A stereoselective synthesis of the highly advanced intermediates towards the revised structure of palmerolide C and 10-epi-palmerolide C is described in this paper. The required key fragments C1-C6, C7-C14 and C15-C23 have been successfully assembled in a convergent manner to access the C1-C23 framework bearing all the five stereocenters present in the natural product. The synthesis involves the Julia-Kocienski reaction, Yamaguchi esterification, Takai olefination and regioselective epoxide opening as key steps. The proposed route is flexible and could also be applied to the synthesis of structurally related palmerolides.