Shen et al.
epoxypentane (0.91 mL, 8.8 mmol) was added. After stirring for 2
h, the reaction was quenched with 0.5 M HCl solution until the
pH ) 7. The mixture was extracted with EtOAc (3 × 50 mL), and
the combined organic layers were dried (Na2SO4), filtered, and
concentrated. The residue was purified via column chromatography
(SiO2, 15% EtOAc in hexanes) to give 29 as a yellow oil (1.18 g,
86%): 1H NMR (CDCl3, 400 MHz) δ 6.96 (d, J ) 9.0 Hz, 1H),
6.80 (d, J ) 9.0 Hz, 1H), 5.14 (s, 2H), 5.12 (s, 2H), 3.86 (s, 3H),
3.81 (m, 1H), 3.51 (s, 3H), 3.47 (s, 3H), 2.94 (m, 1H), 2.78 (m,
1H), 2.56 (s, OH), 1.47 (m, 4H), 0.94 (t, J ) 6.8 Hz, 3H); 13C
NMR (CDCl3, 100 MHz) δ 151.3, 149.4, 145.7, 123.3, 115.7, 110.0,
96.1, 95.4, 72.6, 61.1, 56.5, 56.4, 40.2, 32.5, 19.4, 14.5; IR (film)
3.49 (s, 3H), 3.03 (m, 2H), 1.65 (m, 2H), 1.39 (m, 2H), 0.94 (t, J
) 7.3 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 169.2, 162.6, 157.6,
147.8, 141.0, 139.3, 136.3, 130.9, 125.6, 111.6, 107.4, 104.3, 104.1,
100.1, 95.8, 75.8, 61.4, 57.9, 56.6, 36.4, 30.1, 19.2, 14.3; IR (film)
ν
max 3518, 3053, 2939, 1697, 1517, 1155, 1036, 894 cm-1; HRMS
(ES+) m/z: [M + H] calcd for C23H31ClNO9, 500.1687; found,
500.1691.
1-(3-Formamido-6-methoxy-2,5-bis(methoxymethoxy)phenyl)-
pentan-2-yl 5-chloro-2,4-dihydroxybenzoate (50). Compound 45
(200 mg, 0.40 mmol) was dissolved in CH2Cl2 (40 mL) at 0 °C
before PhOCHO (182 mg, 1.5 mmol) was added. The reaction was
warmed to 30 °C and stirred for 12 h. After evaporation of organic
solvent, the residue was purified via column chromatography (SiO2,
10% EtOAc in hexanes) to give 50 as a yellow solid (177 mg,
84%) as a mixture of rotamers: 1H NMR (CDCl3, 400 MHz) δ
8.46 (s, 1H), 8.09 (s, 1H), 7.84 (s, 1H), 6.58 (s, 1H), 5.39 (m, 1H),
5.18 (m, 2H), 5.00 (m, 2H), 3.89 (s, 3H), 3.62 (s, 3H), 3.51 (s,
3H), 3.03 (d, J ) 6.7 Hz, 2H), 1.64 (m, 2H), 1.38 (m, 2H), 0.94
(m, 3H); 13C NMR (CDCl3, 100 MHz) δ 169.2, 169.1, 162.7, 162.6,
159.3, 157.7, 157.6, 147.8, 147.0, 146.7, 145.6, 143.2, 141.8, 130.7,
126.9, 126.6, 125.0, 111.6, 109.6, 107.3, 107.2, 107.1, 104.4, 101.2,
101.1, 96.0, 95.9, 75.5, 75.3, 61.4, 58.0, 57.8, 56.9, 56.8, 36.5, 36.3,
30.2, 30.1, 19.2, 14.3; IR (film) νmax 3392, 2986, 1697, 1529, 1396,
1155, 1113, 960 cm-1; HRMS (ES+) m/z: [M + H] calcd for
C24H31NO10Cl, 528.1636; found, 528.1644.
1-(3-Formamido-2,5-dihydroxy-6-methoxyphenyl)pentan-2-
yl 5-chloro-2,4-dihydroxybenzoate (55). Ester 50 (30 mg, 0.057
mmol) was dissolved in CH2Cl2 (0.3 mL) and CH3CN (0.3 mL) at
25 °C before addition of sodium iodide (85 mg, 0.57 mmol) and
trimethylsilyl chloride (72.4 µM, 0.57 mmol). The turbid solution
was stirred for 15 min before saturated Na2S2O3 (10 mL) was added.
