RESUMO
Reaction of sulfonimidoyl fluorides with anilines and Ca(NTf2)2 results in the formation of chiral sulfonimidamides. The reaction proceeds with inversion of the stereocenter at a sulfur atom. Enantiospecificity of the reaction was observed for all studied non-heterocyclic anilines. Combined experimental and computational mechanistic studies highlight chelate-type coordination of the sulfonimidoyl group to Ca(NTf2)2 and the formation of a SN2-like transition state, in which leaving F- coordinates with the Ca2+ ion.
RESUMO
The products of the SuFEx reaction between sulfonimidoyl fluorides and phenols, sulfonimidates, are shown to display dynamic covalent chemistry with other phenols. This reaction was shown to be enantiospecific, finished in minutes at room temperature in high yields, and useful for both asymmetric synthesis and sustainable polymer production. Its wide scope further extends the usefulness of SuFEx and related click chemistries.
Assuntos
Polímeros , Enxofre , Química Click , Estrutura Molecular , FenóisRESUMO
Novel methods to make synthetic chiral polymers are highly desirable given their potential in a rapidly increasing number of bio-inspired applications. The enantiospecific sulfur-fluorine exchange (SuFEx) reaction of chiral di-sulfonimidoyl fluorides (di-SFs) with diphenols, was used to produce high-molecular-weight chiral polymers with configurational backbone chirality. The resulting new class of polymers, polysulfonimidates, can be efficiently produced via this step-growth mechanism for a wide range of di-SFs and diphenols, yielding MnPS up to 283â kDa with a typical dispersity D around 1.6. The optical activity of the resulting chiral polymers is largely due to the intrinsic asymmetry of the S atoms (configurational chirality). Finally, the enantiospecificity (ee>98 %) of the polymerization reaction was demonstrated by the degradation of a disulfide-containing polysulfonimidate. This novel route towards configurational main-chain chirality opens up new approaches towards tailor-made chiral polymers with precisely defined properties.
RESUMO
Sulfur(VI) fluoride exchange (SuFEx) is a category of click chemistry that enables covalent linking of modular units through sulfur(VI) connective hubs. The efficiency of SuFEx and the stability of the resulting bonds have led to polymer chemistry applications. Now, we report the SuFEx click chemistry synthesis of several structurally diverse SOF4-derived copolymers based on the polymerization of bis(iminosulfur oxydifluorides) and bis(aryl silyl ethers). This polymer class presents two key characteristics. First, the [-N=S(=O)F-O-] polymer backbone linkages are themselves SuFExable and undergo precise SuFEx-based post-modification with phenols or amines to yield branched functional polymers. Second, studies of individual polymer chains of several of these new materials indicate helical polymer structures. The robust nature of SuFEx click chemistry offers the potential for post-polymerization modification, enabling the synthesis of materials with control over composition and conformation.
RESUMO
A new, efficient approach toward the preparation of 2-aryl-2,3-dihydrobenzofuran scaffolds through the Cu/SPDO-catalyzed [3 + 2] cycloaddition between quinone ester and styrene derivatives has been developed. The procedure features excellent enantioselectivities (up to 99% ee), high yields (up to 96%), and broad substrate tolerance. Additionally, asymmetric synthesis of natural corsifurans A and B from commercially available starting materials has also been achieved in two or three steps using this reaction as a key transformation.
RESUMO
We report herein a strategy to construct enantiopure inherently chiral macrocycles, ABCD-type heteracalix[4]aromatics, through a catalytic enantioselective intramolecular C-N bond forming reaction. A chiral ligand-palladium complex was found to efficiently induce the inherent chirality of molecules during the macrocyclization process with ee values up to >99%. The resulting ABCD-type heteracalix[4]aromatics displayed excellent and pH-triggered switchable electronic circular dichroism and circularly polarized luminescence properties.
Assuntos
Calixarenos/síntese química , Complexos de Coordenação/química , Compostos Macrocíclicos/síntese química , Paládio/química , Calixarenos/química , Catálise , Concentração de Íons de Hidrogênio , Ligantes , Compostos Macrocíclicos/química , Estrutura Molecular , EstereoisomerismoRESUMO
SuFEx reactions, in which an S-F moiety reacts with a silyl-protected phenol, have been developed as powerful click reactions. In the current paper we open up the potential of SuFEx reactions as enantioselective reactions, analyze the role of Si and outline the mechanism of this reaction. As a result, fast, high-yielding, "Si-free" and enantiospecific SuFEx reactions of sulfonimidoyl fluorides have been developed, and their mechanism shown, by both experimental and theoretical methods, to yield chiral products.
