S.-K. Chung et al.
7.9 Hz, 1H; H-1’a), 5.26 (dd, J=10.2 Hz, 3.5 Hz, 1H; H-3’a & H-3’b),
5.34 (d, J=1.7 Hz, 1H; H-1b), 5.41 (dd, J=10.3 Hz, 3.1 Hz, 1H; H-2a &
H-2b), 5.64 (d, J=2.5 Hz, 1H; H-1a), 5.70–5.76 (m, 1H; H-4’a & H-2’a),
5.81 (t, J=9.0 Hz, 1H; H-3b), 6.18 (t, J=9.5 Hz, 1H; H-3a), 7.16–
7.98 ppm (m, 35H; aromatic); 13C NMR (CDCl3): d=61.58, 62.81, 62.97,
68.78, 70.40, 70.60, 71.76, 72.19, 72.29, 72.56, 72.89, 73.62, 74.33, 76.35,
76.47, 77.74, 90.71, 101.45, 128.70, 128.86, 129.02, 129.21, 129.80, 129.89,
130.01, 130.07, 130.16, 130.30, 130.36, 130.40, 133.54, 133.74, 133.85,
133.99, 134.28, 165.32, 165.71, 165.77, 165.88, 165.93, 166.08, 166.43,
166.57, 167.02 ppm; MS (FAB): m/z: calcd for C61H50O18Na: 1093.29
[M+Na]+; found: 1093.27.
70.46, 70.83, 72.72, 74.92, 74.98, 76.59, 76.63, 77.25, 80.78, 104.39, 105.25,
128.92, 129.08, 129.60 ppm; MS (FAB): m/z: calcd for C25H39NO13Na:
584.23 [M+Na]+; found: 584.40.
5-(Benzyloxycarbonylamino)pentyl 2,3,4,6-tetra-O-(6-Boc-aminohexano-
yl)-b-d-galactopyranosyl-(1!4)-2,3,6-tri-O-(6-Boc-aminohexanoyl)-d-glu-
copyranoside (6): A solution of 5 (60 mg, 0.10 mmol), N-Boc-6-amino-
hexanoic acid (494 mg, 2.13 mmol), EDC (408 mg, 2.13 mmol), and
DMAP (18.4 mg, 0.15 mmol) in DMF (6.5 mL) was stirred at RT for 48 h
under N2, diluted with EtOAc, and washed several times with sat.
NaHCO3, water, and then brine. The organic phase was dried and con-
centrated to give the crude product, which was purified by column chro-
matography on silica gel to afford 6 (180 mg, 82%) as a white, sticky
solid. 1H NMR (CDCl3): d=1.20–1.61 (m, 111H), 2.11–2.34 (m, 14H),
3.06–3.16 (m, 14H), 3.39 (m, 1H), 3.51 (m, 1H), 3.67–3.85 (m, 2H), 4.03
(m, 2H), 4.42 (m, 2H), 4.82 (m, 6H), 4.91 (dd, J=9.0, 3.0 Hz, 1H), 5.06
(s, 2H), 5.01–5.06 (m, 1H), 5.15 (t, J=9.3 Hz, 1H), 5.29–5.37 (m, 1H),
7.29–7.33 ppm (m, 5H); 13C NMR (CDCl3): d=23.41, 24.50, 24.62, 24.72,
24.80, 24.87, 24.99, 25.12, 26.61, 27.73, 28.82, 29.39, 29.93, 30.09, 33.89,
34.03, 34.14, 34.26, 34.37, 34.52, 40.74, 41.27, 66.75, 68.99, 69.34, 69.93,
70.09, 70.96, 71.20, 71.41, 71.82, 71.92, 72.14, 72.71, 72.82, 73.08, 73.49,
79.37, 100.93, 101.33, 102.28, 128.41, 128.46, 128.85, 137.10, 156.42, 156.86,
172.43, 172.48, 172.56, 172.65, 172.79, 172.94, 173.26, 173.42, 173.53 ppm;
MS (MALDI-TOF): m/z: calcd for C102H172N8NaO34: 2077.19 [M+Na]+;
found: 2077.26.
