合成路线1

A different protection strategy involves masking the ring nitrogens as amide groups. Methyl acrylate (XVII) is reacted with neat ethylenediamine (XVIII) to yield the aminopropionamide derivative (XIX), which is then cyclized with dimethyl malonate (XX), producing the trioxocyclam (XXI). After condensation of (XXI) with p-dibromoxylene (IIIa), the resulting hexaoxo bis-cyclam (XXII) is reduced to the title compound employing borane-dimethyl sulfide complex in refluxing THF (10). Alternatively, protection of the linear tetraamine (XXIII) with pyruvic aldehyde (XXIV) generates the tricyclic bisaminal (XXV) along with its minor isomer (XXVI). The crude mixture of bis-aminals (XXV) and (XXVI) is then cyclized to (XXVIII) with 1,3-dibromopropane (XXVII) and K2CO3. After condensation of (XXVIII) with dibromide (IIIa), the resulting bis-ammonium dimer (XXIX) is hydrolyzed to the title compound upon heating with 3M NaOH (11). Scheme 3.