms and Signaling
Temple University
2014-2023
Vita Care (Brazil)
2023
Universidade Feevale
2023
Faculdade da Serra Gaúcha
2016-2020
Division of Chemistry
2018
National Center for Advancing Translational Sciences
2018
National Institutes of Health
2018
Universidade Federal do Rio Grande do Sul
2010-2017
Universidade Federal Rural do Rio de Janeiro
2017
Wayne State University
2010-2015
Described is an efficient one-pot synthesis of α- and β-glycosyl phosphate dithiophosphate triesters from glycals via 1,2-anhydrosugars. Glycosyl phosphates function as versatile glycosylating agents for the β-glucosidic, β-galactosidic, α-fucosidic, α-mannosidic, β-glucuronic acid, β-glucosamine linkages upon activation with trimethylsilyl trifluoromethanesulfonate (TMSOTf). In addition to serving donors O-glycosylations, glycosyl are effective in preparation S-glycosides C-glycosides....
Differentially protected glycosyl phosphates prepared by a straightforward synthesis from glycal precursors are used as powerful donors. Activation of β-glycosyl TMSOTf at −78 °C achieves the selective formation β-glycosidic linkages in excellent yields with complete stereoselectivity. Reaction thiols results conversion into thioglycosides nearly quantitative yield. An orthogonal coupling strategy using phosphate donors and thioethyl glycoside acceptors allows for rapid trisaccharide.
Concise total syntheses of Strychnos alkaloids strychnine (1) and akuammicine (2) have been realized in 13 6 operations, respectively. Key steps include the vinylogous Mannich reaction; a novel, sequential one-pot spirocyclization/intramolecular aza-Baylis−Hillman (3) Heck cyclization. The synthesis 1 proceeds via Wieland−Gumlich aldehyde (26).
Paper-based analytical devices are the subject of growing interest for development low-cost point-of-care diagnostics, environmental monitoring technologies, and research tools limited-resource settings. However, there limited chemistries available conjugation biomolecules to cellulose use in biomedical applications. Herein, divinyl sulfone (DVS) chemistry was demonstrated immobilize small molecules, proteins, DNA covalently onto hydroxyl groups membranes through nucleophilic addition....
Over half of all antibiotics target the bacterial ribosome-nature's complex, 2.5 MDa nanomachine responsible for decoding mRNA and synthesizing proteins. Macrolide antibiotics, exemplified by erythromycin, bind 50S subunit with nM affinity inhibit protein synthesis blocking passage nascent oligopeptides. Solithromycin (1), a third-generation semisynthetic macrolide discovered combinatorial copper-catalyzed click chemistry, was synthesized in situ incubating either E. coli 70S ribosomes or...
[formula: see text] A beta-(1-->4)-linked trisaccharide was prepared in 53% yield on a polymer support using glycosyl phosphates and released by cross-metathesis of novel linker to reveal the anomeric n-pentenyl glycoside. Heptasaccharide 33 9% 14 steps.
A sequential one-pot biscyclization route to the ABCE tetracyclic framework of Strychnos alkaloids has been developed. Specifically, AgOTf-mediated spirocyclization an appropriately functionalized indole 3-carbinamide afforded a stable spiroindolenine intermediate; subsequent addition DBU reaction mixture effected unprecedented intramolecular aza-Baylis−Hillman reaction, delivering product in 70% isolated yield.
Concise asymmetric total syntheses of Strychnos alkaloids (−)-leuconicine A (14 steps, 9% overall yield) and B (13 10% have been accomplished. Key steps include (1) our sequential one-pot spiro-cyclization/intramolecular aza-Baylis-Hillman method to prepare the ABCE framework; (2) a novel domino acylation/Knoevenagel cyclization F-ring; (3) Heck access D-ring.
Summary While the characterization of biosynthetic pathway monoterpene indole alkaloids ( MIA s) in leaves Catharanthus roseus is now reaching completion, only two enzymes from root counterpart dedicated to tabersonine metabolism have been identified date, namely 19‐hydroxylase (T19H) and minovincine 19‐ O ‐acetyltransferase MAT ). Albeit recombinant catalyzes acetylation at low efficiency vitro , we demonstrated that was inactive when expressed yeast planta suggesting an alternative...
The development and application of the arene-fused domino Michael/Mannich route to tetrahydrocarbazole (ABE) core Aspidosperma alkaloids is described. scope this novel transformation was studied in terms nucleophilic component (i.e., N-sulfinyl metallodienamine) electrophilic Michael acceptor). successful methodology toward concise total syntheses classical indole (-)-aspidospermidine, (-)-tabersonine, (-)-vincadifformine 10-11 steps, respectively, also discussed.
