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Q. V. Vo et al. / Bioorg. Med. Chem. 22 (2014) 856–864
(MgSO4), and concentrated under reduced pressure. The indole thi-
ohydroxymates 15–17 were obtained by flash column chromatog-
raphy on silica gel eluting with 2–5% MeOH/DCM.
(2.5 equiv). After stirring under N2 for 18 h, an additional portion
of the complex (0.3 equiv) was added and stirring was continued
for 2 h. After that, a solution of KHCO3 (4 equiv) in water (40 ml)
was added and the mixture was stirred for 30 min and then it
was concentrated under reduced pressure. The residue was dis-
solved in water and extracted with chloroform (3 ꢂ 40 ml). The or-
ganic layers were dried (MgSO4), filtered and concentrated under
reduce pressure. To remove excess pyridine, the mixture was co-
distilled several times with toluene. The compounds 18–20 were
obtained by flash chromatography eluting with 80–85% DCM/
MeOH.
4.6.1. 2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl-((indol-3-yl)
methyl)thiohydroxymate 15
Pure 15 was obtained as a cream colored solid (1.27 g, 42%(A)).
Rf = 0.2 in 60% hexane/EtOAc; mp = 72–74 °C (dec); ½a D20
ꢃ
= +4 (c 1,
CHCl3); IR (NaCl) mmax 3371, 1751, 1600, 1405, 1041 cmꢀ1
;
1H
NMR (300 MHz, CDCl3) (300 K) d 8.54 (s, 1H, NH), 7.54 (d,
J4i,5i = 7.5 Hz, 1H, H4i), 7.33 (d, J6i,7i = 8.1 Hz, 1H, H7i), 7.17–7.05
(m, 2H, H5i and H6i), 7.01 (s, 1H, H2i), 4.92–4.86 (m, 4H, H1, H2,
H3 and H4), 4.10 (d, JAB = 16.5 Hz, 1H, CHHC@N), 4.03 (d,
JAB = 16.5 Hz, 1H, CHHC@N), 3.99–3.83 (m, 2H, H6a and H6b),
3.19–3.18 (m, 1H, H5), 2.02, 1.96, 1.89, 1.80 (4 ꢂ s, 12H, CH3COO);
13C NMR (75 MHz, CDCl3) (300 K) d 170.3, 169.8, 169.0, 168.9
(4 ꢂ CH3COO), 151.1 (C@N), 135.9 (C-8i), 126.2 (C-9i), 122.4
(C-2i), 121.9 (C-6i), 119.3 (C-5i), 117.8 (C-4i), 111.2 (C-7i), 109.5
(C-3i), 79.1 (C-1), 75.1 (C-5), 73.3 (C-3), 69.7 (C-2), 67.5 (C-4),
61.6 (C-6), 28.8 (CH2C@N), 20.6, 20.3, 20.2, 20.1 (4 ꢂ CH3COO);
HRMS (ESI) m/z for C24H28O10N2NaS [M+Na]+, calcd 559.1362,
found 559.1352.
4.7.1. Potassium 2,3,4,6-tetra-O-acetylglucobrassicin 18
Pure 18 was obtained as a white solid (1.13 g, 86%). Rf = 0.4 in
DCM/MeOH (20%); mp = 120–122 °C (dec);
½
a 2D0
ꢃ
= ꢀ5 (c 1.0,
MeOH); IR (KBr drift) mmax 3376, 1750, 1650, 1237, 1042 cmꢀ1
;
1H NMR (300 MHz, CD3OD) (300 K) d 10.48 (s, 1H, NH), 7.68 (d,
J4i,5i = 7.8 Hz, 1H, H4i), 7.39 (d, J6i,7i = Hz, 1H, H7i), 7.23 (s, 1H,
H2i), 7.16–7.03 (m, 2H, H5i and H6i), 5.09 (d, J1,2 = 9.9 Hz, 1H,
H1), 4.90–4.81 (m, 3H, H2, H3 and H4), 4.17–4.04 (m, 3H, CH2C@N
and H6a), 3.87 (dd, J5,6b = 2.4 Hz, J6a,6b = 12.6 Hz, 1H, H6b),
3.43–3.36 (m, 1H, H5), 2.03, 1.92, 1.87, 1.80 (4 ꢂ s, 12H, CH3COO);
13C NMR (75 MHz, CD3OD) (300 K) d 170.4, 169.6, 169.3, 169.0
(4 ꢂ CH3COO), 157.1 (C@N), 136.4 (C-8i), 126.1 (C-9i), 122.9
(C-2i), 121.1 (C-6i), 118.5 (C-5i), 117.5 (C-4i), 110.8 (C-7i), 108.1
(C-3i), 78.9 (C-1), 75.0 (C-5), 73.2 (C-3), 69.3 (C-2), 67.4 (C-4),
61.3 (C-6), 28.8 (CH2C@N), 18.8, 18.6(2), 18.5 (4 ꢂ CH3COO); HRMS
(ESI) m/z for C24H27O13N2S2 [M-K], calcd 615.0960, found 615.0956.
