Shaonan Wang, Min Sun, Yajuan Su, Zhou Xu, Ang Li, Weiwei He
Deucravacitinib is a selective allosteric inhibitor of tyrosine kinase 2 (TYK2) recently approved by the FDA for the treatment of plaque psoriasis. We discovered that this compound induces proteasomal degradation of YAP1, the downstream effector of the Hippo signaling pathway, in human glioblastoma (GBM) cells (U-87 MG). This degradation is independent of the canonical Hippo pathway, which offers clues to alternative mechanisms for YAP1 regulation.
{"title":"Deucravacitinib Induces Proteasomal Degradation of YAP1 in Human Glioblastoma Cells","authors":"Shaonan Wang, Min Sun, Yajuan Su, Zhou Xu, Ang Li, Weiwei He","doi":"10.1055/a-2331-6463","DOIUrl":"https://doi.org/10.1055/a-2331-6463","url":null,"abstract":"Deucravacitinib is a selective allosteric inhibitor of tyrosine kinase 2 (TYK2) recently approved by the FDA for the treatment of plaque psoriasis. We discovered that this compound induces proteasomal degradation of YAP1, the downstream effector of the Hippo signaling pathway, in human glioblastoma (GBM) cells (U-87 MG). This degradation is independent of the canonical Hippo pathway, which offers clues to alternative mechanisms for YAP1 regulation.","PeriodicalId":22319,"journal":{"name":"Synlett","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141112368","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}
The synthesis of bibenzyl derivatives holds significance in organic chemistry due to their diverse pharmacological and synthetic applications. Herein, we report a novel copper–promoted dimerization reaction for the efficient synthesis of functionalized bibenzyls from benzyl thiocyanates. The coupling reaction proceeds under aerobic and mild conditions via cascade C–S bond cleavage in one pot. Diverse substituents including electron–withdrawing groups on the aryl ring are well–tolerated to afford the desired products in moderate to good yields. The developed protocol could be utilized to obtain the cross coupling product from two different electron–deficient benzyl thiocyanates.
{"title":"Copper−Promoted Dimerization of Benzyl Thiocyanates to Access Functionalized Bibenzyls","authors":"Sandeep Singh, S. R. De","doi":"10.1055/a-2330-9955","DOIUrl":"https://doi.org/10.1055/a-2330-9955","url":null,"abstract":"The synthesis of bibenzyl derivatives holds significance in organic chemistry due to their diverse pharmacological and synthetic applications. Herein, we report a novel copper–promoted dimerization reaction for the efficient synthesis of functionalized bibenzyls from benzyl thiocyanates. The coupling reaction proceeds under aerobic and mild conditions via cascade C–S bond cleavage in one pot. Diverse substituents including electron–withdrawing groups on the aryl ring are well–tolerated to afford the desired products in moderate to good yields. The developed protocol could be utilized to obtain the cross coupling product from two different electron–deficient benzyl thiocyanates.","PeriodicalId":22319,"journal":{"name":"Synlett","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141116655","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}
Cross-coupling methods for the introduction of various substituents into the olefin moiety of cyclooctenes were developed. A range of 1-substituted cis-cyclooctenes were synthesized. These protocols unlocked routes to previously inaccessible derivatives, allowing for the syntheses of cis-cyclooctenes bearing various functional groups. Moreover, the method was applied to the synthesis of a 1,2-disubstituted trans-cyclooctene for the first time, which proved to be a significantly active organocatalyst in relation to the previously developed monosubstituted trans-cyclooctene.
