Design, synthesis, synergistic antimicrobial activity and cytotoxicity of 4-aryl substituted 3,4-dihydropyrimidinones of curcumin

Article abstract of DOI:10.1016/j.bmcl.2012.02.056

3,4-Dihydropyrimidinones of curcumin were synthesized in excellent yield by multi-component one-pot condensation of curcumin, substituted aromatic aldehydes and urea/thiourea under solvent free conditions using SnCl ₂·2H₂O catalyst. All the synthesized compounds have been characterized by IR, ¹H NMR, ¹³C NMR, Mass spectra as well as elemental analyses. The synthesized compounds 4a-n were evaluated for their synergistic antimicrobial (antibacterial and antifungal) activity against bacteria and fungi. Zone of inhibition was measured by adopting disc diffusion method. In vitro minimum inhibitory concentrations were measured using broth microdilution and food poisoning method. In addition to this in vitro cytotoxicity of synthesized compounds against three human cancer lines Hep-G2, HCT-116 and QG-56 were also evaluated. Most of the compounds showed interesting antimicrobial and cytotoxic activity as compared to curcumin, that is, the compounds derived from 2-hydroxy benzaldehyde, 4-hydroxy benzaldehyde and 4-hydroxy-3-methoxy benzaldehyde showed the highest biological activity as compared to other compounds.

Full text of DOI:10.1016/j.bmcl.2012.02.056

Bioorganic & Medicinal Chemistry Letters 22 (2012) 2872–2876
Contents lists available at SciVerse ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Design, synthesis, synergistic antimicrobial activity and cytotoxicity
of 4-aryl substituted 3,4-dihydropyrimidinones of curcumin
Jaggi Lal a,b, , S.K. Gupta a, D. Thavaselvam c, D.D. Agarwal a
⇑
a School of Studies in Chemistry, Jiwaji University, Gwalior 474 011, India
b Department of Industrial Chemistry, Jiwaji University, Gwalior 474 011, India
c Microbiology Division, Defense Research & Development Establishment, Jhansi Road, Gwalior 474 002, India
a r t i c l e i n f o
a b s t r a c t
Article history:
3,4-Dihydropyrimidinones of curcumin were synthesized in excellent yield by multi-component one-pot
condensation of curcumin, substituted aromatic aldehydes and urea/thiourea under solvent free condi-
tions using SnCl2ꢀ2H2O catalyst. All the synthesized compounds have been characterized by IR, 1H
NMR, 13C NMR, Mass spectra as well as elemental analyses. The synthesized compounds 4a–n were eval-
uated for their synergistic antimicrobial (antibacterial and antifungal) activity against bacteria and fungi.
Zone of inhibition was measured by adopting disc diffusion method. In vitro minimum inhibitory concen-
trations were measured using broth microdilution and food poisoning method. In addition to this in vitro
cytotoxicity of synthesized compounds against three human cancer lines Hep-G2, HCT-116 and QG-56
were also evaluated. Most of the compounds showed interesting antimicrobial and cytotoxic activity
as compared to curcumin, that is, the compounds derived from 2-hydroxy benzaldehyde, 4-hydroxy
benzaldehyde and 4-hydroxy-3-methoxy benzaldehyde showed the highest biological activity as com-
pared to other compounds.
Received 3 October 2011
Revised 16 February 2012
Accepted 21 February 2012
Available online 27 February 2012
Keywords:
3,4-Dihydropyrimidinone analogues of
curcumin
Zone of inhibition
MIC
IC50
Cytotoxicity
Ó 2012 Elsevier Ltd. All rights reserved.
