Pub Date : 2024-11-01DOI: 10.1016/j.tet.2024.134355
Nan Liu , Zefei Lin , Ying Li, Chengyan Wu, Mingyu Tian, Lijun Tang
Sulfur dioxide and its derivatives (HSO3−/SO32-) play a crucial role in maintaining the redox balance of biological systems. Therefore, the development of effective detection methods for sulfur dioxide and its derivatives is of paramount importance. Herein, a novel fluorescent probe, QLN, was designed and synthesized using small molecule quinoline, demonstrating the capacity to recognize HSO3− through Michael addition reaction. The probe QLN displayed good selectivity and anti-interference capabilities for HSO3− recognition, effectively operating within a wide pH range (5–9) and exhibiting a rapid response time (<5 s). Practical applications revealed the potential of probe QLN for detecting HSO3− in living cells and food samples.
{"title":"A quinolinium-based fluorescent probe for ultrafast detection of bisulfite and its applications in food detection, SO2 gas detection, and cell imaging","authors":"Nan Liu , Zefei Lin , Ying Li, Chengyan Wu, Mingyu Tian, Lijun Tang","doi":"10.1016/j.tet.2024.134355","DOIUrl":"10.1016/j.tet.2024.134355","url":null,"abstract":"<div><div>Sulfur dioxide and its derivatives (HSO<sub>3</sub><sup>−</sup>/SO<sub>3</sub><sup>2-</sup>) play a crucial role in maintaining the redox balance of biological systems. Therefore, the development of effective detection methods for sulfur dioxide and its derivatives is of paramount importance. Herein, a novel fluorescent probe, <strong>QLN</strong>, was designed and synthesized using small molecule quinoline, demonstrating the capacity to recognize HSO<sub>3</sub><sup>−</sup> through Michael addition reaction. The probe <strong>QLN</strong> displayed good selectivity and anti-interference capabilities for HSO<sub>3</sub><sup>−</sup> recognition, effectively operating within a wide pH range (5–9) and exhibiting a rapid response time (<5 s). Practical applications revealed the potential of probe <strong>QLN</strong> for detecting HSO<sub>3</sub><sup>−</sup> in living cells and food samples.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"168 ","pages":"Article 134355"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654176","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}
Pub Date : 2024-11-01DOI: 10.1016/j.tet.2024.134352
Jia-Lin Tu , Zhengjia Shen , Binbin Huang
The construction of C(sp³)-P bonds is of paramount importance in organic synthesis, catalysis, and materials science. Organophosphorus compounds containing C(sp³)-P bonds serve as pivotal structural motifs in ligands, pharmaceuticals, agrochemicals, and functional materials. While traditional methods for C(sp³)-P bond formation largely rely on nucleophilic substitution or coupling of reactive organometallic reagents, recent years have witnessed significant advancements in metal-catalyzed approaches. This review highlights the recent developments in C(sp³)-P bond formation enabled by metals including Cu, Fe, Bi, Pd, Ni, Ru, Rh, and Co, with particular emphasis on methodologies that activate simple C(sp³)-H bonds or utilize readily available chemical feedstocks. Key mechanistic paradigms, including photoredox/transition metal dual catalysis, metal-catalyzed radical processes, and photo-induced ligand-to-metal charge transfer (LMCT), are critically discussed. This review evaluates the mechanistic insights, applications, and limitations of these methodologies in the synthesis of organophosphorus compounds, and provides perspectives on future directions to promote further advancements in C(sp³)-P bond formation strategies.
