Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

Abstract

SummaryCondensed 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.

Varioloid A, a new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291

“…Clear NOE correlation between H-2 and 3-OMe led to recognition that these protons adopt cis orientation. In order to elucidate the absolute configuration of 1, solution TDDFT-ECD protocol [14–15] was carried out on the arbitrarily chosen (2 R ,3 R ) enantiomer.…”

Biomimetic synthesis and HPLC–ECD analysis of the isomers of dracocephins A and B

“…In order to confirm the assignment of the absolute configurations for the stereoisomers 2a – d independently from the results of Ren et al and to test the applicability of the ECD calculations for the stereochemical studies of flavanoid alkaloids, the solution TDDFT–ECD calculation method [6] was applied to 2a – d and 3a – d . For the validation of our computational approach on flavonoids, the ECD spectra of ( R )-naringenin (( R )- 1 ), the building blocks of dracocephins A and B, were calculated first with different methods to identify which is able to reproduce most precisely the experimental ECD transitions.…”

HPLC‐ECD and TDDFT‐ECD study of hexahydropyrrolo[1,2‐a]quinoline derivatives

“…Due to the different chromophores at the tetrasubstituted C‐4 carbon, the HPLC‐ECD spectra of the separated enantiomers of 1 to 8 were quite different requiring TDDFT‐ECD analysis for most of them to determine the absolute configuration. The combination of HPLC‐ECD measurements and TDDFT‐ECD calculations was proved an efficient tool to study the absolute configuration of stereoisomers derived from racemic or scalemic mixtures of synthetic and natural origin …”

“…The combination of HPLC-ECD measurements and TDDFT-ECD calculations was proved an efficient tool to study the absolute configuration of stereoisomers derived from racemic or scalemic mixtures of synthetic and natural origin. [24][25][26] For the configurational assignment, preliminary MMFF conformers were generated in a conformational search, these conformers were reoptimized at several DFT levels [B3LYP/6-31G(d) in vacuo, B3LYP/TZVP, B97D/TZVP, and CAM-B3LYP with PCM for CHCl 3 ], and ECD spectra were computed with various functionals (B3LYP, BH&HLYP, CAM-B3LYP, and PBE0) and the TZVP basis set with or without the same solvent model as applied in the preceding DFT optimization step.…”