Synthesis of Indoxyl Glycosides
1.73 mmol), TBAHS (360 mg, 1.06 mmol), CH2Cl2 (25 mL), pound 1e (327 mg, 1.21 mmol), compound 11 (520 mg, 1.26 mmol),
K2CO3 solution (1 m aq.; 25 mL). Yield 83% (865 mg, 1.34 mmol),
TBAHS (410 mg, 121 mmol), CH2Cl2 (10 mL), K2CO3 solution
(1 m aq.; 10 mL). Yield 82% (597 mg, 0.997 mmol), slightly yellow
yellow syrup. Rf = 0.19 (petroleum ether/EtOAc, 1:1). [α]2D9 = –8.6
(c = 0.35, CHCl3). H NMR (400 MHz, CDCl3): δ = 8.68 (s, 1 H, solid. Rf = 0.33 (petroleum ether/EtOAc, 1:1). [α]2D5 = 5.6 (c = 0.5,
1
3
1
NH), 7.49 (d, Jarom-H,H = 8.9 Hz, 1 H, CHarom), 7.12 (d,
CHCl3). m.p. 94 °C. H NMR (400 MHz, CDCl3): δ = 8.53 (br. s,
3
3
3
3Jarom-H,H = 8.9 Hz, 1 H, CHarom), 5.40 (dd, J1,2 = 7.8, J2,3
=
1 H, NH), 7.95 (d, Jarom-H,H = 2.0 Hz, 1 H, Harom), 7.39 (dd,
9.4 Hz, 1 H, 2-H), 5.33 (d, J1,2 = 7.8 Hz, 1 H, 1-H), 5.30 (dd~vt, 3Jarom-H,H = 2.0, Jarom-H,H = 8.8 Hz, 1 H, Harom), 7.20 (d,
1 H, 3-H), 5.20 (dd~vt, 1 H, 4-H), 4.16 (dd, J5,6a = 4.6, J6a,6b
12.3 Hz, 1 H, 6a-H), 3.98 (dd, J5,6b = 2.6, J6a,6b = 12.3 Hz, 1 H, 10.5 Hz, 1 H, 2-H), 5.44 (dd, J3,4 = 3.5, J4,5 = 1.0 Hz, 1 H, 4-H),
3
3
3
3
3
3
=
3Jarom-H,H = 8.8 Hz, 1 H, Harom), 5.57 (dd, J1,2 = 7.9, J2,3
=
3
3
3
3
3
3
3
6b-H), 3.96 (s, 3 H, -OCH3), 3.65–3.59 (m, 1 H, 5-H), 2.09, 2.04, 5.11 (d, J1,2 = 7.9 Hz, 1 H, 1-H), 5.11 (dd, J2,3 = 10.5, J3,4
=
2.02, 1.97 [4 s, each 3 H, C(O)CH3] ppm. 13C NMR (125 MHz, 3.5 Hz, 1 H, 3-H), 4.20–4.10 (m, 2 H, 6a-H, 6b-H), 4.00–3.94 (m,
CDCl3): δ = 170.4, 170.3, 169.3 [C(O)CH3], 161.0 [C(O)O-], 133.3
1 H, 5-H), 3.93 (s, 3 H, OCH3), 2.23, 2.13, 2.02, 1.94 [4 s, each 3
(Cquat), 130.5 (CHarom), 126.6, 120.3, 118.5, 115.4 (Cquat), 111.7 H, C(O)CH3] ppm. 13C NMR (101 MHz, CDCl3): δ = 170.4, 170.3,
(CHarom), 101.4 (C-1), 73.0 (C-3), 71.9 (C-2), 71.7 (C-5), 68.5 (C- 170.1, 169.6 [C(O)CH3], 160.7 [C(O)OCH3], 139.7, 132.1, 122.9,
4), 61.5 (C-6), 52.1 (-OCH3), 20.7, 20.6, 20.6, 20.5 [C(O)CH3] ppm. 115.9, 113.8 (Cquat), 129.3, 123.4, 113.3 (CHarom),102.8 (C-1), 71.1
HRMS (ESI): calcd. for C24H25BrClNO12Na [M + Na]+ 656.0146;
found 656.00153.
