The synthesis of a carborane gadolinium-DTPA complex for boron neutron capture therapy

Five-carboxylate DTPA derivatives (5 and 10) were synthesized via the palla dium-catalyzed reaction of allyl ethyl carbonate 9 with diethylenetriamine- N-ethoxycarbonyl acetic-N,N',N ",N "-tetraacetic acid hexaethyl ester 7. Th is method can be applied to the synthesis of a Gd-carborane complex. The re action of the hexaethyl ester 7 with carboranyl allyl carbonate 13a proceed ed very smoothly under Pd(dba)(2)/2dppe catalyst (10 mol%) in THF at 50 deg rees C, giving the C-C bond formation product 14 in 74% yield. Hydrolysis o f the ethyl esters in 14 was carried out with UOH in aqueous methanol follo wed by treatment with diluted hydrochloric acid (IN) to afford the correspo nding pentaacid 15 in 68% yield. Treatment of the carborane containing DTPA derivative 15 with gadolinium(III) chloride hexahydrate gave the desired G d-DTPA carborane complex 16 in quantitative yield. (C) 1999 Elsevier Scienc e S.A. All rights reserved.