title: Alpha-nitro ketone as an electrophile and nucleophile: synthesis of 3-substituted 2-nitromethylenetetrahydrothiophene and -tetrahydrofuran as drosophila nicotinic receptor probes.
abstract: 3-(6-Chloropyridin-3-yl)methyl-2-nitromethylenetetrahydrothiophene 2 and -tetrahydrofuran 3 were synthesized through novel approaches using alpha-nitro ketone intermediates as an electrophile and nucleophile, respectively. The 2-nitromethylenetetrahydrothiophene 2 was formed exclusively as the Z-isomer through intramolecular attack by a thiol substituent at the carbonyl group of an alpha-nitro ketone, in which the alpha-nitro ketone served as an electrophile. In contrast, the corresponding 2-nitromethylenetetrahydrofuran 3, not accessible by the above route due to limited stability, was prepared as a mixture of E- and Z-isomers by intramolecular attack of the alpha-nitro ketone enol anion in which the deprotonated alpha-nitro ketone served as a nucleophile. These compounds, together with the corresponding 2-nitromethylenepyrrolidine (1), were used to probe the Drosophila neonicotinoid-nicotinic acetylcholine receptor interaction.
authors.affiliation: Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California, Berkeley, California 94720-3112, USA.
authors.forename: Nanjing
authors.initials: N
authors.lastname: Zhang
authors.forename: Motohiro
authors.initials: M
authors.lastname: Tomizawa
authors.forename: John E
authors.initials: JE
authors.lastname: Casida
mesh_terms: D000818:Animals; D004330:Drosophila / Q000378:metabolism; D005663:Furans / Q000138:chemical synthesis* / Q000378:metabolism; D007536:Isomerism; D007659:Ketones / Q000737:chemistry*; D015335:Molecular Probes / Q000138:chemical synthesis* / Q000378:metabolism; D009574:Nitro Compounds / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011759:Pyrrolidines / Q000737:chemistry; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism
chemical_list: D005663:Furans; D007659:Ketones; D015335:Molecular Probes; D009574:Nitro Compounds; D011759:Pyrrolidines; D011978:Receptors, Nicotinic; D013876:Thiophenes; C018674:tetrahydrofuran