(A) unified approach toward the isomer specific total synthesis of attenols A and B

Abstract

Both Attenols A and B show cytotoxicity against P388 cell lines with $IC_{50}$ values of 24 and 12 ug/ml, respectively. Structurally, attenol A is composed of a [5,6]-spiroketal core decorated with three hydroxyl groups on two unsaturated side chains, while the minor metabolite attenol B has a unique 6,8-dioxabicyclo[3.2.1]octane (6,8-DOBCO) framework with similarly functionalized side chains. Since isomerization of Attenols A and B occurs under acidic conditions and attenol A is more thermodynamically stable than attenol B, some researchers had no choice but to get a mixture in which attenol A was a major product. Attenols A and B are expected to be synthesized through the same precursor in nature, so we proposed the synthetic plan based on this hypothesis. Different protecting groups were attached to each hydroxyl group to avoid the problem of isomerization under acidic conditions. Total synthesis of attenols A and B through spiroketalization with gold(I) catalyst has been attempted after selective deprotection.