Convenient synthesis of 1,4-dihydroxy-2-(ω-hydroxyalkoxy)anthracene- 9,10-diones and their conjugation with D-glucal

Article abstract of DOI:10.2174/157017812802850195

Purpurin, 1,2,4-trihydroxyanthraquinone, was regioselectively alkylated under basic conditions using bromoalcohol of varying chain length. As a base, potassium carbonate, tetrabutylammonium hydroxide or 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU) was used. The reaction of alkylation proceeded exclusively on the 2-hydroxyl group of the purpurin molecule. Addition of the obtained 2-(α-hydroxyalkoxy)purpurins to protected D-glucal catalysed by triphenylphosphine hydrobromide gave an access to new glycoconjugates with high enantioselectivity. In parallel experiments, the same substrates reacted in the presence of boron trifluoride etherate yielding the appropriate unsaturated adducts as a result of Ferrier rearrangement.

Full text of DOI:10.2174/157017812802850195

Letters in Organic Chemistry, 2012, 9, 539-544
539
Convenient Synthesis of 1,4-Dihydroxy-2-(ꢀ-Hydroxyalkoxy)Anthracene-
9,10-Diones and their Conjugation with D-Glucal
Sebastian Budniok and Krzysztof Z. Walczak*
Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology,
Krzywoustego 4, 44-100 Gliwice, Poland
Received April 25, 2012: Revised June 14, 2012: Accepted June 28, 2012
Abstract: Purpurin, 1,2,4-trihydroxyanthraquinone, was regioselectively alkylated under basic conditions using bromoal-
cohol of varying chain length. As
a base, potassium carbonate, tetrabutylammonium hydroxide or 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) was used. The reaction of alkylation proceeded exclusively on the 2-hydroxyl
group of the purpurin molecule. Addition of the obtained 2-(ꢀ-hydroxyalkoxy)purpurins to protected D-glucal catalysed
by triphenylphosphine hydrobromide gave an access to new glycoconjugates with high enantioselectivity. In parallel ex-
periments, the same substrates reacted in the presence of boron trifluoride etherate yielding the appropriate unsaturated
adducts as a result of Ferrier rearrangement.
Keywords: Addition reaction, alkylation, bromoalcohols, D-glucal, glycoconjugates, purpurin.
H
INTRODUCTION
O
OH
O
O
Purpurin belongs to anthraquinones present in the mad-
der roots (Rubia tinctorum, R. akane, R. cordifolia) and pos-
sesses numerous valuable properties. It has been used mainly
as a red cotton dye [1, 2]. Due to a lower energy level of the
singlet excited state (ꢁ, ꢁ*), purpurin acts as a fluorescent
molecule, as opposed to anthraquinone [3-6]. Purpurin forms
complexes with metal ions like aluminium, iron or chro-
mium, used as the mordant agents in textile dyeing [5, 7, 8].
Moreover, many anthraquinone derivatives are DNA-
complexing or intercalating agents exhibitng activity against
various types of tumours [9-12]. Due to these facts, also pur-
purin derivatives have been considered as potent bioactive
compounds. Purpurin is a specific inhibitor of spermidine-
induced autoactivation of pro-PHBP (Plasma hyaluronan-
binding protein, factor VII activating protease), responsible
for the activation of blood coagulating factor VII [13]. Ac-
cording to the reported data, purpurin is a competitive inhibi-
tor of cytochrome P450 inhibiting the mutagenicity of a
number of heterocyclic amines in the Ames mutagenicity
test thus, decreasing the rate of their degradation [14-17].
The inhibitory effect of purpurin on nitrogen oxide produc-
tion and suppression effects on induced nitrogen synthase
expression were recently reported [18]. In addition, purpurin
has been reported to exhibit various pharmacological and
biological activities including anticancer [19], antiviral [20],
antifungal [21] and enzyme regulatory function [22, 23].
OH
OH
O
O
OH
OH
O
O
O
H
B
A
OH
OH
OH
OH
O
O
O
OH
C
D
OH
OH
O
OH
O
OH
O
OH
OH
F
E
Fig. (1). The representation of hydrogen bonding and tautomers of
1,2,4-trihydroxyanthraquinone.
As a part of our research program, we were interested in
purpurin O-alkylated derivatives as synthons for the synthe-
sis of glycoconjugates. Regioselective O-alkylation of pur-
purin using ꢀ-bromoalcohols of a different length in carbon
chain as alkylating agents followed by the addition reaction
to unsaturated sugars give rise to glycoconjugates. The latter
*Address correspondence to these authors at the Department of Organic
Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of
Technology, Krzywoustego 4, 44-100 Gliwice; Tel: +4832 2371083; Fax:
+4832 2372094; E-mail: krzysztof.walczak@polsl.pl
1875-6255/12 $58.00+.00
© 2012 Bentham Science Publishers

540 Letters in Organic Chemistry, 2012, Vol. 9, No. 8
Budniok and Krzysztof
O
OH
O
O
OH
OH
OH
O
Br(CH2)nOH
2a-d
(CH2)nOH
Base
DMF, 70 oC
O
OH
1
3a-d
2, 3a (CH2)2-OH (50% - 70%)
2, 3b (CH2)3-OH (54% - 65%)
2, 3c (CH2)6-OH (51% - 60%)
2, 3d (CH2)10-OH (50% - 64%)
Scheme 1. Alkylation of purpurin using ꢀ-bromoalcohols.
