Synthesis of the β₃‑Adrenergic Receptor Agonist Solabegron and Analogous <i>N</i>‑(2-Ethylamino)-β-amino Alcohols from <i>O</i>‑Acylated Cyanohydrins – Expanding the Scope of Minor Enantiomer Recycling

Abstract

A novel methodology to produce highly enantioenriched <i>N</i>-(2-ethylamino)-β-amino alcohols was developed. These compounds were obtained from <i>O</i>-(α-bromoacyl) cyanohydrins, which were synthesized by the minor enantiomer methodology employing a Lewis acid and a biocatalyst, followed by nucleophilic substitution with amines and reduction. The importance of the developed methodology was demonstrated by completing a highly enantioselective total synthesis of the β₃-adrenergic receptor agonist Solabegron