New chalcone-3-O-glycoside derivatives: Synthesis and characterization

Article abstract of DOI:10.1177/1747519820915165

Seven novel carbohydrate conjugates of new chalcone-3-O-glycosides were synthesized and characterized. Starting from the substituted 3′-hydroxyarylmethylacetophenone derivatives (chalcones) with α-acetobromoglucose in anhydrous acetone were synthesized 2,

Full text of DOI:10.1177/1747519820915165

915165CHL0010.1177/1747519820915165Journal of Chemical ResearchÇelik
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Journal of Chemical Research
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New chalcone-3-O-glycoside derivatives:
Synthesis and characterization
https://doi.org/10.1177/1747519820915165
DOI: 10.1177/1747519820915165
journals.sagepub.com/home/chl
Gonca Çelik
Abstract
Seven novel carbohydrate conjugates of new chalcone-3-O-glycosides were synthesized and characterized. Starting from
the substituted 3′-hydroxyarylmethylacetophenone derivatives (chalcones) with α-acetobromoglucose in anhydrous
acetone were synthesized 2,3,4,6-tetra-O-acetyl-3′-O-β-d-glucopyranosyloxychalcones. Deblocking the latter with
CH3ONa in dry methanol results in substituted chalcone-3-O-glycosides (3′-O-β-d-glucopyranosyloxychalcones).
1
The structures of the newly synthesized chalcone-3-O-glycosides were characterized based on H nuclear magnetic
resonance, 13C nuclear magnetic resonance, mass spectroscopy, and Fourier-transform infrared spectroscopy.
Keywords
chalcone, chalcone-3-O-glycosides, characterization, nuclear magnetic resonance, synthesis
Date received: 31 August 2019; accepted: 2 March 2020
membranes.9,10 O-glycosides are a family of carbohydrates
Introduction
widely found in plants with carbon–oxygen bond formation
Chalcones, compounds bearing the 1,3-diaryl-2-propen-
employing activated sugar.11,12 Phenolic hydroxyl groups
1-one system, play a vital role in chemical compounds
occur in the free state or in combined form as O-glycosides in
plants where they play many interesting biological activities,
associated with diverse pharmacological activities.1 Due to
their flexible structures, chalcones can bind effectively to
many kinds of enzymes or receptors and exhibit a broad
spectrum of biological activities such as anticancer,2 anti-
HIV,3 anti-inflammatory,4,5 anti-invasive,6,7 and antibacte-
Department of Chemistry, Faculty of Arts and Sciences, Karadeniz
Technical University, Trabzon, Turkey
rial properties.8
Glycosylation of small biologically active molecules,
either of natural or synthetic origin, has an effect on their sol-
ubility, and bioactivity. Notably, β-glucosylation improves
the drug’s targeting to cells as well as their “solubility” in cell
Corresponding author:
Gonca Çelik, Department of Chemistry, Faculty of Arts and Sciences,
Karadeniz Technical University, 61080 Trabzon, Turkey.
Email: mavi_gnc@hotmail.com

2
Journal of Chemical Research 00(0)
Scheme 1. Structures of isolated chalcone glycosides from Brassica rapa L. “hidabeni.”
4′-O-β-d-Glucopyranosyl-4-hydroxy-3′methoxychalcone (1).
4′-O-β-d-Glucopyranosyl-3′,4-dimethoxychalcone (2).
Scheme 2. General route for the synthesis of chalcone-3-O-glycosides (5a–g).
such as antitumor activity and inhibitors of the metabolic temperature according to the Claisen–Schmidt condensa-
process.13
tion method, which is a single-step process and a practical
Much attention has been paid to chalcones as potential method for the synthesis of substituted chalcone derivatives
biological agents after the discovery of the natural chal- (Scheme 2).16
cone-O-glycosides which demonstrated a broad spectrum
In the second step, O-glucosylation reactions were per-
of antibiotic, antifungal, and anti-HIV activity.14 The isola- formed by condensing α-acetobromoglucose (ACBG) and
tion of some chalcone glycosides (see Scheme 1) from the 3-hyroxychalcones (3a–g) at 0–5°C using 5% aqueous potas-
aerial parts of Brassica rapa L. “hidabeni” has been sium hydroxide (KOH) solution in dry acetone under an inert
reported.15 However, to the best of the author’s knowledge, atmosphere.13 Deacetylation by methanolic MeONa solution
few reports have been dedicated to the synthesis and inhibi- gave, after purification, chalcone-3-O-glycosides (5a–g) in
tory activity of chalcone derivatives containing an good yield in favor of the β-anomer from 2,3,4,6-tetra-O-
O-glycoside skeleton.
acetyl-3′-O-β-glucopyranosyloxybenzlideneacetophenones
In this study, preliminary results in the organic synthesis 4a–g see (Scheme 2).17
of some new chalcone-3-O-glycosides will be reported.
The synthesis of chalcone-3-O-glycosides was
Scheme 2 shows the synthetic analysis of the target mole- achieved in this second step. The structures of all the com-
cules. Target molecules in this study are chalcones with pounds were confirmed by nuclear magnetic resonance
various sugar substitutions at 3-position.
(NMR), liquid chromatography–mass spectrometry (LC/
MS–MS), and Fourier-transform infrared spectroscopy
(FTIR; attenuated total reflection (ATR)), spectroscopy.
The results were consistent with the predicted structures
Results and discussion
First, substituted chalcones starting from 3-hydroxyaceto- for all the new chalcone-3-O-glycosides, as described in
phenone and different aldehydes were synthesized at room section “Experiment”.

