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 BF 3 -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 LiBEt 3 H 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.