L-glutamic acid and L-lysine as useful building blocks for the preparationof bifunctional DTPA-like ligands

Bisalkylation of suitably protected L-glutamic acid and L-lysine derivative s with tert-butyl N-(2-bromoethyl)iminodiacetate 2, followed by deprotectio n of the omega functional group affords N,N-bis[2-[bis [2-(1,1- dimethyleth oxy)-2-oxoethyl]amino]ethyl]-L-glutamic acid 1-(1,1-dimethylethyl) ester 4 and N-2,N-2-bis[2-[bis[2-(1,1- dimethylethoxy)-2-oxoethyl]amino]ethyl]-L-ly sine 1,1- dimethylethyl ester 7. Such compounds feature a carboxylic or an amino group, respectively, which are available for conjugation with a suita ble partner via formation of an amide bond. The conjugates, which can be pr epared in this way, contain a chelating subunit in which all five acetic re sidues of DTPA are available for the complexation of metal ions. Direct bis alkylation of glycine with 2 promptly gives N,N-bis[2-[bis[2-(1,1-dimethyle thoxy)-2-oxoethyl]amino]ethyl]glycine 11. The latter allows to achieve conj ugates in which the central acetic group of DTPA is selectively converted i nto an acetamide.