Efficient synthesis of jusbetonin, an indolo[3,2-b]quinoline glycoside, and its derivatives

Article abstract of DOI:10.1016/j.carres.2008.11.015

Jusbetonin, an indolo[3,2-b]quinoline alkaloid glycoside originally isolated from Justicia betonica, and its derivatives were synthesized. The key steps in the synthetic strategy were the construction of indolo[3,2-b]quinoline skeleton and efficient coupl

Full text of DOI:10.1016/j.carres.2008.11.015

Carbohydrate Research 344 (2009) 291–297
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Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Efficient synthesis of jusbetonin, an indolo[3,2-b]quinoline glycoside,
and its derivatives
*
Zhongwei Zhang, Shixi Wang, Shengbiao Wan, Sumei Ren, Wei Li, Tao Jiang
Key Laboratory of Marine Drugs, Ministry of Education of China, School of Pharmacy, Ocean University of China, Qingdao 266003, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Jusbetonin, an indolo[3,2-b]quinoline alkaloid glycoside originally isolated from Justicia betonica, and its
Received 25 September 2008
Received in revised form 14 November 2008
Accepted 25 November 2008
Available online 6 December 2008
derivatives were synthesized. The key steps in the synthetic strategy were the construction of indolo[3,2-
b]quinoline skeleton and efficient coupling with the saccharides, in which the
a-D-glycopyranosyl bro-
mides were shown to be effective donors. Primary screening showed that all synthesized compounds
possessed moderate proliferation inhibitory activity.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Indoloquinoline alkaloid
Jusbetonin
PPA catalyzed cyclization
Glycosylation
Total synthesis
1. Introduction
interactions with DNA. The sugar structure in these compounds
plays a critical role in their anti-cancer activity.11 To improve the
Cryptolepis sanguinolenta, a plant with a rich content of indolo-
quinoline alkaloids, is traditionally used in Central and West Africa
for the treatment of rheumatism, urinary and respiratory infec-
tions. It is also used in folk medicine as an antimalarial agent.1 Cry-
ptolepine 1 (Fig. 1), the major indoloquinoline alkaloid isolated
from C. sanguinolenta, is well known for its anti-tumour, anti-bac-
terial, anti-thrombotic and anti-malarial activities.2–4 It was also
found that Cryptolepine can interact with DNA and Topoisomerase
II.5–7 In addition, some indoloquinoline alkaloid glycoside ana-
logues have shown high anti-tumour activities.8
bioavailability of indoloquinoline alkaloids and search for potential
anti-tumour compounds, we became interested in studying the
synthesis and bioactivity of indoloquinolines derivatives.12 We re-
port here the efficient synthesis of jusbetonin and its glycoside
analogues with different sugar moieties.
2. Results and discussion
Our retrosynthetic analysis of jusbetonin suggested that 9 would
be a promising intermediate for the total synthesis (Scheme 1).
Moreover, the efficient coupling of compound 9 with the saccharide
would be the key step in the synthesis.
Several synthetic methods have been developed to construct
the indoloquinoline skeleton.13–15 A facile strategy for the synthe-
sis of cryptolepine analogues is polyphosphorous-catalyzed cyclic
condensation.16 We have started our synthesis from commercially
available 2-aminobenzoic acid 3 and substituted anilines. Acyla-
Jusbetonin 2a, the first natural indolo[3,2-b]quinoline alkaloid
glycoside isolated from Justicia betonica,9 has a unique structure
containing b-D-glucose. However, to our best knowledge, jusbeto-
nin has not been synthesized. Because of the small quantity iso-
lated from plants, its bioactivities have not been studied
systematically.
Most indolo[3,2-b]quinoline alkaloids are difficult to be dis-
solved in organic solvent or water, which has led to considerable
difficulty in developing formulations for clinical use. However, sol-
ubility can be improved when they are glycosylated.10 On the other
hand, the sugar moiety of indoloquinoline derivatives can improve
their interaction with DNA. For example, some of the DNA interact-
ing agents, such as anthracycline antibiotics and bleomycins, are
well known to possess sugar moieties that stabilize the molecular
H3C
OH
N
N
HO
HO
O
N
H
N
O
HO
2a
1
* Corresponding author. Tel.: +86 0532 2032712; fax: +86 0532 2033054.
E-mail address: jiangtao@ouc.edu.cn (T. Jiang).
Figure 1. Structures of cryptolepine 1 and jusbetonin 2a.
0008-6215/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2008.11.015

292
Z. Zhang et al. / Carbohydrate Research 344 (2009) 291–297
OH
OAc
N
N
HO
HO
O
O
+
AcO
AcO
N
H
O
AcO
N
HO
HO
H
Br
9
2a
H
N
N
MeO
H
O
6
OMe
COOH
O
COOH
MeO
H2N
H
+
N
N
H
Cl
N
O
H
5
4
Scheme 1. Retrosynthetic analysis of jusbetonin.
tion of 3 with chloroacetyl chloride gave intermediate 4 in 86%
yield (Scheme 2). Condensation of 4 with 2-hydroxyaniline at
80 °C in DMF overnight afforded compound A in 49% yield. Subse-
quent cyclization of this anthranilic acid derivative catalyzed by
PPA failed to produce the 9-hydroxy analogue of compound 6. Pos-
sibly, the 9-hydroxy analogue of compound 6 was phosphorylated
in the presence of PPA. Therefore, a methyl ether was chosen as the
protecting group of the hydroxyl group and condensation of 4 with
2-methoxybenzenamine afforded the desired compound 5 in 79%
yield. It has been reported that cyclization of anthranilic acid deriv-
ative can be catalyzed by polyphosphorous acid (PPA) at a fixed
temperature in the range of 100–150 °C. However, this method
was not satisfactory to prepare cyclized product 6 due to the low
yield (9%) at 130 °C. Keeping in mind the mechanism of the cycli-
zation, the temperature was gradually elevated from 100 to
130 °C and the key intermediate 6 was obtained in 49% yield
(Scheme 2).
6 was chlorinated with phosphorous oxychloride (POCl3), and the
resulting chloride was dechlorinated with hydrogen over a palla-
dium catalyst in the presence of triethylamine to obtain product
8. The compound 9 was prepared from 8 through a demethylation
reaction in the presence of boron tribromide.
To synthesize the target product jusbetonin, efficient and ste-
reospecific coupling of compound 9 with the glucosyl donor is
required. 2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl bromide is
commonly used as a b-selective donor.17,18 To find appropriate
reaction conditions, including the proper promoter and solvent,
we first explored the glycosylation of 9 with 2,3,4,6-tetra-O-acet-
yl-a-D-glucopyranosyl bromide (Table 1). The phase transfer
catalysis method was used to ensure the efficient coupling of 9
with the glycosylating agent. Under the optimal conditions, com-
pound 10a was synthesized in 68% yield (Scheme 4). After de-
acetylation with sodium methoxide, jusbetonin 2a was obtained
in 93% yield.
