Synthesis and laccase-mediated oxidation of new condensed 1,4-dihydropyridine derivatives

Abstract

We describe herein the synthesis and laccasemediated oxidation of six novel 1,4-dihydropyridine (DHP)-based hexahydroquinolines (DHP1-DHP3) and decahydroacridines (DHP4-DHP6). We employed different laccase enzymes with varying redox potential to convert DHP1-DHP3 and DHP4- DHP6 to the corresponding pyridine-containing tetrahydroquinoline and octahydroacridine derivatives, respectively. Intensively coloured products were detected in all biocatalytic reactions using laccase from Trametes versicolor (TvLacc), possibly due to the presence of conjugated chromophores formed in products after oxidation. The NMR assessment confirmed that the oxidation product of DHP1 was its corresponding pyridine-bearing tetrahydroquinoline derivative. Laccase from Bacillus subtillis (BacillusLacc) was the most efficient enzyme for this group of substrates using HPLC assessment. Overall, it could be concluded that DHP2 and DHP5, bearing catecholic structures, were easily oxidized by all tested laccases, while DHP3 and DHP6 containing electron-withdrawing nitro-groups are not readily oxidized by laccases. DHP4 with decahydroacridine moiety consisting of three condensed six-membered rings that contribute not only to the volume but also to the higher redox potential of the substrate rendered this compound not to be biotransformed with any of the mentioned enzymes. Overall, we showed that multiple analytical approaches are needed in order to assess biocatalytical reactions.