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nigs–Knorr glycosylation with globally protected glucuronyl bro-
mide (0.403 g, 1.02 mmol). The resulting off-white powder (0.442 g,
0.883 mmol, 85%) was used without further purification. 1H NMR
Protected unsaturated glucuronide 9a: Protected glucuronide 8a
(0.275 g, 0.550 mmol) was subjected to the general method for
DBU-promoted elimination. Purification by flash column chroma-
tography (petroleum ether/ethyl acetate 5:2) gave a white powder
(300 MHz, [D6]DMSO): d=8.22–8.11 (m, 3H; H-3’,4’,6’), 5.98 (d, J1,2
7.4 Hz, 1H; H-1), 5.41 (t, J2,3 =J3,4 =9.2 Hz, 1H; H-3), 5.16 (t, J4,5
=
=
1
(0.133 g, 0.302 mmol, 55%). H NMR (300 MHz, [D6]DMSO): d=8.80
9.5 Hz, 1H; H-4), 5.14 (dd, 1H; H-2), 4.83 (d, 1H; H-5), 3.64 (s, 3H;
OMe), 2.02 (s, 6H; 2OAc), 1.99 ppm (s, 3H; OAc).
(d, J3’,5’ =2.8 Hz, 1H; H-5’), 8.60 (dd, J2’,3’ =9.3 Hz, 1H; H-3’), 7.83 (d,
1H; H-2’), 6.57 (dd, J3,4 =2.1, J2,4 =0.9 Hz, 1H; H-4), 6.25 (dd, J1,2
=
4.8, J1,3 =1.3 Hz, 1H; H-1), 5.27–5.25 (td, J2,3 =2.1 Hz, 1H; H-3), 5.20
(ddd, 1H; H-2), 3.73 (s, 3H; OMe), 2.10 (s, 3H; OAc), 2.09 ppm (s,
3H; OAc).
Protected glucuronide 8e: 3-Nitrophenol (0.220 g, 1.58 mmol,
1.25 equiv) was used as acceptor in the general method for Koe-
nigs–Knorr glycosylation with globally protected glucuronyl bro-
mide (0.505 g, 1.27 mmol). Purification by flash column chromatog-
raphy (petroleum ether/ethyl acetate 2:1) yielded an off-white
Protected unsaturated glucuronide 9b: Protected glucuronide
8b (0.222 g, 0.444 mmol) was subjected to the general method for
DBU-promoted elimination. Purification by flash column chroma-
tography (petroleum ether/ethyl acetate 3:1) gave a white powder
1
powder (0.304 g, 0.668 mmol, 53%). H NMR (300 MHz, [D6]DMSO):
d=7.95 (ddd, J4’,5’ =8.2, J2’,4’ =2.2, J4’,6’ =0.8 Hz, 1H; H-4’), 7.80 (t,
1
(0.098 g, 0.223 mmol, 50%). H NMR (300 MHz, CDCl3): d=8.40 (d,
J
2’,6’ =2.2 Hz, 1H; H-2’), 7.65 (t, J5’,6’ =8.2 Hz, 1H; H-5’), 7.48 (ddd,
J
4’,6’ =2.2 Hz, 1H; H-6’), 8.04 (dd, J3’,4’ =8.8, 1H; H-4’), 7.90 (d, 1H; H-
1H; H-6’), 5.87 (d, J1,2 =7.8 Hz, 1H; H-1), 5.46 (t, J2,3 =J3,4 =9.6 Hz,
1H; H-3), 5.14 (dd, 1H; H-2), 5.09 (t, J4,5 =9.9 Hz, 1H; H-4), 4.76 (d,
1H; H-5), 3.62 (s, 3H; OMe), 2.02 (s, 3H; OAc), 2.01 (s, 3H; OAc),
1.99 ppm (s, 3H; OAc).
3’), 6.35 (dd, J3,4 =4.9, J2,4 =1.4 Hz, 1H; H-4), 6.05 (dd, J1,2 =1.9, J1,3
=
1.1 Hz, 1H; H-1), 5.28 (ddd, J2,3 =1.1 Hz, 1H; H-2), 5.24 (dt, 1H; H-
3), 3.80 (s, 3H; OMe), 2.14 (s, 3H; OAc), 2.13 ppm (s, 3H; OAc).
