Late-stage functionalization of Vouacapane derivatives from Caesalpinia platyloba by a Groebke-Blackburn-Bienayme reaction

An almost underexplored field within the natural products area is the synthesis of pseudo-natural product libraries by employing isocyanide-based multicomponent reactions as powerful synthetic tools and natural products or their functionalized derivatives as starting reagents. In this work, a novel synthetic strategy behind the late-stage functionalization of fused Vouacapane-azoles in a two-step reaction was developed. The first reaction is a Vilsmeier-Haack formylation at furan ring of the natural product 6 & beta;-acetoxyvouacapane, which was isolated from the leaves of Caesalpinia platyloba from its dichloromethane extracts. The second reaction was a Groebke-Blackburn-Bienayme reaction to synthesize the pseudo-natural products 11a-f in moderate yields, containing pharmacophoric fragments furan and imidazo[1,2-a]pyridine. The compounds described here are good candidates for biological activity assays.