Synthesis and cytotoxic activities of goniothalamins and derivatives

Substituted goniothalamins containing cyclopropane-groups were efficiently prepared in high yields and good selectivity. Antiproliferative activity was measured on three human cancer cell lines (A549, MCF-7, HBL-100), to show which of the structural elements of goniothalamins is mandatory for cytotoxicity. We found that the configuration of the stereogenic centre of the δ-lactone plays an important role for cytotoxicity. In our studies only (R)-configured goniothalamins showed antiproliferative activity, whereby (R)-configuration accords to natural goniothalamin (R)-1. Additionally, the δ-lactone needs to be unsaturated whereas our results show that the vinylic double bond is not mandatory for cytotoxicity. Furthermore, with a two-fold in vitro and in vivo strategy, we determined the inhibitory effect of the compounds to the yeast protein Pdr5. Here, we clearly demonstrate that the configuration seems to be of minor influence, only, while the nature of the substituent of the phenyl ring is of prime importance

Total Synthesis of Solandelactones A and B

The total synthesis of solandelactones A and B is presented. The eastern cyclopropyl moiety was prepared following an exceptionally short chemoenzymatic approach whereas enantioselective synthesis of the western side-chain relied on the application of diastereomerically pure allyl boronates. The natural products solandelactones A and B were isolated in good overall yields following convergence of each eastern and western element by application of the Nozaki–Hiyama–Kishi reaction