Protected unsaturated glucuronide 9e: Protected glucuronide 8e
(0.103 g, 0.232 mmol) was subjected to the general method for
DBU-promoted elimination. Purification by flash column chroma-
Protected glucuronide 8 f: 4-Chlorophenol (0.19 g, 1.48 mmol,
1.2 equiv) was used as acceptor in the general method for glycosy-
lation by Schmidt donor with globally protected glucuronyl hemi-
acetal (0.4 g, 1.20 mmol). Purification by flash column chromatog-
raphy (petroleum ether/ethyl acetate 3:1) yielded a white powder
tography (hexanes/ethyl acetate 3:1) gave
a white powder
(0.064 g, 0.166 mmol, 72%). 1H NMR (300 MHz, CDCl3): d=7.93–
7.90 (m, 2H; H-2’,4’), 7.50–7.41 (m, 2H; H-5’,6’), 6.30 (dd, J3,4 =4.0,
1
(0.103 g, 0.232 mmol, 20%). H NMR (300 MHz, CDCl3): d=7.25 (d,
J
2,4 =1.9 Hz, 1H; H-4), 5.88 (dd, J1,2 =1.9, J1,3 =1.1 Hz, 1H; H-1),
J
2’,3’ =J5’,6’ =9.0 Hz, 2H; H-3’,5’), 6.94 (d, 2H; H-2’,6’), 5.36–5.23 (m,
5.30–5.26 (m, 2H; H-2,3), 3.77 (s, 3H; OMe), 2.12 (s, 3H; OAc),
2.10 ppm (s, 3H; OAc).
3H; H-2,3,4), 5.11 (d, J1,2 =7.2 Hz, 1H; H-1), 4.19 (d, J4,5 =9.5 Hz, 1H;
H-5), 3.73 (s, 3H; OMe), 2.06 (s, 3H; OAc), 2.05 (s, 3H; OAc),
2.04 ppm (s, 3H; OAc).
Protected unsaturated glucuronide 9 f: Protected glucuronide 8 f
(0.103 g, 0.232 mmol) was subjected to the general method for
DBU-promoted elimination. Purification by flash column chroma-
Protected glucuronide 8h: 4-tert-Butylphenol (0.25 g, 1.66 mmol,
1.4 equiv) was used as acceptor in the general method for glycosy-
lation by Schmidt donor with globally protected glucuronyl hemi-
acetal (0.4 g, 1.20 mmol). Purification by flash column chromatog-
raphy (petroleum ether/ethyl acetate 3:1) yielded an amorphous
solid (0.158 g, 0.339 mmol, 28%). 1H NMR (300 MHz, CDCl3): d=
7.31 (d, J2’,3’ =J5’,6’ =8.9 Hz, 2H; H-3’,5’), 6.93 (d, 2H; H-2’,6’), 5.36–
tography (hexanes/ethyl acetate 3:1) gave
a
white powder
(0.064 g, 0.166 mmol, 72%). H NMR (300 MHz, CDCl3): d=7.26 (d,
2’,3’ =J5’,6’ =9.0 Hz, 2H; H-3’,5’), 7.03 (d, 2H; H-2’,6’), 6.29 (dd, J3,4
1
J
=
4.5, J2,4 =1.5 Hz, 1H; H-4), 5.77 (dd, J1,2 =2.7, J1,3 =1.0 Hz, 1H; H-1),
5.29–5.26 (m, 2H; H-2,3), 3.80 (s, 3H; OMe), 2.13 (s, 3H; OAc),
2.11 ppm (s, 3H; OAc); 13C NMR (101 MHz, CD3OD): d=170.4 (OAc),
169.7 (OAc), 162.1 (C-6), 154.9 (C-5), 142.1 (Ar), 129.4 (Ar), 128.1
(Ar), 118.5 (Ar), 107.7 (C-4), 95.1 (C-1), 68.2 (C-3), 64.9 (C-2), 51.9
(OMe), 19.47 (OAc), 19.32 ppm (OAc).
5.25 (m, 3H; H-2,3,4), 5.14 (d, J1,2 =7.2 Hz, 1H; H-1), 4.19 (d, J4,5
=
9.5 Hz, 1H; H-5), 3.74(s, 3H; OMe), 2.06 (s, 3H; OAc), 2.05 (s, 3H;
OAc), 2.05 (s, 3H; OAc), 1.30 ppm (s, 9H; tert-butyl).