RESUMO
A number of unprecedented homo heteracalix[2]arene[2]triazines were synthesized by means of a fragment coupling approach. Two directional nucleophilic substitution reactions of N-Boc-protected 1,3-dihydrazobenzene with cyanuric acid chloride and 2-butoxy-4,6-dichloro-1,3,5-triazine led to hydrazo-linked trimers, which underwent an efficient macrocyclic condensation reaction with functionalized resorcinol derivatives to afford (NHNBoc)2,O2-calix[2]arene[2]triazine macrocycles, which contain a functional group either on the upper rim or the lower rim. The use of 1,3-phenylenediamines instead of resorcinol in the reaction produced (NR)2,(NHNBoc)2-calix[2]arene[2]triazines. Postmacrocyclization modifications such as a nucleophilic substitution reaction of chloro on triazine by amines and the removal of Boc from hydrazo moieties produced homo calix[2]arene[2]triazine derivatives. In the solid state, (NHNR)2,O2-bridged calix[2]arene[2]triazines with and without a substituent on the upper rim position and (NMe)2,(NHNBoc)2-calix[2]arene[2]triazine adopted a typical partial cone conformation while the heavily twisted 1,3-alternate conformational structures were observed for both (NHNBoc)2,O2-calix[2]arene[2]triazines bearing a functional group on the lower rim position and (NH)2,(NHNBoc)2-calix[2]arene[2]triazine. In solution, all synthesized homo heteracalix[2]arene[2]triazines existed as the mixture of different macrocyclic conformers, which underwent slow interconversions at room temperature relative to the NMR time scale.
RESUMO
BACKGROUND: Postoperative nausea and vomiting (PONV) is a frequent complication in postoperative period. The aim of this article was to evaluate the effect of dexmedetomidine on PONV. METHOD: RevMan 5.3 software was applied for performing statistic analysis. Twenty-four trials with 2046 patients were included. RESULTS: The PONV of the dexmedetomidine group was significantly lower compared with the placebo group (0.56, 95% CI: 0.46, 0.69). Subgroup analysis further confirmed the effect of dexmedetomidine (irrespective of administration mode) (Pâ<â0.00001). Perioperative fentanyl consumption in dexmedetomidine group were also reduced significantly (Pâ<â0.00001). Whereas, side effects such as bradycardia, hypotension increased in dexmedetomidine group (especially in loading dose mode and loading dose plus continuous infusion mode). CONCLUSIONS: Dexmedetomidine administrated in continuous infusion mode has the advantage to prevent PONV as well as reduce side effects such as bradycardia and hypotension.
Assuntos
Anestesia Geral/efeitos adversos , Dexmedetomidina/administração & dosagem , Náusea e Vômito Pós-Operatórios , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Anestesia Geral/métodos , Humanos , Hipnóticos e Sedativos/administração & dosagem , Infusões Intravenosas , Avaliação de Processos e Resultados em Cuidados de Saúde , Náusea e Vômito Pós-Operatórios/etiologia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Procedimentos Cirúrgicos Operatórios/métodosRESUMO
OBJECTIVE: To investigate whether local A1R of Baihui acupoint mediate cerebral ischemia tolerance induced by electro-acupuncture (EA). METHODS: Sixty SD rats were randomly divided into five groups, i.e., the sham-operation (S) group, the model group (M), the electroacupuncture (E) group, the CCPA group and the DMSO group. The focal cerebral ischemia/reperfusion model was established by middle cerebral artery occlusion (MCAO) in rats. Rats in the E group were received EA pretreatment baihui acupoint at 2 h before established MCAO. The rats in DMSO group and the CCPA group were injected with DMSO (20 µl) and CCPA (0.1 mmol/L) 20 µl into Baihui, respectively, at 2 h before established MCAO. After 24 h reperfusion, the rats' behavior, cerebral infarct volume, the cerebral Bcl-2 protein expression were assessed. RESULTS: Compared with M group, the rats' behavior was improved, the cerebral infarct volume was decreased and the Bcl-2 protein expression was up-regulated (P < 0.05) in the E group. Compared with M and DMSO group, the rats' behavior was improved, the cerebral infarct volume was decreased and the Bcl-2 protein expression was up-regulated (P < 0.05) in the CCPA group. There were no statistical differences between CCPA and E group. CONCLUSIONS: EA induced cerebral ischemia tolerance. Local A1R of Baihui acupoint possible mediate cerebral ischemia tolerance induced by Electroacupuncture.
