LETTER
A Short Synthetic Route to b-C-Glycosides of N-Acetylglucosamine
1007
H-4), 4.30–4.05 (m, 4 H, H-2, H-6, H-6¢ and CH2Ph), 3.96
73.3 (CH2Ph), 69.7 (C-6¢), 60.4 (CH2Ph), 58.6 (CH2Ph), 54.2
(C-2¢), 51.7 (CH2N), 50.8 (CH2N), 23.8 (COCH3). MS
(ESI): m/z (%) = 726.2 (100) [M + H]+, 748.2 (35) [M +
Na]+. HRMS (ESI high resolution): m/z calcd for
C46H52O5N3: 726.3901; found: 726.3914. Anal. Calcd for
C46H51O5N3: C, 76.11; H, 7.08; O, 11.02; N, 5.79. Found: C,
76.02; H, 6.83; N, 5.76.
(d, 1 H, J = 13 Hz, CH2Ph), 3.65–3.50 (m, 4 H, H-5, H-7 and
2 × CH2Ph), 2.95–2.85 (m, 2 H, CH2N), 2.60–2.50 (m, 2 H,
CH2N), 2.03 (s, 3 H, COCH3), 2.01 (s, 3 H, COCH3), 1.99 (s,
3 H, COCH3), 1.75 (s, 3 H, COCH3). 13C NMR (90 MHz,
CDCl3): d = 170.9 (COCH3), 170.5 (COCH3), 169.9
(COCH3), 169.3 (COCH3), 139.0 (Cq Ph), 138.8 (Cq Ph),
128.7 (CH Ph), 128.4 (CH Ph), 128.2 (CH Ph), 127.2 (CH
Ph), 126.8 (CH Ph), 84.9 (C-7), 78.0 (C-1), 75.9 (C-5), 75.0
(C-3), 68.6 (C-4), 62.2 (C-6), 60.1 (CH2Ph), 58.5 (CH2Ph),
51.7 (C-2), 51.0 (CH2N), 50.6 (CH2N), 23.3 (COCH3), 20.7
(COCH3), 20.5 (COCH3). MS (ES): m/z (%) = 582 (100) [M
+ H]+, 604 (50) [M + Na]+. Anal. Calcd for C31H39O8N3: C,
64.01; H, 6.76; O, 22.01; N, 7.22. Found: C, 63.84; H, 7.06;
O, 22.09; N, 6.88.
(17) Preparation of 2-(N-Acetyl)-2-deoxy-1-formyl-3,4,6-tri-
O-benzyl-b-D-glucopyranoside (9).
To a solution of the aminal 8 (30 mg, 0.04 mmol) in a
mixture of THF (1 mL) and H2O (1 mL) was added Dowex-
50 (H+) resin (100 mg). After stirring for 1 h at r.t., the
suspension was filtered, concentrated and coevaporated with
toluene (3 × 10 mL). The aldehyde 9 (20 mg) was obtained
quantitatively. 1H NMR (400 MHz, CDCl3): d = 9.53 (d, 1
H, J = 2 Hz, H-7), 7.45–7.15 (m, 15 H, Ph), 5.24 (d, 1 H,
J = 8 Hz, NH), 4.86 (d, 1 H, J = 12 Hz, CH2Ph), 4.82 (d,
1 H, J = 11 Hz, CH2Ph), 4.65 (d, 1 H, J = 12 Hz, CH2Ph),
4.63 (d, 1 H, J = 12 Hz, CH2Ph), 4.60 (d, 1 H, J = 11 Hz,
CH2Ph), 4.57 (d, 1 H, J = 12 Hz, CH2Ph), 3.96 (q, 1 H, J = 8
Hz, H-2), 3.75 (d, 2 H, J = 3 Hz, 2 × H-6), 3.73–3.69 (m, 2
H, H-3 and H-4), 3.65 (dd, 1 H, J = 2, 10 Hz, H-1), 3.55 (dt,
1 H, J = 3, 9 Hz, H-5), 1.75 (s, 3 H, COCH3). 13C NMR (100
MHz, CDCl3): d = 197.4 (C-7), 170.5 (COCH3), 138.0 (Cq
Ph), 137.8 (Cq Ph), 137.7 (Cq Ph), 128.7 (CH Ph), 128.5
(CH Ph), 128.4 (CH Ph), 128.2 (CH Ph), 128.0 (CH Ph),
127.8 (CH Ph), 127.7 (CH Ph), 81.9 (C-1), 81.5 (C-3 or
C-4), 78.9 (C-5), 78.2 (C-3 or C-4), 75.0 (CH2Ph), 74.6
(CH2Ph), 73.5 (CH2Ph), 68.6 (C-6), 51.0 (C-2), 23.1
(COCH3).
