Synthesis of (R)-1,2,11-trihydroxy-, (R)-2,11-, and (R)-2,10-dihydroxyaporphines — non naturally occurring aporphine alkaloids from pukateine and thebaine

The synthesis of (R)-2,10-dihydroxyaporphine ( 3a ), (R)-2,10-dihydroxy-N-n-propylnoraporphine ( 3b ) from thebaine and (R)-2,11-dihydroxyaporphine (7), and 1,2,11-trihydroxyaporphine ( 9 ), from pukateine is reported. The rearrangement of thebaine and northebaine with methanesulfonic acid to 1a and 1b with subsequent N-propylation gave 1b . Tetrazolyation of 1a, 1b and hydrogenolysis of 2a and 2b on Pd/C in acetic acid with subsequent O-demethylation with hydrobromic acid (48%) led to 3a and 3b . R(-)-2,11-Dihydroxyaporphine ( 7 ) was prepared by lithium/ammonia reduction of pukateine. (R)-1,2,11-Trihydroxyaporphine ( 9 ) was synthesized by reaction of pukateine with boron tribromide in dichloromethane.