Synthesis and Laccase-Mediated Oxidation of New Condensed 1,4-Dihydropyridine Derivatives

Abstract

We describe herein the synthesis and laccase mediated 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.

Trametes hirsuta as an Attractive Biocatalyst for the Preparative Scale Biotransformation of Isosafrole into Piperonal

“…The exceptions were the strains of the species Trametes hirsuta, which turned out to be the only biocatalysts that showed activity towards substrate 1a among all the tested strains (Table 4). The literature data has indicated that strains of the Trametes genus are well-known for having alkene cleaving properties in a wide range of chemical compounds [12][13][14][15][16][17][18][19][20][21]. In particular, very promising results were obtained during the process using T. hirsuta Th2_2 as a biocatalyst, where 38% of piperonal (1b) was obtained after 14 days of biotransformation.…”

Oxidative Aromatization of Some 1,4-Dihydropyridine Derivatives Using Pyritic Ash in Eco-Sustainable Conditions

“…The 1 H and 13 C NMR analyses were carried out using a Bruker AC 250-Magnet (2005, Bruker Center AXS, Karlsruhe, Germany) equipment, operating at 250 MHz. The samples were prepared in 500 µL of CDCl 3 containing, approximately, 5 mg of sample.…”

“…These compounds find extensive applications in pharmacology, agrochemistry, organic synthesis, and industry. Despite the wide range of oxidizing agents available for this process, from inorganic salts, solid supports, microwaves, ultrasound, enzymes, UV-Vis, organo-inorganic molecular systems to Cytochrome P-450 [9][10][11][12][13][14][15][16][17], the oxidative aromatization of dihydropyridines presents real issues. These include the steric constrain and reactivity of functional groups in the molecule, sensitivity to various reagents and reaction conditions, and the formation of secondary products.…”