Preparation and properties of derivatives at the amino group of ristocetin aglycone.

Ristocetin A (synonym of ristomycin A) belongs to the class of glycopeptide antibiotics which act by selective formation of a stable complex with the developing bacterial cell wall peptidoglycan0. It is suggested2>3) that the complex is stabilized by an array of hydrogen, hydrophobic and ionic interactions in particular with participation of the COOHgroup of the C-terminal D-alanine of the growing peptidoglycan and the amino group of the antibiotic aglycone. On the other hand we showed in 1983 that there was no loss of the antimicrobial activity after modification of the ristocetin aglycone amino group4). This fact call in question the direct participation of the amino group in the complexation of the antibiotic with the peptidoglycan precursors. Similar results were reported by other authors5~7). Aim of this paper is to elucidate the influence of acylation of the amino group of the ristocetin aglycone, the effect of an higher positive charge and of the distance of positive charged group from the molecule nucleus on the antimicrobial activity of the molecule and efficiency of its binding to a biospecific sorbent. A brief communication of this study was published earlier8). The ristocetin aglycone (1) was prepared as previously described9). Aminoacyl derivatives of 1 (2~5) were obtained by acylation of the amino group with pentafluorophenyl esters of tert-butyloxycarbonyl amino acids. The JV-acetamidoylaglycone (6) was prepared by reaction of 1 with ethylacetimidate (Scheme 1). Purification of