Turmeric (Curcuma longa L.) is a herbaceous plant of Zingibera-
ceae family, originating from India and Southeast Asia. The pow-
dered rhizome of turmeric is widely used as spice and coloring
agent in food by virtue of its yellowish-orange color and pleasant
aroma.1 Yellowish orange color present in turmeric is chemically
1,6-heptadiene-3,5-dione-1,7-bis(4-hydroxy-3-methoxy phenyl)-
(1E,6E) or diferulolylmethane. The ferulolylmethane skeleton of
curcumin was confirmed and synthesized by Lampe in 1910. It is
insoluble in water and ether whereas soluble in ethanol, methanol,
acetone, dimethylsulfoxide, chloroform and dichloromethane. Cur-
cumin exists in enolic and b-diketonic forms.2 This form is utilized
in the synthesis of 3,4-dihydropyrimidinone analogues of curcu-
min. Curcumin and its derivatives possess a wide variety of phar-
macological activity viz., antibacterial,3 antifungal,4 antiviral,5
anti-HIV,6 anti-inflammatory,7 anti-Parkinson’s,8 anti-Alzheimer’s,9
anti-angiogenesis,10 free radical scavenging activity,11 anti-
rheumatic,12 antimalarial,13 anticancer,14 antiprotozoan,15 anti-
mutagenic,16 wound treatment,17 hepatoprotective activity,18
anti-leishmanial activity19 and amyloid heart disease.20 In
addition to curcumin, resulted 3,4-dihydropyrimidinones also
possess various pharmaceutical properties such as antibacterial,21
antiviral,22 and antioxidant.23 Looking into the biological signifi-
cance of curcumin and resulted dihydropyrimidinone analogues,
it was decided to synthesized, characterized and evaluate their
biological activity. Curcumin also inhibits bacterial lipopolysaccha-
ride-induced TNF-
nuclear factor kappa B (NF-
a
over expression and the transcription factor
B) activation which are involved
j
in several pathogen-infected diseases.24 Preclinical and clinical
studies showed that, however, curcumin possesses several disad-
vantages in pharmacokinetics such as poor bioavailability, fast
metabolism and requires repetitive oral dosages.25 However,
curcumin is still an excellent lead compound for drug design and
development on the basis of explicit bioactivities, non-toxicity
and easy synthesis.26
In this study, isolation, derivatization and biological assessment
of curcumin have been done against standard bacterial strains such
as Escherichia coli, Burkholderia pseudomallei, Pseudomonas aeuri-
ginosa, Salmonella typhi and Staphylococcus aureus, and fungal
strains viz., Aspergillus niger, Aspergillus flavus, Trichoderma viride
and Curvularia lunata by adopting disc diffusion, broth micro dilu-
tion and food poisoning method. Cytotoxicity of the synthesized
derivatives were also evaluated against human cancer lines (hep-
ato carcinoma, colon carcinoma and lung carcinoma) using stan-
dard MTT assay. To the best of our knowledge, antibacterial,
antifungal and cytotoxicity of 3,4-dihydropyrimidinones of curcu-
min are not yet reported.
Targeted compounds 4a–n were synthesized27 (Table 1) in
excellent yield (92–97%) as outlined in Scheme 1 by condensation
of aromatic aldehydes (1), urea/thiourea (2) and curcumin (3) in
the presence of SnCl2ꢀ2H2O under solvent free conditions using
⇑
Corresponding author. Tel.: +91 9039035228.
E-mail address: jaggitajagra@gmail.com (J. Lal).
0960-894X/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.bmcl.2012.02.056

J. Lal et al. / Bioorg. Med. Chem. Lett. 22 (2012) 2872–2876
2873
Table 1
Synthesis of 4-aryl substituted 3,4-dihydropyrimidinones of curcumina
Heat of formationd
(D
Hꢁf )
Entry
Compound
R
X
Time (min)
Mpb (°C)
Yieldc (%)
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
C6H5
4-Cl–C6H4
O
O
O
O
O
O
O
O
S
S
S
S
S
80
80
90
80
90
90
90
90
80
80
90
80
90
90
206–208
201–203
198–199
210–212
225–226
272–273
151–152
158–160
219–220
202–204
278–279
281–282
294–296
261–263
97
94
96
92
94
96
95
92
95
96
94
92
93
93
ꢂ372.26
ꢂ399.47
ꢂ425.65
ꢂ536.59
ꢂ713.90
ꢂ549.57
ꢂ549.57
ꢂ409.37
ꢂ368.86
ꢂ368.23
ꢂ391.89
ꢂ582.45
ꢂ656.87
ꢂ501.21
4-NO2–C6H4
4-OCH3–C6H4
4-OH-3-OCH3–C6H3
2-OH–C6H4
4-OH–C6H4
4-CH3–C6H4
C6H5
9
10
11
12
13
14
4-Cl–C6H4
4-NO2–C6H4
4-OCH3–C6H4
4-OH-3-OCH3–C6H3
4-OH–C6H4
S
a
Reaction conditions: curcumin (2 mmol), aromatic aldehydes (2 mmol), urea/thiourea (2 mmol), (0.02 mmol) SnCl2ꢀ2H2O as catalyst, solvent free conditions for about 80–
90 min at 80 °C.
b
Melting points were uncorrected.
