초록
<P>An 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.</P><P><B>Graphic Abstract</B><BR><IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/2017/jacsat.2017.139.issue-30/jacs.7b05196/production/images/medium/ja-2017-051967_0008.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja7b05196'>ACS Electronic Supporting Info</A></P>