Beilstein Journal of Organic Chemistry最新文献

{"title":"Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments","authors":"Daria A. Burmistrova, Andrey Galustyan, Nadezhda P. Pomortseva, Kristina D. Pashaeva, Maxim V. Arsenyev, Oleg P. Demidov, Mikhail A. Kiskin, Andrey I. Poddel’sky, Nadezhda T. Berberova, Ivan V. Smolyaninov","doi":"10.3762/bjoc.20.202","DOIUrl":"https://doi.org/10.3762/bjoc.20.202","url":null,"abstract":"<p><font size='+1'><b>Abstract</b></font></p>\u0000<p>A series of new RS&#8722;, RS&#8722;CH₂&#8722; and R₂N&#8722;CH₂-functionalized &#1089;atechols with heterocyclic fragments such as 1,3,4-oxadiazole, 1,2,4-triazole, thiazole, or pyridine were synthesized by the reaction of 3,5-di-<i>tert</i>-butyl-<i>o</i>-benzoquinone or 3,5-di-<i>tert</i>-butyl-6-methoxymethylcatechol with different heterocyclic thiols. The S-functionalized catechols were prepared by the Michael reaction from 3,5-di-<i>tert</i>-butyl-<i>o</i>-benzoquinone and the corresponding thiols. The starting reagents such as substituted 1,3,4-oxadiazole-2-thiols and 4<i>H</i>-triazole-3-thiols are characterized by thiol&#8211;thione tautomerism, therefore their reactions with 3,5-di-<i>tert</i>-butyl-6-methoxymethylcatechol can proceed at the sulfur or nitrogen atom. In the case of mercapto-derivatives of thiazole or pyridine, this process leads to the formation of the corresponding thioethers with a methylene linker. At the same time, thiolated 1,3,4-oxadiazole or 1,2,4-triazole undergo alkylation at the nitrogen atom in the reaction with 3,5-di-<i>tert</i>-butyl-6-methoxymethylcatechol to form the corresponding thiones. The yield of reaction products ranges from 42 to 80%. The crystal structures of catechols with 3-nitropyridine or 1,3,4-oxadiazole-2(3<i>H</i>)-thione moieties were established by single-crystal X-ray analysis. The possibility of forming intra- and intermolecular hydrogen bonds has been established for these compounds. The electrochemical behavior of the studied compounds is influenced by several factors: the nature of the heterocycle and its substituents, the presence of a sulfur atom in the catechol ring, or a thione group in the heterocyclic core. The radical scavenging activity and antioxidant properties were determined using the reaction with synthetic radicals, the cupric reducing antioxidant capacity assay, the inhibition process of superoxide radical anion formation by xanthine oxidase, and the process of lipid peroxidation of rat liver (<i>Wistar</i>) homogenates in vitro.</p>\u0000<p align='center'><img src='https://www.beilstein-journals.org/bjoc/content/figures/1860-5397-20-202-graphical-abstract.png?max-width=550' border='0'/></p>\u0000<p><i>Beilstein J. Org. Chem.</i> <b>2024,</b> <i>20,</i> 2378&#8211;2391.&#160;doi:10.3762/bjoc.20.202</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"4 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system","authors":"Yuri A. Sidunets, Valeriya G. Melekhina, Leonid L. Fershtat","doi":"10.3762/bjoc.20.200","DOIUrl":"https://doi.org/10.3762/bjoc.20.200","url":null,"abstract":"<p><font size='+1'><b>Abstract</b></font></p>\u0000<p>A straightforward protocol for the synthesis of a previously unknown [1,2,5]oxadiazolo[3,4-<i>d</i>][1,2,3]triazin-7(6<i>H</i>)-one heterocyclic system was developed. The described approach is based on tandem diazotization/azo coupling reactions of (1,2,5-oxadiazolyl)carboxamide derivatives bearing both aromatic and aliphatic substituents. The NO-donor ability of the synthesized furoxano[3,4-<i>d</i>][1,2,3]triazin-7(6<i>H</i>)-ones was additionally evaluated. The elaborated method provides access to novel nitrogen heterocyclic compounds with potential applications as drug candidates or thermostable components of functional organic materials.</p>\u0000<p align='center'><img src='https://www.beilstein-journals.org/bjoc/content/figures/1860-5397-20-200-graphical-abstract.png?max-width=550' border='0'/></p>\u0000<p><i>Beilstein J. Org. Chem.</i> <b>2024,</b> <i>20,</i> 2342&#8211;2348.