1-O-[2,3,4,6-Tetra-O-benzoyl-b-d-galactopyranosyl-(1!4)-2,3,6-tri-O-
benzoyl-d-glucopyranosyl] trichloroacetimidate (3): Trichloroacetonitrile
(20 mL) and DBU (0.002 mL, 0.012 mmol) were added to a solution of 2
(0.24 g, 0.25 mmol) in dry CH2C12 (5 mL). The reaction mixture was
stirred for 3 h and concentrated in vacuo. Flash chromatography (hexane/
EtOAc 3:1) provided 3 (0.25 g, 92%) as a colorless foam. 1H NMR
(CDCl3): d=3.72–3.89 (m, 3H; H-5’, H-6a’& H-6b’), 4.32 (m, 2H; H-4 &
H-5), 4.55 (m, 2H; H-6a & H-6b), 4.94 (d, J=7.3 Hz, 1H; H-1’), 5.38 (d,
J=10.2 Hz, 1H; H-3’), 5.54 (d, J=10.1 Hz, 1H; H-2), 5.72 (m, 2H; H-2’
& H-4’), 6.16 (t, J=9.9 Hz, 1H; H-3), 6.71 (d, J=3.6 Hz, 1H; H-1a),
7.19–8.03 (m, 35H; aromatic), 8.56 ppm (s, 1H; NH); 13C NMR (CDCl3):
d=61.39, 62.32, 67.90, 70.39, 70.70, 70.92, 71.54, 71.77, 71.81, 72.36, 72.48,
73.25, 73.47, 74.11, 74.42, 76.06, 91.09, 93.49, 101.60, 101.72, 128.69,
128.76, 128.86, 129.01, 129.13, 129.26, 129.80, 129.86, 129.98, 130.04,
130.08, 130.15, 130.17, 130.35, 130.39, 130.54, 131.06, 133.71, 133.82,
133.98, 134.28, 161.08, 165.28, 165.64, 165.89, 165.95, 166.16 ppm; MS
(FAB): m/z: calcd for C63H50Cl3NO18Na: 1236.20 [M+Na]+; found:
1236.22.
5-(Benzyloxycarbonylamino)pentyl 2,3,4,6-tetra-O-(8-Boc-aminooctano-
yl)-b-d-galactopyranosyl-(1!4)-2,3,6-tri-O-(8-Boc-aminooctanoyl)-d-glu-
copyranoside (7): This compound was prepared similarly to 6, from 5
(50 mg, 0.089 mmol), N-Boc-8-aminooctanoic acid (461 mg, 1.78 mmol),
EDC (341 mg, 1.78 mmol), and DMAP (16.3 mg, 0.133 mmol). Colorless,
sticky liquid (184 mg, 92%); 1H NMR (CDCl3): d=1.20–1.25 (m, 46H),
1.40 (m, 93H), 2.18–2.34 (m, 14H), 3.11 (m, 14H), 3.38–3.41 (m, 1H),
3.53 (m, 1H), 3.67–3.85 (m, 2H), 4.01–4.12 (m, 2H), 4.38–4.49 (m, 2H),
4.65 (m, 5H), 4.82 (t, J=9.0 Hz, 1H), 4.90 (dd, J=9.0, 3.0 Hz, 1H), 5.05
(s, 2H), 5.01–5.06 (m, 1H), 5.15 (t, J=9.0 Hz, 1H), 5.27–5.29 (m, 1H),
7.31 ppm (m, 5H); 13C NMR (CDCl3): d=23.41, 24.77, 25.06, 25.09,
25.15, 25.27, 27.01, 28.83, 29.37, 29.50, 29.98, 30.42, 34.20, 34.24, 34.30,
34.45, 40.95, 41.28, 60.77, 66.90, 69.32, 70.06, 71.12, 71.36, 71.81, 79.33,
101.01, 101.38, 128.42, 128.86, 137.11, 156.42, 156.85, 172.08, 178.53,
172.72, 172.92, 173.06, 173.35, 173.42 ppm; MS (MALDI-TOF): m/z:
calcd for C116H200N8O34Na: 2272.41 [M+Na]+; found: 2272.49.
