Resin 23
NMR (CDCl3) d major isomer −105.0 (s, 1F, 4-FPhCO2), −104.5
(s, 1F, 4-FPhCO2), −113.5 (s, 1F, 3-FPhHCO2), −144.6 (s, 1F,
linker F); minor isomer −105.7 (s, 1F, 4-FPhCO2), −106.0 (s, 1F,
4-FPhCO2), −113.2 (s, 1F, 3-FPhHCO2), −145.0 (s, 1F, linker F).
Resin 21 (302 lmol), glycosyl donor 22 (387 mg, 608 lmol) and
NIS (140 mg, 622 lmol) were dried under vacuum overnight in the
absence of light. Distilled CH2Cl2 (4 ml) was added, followed by
TfOH (1 ll, 0.01 mmol). The mixture was agitated mechanically
for 3.5 h in the absence of light. The resin was washed with CH2Cl2,
THF, piperidine (20% in DMF), DMF, and CH2Cl2 (3 × 15 ml
each). Gel-phase 19F NMR spectroscopy indicated that resin 23
was prepared in a yield of 89%. 19F NMR (CDCl3) d −105.1,
−105.4, −108.6, −113.4 and −144.5.
2,3-Di-O-p-fluorobenzoyl-4,6-O-m-fluorobenzylidene-D-galactose
(28)
The resin 27 (0.060 mmol) was treated with 5% TFA in CH2Cl2 for
7 h. The filtrate was washed with CH2Cl2 and the procedure was
repeated. After extensive washing with CH2Cl2 the filtrates were
combined and concentrated. Preparative LC-MS gave 15.4 mg 28
(58% total yield based on Fmoc determination of the linker resin
16). According to NMR spectroscopy two isomers were formed
with the ratio 3.8 : 1. 1H NMR (CDCl3) d 8.11–7.99 (m, 4H, ArH),
7.42–7.24 (m, 3H, ArH), 7.14–7.04 (m, 5H, ArH); major isomer
5.87 (dd, 3.4, 1H, J = 3.4, 10.6, H-3), 5.33–5.75 (m, 2H, H-2, H-1),
5.59 (s, 1H, 3-FPhCHO2), 4.68 (d, 1H, J = 3.3, H-4), 4.36 (dd, 1H,
J = 1.2, 12.5, H-6), 4.23–4.15 (m, 2H, H-5, H-6); minor isomer
5.66 (dd, 1H, J = 8.0, 10.3, H-2), 5.60 (s, 1H, 3-FPhCHO2), 5.49
(dd, 1H, J = 3.6, 10.4, H-3), 4.61 (d, 1H, J = 3.4, H-4), 4.48 (dd,
1H, J = 1.4, 12.4, H-6), 3.77 (s-br, 1H, J = 10.2, H-5); 19F NMR
(CDCl3) d major isomer −105.1 (s, 1F, 4-FPhCO2), −105.2 (s, 1F,
4-FPhCO2), −113.6 (s, 1F, 3-FPhHCO2); minor isomer −104.7
(s, 1F, 4-FPhCO2), −104.8 (s, 1F, 4-FPhCO2), −113.5 (s, 1F, 3-
FPhCHO2); 13C NMR (CDCl3) d 99.9, 91.5, 74.4, 69.3, 69.1, 68.9,
62.4; HRMS (FAB) calcd form C27H21F3NaO8 553.4358 (M +
Na)+, found 553.1089.
4-Fluorobenzoyl-L-glycyl-O-(b-D-galactopyranosyl)-L-seryl-L-
valine (25)
A solution of TFA in H2O (9 : 1, 10 ml) was added to resin 23
(150 lmol). The mixture was agitated mechanically at room tem-
perature for 2 h. The resin was removed by filtration and washed
with H2O, THF and CH2Cl2. The filtrate was concentrated.
Preparative HPLC yielded the partially deprotected glycopeptide
24 (34 mg, 29%). 24 was dissolved in MeOH (5 ml) and aqueous
LiOH (0.81 ml, 0.1 M) was added dropwise. After 1 h the solution
was neutralized with AcOH, concentrated, diluted with AcOH
(2 ml), and lyophilized. Preparative HPLC yielded 25 (10.8 mg,
47%) with analytical data in agreement with those previously
reported15 except for the data for the galactose hydrogens H-1 to
H-4 which instead should be as follows. 1H NMR (DMSO-d6) Gal:
4.15–4.12 (m, 1H, J = 9.2, H-1), 3.97–3.93 (m, 1H, H-4), 3.64–
3.62 (m, 1H, H-3), 3.31–3.28 (m, 1H, H-2) 19F NMR (DMSO-d6)
d −109.2.