{"title":"Synthesis of Substituted Cyclooctenes through Cross-Coupling Reactions","authors":"Ryuichi Murata, Rakuto Yoshida, Daisuke Uraguchi, Keisuke Asano","doi":"10.1055/a-2330-0819","DOIUrl":"https://doi.org/10.1055/a-2330-0819","url":null,"abstract":"Cross-coupling methods for the introduction of various substituents into the olefin moiety of cyclooctenes were developed. A range of 1-substituted cis-cyclooctenes were synthesized. These protocols unlocked routes to previously inaccessible derivatives, allowing for the syntheses of cis-cyclooctenes bearing various functional groups. Moreover, the method was applied to the synthesis of a 1,2-disubstituted trans-cyclooctene for the first time, which proved to be a significantly active organocatalyst in relation to the previously developed monosubstituted trans-cyclooctene.","PeriodicalId":22319,"journal":{"name":"Synlett","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141124948","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}
Ryusei Osawa, Kotaro Ogihara, Fumine Hamasaki, H. Kinoshita, Katsukiyo Miura
We developed an efficient method for the synthesis of dihydrobenzosiloles in 19% to 90% isolated yields from 1-hydrosilyl-2-ethynylbenzenes using two equivalents of diisobutylaluminum hydride. The reaction mechanism involves regioselective double hydroalumination of the alkyne moiety followed by cyclization to 2-alanyldihydrobenzosilole. A silacyclopentane was also synthesized in 97% isolated yield from the corresponding 4-silylbut-1-yne under the same reaction conditions. Although the substrate scope was conducted on a 0.5 mmol scale, a gram-scale reaction of 1-diphenylsilyl-2-ethynylbenzene under the optimized reaction conditions successfully afforded the desired product in 94% isolated yield without loss of reactivity.
{"title":"Synthesis of Dihydrobenzosiloles and Silacyclopentane via Double Hydroalumination of Terminal Alkynes","authors":"Ryusei Osawa, Kotaro Ogihara, Fumine Hamasaki, H. Kinoshita, Katsukiyo Miura","doi":"10.1055/a-2330-0874","DOIUrl":"https://doi.org/10.1055/a-2330-0874","url":null,"abstract":"We developed an efficient method for the synthesis of dihydrobenzosiloles in 19% to 90% isolated yields from 1-hydrosilyl-2-ethynylbenzenes using two equivalents of diisobutylaluminum hydride. The reaction mechanism involves regioselective double hydroalumination of the alkyne moiety followed by cyclization to 2-alanyldihydrobenzosilole. A silacyclopentane was also synthesized in 97% isolated yield from the corresponding 4-silylbut-1-yne under the same reaction conditions. Although the substrate scope was conducted on a 0.5 mmol scale, a gram-scale reaction of 1-diphenylsilyl-2-ethynylbenzene under the optimized reaction conditions successfully afforded the desired product in 94% isolated yield without loss of reactivity.","PeriodicalId":22319,"journal":{"name":"Synlett","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141125001","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}
An organocatalyzed Fischer indolization is established by combining 2,2′-biphenol (10 mol%) and B(OH)3 (30 mol%) as weak, readily available, and easy-to-handle acids. The inclusion of MgSO4, which efficiently scavenges NH3 (a possible acid catalyst poison), appears to be key to the success of this process. The corresponding indoles are obtained in yields of up to 91% using this method.y
{"title":"Organocatalytic Fischer Indolization Using the 2,2′-Biphenol/ B(OH)3 System","authors":"Kenji Sugimoto, Yuji Matsuya, Yusei Wada, Fumino Kitamura","doi":"10.1055/s-0043-1775363","DOIUrl":"https://doi.org/10.1055/s-0043-1775363","url":null,"abstract":"An organocatalyzed Fischer indolization is established by combining 2,2′-biphenol (10 mol%) and B(OH)3 (30 mol%) as weak, readily available, and easy-to-handle acids. The inclusion of MgSO4, which efficiently scavenges NH3 (a possible acid catalyst poison), appears to be key to the success of this process. The corresponding indoles are obtained in yields of up to 91% using this method.y","PeriodicalId":22319,"journal":{"name":"Synlett","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140963108","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}
A new protocol for accessing 3,4-dihydroquinolin-2(1H)-ones was established through a sequence of iron-catalyzed photoredox generation of carbamoyl radicals from oxamic acids, addition of the carbamoyl radicals to electron-deficient alkenes, intramolecular cyclization, and aromatization. The process is compatible with a variety of N-phenyloxamic acids and monosubstituted, 1,1-disubstituted, and trisubstituted electron-deficient alkenes. Employing cheap, readily available, and environmentally benign iron as the catalyst, the protocol provides an excellent alternative for synthesis of 3,4-dihydroquinolin-2(1H)-ones.
