title: Imino [4+4] cycloaddition products as exclusive and biologically relevant acrolein-amine conjugates are intermediates of 3-formyl-3,4-dehydropiperidine (FDP), an acrolein biomarker.
abstract: We demonstrated synthetically that the eight-membered heterocycles 2,6,9-triazabicyclo[3.3.1]nonanes and 1,5-diazacyclooctanes are the initial and exclusive products of the reaction, through an imino [4+4] cycloaddition, of biologically relevant amines with acrolein. The stabilities of the aminoacetals within the eight-membered heterocycles determined whether the product was subsequently transformed gradually into the 3-formyl-3,4-dehydropiperidine (FDP), which is widely used as an oxidative stress marker. The reactivity profiles discovered in this study suggested that some of the imino [4+4] cycloaddition products are reactive intermediates of FDP and contribute to the mechanisms underlying the oxidative stress response to acrolein.
authors.affiliation: Biofunctional Synthetic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan; Department of Chemistry Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka-shi 560-0043, Japan. Electronic address: kotzenori@riken.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takamatsu
authors.affiliation: Department of Chemistry Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka-shi 560-0043, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukase
authors.affiliation: Biofunctional Chemistry Laboratory, A. Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlyovskaya Street, Kazan 420008, Russia.
authors.forename: Almira
authors.initials: A
authors.lastname: Kurbangalieva
authors.affiliation: Biofunctional Synthetic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan; Biofunctional Chemistry Laboratory, A. Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlyovskaya Street, Kazan 420008, Russia.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000171:Acrolein / Q000737:chemistry*; D000588:Amines / Q000737:chemistry*; D061565:Cycloaddition Reaction; D007097:Imines / Q000737:chemistry*; D009638:Norepinephrine / Q000737:chemistry; D018384:Oxidative Stress; D010880:Piperidines / Q000737:chemistry*; D013110:Sphingosine / Q000737:chemistry
chemical_list: D000588:Amines; D007097:Imines; D010880:Piperidines; C032727:piperidine; D000171:Acrolein; D013110:Sphingosine; D009638:Norepinephrine
keywords: 1,5-Diazacyclooctane; 2,6,9-Triazabicyclo[3.3.1]nonane; 3-Formyl-3,4-dehydropiperidine (FDP); Acrolein; Biologically relevant amine; Biomarker; Imino [4+4] cycloaddition