The aqueous layer was extracted with EtOAc (3 × 30 mL). The
combined organic layers were dried (Na2SO4), filtered, and
concentrated. The residue was purified via column chromatography
(SiO2, 50% EtOAc in hexanes) to afford 55 (21.7 mg, 87%) as a
red oil: 1H NMR (CDCl3, 400 MHz) δ 10.72 (s, 1H), 8.30 (s, 1H),
7.86 (m, 3H), 7.31 (s, 1H), 6.62 (s, 1H), 6.40 (s, 1H), 5.96 (s, 1H),
5.10 (m, 1H), 3.82 (s, 3H), 3.16 (m, 1H), 3.05 (m, 1H), 1.74 (m,
2H), 1.51 (m, 1H), 1.36 (m, 1H), 0.94 (t, J ) 7.4 Hz, 3H); 13C
NMR (CDCl3, 100 MHz) δ 170.3, 162.8, 160.1, 157.9, 144.0, 142.8,
139.9, 130.7, 121.9, 119.4, 112.0, 108.2, 106.9, 104.6, 76.8, 61.7,
36.0, 30.0, 19.3, 14.3; IR (film) νmax 3512, 3392, 3055, 2985, 1618,
1373, 1161, 1045, 896 cm-1; HRMS (ES+) m/z: [M + H] calcd
for C20H23NO8Cl, 440.1112; found, 440.1134.
1-(5-Formamido-2-methoxy-3,6-dioxocyclohexa-1,4-dienyl)-
pentan-2-yl 5-chloro-2,4-dihydroxybenzoate (58). Compound 55
(17 mg, 0.039 mmol) was dissolved in EtOAc (0.4 mL) before
Pd(OAc)2 (34 mg, 200% w/w) was added and stirred for 30 min.
The mixture was filtered through silica gel pad, the filtrate was
concentrated, and the residue was purified via prepared TLC (SiO2,
250 µM, 50% EtOAc in hexane) to afford 58 (11.5 mg, 68%) as a
brown solid: 1H NMR (CDCl3, 400 MHz) δ 10.80 (s, 1H), 8.59
(a, 1H), 8.23 (s, 1H), 7.74 (s, 1H), 7.36 (s, 1H), 6.60 (s, 1H), 5.26
(m, 1H), 4.14 (s, 3H), 3.78 (m, 1H), 2.82 (m, 1H), 2.64 (m, 1H),
1.66 (m, 2H), 1.42 (m, 2H), 0.98 (t, J ) 7.2 Hz, 3H); 13C NMR
(CDCl3, 125 MHz) δ 183.7, 182.5, 168.7, 162.5, 159.4, 157.1,
136.8, 130.0, 129.9, 122.9, 114.2, 111.2, 106.7, 104.2, 74.2, 61.8,
36.5, 27.9, 18.7, 14.2; IR (film) νmax 3603, 3398, 2972, 1664, 1616,
1379, 1161, 1122, 946 cm-1; HRMS (ES+) m/z: [M + NH4] calcd
for C20H24N2O8Cl, 455.1221; found, 455.1218.
3-(2-Azidoethyl)-2-methoxy-1,4-bis(methoxymethoxy)-5-nitro-
benzene (59.1). Compound 27 (1.2 g, 4.41 mmol), triphenylphos-
phine (2.87 g, 11.0 mmol), and diisopropylazodicarboxylate (2.16
mL, 11.0 mmol) were dissolved in THF (20 mL) and stirred at 0
°C for 15 min before diphenyl phosphoryl azide (2.4 mL, 11.0
mmol) was added and stirred at room temperature for 12 h. The
reaction was quenched by addition of saturated aqueous ammonium
chloride (100 mL). The organic layer was removed, and the aqueous
layer was extracted with EtOAc (3 × 100 mL). The combined
νmax 3583, 3053, 2958, 1593, 1465, 1205, 1153, 1056, 946 cm-1
;
HRMS (ES+) m/z: [M + H] calcd for C16H27O6, 315.1808; found,
315.1811.
1-(2-Methoxy-3,6-bis(methoxymethoxy)-5-nitrophenyl)pentan-
2-ol (35). Compound 29 (0.84 g, 2.7 mmol) was dissolved in CH3-
CN (10 mL) and stirred at -10 °C before addition of ammonium
nitrate (749 mg, 9.2 mmol). (CF3CO)2O (11.7 mL, 9.2 mmol) was
added to the mixture, and it stirred for 15 min at room temperature.
