Synthesis and opioid-receptor binding of novel amino-substituted morphan analogues

Starting with methyl 4,6‐O‐benzylidene‐α‐D‐glucopyranoside (4), an optimized procedure is reported for preparation of the bromide 7, which is transformed into the N‐acylated heptopyranosamine 9. After introduction of an axially positioned azido moiety in position 3 intramolecular N/O‐acetal formation succeeds to provide the morphan analogue 17. In receptor binding studies with radioligands the amines 18b‐18d reveal higher affinity for μ‐receptors than for κ‐receptors. The most μ‐active compound 18b (Ki = 14 nM) contains two aryl substituents, which presumably may occupy both aryl binding sites of μ‐receptors.