Synthesis of 2-Fluoro-11-hydroxy-<i>N</i>-propylnoraporphine: A Potential Dopamine D₂ Agonist

Abstract

2-Fluoro-11-hydroxy-N-propylnoraporphine 4 (2-F-11-OH-NPa) was synthesized from thebaine in 13 steps with an overall yield of 1.35%. The key steps included the Pd-catalyzed 3-dehydroxylation of 14-hydroxymorphine, SN2 substitution of Ts- by F-, and CH3SO2OH-promoted rearrangement of the substituted morphinandiene. The dopamine binding affinity of this compound was also investigated on rat brain membranes, and as expected, this compound displayed high affinity and selectivity at the D2 receptor.