4.6.2. 2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl-
((1-methoxyindol-3-yl)methyl)thiohydroxymate 16
Pure 16 was obtained as a foam solid (520 mg, 45% (A)).
Rf = 0.19 in 60% hexane/EtOAc; mp = 65–67 °C; ½a D20
ꢃ
= +10.0 (c 1,
CHCl3); IR (KBr drift) mmax 3306, 2942, 2832, 1750, 1600, 1232,
1045 cmꢀ1 1H NMR (300 MHz, DMSO-d6) (300 K) d 11.35 (s, 1H,
;
OH), 7.63 (s, 1H, H2i), 7.53 (d, J = 7.5 Hz, 1H, H4i), 7.39 (d,
J = 7.5 Hz, 1H, H7i), 7.16 (t, J = 7.5 Hz, 1H, H6i), 7.01 (t, J = 7.5 Hz,
1H, H5i), 5.55 (d, J = 10.2 Hz, 1H, H1), 5.34 (t, J = 9.6 Hz, 1H, H3),
4.91 (t, J = 9.6 Hz, 1H, H4), 4.82 (t, J = 9.6 Hz, 1H, H2), 4.13–3.72
(m, 8H, H5, H6a, H6b, CH3O and CH2CN), 1.96, 1.91, 1.89. 1.86
(4 ꢂ s, 12H, CH3COO); 13C NMR (75 MHz, DMSO-d6) (300 K) d
170.1, 169.6, 169.3, 169.1 (4 ꢂ CH3COO), 148.3 (C@N), 132.2
(C-8i), 123.6 (C-2i), 122.9 (C-6i), 122.4 (C-9i), 119.5(2) (C-4i and
C-5i), 108.3 (C-7i), 106.4 (C-3i), 78.2 (C-1), 74.5 (C-5), 72.9 (C-3),
69.9 (C-2), 68.0 (C-4), 65.8 (CH3O), 62.0 (C-6), 28.1 (CH2C@N),
20.8, 20.5, 20.3, 20.2 (4 ꢂ CH3COO); HRMS (ESI) m/z for
C25H30O11N2NaS [M+Na]+, calcd 589.1468, found 589.1460.
4.7.2. Potassium 2,3,4,6-tetra-O-acetylneoglucobrassicin 19
Pure 19 was obtained as a slight yellow solid (360 mg, 81%).
Rf = 0.2 in 20% DCM/MeOH; mp = 124–126 °C (dec);
ꢀ5 (c 1.0, MeOH); IR (KBr drift) max 2940, 1754, 1582, 1441, 1370,
1231, 1059 cmꢀ1 1H NMR (300 MHz, CD3OD) (300 K) d 7.72 (d,
½
a 2D0
ꢃ
=
m
;
J = 7.5 Hz, 1H, H4i), 7.47 (s, 1H, H2i), 7.44 (d, J = 7.5 Hz, 1H, H7i),
7.23 (t, J = 7.5 Hz, 1H, H6i), 7.11 (t, J = 7.5 Hz, 1H, H5i), 5.18 (d,
J = 10.2 Hz, 1H, H1), 5.00–4.77 (m, 3H, H2, H3 and H4), 4.13–4.07
(m, 6H, H6b, CH3O and CH2CN), 3.85 (dd, J5,6b = 2.1 Hz, J6a,6b
=
12.6 Hz, H6a), 3.54–3.52 (m, 1H, H5), 2.02, 1.94, 1.89, 1.78 (4 ꢂ s,
12H, CH3COO); 13C NMR (75 MHz, CD3OD) (300 K) d 170.4, 169.6,
169.2, 169.0 (4 ꢂ CH3COO), 156.3 (C@N), 132.2 (C-8i), 122.8 (C-9i),
122.1 (C-6i), 121.8 (C-2i), 119.5, 119.3 (C-4i and C-5i), 107.7 (C-7i),
105.3 (C-3i), 79.1 (C-1), 75.1 (C-5), 73.2 (C-3), 69.4 (C-2), 67.4
(C-4), 64.7 (CH3O), 61.3 (C-6), 28.6 (CH2C@N), 18.8, 18.7, 18.6, 18.5
(4 ꢂ CH3COO); HRMS (ESI) m/z for C25H29O14N2S2 [M-K]ꢀ, calcd
645.1066, found 645.1055.
