phaeosphaeride-a and Breast-Neoplasms

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.

Topics: Aldehydes; Biological Products; Breast Neoplasms; Bridged Bicyclo Compounds, Heterocyclic; Cell Proliferation; Cyclization; Female; Humans; Indicators and Reagents; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Pancreatic Neoplasms; STAT3 Transcription Factor; Stereoisomerism