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A. Varadi et al.
260
column chromatography with a chloroform/methanol gra-
dient mixture from 95:5 to 90:10 as eluent. Codeinone,
resulting from the simultaneous oxidation reaction by
Ag2CO3 present in the reaction mixture of the Koenigs-
Knorr glucosylation of 11, could be isolated from crude 12.
The pure product fractions were collected and recrystal-
lized from hot ethanol to yield 0.50 g of 12 (32 %) as white
3H, 60-acetyl), 2.02 (s, 3H, 40-acetyl), 1.99 (s, 3H, 30-
acetyl) ppm; 13C NMR (150 MHz, CDCl3): d = 122.8
(CH), 119.1 (CH), 99.1 (CH), 88.6 (CH), 74.7 (CH), 72.5
(CH), 71.6 (CH), 71.2 (CH), 68.4 (CH), 62.9 (CH2), 20.7 (4
CH3), 20.6 (CH3) ppm; HRMS: m/z calcd. for [M ? H]?
([C33H42NO13]?) 660.2651, found 660.2648.
(5a,6a)-4,5-Epoxy-3-methoxy-17-methylmorphinan-6-yl-b-
D-2,3,4,6-tetraacetylglucopyranoside (tetraacetyl-6-O-
glucopyranosyldihydrocodeine) (14, C32H41NO12)
1
crystals. M.p.: 196–197 °C; H NMR (600 MHz, CDCl3):
d = 6.52 (d, J = 8.1 Hz, H-2), 6.63 (d, J = 8.1 Hz, H-1),
5.69 (d, J = 9.5 Hz, H-7), 5.32 (d, J = 9.5 Hz, H-8), 5.27
(t, J = 9.4 Hz, H-30), 5.12 (t, J = 9.4 Hz, H-40), 5.07 (dd,
J = 9.4, 7.5 Hz, H-20), 4.90 (d, J = 6.0 Hz, H-5), 4.90 (d,
J = 7.5 Hz, H-10), 4.32 (d, J = 6.0 Hz, H-6), 4.28 and
4.16 (2 dd, J = 15.0 Hz, H-60), 3.77 (ddd, J = 4.5, 2.5 Hz,
H-50), 2.16 (s, 3H, 20-acetyl), 2.08 (s, 3H, 60-acetyl), 2.03
(s, 3H, 40-acetyl), 2.02 (s, 3H, 30-acetyl) ppm; 13C NMR
(150 MHz, CDCl3): d = 130.5 (CH), 128.8 (CH), 118.9
(CH), 113.4 (CH), 98.2 (CH), 88.3 (CH), 72.8 (CH), 72.1
(CH), 71.9 (CH), 71.2 (CH), 68.6 (CH), 62.1 (CH2), 20.8
(CH3), 20.6 (CH3), 20.6 (CH3), 20.5 (CH3) ppm; HRMS:
m/z calcd. for [M ? H]? ([C32H40NO12]?) 630.2541,
found 630.2535.
Yield: 47 %; m.p.: 190–192 °C; 1H NMR (600 MHz,
CDCl3): d = 6.69 (d, J = 8.0 Hz, H-2), 6.58 (d,
J = 8.0 Hz, H-1), 5.18 (t, J = 9.5 Hz, H-30), 5.08 (t,
J = 9.5 Hz, H-40), 4.82 (dd, J = 9.5, 7.5 Hz, H-20), 4.91
(d, J = 7.5 Hz, H-10), 4.65 (d, J = 6.0 Hz, H-5), 4.25 and
4.14 (2 dd, J = 15.1 Hz, H-60), 4.09 (d, J = 6.0 Hz, H-6),
3.77 (ddd, J = 4.4, 2.5 Hz, H-50), 2.08 (s, 3H, 60-acetyl),
2.07 (s, 3H, 20-acetyl), 2.02 (s, 3H, 40-acetyl), 1.98 (s, 3H,
30-acetyl) ppm; 13C NMR (150 MHz, CDCl3): d = 118.6
(CH), 113.6 (CH), 98.4 (CH), 88.1 (CH), 72.9 (CH), 72.5
(CH), 71.7 (CH), 71.6 (CH), 68.7 (CH), 62.2 (CH2), 20.8
(CH3), 20.7 (CH3), 20.7 (CH3), 20.6 (CH3) ppm; HRMS:
m/z calcd. for [M ? H]? ([C32H42NO12]?) 632.2702,
found 632.2698.
(5a,6a)-3-Acetyloxy-7,8-didehydro-4,5-epoxy-17-methyl-
morphinan-6-yl-b-D-2,3,4,6-tetraacetylglucopyranoside
(tetraacetyl-6-O-glucopyranosyl-3-O-acetylmorphine)
(5, C33H39NO13)
(5a,6a)-7,8-Didehydro-4,5-epoxy-6-hydroxy-17-methyl-
morphinan-3-yl-b-D-2,3,4,6-tetraacetylglucopyranoside
(tetraacetyl-3-O-glucopyranosylmorphine) (2, C31H37NO12)
Morphine (1, 2.80 g, 9.82 mmol) was suspended in 40 cm3
acetone. Acetobromo-a-D-glucose (5.00 g, 12.16 mmol)
and 6 cm3 2 M aqueous NaOH solution were added and
stirred for 24 h at room temperature. The precipitate was
filtered, and the filtrate was evaporated to dryness under
reduced pressure, suspended in water and basified (pH 9)
with 10 % aqueous NaOH. After extraction with chloro-
form and evaporation of the solvent, the crude product was
purified using silica gel column chromatography with a
chloroform/methanol isocratic mixture of 80:20 as eluent.
