NEW SYNTHESIS OF TRANS-DISUBSTITUTED CYCLAM MACROCYCLES - ELUCIDATIONOF THE DISUBSTITUTION MECHANISM ON THE BASIS OF X-RAY DATA AND MOLECULAR MODELING

A new way to synthesize trans-disubstituted cyclam tetraazamacrocycles 1 is reported. The synthesis proceeds in three steps via the tricycli c 1,4,8,11-tetraazatricyclo-[9.3.1.1(4,8)]hexadecane system 2, which c an be selectively dialkylated and hydrolyzed under basic conditions to give the final product 1. An understanding of the reactivity, based o n the X-ray experimental electrostatic potential and molecular modelin g of the 1,4,8,11-tetraazatricyclo-[9.3.1.1(4,8)]hexadecane macrotricy cle, has permitted the elucidation of a new reaction pathway leading t o the trans-disubstituted cyclam.