Tetrahedron最新文献

{"title":"Unraveling the synthesis and therapeutic potential of FDA-approved Alzheimer's drugs: A comprehensive review","authors":"Anjali Rani ,&nbsp;Javed Khan ,&nbsp;Lakshika Choudhary ,&nbsp;Manas Kumar ,&nbsp;Ayushi Jha ,&nbsp;Garima Pandey ,&nbsp;Bhaskara Nand","doi":"10.1016/j.tet.2025.134517","DOIUrl":"10.1016/j.tet.2025.134517","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a prevalent form of dementia that primarily affects individuals aged 65 and older. This progressive neurodegenerative disorder leads to significant cognitive, memory, and behavioral impairments. While the exact cause remains unclear, AD is thought to result from a combination of genetic predispositions, environmental factors, lifestyle influences, and age-related brain changes. The increasing prevalence of AD highlights the urgent need for effective treatments, as no cure currently exists. This review compiles the synthesis and clinical applications of FDA-approved drugs for AD, including rivastigmine, galantamine, and donepezil—cholinesterase inhibitors that improve cognitive function by inhibiting acetylcholine breakdown. Memantine, an NMDA receptor antagonist, modulates glutamatergic activity to protect neurons from excitotoxicity. Tacrine, an early cholinesterase inhibitor, had limited long-term use due to hepatotoxicity concerns. While these drugs provide symptom management and enhance quality of life, they do not stop disease progression. Recent advancements focus on combination therapies, novel drug delivery systems, and targeting amyloid-beta and tau proteins. Emerging treatments, such as monoclonal antibodies and stem cell approaches, offer hope for disease modification. Continued research is essential for the development of more effective and potentially curative AD therapies.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"175 ","pages":"Article 134517"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143346711","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":"Iron-catalysed synthesis of sulfonamides and sulfonic esters: Greener sulfonation of amines and alcohols under mechanical grinding conditions","authors":"Pandeeshwaran Santhoshkumar,&nbsp;Thangapandiyan Kanagaraj,&nbsp;Palaniswamy Suresh","doi":"10.1016/j.tet.2024.134410","DOIUrl":"10.1016/j.tet.2024.134410","url":null,"abstract":"<div><div>Iron-catalysed synthesis of sulfonamides and sulfonic esters has been reported under simple grinding and neat conditions at ambient temperature. The ferric chloride -catalysed sulfonation of amines and alcohols is mild, efficient, and notably avoids base and quashed impurities. Also, this methodology with iron catalyst showed high functional group tolerance, which accommodates diverse sulfonyl chlorides, amines, and aliphatic alcohols and yields a spectrum of sulfonamides and sulfonic esters with good to excellent yields. The present methodology could open the doors for synthesising sulfonamides and sulfonic esters; on the other hand, it could utilise a mild and simple protection strategy for amines and alcohols.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"171 ","pages":"Article 134410"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143181147","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":"Antiproliferative noscapinoids bearing isoxazoles: Design, synthesis, bioevaluation and molecular docking","authors":"Ravi Kumar Pedapati ,&nbsp;Varshitha Shanigarapu ,&nbsp;Naga Pranathi Abburi ,&nbsp;Nagaraju Chirra ,&nbsp;Devendra Nagineni ,&nbsp;Pratyush Pragyandipta ,&nbsp;Pradeep K. Naik ,&nbsp;Srinivas Kantevari","doi":"10.1016/j.tet.2024.134431","DOIUrl":"10.1016/j.tet.2024.134431","url":null,"abstract":"<div><div>Natural α-noscapine is an antitussive agent approved by the FDA, known for its low cytotoxicity even at high concentrations. Recently, it has shown that noscapine and its derivatives exhibit significant anticancer effects against a variety of cancer cell lines. To improve its therapeutic potential, this study focused on the synthesis of a series of novel isoxazole-conjugated noscapinoids, which were then assessed