Synthetic approaches to iodovinyl amino acids

A site specific radiopharmaceutical for imaging of the pancreas is currently not available. Based on previous studies involving unnatural amino acids, iodovinyl-a-methyla-amino acids appear to be promising candidates. A number of synthetic approaches to the iodovinyl-a-methyl-a-amino acids were investigated. One approach involved the use of an intermediate vinylboronic acid hydantoin (I). By use of this methodology, the synthesis of a model compound, 2- amino-12-iodo-ll-dodecenoic acid (II) was realized.

Detailed investigations of synthetic pathways involving protected hydantoins were carried out. New approaches to hydantoin precursors were also developed. A direct approach involving the hydroboration of acetylenic amino acids was investigated. This approach had never been reported. Protection of the carboxylic acid functionality as the trimethylsilyl ester during the hydroboration reaction was investigated. Hydroboration of unsaturated trimethylsilyl esters was successful with all V hydroborating agents studied, including BH₃THF. The intermediate organoboranes can be converted by standard organoborane transformations, including halogenation, oxidation, and protonolysis.

Isolation of the intermediate trimethylsilyl ester is often unnecessary. A convenient procedure involving the in situ formation of the trimethylsilyl ester followed by hydroboration was developed. This methodology offers a new route to iodovinyl fatty acids (equation 1).