The desired 9-hydroxy-10H-indolo[3,2-b]quinoline 9 was syn-
thesized according to the route depicted in Scheme 3. Compound
Using this method, the jusbetonin analogues, 2b–c and 13a–c,
were also prepared (Fig. 2). Compound 9 reacted with different su-
HO
d
COOH
H
9
N
N
H
b
c
O
A
COOH
O
COOH
NH2
a
Cl
N
H
3
4
MeO
COOH
H
N
d
6
N
H
O
5
Scheme 2. Reagents and conditions: (a) ClCH2COCl, DMF, ice bath, overnight, 86%; (b) 2-hydroxyaniline, DMF, 80 °C, overnight, 49%; (c) 2-methoxybenzenamine, DMF, 80 °C,
overnight, 79%; (d) PPA, 100–130 °C, 49%.

Z. Zhang et al. / Carbohydrate Research 344 (2009) 291–297
293
N
N
a
b
c
9
6
N
H
N
H
MeO
MeO
Cl
8
7
Scheme 3. Reagents and conditions: (a) POCl3, reflux, 4 h, 83%; (b) H2, Pd–C, Et3N, CH3OH, 92%; (c) BBr3, CH2Cl2, 92%.
Table 1
Glycosylation of glucosyl donor glucopyranosyl bromide with 9
Entry
Donor
Promotor
Solvent
Product
Yield (%)
1
2
3
Glucopyranosyl bromide (1 equiv)
Glucopyranosyl bromide (1 equiv)
Glucopyranosyl bromide (5 equiv)
Glucopyranosyl bromide (10 equiv)
Glucopyranosyl bromide (1.5 equiv)
Ag2O (3 equiv)
LiOH (1 equiv)
LiOH (1 equiv)
LiOH (1 equiv)
K2CO3 (3 equiv)/TBAB
THF
DMF
DMF
DMF
—
—
10a
10a
10a
10a
<10
15.8
22.6
68.3
4
5a
H2O/CHCl3
a
Phase transfer catalysis method.
OAc
N
N
a
b
AcO
AcO
2a
O
N
H
N
H
HO
AcO
O
10a
9
Scheme 4. Reagents and conditions: (a) 2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl bromide, K2CO3, H2O, CHCl3, TBAB, 40 °C, 6 h, 68%; (b) CH3ONa, CH3OH, 0 °C, 1 h, 93%.
R2OH
R1
HO
OH
R2
N
N
R1
O
O
HO
N
H
N
H
HO
O
HO
13a
O
Cl
2b
2c
R1=H, R2=OH
HO
,
R1=OH R2=H
OH
O
13b R1=H, R2=OH
R2=H, R1=HO
O
OH
HO
OH
O
13c R2=H, R1=
HO
O
OH
Figure 2. Structures of compounds 2b–c and 13a–c.
OAc
R2
N
N
N
a
b
c
R1
13a-c
O
AcO
N
H
N
H
N
H
AcO
O
MeO
HO
Cl
Cl
Cl
11
12a R1=OAc, R2=H
7
12b
12c
R1=H, R2=OAc
OAc
AcO
O
R2=H, R1=
AcO
O
OAc
Scheme 5. Reagents and conditions: (a) BBr3, CH2Cl2, 86%; (b) glycopyranosyl bromides, K2CO3, H2O, CHCl3, TBAB, 40 °C, 6 h, 63% (12a), 60% (12b), 57% (12c); (c) CH3ONa,
CH3OH, 0 °C, 1 h, 91% (13a), 91% (13b), 89% (13c).
gar donors, 2,3,4,6-tetra-O-acetyl- -galactopyranosyl bromide
a
-
D
The compounds, 13a–c, were obtained from intermediate 7
(Scheme 5). After demethylation in the presence of boron tribro-
mide, the desired compound 11 was obtained. The corresponding
glycoside products, 12a–c, were synthesized through phase trans-
and 2,3,4,20,30,40,60-hepta-O-acetyl-
a-D-lactopyranosyl bromide, to
give the corresponding glycoside products. After deacetylation
with sodium methoxide, the target compounds, 2b–c, were ob-
tained successfully.
fer catalysis, in which the a-D-glycopyranosyl bromides were used

294
Z. Zhang et al. / Carbohydrate Research 344 (2009) 291–297
as donors. After deacetylation with sodium methoxide, jusbetonin
analogues 13a–c were synthesized successfully. The acetylated
indolo[3,2-b]quinoline glycoside derivatives, 10a–c and 12a–c,
have better solubility in common solvents such as methanol, chlo-
roform and THF. Once deacetylated, they are more soluble in water
compared to the parent indolo[3,2-b]quinoline compounds, 7, 8
and 9.
The proliferation inhibition activities of these compounds
against the MDA-231 breast cancer cell line at a concentration of
1 lM were measured using a 3-(4,5-dimethylthioazol-2-yl)-2,5-
diphenyltetrazolium bromide (MTT) cell viability assay. The data
showed that all prepared compounds possessed moderate prolifer-
ation inhibitory activity, and compound 2c was the most potent
(Table 2).
In conclusion, we have developed an efficient and stereoselec-
tive method for the total synthesis of jusbetonin and its analogues.
The gradient temperature-elevating method in the construction of
indolo[3,2-b]quinoline skeleton 6 is critical. The prepared com-
pounds had moderate proliferation inhibitory activity against the
and basified to pH 9 with sodium hydroxide aqueous solution.
After being washed with chloroform (3 ꢀ 30 mL), the water layer
was acidified to pH 4 with an aq acetic acid soln (30%, v/v) and fil-
tered. The solid was washed with water (3 ꢀ 30 mL) to afford acid
5 (3.57 g, 79%); Rf = 0.60 (CHCl3–CH3OH 3:1); mp 182–184 °C; IR
(KBr) 3403, 3325, 1683, 1582, 1522, 1413, 1270, 761, 726 cmꢁ1
;
UV (DMSO) 297, 257 nm; 1H NMR (DMSO-d6, 600 MHz): d 13.45
(br s, 1H, COOH), 11.90 (s, 1H, N–H), 8.71 (dd, 1H, J = 8.6, 1.1 Hz,
Ar-H), 7.93 (dd, 1H, J = 7.8, 1.6 Hz, Ar-H), 7.59 (td, 1H, J = 7.8,
1.6 Hz, Ar-H), 7.13 (td, 1H, J = 7.6, 1.1 Hz, Ar-H), 6.86 (dd, 1H,
J = 8.6, 1.1 Hz, Ar-H), 6.74 (td, 1H, J = 7.6, 1.1 Hz, Ar-H), 6.61 (td,
1H, J = 7.6, 1.6 Hz, Ar-H), 6.36 (dd, 1H, J = 7.8, 1.3 Hz, Ar-H), 5.83
(t, 1H, J = 5.7 Hz, N–H), 3.86 (d, 2H, J = 6.0 Hz, CH2), 3.83 (s, 3H,
O–CH3); 13C NMR (DMSO-d6, 150 MHz): d 170.8, 168.9, 146.8,
140.5, 137.7, 134.1, 131.1, 122.6, 121.1, 119.5, 116.9, 116.1,
110.2, 109.5, 55.5, 49.1. ESIMS m/z: ES+ 301.1 [M+H]+; HRESIMS:
þ
calcd for C16H17N2 O4 301.1188; found 301.1192.
