Synthesis of Lipophilic Paramagnetic Contrast Agents BakerWilliam C. ChoiMichael J. HillDaniel C. ThompsonJulie L. PetilloPeter A. 1999 The facile, high-yielding synthesis of a series of macrocycles <b>7a</b><b>−</b><b>k </b>in 75−100% yield is reported. The transformation of these compounds to their carboxymethylated analogues <b>8a</b><b>−</b><b>k </b>in 75−90% yield and subsequent gadolinium complexes <b>9a</b><b>−</b><b>k </b>provides a series of homologous neutral paramagnetic contrast agents (PCAs) with tunable lipophilicity. Alkylated cationic intermediates <b>6a</b><b>−</b><b>k </b>are prepared in yields of 72−94% from glyoxal adduct of cyclen (<b>5</b>) and slight excesses of alkyl iodides<b>. </b>The methodology is selective for monoalkylation and amenable to large-scale synthesis.