Synthesis of novel macrolides-linked chalcone derivatives and recognition ability toward Cu2+

Article abstract of DOI:10.1007/s11164-013-1510-8

A series of novel macrolides-linked chalcone derivatives 2a-c and 3a-d were synthesized from compounds 1a-d with 1,2-benzenedicarbonyl chloride. Their structures were confirmed by IR, ¹H NMR, and high resolution mass spectrometry. The crystal s

Full text of DOI:10.1007/s11164-013-1510-8

Res Chem Intermed
DOI 10.1007/s11164-013-1510-8
Synthesis of novel macrolides-linked chalcone
derivatives and recognition ability toward Cu2+
•
•
•
Meipan Yang Xianwen Fang Shaoni Li
Bingqin Yang
Received: 2 October 2013 / Accepted: 9 December 2013
Ó Springer Science+Business Media Dordrecht 2013
Abstract A series of novel macrolides-linked chalcone derivatives 2a–c and 3a–d
were synthesized from compounds 1a–d with 1,2-benzenedicarbonyl chloride. Their
1
structures were confirmed by IR, H NMR, and high resolution mass spectrometry.
The crystal structure of compound 2a was characterized by single crystal X-ray
diffractometry. The ions recognition experiments were carried out and showed that
the title compound 3d displayed selective recognition toward Cu2?
.
Keywords Synthesis ꢀ Macrolides-linked chalcone ꢀ Crystal structure ꢀ Cu2?
Introduction
Chalcones, considered as key precursors for flavonoid and isoflavonoid, are widely
present in fruits, vegetables, spices, tea, and soy-based foodstuffs [1]. Chalcones
form an important group of secondary plant metabolites. This class of compounds,
with a common 1,3-diphenyl-2-propen-1-one framework (Fig. 1), demonstrates
extensive pharmacological activities, such as anti-cancer, anti-tuberculosis, anti-
inflammatory, and antiprotozoal [2–5]. In particular, chalcone systems usually show
different levels of inhibition [6–9]. The synthetic methods of chalcones are mainly
by condensing aryl ketones with aromatic aldehydes in the presence of suitable
catalysts. Xia et al. [10] synthesized the novel 20-amino chalcone, which had high
activity towards the multi-drug resistant KB-VIN and the ovarian 1A9 cell lines
(Fig. 2).
Electronic supplementary material The online version of this article (doi:10.1007/s11164-013-1510-8)
contains supplementary material, which is available to authorized users.
M. Yang ꢀ X. Fang ꢀ S. Li ꢀ B. Yang (&)
Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education,
College of Chemistry & Materials Science, Northwest University, Xi’an 710069, China
e-mail: ymp1111@163.com; yangbq@nwu.edu.cn
123

M. Yang et al.
Fig. 1 General framework of
chalcone
O
O
Fig. 2 Chemical structure of a
novel chalcone
O
O
O
NH2
In addition, the development of chalcones for recognizing ions have become an
important area of supramolecular chemistry because of the highly flexible nature of
chalcone’s conjugate structure, such as b-cyclodextrin [11]. Obviously, the structure
modification of chalcones has become the tendency of chalcone’s research, which
leads to the improvement of their bioavailability and other attributes.
Macrolides generally refer to the compounds that have 12 or more rings
containing at least one ester bond, which are important structural units due to their
significant and diverse biological and medicinal properties. So far, scientists have
synthesized a wide variety of macrolides, serving as antibiotics, spices, insecticide,
herbicides, etc. [12–14]. What is more, macrolides have been developing quickly on
the recognition of various ions for the rich heteroatoms of the structure. Chhatra
et al. [15] synthesized a bile acid-based click-macrocycle and studied its application
in selective recognition of chloride ion. Kumar et al. [16] synthesized a pyridine-
based diamide–diester 18-membered macrocycle, which showed remarkable
selectivity in binding of silver (Fig. 3a). Burke and Zhao [17] showed a novel
macrolide which displayed selective recognition toward the potassium ion (Fig. 3b).
They also studied the binding mode and mechanism between macrolide and ion.
In recent years, it has become a focus in related research that chalcones on
incorporation with different biologically active scaffolds and some supramoleculars
can be used to explore more potent and novel activities [18–20]. But, to the best of
our knowledge, there have so far been no literature reports about linking macrolides
to the chalcone framework. In our present study, we designed and synthesized a
series of macrolides-linked chalcone derivatives, then conducted their recognition
experiments toward ions. Further studies of biological activities will be conducted
in the future.
Experimental
Chemistry
The chemicals used for synthesis were commercially available and were used as
supplied. Dichloromethane and pyridine were distilled over calcium hydride.
Melting points are uncorrected and determined by XT-4 micro melting point
1
apparatus. H NMR spectra were recorded on an INOVA-400 NMR spectrometer
and chemical shifts are reported in parts per million (ppm, d) relative to TMS as an
123

