5978
B. Hugon et al. / Bioorg. Med. Chem. 15 (2007) 5965–5980
128.6, 129.2, 144.8 (C tert arom), 148.7 (C@O Boc),
173.5, 173.9 (C@O).
J2 = 5.0 Hz), 5.27 (1H, t, J = 9.8 Hz), 5.37 (1H, t,
J = 8.6 Hz), 5.59 (1H, t, J = 9.5 Hz), 6.98 (1H, t,
0
J = 7.0 Hz), 6.99 (1H, d, J = 8.9 Hz, H1 Þ, 7.11 (1H, d,
4.1.34. 6-Methyl-imidazo[1,2-a]pyrrolopyridinylpyrrolo[2,3-
c:3,4-e]pyridine-5,7-dione (38). To a solution of 36 (32 mg,
0.081 mmol) in CH2Cl2 (5 mL) was added MnO2 (46 mg,
0.478 mmol). The mixture was stirred at room tempera-
ture for 12 h then filtered over Celite. The solid was
washed with CH2Cl2 then methanol. The filtrate was
evaporated to give a yellow solid (31 mg, 0.079 mmol)
which was dissolved in formic acid (40 mL). After stirring
at room temperature for 12 h, the solution was evapo-
rated, the solid residue was washed with water then
EtOAc to give 38 (18 mg, 0.062 mmol, 77% yield) as a yel-
low solid. Physical and spectral data of compound 38 are
given in Ref. 17.
J = 7.0 Hz), 7.15 (1H, br s), 7.17 (1H, br s), 7.83 (1H, s),
8.00 (1H, d, J = 7.1 Hz), 8.55 (1H, s). 13C NMR
(100 MHz, CDCl3): 19.9, 20.5, 20.6, 20.7 (CH3CO), 24.3
0
0
(NCH3), 61.6 (C6 ), 67.8, 71.6, 72.3, 75.6, 84.0 (C1 , C2 ,
0
0
0
0
C3 , C4 , C5 Þ, 112.6, 119.3, 127.0, 130.2, 134.5, 152.1 (C
tert arom), 103.9, 121.7, 126.4, 126.9, 137.6, 151.0 (C quat
arom), 167.5, 169.0, 169.5 (2C), 170.4 (C@O).
4.1.37.6-Methyl-12-(2,3,4,6-tetra-O-acetyl-b-D-glucopyrano-
syl)-imidazo[1,2-a] pyrido[30,20:4,5]pyrrolo[2,3-c]pyrrolo[3,4-
e]pyridine-5,7-(6H,12H)-dione 41 6-methyl-12-(2,3,4,6-tetra-
O-acetyl-b-D-glucopyranosyl)-7a,12-dihydroimidazo[1,2-
a]pyrido[30,20:4,5]pyrrolo[2,3-c]pyrrolo[3,4-e]pyridine-
5,7-(4aH,6H)-dione 42 2-methyl-8-(2,3,4,6-tetra-O-acet-
yl-b-D-glucopyranosyl)-8,12-dihydroimidazo[1,5-a]pyr-
ido[30,20:4,5]pyrrolo[2,3-c]pyrrolo[3,4-e]pyridine-1,3-
(2H,3aH)-dione (43). A solution of 40 (130 mg,
0.208 mmol) in acetonitrile (10 mL) was irradiated
with a halogen lamp (500 W) for 6h with cooling.
The solvent was removed and the residue purified
by flash chromatography (eluent : EtOAc/cyclohex-
ane 3:7 to 100% EtOAc) to give 41 (6 mg, 9.66 lmol,
5% yield) as a yellow solid, 42 (64 mg, 0.103 mmol,
50% yield) as a salmon-colored solid, and 43
(23 mg, 0.037 mmol, 18% yield) as a pale yellow solid.
4.1.35. 6-Methyl-imidazo[1,5-a]pyrrolopyridinylpyrrolo-
[2,3-c:3,4-e]pyridine-5,7-dione (39). Identical procedure
as described for 38 gave from 37 (47 mg, 0.119 mmol)
compound 39 (16 mg, 0.055 mmol, 47% yield) as a red
solid. Physical and spectral data of compound 39 are gi-
ven in Ref. 17.
4.1.36. 3-(1H-Imidazol-1-yl)-1-methyl-4-[1-(2,3,4,6 tetra-
O-acetyl-b-D-glucopyranosyl)-1H-pyrrolo[2,3-b]pyridin-3-
yl]-1H-pyrrole-2,5-dione 40 and 3-(1H-imidazol-1-yl)-1-
methyl-4-[7-(2,3,4,6 tetra-O-acetyl-b-D-glucopyranosyl)-
1H-pyrrolo[2,3-b]pyridin-3-yl]-1H-pyrrole-2,5-dione (40a).
