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Download fileEnantioselective Total Synthesis of Nigelladine A via Late-Stage C–H Oxidation Enabled by an Engineered P450 Enzyme
journal contribution
posted on 19.07.2017, 00:00 authored by Steven
A. Loskot, David K. Romney, Frances H. Arnold, Brian M. StoltzAn
enantioselective total synthesis of the norditerpenoid
alkaloid nigelladine A is described. Strategically, the synthesis
relies on a late-stage C–H oxidation of an advanced intermediate.
While traditional chemical methods failed to deliver the desired outcome,
an engineered cytochrome P450 enzyme was employed to effect
a chemo- and regioselective allylic C–H oxidation in
the presence of four oxidizable positions. The enzyme variant was
readily identified from a focused library of three enzymes, allowing
for completion of the synthesis without the need for extensive screening.