A Novel and Efficient Synthesis of 14-Alkoxy-Substituted Indolo- and Benzofuromorphinans in the Series of Selective δ Opioid Receptor Antagonists.

A novel and more efficient synthesis of 14-alkoxy-substituted indolo- and benzofuro-morphinans in three steps starting from either naltrindole (1) or naltriben (2), using methoxymethyl or silyl protecting groups, is reported. The 14-O-alkyl group is introduced at the penultimate step of the procedure. This is an additional advantage of the described procedure since the late introduction of the 14-O-alkyl group makes it much easier to produce a greater diversity of 14-alkoxy derivatives in this series of δ opioid receptor antagonists. Thus, compounds 14–19, 20–25, and 27–29 were synthesized.