{"title":"Generation of Carbamoyl Radicals and 3,4-Dihydroquinolin-2(1H)-ones Enabled by Iron Photoredox Catalysis","authors":"Tao Cai, Gaofeng Feng, Yanhua Fu, Chao Zhang","doi":"10.1055/s-0043-1763753","DOIUrl":"https://doi.org/10.1055/s-0043-1763753","url":null,"abstract":"A new protocol for accessing 3,4-dihydroquinolin-2(1H)-ones was established through a sequence of iron-catalyzed photoredox generation of carbamoyl radicals from oxamic acids, addition of the carbamoyl radicals to electron-deficient alkenes, intramolecular cyclization, and aromatization. The process is compatible with a variety of N-phenyloxamic acids and monosubstituted, 1,1-disubstituted, and trisubstituted electron-deficient alkenes. Employing cheap, readily available, and environmentally benign iron as the catalyst, the protocol provides an excellent alternative for synthesis of 3,4-dihydroquinolin-2(1H)-ones.","PeriodicalId":22319,"journal":{"name":"Synlett","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140970643","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}
A simple, efficient, and environmentally benign method for the direct C-3-alkoxycarbonylation of 2H-indazoles using alkyl carbazates has been developed under metal-free conditions at room temperature. This current protocol represents a facile access to C-3-carboxylic ester derived 2H-indazoles with wide functional group tolerance in good to excellent yields. The mechanistic studies suggest that the reaction proceeds through a radical pathway.
{"title":"Metal-Free Synthesis of C-3-Alkoxycarbonylated 2H-Indazoles Using Alkyl Carbazates","authors":"Dipti Lai, Suvam Bhattacharjee, Sumit Ghosh, Subrata Sinha, Alakananda Hajra","doi":"10.1055/a-2316-5066","DOIUrl":"https://doi.org/10.1055/a-2316-5066","url":null,"abstract":"<p>A simple, efficient, and environmentally benign method for the direct C-3-alkoxycarbonylation of 2<i>H</i>-indazoles using alkyl carbazates has been developed under metal-free conditions at room temperature. This current protocol represents a facile access to C-3-carboxylic ester derived 2<i>H</i>-indazoles with wide functional group tolerance in good to excellent yields. The mechanistic studies suggest that the reaction proceeds through a radical pathway.</p> ","PeriodicalId":22319,"journal":{"name":"Synlett","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141062053","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}
A novel method was developed to synthesise chromene-lactone analogues of podophyllotoxin using an ultrasound-assisted multicomponent reaction (MCR). The MCR involved tetronic acid, phenols, and aromatic aldehydes and was promoted by BF3·OEt2, resulting in the production of ten derivatives with different substituents on the aromatic rings in yields ranging from 32% to 93%. These compounds are of interest due to their reported activity against tumour cells. Their ease of synthesis through the MCR may allow for more in-depth studies on anticancer activity, as well as investigations of other biological targets. The synthesised derivatives contain important pharmacophoric groups for potential applications in medicinal chemistry.
