ja9810639_si_001.pdf (471.23 kB)
Total Synthesis of Eleutherobin and Eleuthosides A and B
journal contribution
posted on 1998-08-13, 00:00 authored by K. C. Nicolaou, T. Ohshima, S. Hosokawa, F. L. van Delft, D. Vourloumis, J. Y. Xu, J. Pfefferkorn, S. KimThe total synthesis of the cytotoxic marine natural products eleutherobin (1) and eleuthosides A (2)
and B (3) is described. The strategy involves glycosidation of the (+)-carvone-derived intermediate 7 with
the arabinose-derived trichloroacetimidate 9 followed by base-induced ring closure and elaboration to afford
the dihydroxy eneynone 19. Selective hydrogenation of 19 led to the generation and intramolecular collapse
of dienone 20 furnishing 21 and thence 22 with the required structural framework of the target molecules.
Finally, esterification with mixed anhydride 24 followed by deprotection gave eleutherobin (1) which served
as a precursor to eleuthosides A (2) and B (3). The α-glycoside anomer of eleutherobin, compound 27, was
also synthesized by application of the developed chemistry, demonstrating the flexibility of the sequence in
generating designed analogues for biological screening.