C, 55.79; H, 6.30; N, 4.14. C31H42N2O14 requires C, 55.85; H,
6.35; N, 4.20%); δH (300 MHz; CDCl3) 1.43 (9H, s, C(CH3)3),
1.91–2.27 (16H, m, C(O)CH3, CβH2, CγH2), 4.09 (3H, m, C5H,
C6H2), 4.32 (1H, m, CαH ), 5.09–5.27 (5H, m, C1H, C2H, C3H,
ArCH2), 5.33 (1H, br d, BocNH ), 5.44 (1H, d, C4H ), 6.62
(1H, br d, C1NH ), 7.32 (5H, m, ArH ); δC (75.5 MHz; CDCl3)
20.4, 20.4, 20.5, 20.9 (C(O)CH3), 27.9 (Cβ), 28.1 (C(CH3)3),
32.0 (ArCH2), 52.7 (Cα), 61.0 (C6), 67.1 (Cγ), 67.1, 68.1,
70.9, 72.1 (C2, C3, C4, C5), 78.3 (C1), 80.0 (C(CH3)3), 128.3,
128.4, 128.5, 135.1 (ArC), 155.5, 169.7, 169.9, 170.3, 170.9,
171.8, 172.1 (C᎐O); m/z (ESI) 689.30 ([M ϩ Na]ϩ. C H -
C, 54.20; H, 6.31; N, 4.11. C45H63N3O22 requires C, 54.16; H,
6.36; N, 4.21%); δH (300 MHz; CDCl3) 1.35–1.53 (6H, m, CβH2,
CγH2, CδH2), 1.43 (9H, s, C(CH3)3), 1.96–2.15 (21H, 7 s,
C(O)CH3), 3.15 (2H, m, CεH2), 3.75–4.17 (7H, m, CαH, C5H,
C6H2, C5ЈH, C6ЈH2), 4.29 (2H, m, C4H, C1ЈH ), 4.84–5.36 (9H, m,
ArCH2, NHBoc, C1H, C2H, C3H, C2ЈH, C3ЈH, C4ЈH ), 7.12 (1H,
br d, NHC1), 7.34 (5H, m, ArH ); δC (75.5 MHz; CDCl3) 20.5,
20.5, 20.6, 20.6, 20.7, 20.8, 21.0 (C(O)CH3), 22.2 (Cβ), 28.2
(Cγ), 29.3 (Cδ), 40.3 (ArCH2), 54.3 (Cα), 60.8, 61.7 (C6, C6Ј),
66.6 (Cε), 69.0, 70.7, 70.9, 72.4, 74.5, 74.9, 75.9 (C2, C3, C4, C5,
C2Ј, C3Ј, C4Ј, C5Ј), 77.9 (C1), 80.2 (C(CH3)3), 101.0 (C1Ј), 128.0,
128.5, 136.6 (ArC), 155.5, 156.5, 168.9, 169.3, 170.0, 170.0,
᎐
31 42
N2NaO14 requires m/z, 689.25), 611.50 ([M Ϫ t-Bu ϩ H]ϩ,
567.30 ([M Ϫ Boc ϩ H]ϩ).
170.1, 170.3, 171.0, 172.6 (C᎐O); m/z (ESI) 998.30 ([M ϩ H]ϩ.
᎐
C45H64N3O22 requires m/z, 998.40), 1022.10 ([M ϩ Na]ϩ),
942.24 ([M Ϫ t-Bu ϩ H]ϩ), 898.30 ([M Ϫ Boc ϩ H]ϩ).
Boc-Lys(Cbz)-NH-[Gal(OAc)4] (6f ). After column chromato-
graphy (eluent: EtOAc–hexanes 1 : 1 v/v), 6f (585 mg, 82%) was
obtained as a white foam. Rf (5% MeOH–DCM) 0.34 (Found:
C, 55.55; H, 6.61; N, 5.74. C33H47N3O14 requires C, 55.84; H,
6.67; N, 5.92%); δH (300 MHz; CDCl3) 1.33–1.85 (6H, m, CβH2,
CγH2, CδH2), 1.45 (9H, s, C(C3)3), 1.96–2.15 (12H, 4 s,
C(O)CH3), 3.17 (2H, m, CεH2), 4.04–4.15 (4H, m, C5H, C6H2,
CαH ), 5.10–5.30 (6H, m, C1H, C2H, C3H, BocNH, ArCH2),
5.43 (1H, d, C4H ), 6.99 (1H, br d, C1NH ), 7.33 (5H, m, ArH );
δC (75.5 MHz; CDCl3) 20.4, 20.5, 20.5 (C(O)CH3), 22.3 (Cβ),
28.1 (C(CH3)3), 29.3 (Cγ), 31.4 (Cδ), 40.2 (ArCH2), 54.5 (Cα),
61.0 (C6), 66.4 (Cε), 67.0, 68.2, 70.7, 72.2 (C2, C3, C4, C5), 78.3
(C1), 80.0 (C(CH3)3), 127.9, 128.0, 128.3, 136.5 (ArC), 155.4,
General procedure II: Fmoc-protected N-linked glycopeptide
monomers 10a–h
A t-Bu-protected amino acid 9a or 9b (1.0 mmol), hexoseamine
4a, 4b, 4c or 4d (1.0 mmol), and BOP (1.0 mmol) were dissolved
in DCM (10 ml). DIPEA (2.0 mmol) was added. The resulting
mixture was stirred at room temperature (24 h). Subsequently,
the reaction mixture was washed successively with 1 M KHSO4,
5% aq. NaHCO3, water, and brine. The organic layer was dried
over Na2SO4. Evaporation of the solvent yielded the crude
product, which was purified using column chromatography
over silica.