Novel macrolides-linked chalcone derivatives
Me
Fig. 3 Structures of selected
macrolide compounds
O
O
O
Me
O
O
N
H
3C
H
H
CH3
N
O
N
O
O
O
O
H
O
Me
H
O
Me
H
H
O
N
O
O
Me
Me
(a)
(b)
internal standard. IR spectra were obtained on an EQUINOX-55 FTIR spectrometer
using KBr pellets and values are expressed in cm-1. ESI–MS data were recorded on
an AXIMA-CFRTM plus MALDI-TOF mass spectrometer. Column flash chroma-
tography was carried out on Merck silica gel (250–400 mesh ASTM). Thin-layer
chromatography (TLC) was performed on silica gel GF254. Absorbance spectra
measurements were carried out on a Shimadzu UV-1700 Spectrophotometer. The
inorganic salts were purchased from Alfa Aesar Chemical Reagent (Tianjin, China).
Synthesis
[N,N-Bis(2-hydroethyl)-3-amino] acetophenone (A)
A mixture of 3-aminoacetophenone (47.5 mmol), 2-chloroethanol (240 mmol), and
CaCO3 (65 mmol) in water (60 mL) was heated under reflux with vigorous stirring
for 7 h. After hot filtering, the unreacted CaCO3 was washed with a few portions of
hot water; then, the filtrate was extracted with CH2Cl2 (40 mL 93), dried over
anhydrous MgSO4, and concentrated under reduced pressure to afford a yellow oil.
The residue was further purified by SiO2 flash column chromatography to give the
1
required diol A. Yield: 68 % of faint yellow liquid; H NMR (400 MHz, CDCl3) d
7.20–7.24 (m, 3H, ArH), 6.85–6.87 (m, 1H, ArH), 4.74 (s, 2H, –OH), 3.77 (s, 4H,
–OCH2–), 3.53–3.54 (d, 4H, J = 4.8 Hz, –NCH2–), 2.49 (s, 3H, –CH3); IR (cm-1
,
KBr): 3,378, 2,933, 2,880, 1,673, 1,597, 1,494, 1,444, 1,357, 1,267, 1,178, 1,010,
779, 688; high resolution mass spectrometry (HRMS) calcd for C12H17NO3:
246.1101 (M?Na)?; Found: 246.1105.
General procedure for the preparation of 1
To a solution of [N,N-bis(2-hydroethyl)-3-amino]acetophenone A (5 mmol) and
substituted aldehydes (5 mmol) in ethanol (20 mL), a solution of 2.5 M sodium
hydroxide (1 mL) was added slowly within 20 min in an ice bath. The formed
precipitate was gradually left, and the reaction was monitored by TLC. After
completion of the reaction, the mixture was extracted with CH2Cl2 (10 mL 93) and
dried over Na2SO4. The solvent was evaporated under reduced pressure. Then, the
residue was purified by flash column chromatography on silica gel. The yield,
melting point, and spectral data of each compound were collected as below.
123

