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Synthesis of gem-difluorinated nucleoside analogues of the liposidomycins and evaluation as MraY inhibitors

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Xu, Xiu-Hua, Trunkfield, Amy E., Bugg, Tim and Qing, Feng-Ling. (2008) Synthesis of gem-difluorinated nucleoside analogues of the liposidomycins and evaluation as MraY inhibitors. Organic & Biomolecular Chemistry, Vol.6 (No.1). pp. 157-161. ISSN 1477-0520

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Official URL: http://dx.doi.org/10.1039/b713068f

Abstract

Two gem-difluoromethylenated nucleoside moieties of liposidomycins, 3 and 4, were designed and synthesized. Compound 3 was assembled from lactol 5 and gem-difluoromethylenated nucleoside 6. In the synthesis of target molecule 4, the coupling of the trichloroacetimidate derivative of gem-difluoromethylenated furanose 7 with nucleoside 8 in the presence of TMSOTf gave the unexpected compound 16 when CH3CN was used as solvent. This results from acetonitrile acting as a nucleophile and participating in the glycosylation reaction. This unusual process may be correlated with the presence of the electron-withdrawing gem-difluoro substituents at the C-2 position of furanose. Compound 3 demonstrated 29% inhibition of MraY at 11.4 mM.

Item Type:

Journal Article

Subjects:

Q Science > QD Chemistry
R Medicine > RS Pharmacy and materia medica

Divisions:

Faculty of Science > Chemistry

Library of Congress Subject Headings (LCSH):

Antiviral nucleosides -- Synthesis, Chemical inhibitors

Journal or Publication Title:

Organic & Biomolecular Chemistry

Publisher:

Royal Society of Chemistry

ISSN:

1477-0520

Official Date:

2008

Dates:

Date	Event
2008	Published

Volume:

Vol.6

Number:

No.1

Number of Pages:

Page Range:

pp. 157-161

Identification Number:

10.1039/b713068f

Status:

Peer Reviewed

Publication Status:

Published

Funder:

Guo jia zi ran ke xue ji jin wei yuan hui (China) (NSFC), China. Jiao yu bu (China. Ministry of Education), Shanghai Municipal Scientific Committee

References:

