合成路线1

BI 397 is the 3-(dimethylamino)-1-propylamide at the peptide-carboxy group of the natural glycopeptide A-40,926. BI 397 is prepared from A-40,926 following a three-step procedure which consists of: 1) selective methyl esterification of the N-acylaminoglucuronic acid function, 2) amidation of the peptide-carboxy group and 3) saponification of the sugar methyl ester. Steps 2 and 3 are performed in one-pot. Step 1): Reaction of A-40,926 (A) (I) in methanol in the presence of H2SO4 at 0-5 C for 24 h gives the monomethyl ester (MA) (II) at the sugar-carboxy group (80% yield). Step 2): Amidation at the peptide-carboxy group is carried out by reaction of MA (II) with 3-(dimethylamino)-1-propylamine (DMEPA) (III) in DMSO in the presence of PyBOP to obtain the methyl ester (MA-A-1) (IV) of BI 397; this compound is not isolated. Step 3): Hydrolysis of MA-A-1 (IV) in the above DMSO solution with 15% NAOH gives BI 397 (A-A-1, 63% yield from MA).