Development of Ketoside-Type Analogues of Trehalose
97.2 (C-1), 84.8 (C-3), 84.3 (C-3Ј), 83.0 (C-4Ј), 81.7 (C-2), 78.4 (C- 6-H), 4.31 (d, J = 12.0 Hz, 2 H, PhCH2-), 4.01 (dd, J = 2.8, 9.5 Hz,
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5Ј), 77.7 (C-4), 75.8 (PhCH2-), 75.6 (PhCH2-), 75.4 (PhCH2-), 74.9,
74.9, 74.7 (PhCH2-), 74.4 (PhCH2-), 73.3 (PhCH2-), 73.3
2 H, 4-H), 3.85 (m, 2 H, 5-H), 3.65 (d, J = 9.5 Hz, 2 H, 3-H), 3.45
(dd, J = 6.3, 9.4 Hz, 2 H, 7-H), 3.40 (dd, J = 6.9, 9.4 Hz, 2 H, 7-
(PhCH2-), 72.2 (C-6Ј), 69.0 (C-6), 68.4 (C-7Ј), 22.2 (C-1Ј) ppm. IR H), 1.55 (s, 6 H, -CH3) ppm. 13C NMR (150 MHz, CDCl3): δ =
(neat): ν = 3032.47, 2912.87, 2858.85, 1495.01, 1454.50, 1361.91, 139.1, 139.1, 138.8, 138.4, 128.2, 128.2, 128.1, 128.1, 128.0, 127.7,
˜
1068.69, 734.97, 698.32 cm– 1 . HRMS (FAB): calcd. for
C69H72O11Na 1099.4972; found 1099.4988.
127.5, 127.5, 127.4, 127.3, 127.1, 101.2 (C-2), 82.7 (C-3), 80.6 (C-
4), 75.3 (PhCH2- or C-5), 75.2 (PhCH2- or C-5), 74.4 (PhCH2-),
73.2 (PhCH2-), 72.6 (PhCH2-), 69.7 (C-6), 69.3 (C-7), 22.5 (C-1)
General Procedure 2: Deprotection of Disaccharide.[23] 1-Deoxy-α-
ppm. IR (neat): ν = 3030.54, 2922.51, 2864.64, 1469.94, 1454.50,
˜
D-gluco-hept-2-ulopyranosyl α-D-Glucopyranoside (9aa): To a solu-
1097.63, 1060.98 cm–1. HRMS (FAB): calcd. for C70H74O11Na
1113.5129; found 1113.5132. C70H74O11 (1090.77): calcd. C 77.04,
H 6.83; found C 77.02, H 6.80.
tion of 7aa (51 mg, 0.047 mmol) in THF (1.6 mL) was added basic
alumina (13 mg), and 20% Pd(OH)2/C (23 mg) was added under
an argon atmosphere, and then the mixture was stirred under a
hydrogen atmosphere (balloon) at room temperature. After 90 min, 3,4,5,7-Tetra-O-benzyl-1-deoxy-α-
D
-manno-hept-2-ulopyranosyl
MeOH (1.6 mL) was added to the mixture and stirred for 30 min.
The reaction mixture was filtered through filter paper, and the fil-
3,4,5,7-Tetra-O-benzyl-1-deoxy-α-D-manno-hept-2-ulopyranoside
(11cc): To a stirred mixture of 3c (56 mg, 0.094 mmol), 2c (58 mg,
0.104 mmol), and 4 Å MS (110 mg) in CH2Cl2 (1.9 mL) was added
trate was evaporate and dried to give 9aa (17 mg, quant.). [α]2D7
=
+140.0° (c = 0.85, CH3OH). 1H NMR (600 MHz, CD3OD): δ = TMSOTf (3.4 µL, 0.019 mmol) at –78 °C. After being stirred for
5.13 (d, J = 3.6 Hz, 1 H, 1-H), 3.98 (ddd, J = 10.2, 2.5, 5.2 Hz, 1
H, 6Ј-H), 3.72 (m, 1 H, 5-H), 3.72 (dd, J = 9.6, 9.9 Hz, 1 H, 3-H),
