A Multicomponent Approach to the First Total Synthesis of Bisavenanthramide B

Oats have an ancient history of anti-inflammatory and anti-itch properties. Avenanthramides, a family of phytoalexins specific to oats, have been suggested to play a major role in the immune response pathway by acting on pathogenic duress as anti- oxidants, anti-microbial and even anti-atherogenic agents. These compounds are of great interest because both their monomers and dimers are biologically active, often with the latter form being more potent. In 2004, Okazaki et al. isolated a dehydrodimer of avenanthramide B, as a penta-substituted γ-lactam with two stereogenic centers and four trisubstituted aryl rings. The first total synthesis of bisavenanthramide B is described using a four-component reaction (4CR) to diastereoselectively construct the core as an NH-γ-lactam. From this key intermediate, Chan-Lam boronic acid coupling conditions and aldol condensation install the remaining three aryl rings. Completing the synthesis of bisavenanthramide B will confirm its structure, particularly the alkene geometry after aldol condensation, and demonstrate the utility this 4CR in accessing highly decorated related natural products.