Synthesis of some chromanone derivatives and the use of DNA in evaluation of their biological activity

Article abstract of DOI:10.1515/znb-1998-0823

6-Formyl-7-hydroxy-5-methoxy-2-pentamethylenechromanone (2) was prepared from the naturally occurring "Visnagin" and condensed with benzil, o-phenylenediamine and 3,4-diaminobenzophenone to give the corresponding imidazolylchromanone derivatives 3-5. Knoevenagel reaction of compound 2 with different active methylene compounds afforded benzodipyranone derivatives 12a-c which may be considered as analogues to the naturally occurring "Xanthyletin and Graveolone Compounds". The structural formula of the new compounds were established by using different methods for their preparation in addition to the instrumental analyses. Some compounds in this study were biologically evaluated for their ability to bind to DNA.

Full text of DOI:10.1515/znb-1998-0823

Synthesis of Some Chromanone Derivatives and the Use of
DNA in Evaluation of their Biological Activity
El-Sayed I. El-Desokya, Emad. M. El-Telbanib, M ahmoud A. H am m adb,
Farid A. Badriac, A bdel-Rahm an H. A bdel-R ahm an3
a Department of Chemistry, Faculty of Science, University of Mansoura, Egypt
b National Research Centre, Dokki, Giza, Egypt
c Faculty of Pharmacy, University of Mansoura, Egypt
Z. Naturforsch. 53b, 909-915 (1998); received December 19, 1997
Chromanone, Visnagin, Dibenzopyranone, Benzimidazole, Furochromone
6-Formyl-7-hydroxy-5-methoxy-2-pentamethylenechromanone (2) was prepared from the
naturally occurring “Visnagin” and condensed with benzil, o-phenylenediamine and 3,4-di-
aminobenzophenone to give the corresponding imidazolylchromanone derivatives 3-5.
Knoevenagel reaction of compound 2 with different active methylene compounds afforded
benzodipyranone derivatives 12a -c which may be considered as analogues to the naturally
occurring “Xanthyletin and Graveolone Compounds”. The structural formula of the new
compounds were established by using different methods for their preparation in addition to
the instrumental analyses. Some compounds in this study were biologically evaluated for
their ability to bind to DNA.
Introduction
man-4-one (3). Compound 3 was established by
elemental and spectral analyses and by using an-
other m ethod for its preparation via spirocycliza-
tion of com pound 4 [13] with cyclohexanone (cf.
Scheme 1).
Furochromones and related compounds are use-
ful as protective against atherosclerosis [1-3].
Also, benzopyranones occur abundantly in plants
and exhibit different biological and pharmacologi-
cal activities e.g. spasmolytic, cytotoxic, antihepa-
totoxic and antidiabetic [4-7]. Furocoumarins and
pyranocoumarin exhibit antifertility, antifungal,
antibacterial and insecticidal activities [8-10]. In
continuation of our research program for the syn-
thesis of simple and fused furochromones [11-13].
This work deals with the synthesis and biological
evaluation of series from furochromanones com-
pounds.
Compound 2 was allowed to react with o-phe-
nylenediamine or 3,4-diaminobenzophenone to
give the corresponding benzimidazolyl chroman-
4-one 5a and 5b respectively which were estab-
lished by another method for their preparation
as outlined in Scheme 2. W hen 6-formyl-7-hy-
droxy-5-methoxy-2-methylchrom-4-one (6) [14]
was treated with o-phenylenediamine or 3,4-dia-
m inobenzophenone, the corresponding benzimi-
dazolyl chromones 8 a,b were obtained via the an-
ils 7a,b. Thereafter hydrolysis of 8 in alkaline
medium to give 9a,b which were spirocyclized
using cyclohexanone to yield the desired products
5 a and 5 b.
