Laccase-mediated oxidation of steroid alcohols in the presence of methylated beta-cyclodextrin: from inhibition to selective synthesis

BACKGROUND Laccase mediator systems (LMS) possess great potential in organic synthesis for selective oxidation in mild conditions. However, their usage in steroid synthetic chemistry is limited by low aqueous solubility of the substrates. In this study, the effect of steroid complexation with methylated cyclodextrin (mCD) on LMS oxidation has been studied. RESULTS LMS consisted of Trametes versicolor laccase and 1-hydroxybenzotriazole or TEMPO as redox mediators were used. The only product, - 3 beta-hydroxyandrost-5-en-7,17-dione (7-keto-DHEA) was detected during LMS oxidation of 3 beta-hydroxyandrost-5-en-17-one (DHEA) at substrate concentrations within solubility. The formation of mCD complex with DHEA led to a decrease in the concentration of the reaction form of the substrate and inhibited bioconversion. When DHEA concentrations over its aqueous solubility was used, 3 beta,7 alpha- and 3 beta,7 beta-dihydroxyandrost-5-en-17-one (7 alpha- and 7 beta-OH-DHEA) along with 7-keto-DHEA were formed. Both isomeric 7 alpha- and 7 beta-OH-DHEA were efficiently converted to 7-keto-DHEA by LMS in the presence of mCD. LMS-catalyzed oxidation of 20-hydroxymethylpregn-4-en-3-one (HMP) in the presence of mCD resulted in a single product, pregn-4-en-3-one-20-carbaldehyde (20-POA) and the reaction rate increased under elevated mCD concentrations. A preparative biochemical synthesis of 20-POA was carried out, which has not been so far reported. CONCLUSIONS mCD affects LMS-catalyzed oxidation of steroid alcohols. The mechanism includes formation of steroid-mCD inclusion complexes that could inhibit, or facilitate oxidation depending on the structure of steroid-CD complex and accessibility of the hydroxyl functions to the LMS action. (c) 2021 Society of Chemical Industry (SCI).