Y. Fujimoto, K. Fukase et al.
Compound 6: 1H NMR (500 MHz, CD3OH): d=5.32 (1H, s; Hanh-1),
4.62 (1H, d, J=5.5 Hz; H-6), 4.51 (1H, d, J=8.5 Hz; H-6’), 4.47–4.42
(1H, m; Lac-aH), 4.40–4.37 (2H, m; Glu-aH, DAP 2-H), 4.30 (1H, d,
J=7 Hz; H-1), 4.12 (1H, q, J=6.5 Hz; Ala-aH), 3.98 (1H, s; Hanh-2),
3.91- 3.86 (2H, m; Hanh-4, Hanh-5), 3.79–3.72 (3H, m; H-2, H-5, DAP 6-
CH2), 3.71–3.68 (1H, m; Hanh-6), 3.55 (1H, brs; Hanh-3), 3.47–3.44 (1H,
m; H-4), 3.36–3.34 (1H, m; Hanh-6), 3.32–3.30 (1H, m; H-3), 2.38–2.33
(2H, m; Glu-gCH2), 2.23–2.15 (1H, m; Glu-bCH2), 2.07 (3H, s; NHAc),
2.03 (3H, s; NHAc), 1.99–1.92 (1H, m; Glu-bCH2), 1.87–1.71 (4H, m;
DAP 3-CH2, DAP 5-CH2), 1.57–1.54 (2H, m; DAP 4-CH2), 1.42–
1.36 ppm (6H, m; Lac-bCH3, Ala-bCH3); HRMS-ESI QTOF-MS (posi-
tive): m/z: calcd for C29H48N6O16: 851.3522 [M+H]+; found: 851.3531.
was purified by silica-gel flash column chromatography (CHCl3/MeOH
30:1) to give 50 (4.6 mg, quant.). 1H NMR (500 MHz, CDCl3): d=7.39–
À
7.27 (20H, m; ArH), 5.56 (1H, s; Ph CH=O2), 5.26 (1H, d, J=3 Hz; H-
À
À
À
1), 5.17–5.04 (8H, m; COO CH2 Ph ꢃ4), 4.51–4.19 (7H, m; Glu-aH,
DAP 2-H, DAP 6-H, Lac-aH, Ala-aH, d-Ala-aH, H-4, H-2), 4.14–4.11
(1H, m; H-2), 3.79–3.63 (3H, m; H-6, H-6’, H-3), 3.41–3.40 (1H, m; H-
5), 2.35–1.79 (4H, m; Glu-bCH2, Glu-g CH2), 1.65–1.57 (4H, m; DAP 3-
CH2, DAP 5-CH2), 1.95 (3H, s; NHAc), 1.39–1.32 ppm (8H, m; DAP 4-
CH2, Lac-bCH3, Ala-bCH3); HRMS-ESI QTOF-MS (positive): m/z:
calcd for C65H76N6O18: 1251.5114 [M+Na]+; found: 1251.5114.
