In the research from the twentieth century, a solid foundation was set for the development of N-C-SPPS. Systematic analysis of peptide quality during synthesis was facilitated by employing the 2-chloro trityl anchor which could be cleaved under mild conditions. Key observations were made for minimizing racemization. Pioneering research on N-C-SPPS was not focused on improving PMI; however, the shift of protection from the amine to the carboxylate side of the amino acid building block offered in principle means to improve atom economy. Significant excess of activating agent and amino ester were however employed in methods using thiopyridyl esters, and DIC, TBTU and HATU couplings. In addition, such chemistry was often performed using toxic solvents that should be avoided today. resins (e.g., 46) gave the corresponding ketones. Resin cleavage with concomitant removal of borate protection was performed using 10% trifluoromethanesulfonic acid in TFA.