3.3. 9-methoxy-5H-indolo[3,2-b]quinolin-11(10H)-one (6)
MDA-231 breast cancer cell line at a concentration of 1
lM. Com-
pound 2c, 9-(b- -lactosyl)-10H-indolo[3,2-b]quinoline, showed the
most potent inhibitory activity.
D
PPA (10 g) was added to 5 (300 mg, 1 mmol) and the syrup was
stirred at 100 °C for 0.5 h, then 110 °C for 0.5 h, 120 °C for 0.5 h,
130 °C for 0.5 h. The mixture was poured into ice water (100 mL).
The resulting precipitate was collected, washed with water and
air-dried to provide the crude product. Purification by column
chromatography afforded 6 as a light yellow solid (130 mg, 49%);
Rf = 0.45 (EtOAc); mp >300 °C; IR (KBr) 3224, 2995, 1639, 1582,
1493, 1260, 755 cmꢁ1; UV (DMSO) 395, 305, 270 nm; 1H NMR
(DMSO-d6, 600 MHz): d 12.33 (s, 1H, N–H), 11.63 (s, 1H, N–H),
8.35 (d, 1H, J = 7.8 Hz, Ar-H), 7.75 (d, 1H, J = 8.3 Hz, Ar-H), 7.66–
7.72 (m, 2H, Ar-H), 7.27 (t, 1H, J = 7.3 Hz, Ar-H), 7.13 (t, 1H,
J = 7.8 Hz, Ar-H), 7.01 (d, 1H, J = 7.7 Hz, Ar-H), 3.95 (s, 3H, O–
CH3); 13C NMR (DMSO-d6, 150 MHz): d 167.3, 146.7, 139.0, 130.6,
129.4, 129.3, 125.2, 122.9, 120.3, 119.5, 117.5, 117.1, 112.6,
3. Experimental
3.1. General methods
Solvents were purified in a conventional manner. Thin layer
chromatography (TLC) was performed on precoated E. Merck Silica
Gel 60 F254 plates. Flash column chromatography was performed
on silica gel (200–300 mesh, Qingdao, China). Melting points were
determined on a Mitamura–Riken micro hot stage without correc-
tion. Optical rotations were determined with a Perkin–Elmer Mod-
el 241 MC polarimeter. IR spectra were recorded by KBr pellets for
solid samples on a Nicolet Nexus 470 FTIR spectrophotometer. UV–
vis (UV–vis) spectra were obtained on Varian Cary-300 spectrom-
eter. 1H NMR and 13C NMR spectra were obtained on a Jeol JNM-
ECP 600 spectrometer with tetramethylsilane (Me4Si) as the inter-
nal standard, and chemical shifts are recorded in d values. Mass
spectra were recorded on a Q-TOF Global mass spectrometer. The
primary screening for proliferation inhibition activities of com-
pounds was tested in vitro against the human breast cancer cell
line (MDA-231) using an MTT cell viability assay.
þ
107.2, 55.5. HRESIMS: calcd for C16H13N2 O2 265.0977; found
265.0921.
3.4. 11-chloro-9-methoxy-10H-indolo[3,2-b]quinoline (7)
Phosphorous oxychloride (20 mL) was added to 6 (530 mg,
2 mmol) and the mixture was stirred under reflux for 4 h. The ex-
cess POCl3 was removed under reduced pressure and water
(20 mL) was added. The solution was adjusted to pH 7 with an
aq sodium hydroxide soln (20%) and extracted with CH2Cl2
(3 ꢀ 100 mL). The organic phase was washed with brine
(3 ꢀ 50 mL) and dried over MgSO4. After filtration and evaporation
of the solvent, a yellow solid was obtained. Purification by column
chromatography afforded 7 as a light yellow solid (470 mg, 83%);
Rf = 0.3 (EtOAc–n-hexane 1:3); mp 190–192 °C; IR (KBr) 3413,
3206, 1591, 1440, 1392, 1245, 735 cmꢁ1; UV (DMSO) 400, 343,
276 nm; 1H NMR (DMSO-d6, 600 MHz): d 11.86 (s, 1H, N–H);
8.31 (dd, 1H, J = 7.8, 0.9 Hz, Ar-H), 8.27 (dd, 1H, J = 8.28, 0.96 Hz,
Ar-H), 7.9 (m, 2H, Ar-H), 7.7 (m, 2H, Ar-H), 4.05 (s, 3H, O–CH3);
13C NMR (DMSO-d6, 150 MHz): d 146.2, 146.1, 143.9, 134.2,
130.2, 129.2, 129.1, 127.0, 126.9, 126.3, 123.7, 122.3, 121.0,
113.6, 111.1, 55.7. ESIMS m/z: ES+ 283.1 [M+H]+. HRESIMS: calcd
for C16H12N2OCl+ 283.0638; found 283.0625.
3.2. 2-(N-(2-methoxyphenylamino)acetamido)benzoic acid (5)
To a solution of 4 (3.20 g, 15 mmol) in DMF (10 mL) was added
dropwise 2-methoxybenzenamine (6 mL, 50 mmol) at rt. The reac-
tion mixture was stirred at 80 °C for 10 h under nitrogen atmo-
sphere. Then the mixture was poured into ice water (100 mL),
Table 2
Proliferation inhibition activities of compounds (1
l
m) against tumour cell MDA-231
Proliferation inhibition (%)
Compound (1 lm)
6
7
8
9
11
10a
10c
2c
12a
13a
12c
13c
30.3
26.8
27.1
25.8
25.8
28.4
26.9
37.9
28.8
30.6
21.1
27.1
3.5. 9-methoxy-10H-indolo[3,2-b]quinoline (8)
Pd/C (10%) was added to a solution of 7 (560 mg, 2 mmol) and
triethylamine (0.28 mL, 2 mmol) in CH3OH (30 mL) and the reac-
tion mixture was stirred under hydrogen at rt for 10 h. The mixture
was filtered through diatomite and was concentrated to give a yel-
low solid. Purification of this solid by column chromatography
afforded 8 as a yellow solid (460 mg, 92%); Rf = 0.25 (EtOAc–n-hex-

Z. Zhang et al. / Carbohydrate Research 344 (2009) 291–297
295
ane 1:3); mp 170–172 °C; IR (KBr) 3423, 2926, 1586, 1507, 1396,
yellow powder; Rf = 0.4 (EtOAc–CH3OH, 2:1); mp >300 °C; ½a D26
ꢂ
1260, 738 cmꢁ1; UV (DMSO) 390, 342, 276 nm; 1H NMR (CDCl3,
600 MHz): d 8.33 (d, 1H, J = 9.7 Hz, H-4), 8.27 (s, 1H, N–H), 8.13
(d, 1H, J = 7.8 Hz, H-1), 8.07 (s, 1H, H-11), 7.93 (d, 1H, J = 7.8 Hz,
H-6), 7.65 (m, 1H, H-3), 7.52 (m, 1H, H-2), 7.26 (t, 1H, J = 7.8 Hz,
H-7), 7.08 (d, 1H, J = 7.8 Hz, H-8), 4.04 (s, 3H, O–CH3); 13C NMR
(CDCl3, 150 MHz): d 146.7, 145.6, 144.4, 133.9, 132.1, 129.2,
127.2, 126.9, 126.6, 125.2, 122.9, 120.6, 114.3, 113.6, 109.7, 55.6.