&#160;doi:10.3762/bjoc.20.200</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"64 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asymmetric organocatalytic synthesis of chiral homoallylic amines","authors":"Nikolay S. Kondratyev, Andrei V. Malkov","doi":"10.3762/bjoc.20.201","DOIUrl":"https://doi.org/10.3762/bjoc.20.201","url":null,"abstract":"<p><font size='+1'><b>Abstract</b></font></p>\u0000<p>In recent decades, the chiral allylation of imines emerged as a key methodology in the synthesis of alkaloids and natural products with 4-, 5- and 6-membered cyclic amine motifs. Initially reliant on stoichiometric reagents, synthetic chemists predominantly used <i>N</i>-substituted chiral imines, organometallic chiral reagents and achiral reagents with an equimolar chiral controller. However, recent years have witnessed the rise of asymmetric transition-metal catalysts and, importantly, organocatalytic allylation, reshaping the landscape of modern synthetic chemistry. This review explores the latest developments in the asymmetric allylation of imines, encompassing cutting-edge advances in hydrogen-bond catalysis and non-classical approaches. Furthermore, practical examples showcasing the application of these innovative methodologies in total synthesis are presented.</p>\u0000<p align='center'><img src='https://www.beilstein-journals.org/bjoc/content/figures/1860-5397-20-201-graphical-abstract.png?max-width=550' border='0'/></p>\u0000<p><i>Beilstein J. Org. Chem.</i> <b>2024,</b> <i>20,</i> 2349&#8211;2377.&#160;doi:10.3762/bjoc.20.201</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"38 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines","authors":"Michał Błauciak, Dominika Andrzejczyk, Błażej Dziuk, Rafał Kowalczyk","doi":"10.3762/bjoc.20.198","DOIUrl":"https://doi.org/10.3762/bjoc.20.198","url":null,"abstract":"<p><font size='+1'><b>Abstract</b></font></p>\u0000<p>The study presents a novel approach utilizing iminium salt activation and mild enolization of thioesters, offering an efficient and rapid synthesis of Michael adducts with promising stereoselectivity and marking a significant advancement in mechanocatalysis. The stereoselective addition of bisthiomalonates <b>1</b>&#8211;<b>4</b> to cyclic enones and 4-chlorobenzylideneacetone proceeds stereoselectively under iminium activation conditions secured by chiral primary amines, in contrast to oxo-esters as observed in dibenzyl malonate addition. Mild enolization of thioesters allows for the generation of Michael adducts with good yields and stereoselectivities. Reactions in a ball mill afford product formation with similar efficacy to solution-phase reactions but with slightly reduced enantioselectivity, yet they yield products in just one hour compared to 24 or even 168 hours in solution-based reactions. It is noteworthy that this represents one of the early reports on the application of iminium catalysis using first-generation chiral amines under mechanochemical conditions, along with the utilization of easily enolizable thioesters as nucleophiles in this transformation.</p>\u0000<p align='center'><img src='https://www.beilstein-journals.org/bjoc/content/figures/1860-5397-20-198-graphical-abstract.png?max-width=550' border='0'/></p>\u0000<p><i>Beilstein J. Org. Chem.</i> <b>2024,</b> <i>20,</i> 2313&#8211;2322.&#160;doi:10.3762/bjoc.20.198</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"11 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142184996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers","authors":"Andreas Wiest, Pavel Kielkowski","doi":"10.3762/bjoc.20.199","DOIUrl":"https://doi.org/10.3762/bjoc.20.199","url":null,"abstract":"<p><font size='+1'><b>Abstract</b></font></p>\u0000<p>Identification of interactions between proteins and natural products or similar active small molecules is crucial for understanding of their mechanism of action on a molecular level. To search elusive, often labile, and low-abundant conjugates between proteins and active compounds, chemical proteomics introduces a feasible strategy that allows to enrich and detect these conjugates. Recent advances in mass spectrometry techniques and search algorithms provide unprecedented depth of proteome coverage and the possibility to detect desired modified peptides with high sensitivity. The chemical &#8216;linker&#8217; connecting an active compound&#8211;protein conjugate with a detection tag is the critical component of all chemical proteomic workflows. In this review, we discuss the properties and applications of different chemical proteomics linkers with special focus on their fragmentation releasing diagnostic ions and how these may improve the confidence in identified active compound&#8211;peptide conjugates. The application of advanced search options improves the identification rates and may help to identify otherwise difficult to find interactions between active compounds and proteins, which may result from unperturbed conditions, and thus are of high physiological relevance.