Acknowledgements
This work was supported by the Swedish Research Council. We
thank Johan Vestergren for practical assistance.
Resin 26
Resin 1 (0.120 mmol) and the glycosyl donor 22 (0.305 g, 0.479
mmol) were put under vacuum for one hour followed by addition
of NIS (0.102 g, 0.453 mmol) in the absence of light. Distilled
CH2Cl2 (4 ml) and a catalytic amount of TfOH were added. The
mixture was stirred at room temperature for 3.5 h in the absence of
light. The resin was washed with CH2Cl2, THF, 20% piperidine in
Notes and references
1 G. B. Fields, Z. Tian and G. Barany, in Synthetic Peptides: A User’s
Guide, ed. G. A. Grant, W. H. Freeman and Company, New York,
1992, pp. 77–183.
2 M. H. Caruthers, Science, 1985, 230, 281–285.
3 P. H. Seeberger and W.-C. Haase, Chem. Rev., 2000, 100, 4349–4393.
4 A. Svensson, K.-E. Bergquist, T. Fex and J. Kihlberg, Tetrahedron Lett.,
1998, 39, 7193–7196.
5 J. M. Salvino, N. V. Kumar, E. Orton, J. Airey, T. Kiesow, K. Crawford,
R. Mathew, P. Krolikowski, M. Drew, D. Engers, D. Krolikowski, T.
Herpin, M. Gardyan, G. McGeehan and R. Labaudiniere, J. Comb.
Chem., 2000, 2, 691–697.
DMF, DMF, and CH2Cl2 (3 × 15 ml). According to gel-phase 19
F
NMR spectroscopy the yield was 100% and only one isomer was
formed. 19F NMR (CDCl3) d −105.0 (s, 1F, 4-FPhCO2), −105.4
(s, 1F, 4-FPhCO2), −113.5 (s, 1F, 3-FPhCHO2), −134.0 (s, 1F,
linker F).
6 A. Svensson, T. Fex and J. Kihlberg, J. Comb. Chem., 2000, 2, 736–748.
7 M. Mogemark, M. Elofsson and J. Kihlberg, Org. Lett., 2001, 3, 1463–
1466.
8 Y. Pan and C. P. Holmes, Org. Lett., 2001, 3, 2769–2771.
9 Y. Pan, B. Ruhland and C. P. Holmes, Angew. Chem., Int. Ed., 2001,
40, 4488–4491.
Resin 27
Resin 15 (0.120 mmol) and the glycosyl donor 22 (0.301 g, 0.473
mmol) were put under vacuum for 1 h followed by addition of NIS
(0.108 g, 0.480 mmol) in the absence of light. Distilled CH2Cl2
(4 ml) and TfOH (1.0 M in CH2Cl2, 0.017 mmol, 17 lmol) were
added. The mixture was stirred at room temperature for 4 h in
absence of light. The resin was washed with CH2Cl2, THF, 20%
piperidine in DMF, DMF and CH2Cl2 (3 × 15 ml). According
to gel-phase 19F NMR spectroscopy the yield was ∼40%. When
the glycosylation was repeated with glycosyl donor 22 (0.153 g,
0.240 mmol), NIS (0.051 g, 0.227 mmol) and catalytic amount
of TfOH (1.0 M in CH2Cl2, 0.017 mmol, 17 lmol) for 2 h, the
yield was increased to 63%. According to gel-phase 19F NMR
spectroscopy two isomers were formed with the ratio 1 : 10. 19F
10 J. M. Salvino, S. Patel, M. Drew, P. Krowlikowski, E. Orton, N. V.
Kumar, T. Caulfield and R. Labaudiniere, J. Comb. Chem., 2001, 3,
177–180.
˚
11 H. Emtena¨s, K. Ahlin, J. S. Pinkner, S. J. Hultgren and F. Almqvist,
J. Comb. Chem., 2002, 4, 630–639.
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1266–1269.
13 M. Mogemark, M. Elofsson and J. Kihlberg, J. Org. Chem., 2003, 68,
7281–7288.
14 M. Mogemark, L. Gustafsson, C. Bengtsson, M. Elofsson and J.
Kihlberg, Org. Lett., 2004, 6, 4885–4888.
15 M. Mogemark, F. Ga˚rdmo, T. Tengel, J. Kihlberg and M. Elofsson,
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2470 | Org. Biomol. Chem., 2007, 5, 2464–2471
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