Total Synthesis of Plakortide E and Biomimetic Synthesis of Plakortone B

The total synthesis of plakortide E (1a) is reported. A novel palladium-catalyzed approach towards 1,2-dioxolanes as well as an alternative substrate-controlled route leading exclusively to cis-highly substituted 1,2-dioxolanes have been developed. A lipase-catalyzed kinetic resolution was employed to provide optically pure 1,2-dioxolane central cores. Coupling of the central cores and side chains was achieved by a modified Negishi reaction. All four isomeric structures of plakortide E methyl ester, namely, 26a-d were synthesized. One of the structures, 26d, was shown to be identical with the natural plakortide E methyl ester on the basis of H-1, C-13 NMR spectra and specific rotation comparisons. With the plakortide E methyl ester (4S, 6R, 10R)-(-)-cis-26d and its other three isomers in hand, we successfully converted them into (3S, 4S, 6R, 10R)-plakortone B (2a), and its isomers ent-2a, 2b and ent-2b via an intramolecular oxa-Michael addition/lactonization cascade reaction. Finally, saponification converted 1,2-dioxolane 26d into plakortide E (1a) whose absolute configuration (4S, 6R, 10R) was confirmed by comparison of spectral and physical data with those reported.