Stereoselective Modification of Cytisine: T-Reaction for Construction of Benzoannelated Anagyrine Skeleton

Three-step transformation of cytisine into a heterocyclic system closely related to the alkaloid anagyrine was achieved by using the T-reaction as a key stage. In this way, N-(2-formyl-4-nitro)cytisine (generated upon arylation of cytisine with 2-cloro-5-nitrobenzaldehyde) was condensed with 1,3-dimethylbarbituric acid to obtain a corresponding 5-arylidenebarbiturate. The latter was found to undergo stereoselective cyclization (T-reaction) into 1,3-dimethyl-5,13'-spiro-[5-nitro-2-(6-oxo-7,11-diazatricydo[7,3,1,0 2,7 ]trideca-2,4 -diene-1-yl)phenylmethyleno]hexahydro-2,4,6-pyrimidinetrione containing a benzoannelated anagyrine skeleton. Subsequent alkaline hydrolysis of the spiro compound led to cleavage of the spiropyrimidine moiety followed by stereoselective decarboxylation to afford an enantiomerically pure carboxylic acid derivative of the benzoanagyrine series.