Preparation of new substituted alkylamide derivatives of teicoplanin as antibacterials

The title compds. [I; R = H, protecting group; Y = NR1X1(XX2)p(TX3)qW; R1 = H, alkyl; T, X = O, (substituted) imino; X1, X2, X3 = C2-10 alkylene; W = OH, amino; p = 1-50; q = 0-12; A = H, N-acylated β-D-2-deoxy-2-aminoglucopyranosyl; B = H, N-acetyl-β-D-2-deoxy-2-aminoglucopyranosyl; M = H, α-D-mannopyranosyl; B = H only when both A, M = H], were prepd. Thus, teicoplanin A1 component 2 in ET3N/DMF was treated with PhCH2O2CCl in acetone to give ∼96% of the N-15 CBZ deriv. This was esterified with ClCH2CN in DMF/Et3N in ∼98% yield and the ester was treated with H2N(CH2)2NH(CH2)2NH2 in DMF followed by hydrogenolysis to give I [A = N-(8-methylnonanoyl)-β-D-2-deoxy-2-aminoglucopyranosyl, B = N-acetyl-β-D-2-deoxy-2-aminoglucopyranosyl, M = α-D-mannopyranosyl, Y = H2NCH2CH2NHCH2CH2NH, R = H] (II). II had an ED50 of 0.09 mg/kg s.c. against Streptomyces pyrogenes C203 in mice. Several I were active against multi-resistant Pseudomonas aeruginosa with MIC of 4-128 μg/mL.