Total Synthesis of Eleutherobin and Eleuthosides A and B
K. C. Nicolaou
T. Ohshima
S. Hosokawa
F. L. van Delft
D. Vourloumis
J. Y. Xu
J. Pfefferkorn
S. Kim
10.1021/ja9810639.s001
https://acs.figshare.com/articles/journal_contribution/Total_Synthesis_of_Eleutherobin_and_Eleuthosides_A_and_B/3670182
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.
1998-08-13 00:00:00
Selective hydrogenation
target molecules
intramolecular collapse
dienone 20 furnishing 21
eleuthoside
cytotoxic marine
anhydride 24
products eleutherobin
Total Synthesis
dihydroxy eneynone 19
compound 27