Enantioselective Synthesis of the Tricyclic Core of GKK1032, Novel Antibiotic Anti-Tumor Agents, by Employing an Intramolecular DielsAlder Cycloaddition Strategy

An efficient and enantioselective synthesis of a decahydrofluorene nucleus, the tricyclic core (ABC-ring system) of GKK1032s, novel antimicrobial and anti-tumor agents, was achieved using a highly diastereoselective intramolecular Diels-Alder (IMDA) reaction. The substrate for the IMDA reaction was synthesized through intermolecular Diels-Alder reaction of Kitahara-Danishefsky’s diene and an enone derived from enulose to construct the functionalized C-ring. CuCl-promoted Stille coupling of a vinyl iodide and a vinylstannane installed the requisite triene side chain.