Chiral alkaloid derivatives: Synthesis and medicinal chemistry applications

摘要

The preparation of a selection of novel opioid alkaloids based on alteration at the 1, 3 and 6 positions of codeine and morphine has been achieved. Herein we present the synthetic methodology, structural characterisation and biological evaluation of these novel opioid species. ududA range of opioid derivatives with modification at the 6 position to form linked bis-opioid species were successfully synthesised. The derived compounds contain both ester and ether linked moieties. A selection of derivatives with modification at the 1 position of codeine were also generated through Heck, Stille and Suzuki palladium catalysed carbon-carbon coupling. A combination of both synthetic approaches has led to a variety of opioid species with modification at both the 1 and 6 positions.ududA selection of the opioid species generated were analysed for their binding affinity to the mu opioid receptor through radioligand binding techniques. Binding affinities of a variety of the opioid species to a selection of metals were also assessed by metal picrate extraction studies.ud