第四节 大环内酯类抗生素（Fourth macrolides antibiotics）.docVIP

第四节 大环内酯类抗生素（Fourth macrolides antibiotics） Fourth macrolides antibiotics Structural features (Tang Gan) A part of a fourteen, fifteen, or sixteen element ring containing a lactone structure. Glycogen: 6- or 6- deoxy amino sugar Deoxysugar In the process of microbial fermentation, natural antibiotics often produce many components with similar structure and similar properties. When the strains or production processes are different, the proportion of each component in the product is different, which affects the quality of the product. * erythromycin usually refers to erythromycin A * impurity components B and C: low activity and high toxicity Structural features of erythromycin A * Basic glycoside Structure characteristics * 14 yuan lactone ring key even carbon has six methyl groups 1 and 9 carbonyl groups C-3, C-5, C-6, C-11 and C-12 have five hydroxyl groups * C-3 is associated with the red mold sugar * C-5 is linked to deoxy glucosamine stability * five hydroxyl groups and 9 carbonyl groups * unstable under acidic conditions The C9 carbonyl group and C6 hydroxy most easily dehydration cyclization reaction occurs within the molecule. In acidic solutions, the hydroxyl group on the erythromycin C-6 and the carbonyl group of C-9 first form the hydroxyl group of the semi ketal, and then hydrogen molecules are removed with C-8 to produce 8, 9-, dehydrated -6, 9- semi ketal derivatives. Then the hydroxyl and C-8-C-9 on the C-12 double bond addition to intramolecular cyclization, generation 6, 9, -9, 12- spiral ketone; finally the hydrogen elimination hydroxyl of C-11 and C-10 on a water molecule, and hydrolysis of erythromycylamine and cladinose. This degradation resulted in the loss of antimicrobial activity of erythromycin One of the measures to increase the stability of erythromycin - salt modification (injection) Because it is unstable in acid (acid), it is easy to be destroyed. Erythromycin is alkaline (containing tertiary amine group). It can be salt with acid