TOTAL SYNTHESIS OF ELEUTHEROBIN AND ELEUTHOSIDE-A AND ELEUTHOSIDE-B

The total synthesis of the cytotoxic marine natural products eleuthero bin (1) and eleuthosides A (2) and B (3) is described. The strategy in volves glycosidation of the (+)-carvone-derived intermediate 7 with th e arabinose-derived trichloroacetimidate 9 followed by base-induced ri ng closure and elaboration to afford the dihydroxy eneynone 19. Select ive hydrogenation of 19 led to the generation and intramolecular colla pse of dienone 20 furnishing 21 and thence 22 with the required struct ural framework of the target molecules. Finally, esterification with m ixed anhydride 24 followed by deprotection gave eleutherobin (1) which served as a precursor to eleuthosides A (2) and B (3). The a-glycosid e anomer of eleutherobin, compound 27, was also synthesized by applica tion of the developed chemistry, demonstrating the flexibility of the sequence in generating designed analogues for biological screening.