Оцінка якості надання медичної допомоги хворим стаціонарних відділень Сумської ЦРКЛ на основі цільового соціологічного опитування

У загальносвітових тенденціях стосовно покращання якості медичної допомоги превалює залучення механізмів безпосереднього впливу у самому закладі охорони здоров’я через систематичне оцінювання роботи персоналу та вивчення думки пацієнтів. Мета: визначити оцінку задоволеності пацієнтів стаціонарних відділень якістю медичної допомоги на основі цільового соціологічного опитування

A New Synthesis of α-Amino Acid Thioesters by Pummerer Reaction of 3-Substituted-4-sulfinyl-β-sultams

α-Amino acid thioesters were synthesized by the Pummerer reaction of 3-substituted-4-sulfinyl-β-sultams with TFAA. The 3-substituted-4-sulfinyl-β-sultams were prepared from the corresponding β-sultams by sulfenylation with diphenyl disulfide followed by m-CPBA oxidation. Diastereoselective synthesis of β-sultams by 1,3-asymmetric induction in [2 + 2] cycloaddition of a sulfene intermediate and chiral imines in solution-phase was studied, and it was found that N-alkylimines gave better diastereoselectivities than N-aralkylimines. The use of imines derived from (R)- and (S)-α-methylbenzylamine followed by separation of the major and minor diastereomers gave enantiopure 3-substituted-N-methylbenzyl-β-sultams. These β-sultams were then converted to N-methylbenzyl-α-amino acid thioesters via sulfenylation and Pummerer rearrangement with high or complete retention of configuration

A New Synthesis of α-Amino Acid Thioesters by Pummerer Reaction of 3-Substituted-4-sulfinyl-β-sultams

α-Amino acid thioesters were synthesized by the Pummerer reaction of 3-substituted-4-sulfinyl-β-sultams with TFAA. The 3-substituted-4-sulfinyl-β-sultams were prepared from the corresponding β-sultams by sulfenylation with diphenyl disulfide followed by m-CPBA oxidation. Diastereoselective synthesis of β-sultams by 1,3-asymmetric induction in [2 + 2] cycloaddition of a sulfene intermediate and chiral imines in solution-phase was studied, and it was found that N-alkylimines gave better diastereoselectivities than N-aralkylimines. The use of imines derived from (R)- and (S)-α-methylbenzylamine followed by separation of the major and minor diastereomers gave enantiopure 3-substituted-N-methylbenzyl-β-sultams. These β-sultams were then converted to N-methylbenzyl-α-amino acid thioesters via sulfenylation and Pummerer rearrangement with high or complete retention of configuration

Electronic supplementary material for 'Exploring a chemical scaffold for rapid and selective photoaffinity labeling of nonribosomal peptide synthetases in living bacterial cells'

Non-ribosomal peptide synthetases (NRPSs) biosynthesize many pharmaceuticals and virulence factors. The biosynthesis of these natural peptide products from biosynthetic gene clusters depends on complex regulations in bacteria. However, our current knowledge of NRPSs is based on enzymological studies using full NRPS systems and/or a single NRPS domain in heterologous hosts. Chemical and/or biochemical strategies to capture the endogenous activities of NRPSs facilitate studies on NRPS cell biology in bacterial cells. Here, we describe a chemical scaffold for the rapid and selective photoaffinity labelling of NRPSs in purified systems, crude biological samples and living bacterial cells. We synthesized photoaffinity labelling probes coupled with 5′-O-N-(phenylalanyl)sulfamoyladenosine with clickable alkyl diazirine or trifluoromethyl phenyl diazirine. We found that a trifluoromethyl phenyl diazirine-based probe cross-linked the Phe-activating domain of a GrsA-NRPS with high selectivity and sensitivity at shorter ultraviolet (UV) irradiation times (less than 5 min) relative to a prototypical benzophenone-based probe. Our results demonstrated that this quick labelling protocol can prevent damage to proteins and cells caused by long UV irradiation times, providing a mild photoaffinity labelling method for biological samples.This article is part of the theme issue ‘Reactivity and mechanism in chemical and synthetic biology’

Development of Novel Diastereoselective Alkenylation of Enolates Using Alkenylselenonium Salts

A novel alkenylation of enolates using alkenylselenonium salts is described. A reaction of lithium enolates, which were prepared in situ by the reaction of LiHMDS and carbonyl compounds, with alkenylselenonium salts gave the ethenylation products of carbonyl compounds in high yield. Diastereoselective alkenylation was also accomplished by the reaction of the enolates derived from N-acyl-1,3-oxazolidin-2-ones with the alkenylselenonium salt to afford good results (up to 92% yield and up to 95% de)

Stereospecific Syntheses of 5-Alkyl-3-ethoxy-2-((phenylchalcogeno)methylene)tetrahydrofurans

2-Ethoxy-4-(phenylchalcogeno)but-3-ynyl ketones 1−10 were reduced with LiBH4 in Et2O diastereoselectively to give 5-(phenylchalcogeno)pent-4-yn-1-ols 11−20. Treatment of the phenylchalcogen-substituted alkynyl alcohols 11−20 with t-BuOK in t-BuOH provided useful (Z)-2-((phenylchalcogeno)methylene)tetrahydrofurans 21−31 stereoselectively

Development of Novel Diastereoselective Alkenylation of Enolates Using Alkenylselenonium Salts

A novel alkenylation of enolates using alkenylselenonium salts is described. A reaction of lithium enolates, which were prepared in situ by the reaction of LiHMDS and carbonyl compounds, with alkenylselenonium salts gave the ethenylation products of carbonyl compounds in high yield. Diastereoselective alkenylation was also accomplished by the reaction of the enolates derived from N-acyl-1,3-oxazolidin-2-ones with the alkenylselenonium salt to afford good results (up to 92% yield and up to 95% de)

Reactions of Diphenyl(phenylethynyl)selenonium Salts with Active Methylene Compounds and Amides: First Isolation of Oxyselenuranes [10-Se-4(C3O)] as a Reaction Intermediate

The reaction of the diphenyl(phenylethynyl)selenonium triflate 1a with active methylene compounds 5 and t-BuOK in THF gave furan derivatives 6. The [10-Se-4(C3O)] selenuranes 8a and 8b could be isolated from the reactions with benzoylacetonitrile 5f and with 1,3-indandione 5g, respectively, as reaction intermediates. The structures of the selenuranes 8 were elucidated by X-ray crystallography and 77Se high-resolution solid-state NMR spectroscopy. The selenuranes 8 underwent ligand coupling on standing at room temperature or refluxing in chloroform and gave the furan derivatives 6 and the ring-opened product 9. Similarly, the reaction of 1a with benzamide 13a and pivalamide 13d in the presence of NaH in THF afforded oxazole derivatives 14

Radical Nitrososulfonation of Propargyl Alcohols: Thiazolidine-2,4-dione-Assisted Synthesis of 5‑Alykyl-4-sulfonylisoxazoles

In this study, we discover a good NO/HNO precursor, N-hydroxypyridinesulfonamide, and the regioselective radical nitrososulfonylation reaction of propargyl alcohols. Direct and unique isoxazole synthesis afforded a good-to-high yield of 5-alkyl-3-aryl-4-pyridinesulfonylisoxazoles. Copper-catalyzed aerobic oxidation could efficiently proceed in the presence of thiazolidine-2,4-dione. This work provides a powerful method for the synthesis and functionalization of alkyl-substituted isoxazoles and explores a new investigation route for drug–drug discovery