4
Zhang et al. Sci China Chem
(2:1) as eluent to give compound 12a (0.124 g, >99%) as a
1.42 (s, 3H), 1.30 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ 179.2, 156.2, 141.0, 132.4, 131.8, 130.2, 125.3, 116.6,
110.0, 109.8, 94.6,78.0, 67.4, 57.1, 56.1, 47.8, 37.0, 26.6,
25.0; HRMS-ESI: m/z [M+Na+] calcd for C22H29NNaO6:
426.1887; found: 426.1889.
pale yellow oil. [ ]29: −9.1 (c 0.396, CHCl3); IR (thin film):
D
3425, 2931, 2119, 1659, 1512, 1461, 1375, 1235, 1153, 1074,
1
1007, 922, 852, 787 cm−1; H NMR (400 MHz, CDCl3): δ
9.55 (s, 1H), 7.01 (d, J=8.8 Hz, 2H), 6.96–6.93 (m, 3H),
6.18 (d, J=4.0 Hz, 1H), 5.14 (m, 2H), 4.71 (dt, J=13.6, 6.8
Hz, 1H), 4.38 (d, J=5.6 Hz, 1H), 4.34 (dd, J=13.6, 7.6 Hz,
1H), 4.16 (dd, J=12.0,6.0 Hz, 1H), 4.08–3.99 (m, 2H), 3.46
(s, 3H), 2.98 (t, J=7.2 Hz, 2H), 1.43 (s, 3H), 1.33 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 179.5, 156.1, 142.2, 132.0,
131.9, 130.3, 125.2, 116.7, 109.8, 108.5, 94.7, 77.7, 66.7,
65.9, 56.1, 47.8, 37.1, 26.6, 24.9; HRMS-ESI: m/z [M+Na+]
calcd for C21H27NNaO6: 412.1731; found: 412.1735.
2.2.11 5-((R)-((R)-2,2-dimethyl-1,3-dioxolan-4-
yl)(methoxy)methyl)-1-(4-(methoxymethoxy)phenethyl)-
1H-pyrrole-2-carbaldehyde (13b)
Similar procedure to that of 13a. Compound 13b: pale yellow
oil; yield: 83%; [ ]29: −18.6 (c 0.226, CHCl3); IR (thin film):
D
2931, 1663, 1512, 1465, 1380, 1234, 1153, 1079, 1006, 920,
827, 784 cm−1; 1H NMR (400 MHz, CDCl3): δ 9.56 (s, 1H),
7.14–7.07 (m, 2H), 6.99–6.92 (m, 3H), 6.18 (d, J=4.0 Hz,
1H), 5.14 (s, 2H), 4.60 (ddd, J=14.0, 8.4, 6.0 Hz, 1H), 4.48
(ddd, J=14.0, 8.4, 7.2 Hz, 1H), 4.40 (dd, J=13.2,6.4 Hz, 1H),
4.22 (d, J=7.2 Hz, 1H), 3.83 (dd, J=8.8, 6.8 Hz, 1H), 3.54
(dd, J=8.8, 6.4 Hz, 1H), 3.46 (s, 3H), 3.16 (s, 3H), 3.02–2.88
(m, 2H), 1.33 (s, 3H), 1.25 (s, 4H); 13C NMR (100 MHz,
CDCl3): δ 179.2, 156.3, 139.1, 132.6, 131.8, 130.2, 125.1,
116.6, 110.4, 110.3, 94.6, 77.0, 76.9, 65.9, 57.1, 56.1, 48.2,
37.0, 29.8, 26.4, 25.4; HRMS-ESI: m/z [M+Na+] calcd for
C22H29NNaO6: 426.1887; found: 426.1886.
2.2.9 5-((R)-((R)-2,2-dimethyl-1,3-dioxolan-4-
yl)(hydroxy) mthyl)-1-(4-(methoxymethoxy)phenethyl)-1H-
pyrrole-2-carbaldehyde (12b)
Similar procedure to that of 12a. Compound 12b: pale yellow
oil; yield: >99%; [ ]29: −15.0 (c 0.466, CHCl3). IR (thin
D
film): 3440, 2929, 2119, 1662, 1512, 1464, 1372, 1235, 1153,
1070, 1005, 921, 885, 783 cm−1; 1H NMR (400 MHz, CDCl3):
δ 9.58 (s, 1H), 6.98 (d, J=8.4 Hz, 2H), 6.92 (d, J=8.8 Hz,
2H), 6.92 (d, J=4.4 Hz, 1H), 6.17 (d, J=4.0 Hz, 1H), 5.14 (s,
2H), 4.65–4.49 (m, 2H), 4.27 (dd, J=12.4,6.0Hz, 1H), 4.04
(t, J=5.6 Hz, 1H), 3.91 (dd, J=8.8, 6.8 Hz, 1H), 3.49 (dd,
J=8.8, 6.4 Hz, 1H), 3.47 (s, 3H), 3.03–2.97 (m, 2H), 1.40
(s, 3H), 1.38 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 179.6,
156.3, 141.3, 132.2, 132.1, 130.3, 124.7, 116.6, 110.3, 108.8,
94.7, 77.3, 66.4, 66.3, 56.1, 47.9, 37.0, 26.8, 25.5; HRMS-
ESI: m/z [M+Na+] calcd for C21H27NNaO6: 412.1731; found:
412.1740.
