4-Phenylpyridine glucagon receptor antagonists: synthetic approaches to the sterically hindered chiral hydroxy group

Systematic evaluation of the structure–activity relationships of a new class of 4-aryl-pyridine glucagon antagonists led to the discovery of potent analogues bearing a key secondary hydroxy moiety as seen in compound 1a. Due to the importance of this new class of compounds, it became necessary to establish an efficient synthesis of the pure enantiomer. A resolution and two chiral syntheses of alcohol 1a were discovered and herein presented.