Total Synthesis and Biological Activity of the Proposed Structure of Phaeosphaeride A

The total synthesis of the structure assigned to the
natural product
phaeosphaeride A 1a was accomplished. The key steps involve
the addition of vinyllithium reagent 7 to the acetonide-protected
aldehyde 8 to access the carbon backbone of 1a, the introduction of the methoxylamino group followed by intramolecular
hetero-Michael cyclization, and methanol elimination to form the dihydropyran
ring. In this study, both enantiomers of 1a were synthesized
and tested for biological activity. Preliminary results showed that
(6R,7R,8R)-1a and (6S,7S,8S)-1a inhibit STAT3-dependent transcriptional activity
in a dose-dependent manner and exhibit antiproliferative properties
in breast (MDA-MB-231) and pancreatic (PANC-1) cancer cells.