Esta pesquisa experimental, com práticas laboratoriais, teve como objetivo analisar a qualidade da água em um município no interior de Goiás, comparando seus aspectos físico-químicos os parâmetros estabelecidos pela Portaria GM/MS n° 888, 4 maio 2021 e o Ministério Saúde, 2006. O rápido crescimento populacional algumas regiões, impulsionado expansão universidades, indústrias agronegócios, tem aumentado significativamente demanda local por água, que pode gerar problemas escassez comprometer...
A linear synthesis of a fully protected H-type II blood group determinant pentasaccharide utilizing glycosyl phosphate and trichloroacetimidate building blocks is reported. Envisioning an automated solid-phase determinants, the utility phosphates in stepwise construction complex oligosaccharides, such as antigen, demonstrated. Installation central glucosamine block required screening variety nitrogen protecting groups to ensure good donor reactivity compatibility. The challenge differentiate...
Silicon photonic microring resonators have established their potential for label-free and low-cost biosensing applications. However, the long-term performance of this optical sensing platform requires robust surface modification biofunctionalization. Herein, we demonstrate a conjugation strategy based on an organophosphonate coating vinyl sulfone linker to biofunctionalize silicon biomolecular sensing. To validate method, series glycans, including carbohydrates glycoconjugates, were...
Graphical Abstract 'Melo' out: A concise asymmetric synthesis of (−)-melotenine has been accomplished in fourteen steps and 1 % overall yield from commercial N-tosylindole-3-carboxaldehyde. Key include a Piers annulation, an intermolecular vinylogous aldol reaction, novel one-pot sequence to prepare the ABCE tetracycle. Boc=tert-butoxycarbonyl, Ts=4-toluenesulfonyl.
Lochnericine is a major monoterpene indole alkaloid (MIA) in the roots of Madagascar periwinkle (Catharanthus roseus). derived from stereoselective C6,C7-epoxidation tabersonine and can be metabolized further to generate other complex MIAs. While enzymes responsible for its downstream modifications have been characterized, those involved lochnericine biosynthesis remain unknown. By combining gene correlation studies, functional assays, transient inactivation, we identified two highly...
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...
Efficiency is a key organizing principle in modern natural product synthesis. Practical criteria include time, cost, and effort expended to synthesize the target, which tracks with step-count scale. The execution of synthesis, that is, sum identity each reaction employed therein, falls along continuum chemical (abiotic) synthesis on one extreme, followed by hybrid chemoenzymatic approach, ultimately biological (biosynthesis) other, acknowledging first belongs Nature. Starting materials also...
Concise formal syntheses of marine alkaloids (±)-pinnaic acid (1) and (±)-halichlorine (2) have been accomplished from a common intermediate. The illustrate the utility selective olefin cross metathesis methodologies for elaboration advanced synthetic intermediates in complex molecule synthesis.
Homocystinuria is a neurometabolic disease caused by severe deficiency of cystathionine beta-synthase activity, resulting in hyperhomocysteinemia. Affected patients present several symptoms including variable degree motor dysfunction. In this study, we investigated the effect chronic hyperhomocysteinemia on cell viability mitochondrion, as well some parameters energy metabolism, such glucose oxidation and activities pyruvate kinase, citrate synthase, isocitrate dehydrogenase, malate...
Novel sources of antibiotics are required to address the serious problem antibiotic resistance. Telithromycin (2) is a third-generation macrolide prepared from erythromycin (1) and used clinically since 2004. Herein we report details our efforts that ultimately led total synthesis (−)-4,8,10-tridesmethyl telithromycin (3) wherein methyl groups have been replaced with hydrogens. The desmethyl macrolides has emerged as novel strategy for preparing bioactive antibiotics.
Novel sources of antibiotics are needed to address the serious threat bacterial resistance. Accordingly, we have launched a structure-based drug design program featuring desmethylation strategy wherein methyl groups been replaced with hydrogens. Herein report total synthesis, molecular modeling, and biological evaluation 4-desmethyl telithromycin (6), novel desmethyl analogue third-generation ketolide antibiotic (2) our final in this series. While (6) was found be equipotent against...
Complexes of 9-methyladenine with 46 heterocycles commonly found in drugs were located using dispersion-corrected density functional theory, providing a representative set 408 unique stacked dimers. The predicted binding enthalpies for each heterocycle span broad range, highlighting the strong dependence stacking interactions on relative orientation interacting rings. Overall, presence NH and carbonyl groups lead to strongest 9-methyadenine, strength π-stacking is sensitive distribution...