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The Journal of Organic Chemistry Jun 2024The Beckmann reaction is one of the most atom-economical methods for the preparation of amides from ketones. Unlike ketones, the multiple competing reactivities of...
The Beckmann reaction is one of the most atom-economical methods for the preparation of amides from ketones. Unlike ketones, the multiple competing reactivities of enones as well as the requirement of demanding reaction conditions for in situ generation of oximes have severely impacted the application of this reaction for the preparation of α,β-unsaturated amides. Herein, we describe the first chemoselective method for the direct conversion of enones to the corresponding α,β-unsaturated amides using -Boc--tosylhydroxylamine.
PubMed: 38800985
DOI: 10.1021/acs.joc.3c02478 -
Neoadjuvant BRAF-targeted therapy for ameloblastoma of the mandible: an organ preservation approach.Journal of the National Cancer Institute Apr 2024Ameloblastoma is a rare odontogenic neoplasm frequently located in the mandible. Standard treatment involves radical bone resection and immediate reconstruction, causing...
BACKGROUND
Ameloblastoma is a rare odontogenic neoplasm frequently located in the mandible. Standard treatment involves radical bone resection and immediate reconstruction, causing functional, aesthetic, and psychological impairments. The BRAF V600E mutation is present in approximately 80% of mandible ameloblastomas, and BRAF inhibitors have demonstrated sustained responses in unresectable cases.
METHODS
We identified ameloblastoma patients planned for ablative surgery and screened them for BRAF V600E mutation. Neoadjuvant BRAF inhibitors were offered to facilitate jaw preservation surgery. Retrospective data collection encompassed treatment regimens, tolerability, tumor response, and conversion to mandible preservation surgery.
RESULTS
Between 2017 and 2022, a total of 11 patients received dabrafenib (n = 6) or dabrafenib with trametinib (n = 5). The median age was 19 (range = 10-83) years. Median treatment duration was 10 (range = 3-20) months. All (100%) patients achieved a radiological response. Ten (91%) patients successfully converted to mandible preservation surgery with residual tumor enucleation. One patient attained complete radiological response, and surgery was not performed. Among the 10 surgically treated patients, all exhibited a pathological response, with 4 achieving near complete response and 6 partial response. At a median follow-up of 14 (range = 7-37) months after surgery, 1 case of recurrence was observed. Grade 1-2 adverse effects were reported in 8 (73%) patients, with a single case of grade 3 (hepatitis). Dose modification was necessary for 3 patients, and 4 experienced treatment interruptions, while 1 patient permanently discontinued therapy.
CONCLUSIONS
Neoadjuvant BRAF inhibition may offer a safe and effective strategy for organ preservation in mandible ameloblastoma treatment.
Topics: Humans; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Ameloblastoma; Proto-Oncogene Proteins B-raf; Neoadjuvant Therapy; Retrospective Studies; Organ Preservation; Mutation; Protein Kinase Inhibitors; Mandible; Imidazoles; Oximes
PubMed: 37966914
DOI: 10.1093/jnci/djad232 -
Science Advances Mar 2024The limited capacity of typical materials to resist stress loading, which affects their mechanical performance, is one of the most formidable challenges in materials...
The limited capacity of typical materials to resist stress loading, which affects their mechanical performance, is one of the most formidable challenges in materials science. Here, we propose a bone-inspired stress-gaining concept of converting typically destructive stress into a favorable factor to substantially enhance the mechanical properties of elastomers. The concept was realized by a molecular design of dynamic poly(oxime-urethanes) network with mesophase domains. During external loading, the mesophase domains in the condensed state were aligned into more ordered domains, and the dynamic oxime-urethane bonds served as the dynamic molecular locks disassociating and reorganizing to facilitate and fix the mesophase domains. Consequently, the tensile modulus and strength were enhanced by 1744 and 49.3 times after four cycles of mechanical training, respectively. This study creates a molecular concept with stress-gaining properties induced by repeated mechanical stress loading and will inspire a series of innovative materials for diverse applications.
PubMed: 38517961
DOI: 10.1126/sciadv.adk5177 -
Sustainable ionic liquids-based molecular platforms for designing acetylcholinesterase reactivators.Chemico-biological Interactions Nov 2023We report a green chemistry approach for preparation of oxime-functionalized ILs as AChE reactivators: amide/ester linked IL, l-alanine, and l-phenylalanine derived...
