Synthesis of a new opioid ligand having the oxabicyclo[3.2.1]octane skeleton using a new rearrangement reaction

An attempt to prepare a trimer having the 1,3,5-trioxazatriquinane skeleton led to discovery of a novel rearrangement reaction that afforded a compound with an oxabicyclo[3.2.1]octane skeleton whose reaction mechanism was proposed. On the basis of this mechanism, we synthesized the rearranged product from a dimethyl acetal intermediate in excellent yield. The compound with an oxabicyclo[3.2.1]octane skeleton showed high affinity for μ and κ but not δ opioid receptor types. The compound expected to be a key intermediate for novel κ selective ligands.

Graphical abstractNovel morphinan derivative having oxabicyclo[3.2.1]octane skeleton was prepared from dimethyl acetal derivative. The novel compound showed strong affinity for μ and κ opioid receptor types.Figure optionsDownload full-size imageDownload as PowerPoint slide