Chemical Modification of Aminoglycoside Antibiotics. Some N-Alkyl Derivatives of Sorbistin A1 (P-2563 P) and Butirosin A

Some N-alkyl derivatives of sorbistin A1 (P-2563 P) (1) and butirosin A (10) were prepared by reductive alkylation with aldehyde and NaBH4 or NaBH3CN. Among them, 4'-N-propylsorbistin A1 (8b) showed antimicrobial activity against gram-positive bacteria comparable to sorbistin A1 (1) and showed broader spectrum of activity against gramnegative bacteria including some of the sorbistin A1-resistant strains (K. pneumoniae, Ps. aeruginosa) than sorbistin A1 (1). 2'-N-Propylbutirosin A (14c) showed antimicrobial activity similar to butirosin A (10) and showed weak antimicrobial activity against some of butirosin A-resistant bacteria including E. coli JR 66/W 677 which is reported to produce 3'-phosphotransferase II. It was shown that 2'-N-propylbutirosin A (14c) was hardly phosphorylated under the condition where butirosin A (10) was almost completely phosphorylated with the purified E. coli JR 66/W 677 3'-phosphotransferase II.