{"title":"Recent progress in metal-catalyzed C(sp³)-P bond formation","authors":"Jia-Lin Tu , Zhengjia Shen , Binbin Huang","doi":"10.1016/j.tet.2024.134352","DOIUrl":"10.1016/j.tet.2024.134352","url":null,"abstract":"<div><div>The construction of C(sp³)-P bonds is of paramount importance in organic synthesis, catalysis, and materials science. Organophosphorus compounds containing C(sp³)-P bonds serve as pivotal structural motifs in ligands, pharmaceuticals, agrochemicals, and functional materials. While traditional methods for C(sp³)-P bond formation largely rely on nucleophilic substitution or coupling of reactive organometallic reagents, recent years have witnessed significant advancements in metal-catalyzed approaches. This review highlights the recent developments in C(sp³)-P bond formation enabled by metals including Cu, Fe, Bi, Pd, Ni, Ru, Rh, and Co, with particular emphasis on methodologies that activate simple C(sp³)-H bonds or utilize readily available chemical feedstocks. Key mechanistic paradigms, including photoredox/transition metal dual catalysis, metal-catalyzed radical processes, and photo-induced ligand-to-metal charge transfer (LMCT), are critically discussed. This review evaluates the mechanistic insights, applications, and limitations of these methodologies in the synthesis of organophosphorus compounds, and provides perspectives on future directions to promote further advancements in C(sp³)-P bond formation strategies.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"168 ","pages":"Article 134352"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592592","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}
Pub Date : 2024-11-01DOI: 10.1016/j.tet.2024.134354
Javier Ordóñez-Hernández, Fernanda Ferrusca-Martínez, Arturo Jiménez-Sánchez
Lipid droplets (LDs) are ubiquitous intracellular organelles present in various cell types, ranging from adipocytes to cancer cells. Despite their involvement in numerous diseases, current methodologies for monitoring LD dynamics rely primarily on static imaging with a limited selection of fluorescent dyes. In this study, we introduce two novel BODIPY-derived fluorophores designed to facilitate real-time monitoring of LD dynamics. By incorporating triphenylamino (TPA) moieties into the BODIPY core both asymmetrically and symmetrically, we modulated the fluorescence response to the green (GFP) and deep-red (Cy5) confocal channels, respectively, thus allowing dual-channel fluorescence capability for high-resolution, dynamic imaging of LDs within live cells, providing new insights into their behavior.
{"title":"BODIPY-derived fluorescent probes for targeting and tracking lipid droplets dynamics","authors":"Javier Ordóñez-Hernández, Fernanda Ferrusca-Martínez, Arturo Jiménez-Sánchez","doi":"10.1016/j.tet.2024.134354","DOIUrl":"10.1016/j.tet.2024.134354","url":null,"abstract":"<div><div>Lipid droplets (LDs) are ubiquitous intracellular organelles present in various cell types, ranging from adipocytes to cancer cells. Despite their involvement in numerous diseases, current methodologies for monitoring LD dynamics rely primarily on static imaging with a limited selection of fluorescent dyes. In this study, we introduce two novel BODIPY-derived fluorophores designed to facilitate real-time monitoring of LD dynamics. By incorporating triphenylamino (TPA) moieties into the BODIPY core both asymmetrically and symmetrically, we modulated the fluorescence response to the green (GFP) and deep-red (Cy5) confocal channels, respectively, thus allowing dual-channel fluorescence capability for high-resolution, dynamic imaging of LDs within live cells, providing new insights into their behavior.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"168 ","pages":"Article 134354"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654180","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}
The Brook Rearrangement holds significant applications in organic synthesis and has been investigated extensively in past decades. Among the various types of Brook rearrangements, catalytic versions have gained increased attention from the chemical community due to their superior control over stereoselectivity and high reaction efficiency. This review provides a comprehensive summary of recent examples of transition metal-promoted Brook rearrangement and related reactions. It encompasses copper-catalyzed migration of a silyl or boryl group, which represents the most intensively studied reactions, along with zinc-promoted reactions and other transition metal-catalyzed reactions. The substrate scope and reaction mechanisms of these examples are meticulously detailed and analyzed.
