Resin-supported arylstannanes as precursors for radiolabeling with iodine: benzaldehydes, benzoic acids, benzamides, and NHS esters

A highly cross-linked polystyrene resin bearing a reactive chlorostannane moiety 1 has been used to generate a variety of arylstannane radiopharmaceutical precursors for no-carrier-added radioiodination. The resins were characterized for their solvent compatibility and sensitivity to acid cleavage. Resin-supported arylstannanes synthesized via their aryllithium analogues include 3-and 4-stannylbenzaldehydes, 3-and 4-stannylbenzoic acids, and 3-and 4-N-succinimidyl benzoates. A three-step route to the resin-supported stannylbenzoic acids 12a/b was developed through resin-supported benzaldehydes 11a/b. The aldehyde to acid conversion efficiency is >90%, and acid loading capacities of 0.66-0.94 mmol/g were obtained. Resin-supported N-succinimidyl benzoates 16a/b were prepared from the acid with 78%-84% conversion efficiency. Libraries of resin-supported benzamides 19a/b prepared from amine conjugation to corresponding benzoic acids or N-succinimidyl benzoates are described. A third approach describes the preparation of resin-supported benzamides via direct conjugation of the dilithio salt of the intact benzamide to the chlorostannane resin 1. Lastly, as proof-of-principle, a radiolabeling study with iodine-131 (I-131) was performed with a resinsupported benzamide to afford the corresponding radioligand in moderate yields, and high radiochemical purity.