LARGE-SCALE PRODUCTION OF PEPTIDES USING THE SOLID-PHASE CONTINUOUS-FLOW METHOD - PART 2 - PREPARATIVE SYNTHESIS OF A 26-MER PEPTIDE THROMBIN INHIBITOR

A preparative method for the preparation of large peptides is describe d. An advantageous theoretical weight of peptide/weight of starting re sin ratio (tP(w)/R-w) of about 0.3 was successfully experimented. The esterification of the first amino acid was realized with a racemizatio n of less than 1%. The study of the coupling conditions led to the use of a diluted acylating mixture that allowed a 56% consumption of the amino acid derivatives (percentage use of amino acids) introduced in t he synthesis. The cost analysis of the synthesis showed that the recov ery of the amino acid derivatives was not worthwhile. (C) 1998 Europea n Peptide Society and John Wiley & Sons, Ltd.