Table 1. 2-(ꢀ-Hydroxyalkoxy)purpurins 3a-d.
Time
[h]
Yield
[%]
Mp.
[oC]
Entry
ꢀ-Bromoalcohol
Base
1
2
2-bromoethanol
2-bromoethanol
2-bromoethanol
3-bromopropanol
3-bromopropanol
3-bromopropanol
6-bromohexanol
6-bromohexanol
6-bromohexanol
10-bromodecanol
10-bromodecanol
10-bromodecanol
K2CO3
(Bu)4NOH
DBU
12
12
12
7
70
53
70*
60
54
65
57
51
60
61
50
64
205-206
3
4
K2CO3
168-169
164-165
118-120
5
(Bu)4NOH
DBU
7
6
7
7
K2CO3
6
8
(Bu)4NOH
DBU
6
9
6
10
11
12
K2CO3
6
(Bu)4NOH
DBU
6
6
*69 % of yield was obtained when the reaction was carried out for 6 h
compounds revealed higher solubility in aqueous media as
compared with the unsubstituted purpurin, being sparingly
soluble in water. Solubility of anthraquinones in water being
crucial for their bioavailability would be the matter of our
further investigation.
solution gave 2-O-methyl ether in 95% yield [25]. Alkyla-
tion using other alkyl halides usually gave a mixture of
mono-, di- and triethers in moderate yields [2].
RESULTS AND DISCUSSION
Purpurin is formally the 1,2,4-trihydroxy-anthraquinone,
where two hydroxyl groups, namely OH-1 and OH-4 are
involved in the formation of hydrogen bonds with two car-
bonyl groups present in the molecule. It suggests that alkyla-
tion should mainly occur on 2-OH group (Fig. 1, structures
A and B). On the other hand, a possible tautomerism should
be considered since protons can shift to the carbonyl groups
and create new reactions centers (Fig. 1, structures C-F).
Similar effects can also be expected for anions formed under
basic conditions where the stabilization by resonance oper-
ates [24]. Experimental results of purpurin acylation and
alkylation confirmed the expectations about reactivity of the
hydroxyl groups. Thus purpurin acylated with acetic anhy-
dride in pyridine at low temperature gave 2-acetate in 50%
yield [25]. Similar results were obtained with other acylating
agent [6]. Purpurin treated with diazomethane at 0 oC in THF
Our primary synthetic targets, 2-(ꢀ-hydroxyalkoxy) pur-
purins, bearing terminal hydroxyl group were obtained in
reaction of purpurin with ꢀ-bromoalcohols under basic con-
ditions. Three different deprotonating agents, namely potas-
sium carbonate, tetrabutylammonium hydroxide (TBAOH)
and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) were used
for generation of the purpurin anion. DBU and TBAOH
were used in a molar ratio of base to purpurin as 0.95 to 1
equiv., whereas potassium carbonate as of 0.5. The alkyla-
o
tion reactions were carried out in DMF at 70 C (Scheme 1,
Table 1). In the primary trials (1, 2 and 3) the time of the
reactions was 12 h. The next experiments were performed in
shorter time of 7h to 6 h (entries 4-12), without significant
decrease in the yield of the expected 2-(ꢀ-hydroxyalkoxy)
purpurin derivatives. In all the experiments performed, the
best results were obtained when DBU was used as a depro-

The Purpurin Conjugates
Letters in Organic Chemistry, 2012, Vol. 9, No. 8 541
O
OH
OR
O
OR
O
O
(CH2)nOH
Ph3P*HBr
OR
O
OH
OH
OR
+
CH2Cl2, r.t.
O(CH2)nO
RO
OR
O
OH
4a, b
3b, d
3b, n = 3
3d, n = 10
4a, R = Ac; 4b, R = Bn
5a, n = 3, R = Ac
5b, n = 10, R = Ac
5c, n = 3, R = Bn
5d, n = 10, R = Bn
O
CompoundꢀYield (%)ꢀꢀ : ꢁ ratio
5aꢀ
5bꢀ
5cꢀ
5dꢀꢀ
76ꢀ
72ꢀ
71ꢀ
70
4 : 1
5 : 1
8 : 1
10 : 0
5a-d
Scheme 2. Addition of 2-(ꢀ-hydroxyalkoxy)purpurins to protected D-glucal.
O
OH
OAc
O
OAc
O
O
(CH2)nOH
BF3*Et2O
O
O
OH
OH
OAc
+
CH2Cl2, 0 oC then r.t.,
20 - 24 h.
