Synthesis of Neocaesalpin A, AA, and Nominal Neocaesalpin K.

Abstract

The first total synthesis of heavily oxidized cassane-type diterpenoid neocaesalpin A (1) is disclosed. At the heart of the synthesis lies an intermolecular Diels-Alder reaction that rapidly assembles the target framework from commercial materials. A carefully orchestrated sequence of oxidations secured the desired oxygenation pattern. Late-stage release of the characteristic butenolide occurred through a novel mercury(II)-mediated furan oxidation. Successful extension of the route allowed preparation of neocaesalpin AA (2) as well as nominal neocaesalpin K (3) and suggested structural revision of neocaesalpin K, leading to the hypothesis that the two are likely the same natural product with correct assignment as 2.