5-(Benzyloxycarbonylamino)pentyl 2,3,4,6-tetra-O-benzoyl-b-d-galacto-
pyranosyl-(1!4)-2,3,6-tri-O-benzoyl-d-glucopyranoside (4): A mixture of
trichloroacetimidate 3 (0.25 g, 0.21 mmol) and 5-(benzyloxycarbonylami-
no)pentanol (0.054 g, 0.23 mmol) in dry CH2Cl2 (5 mL) was stirred for
1 h under N2. It was then cooled to ꢀ108C, and neat TMSOTf (0.004 mL,
0.023 mmol) was added. After stirring for 0.5 h at ꢀ108C, the reaction
was terminated by addition of solid NaHCO3 (100 mg). The mixture was
diluted with CH2Cl2, washed with sat. aq NaHCO3, dried, and concentrat-
ed. Chromatography (EtOAc/petroleum ether 2:3) of the crude product
on silica gel afforded 4 (0.21 g, 80%) as a foamy solid. [a]1D8 =26.66 (c=
1.15 in CHCl3); 1H NMR (500 MHz, CDCl3): d=1.30–1.55 (m, 6H), 2.94
(m, 2H), 3.44–3.48 (m, 1H), 3.77–3.87 (m, 4H; H-6a’, H-6b’, H5, CH-
glycosyl), 3.95 (t, J=6.5 Hz, 1H; H-5’), 4.29 (t, J=9.5 Hz, 1H; H-4),
4.51–4.67 (m, 2H; H-6a, H-6b), 4.70 (d, J=8.0 Hz, 1H; H-1), 4.93 (d, J=
7.5 Hz, 1H; H-1’), 5.10 (s, 2H; CH2-Ph), 5.43 (dd, J=10.5, 3.5 Hz, 1H;
H-3’), 5.48 (dd, J=9.5, 8.0 Hz, 1H; H-2), 5.74–5.78 (m, 2H; H-2’, H-4’),
5.84 (t, J=9.5 Hz, 1H; H-3), 7.16–8.06 ppm (m, 40H; aromatic) [chemi-
cal shift assignments are made by 1H–1H COSY]; 13C NMR (125 MHz,
CDCl3): d=22.99, 28.89, 29.36, 29.69, 40.82, 61.17, 62.46, 66.49, 67.65,
69.89, 70.03, 71.49, 71.83, 71.94, 72.96, 73.12, 76.14, 101.01, 101.18, 128.04,
128.25, 128.40, 128.49, 128.52, 128.56, 128.59, 128.63, 128.71, 128.79,
128.94, 129.47, 129.51, 129.59, 129.63, 129.67, 129.70, 129.74, 130.00,
133.15, 133.24, 133.38, 133.52, 136.79, 156.30, 163.36, 164.85, 165.172,
165.25, 165.41, 165.45, 165.59, 165.87 ppm; MS (FAB): m/z: calcd for
C74H67NO20Na: 1312.42 [M+Na]+; found: 1312.57.