ESIMS m/z ES+ 249.1 [M+H]+; HRESIMS: calcd for C16H13N2O+
249.1028; found 249.1039.
ꢁ46.5 (c 0.1, CH3OH); IR (KBr) 3562, 3224, 1502, 1399, 1062,
778, 739 cmꢁ1; UV (DMSO) 387, 342, 277 nm; 1H NMR (DMSO-
d6, 600 MHz): d 11.22 (s, 1H, N–H), 8.30 (s, 1H, H-11), 8.18 (d,
1H, J = 8.3 Hz, H-4), 8.11 (d, 1H, J = 7.3 Hz, H-1), 8.02 (d, 1H,
J = 7.8 Hz, H-6), 7.64 (m, 1H, H-3), 7.56 (m, 1H, H-2), 7.43 (d,
1H, J = 7.7 Hz, H-8), 7.20 (t, 1H, J = 7.8 Hz, H-7), 5.42 (br s, 1H,
–OH), 5.20 (br s, 1H, –OH), 5.14 (br s, 1H, –OH), 5.00 (d, 1H,
J = 7.8 Hz, H-10), 4.85 (br s, 1H, –OH), 3.81–3.78 (m, 1H, H-60a),
3.53 (m, 1H, H-60b), 3.47–3.34 (m, 3H, H-20, H-30, H-50), 3.26–
3.23 (m, 1H, H-40); 13C NMR (DMSO-d6, 150 MHz): d 145.8 (C-
5a), 143.7 (C-9), 143.5 (C-4a), 134.8 (C-9a), 132.4 (C-10a),
128.7 (C-4), 127.5 (C-1), 126.7 (C-11a), 126.2 (C-3), 124.9 (C-2),
122.6 (C-5b), 119.8 (C-7), 115.7 (C-8), 115.3 (C-6), 113.6 (C-
11), 102.5 (C-10), 77.3 (C-50), 76.2 (C-30), 73.6 (C-20), 70.0 (C-40),
60.9 (C-60). ESIMS m/z ES+ 397.1 [M+H]+; HRESIMS: calcd for
3.6. 9-hydroxy-10H-indolo[3,2-b]quinoline (9)
Boron tribromide (0.3 mL, 3 mmol) was added to a solution of 8
(250 mg, 1 mmol) in absolute CH2Cl2 (20 mL) at 0 °C under a nitro-
gen atmosphere. After stirring for 4 h, ice water (20 mL) was added
dropwise. The mixture was adjusted to pH 7 with aq sodium
hydroxide soln (20%). The resulting precipitate was collected,
washed with water and dried to obtain compound 9 (210 mg,
92%) as a yellow solid; Rf = 0.35 (EtOAc–n-hexane 1:1); mp 195–
198 °C; IR (KBr) 3430, 3209, 3055, 1588, 1504, 1398, 1268, 775,
þ
C21H21N2O6 397.1400; found 397.1404.
3.9. 9-(20,30,40,60-tetra-O-acetyl-b-
indolo[3,2-b] quinoline (10b)
D-galactopyranosyl)-10H-
738 cmꢁ1
;
UV (DMSO) 397, 344, 278 nm; 1H NMR (CD3OD,
This compound was prepared from 9 (230 mg, 1 mmol) and
2,3,4,6-tetra-O-acetyl- -galactopyranosyl bromide (615 mg,
600 MHz): d 8.25 (s, 1H, H-11), 8.18 (d, 1H, J = 8.7 Hz, H-4), 8.01
(dd, 1H, J = 8.2, 1.4 Hz, H-1), 7.96 (dd, 1H, J = 7.8, 0.9 Hz, H-6),
7.64 (m, 1H, H-3), 7.52 (m, 1H, H-2), 7.10 (t, 1H, J = 7.8 Hz, H-7),
7.03 (dd, 1H, J = 7.8, 0.9 Hz, H-8); 13C NMR (CD3OD, 150 MHz): d
147.5, 144.8, 144.5, 135.8, 134.4, 128.6, 128.5, 128.4, 127.7,
126.1, 123.2, 121.4, 115.6, 115.3, 113.9. ESIMS m/z ES+ 235.1
[M+H]+; HRESIMS: calcd for C15H11N2O+ 235.0871; found
235.0867.
a-D
1.5 mmol) using the same procedure as described for 10a. Purifica-
tion of the residue resulted in 10b (398 mg, 71%) as a yellow pow-
der; Rf = 0.4 (EtOAc–n-hexane 2:1); mp 106–108 °C; IR (KBr) 3209,
1755, 1501, 1435, 1229, 1039, 780, 743 cmꢁ1; UV (DMSO) 386,
341, 276 nm; 1H NMR (CDCl3, 600 MHz): d 8.45 (s, 1H, N–H),
8.32 (d, 1H, J = 8.3 Hz, H-4), 8.28 (d, 1H, J = 7.8 Hz, H-1), 8.15 (s,
1H, H-11), 7.95 (d, 1H, J = 8.2 Hz, H-6), 7.66 (m, 1H, H-3), 7.55
(m, 1H, H-2), 7.25 (m, 1H, H-7), 7.20 (dd, 1H, J = 7.7, 0.9 Hz, H-8),
5.60 (dd, 1H, J = 7.8, 10.05 Hz, H-40), 5.52 (d, 1H, J = 8.8 Hz, H-10),
5.17 (m, 2H, H-30, H-20), 4.33 (dd, 1H, J = 7.3, 11.9 Hz, H-60a), 4.21
(dd, 1H, J = 5.5, 11.5 Hz, H-60b), 4.11 (m, 1H, H-50), 2.24–1.97 (4s,
12H, Ac-H); 13C NMR (CDCl3, 150 MHz): d 170.4, 170.2, 170.1,
170.0, 146.1, 144.2, 142.3, 135.0, 132.3, 128.9, 127.2, 126.9,
126.7, 125.3, 123.7, 120.2, 117.5, 115.6, 114.1, 101.1, 71.4, 70.5,
68.9, 66.9, 61.4, 20.9, 20.6, 20.5. ESIMS m/z ES+ 565.1 [M+H]+; HRE-
3.7. 9-(20,30,40,60-tetra-O-acetyl-b-
indolo[3,2-b]quinoline (10a)
D-glucopyranosyl)-10H-
To a solution of water (5 mL) and chloroform (5 mL) was added
tetrabutylammonium bromide (320 mg, 1 mmol). After heating to
40 °C, a mixture of 9 (230 mg, 1 mmol) and K2CO3 (414 mg,
3 mmol) in water (20 mL) was added. Then, a solution of 2,3,4,6-
þ
tetra-O-acetyl-
a-
D-glucopyranosyl bromide (615 mg, 1.5 mmol)
SIMS: calcd for C29H29N2O10 565.1822; found 565.1812.
