title: Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel-[1,5]-hydride shift cyclization reaction.
abstract: Condensed O,N-heterocycles containing tetrahydro-1,4-benzoxazepine and tetrahydroquinoline moieties were prepared by a regio- and diastereoselective domino Knoevenagel-[1,5]-hydride shift cyclization reaction of a 4-aryl-2-phenyl-1,4-benzoxazepine derivative obtained from flavanone. The relative configuration of products were determined by the correlation of (3) J H,H coupling data with the geometry of major conformers accessed by DFT conformational analysis. Separated enantiomers of the products were characterized by HPLC-ECD data, which allowed their configurational assignment on the basis of TDDFT-ECD calculation of the solution conformers. Two compounds showed neuroprotective activities against hydrogen peroxide (H2O2) or β-amyloid25-35 (Aβ25-35)-induced cellular injuries in human neuroblastoma SH-SY5Y cells in the range of those of positive controls.
authors.affiliation: Department of Organic Chemistry, Semmelweis University, Hőgyes u. 7., 1092 Budapest, Hungary, ; Department of Organic Chemistry, University of Debrecen, Debrecen, P. O. Box 20, 4010 Debrecen, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Tóth
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhang Jiang Hi-Tech Park, Shanghai 201203, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Fu
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhang Jiang Hi-Tech Park, Shanghai 201203, PR China.
authors.forename: Hai Yan
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: Department of Organic Chemistry, University of Debrecen, Debrecen, P. O. Box 20, 4010 Debrecen, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Mándi
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Debrecen, H-4010 Debrecen, Hungary.
authors.forename: Katalin E
authors.initials: KE
authors.lastname: Kövér
authors.affiliation: Department of Organic Chemistry, University of Debrecen, Debrecen, P. O. Box 20, 4010 Debrecen, Hungary.
authors.forename: Tünde-Zita
authors.initials: TZ
authors.lastname: Illyés
authors.affiliation: Department of Organic Chemistry, University of Debrecen, Debrecen, P. O. Box 20, 4010 Debrecen, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Kiss-Szikszai
authors.affiliation: Department of Organic Chemistry, Semmelweis University, Hőgyes u. 7., 1092 Budapest, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Balogh
authors.affiliation: Department of Organic Chemistry, University of Debrecen, Debrecen, P. O. Box 20, 4010 Debrecen, Hungary ; Porfirin Ltd., Mikszáth K. u. 7. III/3, 4032 Debrecen, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Kurtán
authors.affiliation: Department of Organic Chemistry, University of Debrecen, Debrecen, P. O. Box 20, 4010 Debrecen, Hungary.
authors.forename: Sándor
authors.initials: S
authors.lastname: Antus
authors.affiliation: Department of Organic Chemistry, Semmelweis University, Hőgyes u. 7., 1092 Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Mátyus
keywords: 1,4-benzoxazepine; TDDFT-ECD calculation; diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization; neuroprotective; tert-amino effect