LITHIUM-SALT EFFECTS IN PEPTIDE-SYNTHESIS .2. IMPROVEMENT OF DEGREE OF RESIN SWELLING AND OF EFFICIENCY OF COUPLING IN SOLID-PHASE SYNTHESIS

The course of solid-phase peptide-coupling reactions as well as the swelling properties of a peptide-resin are influenced by the addition of inorganic salts (LiCl, LiBr, LiClO4, KSCN). Used as additives, these salts can i) improve coupling yields (e.g., for Fmoc-(Ala)5-Phe-resin --> Fmoc-(Ala)6-Phe-resin in DMF/CH2Cl2 1:1 from 89.4 to 97.1% (for poly(ethylene oxide) on polystyrene (= PEO-PS) resin) or from 77.5 to 93.8% (for poly-(N, N'-dimethylacrylamide) on 'Kieselgur' (= PDMAA-KG) resin) without and with 0.4M LiCl, respectively), ii) increase resin swelling (e.g. for Fmoc-(Ala)5-Phe-(polystyrene resin) from 2.42- to 5.71-fold in 1-methylpyrrolidin-2-one (= NMP) without and with LiCl, respectively), and iii) change coupling rates. Examples of coupling reactions and swelling behaviour (degree and rate) in different solvents (DMF, DMF/CH2Cl2 1:1, THF, NMP, N,N-dimethylpropyleneurea (= DMPU) with and without salts) using different resins (polystyrene (PS); PEO-PS, and PDMAA-KG) and an improved analysis of alanine oligomers up to Ala12-Phe by HPLC and FAB-MS are reported.