1-(N,N-Dialkylcarbamoyl)-1,1-difluoromethanesulfonyl ester as a stable and effective precursor for a neopentyl labeling group with astatine-211

Abstract

Radiohalogens with a short half-life are useful radioisotopes for radiotheranostics. Astatine-211 is an α-emitting radiohalogen and is expected to be applicable to targeted α therapy. A neopentyl labeling group is an effective hydrophilic labeling unit for various radiohalogens, which includes ²¹¹At. In this study, a 1-(N,N-dialkylcarbamoyl)-1,1-difluoromethanesulfonyl (CDf) ester was developed as a stable precursor for labeling with ²¹¹At, ⁷⁷Br and ¹²⁵I through a neopentyl labeling group. The CDf ester remained stable in an acetonitrile solution at room temperature and enabled the successful syntheses of ²¹¹At-labeled compounds in a highly radiochemical conversion in the presence of K₂CO₃. ⁷⁷Br- and ¹²⁵I-labeled compounds can be prepared from the CDf ester without a base. The utility of the CDf ester was demonstrated in the synthesis of a benzylguanidine with a neopentyl ²¹¹At-labeling group. The developed method afforded a 32% radiochemical yield of ²¹¹At-labeled benzylguanidine. However, a partial deastatination was observed under acidic conditions during the removal of an N-Boc protecting group. Deprotecting these groups under milder acidic conditions may improve the radiochemical yield. In conclusion, the CDf ester facilitates the syntheses of ²¹¹At, ¹²⁵I and ⁷⁷Br-labeled compounds that use a neopentyl labeling group for radiotheranostic applications. Further optimization of protecting groups and reaction conditions should enhance the total radiochemical yield of the ²¹¹At-labeled compounds.