To a solution of 34 (100 mg, 0.341 mmol) in THF (11 mL)
were added 2,3,4,6-O-acetylglucopyranose (263 mg,
Compound 41. HRMS (FAB+) (M+H+) calcd for
C29H28N5O11 622.1785, found 622.1803. 1H NMR
(400 MHz, CDCl3) (mixture of 2 conformers in 1:1 ra-
tio): 1.55 (3H, s, CH3CO), 1.58 (3H, s, CH3CO), 1.97
(3H, s, CH3CO), 2.01 (3H, s, CH3CO), 2.09 (3H, s,
CH3CO), 2.12 (6H, s, CH3CO), 2.14 (3H, s, CH3CO),
3.29 (6H, s, CH3), 4.10–4.32 (6H, m), 5.52-5.66 (3H,
m), 5.90 (1H, t, J = 9.7 Hz), 6.86 (1H, d, J = 9.3 Hz),
7.12 (1H, t, J = 9.4 Hz), 7.14 (1H, t, J = 9.2 Hz), 7.42
(1H, dd, J1 = 7.0 Hz, J2 = 5.3 Hz), 7.44 (1H, dd,
J1 = 7.4 Hz, J2 = 5.8 Hz), 7.76 (1H, d, J = 9.4 Hz), 7.94
(1H, s), 8.07 (1H, s), 8.59 (2H, dd, J1 = 5.5 Hz,
J2 = 1.2 Hz), 8.62 (1H, dd, J1 = 5.0 Hz, J2 = 1.4 Hz),
8.65 (1H, dd, J1 = 4.7 Hz, J2 = 1.4 Hz), 9.04 (1H, d,
J = 7.6 Hz), 9.12 (1H, dd, J1 = 7.9 Hz, J2 = 1.4 Hz).
Compound 42. Mixture of 4 isomers. HRMS (FAB+)
(M+H+) calcd for C29H30N5O11 624.1942, found
624.1943. Compound 43. mixture of 2 isomers in 1:1 ra-
0.756 mmol)
and
triphenylphosphine
(199 mg,
0.756 mmol). The mixture was cooled to ꢀ78 ꢁC then
DEAD (120 lL, 0.756 mmol) was added dropwise. The
mixture was allowed to reach room temperature with stir-
ring and then was stirred at room temperature for 15 h.
After addition of water (50 mL), then extraction with
EtOAc, the organic phase was dried over MgSO4 and
the solvent was removed. The residue was purified by flash
chromatography (eluent: EtOAc/cyclohexane 3:7 to
100% EtOAc) to give 40 (139 mg, 0.223 mmol, 65% yield)
as a yellow solid and 40a (50 mg, 0.080 mmol, 24% yield)
as an orange solid.
Compound 40. Mp 88–90 ꢁC. IR (KBr) mC@O 1710,
1
1750 cmꢀ1. H NMR (400 MHz, CDCl3): 1.58 (3H, s,
CH3CO), 1.99 (6H, s, CH3CO), 2.06 (3H, s, CH3CO),
3.14 (3H, s, NCH3), 4.06 (1H, m), 4.15 (1H, d,
J = 12.4 Hz), 4.28 (1H, dd, J1 = 12.6 Hz, J2 = 4.7 Hz),
5.27 (1H, m), 5.48–5.50 (2H, m), 6.26 (1H, d,
1
tio. H NMR(400 MHz, CDCl3): 1.27 (3H, s, CH3CO),
1.31 (3H, s, CH3CO), 1.93 (3H, s, CH3CO), 2.00 (3H, s,
CH3CO), 2.07 (3H, s, CH3CO), 2.09 (3H, s, CH3CO),
2.26 (3H, s, CH3CO), 2.30 (3H, s, CH3CO), 3.02 (3H,
s, CH3), 3.04 (3H, s, CH3), 4.12 (2H, m), 4.24 (1H, d,
J = 12.7 Hz), 4.32 (1H, d, J = 13.0 Hz), 4.36 (1H, d,
J = 13.0 Hz), 4.45 (1H, d, J = 12.7 Hz), 4.72 (1H, d,
J = 9.0 Hz), 4.80 (1H, d, J = 9.9 Hz), 5.47 (5H, m),
5.57 (3H, m), 6.53 (1H, d, J = 5.3 Hz), 6.68 (1H, d,
J = 9.0 Hz), 7.12–7.20 (2H, m), 7.89 (1H, s), 7.95 (1H,
s), 7.99 (1H, s), 8.09 (1H, s), 8.27–8.36 (4H, m).
0
J = 8.9 Hz, H1 Þ, 6.66 (1H, d, J = 7.4 Hz), 6.94 (1H, dd,
J1 = 8.8 Hz, J2 = 4.7 Hz), 7.09 (1H, s), 7.21 (1H, s), 7.83
(1H, s), 8.17 (1H, s), 8.28 (1H, d, J = 5.1 Hz). 13C NMR
(100 MHz, CDCl3): 19.9, 20.5, 20.7, 21.0 (CH3CO), 24.4
0
(NCH3), 61.6 (C6 ), 67.9, 70.8, 72.8, 74.9, 80.3 (C1 , C2 ,
0
0
0
0
0
C3 , C4 , C5 Þ, 103.1, 117.6, 122.1, 126.4, 137.6, 147.8 (C
quat arom), 118.5, 129.2, 130.1, 130.2, 144.6 (C tert
arom), 166.7, 168.8 (2C), 169.4, 169.8, 170.5 (C@O).
Compound 40a. Mp 81–83 ꢁC. IR (KBr) mC@O 1710, 1750
cmꢀ1. 1H NMR (400 MHz, CDCl3): 1.58 (3H, s, CH3CO),
2.01 (3H, s, CH3CO), 2.09 (6H, s, CH3CO), 3.17 (3H, s,
NCH3), 4.18 (2H, m), 4.36 (1H, dd, J1 = 12.7 Hz,
4.1.38. 2-Methyl-8-(2,3,4,6-tetra-O-acetyl-b-D-lucopyr-
anosyl)-imidazo[1,5-a]pyrido[30,20:4,5]pyrrolo[2,3-c]pyr-
rolo[3,4-e]pyridine-1,3-(2H,8H)-dione (43a). To
solution of 43 (38 mg, 0.061 mmol) in CH2Cl2 (5 mL)
a