Tetrahedron最新文献

{"title":"Exploring the reaction mechanistic pathway for the sensing of G-Series nerve agent with Kemp's triacid derivative: A computational study","authors":"Dipankar Das ,&nbsp;Bishwajit Ganguly","doi":"10.1016/j.tet.2024.134281","DOIUrl":"10.1016/j.tet.2024.134281","url":null,"abstract":"<div><div>Kemp's triacid derivative have been reported as a candidate for sensing of nerve agents employing the photoinduced electron transfer (PET) processes. The sensor probe molecules were prepared with primary alcohol in very close proximity to a tertiary amine to acylate the alcohol with rapid intramolecular N-alkylation to produce quaternary ammonium salt. The reaction pathways for the formation of quaternary ammonium salt and isomethyl propyl phosphonate remain unexplored. In this report, the mechanistic pathways of G-series nerve agents sarin and its simulant diethylcholorophosphate (DCP) with Kemp's triacid derivatives has been explored computationally. The calculations performed with B3LYP-D3/6-311+G(d,p) level of theory in DCM solvent revealed that the reaction proceeds via intermolecular and intramolecular S_N2 pathways. The probe molecule is sterically hindered, therefore, the frontside and backside S_N2 reaction pathways have been examined. The computed results suggest that the first intermolecular S_N2 reaction of Kemp's triacid derivatives (<strong>I</strong> &amp; <strong>II</strong>) with sarin for the backside attack is energetically favored compared to the frontside attack and the following intramolecular S_N2 reaction is a barrierless process. The calculations performed with simulant diethylcholorophosphate (DCP) and Kemp's triacid derivatives (<strong>I</strong> &amp; <strong>II</strong>) show that the reactions are energetically more facile compared to the nerve agent sarin molecule. The Distortion-Interaction model and ΔNBOSteric analysis showed that the back side is energetically favored over the front side attack in such S_N2 reactions. The designed Kemp's triacid derivative (<strong>II</strong>) with phosphorus center for sensing sarin and (DCP) suggests that the size of the hetero centers are important to facilitate the reaction in the probe molecule.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"167 ","pages":"Article 134281"},"PeriodicalIF":2.1,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Desulfonation-associated direct amide bond formation between N-sulfonyl-1,2,3-triazoles with carboxylic acids","authors":"Zongjing Hu ,&nbsp;Yaqi Deng ,&nbsp;Jian Ji ,&nbsp;Jinhua Liu ,&nbsp;Yun Zhao ,&nbsp;Shunying Liu ,&nbsp;Shi-Hua Luo","doi":"10.1016/j.tet.2024.134268","DOIUrl":"10.1016/j.tet.2024.134268","url":null,"abstract":"<div><div>We have developed a highly <em>N</em>²-regioselective method for direct construction of amide bond from <em>N</em>-sulfonyl-1,2,3-triazoles and carboxylic acids in the presence of bases at 60 °C in air. The developed reaction provides the corresponding products with high yields (up to 90 %) and a broad substrate compatibility including aryl acids, heterocyclic acids, and alkyl acids. Mechanistic studies show that the reaction proceeds through a direct nucleophilic attack of <em>N</em>-sulfonyl-1,2,3-triazoles to carboxylate anions via a base- and water-involved synergistic desulfonation process. This work presents an unusual water-involved example for direct synthesis of amides utilizing readily available starting materials under mild conditions.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"167 ","pages":"Article 134268"},"PeriodicalIF":2.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physicochemical properties and cytochromes P-450 kinetics of 5,5-bis(4-fluorophenyl)imidazolidine-2,4-dione, the bis(para-fluorophenyl) derivative of phenytoin","authors":"Presley C. Cole,&nbsp;Briana I. Martinez,&nbsp;Thomas A. Shell","doi":"10.1016/j.tet.2024.134275","DOIUrl":"10.1016/j.tet.2024.134275","url":null,"abstract":"<div><div>Phenytoin (PHT, brand name: Dilantin) is an anticonvulsant drug that is used in the treatment of epilepsy. PHT is metabolically inactivated by cytochromes P-450 (CYP) catalyzed aromatic hydroxylation at the <em>para</em> position. Therefore, Nelson et al. hypothesized that this metabolic pathway would be slowed or blocked for a PHT derivative with fluorines at the <em>para</em> positions of the aromatic rings (<em>p</em>F-PHT) resulting in a molecule with increased antiseizure activity and longer duration of action relative to PHT. Interestingly, <em>p</em>F-PHT is less active than PHT, but has a much longer duration of action. Nelson et al. hypothesized that differences in physicochemical properties must contribute to the poor activity of <em>p</em>F-PHT. Thus, <em>p</em>F-PHT was synthesized to compare its physicochemical properties with those of PHT. In addition, the kinetics of CYP catalyzed