COMMUNICATIONS
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Ed. Engl. 1986, 25, 212 ± 235, and references therein.
Experimental Section
[3] a) S. Hakamori, Annu. Rev. Biochem. 1981, 50, 733 ± 764, and
references therein.
[4] J. Montreuil, Adv. Carbohydr. Chem. Biochem. 1980, 37, 157 ± 223.
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Nature (London) 1985, 314, 53 ± 57.
The experimental data of the threonine derivates 10, 14, and 17 only are
presented as examples. The NMR data have been assigned from 1H, 13C,
APT, H,H-COSY, and HMQC spectra.
10: HFA-Thr 6,[15] (2 mmol, 534 mg), 2,3,4,6-tetra-O-acetyl-b-d-glucopyr-
anosyl trichloroacetimidate (2 mmol, 984 mg) and BF3 ´ Et2O (1 mmol,
142 mg, 125 mL) were stirred at room temperature in anhydrous CH2Cl2
(20 mL) for 1 h. H2O (10 mL) and CH2Cl2 (20 mL) were added, and the
resulting mixture was stirred vigorously for an additional 5 min. The
organic layer was separated, dried (MgSO4), and the solvent was removed
in vacuo. The residue was purified by flash chromatography on silica gel
(toluene/ethyl acetate, 5/1). Yield: 1 g (68%), amorphous solid; m.p. 112 ±
[6] C. M. Taylor, Tetrahedron 1998, 54, 11317 ± 11362, and references
therein.
[7] a) J. Kihlberg, J. hman, B. Walse, T. Drakenberg, A. Nilsson, C.
Söderberg-Ahlm, B. Bengtsson, H. Olsson, J. Med. Chem. 1995, 38,
161 ± 169; b) M. F. Powell, T. Stewart, L. Otvos, Jr., L. Urge, F. C. A.
Gaeta, A. Sette, T. Arrhenius, D. Thomson, K. Soda, S. M. Colon,
Pharm. Res. 1993, 10, 1268 ± 1273.
1138C; IR (KBr): nÄ 1830, 1750 cm 1; MS (70 eV): m/z: 597.42 [M ];
[8] J. F. Fisher, A. W. Harrison, G. L. Bundy, K. F. Wilkinson, B. D.Rush,
M. J. Ruwart, J. Med. Chem. 1991, 34, 3140 ± 3143.
1H NMR (CDCl3): d 1.38 (d, J 6.5 Hz, 3H), 2.01 (s, 3H), 2.02 (s, 3H),
2.06 (s, 3H), 2.07 (s, 3H), 3.66 ± 3.76 (m, 3H), 4.06 ± 4.13 (m, 2H), 4.22 (dd,
J 12.5 Hz, 4.2 Hz, 1H), 4.57 (d, J 8.0 Hz, 1H), 4.95 (dd, J 9.6 Hz,
8.0 Hz, 1H), 5.09 (dd, J 9.7, 9.7 Hz, 1H), 5.20 (dd, J 9.7, 9.6 Hz, 1H);
13C NMR (CDCl3): d 18.1, 20.4, 20.5, 20.8, 59.9, 61.3, 68.0, 71.2, 72.2, 72.6,
75.7, 89.3 (qq, J 34, 34 Hz), 100.2, 120.2 (q, J 286 Hz), 121.1 (q, J
287 Hz), 169.2, 169.3, 169.4, 170.2, 170.7; 19F NMR (CDCl3): d 0.94 (q,
J 8.6 Hz, 3F), 2.89 (q, J 8.6 Hz, 3F).
[9] a) ¹Glycopeptide Synthesesª: M. Meldal in Neoglycoconjugates:
Preparation and Applications (Eds.: Y. C. Lee, K. T. Lee), Academic
Press, San Diego, 1994, p. 145 ± 198, and references cited therein; b) H.