Çelik
3
The β-configuration of the glycosidic bond was con- The high-resolution accurate masses were determined
firmed from 1H NMR and 13C NMR. In the 1H NMR spec- using Micromass Quattro LC–MS/MS. The IR spectra
trum of 5a–g, the anomeric proton appeared as a doublet at were recorded on a Perkin Elmer 1600 Fourier transform
~δ 5.03 (d, ~7.6Hz) that confirmed the β-orientation of the infrared (FTIR-ATR) spectrophotometer. Compounds 3a–g
sugar unit.18 Characteristic pyranosyl ring protons were were synthesized by the method described by Narender
located at δ 3.40–3.96.
et al.21 NMR, MS, IR data, and melting point of the known
In the proton-decoupled 13C NMR, the anomeric carbon compounds were consistent with those reported
was located at δ ~101.00, which is consistent with the for- previously.22–28
mation of the β-glucoside 5a–g. The mass spectrum of
3-((2E)-3-(2-thienyl)prop-2-enol-yl)phenyl hexopyrano-
Synthesis of chalcones (3a–g): general
side (5a) also confirmed the proposed structure of the chal-
procedure
cone-3-O-glycoside. The molecular ion peak was observed
at m/z 393.0825 as (M+H)+, (100; see Electronic Compounds 3a–g were synthesized according to the previ-
Supplementary Information (ESI)).
ously reported procedure.22–28
The structure of 3-((2E)-3-(2-thienyl)prop-2-enol-yl)
phenyl hexopyranoside (5a) was confirmed by the appear-
ance of the –C=O band at 1651cm−1 in the FTIR spectrum.
The characteristic bands at 3343 and 1651cm−1 indicated
the existence of –OH and –C=O groups, respectively.
In the 1H NMR spectra of the synthesized chalcone-3-O-
glycoside derivatives (5a–g), the α,β-protons resonated as
doublet doublets (dd) between δ 7.74 and 7.59, which is
characteristic for α,β-unsaturated carbonyl compounds.
The olefinic H-atoms of chalcone-3-O-glycoside (5a–g)
were shown to be trans based on their J values of 15.4–
15.7Hz for Hα and Hβ.19
Synthesis of 2,3,4,6-tetra-O-acetyl-3′-O-β-
glucopyranosyloxybenzlideneacetophenones
(4a–g): general procedure
The 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide
(0.411g, 1mmol) was dissolved in dry acetone (20mL) and
cooled to 0–3°C. To this, a solution of the potassium salt of
3′-hydroxybenzylideneacetophenones (1mmol) in 5%
methanolic KOH (10mL) was added dropwise under a
nitrogen atmosphere. The resulting mixture was stirred at
0–3°C for 8h and the reaction was allowed to proceed for
an additional 10h at room temperature. After stirring for
19h, the resultant solution was partitioned with EtOAc, dis-
tilled water and brine, dried over anhydrous Na2SO4, and
concentrated in vacuo. The residue was purified using silica
gel 230–400 mesh eluting with 20% MeOH in CHCl3 to
obtain compounds 4a–g as orange syrups.
