Synthesis of novel 3-[(2R)-2-[(2S)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]-2-hydroxyethyl]-urea/thiourea derivatives and evaluation of their antimicrobial activities

• Published in: Phosphorus, sulfur, and silicon and the related elements Vol. 195; no. 1; pp. 65 - 74
• Main Authors: Mannam, Madhava Rao, S., Srimurugan, Kumar, Pramod, Chamarthi, Naga Raju, K. R. S., Prasad
• Format: Journal Article
• Language: English
• Published: Abingdon Taylor & Francis 02-01-2020; Taylor & Francis Ltd
• Subjects: Antiinfectives and antibacterials; antimicrobial activity; Chemical synthesis; Chromane; Ethanol; Fungi; Lead compounds; nebivolol intermediate; NMR; Nuclear magnetic resonance; Thiourea derivatives; Thioureas; urea and thiourea derivatives; Ureas
• ISSN: 1042-6507; 1563-5325
• DOI: 10.1080/10426507.2019.1635596

A new series of biologically active 3-[(2R*)-2-[(2S*)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]-2-hydroxyethyl]-urea/thiourea derivatives (1) have been designed and synthesized in four steps from 6-fluoro-3,4-dihydro-2-(oxiran-2-yl)-2H-chromene (2). The structures of newly synthesized compounds (1a-j) were confirmed by
1
H,
13
C NMR, and HRMS. The major advantages of the present article include the development of an efficient eluent system for good separation of diastereomers (2a and 2b) with high yields and synthesis of (R*)-2-(benzylamino)-1-((S*)-6-fluoro-3,4-dihydro-2H-chromen-2-yl)ethanol (3) in high yields (87%) from epoxide (2a) through new reaction conditions. The synthesized compounds (1a-j) exhibited moderate to excellent antimicrobial activities against both bacterial strains (gram + Ve and gram -Ve strains) and fungal strains. Among the tested compounds, promising lead compounds were identified (compounds 1a and 1d against bacterial strains and compound 1h and 1j against fungal strains) and their antimicrobial activities are comparable with the reference standard.