1 research outputs found
Synthesis of the Antiproliferative Agent Hippuristanol and Its Analogues from Hydrocortisone via Hg(II)-Catalyzed Spiroketalization: Structure–Activity Relationship
An
efficient synthesis of hippuristanol (<b>1</b>), a marine-derived
highly potent antiproliferative steroidal natural product, and nine
closely related analogues has been accomplished from the commercially
available hydrocortisone utilizing HgÂ(II)-catalyzed spiroketalization
of 3-alkyne-1,7-diol motif as a key strategy. This practical synthetic
sequence furnished <b>1</b> in 11% overall yield from hydrocortisone
in 15 linear steps. Modifications to the parent molecule <b>1</b> encompassed changing the functional groups on rings A and E. Each
analogue was screened for their effects on inhibition of cap-dependent
translation, and the assay results were used to establish structure–activity
relationships. These results suggest that the stereochemistry and
all substituents of spiroketal portion (rings E and F) and C3-α
and C11-β hydroxyl functional groups on rings A and C, respectively,
are critical for the inhibitory activity of natural product <b>1</b>