In the 13C NMR spectra of the compound 5e, the charac-
teristic carbon–fluorine signals appear at 131.32/131.29
′′
′′
′′
(C3 ) , 165.44/162.95 (C4 ) ,
(C2 ) , 115.74/115.52
′′
(C )
′′
(C6 )
(see
131.32/131.29
, and 115.74/115.52
5
ESI).20
The mass spectra of compounds 5a–g showed molecular
ion peaks at the appropriate m/z values confirming their
1
molecular mass. In the H and 13C NMR spectra of com-
The general method for 3′-O-β-glucopyranos
yloxybenzlideneacetophenones 5a–g
pounds 5a–g, in particular, anomeric protons and anomeric
carbons showed peaks at, respectively, δH 5.03 (1H, d) and
δC 101.00ppm;whichareanindicationoftheβ-configuration
of the chalcone-3-O-glycosides (5a–g).
A freshly prepared solution of MeONa–MeOH (3mL,
0.05M) was added to a solution of 2,3,4,6-tetra-O-acetyl-
3′-O-β-glucopyranosyloxybenzlideneacetophenones 4a–g
(0.1g) in 20mL dry methanol and kept at room temperature
under a nitrogen atmosphere. The progress of the reaction
was followed by silica gel thin-layer chromatography
(TLC; CHCl3–MeOH, 3:1). The reaction was stopped after
24h. The mixture was extracted with EtOAc (3×10mL),
the combined organic phases were successively washed
with H2O (2×10mL), dried over Na2SO4 and concen-
trated. The syrupy residue was purified on silica gel using
CHCl3–MeOH (9/1 to 7/3, then 6/4, v/v).
Conclusion
The synthesis of seven new chalcone-3-O-glycosides,
which can be used to make more glycosylated chalcone, is
reported in this study. The structures of the synthesized
chalcone and chalcone-3-O-glycoside have been confirmed
by NMR, LC/MS–MS, and FTIR (ATR) spectroscopy.
Chalcones are important α,β-unsaturated ketones and con-
stitute a class of naturally occurring substances, which are
very attractive bioactive starting materials for the synthesis
of substituted chalcone-O-glycosides.
3-[(2E)-3-(2-thienyl)prop-2-enol-yl]phenyl hexopyra-
noside (5a): Orange oil; yield 98mg (25%); H NMR
1
(CD3OD): δ 7.45 (d, J=15.6Hz, 1H), 7.94 (d, J=15.6Hz,
1H), 7.75 (bs, 1H), 7.40 (bd, J=7.8Hz, 1H), 7.49 (t,
J=7.9Hz, 1H), 7.72 (d, J=7.8Hz, 1H), 7.63 (d, J=7.9Hz,
1H), 7.16 (dd, J=8.2, 4.6Hz, 1H), 7.54 (d, J=8.2Hz,
1H), 5.06 (d, J=7.6Hz, 1H), 3.60–3.40 (m, 4H), 3.72 (dd,
J=12.4, 4.1Hz, 1H), 3.94 (dd, J=12.4, 2.1Hz, 1H); 13C
NMR (CD3OD): δ 189.84, 122.13, 137.45, 139.21, 116.97,
158.03, 122.98, 129.60, 122.13, 140.01, 132.36, 128.24,
129.53, 101.00, 73.49, 76.84, 69.95, 76.52, 61.04; MS
Experiment
1H and 13C NMR spectra were recorded on a 400 (100)-
MHz Bruker Avance spectrometer in methanol-d4; δ is
given in ppm relative to Me4Si (tetramethylsilane (TMS))
as an internal standard. The following abbreviations are
used: s=singlet, d=doublet, dd=doublet doublet, t=tri-
plet, m=multiplet, bs=broad singlet, bd=broad doublet.

