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K. Jayakanthan, Y. D. Vankar / Tetrahedron Letters 47 (2006) 8667–8671
3. (a) Nishimura, Y.; Satoh, T.; Adachi, H.; Kondo, S.;
Takeuchi, T.; Azetaka, M.; Fukuyasu, H.; Iizuka, Y. J.
Med. Chem. 1997, 40, 2626; (b) Zitzmann, N.; Mehta, A.
For the synthesis of 2-deoxy-2-amino-C-glycosyl ala-
nines 18a and 18b (Scheme 4), we treated compounds
2a and 2b with MsCl and triethylamine followed by det-
ritylation, which gave alcohols 16a and 16b. Replace-
ment of the mesylate group by azide, reduction of the
azido group followed by protection as NHBoc gave
amino alcohols 17a and 17b20 in 85% and 79% yields,
respectively. Oxidation of 17a and 17b using Jones’
reagent gave the corresponding acids, which were ester-
ified using diazomethane. Finally, reduction of the nitro
group with zinc–hydrochloric acid in tetrahydrofuran-
acetic acid to the amine and subsequent protection as
the acetates gave the 2-deoxy-2-amino-C-glycosyl ala-
nines 18a and 18b in 78% and 76% yields, respectively.
The stereochemistry of the C-glycosyl alanines 18a and
18b was confirmed by analyzing the spectra14 of the cor-
responding bicyclic derivatives 4a and 4b (Scheme 1).
´
S.; Carrouee, S.; Butters, T. D.; Platt, F. M.; McCauley,
J.; Blumberg, B. S.; Dwek, R. A.; Block, T. M. Proc. Natl.
Acad. Sci. U.S.A. 1999, 96, 11878.
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B.; Butter, T. D.; Dwek, R. A.; Platt, F. M. J. Biol. Chem.
1993, 268, 570.
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Chem. Soc. 1990, 112, 6137; (b) Heck, M.-P.; Vincent, S.
P.; Murray, B. W.; Bellamy, F.; Wong, C.-H.; Mioskow-
ski, C. J. Am. Chem. Soc. 2004, 126, 1971.
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2405; (c) Nishimura, Y.; Adachi, H.; Satoh, T.; Shitara,
E.; Nakamura, H.; Kojima, F.; Takeuchi, T. J. Org.
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dron Lett. 2005, 46, 3619.
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Deredas, D.; Frankowski, A.; Picasso, S.; Steiner, H.;
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In summary, this letter describes the first example of the
synthesis of the hybrids of nojirimycin d-lactam and pyr-
rolidine with D-galactose and their evaluation against a
variety of enzymes, which has shown them to be a new
class of glycosidase inhibitors. Although the enzyme
inhibition activity is moderate, it may be possible to
improve the same by appropriately changing the struc-
tural features of these molecules. Work in this direction
is being pursued. Additionally, 2-deoxy-2-amino-C-gly-
cosyl glycines and alanines have been synthesized using
a general strategy. This new class of amino acids can be
useful in modifying the properties of certain oligopep-
tides by virtue of the presence of a stable C-glycosidic
linkage at C-1 and an additional amino group at C-2.
10. (a) Krulle, T. M.; de la Fuente, C.; Pickering, L.; Aplin, R.
¨
T.; Tsitsanou, K. E.; Zographos, S. E.; Oikonomakos, N.
G.; Nash, R. J.; Griffiths, R. C.; Fleet, G. W. J.
Tetrahedron: Asymmetry 1997, 8, 3807; (b) Tezuka, K.;
Compain, P.; Martin, O. R. Synlett 2000, 1837.
11. Ermert, P.; Vasella, A.; Weber, M.; Rupitz, K.; Withers, S.
G. Carbohydr. Res. 1993, 250, 113.
12. (a) Tietze, L. F.; Bell, H. P.; Chadrasekhar, S. Angew.
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Chem. Soc. Rev. 2002, 31, 324.
Acknowledgements
We thank the Department of Science and Technology,
New Delhi, for financial support (Grant No. SP/S1/
G-21/2001). One of us (K.J.) thanks IIT Kanpur, for a
senior research fellowship.
13. Reddy, B. G.; Vankar, Y. D. Angew. Chem., Int. Ed. 2005,
44, 2001.
14. See the Supplementary data.
15. (a) We thank the referee to make this point and to advise
us to cite the following two references; (b) Cha, J. K.;
Christ, W. J.; Kishi, Y. Tetrahedron 1984, 40, 2247;
(c) Haller, J.; Strassner, T.; Houk, K. N. J. Am. Chem.
Soc. 1997, 119, 8031.
Supplementary data
16. Dondoni, A.; Marra, A. Chem. Rev. 2000, 100, 4395.
17. Jayakanthan, K.; Vankar, Y. D. Org. Lett. 2005, 7, 5441.
18. (a) Werner, R. M.; Williams, L. M.; Davis, J. T.
Tetrahedron Lett. 1998, 39, 9135; (b) Burkhart, F.;
Hoffmann, M.; Kessler, H. Angew. Chem., Int. Ed. 1997,
36, 1191; (c) Koviach, J. L.; Chappel, M. D.; Halcomb, R.
L. J. Org. Chem. 2001, 66, 2318; (d) Dondoni, A.;
Mariotti, G.; Marra, A.; Massi, A. Synthesis 2001, 2129;
(e) Knapp, S.; Myers, D. S. J. Org. Chem. 2002, 67, 2995;
(f) Westermann, B.; Walter, A.; Diedrichs, N. Angew.
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Supplementary data (detailed experimental procedures
and 1H and 13C NMR spectra of the compounds synthe-
sized) associated with this article can be found, in the
References and notes
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20. Compounds 14a and 17b, obtained from mesylates 13a
and 16b by reacting with NaN3, were converted to the
corresponding cyclic compounds 19 and 20 (see the
Supplementary data), respectively, whose spectral data