A new generation of reversible backbone-amide protection for the solid phase synthesis of difficult sequences

A versatile safety catch backbone-amide protection system (1, 2) has been d eveloped to inhibit interchain aggregation during solid phase peptide synth esis. The strategy utilises the N-alpha-Fmoc derivative of an N-(3-methylsu lfinyl-4-methoxy-6-hydroxybenzyl) (SiMB, 2) substituted amino acid (5b), a group which exhibits excellent all round coupling kinetics. The value of th ese improved derivatives is demonstrated through the syntheses of leucine e nkephalinamide (9) and the well known 'difficult sequence' from the acyl ca rrier protein, residues (65-74) (10) via standard uronium activation and pe ntafluorophenyl eater chemistry. (C) 2000 Elsevier Science Ltd. All rights reserved.