Synthesis of a Bifunctional Monophosphinate DOTA Derivative Having a Free Carboxylate Group in the Phosphorus Side Chain

Abstract

A new bifunctional cyclen-based ligand, 3-[hydroxy({4,7,10-tris[(tert-butoxycarbonyl)methyl]-1,4,7,10-tetraazacyclododecan-1-yl}methyl)phosphoryl]propanoic acid, was synthe-sized by alkylation of tri-tert-butyl 1,4,7,10-tetraazacyclododecane-1,4,7-triacetate (t-Bu₃DO3A) by ethyl 3-{ethoxy[(mesyloxy)methyl]phosphoryl}propanoate [MsOCH₂P(O)(OEt)CH₂CH₂CO₂Et]. The ethyl carboxylate group in the side chain was selectively deprotected to obtain the esterified bifunctional ligand. More efficient syntheses of some phosphinopropanoic acid derivatives were devised and the phosphorus alkylation reagent was prepared starting from hypophosphorus acid or its salt.

Key words

macrocycles - MRI contrast agents - phosphinate ligands - phosphorus - radiopharmaceuticals

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Försterová, M.; Petřík, M.; Lázničková, A.; Lázníček, M.; Hermann, P.; Luke, I.; Melichar, F. Appl. Radiat. Isotop. 2008, submitted.