Synthesis of biologically active [1, 5]diazocino[2, 1-b]quinazolinones through [4 + 4] cycloaddition of 2-alkynyl quinazolinones with aza-ortho-quinone methides. Issue 7 (7th March 2023)

• Record Type: Journal Article
• Authors: Pang, Li; Fang, Shu-Jun; Zou, Pei-Sen; Wang, Wang; Su, Jun-Cheng; Liu, Xiao-Qing; Pan, Cheng-Xue; Mo, Dong-Liang; Su, Gui-Fa
• Is Part Of: Organic chemistry frontiers. Volume 10:Issue 7(2023)
• Page Start: 1780
• Page End: 1787
• Publication Date: 2023-03-07
• Subjects: Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1039/d3qo00056g
• Languages: English
• ISSNs: 2052-4110

Abstract

Abstract : Biologically active [1, 5]diazocino[2, 1- b ]quinazolinones were synthesized via base-promoted [4 + 4] cycloaddition of 2-alkynyl quinazolinones with aza- ortho -quinone methides. Abstract : We report an atom-economical [4 + 4] cycloaddition of 2-alkynyl quinazolines with aza- ortho -quinone methides (ao-QMs) generated from 2-(bromomethyl)anilines to prepare various [1, 5]diazocino[2, 1- b ]quinazolinones in good to excellent yields in a short reaction time and under mild reaction conditions. Moreover, an estrone-derived [1, 5]diazocino[2, 1- b ]quinazolinone could be easily prepared in 30% total yield over five steps and biological assays reveal that the obtained [1, 5]diazocino[2, 1- b ] quinazolinones significantly inhibited nitric oxide generation in LPS-stimulated RAW264.7 cells. The present method features transition-metal free nature, broad substrate scope, good functional group tolerance, gram-scale preparation, and simple purification operation without flash column chromatography.