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J. Zurek et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
10
8.01 (d, J = 7.9 Hz, 1H, ArH) ppm. (Diastereomer B) d = 3.25 (s, 3H,
CH3N), 3.74–3.96 (m, 2H, CH2Ph), 4.17–4.30 (m, 1H, CH2OH), 5.13
(dd, J = 5.9, 5.0 Hz, 1H, CH2OH), 6.50–6.63 (m, 1H, CHN), 6.92–7.26
(m, 5H, ArH), 7.65 (dd, J = 7.3, 7.3 Hz, 1H, ArH), 7.92 (dd, J = 8.8, 5.0
Hz, 1H, ArH), 8.16 (d, J = 9.1 Hz, 1H, ArH), d = 8.33 (d, J = 8.8 Hz, 1H,
ArH) ppm. For C20H18N4O3 (362.38) calculated: C 66.29, H 5.01, N
15.46, found: C 66.32, H 5.30, N 14.98. HR-MS (ESI): calculated
for C20H19N4O+3 (M+H+): 363.14517, found: 363.14536.
4.6.2. (1S)-(5H)-1,2-Dihydro-5-methyl-1-(1-methylethyl)-4,6-
dioxobenzo[g]imidazo-[1,2,3-ij]pteridin-12-ium chloride 4a
Prepared by general procedure from isoalloxazine 9a (100 mg,
0.32 mmol). 101 mg (95%) of 4a was obtained as yellow crystals,
mp 157.6–164.3 °C, [
a]
D
25 = À195.0 (c 0.502, methanol). 1H NMR
(300 MHz, DMSO-d6): d = 0.73 (d, J = 6.6 Hz, 3H, (CH3)2CH), 1.15
(d, J = 6.6 Hz, 3H, (CH3)2CH), 2.78–2.92 (m, 1H, (CH3)2CH), 4.40 (s,
3H, CH3N), 4.61 (dd, J = 11.4, 10.5 Hz, 1H, CH2N), 4.78 (dd, J =
11.4, 4.5 Hz, 1H, CH2N), 6.04–6.15 (m, 1H, CHN+), 8.13 (dd, J =
8.1, 7.2 Hz, 1H, ArH), 8.35 (dd, J = 7.8, 7.8 Hz, 1H, ArH), 8.52 (d, J
= 8.7 Hz, 1H, ArH), 8.63 (d, J = 8.1 Hz, 1H, ArH) ppm. 13C NMR
(75 MHz, DMSO-d6): d = 14.5, 18.7, 29.4, 29.9, 46.7, 69.4, 118.6,
128.7, 131.7, 133.5, 135.0, 138.8, 140.4, 143.3, 147.5, 158.3 ppm .
For C16H17ClN4O2 2H2O (368.82) calculated: C 52.10, H 5.74, N
15.19, found: C 51.77, H 5.97, N 15.20. HR-MS (ESI) calculated for
4.5.5. 10-[(1S)-2-Hydroxy-1-(4-methoxybenzyl)ethyl]-3-methyl-
benzo[g]pteridin-2,4-dione 9d
Prepared by general procedure from isoalloxazine 8d (1.08 g,
2.86 mmol) and methyl iodide (2 mL, 31.99 mmol). 1.12 g (95%)
of 9d was obtained as yellow crystals (cryst. methanol). 1H NMR
(300 MHz, DMSO-d6): mixture of diastereomers A and B in ratio
A/B = 3.3:1. (Diastereomer A) d = 3.12–3.21 (m, 1H, CH2Ar), 3.30
(s, 3H, CH3N), 3.55 (s, 3H, CH3O), 3.74 (dd, J = 13.5, 10.0 Hz, 1 H;
CH2Ar), 3.83–3.93 (m, 1H, CH2OH), 4.58–4.70 (m, 1H, CH2OH),
4.93 (dd, J = 6.2, 6.2 Hz, 1H, OH), 5.36–5.48 (m, 1H, CHN), 6.61 (d,
J = 8.5 Hz, 2H, ArH), 7.07 (d, J = 8.5 Hz, 2H, ArH), 7.51 (dd, J = 7.6,
7.3 Hz, 1H, ArH), 7.74 (dd, J = 7.9, 7.3 Hz, 1H, ArH), 7.87 (d, J =
8.8 Hz, 1H, ArH), 8.03 (d, J = 7.9 Hz, 1H, ArH) ppm. (Diastereomer
B) d = 3.12–3.21 (m, 1H, CH2Ar), 3.25 (s, 3H, CH3N), 3.65 (s, 3H,
CH3O), 3.83–3.94 (m, 2H, CH2Ar+CH2OH), 4.18–4.28 (m, 1H, CH2-
OH), 5.13 (dd, J = 5.3, 5.0 Hz, 1H, OH), 6.46–6.60 (m, 1H, CHN),
6.78 (d, J = 8.5 Hz, 2H, ArH), 7.10 (d, J = 8.5 Hz, 2H, ArH), 7.64 (dd,
J = 7.9, 7.6 Hz, 1H, ArH), 7.91 (dd, J = 8.0, 7.6 Hz, 1H, ArH), 8.15 (d,
J = 7.6 Hz, 1H, ArH), 8.32 (d, J = 8.8 Hz, 1H, ArH) ppm. For
C
16H17N4O+2: (MÀCl+): 297.13460, found: 297.13475.
