J. Huchting, C. Meier
FULL PAPER
3
10.9, JHH = 7.5 Hz, 2 H, Har,fluorenyl), 7.44–7.40 (m, 2 H,
dichloromethane and washed with water. The organic layer was
dried with sodium sulfate and the solvent was evaporated. The
crude product was purified by chromatography on silica gel with
Har,fluorenyl), 7.35–7.31 (m, 2 H, Har,fluorenyl), 7.13 (d, 4JHH = 1.0 Hz,
3
3
1 H, 6-H), 5.87 (d, JHH = 9.5 Hz, 1 H, 1Ј-H), 5.40 (d, JHH
=
3
9.5 Hz, 1 H, 3Ј-H), 5.21–5.16 (m, 2 H, 2Ј-H, 4Ј-H), 4.47 (dd, JHH petroleum ether/ethyl acetate, 1:2 + 2% acetic acid as eluent. A
= 10.5, JHH = 7.2 Hz, 1 H, 6Ј-Ha), 4.39–4.32 (m, 2 H, fluorenyl- yield of 0.129 g (0.206 mmol, 66%, diastereomeric ratio 1:1.1) of
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3
H2), 4.27–4.24 (m, 2 H, 6Ј-Hb, fluorenyl-CH), 3.96 (ddd, JHH
=
the product was obtained. Rf (petroleum ether/ethyl acetate, 1:2 v/
10.2, JHH = 5.1, JHH = 2.5 Hz, 5Ј-H), 2.06, 2.03, 2.00 [s, 3 H, v + 2% HOAc): 0.40. 1H NMR: δ = (400 MHz, CDCl3): 8.32 (s,
3
4
C(O)CH3]. 1.91 (s, 3 H, 7-H3) ppm. 13C NMR: δ = (101 MHz, 2.1 H, NH), 8.27–8.23 (m, 2.1 H, HNO2-ar), 8.08 (d, 4JHH = 2.3 Hz,
3
CDCl3): 169.7, 169.5, 169.4 [C(O)CH3], 162.6 (4), 154.7 (fluorenyl-
2.1 H, HNO2-ar), 7.23 (d, JHH = 9.0 Hz, 1 H, HNO2-ar), 7.19 (d,
C=O), 150.1 (2), 143.3 (Cq, ar), 141.3 (Cq, ar), 134.4 (6), 128.0 (Car), 3JHH = 8.9 Hz, 1.1 H, HNO2-ar), 7.15–7.14 (m, 2.1 H, 6-H), 5.86 (d,
127.2 (Car), 125.1 (Car), 120.1 (Car), 112.2 (5), 80.3 (1Ј) 74.7 (5Ј), 3JHH = 9.5 Hz, 1.1 H, 1Ј-Hβ2), 5.86 (d, JHH = 9.5 Hz, 1 H, 1Ј-
3
72.7 (3Ј), 70.4 (fluorenyl-CH2), 69.3 (4Ј), 68.0 (2Ј), 65.3 (6Ј), 46.7
(fluorenyl-CH), 20.5, 20.5, 20.3 [C(O)CH3], 12.5 (7) ppm. HRMS
Hβ1), 5.53–5.35 (m, 6.3 H, P-O-CH2-ar, 3Ј-H), 5.21–5.10 (m, 4.2 H,
4Ј-H, 2Ј-H), 4.46–4.39 (m, 2.1 H, 6Ј-Ha), 4.35–4.27 (m, 2.1 H, 6Ј-
Hb), 3.98–3.95 (m, 2.1 H, 5Ј-H), 2.08, 2.01, 1.99 [s, 18.9 H, C(O)
CH3], 1.94, 1.94 (s, 6.3 H, 7-H3) ppm. 13C NMR: δ = (151 MHz,
(ESI+): calcd. for C32H32N2O12 [M
+
H+] 637.2028; found
637.2034. Calcd. for C32H32N2O12 [M + NH4+] 654.2294; found
654.2298. Calcd. for C32H32N2O12 [M + Na+] 659.1847; found CDCl3): 169.7, 169.4, 169.3 [C(O)CH3], 162.7 (4), 150.2 (2), 144.1
659.1855. [α]2D0 = 7 (c = 0.1, CH2Cl2).
