Process for the preparation of glycopeptides having asparagine-linked oligosaccharides

摘要

Process for the solid phase synthesis of a glycopeptide having at least one oligosaccharide attached auna asparagine at a desired position of the peptide chain thereof, the process comprising lasetapas of: (1) esterifying a hydroxyl group of a resin having the hydroxyl group and a grupocarboxilo of an amino acid having an amino nitrogen protected liposoluble grupoprotector, (2) removing the fat-soluble protective group to form a free amino group, (3) amidating the free amino group and a carboxyl group an amino acid having unnitrógeno amino group protected by a fat-soluble protecting group, (4) removing the fat-soluble protective group to form a free amino group, (5) repeating steps (3) and (4) at least once, ( 6) preparation of a disialooligosacárido attached to an asparagine or monosialooligosacárido attached to an asparagine having the noprotegidos hydroxyl groups and having a nitrogen or the amino group protected by a protectorliposoluble group and the carboxyl group of the sialic acid protected by a benzyl group, odifenilmetilo allyl, (7) amidating the free amino group and a carboxyl group of the asparagine portion deldisialooligosacárido attached to an asparagine or monosialooligosacárido joined unaasparagina having an amino nitrogen protected protectorliposoluble group and the carboxyl group of the sialic acid protected by a benzyl group, odifenilmetilo allyl, (8) removing the fat-soluble protective group to form a free amino group, (9) amidation the free amino group and a carboxyl group of an amino acid having unnitrógeno the amino group protected by a fat-soluble protective group, (10) repeating steps (8) and (9) at least once, (11) removing the protecting group liposoluble to form a free amino group, (12) cutting the resin with an acid.