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Volumn 9, Issue 18, 2007, Pages 3523-3525

A practical, enantioselective synthetic route to a key precursor to the tetracycline antibiotics

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; PRODRUG; TETRACYCLINE;

EID: 34548542101     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol071377d     Document Type: Article
Times cited : (66)

References (30)
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    • Myers, A. G.; Charest, M. G.; Lerner, C. D.; Brubaker, J. D.; Siegel, D. R. Synthesis of Tetracyclines and Analogues Thereof. PCT/US05/ 17831, May 20. 2005.
    • (a) Myers, A. G.; Charest, M. G.; Lerner, C. D.; Brubaker, J. D.; Siegel, D. R. Synthesis of Tetracyclines and Analogues Thereof. PCT/US05/ 17831, May 20. 2005.
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    • Myers, A. G. PCT/US07/66253, April 6, 2007.
    • (b) Myers, A. G. PCT/US07/66253, April 6, 2007.
  • 8
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    • The Muxfeldt route to the tetracyclines (involving late-stage C- and D-ring constructions) was used to synthesize a number of analogs, and was scaled to provide (±)-6-thiatetracycline for early clinical trials (discontinued due to an apparent CNS-based toxicity), (a) Cunha, B. A. Clinical Uses of the Tetracyclines. In Handbook of Experimental Pharmacology; Hlavka, J. J., Boothe, J. H., Eds.; Springer-Verlag: New York, 1985; 78, p 393.
    • The Muxfeldt route to the tetracyclines (involving late-stage C- and D-ring constructions) was used to synthesize a number of analogs, and was scaled to provide (±)-6-thiatetracycline for early clinical trials (discontinued due to an apparent CNS-based toxicity), (a) Cunha, B. A. Clinical Uses of the Tetracyclines. In Handbook of Experimental Pharmacology; Hlavka, J. J., Boothe, J. H., Eds.; Springer-Verlag: New York, 1985; Vol. 78, p 393.
  • 9
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    • Nelson, M, Hillen, W, Greenwald, R. A, Eds, Birkhäuser Verlag: Boston, MA
    • (b) Tetracyclines in Biology, Chemistry, and Medicine; Nelson, M., Hillen, W., Greenwald, R. A., Eds.; Birkhäuser Verlag: Boston, MA, 2001; p 237.
    • (2001) Tetracyclines in Biology, Chemistry, and Medicine , pp. 237
  • 12
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    • Use of lithium N-methylephedrate for the enantioselective addition of 1-alkenylzinc bromides to aldehydes: Oppolzer, W.; Radinov, R. N. Tetrahedron Lett 1991, 32, 5777.
    • (a) Use of lithium N-methylephedrate for the enantioselective addition of 1-alkenylzinc bromides to aldehydes: Oppolzer, W.; Radinov, R. N. Tetrahedron Lett 1991, 32, 5777.
  • 13
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    • Synthesis of dialkylzinc reagents by addition of Grignard, reagents to zinc chloride followed by precipitation with 1,4-dioxane: von dem Bussche-Hünnefeld, J. L.; Seebach, D. Tetrahedron 1992, 48, 5719.
    • (b) Synthesis of dialkylzinc reagents by addition of Grignard, reagents to zinc chloride followed by precipitation with 1,4-dioxane: von dem Bussche-Hünnefeld, J. L.; Seebach, D. Tetrahedron 1992, 48, 5719.
  • 14
    • 0001064329 scopus 로고    scopus 로고
    • Use of (1S,2R)-2-morpholin-4-yl-lphenylpropanol for the enantioselective addition of diisopropylzinc to aldehydes: Soai, K.; Hayase, T.; Takai, K.; Sugiyama, T. J. Org. Chem. 1994, 59, 7908.
    • (c) Use of (1S,2R)-2-morpholin-4-yl-lphenylpropanol for the enantioselective addition of diisopropylzinc to aldehydes: Soai, K.; Hayase, T.; Takai, K.; Sugiyama, T. J. Org. Chem. 1994, 59, 7908.
  • 15
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    • Synthesis of (lS,2R)-2-pyrrolidiny-l-phenylpropanol by alkylation of norephedrine with 1,4-dibromobutane: Pierce, M. E. et al. J. Org. Chem. 1998, 63, 8536.
    • (d) Synthesis of (lS,2R)-2-pyrrolidiny-l-phenylpropanol by alkylation of norephedrine with 1,4-dibromobutane: Pierce, M. E. et al. J. Org. Chem. 1998, 63, 8536.
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    • Furan 2-carboxaldehydes: (a) Noyori, R.; Suga, S.; Kawai, K.; Okada, S.; Kitamura, M.; Oguni, N.; Hayashi, M.; Kaneko, T.; Matsuda, Y. J. Organomet. Chem. 1990, 382, 19.
    • Furan 2-carboxaldehydes: (a) Noyori, R.; Suga, S.; Kawai, K.; Okada, S.; Kitamura, M.; Oguni, N.; Hayashi, M.; Kaneko, T.; Matsuda, Y. J. Organomet. Chem. 1990, 382, 19.
  • 22
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    • Prepared by Villsmeier-Haack formylation (Jones, G.; Stanforth, S. P. Org. React. 1997, 49, 1) of 3-methoxyfurfural, synthesized in hundredgram amounts-without chromatography-in four steps from 3-chloro-l,2propanediol:
    • Prepared by Villsmeier-Haack formylation (Jones, G.; Stanforth, S. P. Org. React. 1997, 49, 1) of 3-methoxyfurfural, synthesized in hundredgram amounts-without chromatography-in four steps from 3-chloro-l,2propanediol:
  • 24
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    • Allylic metalation (removal of the proton a to the dimethylamino group) is competitive with metalation of the isoxazole ring at higher temperatures and it is the predominant reaction pathway when bases other than n-butyllithium are used for deprotonation. A preliminary experiment with the 4-iodoisoxazole 9 (see Supporting Information) reveals that magnesium-halogen exchange at -20°C provides an efficient means of anion formation; trapping with 3-methoxyfurfural (6) gives a higher proportion of the (S)-alcohol 7. Magnesium-halogen exchange: (a) Wakefield, B. J. Preparation of Organomagnesium Compounds. In Organomagnesium Compounds in Organic Synthesis; Academic Press, Inc.: San Diego, 1995; pp 51-59.
    • Allylic metalation (removal of the proton a to the dimethylamino group) is competitive with metalation of the isoxazole ring at higher temperatures and it is the predominant reaction pathway when bases other than n-butyllithium are used for deprotonation. A preliminary experiment with the 4-iodoisoxazole 9 (see Supporting Information) reveals that magnesium-halogen exchange at -20°C provides an efficient means of anion formation; trapping with 3-methoxyfurfural (6) gives a higher proportion of the (S)-alcohol 7. Magnesium-halogen exchange: (a) Wakefield, B. J. Preparation of Organomagnesium Compounds. In Organomagnesium Compounds in Organic Synthesis; Academic Press, Inc.: San Diego, 1995; pp 51-59.
  • 26
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    • After 105 h at 95 °C cyclization of the (S)-alcohol 7 had proceeded to 89% conversion whereas cyclization of the (R)-alcohol 7 had proceeded to 77% conversion.
    • After 105 h at 95 °C cyclization of the (S)-alcohol 7 had proceeded to 89% conversion whereas cyclization of the (R)-alcohol 7 had proceeded to 77% conversion.
  • 30
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    • 1
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* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.