Synthesis of lipophilic paramagnetic contrast agents

The facile, high-yielding synthesis of a series of macrocycles 7a-k in 75-1 00% yield is reported. The transformation of these compounds to their carbo xymethylated analogues 8a-k in 75-90% yield and subsequent gadolinium compl exes 9a-k provides a series of homologous neutral paramagnetic contrast age nts (PCAs) with tunable lipophilicity. Alkylated cationic intermediates 6a- k are prepared in yields of 72-94% from glyoxal adduct of cyclen (5) and sl ight excesses of alkyl iodides. The methodology is selective for monoalkyla tion and amenable to large-scale synthesis.