The pure fractions were collected and crystallized from
diethyl ether to yield 0.76 g of 2 (12 %) as white crystals.
M.p.: 160–161 °C; 1H NMR (600 MHz, CDCl3): d = 6.77
(d, J = 8.0 Hz, H-2), 6.53 (d, J = 8.0 Hz, H-1), 5.67 (d,
J = 9.4 Hz, H-7), 5.28 (t, J = 9.4 Hz, H-30), 5.27 (d,
J = 9.4 Hz, H-8), 5.25 (d, J = 7.5 Hz, H-10), 5.20 (t,
J = 9.4 Hz, H-40), 5.16 (dd, J = 9.4, 7.5 Hz, H-20), 4.87
(d, J = 6.0 Hz, H-5), 4.17 (d, J = 6.0 Hz, H-6), 4.27 and
4.19 (2 dd, J = 15.0 Hz, H-60), 3.84 (ddd, J = 4.5, 2.5 Hz,
H-50), 2.08 (s, 3H, 40-acetyl), 2.05 (s, 3H, 60-acetyl), 2.03
(s, 3H, 20-acetyl), 2.03 (s, 3H, 30-acetyl) ppm; 13C NMR
(150 MHz, CDCl3): d = 133.8 (CH), 128.4 (CH), 120.2
(CH), 119.7 (CH), 100.1 (CH), 91.8 (CH), 72.8 (CH), 72.4
(CH), 71.9 (CH), 68.5 (CH), 66.4 (CH), 62.0 (CH2), 20.8
(CH3), 20.7 (3 CH3) ppm; HRMS: m/z calcd. for [M ? H]?
([C31H38NO12]?) 616.2389, found 616.2382.
Yield: 34 %; m.p.: 99–100 °C; 1H NMR (600 MHz,
CDCl3): d = 6.73 (d, J = 8.0 Hz, H-2), 6.55 (d,
J = 8.0 Hz, H-1), 5.70 (d, J = 9.4 Hz, H-7), 5.29 (d,
J = 9.4 Hz, H-8), 5.24 (t, J = 9.5 Hz, H-30), 5.12 (t,
J = 9.5 Hz, H-40), 5.08 (dd, J = 9.5, 7.7 Hz, H-20), 4.88
(d, J = 6.0 Hz, H-5), 4.82 (d, J = 7.7 Hz, H-10), 4.26 and
4.15 (2 dd, J = 15.3 Hz, H-60), 4.23 (d, J = 6.0 Hz, H-6),
3.76 (ddd, J = 4.5, 2.4 Hz, H-50), 2.31 (s, 3H, 3-acetyl),
2.10 (s, 3H, 20-acetyl), 2.08 (s, 3H, 40-acetyl), 2.05 (s, 3H,
60-acetyl), 2.03 (s, 3H, 30-acetyl) ppm; 13C NMR
(150 MHz, CDCl3): d = 130.7 (CH), 128.7 (CH), 121.9
(CH), 119.2 (CH), 99.9 (CH), 89.8 (CH), 74.1 (CH), 72.8
(CH), 71.9 (CH), 71.2 (CH), 68.4 (CH), 62.0 (CH2), 20.7 (4
CH3), 20.7 (CH3) ppm; HRMS: m/z calcd. for [M ? H]?
([C33H40NO13]?) 658.2494, found 658.2487.
(5a,6a)-3-Acetyloxy-4,5-epoxy-17-methylmorphinan-
6-yl-b-D-2,3,4,6-tetraacetylglucopyranoside (tetra-
acetyl-6-O-glucopyranosyl-3-O-acetyldihydromorphine)
(9, C33H41NO13)
1
Yield: 32 %; H NMR (600 MHz, CDCl3): d = 6.81 (d,
J = 7.8 Hz, H-2), 6.63 (d, J = 7.8 Hz, H-1), 5.19 (t,
J = 9.5 Hz, H-30), 5.07 (dd, J = 9.5, 7.7 Hz, H-20), 4.90 (t,
J = 9.5 Hz, H-40), 4.76 (d, J = 7.7 Hz, H-10), 4.67 (d,
J = 6.0 Hz, H-5), 4.23 and 4.13 (2 dd, J = 15.0 Hz, H-60),
3.96 (d, J = 6.0 Hz, H-6), 3.75 (ddd, J = 4.5, 2.5 Hz,
H-50), 2.32 (s, 3H, 3-acetyl), 2.13 (s, 3H, 20-acetyl), 2.07 (s,
123