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.
Faculty of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
Anthoula
A
Chatzimpaloglou
Maria P
MP
Yavropoulou
Karien E
KE
Rooij
Ralf
R
Biedermann
Uwe
U
Mueller
Stefan
S
Kaskel
Vasiliki
V
Sarli
D000447:Aldehydes / Q000737:chemistry*; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D003500:Cyclization; D005260:Female; D006801:Humans; D007202:Indicators and Reagents / Q000737:chemistry*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010190:Pancreatic Neoplasms / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism
D000447:Aldehydes; D001688:Biological Products; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007202:Indicators and Reagents; D050796:STAT3 Transcription Factor; C520910:phaeosphaeride A