M. Yang et al.
1
Chalcone derivative 1a Yield: 86 % of faint yellow solid, mp 105–107 °C; H
NMR (400 MHz, CDCl3): 7.78 (1H, d, J = 15.4 Hz, H16), 7.54 (2H, d,
J = 8.2 Hz, H17 and ArH), 7.34 (4H, d, J = 23.5 Hz, ArH), 6.89 (1H, s, ArH),
6.68 (2H, d, J = 8.1 Hz, ArH), 3.79 (4H, d, J = 6.1 Hz, –CH2Cl), 3.67 (4H, d,
J = 6.2 Hz, –NCH2–), 3.03 (6H, s, –N(CH3)2). IR (cm-1, KBr): 2,923, 2,855,
1,644, 1,605, 1,559, 1,521, 1,440, 1,360, 1,170, 810, 728. HRMS calcd for
C21H24Cl2N2O: 391.1349 (M?H)?; Found: 391.1338.
1
Chalcone derivative 1b Yield: 83 % of yellow solid, mp 74–75 °C; H NMR
(400 MHz, CDCl3) d 7.54–7.48 (m, 2H), 7.35 (d, J = 15.4 Hz, 1H), 7.27 (m, 3H),
6.87 (dd, J = 7.7, 3.9 Hz, 1H), 6.70 (d, J = 3.2 Hz, 1H), 6.49 (dd, J = 3.2, 1.6 Hz,
1H), 4.52 (s, 2H), 3.80 (t, J = 4.8 Hz, 4H), 3.57 (t, J = 4.7 Hz, 4H). IR (cm-1, KBr):
3,229, 2,945, 2,884, 1,661, 1,592, 1,486, 1,451, 1,346, 1,220, 1,182, 1,058, 1,008, 971,
760, 724, 687. HRMS calcd for C17H20NO4: 302.1387 (M?H)?; Found: 302.1383.
1
Chalcone derivative 1c Yield: 85 % of yellow solid, mp 73–75 °C; H NMR
(400 MHz, CDCl3): d 7.84 (d, J = 15.3 Hz, 1H), 7.39 (d, J = 4.1 Hz, 1H), 7.32 (s,
1H), 7.30–7.19 (m, 4H), 7.06 (s, 1H), 6.86 (d, J = 7.6 Hz, 1H), 4.60 (s, 2H), 3.81 (s,
4H), 3.57 (s, 4H); IR (cm-1, KBr): 3,073, 2,924, 2,852, 1,653, 1,573, 1,492, 1,456,
1,277, 1,182, 1,063, 1,004, 971, 780, 721; HRMS calcd for C25H21NO5S: 470.1033
(M?Na)?; Found: 470.1041.
1
Chalcone derivative 1d Yield: 85 % of orange-yellow solid, mp 69–71 °C; H
NMR (400 MHz, CDCl3): 8.57 (dd, J = 44.4, 3.9 Hz, 1H), 8.00 (d, J = 15.4 Hz,
1H), 7.72 (dd, J = 15.1, 11.6 Hz, 2H), 7.48 (d, J = 7.7 Hz, 1H), 7.39 (d,
J = 7.5 Hz, 1H), 7.34–7.28 (m, 3H), 6.90 (dd, J = 8.1, 1.9 Hz, 1H), 4.31 (d,
J = 6.6 Hz, 2H), 3.88–3.81 (m, 4H), 3.61 (dd, J = 11.1, 6.5 Hz, 4H); IR (cm-1
,
KBr): 2,962, 2,876, 1,663, 1,588, 1,493, 1,484, 1,442, 1,364, 1,325, 1,291, 1,222,
1,163, 1,048, 990, 796, 772, 685; HRMS calcd for C26H20N2O5: 463.12564
(M?Na)?; Found: 463.12564.
General procedure for the preparation of title compounds 2 and 3
A dry three-necked flask was charged with 0.04 mmol of compound 1, 0.65 mL of
pyridine, and 400 mL of CH2Cl2. To the above vigorously stirred system, 3 mmol
1,2-benzenedicarbonyl chloride in CH2Cl2 (200 mL) was added dropwise over a
period of 12 h. The reaction solution was stirred for 12 h at room temperature
(reaction monitored by TLC). When the reaction was complete, the solvent was
evaporated under reduced pressure, and the residual solution was washed with water
(20 mL 93) and dried over anhydrous MgSO4. The residue was purified by TLC to
give the compounds 2 and 3 in one pot. The yield, melting point, and spectral data
of each compound were collected as below.
Macrolides-linked chalcone derivative 2a Yield: 46 % of yellow solid, mp
137–139 °C; IR (cm-1, KBr): 3,060, 2,924, 2,856, 1,709, 1,655, 1,593, 1,495,
123

