Metal-mediated alkynediol cycloisomerization: first and second generation formal total syntheses of didemniserinolipid B

A formal total synthesis of didemniserinolipid B was developed by employing a regioselective metal-mediated 6-endo-dig alkynol-cycloisomerization reaction. Two routes for the synthesis of key Burke's intermediate have been developed. Our initial approach involved the introduction of a C17-alkynol followed by Pd-mediated cycloisomerization and then coupling with the serinol unit prior to the introduction of an α,β-unsaturated ester unit through selective oxidation of 1°-OH followed by a two-carbon Wittig homologation. Alternatively, the second generation strategy featuring the serinol coupling with the C17-alkynol followed by alkyne addition to the epoxide and subsequent Au-mediated cycloisomerization of an acetonide protected alkynediol unit has been executed. This approach has avoided several late stage protection-deprotection events.