The Quest for New Mild and Selective Modifications of Natural Structures: Laccase-Catalysed Oxidation of Ergot Alkaloids Leads to Unexpected Stereoselective C-4 Hydroxylation

Laccase-catalysed oxidation of ergot alkaloids in the absence of chemical mediators allowed the unexpected isolation of the mono-hydroxylated derivatives of compounds 27. Structure determination by NMR techniques clearly indicated that hydroxylation took place at the C-4 benzylic position. Quite notably, the proposed protocol allowed, for the first time, functionalisation at the C-4 position of the ergoline skeleton. Depending on the absence or on the presence of a C-10 a-methoxy substituent, hydroxylation was either stereoselective (furnishing C-4a OH derivatives) or gave rise to a C-4a/C-4 beta OH mixture in a 2:1 ratio, respectively.