in chloroform (20 mL) was added dropwise. After stirring for 6 h,
the organic layer was separated and washed successively with
water, aq NaHCO3 soln and water, dried over Na2SO4 and concen-
trated under reduced pressure. Purification of the crude reaction
product by column chromatography afforded compound 10a
(385 mg, 68%) as a yellow powder; Rf = 0.3 (EtOAc–n-hexane
1:1); mp 101–104 °C. IR (KBr) 3206, 1756, 1501, 1436, 1228,
1039, 780, 743 cmꢁ1; UV (DMSO) 385, 341, 276 nm; 1H NMR
(CDCl3, 600 MHz): d 8.72 (s, 1H, N–H), 8.31 (m, 2H, H-1, H-4),
8.21 (s, 1H, H-11), 7.96 (d, 1H, J = 7.8 Hz, H-6), 7.66 (m, 1H, H-3),
7.54 (m, 1H, H-2), 7.23 (t, 1H, J = 7.8 Hz, H-7), 7.18 (dd, 1H,
J = 7.8, 0.9 Hz, H-8), 5.39 (dd, 1H, J = 7.6, 9.6 Hz, H-20), 5.33 (dd,
1H, J = 9.2, 9.6 Hz, H-40), 5.24 (t, 1H, J = 9.6 Hz, H-30), 5.13 (d, 1H,
J = 7.8 Hz, H-10), 4.48 (dd, 1H, J = 1.9, 12.4 Hz, H-60a), 4.18 (dd,
1H, J = 4.6, 12.4 Hz, H-60b), 3.84 (m, 1H, H-5’), 2.16–2.08 (4s, 12H,
Ac-H); 13C NMR (CDCl3, 150 MHz): d 171.0, 170.2, 169.8, 169.4,
146.2, 144.5, 142.3, 135.8, 132.6, 129.3, 127.3, 127.2, 126.7,
125.4, 124.3, 120.2, 118.2, 117.5, 114.2, 101.7, 72.5, 72.4, 71.3,
68.1, 61.3, 20.9, 20.8, 20.6. ESIMS m/z ES+ 565.2 [M+H]+; HRESIMS:
3.10. 9-(b-D-galatopyranosyl)-10H-indolo[3,2-b]quinoline (2b)
This compound was prepared from 10b (140 mg, 0.25 mmol)
using the same procedure as described for 2a. Purification of the
precipitate resulted in 2b (88 mg, 89%) as a yellow powder;
Rf = 0.4 (EtOAc–CH3OH 2:1); mp >300 °C;
½
a 2D6
–61.1 (c 0.1,
ꢂ
CH3OH); IR (KBr) 3555, 3350, 3213, 1500, 1427, 1076, 777,
738 cmꢁ1; UV (DMSO) 385, 342, 276 nm; 1H NMR (DMSO-d6,
600 MHz): d 11.22 (s, 1H, N–H), 8.31 (s, 1H, H-11), 8.18 (d, 1H,
J = 8.7 Hz, H-4), 8.11 (d, 1H, J = 8.2 Hz, H-1), 8.02 (d, 1H,
J = 7.8 Hz, H-6), 7.64 (m, 1H, H-3), 7.56 (m, 1H, H-2), 7.44 (d, 1H,
J = 7.8 Hz, H-8), 7.20 (t, 1H, J = 7.8 Hz, H-7), 5.25 (d, 1H, J = 4.6 Hz,
–OH), 4.98 (d, 1H, J = 5.5 Hz, –OH), 4.95 (d, 1H, J = 7.8 Hz, H-10),
4.88 (t, 1H, J = 5.5 Hz, –OH), 4.64 (d, 1H, J = 4.6 Hz, –OH), 3.78 (m,
1H, H-40), 3.74 (m, 1H, H-60a), 3.68 (m, 1H, H-60b), 3.70–3.67 (m,
2H, H-20, H-30), 3.48(m, 1H, H-50); 13C NMR (DMSO-d6, 150 MHz):
d 145.8, 143.9, 143.5, 134.8, 132.4, 128.7, 127.5, 126.7, 126.2,
124.9, 122.6, 119.8, 115.7, 115.3, 113.6, 103.2, 75.9, 72.9, 70.6,
þ
þ
calcd for C29H29N2O10 565.1822; found 565.1816.
68.2, 60.6. HRESIMS: calcd for C21H21N2O6 397.1400; found
397.1385.
3.8. 9-(b-D-glucopyranosyl)-10H-indolo[3,2-b]quinoline (2a)
3.11. 9-(2,3,6,20,30,40,60-hepta-O-acetyl-b-
indolo[3,2-b]quinoline (10c)
D-lactosyl)-10H-
To a solution of 10a (140 mg, 0.25 mmol) in CH3OH–CH3Cl
(1:1) was added CH3ONa in CH3OH (0.63 M, 1 mL) at 0 °C. After
stirring at rt for 1 h, the resulting precipitate was collected and
washed with CH3OH to obtain compound 2a (92 mg, 93%) as a
This compound was prepared from 9 (230 mg, 1 mmol) and
2,3,6,20,30,40,60-hepta-O-acetyl-
-lactosyl bromide (1.04 g,
a-D

296
Z. Zhang et al. / Carbohydrate Research 344 (2009) 291–297
1.5 mmol) using the same procedure as described for 10a. Purifica-
tion of the residue resulted in 10c (538 mg, 63%) as a yellow pow-
der; Rf = 0.2 (EtOAc–n-hexane 1:1); mp 98–102 °C; IR (KBr) 3209,
1752, 1434, 1228, 1054 cmꢁ1; UV (DMSO) 385, 341, 277 nm; 1H
(414 mg, 3 mmol) in water (20 mL) was added. Then the solution
of glucose donor 2,3,4,6-tetra-O-acetyl- -glucopyranosyl bro-
a-D
mide (615 mg, 1.5 mmol) in chloroform (20 mL) was added drop-
wise. After 6 h of stirring, the organic layer was separated and
washed successively with water, aq NaHCO3 soln and water,
dried over Na2SO4 and concentrated under reduced pressure.
Purification of the crude reaction product by column chromatog-
raphy afforded compound 12a (374 mg, 63%) as a yellow pow-
der; Rf = 0.35 (EtOAc–n-hexane 1:1); mp 200–202 °C; IR (KBr)
3404, 3224, 1748, 1499, 1390, 1228, 1073 cmꢁ1; UV (DMSO)
397, 342, 277 nm; 1H NMR (CDCl3, 600 MHz): d 8.59 (s, 1H, N–
H), 8.31 (m, 2H, H-1, H-4), 8.26 (d, 1H, J = 6.9 Hz, H-6), 7.72
(m, 1H, H-3), 7.66 (m, 1H, H-2), 7.27 (m, 1H, H-7), 7.26 (d, 1H,
J = 8.2 Hz, H-8), 5.42 (dd, 1H, J = 6.9 Hz, H-20), 5.36 (dd, 1H,
J = 9.2, 9.6 Hz, H-40), 5.24 (dd, 1H, J = 9.6 Hz, H-30), 5.18 (d, 1H,
J = 7.8 Hz, H-10), 4.35 (dd, 1H, J = 5.5, 12.4 Hz, H-60a), 4.23 (dd,
1H, J = 2.3, 12.4 Hz, H-60b), 3.90 (m, 1H, H-50), 2.16–2.03 (4s,
12H, Ac-H); 13C NMR (CDCl3, 150 MHz): d 170.5, 170.2, 169.9,
169.4, 142.5, 135.1, 130.1, 129.5, 127.4, 126.5, 124.4, 122.6,
121.2, 118.2, 117.4, 101.5, 72.3, 71.5, 68.1, 61.8, 20.9, 20.6,
20.5. ESIMS m/z ES+ 599.5 [M+H]+; HRESIMS: calcd for
C29H28N2O10Cl+ 599.1432; found 599.1444.
