Lithium-salt effects in peptide synthesis: Part II. Improvement of degree of resin swelling and of efficiency of coupling in solid-phase synthesis

Article abstract of DOI:10.1002/hlca.19910740320

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(ethy1ene 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 l-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 Ala ₁₂-Phe by HPLC and FAB-MS are reported.