Based on the known coumarin-based prodrug system, a new meptazinol (Z)-3-[2-(propionyloxy) phenyl]-2-propenoic ester (3) was designed and synthesized as prodrug to minimize the first-pass effect of meptazinol (1) and improve the oral bioavailability. The prodrug (3) showed a 4-fold increase in oral bioavailability over the parent drug meptazinol in rats.

A new rearrangement byproduct, 3-methyl-1,2,3,4,4a,4b,9a,15,15a,15b-decahydro-(4,5); (4a,15)-dimethanotricyclo-(4,3,1,02,7) deca [8,9,1,10-a,b,c]pyrido [4,3-a]-acridin-6-en-9-ol-8-one, has been isolated from the acid-catalyzed O-demethylation of 7-o-aminophenyl-6,14-endo-thenotetrahydrothebaine. The mechanism of its formation involving a novel annulation of the 6,14-endo-ethenylene moiety with the A ring aromatic carbons is discussed