NMR (CDCl3, 600 MHz):
d 8.93 (s, 1H, N–H), 8.34 (d, 1H,
J = 7.8 Hz, H-4), 8.32 (d, 1H, J = 8.2 Hz, H-1), 8.28 (s, 1H, H-11),
7.97 (d, 1H, J = 8.3 Hz, H-6), 7.66 (m, 1H, H-3), 7.53 (m, 1H, H-2),
7.22 (t, 1H, J = 7.8 Hz, H-7), 7.16 (dd, 1H, J = 7.8, 0.9 Hz, H-8), 5.38
(d, 1H, J = 3.2 Hz, H-400), 5.34–5.29 (m, 2H, H-20, H-30), 5.11 (m,
2H, H-200, H-300), 5.02 (d, 1H, J = 7.8 Hz, H-10), 4.91 (dd, 1H, J = 1.8,
12.4 Hz, H-60a), 4.62 (d, 1H, J = 8.3 Hz, H-100), 4.17 (dd, 1H, J = 6.0,
11.4 Hz, H-60b), 4.09 (m, 2H, H-600a, H-600b), 3.93 (m, 2H, H-500, H-
40), 3.68 (m, 1H, H-50), 2.20–1.98 (7s, 21H, Ac-H); 13C NMR (CDCl3,
150 MHz): d 171.0, 170.4, 170.1, 170.0, 169.7, 168.9, 146.2, 144.4,
142.3, 136.3, 132.7, 129.2, 127.4, 127.2, 126.6, 125.3, 124.3,
120.1, 119.0, 118.7, 114.4, 102.3, 101.0, 75.5, 73.5, 72.5, 71.5,
70.8, 70.7, 69.2, 66.6, 60.7, 21.1, 20.9, 20.8, 20.6, 20.5. ESIMS m/z
ES+ 853.2 [M+H]+; HRESIMS: calcd for C41H45N2O18 853.2667;
þ
found 853.2695.
3.12. 9-(b-D-lactosyl)-10H-indolo[3,2-b]quinoline (2c)
This compound was prepared from 10c (213 mg, 0.25 mmol)
using the same procedure as described for 2a. Purification of the
precipitate resulted in 2c (130 mg, 94%) as a yellow powder;
3.15. 9-(b-D-glucopyranosyl)-11-chloro-10H-indolo[3,2-
b]quinoline (13a)
Rf = 0.3 (EtOAc–CH3OH 1:1); mp >300 °C; ½a D26
ꢁ65.6 (c 0.04,
ꢂ
CH3OH). IR (KBr) 3555, 3350, 1500, 1430, 1400, 1064, 777,
738 cmꢁ1; UV (DMSO) 385, 342, 276 nm; 1H NMR (DMSO-d6,
600 MHz): d 11.23 (s, 1H, N–H), 8.32 (s, 1H, H-11), 8.19 (d, 1H,
J = 8.7 Hz, H-4), 8.11 (d, 1H, J = 8.2 Hz, H-1), 8.03 (d, 1H,
J = 7.8 Hz, H-6), 7.65 (m, 1H, H-3), 7.56 (m, 1H, H-2), 7.44 (d, 1H,
J = 8.3 Hz, H-8), 7.22 (t, 1H, J = 7.8 Hz, H-7), 5.53 (d, 1H, J = 4.1 Hz,
–OH), 5.16 (d, 1H, J = 4.6 Hz, –OH), 5.14 (d, 1H, J = 7.3 Hz, H-10),
4.89 (s, 1H, –OH), 4.84 (m, 2 H, –OH), 4.72 (t, 1H, J = 5.0 Hz, –
OH), 4.57 (d, 1H, J = 4.6 Hz, –OH), 4.28 (d, 1H, J = 7.3 Hz, H-100),
3.88–3.33 (m, 11H, Lac-H); 13C NMR (DMSO-d6, 150 MHz): d
145.7, 143.5, 134.7, 132.4, 128.7, 127.5, 126.7, 126.2, 124.9,
122.6, 119.8, 115.5, 115.4, 113.6, 103.8, 101.7, 99.4, 80.4, 75.6,
75.2, 74.5, 73.3, 73.2, 70.5, 68.2, 60.5, 60.3. ESIMS m/z ES+ 559.2
To a solution of 12a (149 mg, 0.25 mmol) in CH3OH–CH3Cl (1:1)
was added CH3ONa in CH3OH (0.63 M, 1 mL) at 0 °C. After stirring
at rt for 1 h, the resulting precipitate was collected and washed
with CH3OH to obtain compound 13a (97.3 mg, 91%) as a yellow
powder; Rf = 0.45 (EtOAc–CH3OH 2:1); mp >300 °C; ½a D26
ꢁ70.3 (c
ꢂ
0.03, CH3OH); IR (KBr) 3224, 1493, 1427, 1082, 738 cmꢁ1; UV
(DMSO) 397, 343, 278 nm; 1H NMR (DMSO-d6, 600 MHz): d 11.41
(s, 1H, N–H), 8.32 (m, 1H, H-1), 8.28 (m, 1H, H-4), 8.02 (d, 1H,
J = 7.8 Hz, H-6), 7.75 (m, 2H, H-3, H-2), 7.52 (d, 1H, J = 7.3 Hz, H-
8), 7.27 (t, 1H, J = 7.8 Hz, H-7), 5.62 (d, 1H, J = 3.6 Hz, –OH), 5.19
(d, 1H, J = 4.6 Hz, –OH), 5.14 (d, 1H, J = 5.4 Hz, –OH), 4.94 (d, 1H,
J = 7.8 Hz, H-10), 4.72 (t, 1H, J = 5.9 Hz, –OH), 3.80 (m, 1H, H-60a),
3.53 (m, 1H, H-60b), 3.51–3.32 (m, 3H, H-20, H-30, H-50), 3.26–3.23
(m, 1H, H-40); 13C NMR (DMSO-d6, 150 MHz): d 146.2, 144.2,
144.0, 134.6, 130.1, 129.3, 127.1, 126.5, 123.6, 122.7, 122.2,
121.1, 118.6, 115.9, 115.4, 102.9, 77.4, 75.5, 73.5, 69.9, 60.8. ESIMS
[M+H]+; HRESIMS: calcd for C27H31N2O11 559.1928; found
þ
559.1909.
m/z ES+ 430.9 [M+H]+; HRESIMS: calcd for C21H20ClN2O6
þ
3.13. 9-hydroxy-11-chloro-10H-indolo[3,2-b]quinoline (11)
431.1010; found 431.1008.