(Cq,NO2-ar), 134.5, 134.4 (6), 125.8, 125.7 (CNO2-ar), 121.7 (CNO2-ar),
4
4
119.7 (d, JCP = 9.7 Hz, CNO2-ar), 119.7 (d, JCP = 9.9 Hz, CNO2-
(2Ј,3Ј,4Ј-Tri-O-acetyl-6Ј-O-Fmoc-β-
D
-galactopyranoside)-thymine
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3
ar), 112.3 (5), 80.3 (1Ј), 75.2 (d, JCP = 6.7 Hz, 5Ј), 75.1 (d, JCP
6.7 Hz, 5Ј), 72.7, 72.6 (3Ј), 69.0, 68.9 (2Ј), 68.0 (d, JCP = 7.7 Hz,
P-O-CH2-ar), 67.8 (d, JCP = 6.6 Hz, P-O-CH2-ar), 67.5, 67.4 (4Ј),
66.7 (d, JCP = 5.6 Hz, 6Ј), 66.5 (d, JCP = 4.5 Hz, 6Ј), 20.6, 20.5,
20.3 [C(O)CH3], 12.6 (7) ppm. 31P NMR: δ = (162 MHz, CDCl3):
–10.4, –10.7 ppm. HRMS (ESI+): calcd. for C24H26N3O15P [M +
H+] 628.1174; found 628.1171. Calcd. for C24H26N3O15P [M +
NH4+] 645.1440; found 645.1443. Calcd. for C24H26N3O15P [M +
Na+] 650.0994; found 650.0989.
=
(12): The preparation of compound 12 was conducted on the basis
of our procedure described in the literature.[14] (2Ј,3Ј,4Ј-tri-O-
Acetyl-6Ј-O-TBDMS-β-d-galactpyranoside)-thymine (11; 364 mg,
0.689 mmol) was dissolved in dichloromethane (3 mL) and triethyl-
amine trihydro fluoride (1.68 mL, 10.3 mmol) was added and the
reaction mixture was stirred at room temperature. The course of
the reaction was followed by TLC (petroleum ether ether/ethyl acet-
ate, 1:2). After almost all of the starting material was consumed
(one hour), the reaction mixture was diluted with dichloromethane
(10 mL) and FmocCl (536 mg, 2.07 mmol) and pyridine (0.50 mL,
6.2 mmol) were added. After stirring for three hours at room tem-
perature the reaction mixture was washed with water, the organic
layer was dried with sodium sulfate and the solvent was evaporated.
The crude product was purified by column chromatography on sil-
ica gel with petroleum ether and an ethyl acetate gradient from 3:1
to 1:2. A yield of 291 mg (0.457 mmol, 66%) of the product was
3
3
3
3
5-Nitro-cycloSal-[(2Ј,3Ј,4Ј-tri-O-acetyl-β-D-galactopyranoside)-
thymine-6Ј]-phosphate (14): (2Ј,3Ј,4Ј-Tri-O-acetyl-6Ј-O-Fmoc-β-d-
galactopyranoside)-thymine (11; 0.228 g, 0.358 mmol) was dis-
solved in anhydrous acetonitrile (3 mL) and 5-nitro-cycloSaligen-
ylchlorophosphite (15; 167 mg, 0.716 mmol), dissolved in anhy-
drous acetonitrile (0.54 mL) was added. After addition of triethyl-
amine (0.300 mL, 2.15 mmol) the reaction mixture was stirred at
room temperature. After completion of the reaction (2 h, monitor-
ing by TLC, petroleum ether/ethyl acetate, 1:2) oxone® (1.10 g,
1.79 mmol), dissolved in water, was added at 0 °C. The reaction
mixture was stirred at room temperature for 10 min, diluted with
dichloromethane and washed with water. The organic layer was
dried with sodium sulfate and the solvent was evaporated. The
crude product was purified by chromatography on silica gel with
petroleum ether/ethyl acetate, 1:2 + 2% acetic acid as eluent. A
yield of 0.149 g (0.237 mmol, 66%, diastereomeric ratio 1:1.1) of
the product was obtained. Rf (petroleum ether/ethyl acetate, 1:2 v/
v + 2% HOAc): 0.43. 1H NMR: δ = (400 MHz, CDCl3): 8.60 (s,
2.1 H, NH), 8.25–8.23 (m, 2.1 H, HNO2-ar), 8.05 (d, 4JHH = 2.6 Hz,
obtained. Rf (petroleum ether/ethyl acetate, 1:2 v/v): 0.55. 1H
3
NMR: δ = (400 MHz, CDCl3): 7.97 (s, 1 H, NH), 7.77 (d, JHH
=
3
3
7.6 Hz, 2 H, Har,fluorenyl), 7.59 (dd, JHH = 7.1, JHH = 4.3 Hz, 2
3
3
H, Har,fluorenyl), 7.42 (dd, JHH = 7.5, JHH = 7.5 Hz, 2 H,
Har,fluorenyl), 7.33 (dd, 3JHH = 8.0, JHH = 7.6 Hz, 2 H, Har,fluorenyl),
3
7.15 (s, 1 H, 6-H), 5.83 (d, 3JHH = 9.1 Hz, 1 H, 1Ј-H), 5.55 (d, 3JHH
3
3
= 3.0 Hz, 1 H, 4Ј-H), 5.32 (dd, JHH = 9.7, JHH = 9.7 Hz, 1 H,
2Ј-H), 5.22 (dd, 3JHH = 10.1, JHH = 3.3 Hz, 1 H, 3Ј-H), 4.45–4.37
3
(m, 2 H, fluorenyl-H2), 4.25–4.23 (m, 3 H, 6Ј-H2, fluorenyl-CH),
4.19–4.16 (m, 1 H, 5Ј-H), 2.23 [s, 3 H, C(O)CH3], 2.02 [s, 6 H,
2ϫC(O)CH3], 1.95 (s, 3 H, 7-H3) ppm. 13C NMR: δ = (101 MHz,
CDCl3): 169.8, 169.8, 169.6 [C(O)CH3], 162.8 (4), 154.6 (fluorenyl-
C=O), 150.2 (2), 143.1 (Cq, ar), 141.3 (Cq, ar), 134.7 (6), 128.0 (Car),
127.2 (Car), 125.2 (Car), 120.1 (Car), 112.1 (5), 80.7 (1Ј), 73.7 (5Ј),
70.8 (3Ј), 70.4 (fluorenyl-CH2), 67.1 (2Ј), 67.0 (4Ј), 64.9 (6Ј), 46.6
(fluorenyl-CH), 20.7, 20.5, 20.4 [C(O)CH3], 12.6 (7) ppm. HRMS
(ESI+): calcd. for C32H32N2O12 [M + H+] 637.2028; found
637.2031. [α]2D0 = 33 (c = 0.1, CH2Cl2).