4
Journal of Chemical Research 00(0)
(ESI) m/z for C19H20O7S [M+1]+: 393 (90), 282 (50); IR
(ATR) (v, cm–1): 3343, 2962, 1651, 1574, 1251, 1071,
711.
(d, J=7.7Hz, 1H), 3.60–3.40 (m, 4H), 3.74 (dd, J=12.3,
4.1Hz, 1H), 3.94 (bd, J=12.3Hz, 1H); 13C NMR (CD3OD):
δ 190.09, 122.33, 143.33, 139.16, 116.16, 158.05, 122.20,
129.88, 122.33, 133.61, 129.59, 129.38, 136.12, 129.38,
129.88, 100.99, 73.50, 76.91, 69.98, 76.54, 61.13; MS
(ESI) m/z for C21H21CIO7 [M+1]+: 421 (90); IR (ATR) (v,
cm−1): 3348, 2919, 1658, 1579, 1245, 1010, 822, 782.
3-[(2E)-3-(4-bromophenyl)prop-2-enol-yl]phenyl
3-[(2E)-3-(4-nitrophenyl)prop-2-enol-yl]phenyl hexopyra-
1
noside (5b): Orange oil; yield 87mg (20%); H NMR
(CD3OD): δ 7.83 (d, J=15.6Hz, 1H), 7.93 (d, J=15.6Hz,
1H), 7.80 (bs, 1H), 7.40 (dd, J=7.6, 3.2Hz, 1H), 7.52 (t,
J=7.6Hz, 1H), 7.84 (m, 1H), 8.00 (d, J=7.8Hz, 2H), 8.32
(d, J=7.8Hz, 2H), 5.06 (d, J=7.6Hz, 1H), 3.60–3.40 (m,
4H), 3.72 (dd, J=12.4, 4.1Hz, 1H), 3.94 (dd, J=12.4,
2.1Hz, 1H); 13C NMR (CD3OD): δ 189.57, 123.68, 141.56,
138.83, 115.84, 158.08, 121.73, 129.65, 122.43, 141.12,
129.27, 125.42, 148.59,125.42, 129.27, 100.97, 74.34,
76.95, 70.22, 76.55, 61.17; MS (ESI) m/z for C21H21NO9
[M+Na]+: 454 (25), 282 (100); IR (ATR) (v, cm−1): 3364,
2926, 1669, 1515, 1337, 1246, 1046, 754.
3-[(2E)-3-(4-dimethylaminophenyl)prop-2-enol-yl]phe-
nyl hexopyranoside (5c): Orange oil; yield 94mg (22%); 1H
NMR (CD3OD): δ 7.72 (d, J=15.4Hz, 1H), 7.78 (d,
J=15.4Hz, 1H), 7.42 (s, 1H), 7.34 (dd, J=9.4, 2.1Hz, 1H),
7.48 (m, 1H), 7.50 (d, J=7.8Hz, 1H), 7.64 (d, J=7.8Hz,
1
hexopyranoside (5g): Yellow oil; yield 116mg (25%); H
NMR (CD3OD): δ 7.45 (d, J=15.4Hz, 1H), 7.48 (d,
J=15.4Hz, 1H), 7.74 (bs, 1H), 7.33 (m, 1H), 7.40 (m, 1H),
7.78 (m, 1H), 7.60 (d, J=7.6Hz, 2H), 7.69 (d, J=7.6Hz,
2H), 5.03 (d, J=7.8Hz, 1H), 3.60–3.40 (m, 4H), 3.72 (dd,
J=12.1, 3.9Hz, 1H), 3.95 (dd, J=12.1, 1.3Hz, 1H); 13C
NMR (CD3OD): δ 190.09, 124.40, 143.42, 139.13, 116.48,
158.02, 122.24, 129.60, 122.73, 133.96, 129.60, 131.58,
124.42, 129.60, 131.58, 100.97, 74.19, 76.89, 69.97, 76.53,
61.13; MS (ESI) m/z for C21H21BrO7 [M]+: 465 (95); IR
(ATR) (v, cm−1): 3362, 2921, 1662, 1579, 1249, 1069, 776.
Declaration of conflicting interests
2H), 6.78 (d, J=7.8Hz, 2H), 3.06 (s, 6H), 5.02 (d, J=7.7Hz, The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
1H), 3.60–3.40 (m, 4H), 3.74 (dd, J=12.2, 3.7Hz, 1H), 3.94
(dd, J=12.2, 2.1Hz, 1H); 13C NMR (CD3OD): δ 190.70,
122.27, 146.83, 140.11, 116.00, 157.97, 122.27, 129.41,
122.06, 122.27, 130.58, 111.60, 152.65, 111.60, 130.28,
58.09, 101.03, 73.51, 76.88, 70.17, 76.53, 61.09; MS (ESI)
Funding
The author(s) disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article: The
m/z for C23H27NO7 [M+1]+: 430 (95), 282 (15); IR (ATR) author acknowledges the financial support from The Scientific
(v, cm−1): 3376, 2923, 1644, 1571, 1243, 1076, 785.
and Technological Research Council of Turkey (TUBITAK) with
Project 116R016.
3-[(2E)-3-(4-methoxyphenyl)prop-2-enol-yl]phenyl
1
hexopyranoside (5d): Yellow oil; yield 124mg (30%); H
ORCID iD
NMR (CD3OD): δ 7.60 (d, J=15.7Hz, 1H), 7.72 (d,
J=15.7Hz, 1H), 7.74 (m, 1H), 7.38 (m, 1H), 7.49 (t,
J=7.7Hz, 1H), 7.74 (m, 1H), 7.73 (d, J=7.6Hz, 2H), 7.00
(d, J=7.6Hz, 2H), 3.75 (s, 3H), 5.01 (d, J=7.8Hz, 1H),
3.60–3.40 (m, 4H), 3.74 (dd, J=12.2, 4.1Hz, 1H), 3.94 (dd,
J=12.3, 2.2Hz, 1H); 13C NMR (CD3OD): δ 190.56, 123.33,
146.83, 140.14, 139.57, 116.52, 158.00, 122.21, 129.41,
122.60, 127.79, 131.42, 114.13, 162.16, 131.42, 114.13,
54.53, 101.00, 73.50, 76.88, 69.94, 76.52, 61.10; MS (ESI)
m/z for C22H24O8 [M+1]+: 417 (100); IR (ATR) (v, cm−1):
3290, 2924, 1656, 1585, 1250, 1022, 793.
Gonca Çelik
https://orcid.org/0000-0002-4634-3354
Supplemental material
Supplemental material for this article is available online.
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