Avoiding Undesired Intramolecular Diketopiperazine Formation during Peptoid Chain Elongation Using a Microflow Reactor.

Avoiding undesired intramolecular reactions during desired intermolecular reactions is an important challenge in synthetic organic chemistry. We successfully avoided undesired intramolecular diketopiperazine formation during desired N-alkylation in the synthesis of peptoids using a microflow reactor. Fifteen peptoids were synthesized in good to high yields, and a cyclic peptoid was synthesized on the gram scale using the developed microflow approach. The productivity and cost of our approach are significantly superior to those of the conventional solid-phase approach.