Improved Synthesis of Pseudoproline and DMB Dipeptide Carboxylic Acids

We report a mild method for the preparation of Fmoc-protected dipeptides containing a 2,4-dimethoxybenzyl (DMB) or 2-hydroxy-4-methoxybenzyl (HMB) group or modified as pseudoprolines. To minimize the loss of the Fmoc protection, we optimized the saponification conditions and included a calcium additive that protected the other base-sensitive functionalities and improved the yield of the free acid (36–82%). The reaction requires a combination of CaCl2 and NaOH in a mixture of iPrOH and water at room temperature.