oxidation were compared using Sprague Dawley (SD) rat liver microsomes because PHT is metabolically inactivated by CYP in the liver. The previously reported synthesis of <em>p</em>F-PHT employs a highly toxic reagent and produces a highly poisonous gas. Therefore, a safer synthetic route for <em>p</em>F-PHT was developed. This synthetic approach utilizes three steps: 1) a thiamine catalyzed benzoin condensation of <em>para</em>-fluorobenzaldehyde, 2) a nitric acid oxidation of the benzoin product to the corresponding benzil derivative, and 3) a microwave-assisted phenytoin synthesis of this benzil derivative with urea. There are no significant differences in conjugation, acidity, and lipophilicity between PHT and <em>p</em>F-PHT. Therefore, our results do not support the hypothesis that the low activity of <em>p</em>F-PHT relative to PHT results from variations in physicochemical properties. While PHT and <em>p</em>F-PHT have the same apparent binding affinity for the CYP proteome of the SD rat liver microsome, <em>p</em>F-PHT undergoes CYP catalyzed oxidation at half the rate in comparison to PHT.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"167 ","pages":"Article 134275"},"PeriodicalIF":2.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One-pot multi-component synthesis of 2-Amino-4H-chromenes catalyzed by a fiber super base under mild conditions","authors":"Haitao Cui ,&nbsp;Pengyu Li ,&nbsp;Huijun Zhao ,&nbsp;Yongqiang Chen ,&nbsp;Yahui Yuan ,&nbsp;Yuan Liu ,&nbsp;Wenying Ai ,&nbsp;Mingli Jiao","doi":"10.1016/j.tet.2024.134282","DOIUrl":"10.1016/j.tet.2024.134282","url":null,"abstract":"<div><p>Heterogeneous catalysis is a crucial component of green chemistry. In this study, a series of polyacrylonitrile fiber (PANF) catalysts, specifically PANF-TBDs, were developed by immobilizing the commonly utilized super organic base 1,5,7-triazabicyclo [4.4.0] dec-5-ene (TBD) onto commercially accessible PANF. This novel catalyst facilitates the effective and eco-friendly one-pot synthesis of 2-amino-4<em>H</em>-chromene. Moreover, an investigation into the impact of modification density on the catalytic efficacy of PANF-TBDs have been conducted. It was observed that PANF-TBD(2.0) with a higher TBD graft density can yield exceptional results, even surpassing 96 %, in a mere 30 min at a mild temperature 30 °C when utilizing water as a green and easily available solvent. Furthermore, the catalyst can be effortlessly isolated from the reaction system and displays notable reusability for a minimum of 10 cycles without show obvious decline in performance.</p></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"167 ","pages":"Article 134282"},"PeriodicalIF":2.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"I2-promoted one-pot synthesis of 1,3,4-oxadiazoles from aroyl hydrazides and methyl/ethyl acetate","authors":"Jianxi Du ,&nbsp;Qin Su ,&nbsp;Ying-Ming Pan ,&nbsp;Keyume Ablajan","doi":"10.1016/j.tet.2024.134280","DOIUrl":"10.1016/j.tet.2024.134280","url":null,"abstract":"<div><div>This study aimed to propose an unprecedented I₂-promoted one-pot tandem synthesis of 1,3,4-oxadiazoles through the cyclization between aroyl hydrazides and methyl/ethyl acetate. A diverse array of 2-arylated 1,3,4-oxadiazoles and 5-methyl 1,3,4-oxadiazoles were successfully synthesized in good to excellent yields. The significant advantage of this protocol was its full exploitation of the principle of atomic economy, whereby the reactant served as the reaction solvent directly. Moreover, the reaction demonstrated a broad substrate scope, and the product was readily separable.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"167 ","pages":"Article 134280"},"PeriodicalIF":2.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One-pot sequential synthesis of fused and non-fused poly-substituted dihydropyridine derivatives under catalyst-free conditions","authors":"Fatemeh Asilpour,&nbsp;Dariush Saberi,&nbsp;Alireza Hasaninejad","doi":"10.1016/j.tet.2024.134279","DOIUrl":"10.1016/j.tet.2024.134279","url":null,"abstract":"<div><p>A one-pot, sequential, three-component procedure is reported for the synthesis of poly-substituted dihydropyridines <em>via</em> the condensation reaction of diamines or aminophenoles, 1,1-bismethylmethio-2-nitroethylene and <em>α</em>,<em>β</em>-unsaturated aromatic ketones in acetonitrile under reflux conditions. A range of fused and non-fused poly-substituted dihydropyridines were prepared in good to high yields with short reaction times.</p></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"167 ","pages":"Article 134279"},"PeriodicalIF":2.