A new series of glycopeptide antibiotics incorporating a squaric acid moiety -: Synthesis, structural and antibacterial studies

The aglycones of the antibiotics eremomycin, vancomycin and ristocetin (3, 4 and 6, respectively) were prepared by deglycosidation of the parent antibiotics with hydrogen fluoride, and complete assignation of their H-1, C-13 and N-15 spectra was performed. The squaric acid amide esters (11 similar to 14), were prepared from dimethyl squarate. The corresponding asymmetric diamides (16 similar to 19, 22, 23) were also synthesized using 4-phenylbenzylamine and triglycine. The advantage of the method is the high regioselectivity and that no protecting group strategy is required. Electrospray mass spectroscopic method was elaborated for the determination of the site of substitution of the modified antibiotics. The antibacterial activity of the prepared compounds is discussed in detail.