Synthesis and Conformational Analysis of Naphthoxazine-Fused Phenanthrene Derivatives
Khadija Belasri,
Leila Topal,
Matthias Heydenreich,
Andreas Koch,
Erich Kleinpeter,
Ferenc Fülöp,
István Szatmári
Affiliations
Khadija Belasri
Institute of Pharmaceutical Chemistry and MTA-SZTE Stereochemistry Research Group, Hungarian Academy of Sciences, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
Leila Topal
Institute of Pharmaceutical Chemistry and MTA-SZTE Stereochemistry Research Group, Hungarian Academy of Sciences, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
Matthias Heydenreich
Department of Chemistry, University of Potsdam, Karl-Liebknecht-Str. 24-25, D-14476 Potsdam (Golm), Germany
Andreas Koch
Department of Chemistry, University of Potsdam, Karl-Liebknecht-Str. 24-25, D-14476 Potsdam (Golm), Germany
Erich Kleinpeter
Department of Chemistry, University of Potsdam, Karl-Liebknecht-Str. 24-25, D-14476 Potsdam (Golm), Germany
Ferenc Fülöp
Institute of Pharmaceutical Chemistry and MTA-SZTE Stereochemistry Research Group, Hungarian Academy of Sciences, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
István Szatmári
Institute of Pharmaceutical Chemistry and MTA-SZTE Stereochemistry Research Group, Hungarian Academy of Sciences, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
The synthesis of new phenanthr[9,10-e][1,3]oxazines was achieved by the direct coupling of 9-phenanthrol with cyclic imines in the modified aza-Friedel–Crafts reaction followed by the ring closure of the resulting bifunctional aminophenanthrols with formaldehyde. Aminophenanthrol-type Mannich bases were synthesised and transformed to phenanthr[9,10-e][1,3]oxazines via [4 + 2] cycloaddition. Detailed NMR structural analyses of the new polyheterocycles as well as conformational studies including Density Functional Theory (DFT) modelling were performed. The relative stability of ortho-quinone methides (o-QMs) was calculated, the geometries obtained were compared with the experimentally determined NMR structures, and thereby, the regioselectivity of the reactions has been assigned.