{"title":"Transition metal promoted Brook rearrangement and its related reactions","authors":"Fazhou Yang, Jinbao Wang, Yujie Dong, Nianci Zhang, Cheng Zhang","doi":"10.1016/j.tet.2024.134351","DOIUrl":"10.1016/j.tet.2024.134351","url":null,"abstract":"<div><div>The Brook Rearrangement holds significant applications in organic synthesis and has been investigated extensively in past decades. Among the various types of Brook rearrangements, catalytic versions have gained increased attention from the chemical community due to their superior control over stereoselectivity and high reaction efficiency. This review provides a comprehensive summary of recent examples of transition metal-promoted Brook rearrangement and related reactions. It encompasses copper-catalyzed migration of a silyl or boryl group, which represents the most intensively studied reactions, along with zinc-promoted reactions and other transition metal-catalyzed reactions. The substrate scope and reaction mechanisms of these examples are meticulously detailed and analyzed.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"168 ","pages":"Article 134351"},"PeriodicalIF":2.1,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578727","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}
Pub Date : 2024-10-31DOI: 10.1016/j.tet.2024.134334
José G. Becerra-González , Eduardo Peña-Cabrera , José L. Belmonte-Vázquez
BODIPYs (Boron-dipyrromethenes) are a class of fluorophores widely used in a plethora of scientific applications in material science and biomedicine due to their exceptional optical properties. The modulation of the absorption and emission wavelengths of BODIPYs is an area with significant growth opportunities, allowing these compounds to be tailored for specific applications. This review addresses different synthetic strategies that could modify their electronic and optical properties of the BODIPY core, mainly the absorption and emission wavelengths (λabs = 422 nm - λemis = 753 nm and quantum yields up to Φc-hex = 100 %). These methodologies include reactions like nucleophilic substitutions with (chiral/achiral) primary and secondary amines, alkyl/aryl alcohols, active methylenes, as well as Liebeskind-Srogl, Sonogashira, Heck, and Suzuki cross-coupling reactions at the meso and peripheral positions of the BODIPY core. These synthetic strategies incorporate specific functional groups that influence the π-system conjugation, generation of AIEgens, and Donor-Acceptor (D-A) or Donor-Acceptor-Donor (D-A-D) architectures, enabling the labeling of biomolecules such as estrone and tyrosine.
{"title":"From blue to red. Reaching the full visible spectrum with a single fluorophore: BODIPY","authors":"José G. Becerra-González , Eduardo Peña-Cabrera , José L. Belmonte-Vázquez","doi":"10.1016/j.tet.2024.134334","DOIUrl":"10.1016/j.tet.2024.134334","url":null,"abstract":"<div><div>BODIPYs (Boron-dipyrromethenes) are a class of fluorophores widely used in a plethora of scientific applications in material science and biomedicine due to their exceptional optical properties. The modulation of the absorption and emission wavelengths of BODIPYs is an area with significant growth opportunities, allowing these compounds to be tailored for specific applications. This review addresses different synthetic strategies that could modify their electronic and optical properties of the BODIPY core, mainly the absorption and emission wavelengths (λ<sub>abs</sub> = 422 nm - λ<sub>emis</sub> = 753 nm and quantum yields up to Φ<sub>c-hex</sub> = 100 %). These methodologies include reactions like nucleophilic substitutions with (chiral/achiral) primary and secondary amines, alkyl/aryl alcohols, active methylenes, as well as Liebeskind-Srogl, Sonogashira, Heck, and Suzuki cross-coupling reactions at the <em>meso</em> and peripheral positions of the BODIPY core. These synthetic strategies incorporate specific functional groups that influence the π-system conjugation, generation of AIEgens, and Donor-Acceptor (D-A) or Donor-Acceptor-Donor (D-A-D) architectures, enabling the labeling of biomolecules such as estrone and tyrosine.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"168 ","pages":"Article 134334"},"PeriodicalIF":2.1,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654181","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}
Pub Date : 2024-10-30DOI: 10.1016/j.tet.2024.134349
Akrti Sharma, Mangalampalli Ravikanth
The β-arylated meso-tetra(p-tolyl) triphyrins[2.1.1] containing two, three, and four p-fluorophenyl groups were synthesized by reacting appropriate β-bromo triphyrin[2.1.1] with p-fluorophenyl boronic acid in toluene/THF/H2O (1:1:1) at 80 οC for 8 h–12 h and their properties were compared with our previously reported β-arylated triphyrins[2.1.1] containing one and six p-fluorophenyl groups. The increase of the number of p-fluorophenyl groups at the β-pyrrole carbons induces steric hindrance at the periphery of triphyrin[2.1.1] that results in the alteration of electronic properties due to distortion in the macrocycle which is reflected in their structure, spectral and redox properties. The X-ray structure analysis revealed that β-di(p-fluorophenyl) meso-tetra(p-tolyl) triphyrin[2.1.1] was almost planar like meso-tetra(phenyl) triphyrin[2.1.1] whereas the β-hexa(p-fluorophenyl) meso-tetra(p-tolyl) triphyrin[2.1.1] was significantly distorted. The absorption spectra of β-arylated triphyrins[2.1.1] showed bathochromically shifted Soret and Q-bands with reduction in absorption coefficients and increase in the bandwidth compared to the β-unsubstituted meso-tetra(p-tolyl) triphyrin[2.1.1] and the maximum effects were noted for β-hexa(p-fluorophenyl) meso-tetra(p-tolyl) triphyrin[2.1.1]. The β-arylated meso-tetra(p-tolyl) triphyrins[2.1.1] are stable under electrochemical conditions and DFT/TD-DFT studies are in agreement with the experimental observations.
