Oxazolidinone antibacterial agents. An enantioselective synthesis of the [6,5,5] tricyclic fused oxazolidinone ring system and application to the synthesis of a rigid DuP 721 analogue

Journal of Organic Chemistry

Volumn 61, Issue 18, 1996, Pages 6470-6474

  Glave, D Mark ^a   Brickner, Steven J ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; OXAZOLIDINONE DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS;

EID: 0029790883     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo960945s     Document Type: Article

References (24)

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2. (b) Barbachyn, M. R..; Hutchinson, D. K.; Brickner, S. J.; Cynamon, M. H.; Kilburn, J. O.; Klemens, S. P.; Glickman, S. E.; Grega, K. C.; Hendges, S. K.; Toops, D. S.; Ford, C. W.; Zurenko, G. E. J. Med. Chem. 1996, 39, 680.
3. (c) Grega, K. C.; Barbachyn, M. R.; Brickner, S. J.; Miszak, S. A. J. Org. Chem. 1995, 60, 5255.
4. (a) Slee, A. M.; Wunonola, M. A.; McRipley, R. J.; Zajac, I.; Zawada, M. J.; Bartholomew, P. T.; Gregory, W. A.; Forbes, M. Antimicrob. Agents Chemother. 1987, 31, 1791.
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7. (a) Brickner, S. J.; Manninen, P. R.; Ulanowicz, D. A.; Lovasz, K. D.; Rohrer, D. C. 206th ACS National Meeting, Chicago, II., August 22-27, 1993. Abst. Pap. Am. Chem. Soc. 206 (1-2).
8. (b) Brickner, S. J. U. S. Patent 5,231,188, Jul 27, 1993.
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10. The most active aryl analog was that having a 3-pyridyl appendage. This compound was equipotent to vancomycin in vivo.
11. (a) Johnson, R. A.; Sharpless, K. B. in Comprehensive Organic Synthesis ed. Trost, B. M. Pergamon Press: New York, 1991; Vol. 7, Chapter 3.2.
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15. Isolated yields of the cis olefin 10Z were often only 40-50%. This was due to partial isomerization of the olefin upon silica gel or on prolonged storage. It isomerized fairly readily to an inseparable mixture, presumed to be the trans α,β-unsaturated ester and the transstyrene. To circumvent this, the ester 10 was immediately reduced to 11 with DIBALH.
16. Yoon, N. M.; Gyoung, Y. S. J. Org. Chem. 1985, 50, 2443.
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18. 2OH, 83% yield, 91% ee).
19. Ward, D. E.; Rhee, C. K. Tetrahedron Lett. 1991, 49, 7165.
20. Baldwin, J. E. J. Chem. Soc. Chem. Commun. 1976, 734.
21. The structure of the [6,5,6] isomer 16 was confirmed by X-ray crystallography (W. Watt and F. Han, Pharmacia & Upjohn, Inc.).
22. The reaction was unsuccessful when KHMDS was used as base. Less than 10% of the desired oxazolidinone was observed. Isolated reaction products seemed to indicate that 6-endo cyclization of the epoxide had occurred.
23. R = 12.0 and 15.4 min.
24. Compound 25 exhibits strong antibacterial activity. It is approximately 2-fold less active than DuP 721.