Assuntos
Isquemia Encefálica/metabolismo , Isquemia Encefálica/terapia , Eletroacupuntura , Receptor A1 de Adenosina/metabolismo , Pontos de Acupuntura , Animais , Precondicionamento Isquêmico/métodos , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Inflammatory and immune responses, as well as melatonin secretion, are affected by circadian regulation. Abnormal circadian rhythm of melatonin release has been reported to be associated with the later stages of sepsis; however, its role in the early stages of sepsis is unclear. We studied 11 septic and 11 non-septic patients in our intensive care unit (ICU). Peripheral blood was drawn at 4-h intervals on the first day, beginning at 2:00 p.m., over a total period of 24 h. Plasma levels of melatonin, tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) were measured by radioimmunoassay or enzyme-linked immunosorbent assay (ELISA). Messenger RNA levels of circadian genes Cry-1 and Per-2 were analyzed using quantitative real-time PCR. Results show the circadian rhythm of melatonin secretion was altered in the early stages of sepsis. The melatonin secretion acrophase occurred earlier in septic patients at 6:00 p.m., compared with at 2:00 a.m. in non-septic ICU patients. Compared with the non-septic group, both Cry-1 and Per-2 expression were significantly decreased while TNF-α and IL-6 expression were significantly increased in septic patients [TNF-α, 64.1 (43.6-89.1) vs. 11.4 (10.4-12.5) ng/ml; IL-6, 41.2 (35.7-50.8) vs. 19.1 (16-136.7) ng/ml; median (range), both P=0.04]. The peak concentrations of TNF-α and IL-6 were shown to be in concordance with the rhythm of melatonin secretion. The circadian rhythm of melatonin secretion and circadian gene expression were altered in the early stages of sepsis, which likely led to the changes in pro-inflammatory cytokine release. These findings shed light on the potential link between circadian rhythm and the progression of early-stage sepsis.
Assuntos
Ritmo Circadiano/genética , Interleucina-6/biossíntese , Melatonina/genética , Sepse/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Adulto , Idoso , Criptocromos/biossíntese , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Melatonina/metabolismo , Pessoa de Meia-Idade , Proteínas Circadianas Period/biossíntese , Sepse/genética , Sepse/patologiaRESUMO
OBJECTIVE: To investigate the effects of nimodipine on symptomatic cerebral vasospasm in rabbits. METHODS: Twenty four japanese white rabbits which ligation of bilateral common carotid arteries and no neurological deficits were randomized to sham-operation, subarachnoid hemorrhage (SAH) and nimodipine which injected of nimodipine 0.1 mg/kg, continuous vein administration 5 day. The behavior scores, neurological scores were observed everyday and cerebral angiography changes were measured twice by 3D-CTA, and basilar artery was removed for pathological examination after last CTA examination. RESULTS: In SAH group, The basilar artery were significantly vasoconstrictive on 5 days, neurological scores were increased, and the basilar artery was found apoptosis-like changes under light microscopic and electron microscope. Nimodipine group could not dilated the basilar artery arteriospasm after SAH, but it could attenuate neurological deficit, and obviously alleviate the pathological changes of basilar artery. CONCLUSION: Nimodipine could not vasodilation of basilar artery in SCVS, but obviously could alleviate neurological changes and pathological changes of basilar artery in rabbits with symptomatic cerebral vasospasm.
Assuntos
Nimodipina/uso terapêutico , Vasodilatadores/uso terapêutico , Vasoespasmo Intracraniano/prevenção & controle , Animais , Artéria Basilar/efeitos dos fármacos , Modelos Animais de Doenças , Nimodipina/farmacologia , Coelhos , Vasodilatadores/farmacologiaRESUMO
Four new neo-clerodane diterpenoid alkaloids, named scutebarbatines I-L (1-4), were isolated from the whole plant of Scutellaria barbata D. DON. Their structures were established on the basis of detailed spectral analyses. In vitro, the four new compounds showed significant cytotoxic activities against three human cancer lines (HONE-1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells), and gave IC(50) values in the range 3.2-8.3 microM.