AN IMPROVED SYNTHESIS OF HOMOPROLINE AND DERIVATIVES

An improved, general synthesis of substituted homoprolines has been developed by using readily available substituted pyridines (1). A key step in this synthetic procedure involves the known conversion of pyridine N-oxides to 2-cyanopyridines (3) in nearly quantitative yields. The resulting nitriles are hydrolyzed to the corresponding pyridine-2-carboxylic acids (4). Subsequent reduction of the aromatic ring with PtO2/H2 gives the homoprolines (5) in good yields as racemic cis isomers. This procedure also can be utilized for the preparation of 5,6-benzohomoprolines from the appropriate quinoline precursors. The N-tert-butyloxycarbonyl (Boc) derivatives of these amino acids (useful intermediates for peptide synthesis) were also prepared in good yields. © 1990, American Chemical Society. All rights reserved.