To a solution of 7 (560 mg, 2 mmol) in absolute CH2Cl2 (30 mL)
was added BBr3 (0.57 mL, 6 mmol) at 0 °C under nitrogen atmo-
sphere. After 4 h of stirring, ice water (30 ml) was added dropwise.
The mixture was adjusted to pH 7 with aq sodium hydroxide soln
(20%). The resulting precipitate was collected, washed with water
and dried to provide 11 (458 mg, 86%) as a yellow solid; Rf = 0.4
(EtOAc–n-hexane 1:1); mp 248–252 °C; IR (KBr) 3209, 1420,
1398, 733 cmꢁ1; UV (DMSO) 406, 345, 279 nm; 1H NMR (CD3OD,
600 MHz): d 8.34 (dd, 1H, J = 8.2, 0.9 Hz, H-1), 8.21 (d, 1H,
J = 8.7 Hz, H-4), 7.93 (dd, 1H, J = 7.8, 0.9 Hz, H-6), 7.73 (m, 1H, H-
3), 7.66 (m, 1H, H-2), 7.15 (t, 1H, J = 7.7 Hz, H-7), 7.07 (dd, 1H,
J = 7.8, 0.9 Hz, H-8); 13C NMR (CD3OD, 150 MHz): d 145.1, 135.6,
132.1, 128.7, 128.6, 127.3, 125.4, 123.7, 122.5, 116.2, 114.0. ESIMS
m/z ES+ 269.0 [M+H]+; HRESIMS: calcd for C15H10N2OCl+ 269.0482;
found 269.0480.
3.16. 9-(20,30,40,60-tetra-O-acetyl-b-
D-galactopyranosyl))-11-
chloro-10H-indolo [3,2-b]quinoline (12b)
This compound was prepared from 11 (268 mg, 1 mmol) and
2,3,4,6-tetra-O-acetyl-a-D-galactopyranosyl bromide (615 mg,
1.5 mmol) using the same procedure as described for 12a. Puri-
fication of the residue resulted in 12b (359 mg, 60%) as a yellow
powder; Rf = 0.3 (EtOAc–n-hexane 1:1); mp 198–200 °C; IR (KBr)
3404, 3210, 1748, 1499, 1368, 1229, 1073 cmꢁ1; UV (DMSO)
396, 342, 277 nm; 1H NMR (CDCl3, 600 MHz): d 8.60 (s, 1H, N–
H), 8.34 (m, 2H, H-1, H-4), 8.26 (d, 1H, J = 9.8 Hz, H-6), 7.74
(m, 1H, H-3), 7.67 (m, 1H, H-2), 7.31–7.28 (m, 2H, H-7, H-8),
5.61 (dd, 1H, J = 8.2, 10.4 Hz, H-20), 5.52 (d, 1H, J = 3.3 Hz, H-
40), 5.18 (dd, 1H, J = 3.3, 10.4 Hz, H-30), 5.18 (d, 1H, J = 8.2 Hz,
H-10), 4.29 (dd, 1H, J = 6.5, 11.6 Hz, H-60a), 4.23 (dd, 1H, J = 6.1,
11.6 Hz, H-60b), 4.13 (m, 1H, H-50), 2.25–1.99 (4s, 12H, Ac-H);
13C NMR (CDCl3, 150 MHz): d 170.4, 170.3, 170.2, 170.1, 142.7,
134.9, 130.1, 126.5, 124.4, 122.7, 121.2, 116.9, 101.8, 71.4,
70.5, 69.1, 66.8, 61.4, 21.1, 20.7, 20.6. ESIMS m/z ES+ 599.1
[M+H]+; HRESIMS: calcd for C29H28N2O10Cl+ 599.1432; found
599.1423.
3.14. 9-(20,30,40,60-tetra-O-acetyl-b-
D-glucopyranosyl)-11-
chloro-10H-indolo[3,2-b] quinoline (12a)
To a solution of water (5 mL) and chloroform (5 mL) was
added tetrabutylammonium bromide (320 mg, 1 mmol). After
heating to 40 °C, a mixture of 11 (268 mg, 1 mmol) and K2CO3

Z. Zhang et al. / Carbohydrate Research 344 (2009) 291–297
297
3.17. 9-(b-
b]quinoline (13b)
D
-galatopyranosyl)-11-chloro-10H-indolo[3,2-
N–H), 8.32 (d, 1H, J = 7.7 Hz, H-1), 8.28 (d, 1H, J = 7.7 Hz, H-4),
8.03 (d, 1H, J = 7.7 Hz, H-6), 7.75 (m, 2H, H-3, H-2), 7.52 (d, 1H,
J = 7.7 Hz, H-8), 7.28 (dd, 1H, J = 7.7, 8.2 Hz, H-7), 5.69 (s, 1H, –
OH), 5.16 (d, 1H, J = 4.4 Hz, –OH), 5.07 (d, 1H, J = 6.6 Hz, H-10),
4.88 (s, 1H, –OH), 4.84 (d, 1H, J = 5.5 Hz, –OH), 4.75 (t, 1H,
J = 5.5 Hz, –OH), 4.72 (t, 1H, J = 4.9 Hz, –OH), 4.57 (d, 1H,
J = 4.4 Hz, –OH), 4.28 (d, 1H, J = 7.1 Hz, H-100), 3.89–3.50 (m, 9H,
Lac-H); 13C NMR (DMSO-d6, 150 MHz): d 146,1, 144.0, 134.6,
130.1, 129.3, 127.1, 126.6, 123.7, 122.8, 122.3, 121.1, 118.7,
115.9, 115.5, 103.9, 102.3, 80.4, 75.6, 75.3, 73.8, 73.3, 70.5, 68.2,
60.5, 60.2. ESIMS m/z ES+ 593.2 [M+H]+; HRESIMS: calcd for
This compound was prepared from 12b (149 mg, 0.25 mmol)
using the same procedure as described for 13a. Purification of
the precipitate resulted in 13b (98 mg, 91%) as a yellow powder;
Rf = 0.4 (EtOAc–CH3OH 2:1); mp >300 °C; ½a D26
ꢁ54.3 (c 0.1,
ꢂ
CH3OH); IR (KBr) 3209, 1493, 1420, 1082, 738 cmꢁ1; UV (DMSO)
399, 343, 278 nm; 1H NMR (DMSO-d6, 600 MHz): d 8.32 (m, 1H,
H-1), 8.28 (m, 1H, H-4), 8.03 (d, 1H, J = 7.3 Hz, H-6), 7.74 (m, 2H,
H-3, H-2), 7.52 (d, 1H, J = 7.7 Hz, H-8), 7.27 (t, 1H, J = 7.8 Hz, H-
7), 5.01 (br s, 1H, –OH), 4.89 (d, 1H, J = 7.8 Hz, H-10), 4.80 (br s,
1H, –OH), 4.65 (br s, 1H, –OH), 3.83 (m, 1H, H-40), 3.77 (m, 1H,
H-60a), 3.70 (m, 1H, H-60b), 3.65 (m, 2H, H-20, H-30), 3.52 (m, 1H,
H-50); 13C NMR (DMSO-d6, 150 MHz): d 146.2, 144.3, 143.9,
129.3, 127.0, 126.5, 123.6, 122.8, 122.2, 121.1, 118.6, 116.2,
115.4, 103.8, 76.0, 72.3, 70.6, 68.2, 60.6. ESIMS m/z ES+ 431.2
þ
C27H30ClN2O11 593.1538; found 593.1516.
