Total Synthesis of Sarcodictyins A and B
1998-08-13T00:00:00Z (GMT) by
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 ) while the second approach proceeds through a more direct but less selective sequence to the similar intermediate 36 (Scheme ). 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 and 37 → 44 → 45 → 46 → 47 → 42, Scheme ) and (36 → 48 → 45, Scheme ). 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.