156.5, 169.7, 169.9, 170.2, 170.9, 172.7 (C᎐O); m/z (ESI) 732.55
᎐
([M ϩ Na]ϩ. C33H47N3NaO14 requires m/z, 732.30), 654.55 ([M
Ϫ t-Bu ϩ H]ϩ), 610.35 ([M Ϫ Boc ϩ H]ϩ).
Fmoc-Asn[Glc(OAc)4]-Ot-Bu (10a). Reaction of 9a and 4a
gave, after work-up and column chromatography (eluent:
EtOAc–hexanes 1 : 1 v/v), 10a (596 mg, 80%) as a white foam.
Rf (5% MeOH–DCM) 0.43 (Found: C, 60.11; H, 5.98; N, 3.76.
C37H44N2O14 requires C, 59.99; H, 5.99; N, 3.78%); δH (300
MHz; CDCl3) 1.43 (9H, s, C(CH3)3), 1.75–2.10 (12H, 4 s,
C(O)CH3), 2.84 (2H, m, CβH2), 3.79 (1H, m, C5H ), 4.06 (1H, t,
C6H ), 4.22 (3H, m, Fmoc-CH, C6HЈ, CαH ), 44.0–4.52 (2H, m,
Fmoc-CH2), 4.93 (1H, t, C2H ), 5.06 (1H, t, C4H ), 5.19–5.35
(2H, m, C1H, C3H ), 5.91 (1H, br d, FmocNH ), 6.42 (1H, br d,
C1NH ), 7.26–7.78 (8H, m, ArH ); δC (75.5 MHz; CDCl3) 19.9,
20.3, 20.3 (C(O)CH3), 27.8 (C(CH3)3), 37.8 (Cβ), 47.1 (Fmoc-
CH), 54.4 (Cα), 67.2 (Fmoc-CH2), 67.9, 70.5, 72.5, 73.6 (C2,
C3, C4, C5), 78.0 (C1), 82.5 (C(CH3)3), 120.0, 127.0, 125.6,
Boc-Ala-NH-[Lac(OAc)7] (6g). After column chromato-
graphy (eluent: EtOAc–hexanes 1 : 1 v/v), 6g (571 mg, 71%) was
obtained as a white foam. Rf (5% MeOH–DCM) 0.34 (Found:
C, 50.65; H, 6.22; N, 3.51. C34H50N2O20 requires C, 50.62; H,
6.25; N, 3.47%); δH (300 MHz; CDCl3) 1.26 (3H, d, CβH3), 1.43
(9H, s, C(CH3)3), 1.97–2.16 (21H, 7 s, C(O)CH3), 3.78–4.17
(7H, m, CαH, C5H, C5ЈH, C6H2, C6ЈH2), 4.47 (2H, m, C4H,
C1ЈH ), 4.83–5.36 (7H, m, NHBoc, C1H, C2H, C3H, C2ЈH, C3ЈH,
C4ЈH ), 7.00 (1H, br d, NHC1); δC (75.5 MHz; CDCl3) 17.7 (Cβ),
20.3, 20.5, 20.6, 20.7 (C(O)CH3), 28.1 (C(CH3)3), 50.0 (Cα),
60.7, 61.8 (C6, C6Ј), 66.5, 68.8, 70.5, 70.8, 72.4, 74.3, 75.8 (C2,
C3, C4, C5, C2Ј, C3Ј, C4Ј, C5Ј), 77.7 (C1), 100.7 (C1Ј), 155.2,
127.7, 141.3 (ArC), 156.1, 169.5, 169.9, 170.6, 171.2 (C᎐O); m/z
᎐
168.8, 169.3, 169.9, 170.0, 170.2, 170.7, 173.2 (C᎐O); m/z (ESI)
᎐
(ESI) 741.75 ([M ϩ H]ϩ. C37H45N2O14 requires m/z, 741.29),
763.25 ([M ϩ Na]ϩ), 685.30 ([M Ϫ t-Bu ϩ H]ϩ).
807.20 ([M ϩ H]ϩ. C34H51N2O20 requires m/z, 807.31), 829.30
([M ϩ Na]ϩ), 751.45 ([M Ϫ t-Bu ϩ H]ϩ), 707.25 ([M Ϫ Boc ϩ
H]ϩ).