Isolated yield.
c
d
Heat of formation was calculated using commercially available semiempirical program package Ampac/Mopac (version 6.0) and measured in kJ/mol.
Scheme 1. Synthesis of 3,4-dihydropyrimidinones of curcumin under solvent free conditions.
Scheme 2. Mechanism of curcumin 3,4-dihydropyrimidinone synthesis.
conventional heating, that is, without microwave irradiations.
Banik28 et al. reported the synthesis of 4-aryl substituted 3,4-
dihydropyrimidinones under microwave irradiations using tradi-
tional dicarbonyl moieties in place of curcumin. In this reaction
in the presence of catalyst, initially urea reacts with substituted
aromatic aldehydes to form Schiff’s base (Scheme 2), which fur-
ther reacts with curcumin to form targeted products (4a–n). In
the present reaction curcumin is used as dicarbonyl moiety in
place of traditional dicarbonyl moieties such as acetyl acetone
and ethyl acetoacetate. Heat of formation (D
Hꢁf ) for all the re-
ported compounds (4a–n) has been calculated (Table 1) using
commercially available semiempirical program package Ampac/
Mopac (version 6.0). Negative values of heat of formation for all
the compounds showed exothermic reaction. Compounds derived
from 4-hydroxy-3-methoxy benzaldehyde (4e & 4m) in both
cases (urea/thiourea) have greater heat of formation than other
compounds, heat of formation decreases in case of thiourea
derivatives.

2874
J. Lal et al. / Bioorg. Med. Chem. Lett. 22 (2012) 2872–2876
The computed molecular structure (ball and stick representa-
in lM/ml in Mueller–Hinton broth (Table 2). The antibacterial
tion) of curcumin and its 3,4-dihydropyrimidinone derivative,
revealing the relative stereochemistry has been represented in
Figure 1.
All compounds were spectroscopically characterized and the
spectral data agree with the proposed structures.
activity of curcumin dihydropyrimidinone analogues were com-
pared with curcumin isolated from Curcuma longa and ampicillin
as standard antibiotic reference drug by known micro dilution
broth susceptibility test method. The lowest concentration of cur-
cumin dihydropyrimidinones in
lM/ml that prevent in vitro
Theoretical physico-chemical parameter, ClogP values were
calculated using commercially available ChemDraw Ultra 8.0.3,
for all synthesized compounds (4a–n) ranged from 2.8 to 5.1. The
thumb rule for ClogP values must be lowers than ‘5’ to by-pass
the cell barrier.29 The ClogP values seem to correlate to some ex-
tent with lipophilicity. Most of the compounds in the designed ser-
ies showed ClogP values less than 5 (Table 3).
The newly synthesized curcumin 3,4-dihydropyrimidinones
(4a–n) were evaluated for their in vitro antibacterial activity
against five bacteria specially causing secondary infections in hu-
man being viz. Staphylococcus aureus, Escherichia coli, Burkholderia
pseudomallei, Salmonella typhi and Pseudomonas aeuriginosa. Zone
of inhibition in mm was measured using disc diffusion method
(Table 2). Minimum inhibitory concentration (MIC) was measured
growth of microorganism has been represented as MIC (minimum
inhibitory concentration) (Tables 2 and 3). In case of E. coli, com-
pounds 4b, 4c, 4e–g, 4i and 4n (MIC 20–40) showed antibacterial
activity with better zone of inhibition at concentrations (20, 40,
80 and 160 lM/ml) in comparison to curcumin (MIC 40); com-
pound 4k (MIC 160) does not show any zone of inhibition and
was completely inactive. All the remaining compounds were less
active comparatively but more active than curcumin. Compounds
4a, 4d, 4e, 4g, 4i, 4l–n (MIC 20–40) showed better antibacterial
activity against B. pseudomallei in comparison to curcumin whereas
remaining compounds are moderately active and compound 4b
(MIC 160) was totally inactive. In case of P. aeuriginosa; compounds
4e and 4j (MIC 160) were totally inactive whereas compounds 4c,
4d, 4f, 4g, 4i, 4l and 4n (MIC 40) showed much antibacterial
Figure 1. The computed molecular structure (ball and stick representation) of curcumin (A), and 3,4-dihydropyrimidinone derivative (B) of curcumin clearly revealing the
relative stereochemistry.
