PRODUCTION OF PEPTIDE DERIVATIVE, INTERMEDIATE TO PRODUCE PEPTIDE DERIVATIVE, AND PRODUCTION OF THE INTERMEDIATE

摘要

PROBLEM TO BE SOLVED: To obtain a peptide derivative, for example, for the prevention of premature miscarriage, which has the low anti-vasopressin action but the anti-oxytocin action, by removing protecting groups of a specific peptide having a plurality of protected SH groups, followed by the oxidation in an acidic aqueous medium. SOLUTION: The peptide derivative (or its salt) shown by formula VII is obtained by the first dehydration condensation between a compound shown by formula I (R<2> is H or a protecting group for the guanidino group of Arg; R<4> is a protecting group for the imino group of Pro) and a compound shown by formula II (R<3> is a protecting group for the thiol group; R<5> is a protecting group for the amino group), the second dehydration condensation with a compound shown by formula III (R<6> is a protecting group for the amino group), the third dehydration condensation with a compound shown by formula IV (R<1> is H or a protecting group for the indolyl group; R<7> is the same as R<2> ), the fourth dehydration condensation with a compound shown by formula V to give a compound shown by formula VI (MBzl is 4-methoxybenzyl), the removal of two MBzl groups, followed by the oxidation in an aqueous medium at pH 4.0-6.0 to form the intramolecular disulfide bond(s).