Synthesis and antibacterial activity of O-methyl derivatives of azalide antibiotics: II. 6-OMe derivatives via clarithromycin

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 11, 1998, Pages 1321-1326

  Waddell, Sherman T ^a   Santorelli, Gina M ^a   Blizzard, Timothy A ^a   Graham, Amy ^a   Occi, James ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AZITHROMYCIN; CLARITHROMYCIN; CLARITHROMYCIN DERIVATIVE; ERYTHROMYCIN DERIVATIVE;

ANTIBACTERIAL ACTIVITY; ARTICLE; DRUG SENSITIVITY; DRUG SYNTHESIS; ISOMERISM; METHYLATION; MINIMUM INHIBITORY CONCENTRATION; REACTION ANALYSIS; REACTION TIME; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; TEMPERAMENT;

ANTI-BACTERIAL AGENTS; AZA COMPOUNDS; CLARITHROMYCIN; GRAM-POSITIVE BACTERIA; METHYLATION; MICROBIAL SENSITIVITY TESTS; MOLECULAR CONFORMATION;

EID: 0032474529     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00227-3     Document Type: Article

References (14)

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10. 13C NMR spectrum. Next, we found that in every case a very strong coupling is seen from the protons on a methoxy group to the carbon bearing that methoxy group. With a complete carbon assignment, this makes it a simple matter to determine the locations of the methoxy groups. This data is summarized in the table which follows: (table presented)
11. 7. The Beckmann reaction of erythromycin-E-oxime was initially reported (ref 3a) to give the 6,9-iminoether exclusively (via trapping of the cationic intermediate by the 6-OH.) Although a subsequent paper (ref 3c) reported a low temperature variation that produced a mixture of the 6,9-and 9,11-iminoethers, it was apparent that trapping by the 6-OH was most facile, and the consequences of blocking it were uncertain.
12. 8. This is again contrary to the report regarding erythromycin-E-oxime, where this set of conditions gave formation of the macrolactam. Our results do, however, parallel those seen for the reaction of erythromycin-Z-oxime (ref 5).
13. 9. Our results here parallel Yang's observation (ref 3c) that the erythromycin-derived 9,11-iminoether is susceptible to lower pressure hydrogenation (50 psi) than that required for hydrogenation of the isomeric 6,9-iminoether (1500 psi).
14. 10. That the 90/10 mix of E/Z oxime is in fact the equilibrium ratio was verified by submitting a sample of purified Z-oxime to the reaction conditions, and observing after several days the same 90/10 mix of E/Z.