1 W. G. Struve, R. K. Sinha and F. C. Neuhaus, Biochemistry, 1966, 5,
82.
2 D. S. Boyle and W. D. Donachie, J. Bacteriol., 1998, 180, 6429.
3 L. A. Mitscher, S. P. Pillai, E. J. Gentry and D. M. Shankel, Med. Res.
Rev., 1999, 19, 477.
4 K. Isono, M. Uramoto, H. Kusakabe, K. Kimura, K. Izaki, C. C.
Nelson and J. A. McCloskey, J. Antibiot., 1985, 38, 1617.
5 K. Kimura, Y. Ikeda, S. Kagami, M. Yoshihama, K. Suzuki, H. Osada
and K. Isono, J. Antibiot., 1998, 51, 1099.
6 C. Dini, P. Collette, N. Drochon, J. C. Guillot, G. Lemoine, P.Mauvais
and J. Aszodi, Bioorg. Med. Chem. Lett., 2000, 10, 1839.
7 A. Takatsuki, K. Kawamura, M. Okina, Y. Kodama, T. Ito and G.
Tamura, Agric. Biol. Chem., 1977, 41, 2307.
8 (a) C. Dini, N. Drochon, S. Feteanu, J. C. Guillot, C. Peixoto and
J. Aszodi, Bioorg. Med. Chem. Lett., 2001, 11, 529; (b) C. Dini, N.
Drochon, J. C. Guillot, P. Mauvais, P. Walter and J. Aszodi, Bioorg.
Med. Chem. Lett., 2001, 11, 533; (c) C. Dini, S. Didier-Laurent, N.
Drochon, S. Feteanu, J. C. Guillot, F. Monti, E. Uridat, J. Zhang and
J. Aszodi, Bioorg. Med. Chem. Lett., 2002, 12, 1209.
9 (a) Organofluorine Chemistry: Principles and Commerical Applications,
ed. R. E. Banks, B. E. Smart and J. C. Tatlow, Plenum, New York,
1994; (b) J. T. Welch, S. Eswaraksrishnan, Fluorine in Bioorganic
Chemistry,Wiley, New York, 1991; (c) Biomedical Frontiers of Fluorine
Chemistry (ACS Symposium Series 639), ed. I. Ojima, J. R. McCarthy
and J. T. Welch, American Chemical Society, Washington, DC, 1996;
(d) Organofluorine Chemicals and Their Industrial Applications, ed.
R. E. Banks, Ellis Harwood, New York, 1979; (e) R. Peters, Carbon-
Fluorine Compounds: Chemistry, Biochemistry and Biological Activities.
A Ciba Foundation Symposium, Elsevier, Amsterdam, 1972.
10 L. Pauling, The Nature of the Chemical Bond, 3rd edn, Cornell
University Press, Ithaca, NY, 1960, p. 93.
11 (a) L. W. Hertel, J. S. Kroin, J. W. Missner and J. M. Tustin, J. Org.
Chem., 1988, 52, 2406; (b)W. Plunkett,V. Gandhi,C.Chubb,B.Nowak,
V. Heinemann, S. Mineishi, A. Sen, L. W. Hertel and G. B. Grindey,
Nucleosides Nucleotides, 1989, 8, 775; (c) V. W. T. Ruiz, V. Haperen,
G. Veerman, J. B. Vermorken and G. J. Peters, Biochem. Pharmacol.,
1993, 46, 762.
12 X.-H. Xu, X.-L. Qiu, X.-G. Zhang and F.-L. Qing, J. Org. Chem., 2006,
71, 2820.
13 M. Cornia,M.Menozzi, E.Ragg, S. Mazzini, A. Scarafoni, F. Zanardic
and G. Casiraghi, Tetrahedron, 2000, 56, 3977.
14 (a)W. J.Middleton, J. Org. Chem., 1975, 40, 574; (b)M. Hudlicky, Org.
React., 1988, 35, 513.
15 (a) K. Biggadike, A. D. Borthwick, D. Evans, A. M. Exall, B. E.
Kirk, S. M. Roberts, L. Stephenson, P. Youds, A. M. Z. Slawin and
D. J. Williams, J. Chem. Soc., Chem. Commun., 1987, 251; (b) A. D.
Borthwick, D. N. Evans, B. E. Kirk, K. Biggadike, A. M. Exall, P.
Youds, S.M. Roberts, D. J. Knight and J. A. V. Coates, J. Med. Chem.,
1990, 33, 179.
16 (a) L. P. Kotra, Y. Xiang, M. G. Newton, R. F. Schinazi, Y.-C. Cheng
and C. K. Chu, J. Med. Chem., 1997, 40, 3635; (b) L. P. Kotra, M. G.
Newton and C. K. Chu, Carbohydr. Res., 1998, 306, 69; (c) W. Zhou,
G. Gumina, Y. Chong, J.-N. Wang, R. F. Schinazi and C. K. Chu,
J. Med. Chem., 2004, 47, 3399; (d) X.-G. Zhang, H.-R. Xia, X.-C.
Dong, J. Jin, W.-D. Meng and F.-L. Qing, J. Org. Chem., 2003, 68,
9026.
17 M. Ebner and A. E. St ¨ utz, Carbohydr. Res., 1998, 305, 331.
18 (a) S. Mehta, M. Meldal, V. Ferro, J. Ø. Duus and K. Bock, J. Chem.
Soc., Perkin Trans. 1, 1997, 1365; (b) J. Wang, J. Li, D. Tuttle, J. Y.
Takemoto and T. C.-W. Chang, Org. Lett., 2002, 4, 3997; (c) B. Elchert,
J. Li, J. Wang, Y. Hui, R. Rai, R. Ptak, P.Ward, J. Y. Takemoto,M.
Bensaci and C.-W. T. Chang, J. Org. Chem., 2004, 69, 1513.
19 S.-J. Deng, B. Yu, Y.-Z. Hui, H. Yu and X.-W. Han, Carbohydr. Res.,
1999, 317, 53.
20 C. G. Boojamra, R. C. Lemoine, J. C. Lee, R. L´eger, K. A. Stein, N. G.
Vernier, A. Magon, O. Lomovskaya, P. K. Martin, S. Chamberland,
M. D. Lee, S. J. Hecker and V. J. Lee, J. Am. Chem. Soc., 2001, 123,
870.
21 R. R. Schmidt, M. Behrendt and A. Toepfer, Synlett, 1990, 694.
22 S. P. Vincent, M. D. Burkart, C.-Y. Tsai, Z. Zhang and C.-H. Wong,
J. Org. Chem., 1999, 64, 5264.
23 E. Breukink, H. E. van Heusden, P. J. Vollmerhaus, E. Swiezewska, L.
Brunner, S. Walker, A. J. R. Heck and B. de Kruijff, J. Biol. Chem.,
2003, 278, 19898.
24 P. E. Brandish, M. Burnham, J. T. Lonsdale, R. Southgate, M. Inukai
and T. D. H. Bugg, J. Biol. Chem., 1996, 271, 7609.
25 S. Ha, D. Walker, Y. Shi and S. Walker, Protein Sci., 2000, 9, 1045.