The total synthesis of swinholide A. Part 1: A stereocontrolled synthesis of a C19-C32 segment

The C 19 -C 32 segment 10 of swinholide A was prepared in 15 steps (8% yield, 82% ds) from (±)- 16 . Key steps include ( i ) the Sharpless epoxidation, 16 → 17 , ( ii ) the acetal allylation, 15 → 23 , ( iii ) the anti aldol addition, 13 + 14 → 12 , and ( iv ) the alkene hydroboration, 30 → 31 . The swinholides are a series of complex polyketide macrodiolides, which display potent cytotoxicity against a variety of human tumour cell lines. 1,2 Swinholide A, isolated from the marine sponge Theonella swinhoei , was first reported as an antifungal agent by Carmely and Kashman in 1985.1 Using NMR methods and chemical