Synthesis and antihypertensive activity of a series of spiro[1,3,4,6,7,11b-hexahydro-2H-benzo[a]quinolizine-2,5'-oxazolidin-2'-one]s

Abstract
The 2R*, 11bS* and 2S* 11bS* diastereoisomers of the spiro[1,3,4,6,7,11b-hexahydro-2H-benzo[a]quinolizine-2,5''-oxazolidin-2''-one] system were prepared by stereoselective methods. Evaluation of these compounds for antihypertensive activity by oral administration to the spontaneously hypertensive rat showed the 2S*, 11bS*, series was the more potent. Within that series, small alkyl substituents at positions 3 and 4'' enhanced antihypertensive activity and methoxyl substitution at positions 9 and 10 was optimal. (2S,3S,11bS)-Spiro-[2-ethyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-benzo[a]quinolizine-2,5''-oxazolidin-2''-one] [(-)-9e] was one of the most efficacious compounds of this series, while its antipode, (+)-9e, was inactive. Selected compounds in this series were .alpha.-adrenoceptor antagonists.