(C-5), 70.8 (C-3), 68.8 (C-2), 67.0 (C-4), 61.4 (C-6), 51.9 [C(O)-
OCH3], 20.9, 20.7, 20.6 [C(O)CH3] ppm. HRMS (ESI): calcd. for
C24H26BrNO12Na [M + Na]+ 622.0536; found 622.0530.
(Methyl 5-Bromo-4-chloroindox-3-ylate) (2,3,4,6-tetra-O-acetyl-β-
D
-galactopyranosyl)-(1Ǟ4)-2,3,6-tri-O-acetyl-β-D-glucopyranoside
(Allyl 5-Bromo-4-chloroindox-3-ylate) 2,3,4,6-Tetra-O-acetyl-β-
glucopyranoside (13a): Prepared according to general procedure 7.
Compound 1a (50 mg, 0.15 mmol), compound (70 mg,
D-
(12b): Prepared according to general procedure 7. Compound 1d
(30 mg, 98 μmol), compound 10 (69 mg, 98 μmol), TBAHS (33 mg,
97 μmol), CH2Cl2 (2.5 mL), K2CO3 solution (1 m aq.; 2.5 mL).
Yield 73% (66 mg, 71 μmol), colourless solid. Rf = 0.12 (petroleum
ether/EtOAc, 1:1). [α]2D5 = +20.6 (c = 0.5, CHCl3). m.p. 81–82 °C.
1H NMR (400 MHz, CDCl3): δ = 8.65 (s, 1 H, NH), 7.48 (d,
3Jarom-H,H = 8.6 Hz, 1 H, Harom), 7.10 (d, 3Jarom-H,H = 8.6 Hz, 1 H,
9
0.17 mmol), TBAHS (51 mg, 0.15 mmol), CH2Cl2 (5 mL), K2CO3
solution (1 m aq.; 5 mL). Yield 77% (76.0 mg, 0.115 mmol), colour-
less solid. Rf = 0.30 (petroleum ether/EtOAc, 1:1). [α]2D5 = –7.5 (c
= 0.55, CHCl3). m.p. 82 °C. 1H NMR (400 MHz, CDCl3): δ = 8.73
3
(s, 1 H, NH), 7.49 (d, Jarom-H,H = 8.8 Hz, 1 H, Harom), 7.12 (d,
3
3Jarom-H,H = 8.8 Hz, 1 H, Harom), 6.08 (dddd, JCH=CH2a,CH=CH2
=
H
arom), 5.37–5.34 (m, 1 H, 4Ј-H), 5.33–5.28 (m, 3 H, 1-H, 2-H, 3-
3
3
3
3
H), 5.10 (dd, J1Ј,2Ј = 7.8, J2Ј,3Ј = 10.1 Hz, 1 H, 2Ј-H), 4.97 (dd,
17.1, JCH=CH2b,CH=CH2 = 11.5, JCH2-CH=,CH2-CH = 5.6 Hz, 1 H,
-CH2-CH=CH2), 5.53–5.47 (m, 1 H, -CH=CH2a), 5.42–5.33 (m, 3
H, 1-H, 2-H, -CH=CH2b), 5.29 (dd~vt, 1 H, 3-H), 5.16 (dd~vt, 1
3J2Ј,3Ј = 10.1, J3Ј,4Ј = 3.5 Hz, 1 H, 3Ј-H), 4.52 (d, J1Ј,2Ј = 7.8 Hz,
3
3
3
3
1 H, 1Ј-H), 4.33 (dd, J5,6a = 2.5, J6a,6b = 12.1 Hz, 1 H, 6a-H),
4.15–4.08 (m, 2 H, 6Јa-H, 6Јb-H), 4.01 (dd, J5,6b = 4.8, J6a,6b