Electrophilic substitution of compound 2 using
bromine or nitric acid afforded the corresponding
8-bromo (or nitro) chroman-4-one derivatives 10 a
and 10 b, respectively. Also, condensation of the
above spirochroman-4-one 2 with hydroxylamine
hydrochloride and different aromatic amines, (ani-
Chemistry and Discussion
In the present work, the furochroman-4-one la
[12] was oxidized to give 6-formyl-7-hydroxy-5-
methoxy-2-pentamethylenechroman-4-one
(2)
which was treated with benzil in acetic acid/ammo-
nium acetate to give 6-(4',5'-diphenyl-2'-imidazo-
lyl)-7-hydroxy-5-methoxy-2-pentamethylene chro-
line, /?-anisidine and p-nitroaniline) yielded
a
quantitive yield of the corresponding oxime and
* Reprint requests to Dr. El-Sayed.
anil derivatives lla -d .
0932 - 0776/98/0800-0909 $06.00 © 1998 Verlag der Zeitschrift für Naturforschung. All rights reserved.
N
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910
E.-S. I. El-Desoky et al. • Synthesis of Some Chrom anone Derivatives and the Use of DNA
OMe
O
OMe
O
Scheme 1
o-ph-diamine or _
3,4-diaminobenzo-
phenone
a: R-H
6
b: R=COPh
7a,b
Scheme 2
Application of Knoevenagel reaction on 2-hy-
droxy aromatic aldehyde substituent with
active methylene compounds to give benzodi-
coum arin derivative 12c which directly reacted
with another molecule to give compound 12d.
The elemental and spectral analyses of 12a-d
2
pyran derivatives 12a - c which may be consid- were in agreem ent with their structural formula
ered as analogues to the naturally occurring also, the mass spectra of 12a and 12d showed
Gravelone and Xathyletin Compounds 13 and 14 M + at m /z = 356 and 452 respectively.
[15]. W hen 2 was condensed with one mole of Claisen condensation of compound la or lb
cyanoacetamide or diethyl malonate, the corre- with diethyl carbonate or ethyl acetate allowed the
isolation of compounds which possessed elemental
analysis and spectral data concordant with the for-
m ation of benzofuran derivatives 17a-c instead of
sponding Knoevenagel derivatives 12a and 12b
were obtained. Also, at treatm ent 2 with two
moles of ethyl cyanoacetate afforded 3-cyano-
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E.-S. I. El-Desoky et al. • Synthesis of Some Chrom anone Derivatives and the Use of DNA
911
Table I. Characterization data of the newly prepared compounds.
Analysis
Comp.
M.p.
°C
Yield
%
M.
Formula
M.
Weight
Calcd
Found
C
H
N
C
H
N
_
_
2
Ci6Hi80 5
C30H28N2O4
C22H22N2O4
6.44
5.69
5.66
5.61
5.22
4.53
4.51
4.09
4.74
4.40
5.43
6.44
6.59
6.60
5.17
5.38
5.59
5.54
6.53
6.07
6.58
200
208-210
>300
270-273
262-263
280-282
90
81
65
70
-
290.315
480.56
378.43
483.53
324.33
428.44
322.32
426.43
402.41
369.21
335.31
305.33
365.43
395.43
410.426
356.38
386.40
452.46
286.33
316.35
300.35
66.20
74.98
69.83
72.19
66.66
70.09
67.08
70.42
68.65
52.05
57.31
62.94
72.31
69.86
64.38
64.04
65.28
63.71
71.31
68.34
71.98
6.25
5.87
5.86
5.43
4.97
4.70
4.38
4.25
4.51
4.64
5.11
6.27
6.34
6.37
5.40
5.66
5.74
5.35
6.34
6.37
6.71
66.07
74.71
69.68
72.34
66.41
70.32
66.91
70.63
68.48
52.25
57.09
62.69
72.49
69.61
64.09
64.29
