Synthesis of (±)-(2R*,11bS*)-3'-Aryl-9,10-dimethoxy-1,3,4,5,7,11b-hexahydrospiro[benzo[a]quinolizin-2,5'-oxazolidine]-2',4'-diones

The synthesis of (i)-(zR*, llbS*)-3'-aryl-9.lO-dimethoxy-1,3,4,6,7,11bhexahydrospiro[benzo[a]qulnolizin-2,5'-oxarolldin~-2',4'-diones (1) was achieved by two alternative routes involving the treatment of cyanohydrin 3 with aryl isocyanates via 4-imino derivatives 5 and 5 or the cyclization of the hydroxy ester 9 with aryl isocyanates.Compounds 1 present a h a n s Conformation in the quinolizidine system and exist in a (a*, llbs*) configuration.The discovery of a2-adrenoceptor antagonism for several 2-substituted benzo[o]quinolizid~nes"~ 3 may provide a basis on which to explain the antihypertensive activity described for some of these derivatives, while, at the same time, it allows the prediction of additional pharmacological 4 5 properties, like antidepressant and hipoglycemic activities, among others.a80hlmann bands.b ~x c e p t (d5-pyridine, 200.16 MHz) and @ (d6-DMSO, 200.16 MHz).5 N P C ~~t detected.z ?