Synthesis of Lipophilic Paramagnetic Contrast Agents.
The facile, high-yielding synthesis of a series of macrocycles 7a-k in 75-100% yield is reported. The transformation of these compounds to their carboxymethylated analogues 8a-k in 75-90% yield and subsequent gadolinium complexes 9a-k provides a series of homologous neutral paramagnetic contrast agents (PCAs) with tunable lipophilicity. Alkylated cationic intermediates 6a-k are prepared in yields of 72-94% from glyoxal adduct of cyclen (5) and slight excesses of alkyl iodides. The methodology is selective for monoalkylation and amenable to large-scale synthesis.
Baker
William C.
WC
Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, Illinois 61801.
Choi
Michael J.
MJ
Hill
Daniel C.
DC
Thompson
Julie L.
JL
Petillo
Peter A.
PA