12.1 Hz, 1 H, 6b-H), 3.97 (dd, J3,4 = 4.0, J4,5 = 9.8 Hz, 1 H, 4-
H), 3.95 (s, 3 H, OCH3), 3.89 (ddd~vt, 1 H, 5Ј-H), 3.53 (ddd, J4,5
3
3
3
3
=
H, 4-H), 4.87–4.84 (m, 2 H, O-CH2-), 4.16 (dd, J5,6a = 4.7, J6a,6b
3
3
3
3
= 12.2 Hz, 1 H, 6a-H), 3.96 (dd, J5,6b = 2.5, J6a,6b = 12.2 Hz, 1
3
3
3
H, 6b-H), 3.62 (ddd, 3J4,5 = 10.0, J5,6a = 4.7, J5,6b = 2.5 Hz, 1 H,
5-H) ppm. 13C NMR (101 MHz, CDCl3): δ = 170.4, 170.3, 169.4
[C(O)CH3], 160.2 [-C(O)O-], 137.1, 133.4, 126.6, 120.2, 118.6, 115.3
(Cquat), 131.6 (-CH=CH2), 130.5 (CHarom), 119.3 (-CH=
CH2),111.7 (CHarom), 101.3 (C-1), 72.9 (C-3), 71.8 (C-2), 71.8 (C-
5), 68.5 (C-4), 65.9 (O-CH2-), 61.5 (C-6), 20.7, 20.6, 20.6, 20.5
[C(O)CH3] ppm. HRMS (ESI): calcd. for C26H27BrClNO12Na [M
+ Na]+ 684.0303; found 684.0292.
= 9.8, 3J5,6a = 2.5, 3J5,6b = 4.8 Hz, 1 H, 5-H), 2.15, 2.09, 2.08, 2.06,
1.99, 1.98, 1.95 [7 s, each 3 H, C(O)CH3] ppm. 13C NMR
(101 MHz, CDCl3): δ = 170.3, 170.1, 170.0, 169.8, 169.7 [C(O)-
CH3], 133.3 (Cquat), 130.5, 111.7 (CHarom), 101.4 (C-1), 101.1 (C-
1Ј), 76.2 (C-4), 73.1, 72.6, 72.3 (C-2, C-3, C-5), 70.9 (C-3Ј), 70.7
(C-5Ј), 69.1 (C-2Ј), 66.6 (C-4Ј), 61.1 (C-6), 60.8 (C-6Ј), 52.1
(OCH3), 20.8, 20.8, 20.7, 20.6, 20.6, 20.5 [C(O)CH3] ppm. HRMS
(ESI): calcd. for C36H41BrClNO20Na [M + Na]+ 944.0992; found
944.1000.
(Allyl 5-Bromo-4-chloroindox-3-ylate) (2,3,4,6-Tetra-O-acetyl-β-
D-
galactopyranosyl)-(1Ǟ4)-2,3,6-tri-O-acetyl-β- -glucopyranoside
D
(Methyl 5-Bromo-4-chloroindox-3-ylate) 2,3,4,6-tetra-O-acetyl-β-D-
(13b): Prepared according to general procedure 7. Compound 1a
(470 mg, 1.42 mmol), compound 10 (1.00 g, 1.43 mmol), TBAHS
(485 mg, 1.43 mmol), CH2Cl2 (15 mL), K2CO3 solution (1 m aq.;
15 mL). Yield 74% (1.01 g, 1.06 mmol), colourless solid. Rf = 0.32
(petroleum ether/EtOAc, 1:1). [α]2D5 = –5.5 (c = 0.75, CHCl3). m.p.