2.2.12 5-((1S,2R)-2,3-dihydroxy-1-methoxypropyl)-1-(4-
hydroxyphenethyl)-1H-pyrrole-2-carbaldehyde (4)
To a solution of 13a (0.0205 g, 0.051 mmol, 1.0 eq.) in DCM
(4.0 mL) was added a solution of BBr3 (0.1279 g, 0.510 mmol,
10.0 eq.) in DCM (1.0 mL) at −60 °C. 5 min later, the re-
action was quenched with aqueous saturated NaHCO3 solu-
tion (15 mL). The aqueous layer was extraced with ethyl ac-
etate (3×15 mL). The combined organic layer was dried over
Na2SO4 and evaporated. The residue was purified by silica
column using petroleum ether-ethyl acetate (1:2) as eluent to
give compound 4 (0.0123 g, 75%) as a white oil. [ ]2D9: +14.5
(c 0.172, CHCl3); IR (thin film): 3787, 3662, 3379, 2924,
2.2.10 5-((S)-((R)-2,2-dimethyl-1,3-dioxolan-4-
yl)(methoxy)methyl)-1-(4-(methoxymethoxy)phenethyl)-
1H-pyrrole-2-carbaldehyde (13a)
To a reaction tube containing NaH (60% in mineral oil,
0.0201 g, 0503 mmol, 10 eq.) was added a solution of
12a (0.0196 g, 0.050 mmol, 1.0 eq.) in THF (1.0 mL) at 0
°C. Then excess methyl iodide (0.2 mL) was added. After
stirring at 0 °C for 0.5 h, the reaction was quenched with
aqueous saturated NH4Cl solution (10 mL). The aqueous
layer was extraced with ethyl acetate (3×10 mL). The com-
bined organic layer was dried over Na2SO4 and evaporated.
The residue was purified by silica column using petroleum
ether-ethyl acetate (2:1) as eluent to give compound 13a
(0.0181 g, 90%) as a pale yellow oil. [ ]2D9: +12.2 (c 0.238,
CHCl3); IR (thin film): 2933, 1662, 1511, 1460, 1376, 1234,
1
2854, 1640, 1516, 1460, 1374, 1240, 1105, 787 cm−1; H
NMR (400 MHz, CD3OD): δ 9.41 (s, 1H), 7.07 (d, J=4.1Hz,
1H), 7.06–7.02 (m, 2H), 6.71–6.67 (m, 2H), 6.28 (d, J=4.1
Hz, 1H), 4.60 (ddd, J=14.0, 8.8, 5.6 Hz, 1H), 4.46 (dt, J=13.6,
8.4 Hz, 1H), 4.32 (d, J=7.2 Hz, 1H), 3.75–3.70 (m, 1H), 3.68
(s, 1H), 3.67 (d, J=1.6 Hz, 1H), 3.09 (s, 3H), 2.97–2.87 (m,
2H); 13C NMR (100 MHz, CD3OD): δ 180.4, 157.2, 144.4,
133.4, 131.1(2C), 130.6, 127.0, 116.4(2C), 111.0, 77.7, 75.6,
64.2, 61.6, 57.5, 49.0, 37.8, ; HRMS-ESI: m/z [M+Na+] calcd
for C17H21NNaO5: 342.1312; found: 342.1322.
2.2.13 5-((1R,2R)-2,3-dihydroxy-1-methoxypropyl)-1-(4-
hydroxyphenethyl)-1H-pyrrole-2-carbaldehyde (3)
1
1154, 1078, 1005, 922, 827, 785 cm−1; H NMR (400 MHz,
CDCl3): δ 9.54 (s, 1H), 7.13 (d, J=8.4 Hz, 2H), 6.98–6.95
(m, 3H), 6.24 (d, J=4.0 Hz, 1H), 5.14 (s, 2H), 4.62 (ddd,
J=14.0, 8.8, 6.0 Hz, 1H), 4.49–4.41 (m, 1H), 4.20–4.15
(m, 1H), 4.11 (dd, J=8.4, 6.0 Hz, 2H), 4.01 (dd, J=8.4, 5.6
Hz, 1H), 3.46 (s, 3H), 3.10 (s, 3H), 3.02–2.94 (m, 2H),
Similar procedure to that of 4. Compound 3: white oil; yield:
78%; [ ]29: −6.3 (c 0.128, CHCl3); IR (thin film): 3788,
D
3662, 3379, 2922, 2847, 1657, 1515, 1455, 1377, 1265, 1042,
790 cm−1; 1H NMR (400 MHz, CD3OD): δ 9.45 (s, 1H), 7.07