Preparation of functionalized, conformationally constrained DTPA analoguesfrom L- or D-serine and trans-4-hydroxy-L-proline. Hydroxymethyl substituents on the central acetic acid and on the backbone

The enantio- and diastereospecific syntheses of conformationally constraine d diethylenetriaminepentaacetic acid (DTPA) analogues that are functionaliz ed with a hydroxymethyl linker substituent on the central acetic acid or on the backbone are described. Key synthetic steps include (i) displacement o f the 4-hydroxyl group of N-BOC-trans-4-hydroxy-L-proline benzyl ester, via activation as the triflate, with suitable amines derived from L- or D-seri ne, (ii) the low-temperature alkylation of diethylenetriamines with the tri flate of benzyl glycolate, thereby minimizing competitive lactamization, to give DTPA pentabenzyl esters, and (iii) deprotection to afford the corresp onding DTPA analogues under very mild hydrogenolysis conditions.