65.50
63.92
71.19
68.52
71.73
3
5.58
7.59
5.59
8.59
6.80
8.44
6.33
5.83
7.40
5.81
8.64
6.54
8.69
6.57
6.96
5a
5b
7a
7b
C29H26N2O5
Ci8Hlf)N20 4
C25H20N2O5
Ci8H14N20 4
C25H18N2O5
C23H18N2O5
Ci6Hi70 5Br
c 16h 17n o 7
Ci6H19N05
C22H23N04
C23H25N05
-
>300
78
80
78
84
92
83
87
92
86
80
83
93
89
79
85
8a
249-250
237-238
179-180
118-120
185-186
110-112
190-192
137-138
220-222
230-233
245-246
108-110
172-174
97-99
8b
9b
7.18
-
10a
10b
11a
lib
11c
lid
12a
12b
12d
17a
17b
17c
4.18
4.36
5.37
3.79
3.66
6.98
7.79
-
4.59
3.83
3.54
6.83
7.86
-
C22H22N2Ö6
C 19H2oN20 5
C21H220-7
C24H24N207
6.41
-
6.19
-
C 17H 180 4
C18H20O5
Ci8H2q0 4
-
-
-
-
OMe
O
OMe
O
b; =0
c; =0
d; =0
=COOEt
=CN
= -Q=C(CN)COOEt
NH2
13
14
Scheme 3
compounds 15a-c. Also, under the effect of obtained instead of compound 16 when compound
ethoxide ion a methyl/ethyl exchange was oc-
curred as reported from 'H NMR of compound
17c [16] (cf. Table II). The same product 17a was
la was reacted with anisaldehyde in sodium ethox-
ide solution as inferred from the complete
agreem ent of the spectral data and the rate of flow
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E.-S. I. El-Desoky et al. • Synthesis of Some Chromanone Derivatives and the Use of DNA
912
precipitate was filtered, dried and crystallized
from ethanol to give compound 5 a and 5 b respec-
tively.
Method B: Compounds 5 a and 5 b were also
prepared from the compounds 9 a and 9 b
following the procedure described above in prepa-
ration of compound 3 “M ethod B ”.
in TLC [petroleum ether/ethyl acetate (4:1) R f =
0.3].
NMR spectrum of compound 17a showed
a characteristic olefinic CH and exchangeable OH
signals at d = 5.4 and 13.1 ppm respectively in ad-
dition to disappearance of methylene protons at
ö = 2.8 ppm.
Experimental
Condensation o f compound 6 with o-phenylenedi-
amine or 3,4-diaminobenzophenone; preparation
o f com pound 7a,b and 8a,b
All melting points are uncorrected. The IR
spectra were recorded (KBr) on a M attson 5000
IT IR spectrometer. The !H NM R were recorded
on a Varian-Gemini at 200 MHz and chemical
shifts are expressed in ppm using TMS as the in-
ternal standard. Elemental analyses were carried
out in the microanalytical unit, Faculty of Science,
M ansoura and Cairo University. Thin layer chro-
matography (TLC): Merck-plates, silica gel 60
F254, layer thickness 0.2 mm [Tables I and II show
the characterization and spectral data of the newly
prepared compounds].
A mixture from compound 6 (2.3 g, 10 mmol)
and o-phenylenediamine or 3,4-diaminobenzo-
phenone (10 mmol) in butanol (30 ml) was
boiled under reflux for 5 h. After cooling the
formed precipitate was filtered dried and recrys-
tallized from ethanol to give a yellow precipitate
from compound 8 a and 8 b, respectively. Concen-
tration of the m other liquor in vacuo and the
residue was crystallized from ethanol to give yel-
low crystals from the corresponding anils 7 a
and 7b.
TTie compounds la ,b , 2, 4, 6 and 9 were pre-
pared following a known procedures [12-14]. The
characterization data of the new products of them
are reported in Table I and II.