Table 2
Zone of inhibitiona and MICb correlation diagram of curcumin dihydropyrimidinones against bacterial strains
Compound
Name of bacteria
P. aeuriginosa
E. coli
B. pseudomallei
S. typhi
S. aureus
Zone of Inhibition
MIC
Zone of Inhibition
MIC
Zone of Inhibition
MIC
Zone of Inhibition
MIC
Zone of Inhibition
MIC
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
17, 9, —, —
19, 16, 11, 9
18, 16, 15, 12
12, 9, —, —
19, 17, 14, 11
22, 19, 18, 15
22, 18, 14, 12
11, 9, —, —
21, 18, 14, 12
19, 15, 9, —
—
18, 14, 9, —
14, 11, 9, —
22, 18, 17, 13
10, 8, —, —
34, 32, 30, 30
40
40
40
80
20
20
20
80
20
80
160
40
40
20
40
20
19, 17, 16, 14
—
40
160
80
40
40
40
40
40
40
80
80
20
40
40
80
80
14, 12, 9, —
9, —, —, —
19, 18, 14, 9
23, 21, 19, 13
—
24, 21, 19, 18
22, 19, 19, 17
10, —, —, —
18, 17, 14, 12
—
10, 9, —, —
23, 20, 19, 18
14, 11, 9, —
18, 14, 12, 9
11, 9, —, —
39, 36, 34, 31
20
160
40
40
160
40
40
40
40
160
40
40
80
40
80
40
11, 8, —, —
11, 9, —, —
10, —, —, —
—
22, 19, 16, 13
—
18, 16, 13, 9
11, 9, —, —
—
22, 19, 17, 13
10, —, —, —
—
80
80
40
80
80
40
20
40
80
40
40
40
40
80
80
20
22, 19, 17, 14
12, 10, —, —
11, 10, —, —
—
—
—
24, 22, 19, 16
—
—
16, 13, 11, 9
12, 10, —, —
—
11, 9, —, —
12, 10, —, —
—
40
320
80
80
40
160
20
80
80
40
80
80
40
80
80
40
12, 10, —, —
23, 19, 15, 11
16, 16, 14, 10
19, 13, 11, —
19, 15, 11, 9
10, 9, —, —
18, 16, 13, 11
16, 12, 9, —
11, 9, —, —
24, 21, 19, 16
21, 18, 16, 13
19, 17, 16, 14
9, 8, —, —
14, 12, 9, —
—
12, 10, 9, —
51, 45, 44, 37
cCurcumin
dAmpicillin
46, 41, 39, 38
37, 30, 29, 28
(—) Resistant.
a
Zone of inhibition measured in mm at concentrations 160, 80, 40 and 20
l
M/ml.
b
c
MIC (minimum inhibitory concentrations) were measured in
Isolated from Curcuma longa.
lM/ml.
d
Purchased from HiMedia Pvt. Ltd.