{"title":"Synthesis and properties of β-arylated triphyrins[2.1.1] by successive introduction of one to six aryl groups at the β-pyrrole carbons","authors":"Akrti Sharma, Mangalampalli Ravikanth","doi":"10.1016/j.tet.2024.134349","DOIUrl":"10.1016/j.tet.2024.134349","url":null,"abstract":"<div><div>The <em>β</em>-arylated <em>meso</em>-tetra(<em>p</em>-tolyl) triphyrins[2.1.1] containing two, three, and four <em>p</em>-fluorophenyl groups were synthesized by reacting appropriate <em>β</em>-bromo triphyrin[2.1.1] with <em>p</em>-fluorophenyl boronic acid in toluene/THF/H<sub>2</sub>O (1:1:1) at 80 <sup>ο</sup>C for 8 h–12 h and their properties were compared with our previously reported <em>β</em>-arylated triphyrins[2.1.1] containing one and six <em>p</em>-fluorophenyl groups. The increase of the number of <em>p</em>-fluorophenyl groups at the <em>β</em>-pyrrole carbons induces steric hindrance at the periphery of triphyrin[2.1.1] that results in the alteration of electronic properties due to distortion in the macrocycle which is reflected in their structure, spectral and redox properties. The X-ray structure analysis revealed that <em>β</em>-di(<em>p</em>-fluorophenyl) <em>meso</em>-tetra(<em>p</em>-tolyl) triphyrin[2.1.1] was almost planar like <em>meso</em>-tetra(phenyl) triphyrin[2.1.1] whereas the <em>β</em>-hexa(<em>p</em>-fluorophenyl) <em>meso</em>-tetra(<em>p</em>-tolyl) triphyrin[2.1.1] was significantly distorted. The absorption spectra of <em>β</em>-arylated triphyrins[2.1.1] showed bathochromically shifted Soret and Q-bands with reduction in absorption coefficients and increase in the bandwidth compared to the <em>β</em>-unsubstituted <em>meso</em>-tetra(<em>p</em>-tolyl) triphyrin[2.1.1] and the maximum effects were noted for <em>β</em>-hexa(<em>p</em>-fluorophenyl) <em>meso</em>-tetra(<em>p</em>-tolyl) triphyrin[2.1.1]. The <em>β</em>-arylated <em>meso</em>-tetra(<em>p</em>-tolyl) triphyrins[2.1.1] are stable under electrochemical conditions and DFT/TD-DFT studies are in agreement with the experimental observations.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"168 ","pages":"Article 134349"},"PeriodicalIF":2.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142572173","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}
Pub Date : 2024-10-29DOI: 10.1016/j.tet.2024.134337
Salma E. Mora-Rodríguez , Selene Lagunas-Rivera , J. Merced Martínez-Rosales , Yolanda Alcaraz-Contreras , Jorge Alberto Mendoza-Pérez , Miguel A. Vázquez
This research introduces a heterogeneous approach utilizing a resin-bound sulfonic acid catalyst (Dowex®-H) to synthesize benzo[f]indole-4,9-dione derivatives using β-enaminones systems and 2-bromonaphtoquinone. This method facilitates synthesizing a diverse range of compounds with varying substitution patterns, achieving yields of 88 %. The catalyst can be reused for up to five cycles without requiring reactivation. These compounds absorption spectra also show absorption (λmax) around 250–260 nm with a significant transition around 400 nm. Their photocatalytic potential was assessed by the model reaction of benzylamine photooxidation, achieving a yield of over 99 % within 36 h.
