Synthesis of 2-fluoro-6-O-propargyl-11,12-carbamate ketolides. A novel class of antibiotics

Organic Letters

Volumn 2, Issue 19, 2000, Pages 2951-2954

  Phan, Ly T ^a   Clark, Richard F ^a   Rupp, Michael ^a   Or, Yat Sun ^a   Chu, Daniel T W ^a   Ma, Zhenkun ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; DRUG DERIVATIVE; ERYTHROMYCIN;

ARTICLE; CHEMISTRY; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

ANTI-BACTERIAL AGENTS; CRYSTALLOGRAPHY, X-RAY; ERYTHROMYCIN;

EID: 0034699267     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol006226o     Document Type: Article

References (26)

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11. (a) Denis, A.; Agouridas, C.; Auger, J.-F.; Benedetti, Y.; Bonnefoy, A.; Bretin, F.; Chantot, J.-F.; Dussarat, A.; Fromentin, C.; D'Ambrieres, S. G.; Lachaud, S.; Laurin, P.; Le Martret, O.; Loyau, V.; Tessot, N.; Pejac, J. M.; Perron, S. Bioorg. Med. Chem. Lett. 1999, 9, 3075-3080.
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14. 2′-O-Benzoate was also prepared and carried through the synthetic sequence with similar result.
15. C10-epimers also observed in other macrolide systems: (a) Baker, W. R.; Clark, J. D.; Stephens, R. L.; Kim, K. H. J. Org. Chem. 1988, 53, 2340-2345.
16. (b) Griesgraber, G.; Or, Y. S.; Chu, D. T. W.; Nilius, A. M.; Johnson, P. M.; Flamm, R. K.; Henry, R. F.; Plattner, J. J. J. Antibiot. 1996, 49, 465-477.
17. Corey, E. J.; Kim, C. U.; Misco, P. F. Org. Synth. 1978, 58, 122-126.
18. For the synthesis of 8-chloropyridone, see: (a) Li, Q.; Chu, D. T. W.; Claiborne, A.; Cooper, C.; Lee, C. M.; Raye. K.; Berst, K.; Pamela, D.; et. al. J. Med. Chem. 1996, 39. 3070-3080.
19. (b) Klein, L. L.; DeGoey, D. A.; Thomas, S. A.; Yeung, C. M.; Leone, C. L.; Grampovnik, D.; Lartey, P. A. Bioorg. Med. Chem. Lett. 1997, 1167.
20. Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahetron Lett. 1975, 50, 4467-4470.
21. Excess fluorinating agent resulted in N-demethylation of the desosamine nitrogen.
22. Related fluorination chemistry at the C2 position of ketolides has been reported: (a) Phan, L. T.; Or, Y. S.; Chen, Y.; Chu, D. T. W.; Ewing, P.; Nilius, M. B.; Raney, P.; Hensey-Rudloff, D.; Henry, R. F.; Mitten, M.; Plattner, J. J. Presented at the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, Sept 24-27, 1998; Abstr. No. F-127.
23. (b) Denis, A.; Agouridas, C.; Bonnefoy, A.; Bretin, F.; Fromentin, C.; Bonnet, A. Presented at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, CA, Sept 26-29, 1999; Abstr. No. F-2152.
24. The C2-H analogues of 11d and 11e have also been prepared by coupling with 7 without intramolecular cyclization problems. Only products that were prone to Michael addition were susceptible toward intramolecular cyclization.
25. With the 2′-O-benzoate protecting group, the deprotection occurred in MeOH at room temperature with a longer reaction time, 1-3 days, or at reflux in 3-4 h.
26. The starting material has a 2′-O-benzoate protecting group in place of the 2′-O-acetate.