Synthesis and antibacterial activity of 3-hydroxy-6-O-methylerythromycin-9-O-substituted oxime derivatives

Sheng xi Chen, Xian Dong Xu, Lan Xiang Yu

Research output: Contribution to journalArticlepeer-review

Abstract

AIM: To study the antibacterial activity against erythromycin-resistant organisms of 3-hydroxy-6-O-methylerythromycin-9-O-substituted oxime derivatives, a new route of synthesis with 6 steps was designed. METHODS: The starting material, erythromycin A (1), was reacted with NH2OH · HCI to give 2, which reacted with BzBr to give 3. Selective mediation of C-6 hydroxy group using iodomethane afforded 4, which was hydrolyzed with loss of the 3-cladinosyl to give 5. Compound 5 was reduced by H2 to provide 6, which was treated with substituted benzyl chlorides to provide 7 and 8. RESULTS: Four unreported compounds (5-8) were synthesized. The antibacterial activity of the new compounds were tested in vitro against both erythromycin-susceptible and erythromycin-resistant organisms. The compounds 5 (MIC = 1 μg · mL-1) and 6 (MIC = 1 μg · mL-1) showed significant activity against Staphylococcus epidermidis 26069 compared with erythromycin (MIC = 4 μg · mL-1). Compounds 5 (MIC = 16, 4 μg · mL-1), 7 (MIC = 32, 64 μg · mL-1) and 8 (MIC = 64, 32 μg · mL-1) showed better activity against Streptococcus pneumoniae 64 and Staphylococcus aureus 9525 than erythromycin (MIC > 128, 128 μg · mL-1). CONCLUSION: 3-hydroxy-6-O-methylerythromycin-9-O-substituted oxime derivatives have stronger antibacterial activity against some erythromycin-resistant organisms than erythromycin A.

Original languageEnglish (US)
Pages (from-to)583-584
Number of pages2
JournalYaoxue Xuebao
Volume36
Issue number8
StatePublished - Aug 1 2001
Externally publishedYes

Keywords

  • 3-hydroxy-erythromycin derivatives
  • Antibacterial activity
  • Semisynthesis

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

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