Protected glucuronide 8i: Globally protected glucuronyl hemiace-
tal (see first half of general method for glycosylation by Schmidt
donor, 0.343 g, 1.03 mmol) was dissolved in toluene (2 mL), and
the solution was flushed with nitrogen. Benzyl bromide (0.245 mL,
2 equiv) and silver(I) carbonate (0.885 g, 3 equiv) were added, and
the reaction mixture was stirred overnight at ambient temperature
in the dark. The reaction was subsequently quenched with triethyl-
amine, and the mixture was diluted with dichloromethane and
filtered through Celite, after which the filtrate was washed with
HCl (1m), saturated NaHCO3, water and brine and then dried over
MgSO4. Purification by flash column chromatography (petroleum
ether/ethyl acetate 7:2) followed by recrystallisation from toluene/
petroleum ether yielded white plates (0.135 g, 0.318 mmol, 31%).
1H NMR (300 MHz, CDCl3): d=7.36–7.29 (m, 5H; H-2’,3’,4’,5’,6’),
5.28–5.18 (m, 2H; H-7’a,7’b), 5.08 (brt, J3,4 =8.3, J4,5 =9.2 Hz, 1H; H-
4), 4.92 (d, J1,2 =12.3 Hz, 1H; H-1), 4.64–4.58 (m, 2H; H-2,3), 4.02 (d,
1H; H-5), 3.76 (s, 3H; OMe), 2.01 (s, 3H; OAc), 2.01 (s, 3H; OAc),
1.99 ppm (s, 3H; OAc); 13C NMR (75 MHz, CDCl3): d=170.3 (OAc),
169.51 (OAc), 169.35 (OAc), 167.4 (C-6), 136.6 (Ar), 128.6 (Ar), 128.2
(Ar), 127.9 (Ar), 99.4 (C-1), 72.8 (C-3), 72.2 (C-2), 71.3 (C-4), 71.0
(OCH2Ar), 69.6 (C-5), 53.1 (OMe), 20.74 (2OAc), 20.64 ppm (OAc);
MS: m/z calcd: 447.1 [M+Na]+; found: 447.4.
Protected unsaturated glucuronide 9h: Protected glucuronide
8h (0.158 g, 0.338 mmol) was subjected to the general method for
DBU-promoted elimination. Purification by flash column chroma-
tography (hexanes/ethyl acetate 4:1) gave
a
white powder
(0.061 g, 0.150 mmol, 44%). H NMR (300 MHz, CDCl3): d=7.31 (d,
2’,3’ =J5’,6’ =8.9 Hz, 2H; H-3’,5’), 7.02 (d, 2H; H-2’,6’), 6.28 (dd, J3,4
1
J
=
4.2, J2,4 =1.6 Hz, 1H; H-4), 5.78 (dd, J1,2 =2.6, J1,3 =1.4 Hz, 1H; H-1),
5.31–5.26 (m, 2H; H-2,3), 3.81 (s, 3H; OMe), 2.13 (s, 3H; OAc), 2.11
(s, 3H; OAc), 1.29 ppm (s, 9H; tert-butyl); 13C NMR (101 MHz,
CD3OD): d=171.7 (OAc), 171.0 (OAc), 163.4 (C-6), 155.4 (C-5), 147.4
(Ar), 143.6 (Ar), 127.5 (Ar), 117.8 (Ar), 108.7 (C-4), 96.8 (C-1), 69.7 (C-
3), 66.4 (C-2), 53.1 (OMe), 35.1 (tert-butyl), 31.9 (tert-butyl), 20.73
(OAc), 20.59 ppm (OAc).
Protected unsaturated glucuronide 9i: Protected glucuronide 8i
(32 mg, 0.075 mmol) was subjected to the general method for
DBU-promoted elimination. Purification by flash column chroma-
tography (petroleum ether/ethyl acetate 5:2) gave a colourless
syrup (0.020 g, 0.055 mmol, 73%). 1H NMR (300 MHz, CDCl3): d=
7.37–7.28 (m, 5H; H-2’,3’,4’,5’,6’), 6.23 (dd, J3,4 =4.5, J2,4 =1.1 Hz,
1H; H-4), 5.30 (d, J1,2 =2.5 Hz, 1H; H-1), 5.20 (dd, J2,3 =1.9 Hz, 1H;
H-3), 5.14 (brq, 1H; H-2), 4.87 (d, J7’a,7’b =12.3 Hz, 1H; H-7’a), 4.68
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ChemBioChem 2014, 15, 124 – 134 131