(15) Preparation of 2-(N-Acetyl)-2-deoxy-1-formyl-3¢,4¢,6¢-
tri-O-acetyl-b-D-glucopyranoside (7).
To a solution of the aminal 6 (75 mg, 0.13 mmol) in a
mixture of THF (2 mL) and H2O (2 mL) is added Dowex-50
(H+) resin (150 mg). After stirring for 1 h at r.t., the reaction
mixture was filtered, concentrated and coevaporated with
toluene (3 × 10 mL). The aldehyde 7 (46 mg) was obtained
quantitatively. 1H NMR (360 MHz, CDCl3): d = 9.52 (d, 1
H, J = 3 Hz, H-7), 5.79 (d, 1 H, J = 9 Hz, NH), 5.20–5.10 (m,
2 H, H-4 and H-3), 4.35–4.20 (m, 2 H, H-6 and H-2), 4.17
(dd, 1 H, J = 2, 12 Hz, H-6¢), 3.75–3.65 (m, 1 H, H-5), 3.67
(dd, 1 H, J = 3, 10 Hz, H-1), 2.14 (s, 3 H, COCH3), 2.06 (s,
3 H, COCH3), 2.04 (s, 3 H, COCH3), 1.93 (s, 3 H, COCH3).
13C NMR (90 MHz, CDCl3): d = 195.8 (C-7), 171.6
(COCH3), 170.7 (COCH3), 170.6 (COCH3), 169.2 (COCH3),
82.0 (C-1), 75.9 (C-5), 73.1 (C-3 or C-4), 67.8 (C-3 or C-4),
61.8 (C-6), 50.3 (C-2), 23.0 (COCH3), 20.8 (COCH3), 20.7
(COCH3), 20.6 (COCH3).
(18) Preparation of (1R)- and (1S)-1-(2¢-N-Acetyl)-2¢-deoxy-
3¢,4¢,6¢-tri-O-acetyl-b-D-glucopyranosyl)-1-acetoxy-1-
but-3-ene (11).
(16) Preparation of 2-(2¢-N-Acetyl)-2¢-deoxy-3¢,4¢,6¢-tri-O-
To a solution of the aminal 5 (0.32 mmol, 200 mg) in MeOH
(3 mL) was added sodium methoxide (2 mg). After stirring
for 1 h at r.t. MeOH was evaporated. THF (1.6 mL), H2O
(1.6 mL) and Dowex-50 (H+) resin (400 mg) were added.
After stirring for 1 h at r.t., the suspension was filtered,
concentrated and coevaporated with toluene (3 × 10 mL).
The residue was dissolved in a 1:1 mixture of THF–H2O (3.2
mL) and allyl bromide (0.64 mmol, 55 mL) and In (0.96
mmol, 110 mg) were added. After stirring for 12 h at r.t., the
suspension was filtered over Celite®. After washing with
EtOH and evaporation of the solvents under reduced
pressure, the residue was dissolved in a 2:1 mixture of
pyridine and Ac2O (1.5 mL). After stirring for 12 h at r.t., the
reaction mixture was concentrated and coevaporated with
toluene. Then, EtOAc (15 mL) was added and the mixture
was washed with aq HCl (0.1 N, 5 mL) then with brine (10
mL). The organic phase was dried (Na2SO4) and
benzyl-b-D-glucopyranosyl)-1,3-bis(phenyl-
methyl)imidazolidine (8).
