Palladium-Catalyzed Regioselective Allylic Oxidation of Amorphadiene, a Precursor of Artemisinin

Abstract

A regioselective Pd-catalyzed allylic oxidation of amorphadiene, a key precursor to the antimalarial drug artemisinin, is described. Amorphadiene can be obtained in high yields by fermentation, but it is currently treated as a waste in the industrial semisynthetic artemisinin process. The catalytic step described here is a substitute to the P450 enzymes involved in the artemisinin biosynthesis and opens up new opportunities to supplement a critical step in the current semi-synthetic route and increase the potential of the fermentation process.

A Low-Cost and Scalable Synthesis of a Cyclohexanone-Related Bifunctional Building Block

“…Through the repeated accidental demand for 1 in different projects over the years, we gradually come to realize the so far largely unrecognized potential of this small compound as a versatile building block in synthesis in general. Indeed, a great many natural products and bioactive compounds contain a cyclohexane motif and in quite a few cases, it is even possible to identify an intact carbon framework of 1 incorporated in the given target structures as exemplified by sclerosporin, pumiliotoxin C (alkaloid cis-195 J), qinghaosu, panamonon B, platencin, nandrolone, litosetoenin B, and higginsianin E (Figure ). Also, ketone 1 indeed allows for many different ways to incorporate itself into various target structures.…”

Site-Selective Functionalization of Unactivated Allylic C–H Bonds via Direct Deprotonation with KTMP: Application to the Formal Total Synthesis of (+)-Artemisinin from Amorphadiene

“…In turn, this strategy would complement existing total syntheses of artemisinin that start from commodity raw materials, most notable of these being the graceful approach developed by Cook . Captivated by the recent success of the Cossy and Amara groups on the functionalization of AD, − in particular the Pd-catalyzed regioselective oxidation of AD, we embarked on our own efforts to identify a robust and efficient approach for the direct conversion of AD to artemisinic alcohol as a biomimetic formal total synthesis to artemisinin (Scheme ).…”