Preparation o f 8-bromo (and 8-nitro)-6-formyl-
7-hydroxy-5-methoxy-2-pentamethylene
chroman-4-one 10 a and 10 b
Preparation o f 6-(4',5 '-diphenylimidazol-2'-yl)-
7-hydroxy-5-methoxy-2-pentamethylene
chroman-4-one (3)
Com pound 10 a: To a solution of 2 (2.9 g, 10
mmol) in 20 ml chloroform was added dropwise a
solution from [bromine (1.0 g, 0.3 ml, 12 mmol)
in chloroform (10 ml)]. The reaction mixture was
stirred at room tem perature for 5 h and left to
stand for 24 h. The formed precipitate was filtered
and crystallized from ethanol to give pale yellow
crystals of compound 10 a.
Com pound 10 b: To a suspension of 2 (1 g) in
glacial acetic acid (5 ml) was added a mixture of
concentrated nitric acid (1 ml) and glacial acetic
acid (2 ml). The reaction mixture was stirred at
room tem perature for 3 h then poured onto
crushed ice (100 ml). The formed precipitate was
filtered, dried and crystallized from ethanol to give
yellow crystals of compound 10 b.
Method A: A mixture of aldehyde 2 (2.9 g, 10
mmol), benzil (2.1 g, 10 mmol) and ammonium
acetate (2.3 g, 30 mmol) in glacial acetic acid (40
ml) was refluxed for 3 h. The formed precipitate
was filtered, washed several times with water,
dried and cystallized from ethanol to give com-
pound 3.
Method B: A mixture of compound 4 [13] (4.0
g, 10 mmol), cyclohexanone, (1.0 g, 1.0 ml, 10
mmol) and piperidine (1 ml) in toluene (50 ml)
was boiled using Dean and Stark apparatus. The
solvent was evaporated in vacuo after removing
the calculated amount of water and the residue
was collected, dried and crystallized from ethanol
to give the same compound 3 [melting point and
R f = 0.37 (petroleum ether/ethyl acetate 8:1) are
the same].
Preparation o f compounds l l a - d
General procedure: A mixture of compound 2
(5 mmol) and equimolar ratio of hydroxylamine
hydrochloride or aniline or p-anisidine or /?-nitro
aniline in absolute ethanol (25 ml) was boiled for
a time 3 -5 h. A fter cooling the formed precipitate
was filtered washed with water, dried and crystal-
lized from ethanol to give colourless crystals of
compound 11a and yellow crystals of the corre-
sponding anils l l b - d .
Preparation of 6-[(benzimidazol-2'-yl) and 5'-ben-
Zoylbenzimidazol-2' -yl)]-7-hydroxy-5-methoxy-
2-pentamethylene chroman-4-one 5 a and 5 b
Method A: A mixture of compound 2 (2.9 g, 10
mmol) and o-phenylenediamine or 3,4-diamino-
benzophenone (10 mmol) was refluxed in dry bu-
tanol (30 ml) for 8 h. A fter cooling the formed
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913
E.-S. I. El-Desoky et al. • Synthesis of Some Chrom anone Derivatives and the Use of DNA
Table II. Spectral data of the newly prepared compounds.
Comp.
Spectral data
2
IR: v = 3518 (Free OH), 3480-3150 (bonded OH), 2931, 2850 (CH), 1675 (chromone C=0), 1660
(aldehyde C=0) and 1600 cm-1 (Ar).
3
IR: v = 3427 (OH), 3325 (NH), 2932, 2856 (CH), 1675 (C=0), 1610 (C=N) and 1598 cirr1 (Ar).
'H NMR (CDC13): <5= 1.2-2.1 (m, 10H 5xCH2), 2.7 (s, 2H, CH2) 4.0 (s, 3H, OMe), 6.5 (s, 1H, H-8),
7.3-7.6 (m, 10H, Ar-H) 10.5 (s, 1H, NH) and 13.6 ppm (s, 1H, OH).