4.6.3. (1R)-(5H)-1-Phenyl-1,2-dihydro-5-methyl-4,6-dioxobenzo
[g]imidazo[1,2,3-ij]pteridin-12-ium chloride 4b
Prepared by general procedure from isoalloxazine 9b (100 mg,
0.29 mmol). 94 mg (89%) of 4b was obtained, mp 170.9–177.2 °C,
[a]
25 = +199.2 (c 0.128, methanol). 1H NMR (300 MHz, DMSO-d6):
D
d = 3.44 (s, 3H, CH3N), 4.53 (dd, J = 11.4, 6.5 Hz, 1H, CH2N), 5.19
(dd, J = 11.1, 11.1 Hz, 1H, CH2N), 7.20 (dd, J = 10.5, 6.2 Hz, 1H,
CHN+), 7.43–7.50 (m, 3H, ArH), 7.68 (d, J = 8.5 Hz, 1H, ArH), 7.71–
7.79 (m, 2H, ArH), 8.01 (dd, J = 8.2, 7.3 Hz, 1H, ArH), 8.14 (dd, J =
8.5, 7.3 Hz, 1H, ArH), 8.59 (d, J = 8.5 Hz, 1H, ArH) ppm. 13C NMR
(75 MHz, DMSO-d6): d = 29.5, 54.7, 67.1, 118.0, 128.3, 128.7,
130.3, 130.9, 131.6, 133.6, 135.2, 136.2, 138.8, 140.4, 143.6,
147.4, 158.2 ppm. For C19H15ClN4O2 2H2O (402.83) calculated: C
56.65, H 4.75, N 13.91, found: C 56.77, H 4.67, N 13.92. HR-MS
(ESI): calculated for C19H15N4O+2 (MÀCl+) calculated: 331.11895,
found: 331.11899.
C21H20N4O4 (392.41) calculated: C 64.28, H 5.14, N 14.28, found:
C 64.22, H 5.24, N 14.19. HR-MS (ESI): calculated for C21H20N4O4-
Na+ (M+Na+): 415.13768, found: 415.13740.
4.5.6. 10-{(1S)-1-[4-(Benzyloxy)benzyl]-2-hydroxyethyl}-3-methy-
lbenzo[g]pteridin-2,4-dion 9e
4.6.4. (1S)-(5H)-1-Benzyl-1,2-dihydro-5-methyl-4,6-dioxobenzo
[g]imidazo[1,2,3-ij]pteridin-12-ium chloride 4c
Prepared by general procedure from isoalloxazine 8e (0.42 g,
0.92 mmol) and methyl iodide (1 mL, 15.99 mmol). 0.40 g (92%)
of 9e was obtained as yellow crystals (cryst. dichloromethane).
