LITHIUM-SALT EFFECTS IN PEPTIDE-SYNTHESIS .1. CONDITIONS FOR THE USE OF LITHIUM-SALTS IN COUPLING REACTIONS

The influence of Li-salts on the course of peptide-coupling reactions was investigated. As a model for segment couplings, Ac-Phe-OH was coupled to HCl.H-Ala-OMe using the mixed anhydride, DCCl, DCCl/HOBt, BOP-Castro and TBTU-Knorr methods. As a model for stepwise synthesis Z-Phe-OH was coupled with HCl.Ala-O(t-Bu), using symmetrical anhydrides and active esters. The effects of salt additives such as LiCl, LiBr, LiClO4, and ZnCl2 on yields, side-product formation, racemisation, and reaction rates are reported.