Spirodionic acid, a novel metabolite from Streptomyces sp., part 2: Total synthesis through a twofold Michael addition as a selective spiroannelation strategy

Abstract

To elucidate the structure of the new natural product spirodionic acid, which has three stereogenic centers of hitherto unknown configuration, two 4-ethenylspiro[4.5]dec-6-en-1,8-diones with opposite relative configuration at C4 and C5 were prepared. The first access involved the synthesis of 3-ethenyl-2-formylcyclopentanone (8) using a three-component coupling process. A sequence of Michael addition to penten-3-one (7) and intramolecular aldol condensation then led to the highly selective formation of the 4S ,5S -configured spirocycle 5. In contrast, a selective spiroannelation of a cyclohexenone ring was accomplished by a novel type of twofold Michael addition to the dialkenyl ketone 11 with subsequent dehydrogenation to furnish the 4S ,5R -configured spirocycle 25. Diastereoselective methylation and oxidative degradation then completed a highly efficient synthesis of the natural product as prerequisite for the assignment of its absolute configuration.