Total Synthesis of Eleutherobin and Eleuthosides A and B

The total synthesis of the cytotoxic marine natural products eleutherobin (<b>1</b>) and eleuthosides A (<b>2</b>) and B (<b>3</b>) is described. The strategy involves glycosidation of the (+)-carvone-derived intermediate <b>7</b> with the arabinose-derived trichloroacetimidate <b>9</b> followed by base-induced ring closure and elaboration to afford the dihydroxy eneynone <b>19</b>. Selective hydrogenation of <b>19</b> led to the generation and intramolecular collapse of dienone <b>20 </b>furnishing <b>21</b> and thence <b>22</b> with the required structural framework of the target molecules. Finally, esterification with mixed anhydride <b>24</b> followed by deprotection gave eleutherobin (<b>1</b>) which served as a precursor to eleuthosides A (<b>2</b>) and B (<b>3</b>). The α-glycoside anomer of eleutherobin, compound <b>27</b>, was also synthesized by application of the developed chemistry, demonstrating the flexibility of the sequence in generating designed analogues for biological screening.