Synthetic approaches to iodovinyl amino acids

Author

Donald Elton Bierer

Date of Award

8-1988

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Chemistry

Major Professor

George W. Kabalka

Committee Members

Leaf Huang, Craig E. Barnes, Richard Pagni

Abstract

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).

Recommended Citation

Bierer, Donald Elton, "Synthetic approaches to iodovinyl amino acids. " PhD diss., University of Tennessee, 1988.
https://trace.tennessee.edu/utk_graddiss/11819