J. Lal et al. / Bioorg. Med. Chem. Lett. 22 (2012) 2872–2876
2875
Table 3
Zone of inhibitiona and MICb correlation diagram of curcumin dihydropyrimidinones against fungal strains
Compound
Name of fungi
ClogPe
Aspergillus niger
Zone of Inhibition
Aspergillus flavus
Zone of Inhibition
Curvularia lunata
Zone of Inhibition
18, 12, 9, —
22, 18, 12, 9
11, 9, —, —
17, 16, 14, 11
21, 18, 17, 13
23, 21, 20, 17
21, 20, 20, 18
22, 18, 16, 12
26, 23, 21, 18
15, 13, 12, 9
21, 19, 17, 14
24, 21, 18, 16
24, 22, 21, 19
24, 22, 21, 20
11, 9, —, —
Trichoderma viride
Zone of Inhibition
MIC
MIC
MIC
MIC
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
9, —, —,—
12, —, —, —
—
11, 9, —, —
—
13, 11, 9, —
11, 9, —, —
12, 9, —, —
16, 14,—,—
11, 9, —,—
13, 11, 9, —
11, 9, —, —
16, 12, 11, 9
14, 11, 9, —
—
40
160
160
80
160
80
40
20
20
80
80
40
40
40
—
11, 9, —, —
—
—
—
80
160
80
40
80
80
40
80
80
80
80
40
40
40
—
80
40
40
40
40
40
20
40
40
40
40
40
40
40
80
20
14, 11, 9, —
80
40
40
40
40
40
20
40
40
40
40
40
20
80
80
20
4.3
5.0
4.1
4.3
3.5
3.6
2.8
4.8
4.4
5.1
4.2
4.3
3.6
3.7
2.5
---
18, 17, 17, 15
21, 21, 19, 17
19, 17, 16, 14
21, 18, 16, 15
11, 9, —, —
16, 14, 11, 9
18, 16, 15, 12
24, 21, 21, 18
24, 22, 19, 18
22, 21, 18, 17
23, 19, 18, 17
13, 11, 9, —
—
9, —, —, —
13, 11, 9, —
—
9, —, —, —
9, —, —, —
11, —, —, —
9, —, —, —
11, —, —, —
15, 13, 11, 9
—
20, 17, 14, 11
9, —, —, —
32, 29, 24, 21
Curcuminc
Fluconazoled
—
—
—
80
31, 28, 27, 24
(—) Resistant.
--- ClogP not determined.
a
Zone of inhibition measured in mm at concentrations 160, 80, 40 and 20
l
M/ml.
b
c
MIC (minimum inhibitory concentrations) were measured in
Isolated from Curcuma longa.
lM/ml.
d
e
Purchased from HiMedia Pvt. Ltd.
Theoretical values ClogP were calculated using commercially available ChemDraw Ultra 8.0.3.
activity with better zone of inhibition as comparison to remaining
compounds, but were more active than curcumin (MIC 80).
Compounds 4e, 4g, 4j (MIC 20–40) showed much better activity
as compared to curcumin (MIC 80) whereas compounds 4d, 4f,
4i, 4l and 4n (MIC 80–160) were completely inactive and remain-
ing compounds showed moderate activity against S. typhi. For S.
aureus compounds 4d–f, 4h, 4i and 4l (MIC 80) do not show any
zone of inhibition and were totally inactive and compounds 4a,
4g, 4j (MIC 40–80) were more active than curcumin (MIC 80),
whereas remaining compounds showed moderate antibacterial
activity. No significant antibacterial activity was observed for
electron donating and electron withdrawing moieties.
synthesized curcumin derivatives as shown in Table 4. Sulfur con-
taining dihydropyrimidinones exhibited higher cytotoxicity than
oxygen containing compounds. All the compounds 4a–n exhibited
anticancer activity with IC50 values ranging from <12.5 to 100
ml, while the positive control, adriamycin demonstrated the IC50 in
the range of <2.5 to 5.0 M/ml. The significant anticancer activity
lM/
l
showed by the compound derived from 2-hydroxy benzaldehyde
4g against HCT-116: human colon carcinoma.
In conclusion, the presented work demonstrates the isolation of
curcumin. Curcumin thus obtained was utilized in the three com-
ponent synthesis as a dicarbonyl moiety in place of acetyl acetone
Antifungal activity of the synthesized products 4a–n was eval-
uated against four human pathogenic fungal cultures viz. Aspergil-
lus niger, Aspergillus flavus, Trichoderma viride and Curvularia lunata.
Zone of inhibition was measured in mm by disc diffusion method
using potato dextrose agar (PDA) (Table 3) and minimum inhibi-
tory concentration was measured using food poisoning method.
In the case of fungi it is clear that synthesized compounds were
more effective against Aspergillus niger and Aspergillus flavus, but
the standard antifungal agent fluconazole and curcumin obtained
from Curcuma longa were ineffective against both these species
and no activity was observed. Most of the compounds exhibited
significant antifungal activity against Trichoderma viride and Curvu-
laria lunata (Table 3). When tested against C. lunata and T. viride
compounds 4b, 4d–n (MIC 40–80) showed better antifungal activ-
ity and compounds 4a & 4c (MIC 40–80) showed moderate activity,
and all compounds tested were more active than curcumin. For T.
viride compounds 4b–e, 4g–l and 4n (MIC 20–40) showed better
activity with greater zone of inhibition and remaining compounds
4a, 4f, 4m (MIC 40–80) showed moderate activity. Like bacteria
there is no significant activity was observed for electron donating
and electron withdrawing moieties in case of fungus.
