Contrasting reactivity of fluorinated 2, 6-heptanediones towards amines and ammonia, leading to cyclohexanediones or 2-oxa-6-azabicyclo[2.2.2]octanes and evaluation of their cytotoxicity. (18th June 2019)

• Record Type: Journal Article
• Authors: Pikun, Nadiia V.; Kolesnyk, Natalya P.; Rusanov, Eduard B.; Plotniece, Aiva; Sobolev, Arkadij; Domracheva, Ilona; Shermolovich, Yuriy G.
• Is Part Of: New journal of chemistry. Volume 43:Number 26(2019)
• Page Start: 10537
• Page End: 10544
• Publication Date: 2019-06-18
• Subjects: Chemistry -- Periodicals; Chimie -- Périodiques; 540
• DOI: 10.1039/c9nj01446b
• Languages: English
• ISSNs: 1144-0546

Abstract

Abstract : Synthesis and cytotoxic studies of cyclohexanediones and 2-oxa-6-azabicyclo[2.2.2]octanes obtained in reaction of fluorinated 2, 6-hetanediones with amines and ammonia respectively. Abstract : The reactivity and synthetic utility of dialkyl 2, 4-diacetyl-2, 4-difluoro-3-phenylpentanedioates1 (2, 6-heptanediones) as new fluorinated reagents prepared from the reaction of 1, 4-dihydropyridines with Selectfluor® for the synthesis of carbocycles and heterocyclic bridged systems is described. The contrasting behaviour of fluorinated 2, 6-heptanediones1 towards the reaction with amines or ammonia has been revealed. 2, 6-Heptanediones1 with alkylamines form alkylammonium 3-acetyl-5-(alkyloxycarbonyl)-3, 5-difluoro-2, 6-dioxo-4-phenylcyclohexan-1-ides2 ; however, with the less basic aniline, they do not react under similar conditions. 2, 6-Heptanediones with aqueous ammonia give alkyl 4, 7-difluoro-3-hydroxy-1, 3-dimethyl-5-oxo-8-phenyl-2-oxa-6-azabicyclo[2.2.2]octane-7-carboxylates4 . The cytotoxicity of 2, 6-heptanediones1a, c, the salts of 3-acetyl-5-(alkoxycarbonyl)-3, 5-difluoro-2, 6-dioxo-4-phenylcyclohexan-1-ides2a, c–f, and 2-oxa-6-azabicyclo[2.2.2]octanes4a–c on different cancer cell lines and "normal" cells has been evaluated, thus providing a basis for further studies concerning the potential use of these new compounds.