Kunz, W. K.-D. Brill, Trends Glycosci. Glycotechnol. 1992, 4, 71 ± 82;
c) H. Kunz, Angew. Chem. 1987, 99, 297 ± 311, Angew. Chem. Int. Ed.
Engl. 1987, 26, 294 ± 308, and references therein.
Â
[10] R. E. Rodriguez, F. D. Rodriguez, M. P. Sacristan, J. L. Torres, G.
14: HFA-Thr(TAcGlc) 10 (1 mmol, 597 mg) and l-phenylalanine amide
(1 mmol, 164 mg) were stirred at room temperature in anhydrous ethyl
acetate (20 mL) for 3 d (reaction control by 19F NMR spectroscopy). The
solvent was removed in vacuo and the residue was purified by flash
chromatography on silica gel (CHCl3/MeOH, 8/1). Yield: 403 mg (68%),
amorphous solid; m.p. 75 ± 788C; Mcalcd 595.56, MS (MALDI-TOF): m/z:
Valencia, J. M. Garcia Anton, Neurosci. Lett. 1989, 101, 89 ± 94.
Á
[11] R. Polt, F. Porreca, L. Z. Szabo, E. J. Bilsky, P. Davis, T. J. Abbruscato,
T. P. Davis, R. Horvath, H. Y. Yamamura, V. J. Hruby, Proc. Natl.
Acad. Sci. USA 1994, 91, 7114 ± 7118.
[12] G. Arsequell, G. Valencia, Tetrahedron: Asymmetry 1997, 8, 2839 ±
2876, and references cited therein.
[13] a) M. Schuster, P. Wang, J. C. Paulson, C.-H. Wong, J. Am. Chem. Soc.
1994, 116, 1135 ± 1136; b) G. F. Herrmann, P. Wang, G.-J. Shen, C.-H.
Wong, Angew. Chem. 1994, 106, 1346 ± 1347; Angew. Chem. Int. Ed.
Engl. 1994, 33, 1241 ± 1242.
[14] J. Y. Roberge, X. Beebe, S. J. Danishefsky, Science 1995, 269, 202 ± 203.
[15] a) F. Weygand, K. Burger, K. Engelhardt, Chem. Ber. 1966, 99, 1461 ±
1469; b) S. Fehn, Dissertation, Technische Universität München, 1995.
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Helferich, K.-F. Wedemeyer, Liebigs Ann. Chem. 1949, 562, 139 ± 145.
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Elofson, B. Walse, J. Kihlberg, Tetrahedron Lett. 1991, 32, 7613 ± 7619.
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Chem. Int. Ed. Engl. 1980, 19, 731 ± 732; b) R. R. Schmidt, H. Gaden,
H. Jatzke, Tetrahedron Lett. 1990, 31, 330 ± 333.
618.19 [M Na], 635.25 [M K]; 1H NMR (CD3OD): d 1.12 (d, J
6.5 Hz, 3H), 1.96 (s, 3H), 1.97 (s, 3H), 1.99 (s, 3H), 2.02 (s, 3H), 3.00
(ddABX, J 14, 7.6 Hz, 1H), 3.13 (ddABX, J 14, 5.8 Hz, 1H), 3.28 (d, J
6.5 Hz, 1H), 3.86 (m, 1H), 3.99 (dq, J 5.0, 6.5 Hz, 1H), 4.09 (ddABX, J
12.3, 4.8 Hz, 1H), 4.28 (ddABX, J 12.3, 2.2 Hz, 1H), 4.61 (dd, J 6.0,
8.0 Hz, 1H), 4.73 (d, J 8.0 Hz, 1H), 4.84 (dd, J 8.0, 9.6 Hz, 1H), 4.98
(dd, J 9.6, 9.9 Hz, 1H), 5.26 (dd, J 9.6, 9.6 Hz, 1H), 7.21 ± 7.33 (m, 5H);
13C NMR (CD3OD): d 16.81, 20.52, 20.53, 20.63, 20.65, 38.93, 55.47, 60.25,
63.01, 69.80, 72.83, 72.95, 74.11, 78.91, 100.57, 127.94, 129.54, 130.55, 138.20,
171.17, 171.25, 171.59, 172.37, 174.19, 175.72.