To a solution of the aminal 5 (0.137 g, 0.22 mmol) in MeOH
(2.2 mL) was added MeONa (2 mg). After stirring for 2 h at
r.t., the solvents were coevaporated under reduced pressure
with toluene (2 × 5 mL). DMF (4.4 mL), NaH (60%
dispersion in mineral oil, 34 mg, 0.86 mmol) and benzyl
bromide (82 mL, 0.68 mmol) were then added. After stirring
for 2 h at r.t., MeOH (1 mL) and H2O (10 mL) were added
and the aqueous phase was extracted with EtOAc (4 × 10
mL). The combined organic phases were then dried
(Na2SO4), filtered and concentrated. Flash chromatography
(SiO2, PE–EtOAc +1% Et3N = 7:3 to 5:5) of the crude
residue afforded the pure aminal 8 (0.120 mg, 75% from 4)
as a white solid. Mp 116 °C. [a]D20 +16.7 (c 0.6, CHCl3). IR
(ATR-FTIR, diamond prism): 3278, 3028, 2909, 2854,
1643, 1598, 1552, 1102, 1088, 1070, 745, 694 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.45–7.15 (m, 25 H, Ph),
5.36 (d, 1 H, J = 5 Hz, NH), 4.83 (d, 2 H, J = 12 Hz,
2 × CH2Ph), 4.70 (d, 1 H, J = 11 Hz, CH2Ph), 4.59 (d, 2 H,
J = 11 Hz, 2 × CH2Ph), 4.54 (d, 1 H, J = 12 Hz, CH2Ph),
4.22 (d, 1 H, J = 14 Hz, CH2Ph), 4.08 (t, 1 H, J = 9 Hz, H-
3¢), 3.95 (d, 2 H, J = 13 Hz, 2 × CH2Ph), 3.89–3.82 (m, 2 H,
H-1¢, H-2¢), 3.74 (dd, 1 H, J = 2, 11 Hz, H-6¢a), 3.69 (dd, 1
H, J = 4, 11 Hz, H-6¢b), 3.62–3.51 (m, 5 H, H-4¢, H-5¢, H-1,
2 × CH2Ph), 3.10–3.02 (m, 1 H, CH2N), 3.00–2.90 (m, 1 H,
CH2N), 2.65–2.55 (m, 2 H, 2 × CH2N), 1.68 (s, 3 H,
COCH3). 13C NMR (90 MHz, CDCl3): d = 170.3 (COCH3),
139.7 (Cq Ph), 139.3 (Cq Ph), 138.9 (Cq Ph), 138.5 (Cq Ph),
129.1 (CH Ph), 128.7 (CH Ph), 128.3 (CH Ph), 128.0 (CH
Ph), 127.8 (CH Ph), 127.5 (CH Ph), 127.4 (CH Ph), 127.1
(CH Ph), 126.8 (CH Ph), 85.1 (C-1), 83. 5 (C-3¢), 79.5 (C-
5¢), 79.0 (C-4¢), 77.2 (C-1¢), 75.0 (CH2Ph), 74.6 (CH2Ph),
concentrated. The crude residue was purified by flash
chromatography (PE–EtOAc = 3:7 to 2:8) to afford 11 as a
mixture of two diastereomers (87% from 5).
20
Diastereomer 1 (32 mg, white solid): mp 124 °C; [a]D
–44.3 (c 0.3, CHCl3). IR (ATR-FTIR, diamond prism):
3258, 3075, 2863, 1752, 1734, 1635, 1560, 1453, 1358,
1314, 1101, 1054, 735, 695 cm–1. 1H NMR (400 MHz,
CDCl3): d = 5.85–5.60 (m, 2 H, H-3 and NH), 5.11 (dd, 1 H,
J = 1, 17 Hz, H-4a), 5.09–5.05 (m, 2 H, H-4¢, H-4b), 5.01 (t,
1 H, J = 10 Hz, H-3¢), 4.88 (ddd, 1 H, J = 1, 4, 9 Hz, H-1),
4.23 (dd, 1 H, J = 4, 12 Hz, H-6¢a), 4.19–4.09 (m, 2 H, H-2
and H-6¢b), 3.57 (ddd, 1 H, J = 2, 4, 10 Hz, H-5¢), 3.51 (dd,
1 H, J = 2, 11 Hz, H-1¢), 2.60–2.45 (m, 2 H, 2 × H-2), 2.08
(s, 3 H, COCH3), 2.05 (s, 3 H, COCH3), 2.02 (s, 3 H,
COCH3), 2.01 (s, 3 H, COCH3), 1.96 (s, 3 H, COCH3).
13C NMR (100 MHz, CDCl3): d = 171.3 (COCH3), 171.0
(COCH3), 170.6 (COCH3), 170.2 (COCH3), 169.2 (COCH3),
Synlett 2006, No. 7, 1004–1008 © Thieme Stuttgart · New York