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pd0 catalyst/carboxylic acid-mediated hydrofunctionalization of alkynes and allenes, two plausible hydropalladation mechanisms of a versatile process","authors":"Jacques Muzart","doi":"10.1016/j.tet.2024.134256","DOIUrl":"10.1016/j.tet.2024.134256","url":null,"abstract":"<div><p>The review is focused on C–C and C–heteroatom bond forming methodologies involving reactions arising after hydropalladation of alkynes and allenes using Pd⁰ catalysts associated to catalytic or stoichiometric amounts of carboxylic acids. Most of the procedures occur with complete or high atom-economy, avoiding large generation of waste and producing functionalized compounds. The synthetic scope is presented and mechanistic problems are discussed.</p></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"167 ","pages":"Article 134256"},"PeriodicalIF":2.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural simplification of Osimertinib to elaborate new indolyle-pyrimidine-5-carbonitrile derivatives with Anti-proliferative and Anti-SARS-CoV-2 activities assisted by molecular dynamic simulation","authors":"Safaa I. Elewa ,&nbsp;Ibrahim F. Nassar ,&nbsp;Ahmed F. El-Farargy ,&nbsp;Yaseen A.M.M. Elshaier ,&nbsp;Omnia Kutkat ,&nbsp;Asmaa M. Elfiky ,&nbsp;Ahmed A. El-Rashedy ,&nbsp;Eman Mansour","doi":"10.1016/j.tet.2024.134272","DOIUrl":"10.1016/j.tet.2024.134272","url":null,"abstract":"<div><div>Based on the simplicity and modification of the medication osimertinib, two new series of indolyle-pyrimidine-5-carbonitrile scaffolds were created and synthesized with dual action as anti-SARS-Cov-2 and anticancer. The newly created heterocyclic compounds' chemical structures were effectively characterized. With IC50 values of 18.52, 20.89, and 19.85, respectively, compounds <strong>9b, 10</strong>, and <strong>15</strong> had inhibitory actions against SARS-CoV-2 when compared to remdesivir and chloroquine, which served as pharmacological controls and had IC50 values of 3.38 μM and 24.9 μM, respectively.</div><div>Furthermore, compounds <strong>9a</strong> and <strong>13</strong> showed anti-proliferative activity against HepG2 cell lines with IC_50s of 5.63 μM and 3.06 μM, respectively, in comparison to doxorubicin's IC₅₀ of 7.4 μM. qRT-PCR revealed that HepG2 cells treated with compounds <strong>9a</strong> and <strong>13</strong> showed increased p53 expression levels and decreased CDK1 and PI3K expression levels in comparison to doxorubicin. Molecular dynamics simulations of 20 ns duration were performed with PI3Kα, PI3Kγ, and CDK and active compound complexes. The results confirm that compound <strong>13</strong> has the potential to be a therapeutic candidate for additional preclinical and clinical research, as indicated by the molecular docking data.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"167 ","pages":"Article 134272"},"PeriodicalIF":2.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Palladium-catalyzed ring-opening/defluorinative coupling of gem-DFCPs with pyranones/pyridones","authors":"Ling-Juan Tang ,&nbsp;Shun-Jun Ji ,&nbsp;Zhong-Jian Cai","doi":"10.1016/j.tet.2024.134271","DOIUrl":"10.1016/j.tet.2024.134271","url":null,"abstract":"<div><p>The monofluoroalkenes are found widespread applications in areas such as bioactive molecules, materials science and synthetic organic chemistry, therefore, investigating efficient methodologies to construct monofluoroalkenes is still in demand. In this paper, we reported an efficient synthesis of monofluoroalkenyl substituted pyranones/pyridones by using the <em>gem</em>-difluorocyclopropanes (<em>gem</em>-DFCPs) as monofluoroalkenyl precursors. In the presence of Palladium catalyst, the monofluoroalkenyl group was introduced into the C3 positions of pyranones/pyridones successfully. The reaction was featured with high regioselectivity, mild conditions, broad substrate scope, easy to scale up synthesis, which provided a novel avenue for the late-stagy modification of pyranones/pyridones.</p></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"167 ","pages":"Article 134271"},"PeriodicalIF":2.1,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A green, cheap and robust method for selective hydrogenation of nitroarenes","authors":"Piao Ding ,&nbsp;Eman Fayad ,&nbsp;Ola A. Abu Ali ,&nbsp;Hua-Li Qin","doi":"10.1016/j.tet.2024.134269","DOIUrl":"10.1016/j.tet.2024.134269","url":null,"abstract":"<div><p>A commercially available nickel was utilized as an effective catalyst for the exclusive hydrogenation of nitroarenes to primary anilines in gram-scale without additional column chromatographic purification. This novel synthetic hydrogenation strategy features wide substrate scope, mild conditions and operational simplicity in aqueous media at room temperature. Further transformations resulted in the delivery of important amine-containing drugs and pharmaceutical intermediates.</p></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"167 ","pages":"Article 134269"},"PeriodicalIF":2.1,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}