Unified total synthesis of amorfrutins A and C via the Claisen rearrangement

Abstract

A concise, unified total synthesis of the two prenylated aromatic polyketides amorfrutins A and C, which exhibit various medicinally important biological profiles such as antimicrobial, PPARã modulating and quorum sensing inhibitory activities, has been achieved from commercially available 3,5-dimethoxybenzaldehyde in 38% and 10% overall yields through nine and ten steps, respectively. The key transformation for the synthesis of amorfrutin A was the Claisen rearrangement of a mono-O-(1,1-dimethylallyl)resorcinol derivative to install the C3- prenyl substituent, while that for the synthesis of amorfrutin C was the double Claisen rearrangement of a di-O-(1,1-dimethylallyl)resorcinol derivative to introduce the two prenyl groups at the C3 and C5 positions all at once.