Novel macrolides-linked chalcone derivatives
1
1,439, 1,291, 1,197, 1,130, 1,023, 791, 749, 688; H NMR (400 MHz, CDCl3)
d 7.80 (dd, J = 8.2, 5.9 Hz, 3H), 7.64 (d, J = 3.7 Hz, 2H), 7.59 (d, J = 3.0 Hz,
2H), 7.50 (d, J = 15.8 Hz, 2H), 7.41 (s, 5H), 6.85 (s, 1H), 4.59 (s, 4H), 3.89 (s, 4H);
13C NMR (101 MHz, CDCl3) d 191.01, 165.72, 147.50, 144.62, 143.50, 139.37,
134.86, 134.37, 131.14, 130.46, 129.63, 128.91, 128.39, 126.69, 125.98, 122.39,
122.12, 117.43, 116.79, 111.60, 62.38, 50.05; HRMS calcd for C27H23NO5:
464.1491 (M?Na)?; Found: 464.1491.
Macrolides-linked chalcone derivative 3a Yield: 32 % of yellow-orange solid, mp
65–67 °C; IR (KBr, cm-1): 3,061, 2,930, 1,780, 1,724, 1,657, 1,591, 1,493, 1,448,
1,342, 1,279, 1,245, 1,118, 1,071, 929, 759, 686. H NMR (400 MHz, CDCl3)
1
d 7.87 (d, J = 7.5 Hz, 2H), 7.80 (d, J = 15.7 Hz, 2H), 7.64 (m, 9H), 7.55–7.49 (m,
4H), 7.45–7.35 (m, 11H), 6.97 (dd, J = 6.8, 2.5 Hz, 2H), 4.39–4.29 (m, 4H),
4.16–4.08 (m, 4H), 3.95–3.83 (m, 8H). 13C NMR (101 MHz, CDCl3) d 191.01,
165.72, 147.50, 144.62, 143.50, 139.37, 134.86, 134.37, 131.14, 130.46, 129.63,
128.91, 128.39, 126.69, 125.98, 122.39, 122.12, 117.43, 116.79, 111.60, 62.38,
50.05. HRMS calcd for C54H46N2O10: 905.3045 (M?Na)?; Found: 905.3045.
Macrolides-linked chalcone derivative 2b Yield: 40 % of yellow solid, mp
170–171 °C; IR (KBr, cm-1): 3,082, 2,924, 1,741, 1,711, 1,664, 1,585, 1,487,
1,451, 1,353, 1,279, 1,127, 1,069, 790, 735; 1H NMR (400 MHz, CDCl3) d 7.82 (dd,
J = 5.6, 3.3 Hz, 2H), 7.64–7.56 (m, 3H), 7.54 (s, 1H), 7.43 (m, 3H), 7.29 (s, 1H),
6.87–6.82 (m, 1H), 6.74 (d, J = 3.3 Hz, 1H), 6.52 (dd, J = 3.2, 1.7 Hz, 1H),
4.62–4.57 (m, 4H), 3.93–3.87 (m, 4H); 13C NMR (101 MHz, CDCl3) d 190.14,
167.88, 146.71, 144.88, 139.30, 131.53, 131.51, 130.59, 129.85, 129.69, 119.56,
117.41, 116.21 115.63, 112.64, 110.41, 64.15, 52.95; HRMS calcd for C25H21NO6:
454.1261 (M?Na)?; Found: 454.1261.
Macrolides-linked chalcone derivative 3b Yield: 30 % of red solid, mp
170–171 °C; IR (KBr, cm-1): 2,925, 1,780, 1,724, 1,654, 1,591, 1,548, 1,491,
1,466, 1,387, 1,280, 1,118, 1,071, 926, 757, 727, 687; 1H NMR (400 MHz, CDCl3)
d 7.88 (d, J = 7.3 Hz, 2H), 7.75–7.65 (m, 3H), 7.58 (m, 8H), 7.48–7.35 (m, 7H),
6.96 (s, 2H), 6.72 (s, 1H), 6.52 (s, 1H), 4.40–4.29 (m, 4H), 4.18–4.08 (m, 4H), 3.90
(s, 8H); 13C NMR (101 MHz, CDCl3) d 190.21, 165.72, 151.59, 147.43, 144.85,
143.46, 139.24, 134.37, 131.00, 130.89, 130.49, 129.63, 126.65, 125.94, 122.13,
119.50, 117.40, 116.79, 116.18, 112.62, 111.48, 62.37, 50.02. HRMS calcd for
C50H42N2O12: 885.2630 (M?Na)?; Found: 885.2613.
Macrolides-linked chalcone derivative 2c Yield: 41 % of yellow-orange solid, mp
69–71 °C; IR (KBr, cm-1): 3,077, 1,707, 1,659, 1,588, 1,489, 1,445, 1,356, 1,289,
1,197, 1,134, 1,022, 770, 726; 1H NMR (400 MHz, CDCl3) d 7.93 (d, J = 15.4 Hz,
1H), 7.81 (dd, J = 5.6, 3.3 Hz, 2H), 7.59 (dd, J = 5.6, 3.3 Hz, 2H), 7.47–7.35 (m,
4H), 7.33 (s, 1H), 7.29 (s, 1H), 7.14–7.07 (m, 1H), 6.85 (d, J = 7.3 Hz, 1H),
4.69–4.56 (m, 4H), 3.90 (d, J = 3.6 Hz, 4H); 13C NMR (101 MHz, CDCl3)
d 190.72, 148.05, 140.23, 138.68, 136.96, 131.98, 129.19, 129.18, 128.97, 128.24,
123