{"title":"Heterogeneous synthesis of benzo[f]indole-4,9-diones derivatives using sulfonic resin and photocatalytic study","authors":"Salma E. Mora-Rodríguez , Selene Lagunas-Rivera , J. Merced Martínez-Rosales , Yolanda Alcaraz-Contreras , Jorge Alberto Mendoza-Pérez , Miguel A. Vázquez","doi":"10.1016/j.tet.2024.134337","DOIUrl":"10.1016/j.tet.2024.134337","url":null,"abstract":"<div><div>This research introduces a heterogeneous approach utilizing a resin-bound sulfonic acid catalyst (Dowex®-H) to synthesize benzo[<em>f</em>]indole-4,9-dione derivatives using β-enaminones systems and 2-bromonaphtoquinone. This method facilitates synthesizing a diverse range of compounds with varying substitution patterns, achieving yields of 88 %. The catalyst can be reused for up to five cycles without requiring reactivation. These compounds absorption spectra also show absorption (<em>λ</em><sub>max</sub>) around 250–260 nm with a significant transition around 400 nm. Their photocatalytic potential was assessed by the model reaction of benzylamine photooxidation, achieving a yield of over 99 % within 36 h.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"168 ","pages":"Article 134337"},"PeriodicalIF":2.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142572171","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}
We developed an efficient mechanochemical method for the synthesis of 1,2-dihydropyridine derivatives from push-pull enamines and tert-propargyl alcohols under ball milling with p-TsOH/HFIP. The reaction proceeds smoothly under metal-free conditions with fast, efficient, and high-yielding synthesis of 1,2-dihydropyridines. The reaction shows excellent atom economy, with a broad substrate generality.
{"title":"Mechanochemical cyclization of push-pull enamines with propargyl alcohols","authors":"Srinivasarao Yaragorla, Megavath Vinod, Dandugula Sneha Latha","doi":"10.1016/j.tet.2024.134339","DOIUrl":"10.1016/j.tet.2024.134339","url":null,"abstract":"<div><div>We developed an efficient mechanochemical method for the synthesis of 1,2-dihydropyridine derivatives from push-pull enamines and <em>tert</em>-propargyl alcohols under ball milling with <em>p</em>-TsOH/HFIP. The reaction proceeds smoothly under metal-free conditions with fast, efficient, and high-yielding synthesis of 1,2-dihydropyridines. The reaction shows excellent atom economy, with a broad substrate generality.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"168 ","pages":"Article 134339"},"PeriodicalIF":2.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578731","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}
Pub Date : 2024-10-29DOI: 10.1016/j.tet.2024.134336
Zuleyma Martínez-Campos , Francisco José Palacios-Can , Susana T. López-Cortina , Rodrigo Said Razo-Hernández , Mario Fernández-Zertuche
In this work, we report the synthesis of three series of 3,5-disubstituted isoxazoles (4a-d, 5a-d and 6a-d), as analogues of the clinically important drug baclofen. The isoxazole ring systems were assembled through the key copper-catalyzed 1,3-dipolar cycloaddition reaction between a nitrile oxide (generated in situ from nitro compounds) and an alkyne. An X-ray crystallography study shows that the 1,3-dipolar cycloaddition reactions proceeded with very high regioselectively, leading exclusively to the formation of the 3,5-disubstituted regio isomers. Additionally, it was possible to obtain these compounds in enantiomerically pure form using SuperQuat-type chiral auxiliary. As suggested by our QSAR analysis and docking studies, these analogues have the potential to be biologically active as GABAB receptor modulators. Finally, the absorption, distribution, properties of metabolism and excretion (ADME) of the synthesized molecules was also determined by a computational approach. From this work we obtained five molecules ((S)-4d, (S)-5b, (S)-6b, (S)-6c and (S)-6d) as potential GABAB receptor agonists.