4.6.3. 2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl-
((4-methoxyindol-3-yl)methyl)thiohydroxymate 17
Pure 17 was obtained as a foam solid (350 mg, 46% (A)). Rf = 0.37
in 40% hexane/EtOAc; mp = 93–95 °C; ½a D20
= ꢀ3 (c 1, CHCl3); IR (KBr
ꢃ
drift) m
max 3337, 2940, 2838, 1754, 1650, 1231, 1046 cmꢀ1; 1H NMR
(300 MHz, CD3OD) (300 K) d 7.04 (t, J6i,7i = J5i,6i = 8.1 Hz, 1H, H6i),
6.99 (d, J6i,7i = 8.1 Hz, 1H, H7i), 6.89 (s, 1H, H2i), 6.55 (d, J5i,6i = 8.1 Hz,
1H, H5i), 5.13 (d, J1,2 = 9.6 Hz, 1H, H1), 4.87–4.77 (m, 3H, H2, H3 and
H4), 4.24 (d, JAB = 18.3 Hz, 1H, CHHC = N), 4.21 (d, JAB = 18.3 Hz, 1H,
CHHC@N), 4.05 (dd, J5,6a = 5.4 Hz, J6a,6b = 12.6 Hz, 1H, H6a), 3.94 (s, 3H,
CH3O), 3.75 (dd, J5,6b = 2.4 Hz, J6a,6b = 12.6 Hz, 1H, H6b), 3.05–3.00 (m,
1H, H5), 1.98, 1.93, 1.90, 1.89 (4 ꢂ s, 12H, CH3COO); 13C NMR
(75 MHz, CD3OD) (300 K) d 169.6, 169.2, 169.1, 169.0 (4 ꢂ CH3COO),
153.8 (C-4i), 151.3 (C@N), 137.8 (C-8i), 121.8 (C-6i), 121.2 (C-2i),
115.8 (C-9i) 109.5 (C-3i), 104.5 (C-7i), 98.6 (C-5i), 79.1 (C-1), 74.7
(C-5), 73.4 (C-3), 69.6 (C-2), 67.3 (C-4), 60.8 (C-6), 53.9 (CH3O),
29.4 (CH2C@N), 18.7(2), 18.6(2) (4 ꢂ CH3COO); HRMS (ESI) m/z for
C25H30O11N2NaS [M+Na]+, calcd 589.1468, found 589.1444.
4.7.3. Potassium 2,3,4,6-tetra-O-acetyl-4-
methoxyglucobrassicin 20
Pure 20 was obtained as a white solid (340 mg, 82%). Rf = 0.17 in
DCM/MeOH (20%); mp = 126–127 °C (dec.); ½a D20
= ꢀ26 (c 0.58,
ꢃ
MeOH); IR (KBr drift) mmax 3325, 2940, 2839, 1746, 1584, 1236,
1058 cmꢀ1 1H NMR (300 MHz, CD3OD) (300 K) d 10.53 (s, 1H,
;
NH), 7.06–6.97 (m, 3H, H2i, H6i and H7i), 6.57 (d, J5i,6i = 7.2 Hz,
1H, H5i), 5.15 (d, J1,2 = 9.9 Hz, 1H, H1), 4.90–4.78 (m, 3H, H2, H3
and H4), 4.38 (d, JAB = 16.6 Hz, 1H, CHHC@N), 4.33 (d, J AB = 16.6 Hz,
1H, CHHC@N), 4.04 (dd, J5,6a = 4.2 Hz, J6a,6b = 12.6 Hz, 1H, H6a), 3.96
(s, 3H, CH3O), 3.72 (dd, J5,6b = 2.1 Hz, J6a,6b = 12.6 Hz, 1H, H6b),
3.01–2.98 (m, 1H, H5), 1.99, 1.90(2), 1.88 (4 ꢂ s, 12H, CH3COO);
13C NMR (75 MHz, CD3OD) (300 K) d 170.4 169.6, 169.2, 169.0
(4 ꢂ CH3COO), 158.2 (C@N), 153.7 (C-4i), 137.6 (C-8i), 122.0
(C-6i), 121.9 (C-2i), 115.6 (C-9i), 108.3 (C-3i), 104.6 (C-7i), 98.7
(C-5i), 79.4 (C-1), 74.8 (C-5), 73.3 (C-3), 69.2 (C-2), 67.1 (C-4),
60.7 (C-6), 53.9 (CH3O), 29.6 (CH2C@N), 18.7(2), 18.6(2) (4 ꢂ
CH3COO); HRMS (ESI) m/z for C25H29O14N2S2 [M-K]ꢀ, calcd
645.1066, found 645.1058.
4.7. General procedure for the preparation of potassium sulfate
salts of thiohydroxymates (18–20)
To a stirred solution of the thiohydroxymate 15–17 (1 equiv) in
dry pyridine (40 ml) was added pyridine sulfur trioxide complex