REACTIONS OF MUCONALDEHYDE ISOMERS WITH NUCLEOPHILES INCLUDING TRI-O-ACETYLGUANOSINE - FORMATION OF 1,2-DISUBSTITUTED PYRROLES FROM REACTIONS OF THE (Z,Z)-ISOMER WITH PRIMARY AMINES

(Z,Z)-Muconaldehyde reacts with primary amines, including valine and l ysine (epsilon-amino), to afford N-substituted-2-(oxoethyl)pyrroles, w hich were reduced with sodium borohydride to the more stable N-substit uted-2-(hydroxyethyl)pyrroles. The formation of the pyrrole aldehydes was performed in a variety of solvents including aqueous methanol. Wit h tri-O-acetylguanosine, the putative pyrrole aldehyde derived from re action at NH2 condenses with N-1 (guanine component) to afford a bicyc lic adduct: pyr-rolo[1',2':3,4]pyrimido[1,2-a]purin-7(10H)-one (5a). T his was hydrolyzed to olo[1',2':3,4]pyrimido[1,2-a]purin-7(10H)-one(5b ). The structures of 5a and 5b were primarily based on NMR evidence an d comparison with rrolo[1',2':3,4]pyrimido[2,1-b]pyrimidin-7-one(7), o btained from reacting (Z,Z)-muconaldehyde with 2-amino-4-hydroxy-6-met hylpyrimidine. (E,Z)-Muconaldehyde also reacted with primary amines to give N-substituted-2-(oxoethyl)pyrroles, whereas (E,E)-muconaldehyde gave bis-imines. The results described are discussed in the context of the carcinogenicity of benzene.