{"title":"Design and synthesis of 3,5-disubstituted isoxazoles by Cu-mediated 1,3-dipolar cycloaddition and their in silico evaluation as potential GABAB receptor modulators","authors":"Zuleyma Martínez-Campos , Francisco José Palacios-Can , Susana T. López-Cortina , Rodrigo Said Razo-Hernández , Mario Fernández-Zertuche","doi":"10.1016/j.tet.2024.134336","DOIUrl":"10.1016/j.tet.2024.134336","url":null,"abstract":"<div><div>In this work, we report the synthesis of three series of 3,5-disubstituted isoxazoles (<strong>4a-d</strong>, <strong>5a-d</strong> and <strong>6a-d</strong>), as analogues of the clinically important drug baclofen. The isoxazole ring systems were assembled through the key copper-catalyzed 1,3-dipolar cycloaddition reaction between a nitrile oxide (generated <em>in situ</em> from nitro compounds) and an alkyne. An X-ray crystallography study shows that the 1,3-dipolar cycloaddition reactions proceeded with very high regioselectively, leading exclusively to the formation of the 3,5-disubstituted regio isomers. Additionally, it was possible to obtain these compounds in enantiomerically pure form using SuperQuat-type chiral auxiliary. As suggested by our QSAR analysis and docking studies, these analogues have the potential to be biologically active as GABA<sub>B</sub> receptor modulators. Finally, the absorption, distribution, properties of metabolism and excretion (ADME) of the synthesized molecules was also determined by a computational approach. From this work we obtained five molecules ((<em>S</em>)-<strong>4d</strong>, (<em>S</em>)-<strong>5b</strong>, (<em>S</em>)-<strong>6b</strong>, (<em>S</em>)-<strong>6c</strong> and (<em>S</em>)-<strong>6d</strong>) as potential GABA<sub>B</sub> receptor agonists.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"168 ","pages":"Article 134336"},"PeriodicalIF":2.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578730","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}
Pub Date : 2024-10-29DOI: 10.1016/j.tet.2024.134345
Chuan Wu , Li-Rong Han , Jin-Song Hou , Qing-Han Li
A simple and mild catalytic SN2′-type displacement of propargyl halides with organotitanium reagents is reported. The SN2′-type displacement of propargyl bromides with organotitanium reagents mediated by CuI (2 mol%)/MePPh2(4 mol%) in dichloro methane afforded multi-substituted allenes in good yields (up to 95 %) at 40 °C for 5 h. The aryls bearing electron-donating or electron-withdrawing groups in aryltitanium reagents gave multi-substituted allenes in good yields. In addition, the di-substituted allenes bearing a naphthyl group was obtained in 54–99 % selectivities with isolated yields of 43–83 %. The process was simple and easily performed, and it provides an efficient method for the synthesis of di-substituted allene derivatives. On the basis of the experimental results, a possible catalytic cycle has been proposed.
报告了一种简单温和的有机钛试剂催化 SN2′型置换丙炔卤化物的方法。在二氯甲烷中，以 CuI (2 mol%)/MePPh2(4 mol%)为介导，在 40 °C 下催化 5 小时，丙炔基溴化物与有机钛试剂发生 SN2′型置换反应，得到了多取代烯。此外，带有萘基的二取代烯烃的选择性为 54-99%，分离产率为 43-83%。该工艺简单易行，为合成二取代烯烃衍生物提供了一种有效的方法。根据实验结果，提出了一种可能的催化循环。
{"title":"Highly efficient synthesis of di-substituted allenes via copper-catalyzed SN2′- substitution reaction of organotitanium reagents with propargyl bromides","authors":"Chuan Wu , Li-Rong Han , Jin-Song Hou , Qing-Han Li","doi":"10.1016/j.tet.2024.134345","DOIUrl":"10.1016/j.tet.2024.134345","url":null,"abstract":"<div><div>A simple and mild catalytic S<sub>N</sub>2′-type displacement of propargyl halides with organotitanium reagents is reported. The S<sub>N</sub>2′-type displacement of propargyl bromides with organotitanium reagents mediated by CuI (2 mol%)/MePPh<sub>2</sub>(4 mol%) in dichloro methane afforded multi-substituted allenes in good yields (up to 95 %) at 40 °C for 5 h. The aryls bearing electron-donating or electron-withdrawing groups in aryltitanium reagents gave multi-substituted allenes in good yields. In addition, the di-substituted allenes bearing a naphthyl group was obtained in 54–99 % selectivities with isolated yields of 43–83 %. The process was simple and easily performed, and it provides an efficient method for the synthesis of di-substituted allene derivatives. On the basis of the experimental results, a possible catalytic cycle has been proposed.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"168 ","pages":"Article 134345"},"PeriodicalIF":2.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654179","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}
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