Synthesis of Di- and Tripeptides Using A Flow Process

Significance

A flow process for the multi-step assembly of peptides was developed. Thus, N-protected (Boc, Cbz) amino acids 1, DIPEA and PyBroP in DMF were injected in a polymer-supported HOBt column. Acids 1 were trapped by the HOBt polymer as activated amino acids, and any by-products and non-trapped reagents were washed out. Amino acids·HCl 2 were converted into free amino acids through a polymer-supported DMAP column, and the resulting free amines were reacted with the trapped amino acids to give a mixture of dipeptides and the unreacted amines. The mixture was passed through a polymer-supported sulfonic acid which scavenged the unreacted amines to afford pure dipeptides (9 entries, 61-83%, >95% purity).