M. Yang et al.
120.97, 116.83, 116.75, 111.23, 60.19, 54.94; HRMS calcd for C25H21NO5S:
470.1033 (M?Na)?; Found: 470.1041.
Macrolides-linked chalcone derivative 3c Yield: 32 % of yellow solid, mp
141–143 °C; IR (KBr, cm-1): 3,070, 2,928, 1,779, 1,732, 1,651, 1,573, 1,493,
1,453, 1,355, 1,278, 1,117, 1,070, 929, 763, 691; H NMR (400 MHz, CDCl3)
1
d 7.93 (d, J = 15.4 Hz, 2H), 7.86 (d, J = 7.4 Hz, 2H), 7.68 (t, J = 7.4 Hz, 2H),
7.60 (t, J = 7.4 Hz, 2H), 7.52 (d, J = 7.4 Hz, 2H), 7.44–7.28 (m, 10H), 7.13–7.05
(m, 2H), 6.96 (d, J = 7.4 Hz, 2H), 4.43–4.27 (m, 4H), 4.17–4.07 (m, 4H),
3.97–3.78 (m, 8H); 13C NMR (101 MHz, CDCl3) d 190.33, 165.72, 147.48, 143.47,
140.35, 139.24, 137.01, 134.37, 131.96, 131.12, 129.63, 128.74, 128.30, 126.66,
125.93, 122.13, 121.08, 117.42, 117.30, 116.78, 111.48, 62.36, 50.01; HRMS calcd
for C50H42N2O10S2: 917.2173 (M?Na)?; Found: 917.2135.
Macrolides-linked chalcone derivative 3d Yield: 34 % of yellow solid, mp
62– 64 °C; IR (KBr, cm-1): 3,067, 2,933, 1,781, 1,726, 1,661, 1,591, 1,493, 1,352,
1
1,281, 1,118, 1,072, 990, 928, 766, 685 cm-1; H NMR (400 MHz, CDCl3) d 8.72
(d, J = 4.3 Hz, 2H), 8.10 (d, J = 15.3 Hz, 2H), 7.87 (d, J = 7.5 Hz, 2H),
7.81–7.73 (m, 4H), 7.69 (dd, J = 9.6, 5.3 Hz, 2H), 7.60 (m, 4H), 7.51 (m, 4H), 7.44
(s, 2H), 7.39 (t, J = 8.0 Hz, 2H), 7.31 (dd, J = 7.4, 4.7 Hz, 2H), 6.98 (dd, J = 8.2,
2.4 Hz, 2H), 4.38–4.30 (m, 4H), 4.17–4.10 (m, 4H), 3.94–3.84 (m, 8H); 13C NMR
(101 MHz, CDCl3) d 190.73, 165.71, 153.09, 149.98, 147.49, 143.48, 142.34,
138.89, 136.99, 134.36, 131.52, 131.10, 129.70, 126.66, 125.92, 125.32, 124.38,
122.12, 117.91, 117.27, 111.54, 62.37, 50.01; HRMS calcd for C52H44N4O10:
885.3130 (M?H)?; Found: 885.3164.
UV–Vis spectra measurements
Stock solutions (10-2 mol L-1) of the chloride salts of Al3?, Na?, Mg2?, Cu2?
,
Zn2?, Fe3?, Ni2?, Pd2?, Hg2?, NH4?, Li?, Sn2?, K?, and Co2? in methanol were
prepared. Stock solutions (1.0 9 10-4 M) of title compounds were prepared in
acetone. Before spectroscopic measurements, the high concentration stock solutions
were diluted to 2 9 10-4 mol L-1 with methanol [21]. All the measurements were
made according to the following procedure. To 10-mL glass tubes containing
different metal ions, 1 equivalent of each title compound was added directly, then
diluted with methanol to 10 mL and mixed, and then the absorption sensing of metal
ions was run.
Results and discussion
Synthesis
Macrolides-linked chalcone derivatives 2a–c and 3a–d were prepared in a three-step
synthesis as outlined in Scheme 1. In order to obtain the intermediate 3-[N,N-bis
123

