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(a)For other heterocyclic replacements of the tetrahydropyranyl sidechain, see: Kaneko S., Arai M., Uchida T., Harasaki T., Fukuoka T., Konosu T. Bioorg. Med. Chem. Lett. 12:2002;1705
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(a) Amino alcohols were commercially available or prepared from the corresponding epoxide. For example, see: Schaus S.E., Larrow J.F., Jacobsen E.N. J. Org. Chem. 62:1997;4197
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Amino alcohols were commercially available or prepared from the corresponding epoxide. For example, see:
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(a) Coteron J.M., Chiara J.L., Fernandez-Mayoralas A., Fiandor J.M., Valle N. Tetrahedron Lett. 41:2000;4373
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The greater nucleophilicity of β-alkoxide pyranose anions has been elegantly demonstrated by Schmidt; see: We are grateful to a referee for bringing this reference to our attention
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The greater nucleophilicity of β-alkoxide pyranose anions has been elegantly demonstrated by Schmidt; see: Schmidt R. Angew. Chem., Int. Ed. Engl. 25:1986;212. We are grateful to a referee for bringing this reference to our attention.
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Schmidt, R.1
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85031200107
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+): 534.2986; found 534.2987.
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0035135564
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The exceptional MIC observed with several analogues versus C. neoformans and Asp. fumigatus is interesting in light of recent studies which suggest that EF-2 in these fungi should not be susceptible to sordarin derivatives. See:
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(a) The exceptional MIC observed with several analogues versus C. neoformans and Asp. fumigatus is interesting in light of recent studies which suggest that EF-2 in these fungi should not be susceptible to sordarin derivatives. See: Shastry M., Nielsen J., Ku T., Hsu M., Liberator P., Anderson J., Schmatz D., Justice M.C. Microbiology. 147:2001;383
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Justice, M.C.8
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23
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85031204509
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The anomeric configuration of 7g was established by X-ray crystallography of the corresponding morpholine precursor 6. The α-anomer of compound 7g was considerably less active against all pathogens tested (C. albicans MIC=0.5 μg/mL; C. glabrata MIC=4 μg/mL; all others > 16 μg/mL).
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Although 7a exhibited high total body clearance after iv administration, the oral bioavailability was 100%, which may be attributed to the rapid absorption of 7a and the resulting saturation of first-pass liver metabolism.
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