An enantioselective total synthesis of (+)-peloruside A (1) is described. Peloruside A (1) is a potent microtubule stabilizer with significant clinical potential. The synthesis is convergent and involves the assembly of C1-C10 segment 2 and C11-C24 segment 3 by a novel aldol protocol followed by Yamaguchi macrolactonization of the resulting seco-acid, selective methylation of hemi-ketal and removal of the protecting groups to peloruside A.
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