1-O-Deprotected monosaccharide tripeptide 51: Compound 49 (5.6 mg,
4.67ꢃ10À6 mol) was suspended in THF/H2O 2:1 (450 mL). I2 (3 mg, 9.35ꢃ
10À6 mol) was added to the solution, and the reaction mixture was stirred
for 30 min. After this time, the reaction mixture was quenched by 10%
Na2S2O4 aq. and the mixture was extracted with AcOEt. The organic
layer was washed with 10% Na2S2O4 aq., saturated aqueous NaHCO3,
and brine, dried over Na2SO4, and concentrated in vacuo. The residue
was purified by silica-gel flash column chromatography (CHCl3/MeOH
30:1) to give 51 (4.1 mg, 76%). 1H NMR (500 MHz, CDCl3): d=7.35–
1-Propenyl-2-acetylamino-4,6-O-benzylidene-2-deoxy-3-O-[(R)-1-(ethoxy-
carbonyl)ethyl]-a-d-glucopyranoside (46): H2 activated [Ir
ACHTUNGTRNE(NUNG cod)-
ACHTUNGTRENNUNG
solution of 45 (200 mg, 0.445 mmol) in dry THF (2 mL). After the reac-
tion mixture had been stirred under an Ar atmosphere at RT for 45 min,
it was extracted with AcOEt. The organic layer was washed with saturat-
ed aqueous NaHCO3 and brine, dried over Na2SO4, and then concentrat-
ed in vacuo. The residue was purified by silica-gel flash column chroma-
tography (CHCl3/acetone 50:1) to give 46 (182 mg, 91%). ESI-TOF-MS
(positive): m/z: 450.2 [M+H]+; 1H NMR (500 MHz, CDCl3): d=7.47–
À
7.26 (20H, m; ArH), 5.56 (1H, s; Ph CH=O2), 5.34 (1H, s; H-1), 5.18–
À
À
À
5.05 (8H, m; COO CH2 Ph ꢃ4), 4.51–4.15 (7H, m; Glu-aH, DAP 2-H,
DAP 6-H, Lac-aH, Ala-aH, H-4, H-2), 3.82–3.61 (3H, m; H-6, H-6’, H-
3), 3.44–3.41 (1H, m; H-5), 2.35–1.66 (8H, m; Glu-bCH2, Glu-g CH2,
DAP 3-CH2, DAP 4-CH2, DAP 5-CH2), 1.95 (3H, s; NHAc), 1.38–
1.32 ppm (6H, m; Lac-bCH3, Ala-bCH3); ESI-TOF-MS (positive): m/z:
1158.50 [M+H]+; HRMS-ESI QTOF-MS (positive): m/z: calcd for
C62H71N5O17: 1180.4743 [M+Na]+; found: 1180.4746.
À
À
À
7.36 (5H, m; ArH), 6.10 (1H, dd, J=12, 1.7 Hz; O CH=CH ), 5.59
À
(1H, s; Ph CH=O2), 5.52 (1H, d, J=3 Hz; H-1), 5.14–5.07 (1H, m, J=
À
À
À
7 Hz; O CH=CH ), 4.51 (1H, q, J=7 Hz; Lac-aH), 4.28–4.15 (4H, m;
H-4, H-6, COOCH2CH3), 3.89–3.68 (4H, m; H-2, H-3, H-5, H-6’), 2.05
(3H, s; NHAc), 1.54 (3H, dd, J=7, 1.5 Hz; CH=CH CH3), 1.43 (3H,
d, J=7 Hz; Lac-bCH3), 1.29 (3H, t, J=7 Hz; COOCH2CH3).
À
À
À
À
Monosaccharide tetrapeptide 3 and monosaccharide tripeptide 4: Com-
pounds 3 and 4 were synthesized from 50 and 51, respectively, in a
manner similar to the synthesis of 5.
1-Propenyl-2-acetylamino-4,6-O-benzylidene-2-deoxy-3-O-[(R)-1-(car-
bonyloxy)ethyl]-a-d-glucopyranoside (47): Compound 46 (93.9 mg,
0.209 mmol) was dissolved in THF/1,4-dioxane/H2O 2:1:0.5 (2.1 mL).
LiOH·H2O (10 mg) was added to the solution and the resulting reaction
mixture was stirred for 1 h. After this time, the reaction was quenched
with Dowex H+, which was subsequently removed by filtration. The mix-
ture was then concentrated in vacuo and the resulting residue was puri-
fied by silica-gel flash column chromatography (CHCl3/MeOH 10:1) to
give 47 (90 mg, quant.).