3.68 (dd, J = 9.6, 9.3 Hz, 1 H, 4Ј-H), 3.68 (dd, J = 2.5, 11.8 Hz, 1
H, 7Ј-H), 3.66 (dd, J = 2.5, 12.1 Hz, 1 H, 6-H), 3.59 (dd, J = 5.0,
6.5 h at the same temperature, the reaction mixture was quenched
with triethylamine and filtered through a pad of celite. The solvent
was evaporated, and the residue was purified by column
chromatography (silica gel, neutral, hexane/ethyl acetate, 10:1) to
12.1 Hz, 1 H, 6-H), 3.56 (dd, J = 5.2, 11.8 Hz, 1 H, 7Ј-H), 3.35 give 11cc (75 mg, 73%). [α]2D2 = +37.5° (c = 0.86, CHCl3). 1H NMR
(dd, J = 3.6, 9.9 Hz, 1 H, 2-H), 3.24 (dd, J = 9.6, 9.9 Hz, 1 H, 4- (600 MHz, CDCl3): δ = 7.36–7.18 (m, 40 H, ArH), 4.92–4.88 (m,
H), 3.20 (dd, J = 9.3, 10.2 Hz, 1 H, 5Ј-H), 3.04 (d, J = 9.6 Hz, 1
4 H, PhCH2-), 4.65 (d, J = 11.8 Hz, 2 H, PhCH2-), 4.64 (d, J =
H, 3Ј-H), 1.42 (s, 3 H, 1Ј-H) ppm. 13C NMR (150 MHz, CD3OD): 12.1 Hz, 2 H, PhCH2-), 4.62 (d, J = 11.8 Hz, 2 H, PhCH2-), 4.56
δ = 102.1 (C-2Ј), 93.2 (C-1), 78.6 (C-3Ј), 74.9 (C-4Ј), 74.6 (C-3), (d, J = 10.5 Hz, 2 H, PhCH2-), 4.55 (d, J = 11.3 Hz, 2 H,
73.9 (C-6Ј), 73.6 (C-2), 73.5 (C-5), 72.1 (C-5Ј), 72.1 (C-4), 62.8 (C- PhCH2-), 4.52 (d, J = 12.1 Hz, 2 H, PhCH2-), 3.98–3.93 (m, 4 H,
7Ј), 62.6 (C-6), 23.7 (C-1Ј) ppm.
4-H, 5-H), 3.76–3.68 (m, 6 H, 6-H, 7-H, 7-H), 3.60 (d, J = 2.2 Hz,
2 H, 3-H), 1.66 (s, 6 H, -CH3) ppm. 13C NMR (150 MHz, CDCl3):
δ = 138.6, 138.6, 138.5, 138.4, 128.5, 128.4, 128.3, 128.2, 128.2,
127.7, 127.7, 127.6, 127.6, 127.4, 127.3, 127.3, 102.4 (C-2), 81.6
(C-4), 79.7 (C-3), 75.3 (PhCH2-), 75.2 (PhCH2-), 75.0 (C-5), 73.4
(PhCH2-), 73.2 (C-6), 72.4 (PhCH2-), 69.4 (C-7), 21.8 (C-1) ppm.
Deoxy-α- -gluco-hept-2-ulopyranosyl β-D-Glucopyranoside (10aa):
D
To a solution of 8aa (19.5 mg, 0.018 mmol) in THF (0.6 mL) was
added basic alumina (5 mg), and 20% Pd(OH)2/C (10 mg) was
added under an argon atmosphere, and then the mixture was
stirred under a hydrogen atmosphere (balloon) at room tempera-
ture. After 60 min, MeOH (0.6 mL) was added to the mixture and
stirred for 30 min. The reaction mixture was filtered through filter
paper, and the filtrate was evaporate and dried to give 10aa (6.2 mg,
97%). [α]2D7 = +71.4° (c = 0.68, CH3OH). 1H NMR (600 MHz,
IR (neat): ν = 3030.54, 2914.80, 2860.78, 1469.94, 1454.50, 1367.70,
˜
1207.59, 1107.27, 1070.62 cm–1. HRMS (FAB): calcd. for
C70H74O11Na 1113.5129; found 1113.5135. C70H74O11 (1090.77): C
77.04, H 6.83; found C 76.89, H 6.96.