Acknowledgements
This work was financially supported by the Key International
Cooperation Project of CMST (Grant No. 2008DFA31040) and Na-
tional Basic Research Program Grant (2003CB716403).
[M+H]+. HRESIMS: calcd for C21H20ClN2O6 431.1010; found
431.1020.
þ
3.18. 9-(2,3,6,20,30,40,60-hepta-O-acetyl-b-
10H-indolo[3,2-b] quinoline (12c)
D-lactosyl)-11-chloro-
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2008.11.015.
This compound was prepared from 11 (268 mg, 1 mmol) and
2,3,6,20,30,40,60-hepta-O-acetyl-
-lactosyl bromide (1.04 g,
a
-D
References
1.5 mmol) using the same procedure as described for 12a. Purifica-
tion of the residue resulted in 12c (501 mg, 57%) as a yellow pow-
der; Rf = 0.2 (EtOAc–n-hexane 1:1); mp 138–140 °C; IR (KBr) 3403,
3212, 1748, 1390, 1368, 1228, 1073 cmꢁ1; UV (DMSO) 401, 342,
278 nm; 1H NMR (CDCl3, 600 MHz): d 8.62 (s, 1H, N–H), 8.34 (d,
1H, J = 8.7 Hz, H-4), 8.32 (d, 1H, J = 8.7 Hz, H-1), 8.26 (d, 1H,
J = 7.3 Hz, H-6), 7.73 (m, 1H, H-3), 7.67 (m, 1H, H-2), 7.29–7.25
(m, 2H, H-8, H-7), 5.38–5.32 (m, 3H, H-20, H-30, H-400), 5.17–5.13
(m, 2H, H-100, H-200), 4.98 (dd, 1H, J = 3.4, 10.1 Hz, H-300), 4.57 (dd,
1H, J = 1.8, 12.4 Hz, H-600a), 4.54 (d, 1H, J = 8.2 Hz, H-10), 4.21 (dd,
1H, J = 6.0, 12.4 Hz, H-600b), 4.17 (dd, 1H, J = 6.4, 10.9 Hz, H-60a),
4.09 (dd, 1H, J = 7.3, 10.9 Hz, H-60b), 3.99–3.91 (m, 2H, H-500, H-
40), 3.82 (m, 1H, H-50), 2.17–1.98 (7s, 21H, Ac-H); 13C NMR (CDCl3,
150 MHz): d 170.4, 170.3, 170.2, 170.1, 170.0, 169.7, 169.1, 142.5,
135.1, 130.2, 129.3, 127.5, 126.5, 124.4, 122.6, 121.2, 118.2,
117.5, 101.1, 76.0, 73.2, 72.3, 71.8, 70.9, 70.8, 69.1, 66.6, 61.9,
60.8, 20.9, 20.8, 20.7, 20.6, 20.5. ESIMS m/z ES+ 887.2 [M+H]+; HRE-
SIMS: calcd for C41H44N2O18Cl+ 887.2278; found 887.2299.
1. Boye, G. L.; Ampofo, O. (1983) Proceedings at the First International Symp osium
on Cryptolepine, Kumasi, Ghana, University of Science and Technology.
2. Hu, H. J.; Gooderham, N. J. Toxicol. Sci. 2006, 91, 132–139.
3. Paulo, A.; Gomes, E. T.; Steele, J.; Warhurst, D. C.; Houghton, P. J. Planta Med.
2000, 66, 30–34.
4. Seville, S.; Phillips, R. M.; Shnyder, S. D.; Wright, C. W. Bioorg. Med. Chem. 2007,
15, 6353–6360.
5. Olajide, O. A.; Heiss, E. H.; Schachner, D.; Wright, C. W.; Vollmar, A. M.; Dirsch,
V. M. Bioorg. Med. Chem. 2007, 15, 43–49.
6. Ou, T. M.; Lu, Y. J.; Zhang, C.; Huang, Z. S.; Wang, X. D.; Tan, J. H.; Chen, Y.; Ma,
D. L.; Wong, K. Y. J. Med. Chem. 2007, 50, 1465–1474.
7. Bonjean, K.; De, M. C.; Defresne, M. P.; Colson, P. Biochem 1998, 37, 5136–
5146.
8. Badowska-Roslonek, K.; Kaczmarek, L.; Rmz, J.; Szelejewski, W.; Godlewska, J.
Polish Patent Application P-353811 Warsaw, 2002.
9. Gottumukkala, V. S.; Jakka, K.; Dodda, R.; Jorge, I. J. J. Nat. Prod. 2004, 67, 461–
462.
10. Honda, T.; Kato, M.; Inoue, M.; Shimamoto, T.; Shima, K.; Nakanishi, T.;
Yoshida, T.; Noguchi, T. J. Med. Chem. 1988, 31, 1295–1305.
11. Li, Z. Z.; Peng, G. Bioorg. Med. Chem. 2005, 13, 6381–6387.
12. Wan, S. B.; Liu, Z. L.; Chen, D.; Dou, Q. P.; Jiang, Tao. Chin. Chem. Lett. 2007, 18,
1179–1181.
13. Radl, S.; Konvicka, P.; Vachal, P. J. Heterocycl. Chem. 2000, 37, 855–862.
14. Bishnupada, D.; Surajit, S.; Jayanta, K. Tetrahedron Lett. 2006, 47, 377–379.
15. Hostyn, S.; Maes, B. U. W.; Pieters, L.; Lemière, G. F.; Mátyus, P.; Hajós, G.;
Dommisse, R. A. Tetrahedron 2005, 61, 1571–1577.
3.19. 9-(b-D-lactosyl)-11-chloro-10H-indolo[3,2-b]quinoline
(13c)
16. Yamato, M.; Takeuchi, Y.; Chang, M.; Hashigaki, K. Chem. Pharm. Bull. 1992, 40,
528–530.
17. Tegdes, A.; Medyges, G.; Boros, S.; Kuszmann, J. Carbohydr. Res. 2006, 341, 776–
781.
18. Boucheron, C.; Toumieux, S.; Compain, P.; Martin, O. R.; Ikeda, K.; Asano, N.
Carbohydr. Res. 2007, 342, 1960–1965.
This compound was prepared from 12c (221 mg, 0.25 mmol)
using the same procedure as described for 13a. Purification of
the precipitate resulted in 13c (131 mg, 89%) as a yellow powder;
Rf = 0.2 (EtOAc/CH3OH, 2:1); mp >300 °C; ½a D26
ꢁ64.6 (c 0.02,
ꢂ
DMSO). IR (KBr) 3206, 1493, 1420, 1082, 738 cmꢁ1; UV (DMSO)
403, 343, 278 nm; 1H NMR (DMSO-d6, 600 MHz): d 11.44 (s, 1H,