We report a green chemistry approach for preparation of oxime-functionalized ILs as AChE reactivators: amide/ester linked IL, l-alanine, and l-phenylalanine derived salts bearing pyridinium aldoxime moiety. The reactivation capacities of the novel oximes were evaluated towards AChE inhibited by typical toxic organophosphates, sarin (GB), VX, and paraoxon (PON). The studied compounds are mostly non-toxic up to the highest concentrations screened (2 mM) towards Gram-negative and Gram-positive bacteria cell lines and both filamentous fungi and yeasts in the in vitro screening experiments as well as towards the eukaryotic cell (CHO-K1 cell line). Introduction of the oxime moiety in initially biodegradable structure decreases its ability to biodegradation. The compound 3d was shown to reveal remarkable activity against the AChE inhibited by VX, exceeding conventional reactivators 2-PAM and obidoxime. The regularities on antidotal activity, cell viability, plasma stability, biodegradability as well as molecular docking study of the newly synthesized oximes will be used for further improvement of their structures.
Topics: Acetylcholinesterase; Ionic Liquids; Molecular Docking Simulation; Oximes; Antidotes; Cholinesterase Reactivators; Cholinesterase Inhibitors; Pyridinium Compounds
PubMed: 37802409
DOI: 10.1016/j.cbi.2023.110735 -
Organic Letters Nov 2023A visible-light-induced β-acyl difunctionalization of alkenes with acyl oxime esters and various nucleophiles was developed to achieve molecular complexity from readily...
A visible-light-induced β-acyl difunctionalization of alkenes with acyl oxime esters and various nucleophiles was developed to achieve molecular complexity from readily available raw materials via oxidative radical-polar crossover. A variety of nucleophiles, including H-sulfoximines, indoles, indazole, and trimethoxybenzene, were all effectively applicable to the sustainable reaction system. The novel synthetic strategy features mild reaction conditions, a broad substrate scope (39 examples), easy scale-up, and excellent regioselectivity.
PubMed: 37939226
DOI: 10.1021/acs.orglett.3c03121 -
Organic Letters Sep 2023An S1-type fluorination method for monofluoroethers is developed. The key to this reaction is fluorinative C-C bond cleavage that is driven by oxygen-assisted Beckmann...
An S1-type fluorination method for monofluoroethers is developed. The key to this reaction is fluorinative C-C bond cleavage that is driven by oxygen-assisted Beckmann fragmentation. To enable this transformation, cyclic α-aryloxyoximes derived from 3-coumaranone and 1-indanones were investigated as substrates, using ,-diethylaminosulfur trifluoride (DAST) as a dual-role reagent of an oxime activator and fluoride donor. This method features the synthesis of an underdeveloped chemical motif with simple and mild operating conditions.
PubMed: 37616502
DOI: 10.1021/acs.orglett.3c02343 -
Journal of Biomolecular Structure &... Dec 2023Up to now, significant research efforts have been directed towards investigating indirubin and its derivatives as potential candidates for developing new compounds with...
Up to now, significant research efforts have been directed towards investigating indirubin and its derivatives as potential candidates for developing new compounds with multiple biological activities. In the present work, natural indirubin and numerous of its chemical derivatives referred to as indirubins have been investigated computationally using DFT method with the B3LYP/6-311 + G(d,p) level of theory, in order to reveal structure- biological activity relationship. We started with a structural properties description. Results analysis indicated that extra interaction sites were provided through the set of substitutions in compounds (1): Indirubin-3'-monoxime, (2): Indirubin-5-sulfonic acid, (3): 5-Nitro-indirubinoxime, (4): 5'-OH-5-nitro-indirubinoxime (AGM130), (5): 7-Bromo-5'-carboxyindirubin-3'-oxime, and (6): 7 BIO and consequently, extra hydrogen bonds may be formed with the active sites of molecular targets, such as GSK-3, CDKs, and Aurora kinases, as well as the aryl hydrocarbon receptor. Subsequently, to get more information on the electronic properties of indirubin and its analogues, HOMO, LUMO, E, and further electronic parameters were carried out. The indirubin derivatives showed an easier interaction with its environment than indirubin, the parent compound. The UV-Visible spectra of indirubin and compounds 1-6 were also produced using TD-DFT with B3LYP functional and 6-311 + G(2d,p) basis set. The relationship between absorption and chemical structure is discussed. Two phototoxic brominated compounds showed important absorption spectra modifications. It was also found that the main absorption bands of all compounds derived from π→π*(HOMO→LUMO) transitions.Communicated by Ramaswamy H. Sarma.
