Synthesis and analgesic activity of stereoisomers of cis-fluoro-ohmefentanyl

Four stereoisomers 1a-d of cis-fluoro-ohmefentanyl have been synthesized. Their absolute configurations were determined by X-ray analysis of (35,4R,2'S)-(-)-cis-l d. The analgesic activity (mice, sc, hot plate) revealed extreme stereodifferences. The ED 50 value of (3R,45,2'S)-(+)-cis-l (1a) was 0.000774 mg/kg (17958 times more potent than that of morphine), while the corresponding antipode 1c was almost inactive.