3
2.1 H, HNO2-ar), 7.22 (d, JHH = 9.0 Hz, 1 H, HNO2-ar), 7.18 (d,
3
3JHH = 9.0 Hz, 1.1 H, HNO2-ar), 7.15 (d, JHH = 1.2 Hz, 2.1 H, 6-
3
3
H), 5.84 (d, JHH = 9.4 Hz, 1 H, 1Ј-Hβ2), 5.82 (d, JHH = 9.4 Hz,
3
3
1.1 H, 1Ј-Hβ1), 5.53 (d, JHH = 2.8 Hz, 1 H, 4Ј-Hβ1), 5.50 (d, JHH
= 2.5 Hz, 1.1 H, 4Ј-Hβ2), 5.43–5.33 (m, 6.3 H, P-O-CH2-ar, 2Ј-H),
5.21–5.16 (m, 2.1 H, 3Ј-H), 4.41–4.32 (m, 2.1 H, 6Ј-Ha), 4.30–4.23
5-Nitro-cycloSal-[(2Ј,3Ј,4Ј-tri-O-acetyl-β-D-glucopyranoside)-thym- (m, 2.1 H, 6Ј-Hb), 4.23–4.16 (m, 2.1 H, 5Ј-H), 2.24, 2.18, 2.01, 2.01,
ine-6Ј]-phosphate (13): (2Ј,3Ј,4Ј-Tri-O-acetyl-6Ј-O-Fmoc-β-d-gluco-
pyranoside)-thymine (10; 0.200 g, 0.314 mmol) was dissolved in an-
hydrous acetonitrile (3 mL) and 5-nitro-cycloSaligenylchloro-
phosphite (15; 146 mg, 0.628 mmol), dissolved in anhydrous aceto-
nitrile (0.33 mL), was added. After addition of triethylamine
(0.260 mL, 1.88 mmol) the reaction mixture was stirred at room
temperature. After completion of the reaction (2 h, monitoring by
TLC, petroleum ether/ethyl acetate, 1:2) oxone® (965 mg,
1.57 mmol), dissolved in water, was added at 0 °C. The reaction
mixture was stirred at room temperature for 10 min, diluted with
2.00, 1.99, 1.98 [s, 25.2 H, C(O)CH3, 7-H3] ppm. 13C NMR: δ =
(151 MHz, CDCl3): 169.8, 169.7, 169.7, 169.7, 169.6 [C(O)CH3],
162.9, 162.9 (4), 154.3, 154.3 (Cq,NO2-ar), 150.3, 150.3 (2), 144.1
(Cq,NO2-ar), 134.7 (6), 125.7 (CNO2-ar), 121.7 (CNO2-ar), 121.4 (d,
4
4JCP = 9.9 Hz, CNO2-ar), 119.8 (d, JCP = 9.5 Hz, CNO2-ar), 119.8
4
3
(d, JCP = 9.4 Hz, CNO2-ar), 112.2 (5), 80.6, 80.6 (1Ј), 74.2 (d, JCP
3
= 7.7 Hz, 5Ј), 70.8, 70.8 (3Ј), 68.1 (d, JCP = 6.9 Hz, P-O-CH2-ar),
3
68.0 (d, JCP = 7.2 Hz, P-O-CH2-ar), 66.6 (2Ј), 66.6 (4Ј), 65.7 (d,
3JCP = 5.7 Hz, 6Ј), 65.7 (d, JCP = 5.4 Hz, 6Ј), 20.7, 20.6, 20.5,
3
20.4 [C(O)CH3], 12.6 (7) ppm. 31P NMR: δ = (162 MHz, CDCl3):
3428
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Eur. J. Org. Chem. 2014, 3423–3429