17: HOAt (0.34 mmol, 46.8 mg) and DIC (0.34 mmol, 53.3 mL) were added
subsequently to a solution of Z-Ala-OH (0.34 mmol, 76.7 mg) in CH2Cl2
while stirring at room temperature. A solution of O-(2,3,4,5-tetra-O-acetyl-
b-d-glucopyranosyl)-l-threonyl-l-phenylalanine amide 14 (0.17 mmol,
100 mg) in DMF (1 mL) was then added to the reaction mixture. After
2 h, the reaction mixture was concentrated, the residue was dissolved in
ethyl acetate and then washed three times each with citric acid, saturated
NaHCO3 solution, and water. The organic layer was dried over Na2SO4 and
concentrated. The crude product was purified by flash chromatography on
silica gel (eluent: CHCl3/CH3OH, 10/1). Yield: 101 mg (73%), crystalline
solid; m.p. 1908C, Mcalcd 800.81, MS (MALDI-TOF): m/z: 823.23
[19] P. S. Chen, H. K. Mitchell, M. Neuweg, Insect. Biochem. 1978, 8, 279 ±
286.
[20] L. A. Salvador, M. Elofson, J. Kihlberg, Tetrahedron 1995, 51, 5643 ±
5656.
[21] a) M. Meldal, K. J. Jensen, J. Chem. Soc. Chem. Commun. 1990, 483 ±
485; b) A. M. Jansson, M. Meldal, K. Bock, Tetrahedron Lett. 1990, 31,
6991 ± 6994.
[M Na], 839.12 [M K]; 1H NMR (CD3OD): d 1.12 (d, J 6.2 Hz,
3H), 1.30 (d, J 7.2 Hz, 3H), 1.93 (s, 3H), 1.98 (s, 3H), 2.00 (s, 3H), 2.03 (s,
3H), 3.04 (ddABX, J 14, 7.7 Hz 1H), 3.17 (ddABX, J 14, 5.5 Hz, 1H), 3.90
(m, 1H), 4.07 (ddABX, J 12.3, 5.3 Hz, 1H), 4.14 (m, 1H), 4.16 (m, 1H), 4.28
(ddABX, J 12.3, 5.3 Hz, 1H), 4.45 (d, J 6.2 Hz, 1H), 4.60 (m, 1H), 4.77 (d,
J 8.0 Hz, 1H), 4.85 (dd, J 9.6, 9.6 Hz, 1H), 5.01 (dd, J 9.6, 9.6 Hz, 1H),
5.05/5.10 (dd, J 12.5, 12.5 Hz, 2H), 5.27 (dd, J 9.6, 9.6 Hz, 1H), 7.15 ±
7.35 (m, 10H); 13C NMR (CD3OD): d 16.47, 17.82, 20.53, 20.55, 20.65,
20.70, 38.62, 52.28, 55.75, 58.58, 63.08, 67.81, 69.80, 72.83, 73.17, 74.06, 76.44,
100.84, 127.98, 128.89, 129.03, 129.50, 129.60, 130.49, 138.25, 138.27, 158.50,
171.26, 171.40, 171.58, 172.42, 175.49, 175.87, 176.86.
Received: October 26, 1998 [Z12564IE]
German version: Angew. Chem. 1999, 111, 1513 ± 1515
Keywords: glycopeptides ´ glycosylations
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b) R. A. Dwek, Chem. Rev. 1996, 96, 683 ± 720; c) A. Varki,
Glycobiology 1993, 3, 97 ± 130; d) A. Kobata, Eur. J. Biochem. 1992,
209, 483 ± 501.
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