LARGE-SCALE SYNTHESIS OF THE BIFUNCTIONAL CHELATING AGENT 2-(P-NITROBENZYL)-1,4,7,10-TETRAAZACYCLODODECANE-N,N',N',N'''-TETRAACETIC ACID, AND THE DETERMINATION OF ITS ENANTIOMERIC PURITY BY CHIRAL CHROMATOGRAPHY

被引:50
作者
RENN, O [1 ]
MEARES, CF [1 ]
机构
[1] UNIV CALIF DAVIS,DEPT CHEM,DAVIS,CA 95616
关键词
D O I
10.1021/bc00018a017
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The attachment of radiometals to monoclonal antibodies for medical applications requires extreme stability under physiological conditions, with no significant release of metal. Chelators that can hold radiometals like In-111, Ga-67, and Y-90 with high stability under these conditions are essential for radiotherapy or immunoscintigraphy. 2-(p-Nitrobenzyl)-1,4,7,10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid (nitrobenzyl-DOTA) is one of the most promising bifunctional chelating agents. A large-scale synthesis of nitrobenzyl-DOTA is described. The overall yield for the nine-step synthesis sequence starting from nitrophenylalanine is 5.6 %. Synthesis of nitrobenzyl-DOTA according to the new procedure yields up to approximately 10 g without special apparatus. Both enantiomers of the chiral chelate nitrobenzyl-DOTA have been prepared, and their enantiomeric purity has been checked by chiral chromatography.
引用
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页码:563 / 569
页数:7
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