5-(Benzyloxycarbonylamino)pentyl
2,3,4,6-tetra-O-(N,N’’-bis-Boc-N’’-
aminohexanoylguanidine)-b-d-galactopyranosyl-(1!4)-2,3,6-tri-O-(N,N’’-
bis-Boc-N’’-aminohexanoylguanidine)-d-glucopyranoside (10): Com-
pound 6 (200 mg, 0.097 mmol) was added at 08C to a saturated HCl (gas)
solution of EtOAc (5 mL), and the solution was stirred for 3 h. The pre-
cipitate was separated and dried under vacuum to give compound 8 as a
white HCl salt (132 mg, quant.). This material was directly used in the
next step. 1H NMR (CD3OD): d=1.42–1.68 (m, 48H), 2.22–2.45 (m,
14H), 2.86–2.99 (m, 14H), 3.06–3.09 (m, 2H), 3.29–3.31 (m, 4H), 3.52–
3.77 (m, 4H), 4.07–4.15 (m, 2H), 4.40–4.85 (m, 6H), 5.06 (m, 3H), 5.17
(m, 2H), 5.37–5.41 (m, 1H), 7.34–7.38 ppm (m, 5H); 13C NMR
(CD3OD): d=23.22, 24.13, 24.21, 24.38, 24.48, 24.55, 24.74, 24.81, 25.91,
25.93, 26.11, 27.23, 27.29, 27.35, 29.12, 29.27, 29.53, 33.42, 33.55, 33.65,
33.85, 34.12, 39.62, 39.67, 40.74, 60.56, 60.92, 62.27, 66.31, 67.44, 67.71,
69.48, 69.71, 69.81, 70.64, 71.33, 71.49, 71.62, 72.05, 72.39, 72.79, 72.89,
73.20, 73.66, 76.59, 100.61, 100.87, 127.69, 127.99, 128.52, 137.50, 157.89,
171.99, 172.57, 172.65, 173.03, 173.39, 173.64 ppm; MS (MALDI-TOF):
m/z: calcd for C67H117N8O20: 1353.84; found: 1353.86 [M+H]+.
5-(Benzyloxycarbonylamino)pentyl b-d-galactopyranosyl-(1!4)-d-gluco-
pyranoside (5): NaOMe (0.04 mL, 0.17 mmol, 25% w/v) was added to a
solution of 4 (200 mg, 0.44 mmol) in MeOH (15 mL), and the solution
was heated at reflux for 3 h. After cooling, the reaction mixture was fil-
tered through acidic resin. The filtrate was concentrated, and the crude
product was washed with EtOAc in n-hexane (5%) to remove the by-
product, methyl benzoate. The washed product was dried under vacuum
and recrystallized from abs. EtOH to afford 5 as a white solid (88 mg,
97%). M.p. 180–1828C (from EtOH); [a]1D8 =ꢀ4.77 (c=0.965 in H2O);
1H NMR (500 MHz, CD3OD): d=1.39–1.67 (m, 6H), 3.14 (t, J=7.0 Hz,
2H), 3.26 (t, J=8.5 Hz, 1H), 3.32 (m, 1H), 3.40–3.43 (m, 1H), 3.49–3.62
(m, 5H), 3.71–3.74 (m, 1H), 3.78–3.93 (m, 5H), 4.30 (d, J=8.0 Hz, 1H),
4.38 (d, J=8.0 Hz, 1H), 5.08 (s, 2H), 7.36 ppm (m, 5H; aromatic);
13C NMR (CD3OD): d=24.41, 30.51, 30.76, 41.87, 62.07, 62.64, 67.45,
Et3N (0.28 mL, 1.96 mmol) and N,N’-di-Boc-N’’-trifluoromethanesulfonyl-
guanidine (767 mg, 1.96 mmol) were sequentially added to a solution of 8
(132 mg, 0.098 mmol) in dioxane/water (5:1, 6 mL). The reaction mixture
was stirred at RT for 3 days, concentrated, and diluted with EtOAc. The
organic layer was washed with NaHSO4 (1n), saturated NaHCO3, and
brine, dried, and concentrated to give the crude product, which was puri-
fied on neutral alumina to afford 10 (181 mg, 61%) as a white, foamy
solid. 1H NMR (CDCl3): d=1.25–1.67 (m, 174H), 2.12–2.39 (m, 14H),
3.15 (m, 1H), 3.38 (m, 15H), 3.51 (m, 2H), 3.68–3.83 (m, 3H), 4.01–4.04
(m, 3H), 4.41–4.48 (m, 3H), 4.82 (m, 1H), 4.93 (m, 1H), 5.02–5.05 (m,
9166
ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 9161 – 9168