Novel macrolides-linked chalcone derivatives
KI
ClCH CH OH CaCO
,
,
2
2
3
HO
HO
O
C
O
C
H2N
120
7h
,
-
R
NaOH
CHO
,
N
O
r.t.
,
EtOH
3-6h
,
CH CH OH
,
2
2
r.t.
,
24h
A
R
O
O
O
O
N
O
O
[1+1]
Cl
C
a-c
2
HO
HO
O
C
Cl
C
O
N
R
O
H
O
H
r.t.
,
, 12h
Py
CH2Cl2
,
R
O
O
R
O
O
O
1a-d
H
H
N
N
O
O
O
[2+2]
3a-d
N
a: R=
b: R=
c: R=
d: R=
S
O
Scheme 1 Synthetic procedure of macrolides-linked chalcone derivatives 2a–c and 3a–d
(2-hydroxyethyl)-amino]-acetophenone A, we first attempted the method of treating
the 3-aminoacetophenone with excess oxirane and catalytic propanoic acid [22].
Unfortunately, it did not give the required bis-hydroxyethylated compound for the
result of electrophilic effect of acetyl. So we adopted another method, using
2-chloroethanol as hydroxyethylation reagent and KI, CaCO3 as catalysts [23].
Chalcone derivatives 1a–d were obtained by a base-catalyzed Claisen–Schmidt
condensation [24] of A with substituted aldehydes. The two types of macrolides-
linked chalcone derivatives 2a–c and 3a–d were also accessed by a familiar method
from the reaction of 1a–d with 1,2-benzenedicarbonyl chloride. In order to avoid
polymerization, the cyclization procedure was run under high dilution conditions
and the reaction solution had to avoid light with high-speed stirring. In addition,
more by-products added a further complication to the purification of title
compounds. The separation of title compounds were all carried out by TLC. It is
a pity that we cannot get the macrolides-linked chalcone which should be
synthesized by 1d and 1,2-benzenedicarbonyl chloride. Considering the use of
pyridine as acid binding agent, pyridine can also react with 1,2-benzenedicarbonyl
chloride. As a result, this effect increased the steric hindrance to obtain the type of
[1 ? 1] product. However, the steric hindrance will not affect the cyclization
procedure of the type of [2 ? 2] product.
123