</p>\u0000<p align='center'><img src='https://www.beilstein-journals.org/bjoc/content/figures/1860-5397-20-199-graphical-abstract.png?max-width=550' border='0'/></p>\u0000<p><i>Beilstein J. Org. Chem.</i> <b>2024,</b> <i>20,</i> 2323&#8211;2341.&#160;doi:10.3762/bjoc.20.199</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"71 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142184997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes","authors":"Phong Thai, Lauv Patel, Diyasha Manna, David C. Powers","doi":"10.3762/bjoc.20.197","DOIUrl":"https://doi.org/10.3762/bjoc.20.197","url":null,"abstract":"<p><font size='+1'><b>Abstract</b></font></p>\u0000<p>Iminoiodinanes comprise a class of hypervalent iodine reagents that is often encountered in nitrogen-group transfer (NGT) catalysis. In general, transition metal catalysts are required to effect efficient NGT to unactivated olefins because iminoiodinanes are insufficiently electrophilic to engage in direct aziridination chemistry. Here, we demonstrate that 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) activates <i>N</i>-arylsulfonamide-derived iminoiodinanes for the metal-free aziridination of unactivated olefins. ¹H NMR and cyclic voltammetry (CV) studies indicate that hydrogen-bonding between HFIP and the iminoiodinane generates an oxidant capable of direct NGT to unactivated olefins. Stereochemical scrambling during aziridination of 1,2-disubstituted olefins is observed and interpreted as evidence that aziridination proceeds via a carbocation intermediate that subsequently cyclizes. These results demonstrate a simple method for activating iminoiodinane reagents, provide analysis of the extent of activation achieved by H-bonding, and indicate the potential for chemical non-innocence of fluorinated alcohol solvents in NGT catalysis.</p>\u0000<p align='center'><img src='https://www.beilstein-journals.org/bjoc/content/figures/1860-5397-20-197-graphical-abstract.png?max-width=550' border='0'/></p>\u0000<p><i>Beilstein J. Org. Chem.</i> <b>2024,</b> <i>20,</i> 2305&#8211;2312.&#160;doi:10.3762/bjoc.20.197</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"14 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142184998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis","authors":"Stefan P. Schmid, Leon Schlosser, Frank Glorius, Kjell Jorner","doi":"10.3762/bjoc.20.196","DOIUrl":"https://doi.org/10.3762/bjoc.20.196","url":null,"abstract":"<p><font size='+1'><b>Abstract</b></font></p>\u0000<p>Organocatalysis has established itself as a third pillar of homogeneous catalysis, besides transition metal catalysis and biocatalysis, as its use for enantioselective reactions has gathered significant interest over the last decades. Concurrent to this development, machine learning (ML) has been increasingly applied in the chemical domain to efficiently uncover hidden patterns in data and accelerate scientific discovery. While the uptake of ML in organocatalysis has been comparably slow, the last two decades have showed an increased interest from the community. This review gives an overview of the work in the field of ML in organocatalysis. The review starts by giving a short primer on ML for experimental chemists, before discussing its application for predicting the selectivity of organocatalytic transformations. Subsequently, we review ML employed for privileged catalysts, before focusing on its application for catalyst and reaction design. Concluding, we give our view on current challenges and future directions for this field, drawing inspiration from the application of ML to other scientific domains.</p>\u0000<p align='center'><img src='https://www.beilstein-journals.org/bjoc/content/figures/1860-5397-20-196-graphical-abstract.png?max-width=550' border='0'/></p>\u0000<p><i>Beilstein J. Org. Chem.</i> <b>2024,</b> <i>20,</i> 2280&#8211;2304.