Preparation of magnetic resonance contrast agents activated by beta-galactosidase.
The preparation of beta-EgadMe and alpha-EgadMe, magnetic resonance (MR) contrast agents that can be used for in vivo detection of beta-galactosidase, is described. Diastereomerically pure beta-EgadMe can be synthesized by kinetically resolving the starting material as described in Step 1. The total time for the preparation of the racemic mixture of beta-EgadMe is about 8 d, and the total time for an diastereomerically resolved agent is about 9 d. The final metallated agent is stable at room temperature as a solid or in aqueous buffer (pH 5.5-10) indefinitely. Diastereomerically pure alpha-EgadMe can be prepared by beginning the synthesis with enantiomerically pure bromopropionic acid. The total time for the preparation of racemic alpha-EgadMe or diastereomerically pure alpha-EgadMe is about 8 d. The final metallated agent is stable at room temperature as a solid or in aqueous buffer (pH 5.5-10) indefinitely.
Urbanczyk-Pearson
Lauren M
LM
Department of Chemistry, Department of Biochemistry and Molecular and Cell Biology, Department of Neurobiology and Physiology, Department of Radiology, Northwestern University, Evanston, Illinois 60201, USA.
Meade
Thomas J
TJ
D002625:Chemistry, Organic / Q000379:methods*; D004852:Epoxy Compounds / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013997:Time Factors; D001616:beta-Galactosidase / Q000032:analysis / Q000378:metabolism
C407367:EgadMe; D004852:Epoxy Compounds; D009942:Organometallic Compounds; D001616:beta-Galactosidase; C009068:propylene oxide