O(CH2)nO
AcO
AcO
O
OH
4a
3b, d
6a, b
Compound Yield (%) ꢀ : ꢁ ratio
3b, 6a, n = 3;
3d, 6b, n = 10; 81
53
9 : 1
9 : 1
Scheme 3. Addition of 2-(ꢀ-Hydroxyalkoxy)purpurins to D-glucal under conditions of Ferrier’s rearrangement.
tonating agent. Even on reducing the time of reaction to 6 h,
the yield of the appropriate 2-(ꢀ-hydroxyalkoxy)purpurins
3a-d isolated by column chromatography exceeded 60% and
was better in comparison with reported data.
satisfactory yield. The NMR data indicated the formation of
both anomers again with ꢀ-anomer as the major product (the
roughly ꢁ:ꢁ ratio 9:1). At this stage of investigation, we are
unable to predict the factors affecting stereochemistry of the
addition reaction. Probably, introduction of the bulky pro-
tecting group on the available hydroxyl groups can turn
stereochemistry of the addition towards exclusively ꢀ-
anomer. Unfortunately, even numerous trials did not allow
separating the anomeric mixture to the particular anomers.
For the synthesis of glycoconjugates, we selected com-
mercially available 3,4,6-tri-O-acetyl-D-glucal and its O-
benzylated analogue. The D-glucal derivative 4a or 4b was
treated at room temperature with a slight excess (0.1 equiv.)
of the appropriate purpurin derivative (3b or 3d) in the pres-
ence of triphenylphosphine hydrobromide as the catalyst
(Scheme 2). Consumption of the starting sugar derivative
was monitored by TLC (toluene : AcOEt, 1:1, v/v). Purifica-
tion on silica gel packed column extracted the expected
product (5a-d) as the anomeric mixture with the predominat-
ing ꢀ-anomer as calculated from the intensity of the H-1 pro-
ton (anomeric proton). The amounts of ꢁ-anomer varied be-
tween 20% in the case of 5a to the undetectable amount in
NMR for 5d. In the case of 3,4,6-tri-O-benzyl-D-glucal, the
amounts of ꢀ-anomer radically increased in comparison with
acetylated derivatives. The ratio of ꢀ:ꢁ anomers varied from
4:1 to 8:1 when compared to propoxy derivatives (5a and
5c). The same proportion was observed for conjugates with
dodecyloxy linker 5b and 5d – 5:1 to 10:0, respectively. The
formation of ꢁ-anomer as a major product was observed
early in addition reaction of simple alcohols to protected D-
glucal [26, 27]. In order to compare the reaction, we decided
to repeat the reactions of the 3b and 3d derivatives with D-
glucal (4a) in the presence of boron trifluoride diethylether-
ate (Scheme 3). This reaction is known as Ferrier reaction,
proceeding via rearrangement [28, 29]. The appropriate
products of Ferrier rearrangement, 4,6-di-O-acetyl-2,3-
dideoxy-D-hexenopyr-anosides 6a and 6b were obtained in
CONCLUSION
In summary, we have developed an effective method for
the regioselective alkylation of purpurin. Use of ꢂ-
bromoalcohols of a different length in carbon chain as alky-
lating agents in the presence of base provided exclusively 2-
O-alkylated products in satisfactory yield. It should be men-
tioned that inspections of the post-reaction mixtures indi-
cated only the presence of unreacted purpurin, while the
products of substitution in other positions of purpurin ring
were not detected by TLC. The obtained alkoxy derivatives
of purpurin when reacted with protected D-glucal derivatives
in the presence of Ph3P*HBr or BF3*Et2O as the catalyst
gave the ꢁ-anomers as a major or sole products. The forma-
tion of adducts proceeded with satisfactory yield.
EXPERIMENTAL
1
NMR spectra were recorded at 300 MHz for H NMR
and 75.5 MHz for 13C NMR on a Varian Inova 300 MHz; (ꢂ)
values are in parts per million (ppm) relative to tetramethyl-
silane as an internal standard. Mass spectra were recorded at

542 Letters in Organic Chemistry, 2012, Vol. 9, No. 8
Budniok and Krzysztof
ESI Mass Spectrometer ABSciex System 4000 QTRAP® at
positive and negative modes of ionisation. Optical rotation
measurements were performed at 25 oC on a JASCO p-2000
Series polarimeter at the D sodium line. Elemental analyses
were obtained using a Perkin–Elmer 240C apparatus. The
reagents were purchased from Lancaster. TLC 60F254 plates
and silica gel 60 (0.040–0.063 mm) were purchased from
Merck.
107.5 (C-3), 111.6 (C-1a), 126.2 (C-5), 126.4 (C-8), 132.4
(C-6), 133.1 (C-7), 134.1 (C-5a), 134.9 (C-8a), 149.6 (C-1),
156.8 (C-2), 160.2 (C-4), 183.5 (C-10), 186.3 (C-9). Anal.
