L-Glutamic acid and L-lysine as useful building blocks for the preparation of bifunctional DTPA-like ligands.
Bisalkylation of suitably protected L-glutamic acid and L-lysine derivatives with tert-butyl N-(2-bromoethyl)iminodiacetate 2, followed by deprotection of the omega functional group affords N, N-bis[2-[bis[2-(1, 1-dimethylethoxy)-2-oxoethyl]amino]ethyl]-L-glutamic acid 1-(1, 1-dimethylethyl) ester 4 and N2,N2-bis[2-[bis[2-(1, 1-dimethylethoxy)-2-oxoethyl]amino]ethyl]-L-lysine 1,1-dimethylethyl ester 7. Such compounds feature a carboxylic or an amino group, respectively, which are available for conjugation with a suitable partner via formation of an amide bond. The conjugates, which can be prepared in this way, contain a chelating subunit in which all five acetic residues of DTPA are available for the complexation of metal ions. Direct bisalkylation of glycine with 2 promptly gives N, N-bis[2-[bis[2-(1,1-dimethylethoxy)-2-oxoethyl]amino]ethyl]glycine 11. The latter allows to achieve conjugates in which the central acetic group of DTPA is selectively converted into an acetamide.
Anelli
P L
PL
Bracco spa, Milano Research Centre, via E. Folli 50, 20134 Milano, Italy.
Fedeli
F
F
Gazzotti
O
O
Lattuada
L
L
Lux
G
G
Rebasti
F
F
D000478:Alkylation; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D018698:Glutamic Acid / Q000737:chemistry*; D008024:Ligands; D008239:Lysine / Q000737:chemistry*; D004369:Pentetic Acid / Q000737:chemistry*
D002614:Chelating Agents; D008024:Ligands; D018698:Glutamic Acid; D004369:Pentetic Acid; D008239:Lysine