Total Synthesis of Spirofungins A and B and Formal Synthesis of the C1-C38 Fragment of (+)-Sorangicin A

The enantioselective total synthesis of spirofungins A and B is reported in 14 steps over the longest linear sequence. The synthesis of three key fragments in six steps or less and excellent overall yield allowed for the assembly of spirofungins A and B in a highly efficient manner. Highlights of the synthesis include the use of thiazolidinethione-mediated aldol reactions to install five of the seven stereocenters, and the appendage of the C1-C6 unsaturated side chain through a challenging cross metathesis reaction.;Efforts towards the total synthesis of (+)-sorangicin A resulted in the completion of a formal synthesis of the C1-C38 fragment. The preparation of three orthogonally differentiated cyclic ether fragments allowed for the investigation of several coupling strategies for assembly of the natural product. A cross metathesis reaction was employed to form the C29-C30 bond and unite the bicyclic ether and tetrahydropyran fragments. It was our intention to utilize a second cross metathesis reaction to install the C15-C16 olefin and append the dihydropyran moiety to the rest of the molecule; however, a low yield for this cross metathesis reaction prompted us to instead use a Julia-Kocienski olefination to arrive at the C1-C38 fragment. Completion of the total synthesis of (+)-sorangicin A can be achieved in six known steps from this advanced intermediate.