PubMed: 38100566
DOI: 10.1080/07391102.2023.2294182 -
Molecules (Basel, Switzerland) Nov 2023A study on the synergistic extraction of Eu(III) ions with a series of chelating ligands and determination of the process parameters is presented by employing ionic...
A study on the synergistic extraction of Eu(III) ions with a series of chelating ligands and determination of the process parameters is presented by employing ionic liquids and typical organic diluents. The investigations of the liquid-liquid extraction, commonly applied in the separation science of 4f and 5f-ions acidic chelating compounds, 4-benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one (HP), 4-benzoyl-3-phenyl-5-isoxazolone (HPBI), and 2-thenoyltrifluoroacetone (HTTA) alone and in combination with two synergistic agents, -hexamethylpropyleneamine oxime (S2: HM-PAO) and its bis-imine precursor (S1: pre-HM-PAO), are presented. The interaction between the two extractants (acidic/neutral) in deuterochloroform was studied using H, C, and H-H NOESY experiments. Several conclusions are given highlighting the role of the ionic diluent in complexation processes and selectivity with an employment of the two synergistic agents for various metal s-, p-, d-, and f-cations in the Periodic table, with almost 25 metal ions. The objective was to optimize a system for 4f-ions solvent extraction based on the new oxime molecules with β-diketone/isoxazolone/pyrazolone partnership. As detailed above, slight enhancements of extraction efficiencies were obtained either by using basic synergistic agents such as HM-PAO and/or using pre-HM-PAO. A competitive solvent extraction test of nearly 18 f-ions by various ligands (HTTA, S1, S2, and HPBI) and the two mixtures HTTA-S1 and HTTA-S2 diluted in ILs or organic diluents was also conducted in order to evaluate the switchable diluent impact. Additionally, electron paramagnetic resonance (EPR) spectroscopy was used to study the established chemical species with Cu cations in the obtained organic extracts involving the two synergistic molecules.
PubMed: 38005189
DOI: 10.3390/molecules28227467 -
Bioscience, Biotechnology, and... Jan 2024Aldoxime (R1R2C=NOH) and nitrile (R-C≡N) are nitrogen-containing compounds that are found in species representing all kingdoms of life. The enzymes discovered from the... (Review)
Review
Aldoxime (R1R2C=NOH) and nitrile (R-C≡N) are nitrogen-containing compounds that are found in species representing all kingdoms of life. The enzymes discovered from the microbial "aldoxime-nitrile" pathway (aldoxime dehydratase, nitrile hydratase, amidase, and nitrilase) have been thoroughly studied because of their industrial importance. Although plants utilize cytochrome P450 monooxygenases to produce aldoxime and nitrile, many biosynthetic pathways are yet to be studied. Cyanogenic millipedes accumulate various nitrile compounds, such as mandelonitrile. However, no such aldoxime- and nitrile-metabolizing enzymes have been identified in millipedes. Here, I review the exploration of novel enzymes from plants and millipedes with characteristics distinct from those of microbial enzymes, the catalysis of industrially useful reactions, and applications of these enzymes for nitrile compound production.
Topics: Animals; Arthropods; Nitriles; Hydro-Lyases; Oximes; Catalysis
PubMed: 38017623
DOI: 10.1093/bbb/zbad168 -
Molecules (Basel, Switzerland) Oct 2023Recent studies have demonstrated the antiproliferative and cytotoxic effects of aza-steroids and steroidal sapogenins on human cancer cell lines. The scientific...
Recent studies have demonstrated the antiproliferative and cytotoxic effects of aza-steroids and steroidal sapogenins on human cancer cell lines. The scientific community has shown a growing interest in these compounds as drug candidates for cancer treatment. In the current work, we report the synthesis of new diosgenin oxime derivatives as potential antiproliferative agents. From (25 )-5α-spirost-3,5,6-triol (), a diosgenin derivative, ketones , , and were obtained and used as precursors of the new oximes. A condensation reaction was carried out between the steroidal ketones (, , , and ) with hydroxylamine hydrochloride in 2,4,6-trimethylpyridine to produce five spirostanic oximes (four of them are not reported before) with a 42-96% yield. Also, a new spirostanic , -unsaturated cyanoketone was synthesized via Beckmann fragmentation using thionyl chloride with a 62% yield. Furthermore, we proposed a reaction mechanism with the aim of explaining such transformation.
Topics: Humans; Cyanoketone; Diosgenin; Steroids; Antineoplastic Agents; Oximes; Ketones
PubMed: 37959702
DOI: 10.3390/molecules28217283