CD3OD): δ = 4.56 (d, J = 7.7 Hz, 1 H, 1-H), 4.13 (ddd, J = 2.2, 1-Deoxy-α-
7.2, 10.2 Hz, 1 H, 6Ј-H), 3.76 (dd, J = 2.2, 11.8 Hz, 1 H, 6-H), 3.75 hept-2-ulopyranoside (13bb): To a solution of 11bb (27.0 mg,
(dd, J = 2.2, 11.8 Hz, 1 H, 7Ј-H), 3.58 (dd, J = 9.1, 9.4 Hz, 1 H, 0.025 mmol) in THF (0.8 mL) was added basic alumina (6.8 mg)
D-galacto-hept-2-ulopyranosyl 1-Deoxy-α-D-galacto-
4Ј-H), 3.49 (dd, J = 7.2, 11.8 Hz, 1 H, 7Ј-H), 3.44 (dd, J = 7.2,
11.8 Hz, 1 H, 6-H), 3.29 (dd, J = 9.1, 9.3 Hz, 1 H, 3-H), 3.20 (m,
1 H, 5-H), 3.13 (dd, J = 7.7, 9.3 Hz, 1 H, 2-H), 3.11–3.07 (m, 3 H,
4-H, 3Ј-H, 5Ј-H), 1.40 (s, 3 H, 1Ј-H) ppm. 13C NMR (150 MHz,
and 20% Pd(OH)2/C (13.5 mg) under an argon atmosphere. The
mixture was then stirred under a hydrogen atmosphere (balloon) at
room temperature. After 2 h, MeOH (0.8 mL) was added to the
mixture and stirred for 1 h. The reaction mixture was filtered
CD3OD): δ = 103.3 (C-2Ј), 98.2 (C-1), 78.3 (C-5), 78.3 (C-3Ј), 77.6 through filter paper, and the filtrate was evaporate and dried to
1
(C-3), 75.0 (C-6Ј), 75.0 (C-2), 74.9 (C-4Ј), 72.5 (C-4), 71.9 (C-5Ј),
63.5 (C-7Ј), 63.2 (C-6), 22.6 (C-1Ј) ppm.
give 13bb (6.6 mg, 71%). [α]2D1 = +152.8° (c = 0.60, CH3OH). H
NMR (600 MHz, CD3OD): δ = 4.10 (m, 2 H, 6-H), 3.85–3.83 (m,
4 H, 4-H, 5-H), 3.59 (dd, J = 6.3, 11.3 Hz, 2 H, 7-H), 3.56 (dd, J
= 6.6, 11.3 Hz, 2 H, 7-H), 3.34 (d, J = 9.4 Hz, 2 H, 3-H), 1.56 (s,
6 H, 1-H) ppm. 13C NMR (150 MHz, CD3OD): δ = 102.7 (C-2),
76.5 (C-3), 72.4 (C-6), 72.3 (C-4), 71.5 (C-5), 71.2 (C-7), 23.1 (C-
1) ppm.
3,4,5,7-Tetra-O-benzyl-1-deoxy-α-
3,4,5,7-Tetra-O-benzyl-1-deoxy-α-
D
-galacto-hept-2-ulopyranosyl
D
-galacto-hept-2-ulopyranoside
(11bb): To a stirred mixture of 3b (56 mg, 0.093 mmol), 2b (57 mg,
0.102 mmol), and 4 Å MS (110 mg) in CH2Cl2(1.9 mL) was added
TMSOTf (3.4 µL, 0.019 mmol) at –78 °C. After being stirred for
17 h at the same temperature, the reaction mixture was quenched
with triethylamine and filtered through a pad of celite. The
solvent was evaporated, and the residue was purified by column
chromatography (silica gel, neutral, hexane/ethyl acetate, 10:1) to
give 11bb (28 mg, 28%). [α]2D2 = +61.7° (c = 1.41 CHCl3). 1H NMR
1-Deoxy-α-D-manno-hept-2-ulopyranosyl 1-Deoxy-α-D-manno-hept-
2-ulopyranoside (13cc): To a solution of 11cc (15.2 mg, 0.014 mmol)
in THF (0.5 mL) was added basic alumina (3.8 mg) and 20 %
Pd(OH)2/C (7.6 mg) under an argon atmosphere. The mixture was
then stirred under a hydrogen atmosphere (balloon) at room tem-
(600 MHz, CDCl3): δ = 7.31–7.14 (m, 40 H, ArH), 4.93 (d, J = perature. After 3.5 h, MeOH (0.5 mL) was added to the mixture
11.5 Hz, 2 H, PhCH2-), 4.92 (d, J = 11.6 Hz, 2 H, PhCH2-), 4.64 and stirred for 30 min. The reaction mixture was filtered through
(d, J = 11.5 Hz, 2 H, PhCH2-), 4.63 (d, J = 12.1 Hz, 2 H,
PhCH2-), 4.60 (d, J = 12.1 Hz, 2 H, PhCH2-), 4.57 (d, J = 11.7 Hz,
2 H, PhCH2-), 4.39 (d, J = 12.0 Hz, 2 H, PhCH2-), 4.39 (m, 2 H,
filter paper, and the filtrate was evaporate and dried to give 13cc
(5.0 mg, 96%). [α]2D2 = +74.7° (c = 0.59, H2O). 1H NMR (600 MHz,
CD3OD): δ = 3.82–3.78 (m, 4 H, 4-H, 7-H), 3.70 (dd, J = 4.9,
Eur. J. Org. Chem. 2007, 3758–3764
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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