Calcd for C17H14O6: C, 64.97; H, 4.49. Found: C, 65.20; H,
4.70. MS m/z (%): 337.3 (100) [M+Na]+, 313.5 (100) [M]-
1,4-Dihydroxy-2-(6-hydroxyhexyloxy)anthracene-9,10-
dione (3c)
1H NMR (CDCl3), ꢀ : 1.45-1.68 (m, 7H, H-6’, H-5’, H-
4’, 6’-OH), 1.96 (dd, J = 6.6, 7.8 Hz, 2H, H-2’), 3.68 (brs,
2H, H-6’), 4.14 (t, J = 6.6 Hz, 2H, H-1’), 6.68 (s, 1H, H-3),
7.77-7.86 (m, 2H, H-5, H-6), 8.33-8.36 (m, 2H, H-7, H-8),
13.49 (s, 1H, 4-OH), 13.57 (s, 1H, 1-OH). 13C NMR (CD-
Cl3), ꢀ: 25.4 (C-4’), 25.7 (C-3’), 28.6 (C-5’), 32.5 (C-2’),
62.8 (C-6’), 69.6 (C-1’), 105.9 (C-1a), 107.4 (C-3), 112.6 (C-
4a), 126.8 (C-6), 126.9 (C-7), 133.3 (C-5a), 133.7 (C-8a),
134.1 (C-5), 134.5 (C-8), 150.6 (C-2), 160.9 (C-4), 161.1 (C-
1), 184.3 (C-10), 187.2 (C-9). Anal. Calcd for C20H20O6: C,
67.41; H, 5.66. Found: C, 67.70; H, 5.91. MS m/z (%): 735.8
(100) [2MNa]+, 379.5 (67) [M+Na]+, 355.4 (100) [M]-
1,4-Dihydroxy-2-(ꢀ-hydroxyalkoxy)anthracene-9,10-
dione (3a-d)
To a solution of 1,3,4-trihydroxyanthraquinone (1; 256
mg, 1mmol) in DMF (5.0 mL) deprotonating agent
(DBU;145 mg, 0.95 mmol; K2CO3; 66 mg, 0.5 mmol) was
o
added and then the resulting mixture was stirred at 70 C for
30 minutes. Next ꢀ-bromoalcohol (2a-d) (1.5 mmol) was
o
added and stirring at 70 C was continued for the defined
time (6 to 12 h). The progress of the reaction was monitored
by TLC (CHCl3/MeOH 95:5, v/v). The reaction mixture was
evaporated to dryness and the residual oil was purified on a
silica gel packed column using a mixture of CHCl3/MeOH
(95:5, v/v). The fractions containing product were collected,
combined and then evaporated giving crystalline orange sol-
ids.
1,4-Dihydroxy-2-(10-hydroxydecyloxy)anthracene-9,10-
dione (3d)
1H NMR (CDCl3), ꢀ: 1.25-1.33 (m, 12H, 6 x CH2), 1.46-
1.63 (m, 3H, CH2, 10’-OH), 1.93 (dd, J = 6.9, 7.8 Hz, 2H, H-
2’), 3.64 (t, J = 6.6 Hz, 2H, H-10’), 4.11 (t, J = 6.6 Hz, 2H,
H-1’), 6.65 (s, 1H, H-3), 7.76-7.82 (m, 2H, H-5, H-6), 8.30-
8.33 (m, 2H, H-7, H-8), 13.45 (s, 1H, 4-OH), 13.54 (s, 1H,
1-OH). 13C NMR (CDCl3), ꢀ: 25.7 (C-6’), 25.8 (C-5’), 28.6
(C-7’), 29.2 (C-4’), 29.4 (C-8’), 29.4 (C-3’), 29.5 (C-9’),
32.8 (C-2’), 63.1 (C-10’), 69.8 (C-1’), 105.9 (C-1a), 107.3
(C-3), 112.3 (C-4a), 126.8 (C-6), 126.9 (C-7), 133.2 (C-5a),
133.7 (C-8a), 134.1 (C-5), 134.5 (C-8), 150.6 (C-2), 157.3
(C-4), 161.0 (C-1), 184.2 (C-10), 187.1 (C-9). Anal. Calcd
for C24H28O6: C, 69.89; H, 6.84 Found: C, 69.71; H, 7.21.
MS m/z (%): 435.7 (100) [M+Na]+, 411.8 (100) [M]-
Procedure with a use of TBAOH as deprotonating agent
To
a
solution of tetrabutylammonium hydroxide
(TBAOH) in methanol (259.5 mg, 1 mmol, 2.56 mL of 12.5
% solution) 1,3,4-trihydroxyanthraquinone (1; 256 mg, 1
mmol) was added and the mixture was stirred at room tem-
perature for 20 minutes, followed by evaporation to dryness.
The traces of methanol were removed by co-evaporation
with toluene (20 mL). The dry tetrabutyloammonium salt of
purpurin was dissolved in anhydrous DMF (5 mL) and ꢀ-
bromoalcohol 2a-d (1.5 mmol) was added while stirring.
The reaction mixture was stirred at 70 oC for fixed time (6 to
12 h). The progress of reaction was monitored by TLC
(CHCl3/MeOH 95:5, v/v). The work-up and isolation of
product were performed as in the procedure described above.