{"title":"Ultrasound-Assisted, BF3·OEt2-Promoted, Multicomponent Synthesis of Chromene-Based Podophyllotoxin Analogues","authors":"RS Laurentiz, Fernanda A. Santos","doi":"10.1055/s-0043-1774865","DOIUrl":"https://doi.org/10.1055/s-0043-1774865","url":null,"abstract":"A novel method was developed to synthesise chromene-lactone analogues of podophyllotoxin using an ultrasound-assisted multicomponent reaction (MCR). The MCR involved tetronic acid, phenols, and aromatic aldehydes and was promoted by BF3·OEt2, resulting in the production of ten derivatives with different substituents on the aromatic rings in yields ranging from 32% to 93%. These compounds are of interest due to their reported activity against tumour cells. Their ease of synthesis through the MCR may allow for more in-depth studies on anticancer activity, as well as investigations of other biological targets. The synthesised derivatives contain important pharmacophoric groups for potential applications in medicinal chemistry.","PeriodicalId":22319,"journal":{"name":"Synlett","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140966740","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}
Rinkal B Bhoraniya, Shiv Rohitbhai Desai, Mahesh Koladiya, Vidhi V Bhopekar, Swati H Patel, Sachin G Modha
A Post-Ugi Brønsted acid catalyzed unprecedented fragmentation followed by in situ trapping of the alkylideneindolenine intermediate by indole nucleophiles is developed to furnish novel bis(indolyl)acetamides. The amide fragment formed during this acid catalyzed fragmentation of Ugi adduct was also isolated and characterized. The carboxylic acid and amine components of Ugi reaction were smartly chosen to allow simple water wash for removal of amide fragment to obtain the desired bis(indolyl)acetamides in pure form.
研究人员开发了一种乌基后布氏酸催化的前所未有的碎裂方法,然后通过吲哚亲核剂对亚烷基吲哚啉中间体进行原位捕获,从而生成新型的双(吲哚基)乙酰胺。在这种酸催化的 Ugi 加合物破碎过程中形成的酰胺片段也被分离出来并进行了表征。巧妙地选择了 Ugi 反应中的羧酸和胺成分,以便通过简单的水洗去除酰胺片段,从而获得所需的纯双(吲哚基)乙酰胺。
{"title":"Post-Ugi acid catalyzed fragmentation and trapping: An unprecedented approach towards novel bis(indolyl)acetamides","authors":"Rinkal B Bhoraniya, Shiv Rohitbhai Desai, Mahesh Koladiya, Vidhi V Bhopekar, Swati H Patel, Sachin G Modha","doi":"10.1055/a-2328-3091","DOIUrl":"https://doi.org/10.1055/a-2328-3091","url":null,"abstract":"A Post-Ugi Brønsted acid catalyzed unprecedented fragmentation followed by in situ trapping of the alkylideneindolenine intermediate by indole nucleophiles is developed to furnish novel bis(indolyl)acetamides. The amide fragment formed during this acid catalyzed fragmentation of Ugi adduct was also isolated and characterized. The carboxylic acid and amine components of Ugi reaction were smartly chosen to allow simple water wash for removal of amide fragment to obtain the desired bis(indolyl)acetamides in pure form.","PeriodicalId":22319,"journal":{"name":"Synlett","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140976753","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}
Here we describe a homocoupling reaction of arylboronic acid facilitated by silver carbonate, which proceeds smoothly in MeOH even at ambient temperature. The reaction exhibits broad functional group compatibility, affording a variety of symmetrical biaryls in satisfactory yields. Silver nanoparticles formed in situ serve as an accelerator in this process. Moreover, initial mechanistic investigations suggest that this transformation may occur via a radical mechanism.
{"title":"Silver-Mediated Homocoupling of Arylboronic Acids","authors":"Tomoya Sakaguchi, Kyuta Fukuoka, Takuya Matsuki, Misa Kawase, Aya Tazawa, Yasuhiro Uozumi, Yoshimasa Matsumura, Osamu Shimomura, Atsushi Ohtaka","doi":"10.1055/a-2315-8369","DOIUrl":"https://doi.org/10.1055/a-2315-8369","url":null,"abstract":"<p>Here we describe a homocoupling reaction of arylboronic acid facilitated by silver carbonate, which proceeds smoothly in MeOH even at ambient temperature. The reaction exhibits broad functional group compatibility, affording a variety of symmetrical biaryls in satisfactory yields. Silver nanoparticles formed in situ serve as an accelerator in this process. Moreover, initial mechanistic investigations suggest that this transformation may occur via a radical mechanism.</p> ","PeriodicalId":22319,"journal":{"name":"Synlett","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141062056","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}