Total synthesis of sarcodictyins A and B

The total synthesis of cytotoxic marine natural products possessing tubulin polymerization and microtubule stabilization properties, sarcodictyins A (7) and B (8), is described. Two related approaches to these target molecules have been developed, both utilizing (+)-carvone (9) as starting material. The first approach involves a stereoselective construction of acetylenic aldehyde 27 (Scheme 2) while the second approach proceeds through a more direct but less selective sequence to the similar intermediate 36 (Scheme 3). Both strategies; involve ring closures of the acetylenic aldehyde precursors to 10-membered rings under basic conditions followed by elaboration and selective reduction of the acetylenic linkage to a cis double bond. This promotes bridging to form the required tricyclic skeleton of the sarcodictyins (27 --> 37 --> 38 --> 39 --> 4, Scheme 4 and 37 --> 44 --> 45 --> 46 --> 47 --> 42, Scheme 5) and (36 --> 48 --> 45, Scheme 6). Installation of the (E)-N(6')-methylurocanic acid residue was achieved by esterification with mixed anhydride 52, while the C-3 ester moieties were installed by standard deprotection, oxidation, and esterification procedures.