1. Strongylophorine-26, an Inhibitor of Cancer Cell Invasion: SAR Revealed by Synthesis of Analogues
- Author
-
Michel Roberge, Brian O. Patrick, Calvin D. Roskelley, Pamela Austin, Kaoru Warabi, and Raymond J. Andersen
- Subjects
Stereochemistry ,Metabolite ,Pharmaceutical Science ,Antineoplastic Agents ,Chemical synthesis ,Analytical Chemistry ,Structure-Activity Relationship ,chemistry.chemical_compound ,X-Ray Diffraction ,Drug Discovery ,Moiety ,Pharmacology ,chemistry.chemical_classification ,Molecular Structure ,Organic Chemistry ,Absolute configuration ,Stereoisomerism ,Complementary and alternative medicine ,chemistry ,Molecular Medicine ,Diterpenes ,Drug Screening Assays, Antitumor ,Enantiomer ,Pharmacophore ,Derivative (chemistry) ,Lactone - Abstract
The absolute configuration of strongylophorine-26 (1) was determined to be 4S, 5R, 8R, 9S, 10S, 13S, 14S by single-crystal X-ray diffraction analysis of the derivative 7 prepared from the co-occurring metabolite strongylophorine-8 (4) and chemical interconversion to the bislactone 8. Synthetic analogues (+)- and (-)-3 have been prepared in order to explore the structure-activity relationship for the anti-invasion pharmacophore of stronglylophorine-26. These studies revealed the unanticipated importance of the A ring lactone moiety for the anti-invasion activity of 1.
- Published
- 2007