Synthesis of conjugates in the presence of Ph3P*HBr
(general procedure)
To a solution of D-glucal 4a, b (1 mmol) in anhydrous
CH2Cl2 (5 mL), Ph3P*HBr (0.15 mmol) was added and the
resulting mixture was stirred at room temperature for 15
minutes. Next the purpurin derivative 3b or 3d (1.1 mmol)
was added and the stirring at room temperature was contin-
ued for the defined time (20 to 24 h). The progress of reac-
tion was monitored by TLC (toluene/ethyl acetate 1:1; to 4:1
v/v). The reaction mixture was evaporated to dryness and the
residual oil was purified on a silica gel packed column using
a mixture of toluene: ethyl acetate (1:1 to 4:1, v/v). The frac-
tion, containing product was collected, combined and evapo-
rated to give the desired product.
1,4-Dihydroxy-2-(2-hydroxyethoxy)anthracene-9,10-
dione (3a)
1H NMR (DMSO-d6), ꢀ: 3.79 (dd, J = 4.5, 5.1 Hz, 2H, H-
2’), 4.14 (t, J = 4.5 Hz, 2H, H-1’), 5.03 (t, J = 5.1 Hz, 1H,
2’-OH), 6.86 (s, 1 H, H-3), 7.85-7.93 (m, 2 H, H-5, H-6),
8.14-8.18 (m, 2H, H-7, H-8), 13.15 (s, 1H, 4-OH), 13.39 (s,
1H, 1-OH). 13C NMR (DMSO-d6), ꢀ: 59.1 (C-2’), 71.4 (C-
1’), 105.4 (C-1a), 107.8 (C-3), 111.9 (C-4a), 126.3 (C-6),
126.5 (C-7), 132.6 (C-5a), 133.2 (C-8a), 134.3 (C-5), 135.0
(C-8), 149.7 (C-2), 157.0 (C-4), 160.2 (C-1), 183.7 (C-10),
186.6 (C-9). Anal. Calcd for C16H12O6: C, 64.00; H, 4,03.
Found: C, 63.80; H, 4.35. MS m/z (%): 323.3 (100)
[M+Na]+, 299.4 (100) [M]-
2-[(1,4-dihydroxy-anthracene-9,10-dione)]propoxy-3-yl
3,4,6-tri-O-acetyl-2-deoxy-D-arabinohexopyranoside (5a)
ꢁ Anomer: 1H NMR (CDCl3), ꢀ: 1.83 (ddd, J = 3.6, 12.0,
13.2 Hz 1H, H-2a), 2.01 (2s, 6H, 2CH3CO), 2.08 (s, 3H,
CH3CO), 2.20 - 2.24 (m, 2H, CH2), 2.27 (ddd, J = 1.2, 5.0,
13.2 Hz 1H, H-2b) 3.63 (dt, J = 6.0, 10.8 Hz, 1H, OCH2a),
3.91 (dt, J = 5.4, 10.8 Hz, 1H, OCH2b), 3.94-3.96 (m, 1H, H-
5), 4.05 (dd, J = 2.4, 12.0 Hz, 1H, H-6b), 4.24-4.28 (m, 3H,
Pur-OCH2, H-6a), 4.95 (dd, J = 9.6, 10.2 Hz 1H, H-4), 5.00
(dd, J = 1.2, 3.6 Hz, 1H, H-1), 5.31 (ddd, J = 5.0, 9.6, 12.0
1,4-Dihydroxy-2-(3-hydroxypropoxy)anthracene-9,10-
dione (3b)
1H NMR (DMSO-d6), ꢀ: 1.94 (dd, J = 6.0, 6.3 Hz, 2H, H-
2’), 3.59 (dd, J = 5.7, 6.0 Hz, 2H, H-3’), 4.23 (t, J = 6.3 Hz,
2H, H-1’), 4.64 (t, J = 5.7 Hz, 1H, 3’-OH), 6.96 (s, 1H, H-3),
7.92-7.99 (m, 2H, H-5, H-6), 8.23-8.28 (m, 2H, H-7, H-8),
13.20 (s, 1H, 4-OH), 13.48 (s, 1H, 1-OH). 13C NMR (DM-
SO-d6), ꢀ: 31.5 (C-2’), 56.9 (C-3’), 66.5 (C-1’), 105.1 (C-4a),

The Purpurin Conjugates
Letters in Organic Chemistry, 2012, Vol. 9, No. 8 543
Hz, 1H, H-3), 6.72 (s, 1H, H-3’), 7.78-7.84 (m, 2H, H-5’, H-
6’), 8.33-8.35 (m, 2H, H-7’, H-8’), 13.42 (s, 1H, 4’-OH),
13.51 (s, 1H, 1’-OH). ꢀ Anomer: ꢁ: 1.62 - 1.79 (m, 1H, H-
2a), 2.21-2.25 (m, 1H, H-2b), 4.61(dd, J = 1.8, 9.6 Hz, 1H,
H-1) 13C NMR (CDCl3), ꢁ: 20.82, 20.87, 21.09 (3CH3),
