Stereodirected synthesis of alkaloid-like quinolizidine systems.

New stereoselective methods for the chemical modification of cytisine based on T-reactions are reported. A reaction of cytisine with 2-chloro-5-nitrobenzaldehyde and followed condensation with 1,3-dimethylbarbituric acid affords -(5-nitro-2-{1,3-dimethylperhydropyrimidine-2,4,6-trione-5-methynyl})cytisine, which undergoes a cyclization with the tetrahydropyridine ring closure. The cyclization proceeds via two competing routes yielding 5,5-spirobarbituric acid derivatives with 11,19-diaza-pentacyclo[11.7.1.0.0.0]henicosane and 11,15-diazapentacyclo-[11.7.1.0.0.0]henicosane skeletons. The cyclization reaction in solutions afford either 24.25- and 15,16- isomers or and isomer mixtures, depending on the specific solvent. Meanwhile, 24,25- isomers are formed stereoselectively under heterogeneous conditions in water suspensions. -5,5-spirobarbiturates under similar conditions undergo isomerization into more stable -analogs by the configuration inversion at the C7 atom. The synthesized 5,5-spirobarbituric acid derivatives were successfully converted into alkaloid-like quinolizidine systems (1,2,3,13)-7-nitro-18-oxo-11,19-diazapentacyclo[11.7.1.0.0.0]henicosa-5(10),6,8,14,16-pentaene-3-carboxylic acid and (1,2,3,13)-nitro-16-oxo-11,15-diazapentacyclo[11,7,1.0,0,0]henicosa-5,7,9,17,19-pentaene-3-carboxylic acid and their derivatives via the spiropyrimidine moiety removal by the stereoselective hydrolysis. The molecular and crystal structures of the target substances were elucidated by X-ray crystallography and NMR.