The mixture was quenched by addition of saturated aqueous sodium
bicarbonate (50 mL) and extracted with EtOAc (3 × 50 mL). The
combined organic layers were dried (Na2SO4), filtered, and
concentrated. The residue was dissolved with THF-MeOH-H2O
(3:1:1, 15 mL) before LiOH (276 mg, 11.5 mmol) was added and
stirred for 5 min. The mixture was quenched by addition of saturated
aqueous sodium bicarbonate (5 mL) and extracted with EtOAc
(3 × 50 mL), and the combined organic layers were dried (Na2-
SO4), filtered, and concentrated. The residue was purified via
column chromatography (SiO2, 20% EtOAc in hexanes) to give
35 as a brown oil (557 mg, 58%): 1H NMR (CDCl3, 400 MHz) δ
7.66 (s, 1H), 5.24 (s, 2H), 5.12 (d, J ) 6.4 Hz, 1H), 5.05 (d, J )
6.4 Hz, 1H), 3.97 (s, 3H), 3.87 (m, 1H), 3.61 (s, 3H), 3.53 (s, 3H),
2.91 (m, 2H), 2.46 (m, OH), 1.55 (m, 2H), 1.45 (m, 2H), 0.97 (m,
3H); 13C NMR (CDCl3, 100 MHz) δ 153.4, 146.6, 146.4, 139.8,
130.1, 111.7, 102.3, 95.8, 71.8, 61.4, 58.0, 56.9, 41.0, 33.4, 19.3,
14.5; IR (film) νmax 3468, 3053, 2985, 1578, 1477, 1155, 1022,
897 cm-1; HRMS (FAB+) m/z: [M + H] calcd for C16H26NO8,
360.1658; found, 360.1672.
1-(2-Methoxy-3,6-bis(methoxymethoxy)-5-nitrophenyl)pentan-
2-yl 5-chloro-2,4-dihydroxybenzoate (40). 2,4-Dihydroxy-5-
chloro-benzoic acid (209 mg, 1.1 mmol) was dissolved in DMF/
THF (1:3, 11 mL) before DMAP (201 mg, 1.65 mmol), DCC (340
mg, 1.65 mmol), and compound 35 (400 mg, 1.1 mmol) were added.
The reaction was warmed to 50 °C and stirred for 12 h. The mixture
was quenched by addition of saturated aqueous ammonium chloride
(20 mL) and extracted with EtOAc (3 × 50 mL). The combined
organic layers were dried (Na2SO4), filtered, and concentrated. The
residue was purified via column chromatography (SiO2, 10% EtOAc
in hexanes) to give 40 as a pale yellow solid (301 mg, 51%): 1H
NMR (CDCl3, 400 MHz) δ 7.88 (s, 1H), 7.63 (s, 1H), 6.57 (s,
1H), 5.42 (m, 1H), 5.19 (m, 2H), 5.06 (m, 2H), 4.00 (s, 3H), 3.61
(s, 3H), 3.50 (s, 3H), 3.21 (m, 1H), 3.11 (m, 1H), 1.69 (m, 2H),
1.45 (m, 2H), 0.97 (t, J ) 7.3 Hz, 3H); 13C NMR (CDCl3, 125
MHz) δ 169.1, 162.8, 157.5, 153.6, 146.2, 139.6, 130.7, 130.6,
127.9, 112.4, 111.6, 107.2, 104.3, 102.2, 95.9, 75.2, 61.6, 58.3,
56.9, 36.7, 30.1, 19.1, 14.3; IR (film) νmax 3055, 2986, 1668, 1525,
1421, 1265, 1157 cm-1; HRMS (ES+) m/z: [M + H] calcd for
C23H29NO11Cl, 530.1429; found, 530.1426.
1-(3-Amino-6-methoxy-2,5-bis(methoxymethoxy)phenyl)pen-
tan-2-yl 5-chloro-2,4-dihydroxybenzoate (45). Compound 40 (200
mg, 0.38 mmol) was dissolved in ethanol (3.8 mL) at the room
temperature before PtO2 (10 mg, 5% w/w) was added. The reaction
was stirred under a hydrogen atmosphere for 12 h. The solution
was filtered through Celite and the filtrate was concentrated. The
residue was purified via column chromatography (SiO2, 10% EtOAc
in hexanes) to give 45 as a brown solid (158 mg, 84%): 1H NMR
(CDCl3, 400 MHz) δ 7.90 (s, 1H), 6.57 (s, 1H), 6.50 (s, 1H), 5.42
(m, 1H), 5.14 (m, 2H), 4.99 (m, 2H), 3.81 (s, 3H), 3.63 (s, 3H),
7628 J. Org. Chem., Vol. 71, No. 20, 2006