1H NMR (300 MHz, DMSO-d6): mixture of diastereomers A and B
in ratio A/B = 3.5:1. (Diastereomer A) d = 3.15 (dd, J = 13.5, 4.7 Hz,
1H, CH2Ar), 3.30 (s, 3H, CH3N), 3.74 (dd, J = 13.5, 9.1 Hz, 1H, CH2Ar),
3.82–4.14 (m, 1H, CH2OH), 4.58–4.70 (m, 1H, CH2OH), 4.90 (s, 2H,
OCH2Ph), 4.93 (dd, J = 6.4, 6.4 Hz, 1H, OH), 5.34–5.48 (m, 1H, CHN),
6.68 (d, J = 8.5 Hz, 2H, ArH), 7.07 (d, J = 8.5 Hz, 2H, ArH), 7.22–7.42
(m, 5H, Ph), 7.52 (dd, J = 7.6, 7.3 Hz, 1H, ArH), 7.72 (dd, J = 8.8, 7.0
Hz, 1H, ArH), 7.86 (d, J = 8.8 Hz, 1H, ArH), 8.03 (d, J = 7.9 Hz, 1H,
ArH) ppm. (Diastereomer B) d = 3.10–3.24 (m, 1H, CH2Ar), 3.25 (s,
3H, CH3N), 3.56–3.94 (m, 2H, CH2Ar+CH2OH), 4.16–4.28 (m, 1H,
CH2OH), 5.00 (s, 2H, OCH2Ph), 5.13 (dd, J = 5.6, 5.6 Hz, 1H, OH),
6.46–6.78 (m, 1H, CHN), 6.86 (d, J = 8.5 Hz, 2H, ArH), 7.15 (d, J =
8.5 Hz, 2H, ArH), 7.22–7.42 (m, 5H, Ph), 7.65 (dd, J = 7.6, 7.3 Hz,
1H, ArH), 7.91 (dd, J = 7.6, 7.6 Hz, 1H, ArH), 8.16 (d, J = 7.9 Hz, 1H,
ArH), 8.31 (d, J = 8.8 Hz, 1H, ArH) ppm. For C27H24N4O4 (468.50)
calculated: C 69.22, H 5.16, N 11.96, found: C 69.01, H 5.37, N
Prepared by general procedure from isoalloxazine 9c (100 mg,
0.28 mmol), 93 mg (88%) of 4c was obtained as yellow crystals,
mp 147.5–151.4 °C, [
a
]
D
25 = À242.5 (c 0.440, methanol). 1H NMR
(300 MHz, DMSO-d6): d = 3.27 (dd, J = 14.1, 9.4 Hz, 1H, CH2Ph),
3.42 (s, 3H, CH3N), 3.66 (dd, J = 13.8, 6.2 Hz, 1H, CH2Ph), 4.48 (dd,
J = 11.1, 3.2 Hz, 1H, CH2N), 4.60 (dd, J = 10.8, 9.1 Hz, 1H, CH2N),
6.42–6.54 (m, 1H, CHN+), 7.30–7.40 (m, 5H, Ph), 8.05–8.12 (m,
1H, ArH), 8.18–8.23 (m, 2H, ArH), 8.60 (d, J = 8.2 Hz, 1H, ArH)
ppm. 13C NMR (75 MHz, DMSO-d6): d = 29.5, 38.4, 50.8, 65.6,
118.7, 128.4, 128.7, 129.6, 130.6, 131.6, 133.3, 135.2, 138.6,
140.4, 143.0, 147.6, 158.2 ppm. For C20H17ClN4O2 2H2O (416.86)
calculated: C 57.62, H 5.08, N 13.44, found: C 57.70, H 4.99, N
13.51. HR-MS (ESI): calculated for C20H17N4O+2 (MÀCl+) calculated:
345.13460, found: 345.13472.
4.6.5. (1S)-(5H)-1,2-Dihydro-1-(4-methoxybenzyl)-5-methyl-
4,6-dioxobenzo[g]imidazo-[1,2,3-ij]pteridin-12-ium chloride 4d
Prepared by general procedure from isoalloxazine 9d (221 mg,
0.56 mmol). 224 mg (97%) of 4d was obtained as yellow crystals,
10.78. HR-MS(ESI): calculated for
491.16898, found: 491.16857.
C
27H24N4O4Na+ (M+Na+):
mp 143.5–146.7 °C, [
a]
25 = À362.2 (c 0.286, methanol). 1H NMR
D
(300 MHz, DMSO-d6): d = 3.21 (dd, J = 13.5, 9.1 Hz, 1H, CH2Ar),
3.40 (s, 3H, CH3N), 3.59 (dd, J = 13.8, 5.2 Hz, 1H, CH2Ar), 3.73 (s,
3H, CH3O), 4.45 (dd, J = 10.8, 2.6 Hz, 1H, CH2N), 4.57 (dd, J = 10.8,
9.1 Hz, 1H, CH2N), 6.35–6.48 (m, 1H, CHN+), 6.88 (d, J = 8.5 Hz,
2H, ArH), 7.29 (d, J = 8.5 Hz, 2H, ArH), 8.02–8.13 (m, 1H, ArH),
8.16–8.28 (m, 2H, ArH), 8.58 (d, J = 8.2 Hz, 1H, ArH) ppm. 13C
NMR (75 MHz, DMSO-d6): d = 29.4, 37.5, 50.6, 55.9, 65.8, 115.0,
118.8, 126.9, 128.8, 131.5, 131.8, 133.2, 134.8, 138.5, 140.3,
143.0, 147.6, 158.2, 159.5 ppm. For C21H19ClN4O3 2H2O (446.88)
calculated: C 56.44, H 5.19, N 12.54, found: C 56.48, H 5.12, N
4.6. Preparation of alloxazinium salts 4
4.6.1. General procedure
Thionyl chloride (1 mL) was added to the solution of isoallox-
azine 8 (0.3 mmol) in dry dichloromethane (5 mL) and the reaction
mixture was stirred at dark for 24 h under an argon atmosphere.
After addition of hexane (3–8 mL), salt 4 was precipitated and col-
lected by filtration.
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