28.88 (CH2), 35.10 (C-2), 62.48 (OCH2), 63.77 (OCH2)
66.45 (C-6), 68.08 (C-3), 69.19 (C-4), 69.51 (C-5), 97.21 (C-
1),106.34 (C-1’a), 107.78 (C-3’), 112.67 (C-4’a), 126.98 (C-
6’), 127.14 (C-7’), 133.43 (C-5’a), 133.96 (C-8’a), 134.22
(C-5’), 134.70 (C-8’), 150.59 (C-2’), 157.08 (C-4’), 160.95
(C-1’), 170.02, 170.31, 170.84 (3C=O)184.59 (C-10’),
187.38 (C-9’). MS m/z (%): 609.2 (100) [M+Na]+, 585.6
(100) [M]-
2-[(1,4-dihydroxy-anthracene-9,10-dione)]decyloxy-10-
yl 3,4,6-tri-O-benzyl-2-deoxy-ꢀ-D-arabinohexopyranoside
(5d)
[ꢀ]D26 +16.5° (c 1.0, CH2Cl2); 1H NMR (CDCl3), ꢁ: 1.23-
1.34 (m, 12H, 6CH2), 1.47-1.54 (m, 2H, OCH2CH2), 1.71
(ddd, J = 3.6, 11.4, 13.2 Hz, 1H, H-2a), 1.92 (dt, J = 6.6, 13.5
Hz, OCH2CH2), 2.28 (dd, J = 4.8, 13.2 Hz, 1H, H-2b), 3.35
(dt, J = 6.9, 9.9 Hz, 1H, OCH2a), 3.57-3.81 (m, 5H, OCH2b,
H-4, H-5, H-6a, H-6b), 3.99 (ddd, J = 4.8, 9.0, 11.4 Hz, 1H,
H-3), 4.07-4.13 (m, 2H, Pur-OCH2), 4.49-4.53 (m, 2H,
CH2Ar), 4.61-4.70 (m, 3H, CH2Ar), 4.88 (d, J = 11.0 Hz,
1H, CH2Ar), 4.94 (d, J = 3.6 Hz, 1H, H-1), 6.64 (s, 1H, H-
3’), 7.14-7.34 (m, 15H, HAr), 7.74-7.84 (m, 2H, H-5’, H-6’),
8.30-8.33 (m, 2H, H-7’, H-8’), 13.46 (s, 1H, 4’-OH), 13.55
(s, 1H, 1’-OH). 13C NMR (CDCl3), ꢁ: 25.86 (CH2), 26.20
(CH2), 28.62 (CH2), 29.27 (CH2), 29.43 (2CH2), 29,52
(2CH2), 35.57 (C-2), 67.37, 69.02, 69.76, 70.71, 71.73,
73.44 (2OCH2, C-3, C-4, C-5, C-6), 74.94, 77.80, 78.38
(3CH2Ph), 97.31 (C-1), 105.95 (C-1’a), 107.34 (C-3’),
112.37 (C-4’a), 126.77 (C-6’), 126.93 (C-7’), 127.45,
127.54, 127.81, 127.92, 128.28, 128.31 (Ph), 133.30 (C-5’a),
133.68 (C-8’a), 134.12 (C-5’), 134.44 (C-8’), 138.23,
138.57, 138.78 (Ph), 150.68 (C-2’), 157.32 (C-4’), 161.00
(C-1’), 184.22 (C-10’), 187.11 (C-9’). MS m/z (%): 851.7
(100) [M+Na]+, 827.4 (100) [M]-
2-[(1,4-dihydroxy-anthracene-9,10-dione)]decyloxy-10-
yl 3,4,6-tri-O-acetyl-2-deoxy-D-arabinohexopyranoside (5b)
1
ꢀ Anomer: H NMR (CDCl3), ꢁ: 1.15 – 1.32 (m, 12H,
6CH2), 1.49-1.58 (m, 2H, OCH2CH2), 1.82 (ddd, J = 3.3,
11.7, 12.6 Hz, 1H, H-2a), 1.93 (dt, J = 5.4, 7.5 Hz,
CH2CH2O), 2.01, 2.04, 2.10 (3s, 9H, CH3CO), 2.23 (dt, J =
5.4, 12.6 Hz, 1H, H-2b), 3.39 (dt, J = 6.6, 12.6 Hz, 1H, O-
CH2a), 3.60 (dt, J = 6.6, 9.3 Hz, 1H, OCH2b), 3.94-3.99 (m,
1H, H-5), 4.05 (dd, J = 12.3, 2.1 Hz, 1H, H-6b), 4.13 (t, J =
6.6, Hz, 2H, Pur-OCH2), 4.31 (dd, J = 4.6, 12.3 Hz, 1H, H-
6a), 4.95 (d, J = 3.3 Hz, 1H, H-1), 5.00 (dd, J = 9.3, 8.4 Hz,
1H, H-4), 5.33 (ddd, J = 9.3, 11.7, 5.4 Hz, 1H, H-3), 6.67 (s,
1H, H-3’), 7.76-7.91 (m, 2H, H-5’, H-6’), 8.31-8.36 (m, 2H,
H-7’, H-8’), 13.48 (s, 1H, 4’-OH), 13.57 (s, 1H, 1’-OH). ꢀ
Anomer, ꢁ: 1.49 – 1.66 (m, 1H, H-2a), 4.55(d, J = 7.8 Hz,
1H, H-1) 13C NMR (CDCl3), ꢁ: 20.74, 20.80, 20.97 (3CH3),
25.85 (CH2), 26.18 (CH2), 28.61 (CH2), 29.25 (CH2), 29.39
(2CH2), 29,42 (2CH2), 35.09 (C-2), 62.43 (OCH2), 67.71
(OCH2) 67.87 (C-6), 69.19 (C-3), 69.51 (C-4), 69.78 (C-5),
