Advances towards the total synthesis of garcinol

Abstract

In 2011, the first total synthesis of trans-type-B PPAPs in 8 steps was recorded. The clear separation of framework decorating steps, in which a new core substituent (like e.g. an iso-prenyl or an acyl group) was introduced from framework constructing steps, in which the [3.3.1]bicyclononatrione core of all PPAPs was built up, allowed for a parallel synthesis of five different trans-type-B PPAPs. Garcinol, a trans-type-B PPAP possessing a lavandulyl side chain at C-1, shows activity against multiresistant Staphylococcus aureus comparable to that of vancomycin. Up to date no total synthesis of this interesting natural product has been accomplished. The development of a short and efficient total synthesis appeared then interesting to us. Different synthetic routes were evaluated. Whereas most of these strategies encountered difficulties at some point, the use of an allyllic activated isoprenyl based side chain led to the lavandulyl residue via a Pd-catalyzed regioselective Suzuki allyl-allyl cross-coupling.