Synthesis and Radiolabeling of Potassium Trifluoroborate Benzylidene Anabaseine Derivatives

Author

Aaron Landon Smith, University of Tennessee - Knoxville

Date of Award

12-2006

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Chemistry

Major Professor

George W. Kabalka

Committee Members

Ziling Xue, Richard Pagni, Daniel Roberts

Abstract

Anabaseine has demonstrated a high, non-selective, affinity for the α7- bungarotoxin sensitive neuronal nicotinic acetylcholine receptor binding site found in small cell lung carcinoma. The benzylidene anabaseine derivatives of anabaseine have shown a selective affinity for these binding sites. These studies suggest that radiolabeled benzylidene anabaseine derivatives could act as potential imaging agents to aid in the early detection of lung cancer.

This dissertation outlines the strategy and methods employed in the synthesis of a family of potassium trifluoroborate derivatives of benzylidene anabaseine and their subsequent halogenation. Two of the trifluoroborate salts were converted to their radiolabeled analogues for potential use as single photon emission tomography (SPECT) agents through incorporation of iodine-123, or positron emission tomography (PET) agents, using bromine-76, for the early detection of lung cancer. One derivative, 5-[¹²³I]-iodo-2,4-dimethoxybenzyidene anabaseine was employed in an investigation using a new hamster lung tumor model.

En route to the synthesis of the radiolabeled benzylidene analogues, an investigation into a convenient synthesis of anabaseine was conducted. The synthesis was achieved in four steps and in high overall yields.

Recommended Citation

Smith, Aaron Landon, "Synthesis and Radiolabeling of Potassium Trifluoroborate Benzylidene Anabaseine Derivatives. " PhD diss., University of Tennessee, 2006.
https://trace.tennessee.edu/utk_graddiss/2039