96.89 (C-1), 105.96 (C-1’a), 107.34 (C-3’), 112.65 (C-4’a),
126.80 (C-6’), 126.96 (C-7’), 133.29 (C-5’a), 133.74 (C-8’a),
134.11 (C-5’), 134.49 (C-8’), 150.64 (C-2’), 157.32 (C-4’),
160.99 (C-1’), 169.92, 170.19, 170.72 (3C=O), 184.29 (C-
10’), 187.19 (C-9’). MS m/z (%): 707.8 (100) [M+Na]+,
683.9 (100) [M]-
Synthesis of glycoconjugates in the presence of boron-
trifluoride (general procedure)
To a solution of glucal 4a (1 mmol) in anhydrous CH2Cl2
o
(5 mL), BF3*Et2O (0.10 mmol) was added at 0 C followed
by the addition of purpurin derivative 3b or 3d (1.1 mmol)
while stirring and then the reaction was continued at room
temperature. The progress of reaction was monitored by
TLC (toluene/ethyl acetate 2:1, or hexane/ethyl acetate 2:1
v/v). When TLC indicated the complete consumption of sub-
strate (20 - 24 h), the reaction mixture was quenched with a
saturated aqueous solution of NaHCO3. The organic layer
was separated, washed with brine, dried over anhydrous
Na2SO4 and then concentrated under reduced pressure to
colourless oil. The residual oil was purified on a silica gel
packed column using a mixture of toluene/ethyl acetate or
hexane/ethyl acetate (1:2, v/v). The fraction containing
product, was collected, combined together and evaporated,
to give desired products.
2-[(1,4-dihydroxy-anthracene-9,10-dione)]propoxy-3-yl
3,4,6-tri-O-benzyl-2-deoxy-ꢀ-D-arabinohexopyranoside (5c)
26
[ꢀ]D +23.6° (c 1.0, CH2Cl2); 1H NMR (CDCl3), ꢁ: 1.72
(ddd, J = 3.6, 12.0, 13.2 Hz 1H, H-2a), 2.10-2.17 (m, 2H,
CH2), 2.26-2.29 (m, 1H, H-2b), 3.60-3.74 (m, 5H, OCH2a,
OCH2b, H-5, H-6a, H-6b), 3.87 (ddd, J = 1.2, 5.0, 8.8 Hz, 1H,
H-4), 3.96 (ddd, J = 5.0, 8.8, 11.5 Hz, 1H, H-3), 4.17-4.23
(m, 2H, Pur-OCH2), 4.47-4.50 (m, 2H, CH2Ar), 4.61-4.64
(m, 2H, CH2Ar), 4.67 (d, J = 11.0 Hz, 1H, CH2Ar), 4.85 (d,
J = 11.0 Hz, 1H, CH2Ar), 4.98 (d, J = 3.0 Hz, 1H, H-1), 6.70
(s, 1H, H-3’), 7.12-7.28 (m, 15H, HAr), 7.78-7.82 (m, 2H,
H-5’, H-6’), 8.30-8.32 (m, 2H, H-7’, H-8’), 13.44 (s, 1H, 4’-
OH), 13.54 (s, 1H, 1’-OH). 13C NMR (CDCl3), ꢁ: 28.80
(CH2), 35.39 (C-2), 63.13, 66.53, 68.83, 70.94, 71.77, 73.45
(2OCH2, C-3, C-4, C-5, C-6), 74.87, 77.49, 78.14 (3CH2Ph),
97.49 (C-1), 106.11 (C-1’a), 107.56 (C-3’), 112.45 (C-4’a),
126.82 (C-6’), 126.96 (C-7’), 127.50, 127.56, 127.62,
127.69, 127.81, 128.24, 128.28, 128.31, 128.34 (Ph), 133.29
(C-5’a), 133.75 (C-8’a), 134.11 (C-5’), 134.51 (C-8’),
138.09, 138.45, 138.64 (Ph), 150.52 (C-2’), 157.04 (C-4’),
160.84 (C-1’), 184.38 (C-10’), 187.21 (C-9’). MS m/z (%):
753.5 (60) [M+Na]+, 729.7 (100) [M]-
2-[(1,4-dihydroxy-anthracene-9,10-dione)]propoxy-3-yl
4,6-di-O-acetyl-2,3-dideoxy-D-erythro-hex-2-enopyranoside
(6a)
1H NMR (CDCl3), ꢁ: 1.25 – 1.34 (m, 2H, CH2), 2.09 (s,
6H, 2CH3CO), 2.23-2.34 (m, 2H, OCH2), 3.75 (td, J = 6.3,
6.3, 9.9 Hz, 1H, OCH2a), 3.99-4.27 (m, 4H, OCH2b, H-6a, H-
