Isolation and structure determination of the main related substances of teicoplanin, a glycopeptide antibiotic.
Teicoplanin is a complex formed by five closely related glycopeptides and by a small amount of a hydrolysis product. Minor quantities of related substances are also present. Two of them (named RS-1 and RS-2) were isolated and purified starting from the tailing fractions of a teicoplanin batch. Preparative reversed-phase liquid chromatography on large low-pressure and medium high-pressure scales, concentration, desalting, and freeze-drying steps were applied. 300 mg of RS-1 and 900 mg of RS-2 were obtained in a purity grade (about 90%) sufficient for structural investigation. Starting from considerations on the HPLC retentivity and on biosynthesis, the structures were assigned on the basis of 1H-N.M.R. spectra and homonuclear CO-SY 2D experiments, FAB-MS spectrometry, and GC-MS of the esters of the fatty acids obtained by hydrolysis. RS-1 and RS-2 are teicoplanins having 10-methyl-undecanoic acid and n-dodecanoic acid, respectively as fatty acid chains. No major difference in the in vitro activity of these teicoplanins emerged in comparison with teicoplanin complex.
Cometti
A
A
Merrell Dow Research Institute, Centro Ricerche Lepetit, Gerenzano (Va), Italy.
Gallo
G G
GG
Kettenring
J
J
Panzone
G B
GB
Tuan
G
G
Zerilli
L F
LF
D002846:Chromatography, Affinity; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D005612:Freeze Drying; D008401:Gas Chromatography-Mass Spectrometry; D006020:Glycopeptides / Q000032:analysis / Q000302:isolation & purification; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008968:Molecular Conformation; D013056:Spectrophotometry, Ultraviolet; D017334:Teicoplanin
D006020:Glycopeptides; D017334:Teicoplanin