for their cytotoxic properties <em>in vitro</em>. The reaction of N-propargylic noscapine with in situ generated (<em>Z</em>)-N-hydroxybenzimidoyl chloride yielded the desired noscapinoids containing isoxazoles. The newly synthesized compounds showed considerable cytotoxic activity, with IC₅₀ ranging from 1.2 to 21.3 μM, surpassing noscapine (IC₅₀: 31 and 65.5 μM) across all evaluated cell lines, while exhibiting minimal toxicity to normal cells (IC₅₀ &gt; 300 μM). Molecular docking analyses of the most promising synthetic derivative, <strong>7p</strong> (IC₅₀ ranging 1.2 and 9.4 μM across different cancer cell lines), indicated the highest binding affinity to tubulin (ΔG binding of −24.99 kcal/mol) and effectively induced apoptosis in cancer cells to a greater degree.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"171 ","pages":"Article 134431"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143182045","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":"Cp∗Co(III)-catalyzed C–H amidation of 2-arylimidazo[1,2-α]pyridines with dioxazolones","authors":"Yongqi Yu ,&nbsp;Jinjin Bai ,&nbsp;Mengdan You ,&nbsp;Jiajia Yu ,&nbsp;Wenguang Li ,&nbsp;Yuanjiu Xiao ,&nbsp;Shiyu Zhang ,&nbsp;Zhenhua Xiong ,&nbsp;Ze Tan","doi":"10.1016/j.tet.2024.134420","DOIUrl":"10.1016/j.tet.2024.134420","url":null,"abstract":"<div><div>A highly simple and practical Cp∗Co(III)-catalyzed C–H amidation of 2-arylimidazo[1,2-α]pyridines was developed, during which dioxazolones were used as the amidating reagents. This method features excellent regioselectivity, operational simplicity, and good substrate compatibility, and various amidated 2-arylimidazoheterocycles were efficiently synthesized in 34–81 % yields. Furthermore, mechanistic studies reveal that the C–H bond cleavage may be involved in the turnover-limiting stage.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"171 ","pages":"Article 134420"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143181107","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":"Drug-linker constructs bearing unique dual-mechanism tubulin binding payloads tethered through cleavable and non-cleavable linkers","authors":"Jacob W. Ford ,&nbsp;Jennifer M. VanNatta ,&nbsp;Deboprosad Mondal ,&nbsp;Chen-Ming Lin ,&nbsp;Yuling Deng ,&nbsp;Ruoli Bai ,&nbsp;Ernest Hamel ,&nbsp;Mary Lynn Trawick ,&nbsp;Kevin G. Pinney","doi":"10.1016/j.tet.2024.134350","DOIUrl":"10.1016/j.tet.2024.134350","url":null,"abstract":"<div><div>Antibody-drug conjugates (ADCs) have advanced as a mainstay among the most promising cancer therapeutics, offering enhanced antigen targeting and encompassing wide diversity in their linker and payload components. Small-molecule inhibitors of tubulin polymerization have found success as payloads in FDA approved ADCs and represent further promise in next-generation, pre-clinical and developmental ADCs. Unique dual-mechanism payloads (previously designed and synthesized in our laboratories) function as both potent antiproliferative agents and promising vascular disrupting agents capable of imparting selective and effective damage to tumor-associated microvessels. These payloads have been incorporated into a variety of drug-linker constructs utilizing the clinically relevant cathepsin B cleavable Val-Cit dipeptide linker, employed within several FDA approved ADCs, along with other non-cleavable constructs. Various synthetic strategies were evaluated to prepare these drug-linker constructs. Aniline-based payloads were incorporated utilizing the Val-Cit dipeptide linker similar to FDA approved ADCs such as Adcetris® (brentuximab vedotin). An additional self-immolative group, previously described in the literature for related model systems, was employed to tether the phenolic payloads. A variety of drug-linker constructs (each bearing a unique dual mechanism payload) were synthesized and evaluated biologically for their enzyme-mediated release of payload and inhibition of tubulin polymerization. Following deactivation of the highly electrophilic maleimido terminus as its corresponding <em>N</em>-acetyl cysteine (NAC) derivative, the most promising construct (NAC-<strong>4</strong>) demonstrated approximately 90% release of an aniline-functionalized payload (<strong>1</strong>) upon treatment with cathepsins B or L over 90 min. Building on these promising results, future studies will examine the conjugation of drug-linker construct <strong>4</strong> to selected antibodies and engineered proteins and evaluate the biological activity of the resultant antibody-drug conjugates (ADCs).