Fmoc-Gln[Glc(OAc)4]-Ot-Bu (10b). Reaction of 9b and 4a
gave, after work-up and column chromatography (eluent:
EtOAc–hexanes 1 : 1 v/v), 10b (605 mg, 80%) as a white foam.
Rf (5% MeOH–DCM) 0.41 (Found: C, 60.40; H, 6.22; N,
3.63. C38H46N2O14 requires C, 60.47; H, 6.14; N, 3.71%); δH (300
MHz; CDCl3) 1.47 (9H, s, C(CH3)3), 1.82 (2H, m, CβH2),
1.90–2.06 (12H, 4 s, C(O)CH3), 2.22 (2H, m, CγH2), 3.81 (1H,
m, C5H2), 4.05 (1H, d, C6H ), 4.20–4.32 (3H, m, Fmoc-CH,
CαH, C6HЈ), 4.42 (2H, m, Fmoc-CH2), 4.95 (1H, t, C2H ), 5.08
(1H, t, C4H ), 5.29 (2H, m, C1H, C3H ), 5.51 (1H, br d,
FmocNH ), 6.68 (1H, br d, C1NH ), 7.27–7.78 (8H, m, ArH );
δC (75.5 MHz; CDCl3) 20.5, 20.6 (C(O)CH3), 27.9 (C(CH3)3),
28.6 (Cβ), 47.2 (Fmoc-CH), 54.9 (Cα), 60.4 (Cγ), 61.6 (Fmoc-
CH2), 67.0 (C6), 68.0, 70.5, 72.9, 73.5 (C2, C3, C4, C5), 78.0
(C1), 84.6 (C(CH3)3), 120.0, 125.1, 127.1, 127.7, 141.3, 144.1
Boc-Glu(Bn)-NH-[Lac(OAc)7] (6h). After column chromato-
graphy (eluent: EtOAc–hexanes 1 : 1 v/v), 6h (694 mg, 73%) was
obtained as a white foam. Rf (5% MeOH–DCM) 0.34 (Found:
C, 53.92; H, 5.98; N, 2.95. C43H58N2O22 requires C, 54.08; H,
6.12; N, 2.93%); δH (300 MHz; CDCl3) 1.41 (9H, s, C(CH3)3),
1.96–2.14 (23H, m, C(O)CH3, CβH2), 2.45 (2H, m, CγH2), 3.80–
4.13 (7H, m, CaH, C5H, C6H2, C5ЈH, C6ЈH2), 3.93–4.57 (2H, m,
C1ЈH, C4H ), 4.86–5.36 (8H, m, ArCH2, C1H, C2H, C3H, C2ЈH,
C3ЈH, C4ЈH ), 5.54 (1H, br d, NHBoc), 7.34 (6H, m, ArH,
NHC1); δC (75.5 MHz; CDCl3) 20.3, 20.5, 20.6, 20.6, 20.7, 20.9
(C(O)CH3), 27.1 (Cβ), 28.1 (C(CH3)3), 30.1 (ArCH2), 53.8
(Cα), 60.8, 61.8 (C6, C6Ј), 66.4 (Cγ), 66.5, 68.9, 70.7, 70.8, 71.2,
72.4, 74.3 (C2, C3, C4, C5, C2Ј, C3Ј, C4Ј, C5Ј), 75.8 (C1), 80.1
(C(CH3)3), 100.7 (C1Ј), 128.1, 128.2, 128.4, 135.5 (ArC), 155.5,
(ArC), 156.8, 169.4, 169.5, 171.2, 172.5 (C᎐O); m/z (ESI)
168.8, 169.3, 169.5, 169.9, 170.0, 170.7, 172.1, 172.7 (C᎐O);
᎐
᎐
755.40 ([M ϩ H]ϩ. C38H47N2O14 requires m/z, 755.30), 777.35
([M ϩ Na]ϩ), 699.45 ([M Ϫ t-Bu ϩ H]ϩ).
m/z (ESI) 955.25 ([M ϩ H]ϩ. C43H59N2O22 requires m/z, 955.36),
977.35 ([M ϩ Na]ϩ), 899.40 ([M Ϫ t-Bu ϩ H]ϩ), 855.50 ([M
Ϫ Boc ϩ H]ϩ).
Fmoc-Asn[Gal(OAc)4]-Ot-Bu (10c). Reaction of 9a and 4b
gave, after work-up and column chromatography (eluent:
EtOAc–hexanes 1 : 1 v/v), 10c (531 mg, 72 %) as a white foam.
Rf (5% MeOH–DCM) 0.42 (Found: C, 59.77; H, 5.98; N, 3.76.
Boc-Lys(Cbz-NH)-[Lac(OAc)7] (6i). After column chromato-
graphy (eluent: EtOAc–hexanes 1 : 1 v/v), 6i (737 mg, 74%) was
obtained as a white foam. Rf (5% MeOH–DCM) 0.34 (Found:
1046
J. Chem. Soc., Perkin Trans. 1, 2002, 1042–1049