Flexible Synthesis of Metacycloprodigiosin and Functional Derivatives Thereof.

A conceptually new approach to m-pyrrolophane derivatives is outlined providing ready access to compound 23 which can be elaborated into the immunosuppressive alkaloid metacycloprodigiosin 2 according to literature procedures. The key steps of this sequence involve a palladium-catalyzed macrocyclization reaction of vinyl epoxide 10, the conversion of the alpha-pyrone derivative 14 into the pyrrole targets, and the attachment of the side chain via a Wittig (or Peterson) olefination followed by hydrogenation of the alkene formed over Crabtree's catalyst. The flexibility of this route is demonstrated by the synthesis of several analogues of the parent compound 23 which may help to assess the structure/activity profile of the prodigiosin family of natural products in more detail. The unusual pyrone structure 14 used to encode the meta-bridged pyrrolophane units was characterized by X-ray crystallography.