{"title":"Synthesis and Reaction Mechanisms for the Construction of Pyrrolo[1,2-a]quinoxalines and Pyrrolo[1,2-a]quinoxalin-4(5H)-ones","authors":"Jiang Nan, Lei Yao","doi":"10.1002/ejoc.202500143","DOIUrl":null,"url":null,"abstract":"Pyrrolo[1,2-a]quinoxalines and pyrrolo[1,2-a]quinoxalin-4(5H)-ones are recognized as important tricyclic scaffolds due to their diverse pharmacological activities, including anticancer, anti-fungi, anti-tuberculosis, and antimalarial, as well as their roles as 5-HT3 receptor agonists and kinase inhibitors targeting CK2 and AKT, and others. Developing efficient and reliable synthetic approaches to access these compounds remains an attractive goal in contemporary medicinal chemistry and drug discovery. This review highlights recent advances in the synthesis of pyrrolo[1,2-a]quinoxalines and pyrrolo[1,2-a]quinoxalin-4(5H)-ones, particularly focusing on strategies that maintain the A and C-rings while constructing the B-ring through the formation of a-, b-, and c-bonds. The information collected describes the two key components of the synthesis process 1-(2-substitued-phenyl)-1H-pyrrole and aldehyde or its surrogate.\nThis review also briefly summarizes the reaction mechanisms for the formation of tricyclic skeletons to determine the key factors governing the issues of productivity and regioselectivity. Through analysis of the advantages and disadvantages of existing synthetic methods, we predict that A-ring formation strategy-based pyrrolo[1,2-a]quinoxaline reactions will be developed in the future. We hope that this review will motivate the search for novel strategies to synthesize pyrrolo[1,2-a]quinoxalines and pyrrolo[1,2-a]quinoxalin-4(5H)-ones, accessing tricyclic skeletons that may have potential applications in medicinal chemistry, materials science, and many branches of chemistry.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"32 1","pages":""},"PeriodicalIF":2.5000,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Organic Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1002/ejoc.202500143","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
引用次数: 0
Abstract
Pyrrolo[1,2-a]quinoxalines and pyrrolo[1,2-a]quinoxalin-4(5H)-ones are recognized as important tricyclic scaffolds due to their diverse pharmacological activities, including anticancer, anti-fungi, anti-tuberculosis, and antimalarial, as well as their roles as 5-HT3 receptor agonists and kinase inhibitors targeting CK2 and AKT, and others. Developing efficient and reliable synthetic approaches to access these compounds remains an attractive goal in contemporary medicinal chemistry and drug discovery. This review highlights recent advances in the synthesis of pyrrolo[1,2-a]quinoxalines and pyrrolo[1,2-a]quinoxalin-4(5H)-ones, particularly focusing on strategies that maintain the A and C-rings while constructing the B-ring through the formation of a-, b-, and c-bonds. The information collected describes the two key components of the synthesis process 1-(2-substitued-phenyl)-1H-pyrrole and aldehyde or its surrogate.
This review also briefly summarizes the reaction mechanisms for the formation of tricyclic skeletons to determine the key factors governing the issues of productivity and regioselectivity. Through analysis of the advantages and disadvantages of existing synthetic methods, we predict that A-ring formation strategy-based pyrrolo[1,2-a]quinoxaline reactions will be developed in the future. We hope that this review will motivate the search for novel strategies to synthesize pyrrolo[1,2-a]quinoxalines and pyrrolo[1,2-a]quinoxalin-4(5H)-ones, accessing tricyclic skeletons that may have potential applications in medicinal chemistry, materials science, and many branches of chemistry.
期刊介绍:
The European Journal of Organic Chemistry (2019 ISI Impact Factor 2.889) publishes Full Papers, Communications, and Minireviews from the entire spectrum of synthetic organic, bioorganic and physical-organic chemistry. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies.
The following journals have been merged to form two leading journals, the European Journal of Organic Chemistry and the European Journal of Inorganic Chemistry:
Liebigs Annalen
Bulletin des Sociétés Chimiques Belges
Bulletin de la Société Chimique de France
Gazzetta Chimica Italiana
Recueil des Travaux Chimiques des Pays-Bas
Anales de Química
Chimika Chronika
Revista Portuguesa de Química
ACH—Models in Chemistry
Polish Journal of Chemistry.