</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"171 ","pages":"Article 134350"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969089","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":"Construction of trifluoromethyl-substituted enaminones via rhodium(III)-catalyzed aldehydic C(sp2)–H bond activation of N-sulfonyl-2-aminobenzaldehydes with CF3-imidoyl sulfoxonium ylides","authors":"Yubo Duan,&nbsp;Zhaolin Quan,&nbsp;Zhengkai Chen","doi":"10.1016/j.tet.2024.134408","DOIUrl":"10.1016/j.tet.2024.134408","url":null,"abstract":"<div><div>A rhodium (III)-catalyzed C (sp²)–H bond activation reaction of <em>N</em>-sulfonyl-2-aminobenzaldehydes with CF₃-imidoyl sulfoxonium ylides (TFISYs) has been achieved, which offers a facile and straightforward access to trifluoromethyl-substituted enaminones in moderate to excellent yields. The reaction involves a cascade aldehydic C (sp²)–H bond imidoylmethylation and imine-enamine tautomerization sequence. The obtained α–CF₃–enaminone products can act as versatile trifluoromethyl-containing synthons to construct a series of structurally diverse fluorinated heterocycles.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"171 ","pages":"Article 134408"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143182086","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":"Synthesis of analogs of dicadalenol, an anti-inflammatory cadinanoid disesquiterpene","authors":"José Luis Ávila,&nbsp;Guillermo Delgado","doi":"10.1016/j.tet.2024.134430","DOIUrl":"10.1016/j.tet.2024.134430","url":null,"abstract":"<div><div>Dicadalenol is a disesquiterpenoid with notable anti-inflammatory activity. It was previously isolated from the plant <em>Heterotheca inuloides</em> but has never been re-isolated or synthesized. Herein, we report a semi-synthetic approach starting from two cadinane metabolites produced by the plant. Retrosynthetic analysis identified suitable fragments containing functional groups that could be used for the formation of the pentacyclic compound. The synthesis proceeded via an oxa-Michael addition, condensation, and dehydration sequence between a semi-synthetic sesquiterpene enal and natural 7-hydroxy-cadalene to afford the corresponding methyl anhydro-dicadalenol. The results show that substituted monomeric sesquiterpenes have reduced reactivity and that the dimerization reaction is retarded compared to model reactions performed with unsubstituted perillaldehyde and 2-naphthol. These results suggested a biogenetic pathway for the formation of dicadalenol.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"171 ","pages":"Article 134430"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143182046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reactions of N-amino isoquinaldinium and N-alkylpicolinium salts with s-tetrazines","authors":"Ilya V. Nechaev ,&nbsp;Georgij V. Cherkaev","doi":"10.1016/j.tet.2024.134426","DOIUrl":"10.1016/j.tet.2024.134426","url":null,"abstract":"<div><div>A dearomative/rearomative reaction between 3,6-diaryl-<em>s</em>-tetrazines and quaternary <em>N</em>-amino isoquinaldinium salt was discovered afford pyrazolo[5,1-<em>a</em>]isoquinolines. Its mechanism was elucidated on the basis of isolated intermediates, stabilized by specific carbon-to-nitrogen atom replacements in the tetrazine counterpart. The reaction pathway includes sequential enamine/tetrazine cycloaddition, bridged [1,2,4,5]-tetrazepine ring closure, spontaneous hydrazone dehydrogenation, and diazo-intermediate fragmentation steps. In turn, with cyanodiazines, <em>N</em>-amino isoquinaldinium salt reacts with an unusual loss of the C1-methyl group to form triazolo[5,1-<em>a</em>]isoquinolines. Additionally, a related reaction of unsymmetrically substituted tetrazines with <em>N</em>-methyl 2-picolinium or quinaldinium salts to give heterostilbenes with high regio- and stereoselectivity was demonstrated. A mechanistic explanation was suggested, and facile photochemical <em>cis</em>→<em>trans</em> isomerization was shown. The findings, outlined in this study could be helpful for researchers involved in tetrazine chemistry, or those, pursuing dyes and photoswitches.