5a
5b
IR: v = 3600-3100 (br. OH), 3365 (NH), 2928, 2850 (CH) 1660-1590 (br., C=N, C=0)
IR: v = 3600-3200 (br. OH), 3365 (NH), 2928, 2856 (CH), 1680-1600. (br., C=0 and C=N).
!H NMR (CDCI ): d = 1.5-2.1 (m, 10H, 5xCH2), 2.7 (s, 2H, COCH2), 4.0 (s, 3H, OMe), 6.5 (s, 1H,
3
H-8) and 7.4-8.1 ppm (m, 9H, Ar-H).
7a
7b
IR: v = 3344, 3281 (NH2), 3069 (OH), 3600-3180 (br. bonded OH), 1640 (C=0), 1605 (C=N) and 1590
cm-1 (Ar).
'H NMR (CDCI3): ö = 1.8 (s, 2H, NH2), 2.3 (s, 3H, CH3), 4.0 (s, 3H, OMe) 6.0 (s, 1H, H-3), 6.7 (s, 1H,
H-8), 7.2-7.5 (m, 4H, Ar-H), 9.1 (s, 1H, C//=N) and 14.5 ppm (s, 1H, OH).
IR: v - 3346, 3285 (NH2), 3063 (free OH), 3600-3100 (br. bonded OH), 1638 (br., two -(C =0), 1607
(C=N) and 1590 cm“1 (Ar).
'H NMR (DMSO): <5= 2.25 (s, 3H, OMe), 3.55 (s, 2H, NH2), 3.93 (s, 3H, OMe) 5.8 (s, 1H, H-3, 6.4 (s,
1H, H-8), 12-1.6 (m, 8H, Ar-H) and 10.5 ppm (br. s, 1H, OH).
8a
8b
IR: v = 3600-3100 (br. OH), 3360 (NH), 1651 (C=0) and 1600-1550 cm“1 (br. C=N and Ar).
*H NMR (CDCI3): d = 2.3 (s, 3H, CH3), 4.1 (3H, OMe), 6.1 (s, 1H, H-3) 6.8 (s, 1H, H-8), 7.3-7.8 (m,
5H, ArH and OH) and 10.8 ppm (s, 1H, NH).
IR: v = 3600-3150 (OH), 3343 (NH), 2924 (CH), 1655 (C=0, chromone), 1629 (ph C=0) and 1595
cm-1 (Ar).
*H NMR (CDC13): <5 = 2.3 (s, 3H, CH3), 4.1 (s, 3H, OMe), 6.0 (s, 1H, H-3), 6.8 (s, 1H, H-8), 7.4-7.9
(m, 8H, Ar-H), 8.2 (s, 1H, NH) and 11.1 ppm (d, 1H, OH).
9b
IR: v = 3370 (NH), 2918 (CH) and 1670-1560 cm“1 (br., C=0 and C=N).
*H NMR (DMSO): ö = 2.51 (s, 3H, COCH3), 3.84 (s, 3H, OMe) 6.36 (s, 1H, Ar-H), 7.57-7.86 (m, 7H,
Ar-H), 8.09 (s, 1H, Ar-H), 12.04 (s, 1H, NH) and 13.6 (s, br. 2H two OH).
IR: v = 3650-3100 (br. bonded OH), 2933, 2862 (CH), 1707 (C=0, chromone), 1645 (C=0, aldehyde)
and 1569 cm-1 (Ar).
10a
10b
IR: v = 3650-3150 (br. bonded OH), 2936, 2861 (CH), 1686 (C=0 chromone), 1638 (C=0 aldehyde),
and 1581 cm-1 (Ar).
'H NMR (DMSO): «5 = 1.4-2.1 (m, 10H, five CH2), 2.7 (s, 2H, CH2) 4.0 (s, 3H, OMe), 10.1 (s, 1H,
CHO) and 12.3 (s, 1H, OH).
11a
lib
IR: v = 3550-3250 (br. OH), 2926 (CH), 1661 (C-O) 1609 (C=N) and 1590 cm“1 Ar.