Table 4
Cytotoxicity evaluation of curcumin dihydropyrimidinones against three carcinoma
cell lines (IC50
l
M/ml)a
Compound
Cytotoxicity (IC50
HCT-116c
)
Hep-G2b
QG-56d
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
50
25
100
50
100
100
100
12.5
50
100
50
100
50
100
50
50
50
100
100
50
25
100
25
50
50
100
50
100
50
100
100
50
50
100
50
100
50
100
50
50
100
50
4m
4n
100
50
2.5
Curcumine
100
2.5
Adriamycinf
5.0
a
IC50, concentration of drug that decreases the cell viability by 50% compared to
non-treated control cells.
The 3,4-dihydropyrimidinone analogues 4a–n synthesized
above were evaluated in vitro cytotoxicity using three selected
human tumor cell lines Hep-G2, HCT-116 and QG-56 using the
standard MTT assay. Inhibitory activities (IC50) were presented in
b
Hep-G2: human hepato carcinoma.
HCT-116: human colon carcinoma.
QG-56: human lung carcinoma.
Isolated from Curcuma longa.
c
d
e
f
micro molar per milliliter
(lM/ml) concentrations of the
Control drug.

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25. Lin, L.; Shi, Q.; Su, C. Y.; Shih, C. C.; Lee, K. H. Bioorg. Med. Chem. 2006, 14, 2527.
26. Park, B. S.; Kim, J. G.; Kim, M. R.; Lee, S. E.; Takeoka, G. R.; Oh, K. B.; Kim, J. H. J.
Agric. Food Chem. 2005, 53, 9005.
Acknowledgments
The authors are indebted to Madhya Pradesh Council of Science
and Technology, Bhopal for financial support (Grant No. 4468/CST/
R&D/2010), the Director, Defense Research & Development Estab-
lishment, Jhansi Road, Gwalior-474 002 (M.P.), for carrying out bio-
logical activity of the synthesized compounds.
27. Selected synthetic procedure (4a–n): A 100 ml round bottom flask was charged
with curcumin (2 mmol), substituted aryl aldehyde (2 mmol), urea/thiourea
(2 mmol) and (0.02 mmol) SnCl2ꢀ2H2O as catalyst was heated at 80 °C under
solvent free conditions for about 80–90 min. The reaction was monitored by
TLC using acetone/hexane (4:6) as eluent. After completion the reaction, the
contents were dissolved in ethanol and stirred for about 10 min. The product
was recrystallized from appropriate solvent. Selected characterization data
(4a): 97%, dark red powder, soluble in ethanol and methanol, stable at room
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.bmcl.2012.02.056.
temperature, Rf (acetone/hexane 7:3) 0.26; IR (m
cmꢂ1, KBr) 3500, 3213, 2937,
1593, 1514, 1435, 1276, 1031, 962; 1H NMR (400 MHz in CDCl3) d 3.93 (s, 6H,
30, 300, OCH3), 5.79 (s, 2H, 40,400, OH), 7.58 (d, J = 15.76 Hz, 2H, H-1,7), 6.47 (d,
J = 15.76 Hz, 2H, H-50, 500), 6.92 (d, J = 8.61 Hz, 2H, H-20, 200), 7.19 (m, 5H, C6H5),
5.39 (d, J = 10.44 Hz, 1H, CH), 7.41 (s, 1H, NH), 8.04 (1H, NH); 13C NMR
(400 MHz in DMSO d6) 48.10, 56.02, 115.46, 112.31, 115.46, 124.06, 126.17,
128.68, 143.22, 144.64, 149.03, 151.46, 152.70, 192.11; MS (ESI) (m/z) 498
(M+); Anal. Calcd for C29H26O6N2: C, 69.87; H, 5.26; N, 5.62. Found: C, 69.89; H,
5.24; N, 5.59.
References and notes
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