Compound 3: 1H NMR (500 MHz, CDCl3): d=5.10 (1H, d, J=4 Hz; H-
1), 4.27–4.19 (5H, m; Glu-aH, DAP 2-H, Ala-aH, d-Ala-aH, Lac-aH),
3.90 (1H, dd, J=3.5, 11 Hz; H-2), 3.83–3.80 (1H, m; H-5), 3.77–3.67
(3H, m; DAP-aH, H-6, H-3), 3.53–3.45 (2H, m; H-4, H-6’), 2.30–2.27
(2H, m; Glu-gCH2), 2.14–1.69 (8H, m; Glu-bCH2, DAP 3-CH2, 5-CH2),
1.92 (3H, s; NHAc), 1.43–1.39 (2H, m; DAP 4-CH2), 1.37 (3H, d, J=
7 Hz; Lac-bH), 1.34–1.30 ppm (6H, m; Ala-bH, d-Ala-bH); ESI-TOF-
MS (negative): m/z: 735.30 [M+H]À; HRMS-ESI QTOF-MS (positive):
m/z: calcd for C29H48N6O16: 737.3205 [M+Na]+; found: 737.3209.
Compound 4: 1H NMR (500 MHz, CDCl3): d=5.10 (1H, d, J=3.5 Hz;
H-1), 4.28–4.21 (4H, m; Glu-aH, DAP-aH, Ala-aH, Lac-aH), 3.90 (1H,
dd, J=3.5, 10.5 Hz; H-2), 3.85–3.79 (1H, m; H-5), 3.77–3.70 (1H, m;
DAP-aH, H-6), 3.63 (1H, d, J=10.5 Hz; H-3), 3.53–3.45 (2H, m; H-4, H-
6’), 2.32–2.21 (2H, m; Glu-gCH2), 2.18–1.67 (6H, m; Glu-bCH2, DAP 3-
CH2, 5-CH2), 1.92 (3H, s; NHAc), 1.43–1.40 (2H, m; DAP 4-CH2), 1.36
(3H, d, J=7.5 Hz; Lac-bH), 1.32 ppm (3H, d, J=6.5 Hz; Ala-bH); ESI-
TOF-MS (negative): m/z: 664.26 [MÀH]À; HRMS-ESI QTOF-MS (posi-
tive): m/z: calcd for C26H43N5O15: 666.2834 [M+Na]+; found: 666.2837.
Protected monosaccharide tetrapeptide 48 and protected monosaccharide
tripeptide 49: Compounds 48 and 49 were synthesized from 47 and 30
(for 48) or 28 (for 49), in a manner similar to the synthesis of 41.
Compound 48: 1H NMR (500 MHz, CDCl3): d=7.46–7.23 (10H, m;
À
À À
ArH), 5.56–5.54 (2H, brs; Ph CH=O2; H-1), 5.17–5.03 (9H, m;
O
À À
À
CH=CH , CH2 Ph ꢃ4), 4.56–4.06 (9H, m; Glu-aH, Lac-aH, DAP 2-H,
À
À
À
DAP 4-H, Ala-aH, d-Ala-aH, H-5, H-2, O CH=CH ), 3.87–3.60 (4H,
m; H-4, H-3, H-6, H-6’), 2.17–1.81 (4H, m; Glu-bCH2, Glu-gCH2), 1.89
(3H, s; NHAc), 1.84–1.34 (11H, m; DAP 3-CH2, DAP 5-CH2, DAP 4-
CH2, Lac-bCH3, Ala-bH, d-Ala-bH), 1.52 ppm (3H, dd, J=7, 1.5 Hz;
O CH=CH CH3); ESI-TOF-MS (positive): m/z: 1269.49 [M+H]+;
HRMS-ESI QTOF-MS (positive): m/z: calcd for C68H80N6O18: 1291.5427
[M+Na]+; found: 1291.5427.
À
À
À
1-Allyl 2-acetylamino-6-O-benzyl-4-O-(2’-acetylamino-3’-O-benzyl-4’,6’-
O-benzylidene-2’-deoxy-b-d-glucopyranosyl)-2-deoxy-3-O-[(R)-1-(ethoxy-
carbonyl)ethyl]-a-d-glucopyranoside (53): Zn/Cu (three microspatula
spoonfuls) was added to a solution of 52 (200 mg, 0.182 mmol) in THF/
AcOH/Ac2O 1:1:1 (2 mL), and the mixture was stirred at RT for 3.5 h.