galactopyranoside (12c): Prepared according to general procedure
7. Compound 1d (370 mg, 1.21 mmol), compound 11 (520 mg,
1.26 mmol), TBAHS (410 mg, 121 mmol), CH2Cl2 (10 mL), K2CO3
solution (1 m aq.; 10 mL). Yield 86% (660 mg, 1.02 mmol), slightly
yellow solid. Rf = 0.29 (petroleum ether/EtOAc, 1:1). [α]2D5 = –28.2
1
112–113 °C. H NMR (400 MHz, CDCl3): δ = 8.75 (s, 1 H, NH),
1
3
3
(c = 0.5, CHCl3). m.p. 108–109 °C. H NMR (400 MHz, CDCl3):
δ = 8.69 (s, 1 H, NH), 7.49 (d, Jarom-H,H = 8.6 Hz, 1 H, CHarom),
7.47 (d, Jarom-H,H = 8.8 Hz, 1 H, Harom), 7.09 (d, Jarom-H,H
=
3
8.8 Hz, 1 H, Harom), 6.06 (dddd~vddd, 1 H, O-CH2-CH=CH2),
5.50–5.44 (m, 1 H, CH2-CH=CH2a), 5.38–5.25 (m, 5 H, 1-H, 2-H,
3
3
7.12 (d, Jarom-H,H = 8.6 Hz, 1 H, CHarom), 5.58 (dd, J1,2 = 7.8,
3J2,3 = 10.3 Hz, 1 H, 2-H), 5.42–5.39 (m, 1 H, 4-H), 5.32 (d, J1,2
3
3
3
3-H, 4Ј-H, CH2-CH=CH2b), 5.10 (dd, J1Ј,2Ј = 8.2, J2Ј,3Ј
=
3
3
3
3
= 7.8 Hz, 1 H, 1-H), 5.13 (dd, J2,3 = 10.3, J3,4 = 3.3 Hz, 1 H, 3-
H), 4.08–3.98 (m, 2 H, 6a-H, 6b-H), 3.97 (s, 3 H, -OCH3), 3.86–
3.81 (m, 1 H, 5-H), 2.20, 2.11, 2.02, 1.89 [4 s, each 3 H, C(O)CH3]
ppm. 13C NMR (125 MHz, CDCl3): δ = 170.2, 170.2, 170.2, 169.5
[C(O)CH3], 161.0 [C(O)O-], 133.3, 126.7, 120.4, 118.4, 115.4
(Cquat), 130.5 (CHarom), 111.6 (CHarom), 101.8 (C-1), 71.0 (C-3),
70.7 (C-5), 69.4 (C-2), 66.9 (C-4), 60.7 (C-6), 52.0 (-OCH3), 20.9,
20.7, 20.6, 20.4 [C(O)CH3] ppm. HRMS (ESI): calcd. for
C24H25BrClNO12Na [M + Na]+ 658.0126; found 658.0121.
10.4 Hz, 1 H, 2Ј-H), 4.96 (dd, J2Ј,3Ј = 10.4, J3Ј4 = 3.5 Hz, 1 H,
3Ј-H), 4.86–4.83 (m, 2 H, CH2-CH=CH2), 4.51 (d, 3J1Ј,2Ј = 8.2 Hz,
3
3
1 H, 1Ј-H), 4.33 (dd, J5,6a = 2.2, J6a,6b = 12.0 Hz, 1 H, 6a-H),
4.17–4.07 (m, 2 H, 6Јa-H, 6Јb-H), 4.00 (dd, J5,6b = 4.7, J6a,6b
3
3
=
12.0 Hz, 1 H, 6b-H), 3.93 (dd~vt, 1 H, 4-H), 3.91–3.87 (m, 1 H,
3
3
3
5Ј-H), 3.53 (ddd, J4,5 = 9.8, J5,6a = 2.2, J5,6b = 4.7 Hz, 1 H, 5-
H), 2.15, 2.08, 2.07, 2.06, 1.99, 1.97, 1.95 [7 s, each 3 H, C(O)CH3]
1
ppm. H NMR (400 MHz, CDCl3): δ = 170.3, 170.1, 170.1, 169.8,
169.7, 169.0 [C(O)CH3], 159.9 [C(O)O-Allyl], 137.5, 133.3 (Cquat),
(Methyl 5-Bromoindox-3-ylate) 2,3,4,6-tetra-O-acetyl-β-D-galacto- 131.7 (CH2-CH=CH2), 130.5 (CHarom), 126.6, 120.4 (Cquat), 119.2
pyranoside (12d): Prepared according to general procedure 7. Com-
(CH2-CH=CH2), 118.0, 115.3 (Cquat), 111.7 (CHarom), 101.2 (C-1Ј),
Eur. J. Org. Chem. 2014, 564–574
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
571