IR: v = 3600-3300 (br. bonded OH), 2936, 2856 (CH), 1674 (C=0, chromone), 1612 (C=N) and 1583
cm-1 (Ar).
‘H NMR (CDCI3): ö = 1.4-2.1 (m, 10H five CH2), 2.7 (s, 2H, CH2) 3.95 (s, 3H, OMe), 6.31 (s, 1H,
H-8), 7.3-7.5 (m, 5H, Ar-H) 8.96 (s, 1H, CH=N), 15.3 (s, 1H, OH).
IR: v = 2936, 2858 (CH), 1676 (C=0), 1613 (C=N) and 1591 cm' 1 (Ar).
'H NMR (CDC13): <3- 1.2-2.2 (m, 10H, five CH2), 2.6 (s, 2H, COCH2) 3.8 (s,3H, OMe), 3.9 (s,3H, OMe),
11c
6.3
(s, 1H, H-8), 6.9 (d, 2H, Ar-H), 7.2 (d, 2H, Ar-H), 8.8 (s, 1H, CH=N) and 15.5 ppm (s, br., OH),
lid
12a
IR: v = 3600-3350 (br. OH), 2932, 2856 (CH), 1676 (C=0) and 1620-1591 cm4 (br., C=N) and Ar).
IR: v = 3422, 3300, 3155 (NH2), 2939, 2860 (CH), 1682 (C-O) and 1600-1590 c irr1(br., C=N and Ar).
lH NMR (CDCI3): <3= 1.5-2.1 (m, 10H, five CH2), 2.7 (s, 2H, H-3), 3.7 (s, 3H, OMe), 5.7 (s, 1H, HN=
), 6.4 (s, 1H, H-10), 7.6 (s, 1H, H-6), 8.7, 8.9 ppm (2H, CONH2).
MS: M+ at m/z = 357; Mj at m/z = 313 from [M-HCONH2],
12b
12d
IR: v = 3580-3200 (br., OH), 2934, 2860 (CH), 1726 (COOEt) 1700, 1678 (C=0, lactone) and 1603
cm-1 (Ar).
IR: v = 3373, 3267, 3203 (NH2), 2928, 2850 (CH), 2211 (C=N), 1738 (COOEt), 1700, 1680 (C=0,
lactone) and 1574 c irr1 (Ar).
>H NMR (CDC13): 6 = 1.3 (t, 3H, C //3CH0), 1.5-2.1 (m, 10H, five CH2) 2.75 (s, 2H, H-3), 4.0 (s, 3H,
OMe), 4.3 (q, 2H, CH3CH2) 6.6 (s, 1H, H-10), 6.9 (s, 1H, H-6) and 8.6, 9.6 ppm (2H, NH2).
MS: M+ at m/z = 453; M1 at m/z = 410 [M -C 02].
17a
17c
17b
IR: v = 3600-3300 (br. OH), 1670 (C=0), 1626 (C=C) and 1586 cm"1 (Ar).
>H NMR (CDC13): (3 = 1.5-2.1 (m, 10H, five CH2), 4.2 (s, 3H, OMe), 5.4 (s, 1H, COC//=C6H10), 6.7
(s, 1H, H-7), 6.8 (d, 1H, H-3, J = 2.7 Hz), 7.4 (d, 1H, H-2, J = 2.7 Hz) and 13.1 ppm (s, 1H, OH which
disappeared when D20 was added).
MS: M+ at m/z = 286.2, M1 (base peak) at m/z = 191 [M+-C 7H 10] and M2 at m/z = 176 [M '-O -].
IR: v = 2925, 2844 (CH), 1670 (C=0), 1622 (C=C) and 1582 (Ar).