6b, H-5), 5.07 (bs, 1H, H-1), 5.29-5.34 (m, 1H, H-4), 5.80-
5.96 (m, 2H, H-2, H-3), 6.70 (s, 1H, H-3’), 7.77-7.85 (m,
2H, H-5’, H-6’), 8.31-8.34 (m, 2H, H-7’, H-8’), 13.41 (s,
1H, 4’-OH), 13.51 (s, 1H, 1’-OH). 13C NMR (CDCl3), ꢁ:
20.71, 20.91 (2CH3), 29,68 (CH2), 62.93, 63.00, 64.82,
65.34, 66.57 (2OCH2, C-4, C-5, C-6), 94.56 (C-1), 106.01
(C-1’a), 107.52 (C-‘3), 112.48 (C-4’a), 126.81 (C-6’), 126.97
(C-7’), 127.61 (C-2’), 129.27 (C-3’), 133.29 (C-5’a), 133.74
(C-8’a), 134.08 (C-5’), 134.48 (C-8’), 150.50 (C-2’), 157.04
(C-4’), 160.79 (C-1’), 170.11, 170.59 (2C=O), 184.33 (C-

544 Letters in Organic Chemistry, 2012, Vol. 9, No. 8
Budniok and Krzysztof
10’), 187.13 (C-9’). MS m/z (%): 549.4 (100) [M+Na]+,
525.7 (100) [M]-
aryl hydrocarbon receptor induced by 2,3,7,8-tetrachlorodibenzo-p-
dioxin. J. Biosci. Bioengin., 2009, 107, 296-300.
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against Trp-P-2 mutagenicity by purpurin: mechanism in vitro an-
timutagenesis. Mutagenesis, 2000, 15, 223-228.
Takahashi, E.; Fujita, K.; Kamataki, T.; Arimoto-Kobayashi, S.;
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1B1, 1A1 and 1A2 by antigenotoxic compounds, purpurin and ali-
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2-[(1,4-dihydroxy-anthracene-9,10-dione)]decyloxy-10-
yl 4,6-di-O-acetyl-2,3-dideoxy-D-erythro-hex-2-enopyrano-
side (6b)
1H NMR (CDCl3), ꢀ: 1.29 - 1.53 (m, 12H, 6CH2), 1.56 -
1.63 (m, 2H, OCH2CH2), 1.92 (q, J = 7.8 Hz, 2H, O-
CH2CH2), 2.08, 2.10 (2s, 6H, 2CH3CO), 3.48-3.52 (m, 1H,
OCH2a), 3.74-3.79 (m, 1H, OCH2b), 4.09-4.26 (m, 5H, Pur-
OCH2, H-6a, H-6b, H-5), 5.02 (bs, 1H, H-1), 5.30-5.32 (m,
1H, H-4), 5.82-5.84 (m, 1H, H-2), 5.87-5.88 (m, 1H, H-3),
6.66 (s, 1H, H-3’), 7.77-7.83 (m, 2H, H-5’, H-6’), 8.32-8.34
(m, 2H, H-7’, H-8’), 13.45 (s, 1H, 4’-OH), 13.54 (s, 1H, 1’-
OH). 13C NMR (CDCl3), ꢀ: 20.77, 20.95 (2CH3), 25.89
(CH2), 26.25 (CH2), 28.65 (CH2), 29.28 (CH2), 29.40 (CH2),
29.45 (CH2), 29,50 (CH2), 29,54 (CH2), 63.06, 65.38, 66.92,
68.98, 69.78 (2OCH2, C-4, C-5, C-6), 94.40 (C-1), 106.01
(C-1’a), 107.38 (C-3’), 112.43 (C-4’a), 126.82 (C-6’), 126.97
(C-7’), 128.00 (C-2’), 128.99 (C-3’), 133.34 (C-5’a), 133.72
(C-8’a), 134.16 (C-5’), 134.48 (C-8’), 150.72 (C-2’), 157.35
(C-4’), 161.02 (C-1’), 170.22, 170.69 (2C=O), 184.27 (C-
10’), 187.17 (C-9’). MS m/z (%): 647.5 (100) [M+Na]+,
623.6 (100) [M]-
[12]
[13]
[14]
[15]
[16]
[17]
CONFLICT OF INTEREST
[18]
[19]
The author(s) confirm that this article content has no con-
flicts of interest.
Son, J.K.; Jung, S.J.; Jung, J.H.; Fang, Z.; Lee, C.S.; Seo, C.S.;
Moon, D.C.; Min, B.S.; Kim, M. R.; Woo, M.H. Anticancer con-
stituents from the roots of Rubia cordifolia L. Chem. Pharm. Bull.,
2008, 56, 213-216.
ACKNOWLEDGEMENTS
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