&#160;doi:10.3762/bjoc.20.196</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"53 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142184999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deuterated reagents in multicomponent reactions to afford deuterium-labeled products","authors":"Kevin Schofield, Shayna Maddern, Yueteng Zhang, Grace E. Mastin, Rachel Knight, Wei Wang, James Galligan, Christopher Hulme","doi":"10.3762/bjoc.20.195","DOIUrl":"https://doi.org/10.3762/bjoc.20.195","url":null,"abstract":"<p><font size='+1'><b>Abstract</b></font></p>\u0000<p>The utility of bio-isosteres is broad in drug discovery and methodology herein enables the preparation of deuterium-labeled products is the most fundamental of known bio-isosteric replacements. As such we report the use of both [D₁]-aldehydes and [D₂]-isonitriles across 8 multicomponent reactions (MCRs) to give diverse arrays of deuterated products. A highlight is the synthesis of several FDA-approved calcium channel blockers, selectively deuterated at a <i>t</i>_1/2 limiting metabolic soft-spot via use of [D₁]-aldehydes. Surrogate pharmacokinetic analyses of microsomal stability confirm prolongation of <i>t</i>_1/2 of the new deuterated analogs. We also report the first preparation of [D₂]-isonitriles from [D₃]-formamides via a modified Leuckart&#8211;Wallach reaction and their use in an MCR to afford products with [D₂]-benzylic positions and likely significantly enhanced metabolic stability, a key parameter for property-based design efforts.</p>\u0000<p align='center'><img src='https://www.beilstein-journals.org/bjoc/content/figures/1860-5397-20-195-graphical-abstract.png?max-width=550' border='0'/></p>\u0000<p><i>Beilstein J. Org. Chem.</i> <b>2024,</b> <i>20,</i> 2270&#8211;2279.&#160;doi:10.3762/bjoc.20.195</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"6 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142224059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu4NBF4 or electrogenerated acid","authors":"Mizuki Yamaguchi, Hiroki Shimao, Kengo Hamasaki, Keiji Nishiwaki, Shigenori Kashimura, Kouichi Matsumoto","doi":"10.3762/bjoc.20.194","DOIUrl":"https://doi.org/10.3762/bjoc.20.194","url":null,"abstract":"<p><font size='+1'><b>Abstract</b></font></p>\u0000<p><i>gem</i>-Difluorination of carbon&#8211;carbon triple bonds was conducted using Br&#248;nsted acids, such as Tf₂NH and TfOH, combined with Bu₄NBF₄ as the fluorine source. The electrochemical oxidation of a Bu₄NBF₄/CH₂Cl₂ solution containing alkyne substrates could also give the corresponding <i>gem</i>-difluorinated compounds (<i>in-cell</i> method). The <i>ex-cell</i> electrolysis method was also applicable for <i>gem</i>-difluorination of alkynes.</p>\u0000<p align='center'><img src='https://www.beilstein-journals.org/bjoc/content/figures/1860-5397-20-194-graphical-abstract.png?max-width=550' border='0'/></p>\u0000<p><i>Beilstein J. Org. Chem.</i> <b>2024,</b> <i>20,</i> 2261&#8211;2269.&#160;doi:10.3762/bjoc.20.194</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142185000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and reactivity of the di(9-anthryl)methyl radical","authors":"Tomohiko Nishiuchi, Kazuma Takahashi, Yuta Makihara, Takashi Kubo","doi":"10.3762/bjoc.20.193","DOIUrl":"https://doi.org/10.3762/bjoc.20.193","url":null,"abstract":"<p><font size='+1'><b>Abstract</b></font></p>\u0000<p>The di(9-anthryl)methyl (DAntM) radical was synthesized and investigated to elucidate its optical, electrical properties, and reactivity. The generation of the DAntM radical was confirmed by its ESR spectrum, which showed two broad signals. The unpaired electron is primarily localized on the central sp² carbon and slightly delocalized over the two anthryl moieties. Although the DAntM radical undergoes dimerization in solution, the radical still remains even at 190 K due to the bulky nature of the two anthryl groups. Interestingly, upon exposure to air, the purple color of the radical solution quickly fades to orange, resulting in decomposition to give 9-anthryl aldehyde and anthroxyl radical derivatives.</p>\u0000<p align='center'><img src='https://www.beilstein-journals.org/bjoc/content/figures/1860-5397-20-193-graphical-abstract.png?max-width=550' border='0'/></p>\u0000<p><i>Beilstein J. Org. Chem.</i> <b>2024,</b> <i>20,</i> 2254&#8211;2260.&#160;doi:10.3762/bjoc.20.193</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"60 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142224058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}