*H NMR (CDCI3): ö = 1.5 (t, 3H, C //3CH2), 1.55-2.1 (m, 10H five CH,), 4.5 (q, 2H, CH3C//2), 5.45
(s, 1H, COC//=C6H10) 6.7 (s, 1H, H-7), 6.8 (d, 1H, H-3, J = 2.7 Hz), 7.4 (d, 1H, H-2, J = 2.7 Hz) and
13.0 ppm (s, 1H, OH).
MS: M+ at m/z = 300.3; M1 at m/z = 205 [M+-C 7H10] and M2 at m/z = 177 (base peak) [M ^CO].
'H NMR (CDCI ): Ö = 1.6-2.3 (m, 10H, five CH2), 4.17 (s, 3H, OMe), 4.23 (s, 3H, OMe), 5.84 (1H,
3
COCH=C6H10), 6.93 (d, 1H, H-3, J = 2.7 Hz), 7.66 (d, 1H, H-2, J = 2.7 Hz) and 10.8 ppm (1H, OH).
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914
E.-S. I. El-Desoky et al. • Synthesis of Some Chrom anone Derivatives and the Use of DNA
Claisen p-Anisaldehyde
^
CHC6H4OMe-4'
15a-c
17a-c
a: R=H;
b: R=H;
c: R=OMe; R'=COOEt
R'=COOEt
R'=COCH3
a: R=H;
b: R=OMe; R'=CH3
c: R=H; R'=Et
R'=CH3
Scheme 4
Reaction o f compound 2 with active methylene
compounds: preparation o f compounds 12a,b,d
Method B: To a mixture of compound l a (2 g,
7 mmol) and /?-anisaldehyde (1.36 g, 10 mmol) in
ethanol (30 ml) was dropwise added sodium
ethoxide solution (1 g sodium/absolute ethanol 10
ml) at room tem perature with stirring. Stirring was
continued for 5 h then left at the same tem per-
ature overnight. The reaction mixture was poured
in crushed ice (100 g) then neutralized with dilute
hydrochloric acid. The precipitate that formed was
filtered, washed with water, dried and crystallized
from ethanol to give the same product 17 a [m.p.
and R f (petroleum ether/ethyl acetate 7:3) are
the same].
To a solution of compound 2 (1.7 g, 6 mmol)
and cyanoacetamide or diethyl m alonate (8 mmol)
or ethyl cyanoacetate (15 mmol) in absolute etha-
nol (30 ml) a few drops of triethyl amine was
added. The reaction mixture was heated for a time
from 4 -6 h. The colourless crystals that formed
after cooling was filtered and crystallized from
ethanol to give the corresponding benzodipyran
derivatives 12a,b,d.
Preparation o f benzofuran derivatives 17 a-c.
General procedure
D NA-binding assay
Method A: A solution of la or lb ( l g ) in
diethylcarbonate (10 ml) was slowly added to
powdered sodium metal (1 g). W hen the initial
vigorous reaction subsided, the reaction mixture
was refluxed for 5 h then left to cool. Ethanol
(10 ml) was added to destroy any excess of so-
dium metal. The reaction mixture was poured on
water then acidified with dilute hydrochloric acid
and the solid that separated was crystallized
from ethanol to give compound 17 a and 17 b,
respectively.
The mechanism of several known antitum or
agents involves interaction with DNA. Examples
include agents (e.g. chlorabucil, cyclophospha-
mide, melphalan, streptozocin), antitumor anti-
biotics (e.g. bleomycin, doxorubicin, mithramycin)
[17-20], Some of the new compounds were
screened towards the affinity to DNA-binding
using a colorimetric assay [21]. Compound 12a
showed the highest affinity, compound 2 followed
by compound 10 b are the most inactive while the
compounds 7 a, 8 a, 9 b, 10 a, llb ,c and 12 d are
equally active but less than 12 a.
N.B.: Compound 17c was prepared from l a and
ethylacetate following the same procedure.
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E.-S. I. El-Desoky et al. • Synthesis of Some Chrom anone Derivatives and the Use of DNA
915
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