Peroxygenase-catalysed selective and scalable synthesis of 25-hydroxy-grundmann's ketone and its derivatives

Abstract

Peroxygenases are selective catalysts for C-H bond oxyfunctionalization reactions, however, their potential for organic synthesis still needs to be explored. 25-Hydroxy-Grundmann's ketone is a key structural motifs in various biologically active vitamin D3 analogues. In this study, we report the use of unspecific peroxygenase from Agrocybe aegerita as a highly selective catalyst for the C25 hydroxylation of Grundmanns's ketone and its analogues. Under the optimised conditions, excellent conversion (> 99%) and regioselectivity (> 99%) was obtained. The selected hydroxylation processes were performed on an increased lab scale (up to 200 mL) with up to 1 mmol substrate, which led in 85.7% isolated yield.This simple biocatalytic method holds great potential in streamlining the synthetic pathways of vitamin D3 analogues.