Synthetic approach to novel crinipellin diterpenes. Construction of the functionalised C20-tetraquinane framework

Abstract

A synthetic approach towards novel tetraquinane diterpenes of the crinipellin group compounds (4–8) is delineated. The main theme of this approach centres around the use of readily available and adequately functionalised triquinane 10 as the key synthon to which an appropriately substituted five-membered ring can be annulated with concurrent generation of the spiro centre. Consequently, compound 10 was elaborated to the enone 22, which was in turn subjected to cyclopentannulation employing three different intramolecular strategies, viz. photochemical cycloaddition (22→23→24), cationic enone–olefin cyclisation (22→24→27) and radical cyclisation (22→32→27). While five of the six stereogenic centres on the carbocyclic framework of tetraquinane 27 could be correctly set, the C(12)-isopropyl group was epimeric with respect to that in the natural products. Nevertheless, compound 27 was further elaborated to the C₂₀-tetraquinane 40 through chemical modifications in ring D, constituting the first synthesis of the complete skeleton of the criniepellins.