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"171 ","pages":"Article 134426"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143181144","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":"Emerging trends in microwave and ultrasound/visible light/ carbene intermediates & carbonylation/metal-catalyzed mediated synthesis of β-lactams (2021–2024)","authors":"Ankita Garg,&nbsp;Rajat Dhiman,&nbsp;Teesha Thakral,&nbsp;Aman Bhalla","doi":"10.1016/j.tet.2024.134429","DOIUrl":"10.1016/j.tet.2024.134429","url":null,"abstract":"<div><div>β-Lactam compounds hold a prominent position in modern organic synthesis, garnering significant attention due to their role as “privileged pharmacological structures” that are widely present in natural products and active pharmaceutical ingredients. The ongoing interest in this class of compounds has led to the development of numerous synthetic methodologies for generating various β-lactam derivatives. Therefore, this review highlights the latest emerging trends in the synthesis of β-lactam compounds, focusing on innovative methodologies such as microwave and ultrasound-assisted synthesis, visible light irradiation, role of carbene intermediates &amp; carbonylation and metal-catalyzed reactions. Here, we have compiled and examined each synthetic strategy, providing detailed mechanistic analysis insights based on current advancements and emerging trends from 2021 to the present. By summarizing these recent developments, this review serves as a valuable resource for synthetic chemists and researchers in the field of β-lactam chemistry, offering insights that could help in the design and development of novel β-lactam-based compounds.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"171 ","pages":"Article 134429"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143182100","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":"Electronic metal−support interaction of Pt1/V2O5 enables efficient and selective hydrogenation of aromatic nitros","authors":"Ziqi Bian ,&nbsp;Xiaojun Zheng ,&nbsp;Guoyong Xiao ,&nbsp;Wanguo Wei ,&nbsp;Cuiping Wang ,&nbsp;Yuhui Zhao ,&nbsp;Zhiqiang Zhang","doi":"10.1016/j.tet.2024.134433","DOIUrl":"10.1016/j.tet.2024.134433","url":null,"abstract":"<div><div>Arylamines play a key role in the synthesis of agricultural chemicals, dyes, medicine, rubber and other fine chemicals. The hydrogenation of aromatic nitro is the most convenient protocol for the preparation of arylamines. Therefore, it is of great research significance to develop a stable, efficient and low-cost catalyst in the hydrogenation of nitro compounds. Therefore, the supported single-atom platinum Pt₁/V₂O₅ (0.1 wt% of Pt by ICP−OES) was prepared for the efficient hydrogenation of variety of aromatic nitros. The Pt₁/V₂O₅ was characterized by SEM, TEM, HAADF−STEM, XRD, XPS, Raman and CO−DRIFT analysis. Amount of aromatic nitros with functional groups (such as CN and carbonyl groups) were hydrogenated smoothly to deliver the amines in 50–95 % yields. The catalytic performances are attributed to the electronic metal−support interactions between Pt₁ atoms and V₂O₅ with the abundant surface oxygen vacancy, resulting in the enhanced electronic density of Pt₁ atoms, which were confirmed by the results of XPS and Raman spectra. The high activity and reusability of Pt₁/V₂O₅ catalyst imply its potential application in fine chemical synthesis.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"171 ","pages":"Article 134433"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143181108","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}