Esters of a number of α-and β-polyaminocarboxylic acids have been selectively hydrolyzed to the corresponding monoacids using pig liver esterase in moderate to good yields. For example, the tetraethyl ester of EDTA is hydrolyzed to the corresponding monoacid using PLE at pH 8 in 4.5 hours in 86% yield. Enzymatic hydrolysis provides ready access to this important class of synthetic intermediates.

The use of metal chelates of ethylenediaminetetraacetic acid (EDTA) and other polyaminocarboxylic acids as probes of biological systems is well known. 1 A number of reports on the use of gadolinium chelates of diethylenetriaminepentaacetic acid (DTPA) and related analogs as magnetic resonance imaging (MRI) agents have also appeared. 2 In this context, DTPA residues have been attached to a variety of macromolecular substrates (both biopolymers and synthetic polymers) to produce new agents that may be particularly useful as blood pool contrast enhancing agents. 3 Also, several chelating polymers that incorporate polyaminocarboxylic acids such as EDTA and DTPA have been prepared and studied for metal ion separation applications. 4 The reaction of anhydrides of EDTA and DTPA with amines has been the conventional method for the introduction of these ligand moieties into a variety of substrates. 2a, 4a, 5 As part of a program to develop polymeric chelators for the selective binding of actinides, we became interested in developing convenient methods for the preparation of the monoacids of EDTA tetraethyl ester and those of other polyamino carboxylic acids. 6, 7 These monoacids can then be conveniently coupled to amino groups in a variety of polymers to give chelating polymers of defined structures (without fear of competing cross-coupling reactions such as those that occur with the corresponding anhydrides). Surprisingly, there are very few reports on the synthesis of EDTA monoacid trialkyl esters. 8 The published synthetic approach involves the complexation of the EDTA tetramethylester with cupric perchlorate followed by monohydrolysis using 1 equivalent of sodium hydroxide. The copper is subsequently removed by precipitation with hydrogen sulfide to obtain the monosodium salt of the product. However, in our hands this procedure gave variable yields and the removal of the copper from the reaction mixture using toxic hydrogen sulfide was quite cumbersome and undesirable.