Acid catalysed degradation of some spiramycin derivatives found in the antibiotic bitespiramycin

Bitespiramycin is a novel antibiotic containing a number of 4-acylated spiramycin derivatives (isovalerylspiramycins 1-III, butanoylspiramycin III. propanoylspiramycin III and acetylspiramycin III) as major components. These spiramycin derivatives are susceptible to degradation in acid Solution. Liquid chromatography-ion trap mass spectrometry (LC/MS) was used to study the degradation of these spiramycin derivatives in Simulated gastric fluid at 37degreesC. All derivatives degraded by first-order reactions for which rate constants (k) and half-lives (t(1/2)) were calculated. Acyl groups at position 3 had less effect on acid-stability of spiramycin derivatives than acyl groups at position 4. The introduction of 4-acyl groups enhanced the acid-stability of spiramycin derivatives and altered the degradation pathway in simulated Gastric fluid such that loss of forosamine rather than loss of mycarose becomes the major degradation pathway. (C) 2004 Elsevier B.V. All rights reserved.