Benzyloxy derivatives of triazine-based coupling reagents designed for an efficient solid phase peptide synthesis on polystyrene resin

Coupling reagents resembling the structure of Merrifield resin were designed and prepared from 2-chloro-4,6-dibenzyloxy-1,3,5-triazine and the different tertiary bases N-methylmorpholine, N-methylpiperidine, and DABCO. As previously observed for DMTMM, the appropriate N-(4,6-dibenzyloxy-1,3,5-triazin-2-yl) ammonium chloride salts were not suitable as efficient coupling reagents because of their low stability. On the other hand, the stability of the N-(4,6-dibenzyloxy-1,3,5-triazin-2-yl) ammonium tetrafluoroborates was suitable enough for prolonged storage and convenient application in SPPS. Moreover, we observed that the superactive intermediates formed during activation of Fmoc-Aib-OH with 4,6-dibenzyloxy-1,3,5-triazine-based coupling reagents lead to an increase in its concentration inside the polystyrene resin. Therefore, we hypothesize that this increase can enhance efficiency of 4,6-dibenzyloxy-1,3,5-triazine-based coupling reagents in SPPS.