Laccase-mediated oxyfunctionalization of 3β-hydroxy-Δ5-steroids

• Fungal laccases were tested in bioconversion of non-phenolic steroids.
• Laccase-mediated systems effectively catalyze oxidation of 3β-hydroxy-Δ5-steroids.
• The oxidation of 3β-hydroxyandrost-5-en-17-one includes the hydroxylation at positions 7α and 7β.
• Regiospecific oxidation of the 7(α/β)-alcohols results in 3β-hydroxy-androst-5-en-7,17-dione.
• 3β-Hydroxypregn-5-ene-7,20-dione is an only laccase product from pregnenolone.

Laccase mediator systems (LMS) were studied as catalysts for steroid oxidation. The fungal laccases from Lentinus strigosus 1566 and Trametes versicolor were used in the work. Among five mediators screened, 1-hydroxybenzotriasol (HBT) excelled in activity. The LMS effectively catalyzed oxidation of 3β-hydroxy-Δ5-steroids like DHEA (3β-hydroxyandrost-5-en-17-one) and pregnenolone (3β-hydroxypregn-5-en-20-one), while no activity was observed towards 3-oxo-4-ene-steroids (androstenedione, 9α-hydroxyandrostenedione, testosterone and 20-hydroxymethylpregn-4-en-3-one). The pathway of DHEA oxidation by LMS included the hydroxylation at positions 7α and 7β followed by oxidation of the corresponding 7(α/β)-alcohols to form 3β-hydroxyandrost-5-ene-7,17-dione. Regiospecific oxidation of allylic hydroxyl functions by LMS was confirmed using 3β,7α- and 3β,7β-dihydroxyandrost-5-en-17-ones as substrates. 3β-Hydroxypregn-5-ene-7,20-dione was produced with LMS as an only product from pregnenolone. The yield of crystalline product reached 58.3% yield with a purity of 96%.The results demonstrate that application of LMS may be a promising approach for steroid oxyfunctionalization.

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