Synthesis of a syn,syn,syn,syn-Stereopentad Precursor of the Marine Sponge Polyketide Callystatin A

A C13−22 syn,syn,syn,syn-stereopentad precursor of the cytotoxic polyketide callystatin A has been prepared. The synthesis involved BF₃-promoted addition of the (M)-allenylstannane 28 to the α-methyl-β-OTBS aldehyde 8 to afford the syn,syn adduct homopropargylic alcohol 29. Protection as the cyclic anisylidene acetal 31 and reduction of the acetylenic triple bond with Red-Al gave the (E)-allylic alcohol 32. This was subjected to Sharpless asymmetric epoxidation and subsequent treatment with an ethylcopper reagent to yield diol 34; hydrogenolysis of the derived tosylate 37 with LiBEt₃H afforded 38. Acetal hydrogenolysis with DIBAl-H and oxidation yielded aldehyde 40 which was subjected to Horner−Emmons homologation to afford ester 41. This ester was converted to ester 44, an intermediate in the Kobayashi synthesis, with which it was found to be identical.