Improved Synthesis of Pseudoproline and DMB Dipeptide Carboxylic Acids

We report a mild method for the preparation of Fmoc-protected dipeptides containing a DMB (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 i-PrOH and water at room temperature.