M. Yang et al.
Fig. 4 a Crystal structure of compound 2a and b packing diagrams of 2a
Fig. 5 UV–Vis spectra of 3d in
methanol solution upon addition
of various metal ions
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
blank and other ions
Cu2+
250 275 300 325 350 375 400 425 450 475 500
wavelength (nm)
Crystallographic structures of compound 2a
The structure of compound 2a is presented in Fig. 4a. Compound 2a crystallizes in
P21/n space group. XRD studies on compound 2a showed that the two ester groups
exist on both sides of the benzene ring plane [C16, C17, C18, C19, C20, C21] and
are almost parallel with it. In the structure of chalcone, the dihedral angle between
two benzene rings is 26.36°. There are several weak intramolecular hydrogen bonds
(Fig. 4b).
UV–Vis spectral characteristics and mechanism
In order to investigate the ions recognition abilities of the macrolides-linked
chalcones, we carried out a series of recognition experiments in methanol. It is as
expected that compound 3d showed selectivity to Cu2? (Fig. 5). The free compound
3d exhibited absorption at 261 and 303 nm. Upon addition of other ions, no
significant absorption changes were observed. However, when adding Cu2? to
solution of compound 3d, the absorption at 303 nm disappeared and a new peak
appeared at 339 nm. There is a nitrogen atom in the structure of pyridine, which can
123

Novel macrolides-linked chalcone derivatives
Scheme 2 Proposed
mechanism for the absorption
changes of 3d upon the addition
of Cu2?
O
O
O
O
O
N
N
O
O
N
N
O
O
O
Cu
Cu
N
O
O
N
O
O
O
O
N
N
O
O
O
O
serve as recognition group. The possible reason that only the macrolides-linked
chalcone derivative 3d can be well applied for the detection of Cu2? is that there are
more nitrogen atoms in the two pyridine rings. To better understand the interaction
of Cu2? with 3d, a proposed mechanism for the absorption changes of 3d upon the
addition of Cu2? is shown in Scheme 2.
Conclusion
In conclusion, seven novel macrolides-linked chalcone derivatives (2a–c and 3a–d)
were successfully prepared. The crystal structure of the title compound 2a was
obtained, and structural analysis revealed that it is monoclinic with the space group
P21/c. Compound 3d exhibits selectivity for sensing Cu2?. Further studies need to
be conducted to recognizing mechanisms and the screening of the biological
activities, and the relevant study is underway.
X-ray crystallography data
All measurements of compound 2a were made on a Bruker Smart APEX II CCD
diffractometer with graphite monochromated Mo-Ka radiation. The data was
collected at a temperature of 296(2) K using the x - 2h scan technique. CIF files of
compound 2a have been deposited with the Cambridge Structural Database (CCDC
No. 955401). Copies of the data can be obtained free of charge via www.ccdc.cam.ac.
uk/conts/retrieving.html or from the CCDC, 12 Union Road, Cambridge CB2 1EZ,
UK; Tel: (?44) 1223-336-408; Fax: (?44) 1223-336-033. E-mail: deposit@
ccdc.cam.ac.uk.
Acknowledgment This work was financially supported by the National Natural Science Foundation of
China (Grant No. 21172178 P. R. China).
123

M. Yang et al.
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