After this time, the insoluble materials were filtered off and the filtrate
was concentrated in vacuo. The residue was extracted with AcOEt and
the organic layer was washed with saturated aqueous NaHCO3 and brine,
dried over Na2SO4, and concentrated in vacuo. The residue was purified
by silica-gel flash column chromatography (toluene/AcOEt 2:1) to give
53 (69 mg, 46%). 1H NMR (500 MHz, CDCl3): d=7.44–7.28 (15H, m;
Compound 49: 1H NMR (500 MHz, CDCl3): d=7.37–7.28 (10H, m;
À
ArH), 5.56 (1H, s; Ph CH=O2), 5.51 (1H, d, J=8 Hz; H-1), 5.12–5.08
À
À
À
(1H, m; O CH=CH ), 5.12–4.38 (4H, m; Glu-aH, Lac-aH, DAP 2-H,
À
À
À
DAP 4-H), 4.34–4.14 (5H, m; H-6, H-2, H-4, O CH=CH , Ala-aH),
3.84–3.69 (2H, m; H-5, H-6’), 2.28–2.06 (4H, m; Glu-bCH2, Glu-gCH2),
1.89 (3H, s; NHAc), 1.83–1.59 (4H, m; DAP 3-CH2, DAP 5-CH2), 1.52
À
À
À
(3H, dd, J=7, 1.5 Hz; O CH=CH CH3), 1.40–1.38 (2H, m; DAP 4-
CH2), 1.38 (3H, d, J=7 Hz; Lac-bCH3), 1.35 (3H, d, J=6.5 Hz; Ala-
bH); ESI-TOF-MS (positive): m/z: 1198.53 [M+H]+; HRMS-ESI QTOF-
MS (positive): m/z: calcd for C65H75N5O17: 1220.5056 [M+Na]+; found:
1220.5055.
À
À
À
À
À
ArH), 5.88–5.81 (1H, m; O CH2 CH=CH2), 5.58 (1H, s; Ph CH O2),
À
À
5.31–5.30 (1H, d, J=3 Hz; H-1), 5.25–5.22 (1H, dd, J=1.5, 17 Hz;
O
À
À
À
À
CH2 CH=CHtransHcis), 5.16–5.13 (1H, dd, J=1.5, 10 Hz; O CH2 CH=
CHtransHcis), 4.88 (1H, d, J=12 Hz; Ph CH2 O ), 4.83 (1H, d, J=12 Hz;
Ph CH2 O ), 4.65 (1H, d, J=12 Hz; Ph CH2 O ), 4.35 (1H, d, J=
12 Hz; Ph CH2 O ), 4.62–4.60 (1H, m; Lac-aH), 4.45–4.39 (2H, m; H-
1’, H-6’), 4.26–4.11 (3H, m; COOCH2CH3, H-6), 3.97–3.92 (2H, m;
O CH2 CH=CH2), 3.78–3.74 (4H, m; H-2, H-2’, H-4’, H-6’), 3.69–3.44
(6H, m; H-4’, H-5, H-6, H-3, H-3’, H-4), 3.32–3.27 (1H, m; H-5’), 2.00
1-O-Deprotected monosaccharide tetrapeptide 50: Compound 48
(4.6 mg, 3.62ꢃ10À6 mol) was suspended in THF/H2O 2:1 (360 mL). I2
(2 mg, 7.25ꢃ10À6 mol) was then added to the solution, and the reaction
mixture was stirred for 30 min. The reaction was quenched by 10%
Na2S2O4 aq. and the mixture was extracted with AcOEt. The organic
layer was washed with 10% Na2S2O4 aq., saturated aqueous NaHCO3,
and brine, dried over Na2SO4, and concentrated in vacuo. The residue
À
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À
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10328
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 10318 – 10330