SYNTHESIS OF XY-12-HYDROXY-10-(TRIFLUOROMETHYL)-DELTA(7)-PGA(1) METHYL-ESTER

Cross-conjugated alkylidene prostaglandins have been; shown to be pote nt cytostatic agents that exert their action through a unique and unus ual mechanism. Compounds in this class also inhibit viral replication and have a role in osteogenesis and adipogenesis; consequently, they a re of considerable current interest as pharmaceutical lead compounds. The purpose of our research was to define an efficient protocol for th e assembly of the C-10 trifluoromethyl prostanoid mentioned in the tit le. This compound was predicted to show strong antitumor activity on t he basis of the known structure-activity relationships within this ser ies. A novel strategy for assembling the carbon skeleton of Delta(7)-u nsaturated prostanoids bearing oxygen functionality at C-12 through an ionic electrocyclic process has been described. Key steps of the synt hesis are the preparation of dieneone 14b through an electrocyclic rin g-opening reaction and the ionic electrocyclization of 26a, which crea tes the functionalized carbon skeleton. The target compound was found to be cytotoxic in vitro against two human tumor cell lines in the low mu M range, confirming our prediction.