The first synthesis of peracetyl glycosyl aurone derivatives and aurone glucosides

Article abstract of DOI:10.1016/j.tet.2020.131528

Aurones, a sub-class of the flavonoids with proven therapeutic importance, also exist in variously glycosylated forms. Although a large number of glycosylated aurone derivatives have been isolated from plant sources, no syntheses have been reported yet. Inspired from this gap, here we report the first synthesis of peracetylated glycosyl derivatives of synthetic aurones. The direct O-glycosylation was achieved by reacting 6-hydroxy aurones with 2, 3, 4, 6-tetra-O-acetyl-α-D glucopyranosyl bromide in the presence of a phase transfer catalyst tetrabutylammonium bromide (TBAB). The successful synthesis of aurone glycosides (33 examples) in 60–92% yield will benefit the synthesis of combinatorial libraries of glycosylated aurones for their biological study and comparison with non-glycosylated aurones.

Full text of DOI:10.1016/j.tet.2020.131528

Tetrahedron 76 (2020) 131528
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
The first synthesis of peracetyl glycosyl aurone derivatives and aurone
glucosides
, b, *
Arjun Kafle a, Shrijana Bhattarai a, Scott T. Handy a
a Molecular Biosciences Program, Middle Tennessee State University, Murfreesboro, TN, 37132, United States
b Department of Chemistry, Middle Tennessee State University, Murfreesboro, TN, 37132, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Aurones, a sub-class of the flavonoids with proven therapeutic importance, also exist in variously gly-
cosylated forms. Although a large number of glycosylated aurone derivatives have been isolated from
plant sources, no syntheses have been reported yet. Inspired from this gap, here we report the first
synthesis of peracetylated glycosyl derivatives of synthetic aurones. The direct O-glycosylation was
Received 17 April 2020
Received in revised form
18 August 2020
Accepted 20 August 2020
Available online 26 August 2020
achieved by reacting 6-hydroxy aurones with 2, 3, 4, 6-tetra-O-acetyl-a-D glucopyranosyl bromide in the
presence of a phase transfer catalyst tetrabutylammonium bromide (TBAB). The successful synthesis of
aurone glycosides (33 examples) in 60e92% yield will benefit the synthesis of combinatorial libraries of
glycosylated aurones for their biological study and comparison with non-glycosylated aurones.
© 2020 Elsevier Ltd. All rights reserved.
Keywords:
Aurones
Aurone glycosylation
Peracetylglycosyl bromide
Phase transfer catalyst
Glycosyl donor
O-Glycosylation of phenol
To create your abstract, type over the instructions in the tem-
plate box below. Fonts or abstract dimensions should not be
changed or altered.
connected to a phenyl ring by an exocyclic double bond forming the
thermodynamically more stable (Z) isomer [4,5,9]. Despite their
limited skeletal variation, aurones are found to maintain their
structural diversity through different substitution patterns, mostly
hydroxylation, methoxylation and glycosylation [2]. At the same
time, the development of a significant number of synthetic strate-
gies has tremendously contributed to structural diversification of
the aurone scaffold, providing access to various different types of
aurone derivatives for application in drug discovery [8,10e14].
Aurones are biosynthesized in plants via oxidative cyclization
followed by rearrangement of, typically, 20 and 40-hydroxylated
chalcones in the presence of aureusidin synthase. During this pro-
cess a chalcone is glycosylated in the cytoplasm which eventually is
converted into an aurone-glucoside [15,16]. Although various types
of glycosylated aurone derivatives have been isolated from plant
sources (Fig. 1) [2], they lack variation in the substitution pattern,
and there is only a single report of their synthesis. This paper by
Tronina used an enzymatic reaction catalyzed by fungal strains to
prepare two glycosylated aurones in modest yield with reaction
times of several days [17].
1. Introduction
Aurones, a minor sub-class of flavonoid family, are naturally
occurring pigments. They are primarily responsible for imparting
bright yellow color to flowers and fruits [1]. Mainly found in
eudicots and advanced monocots such as Cyperaceae, aurones are
one of the less explored sub-families of the flavonoids [2,3]. Besides
their primary role in plants, as a secondary metabolite, they are
found to exhibit a number of useful biological activities against
both metabolic and infective diseases. Both natural as well as
synthetic analogs are reported to possess a broad spectrum of
bioactivity, including antimicrobial, antiviral, antiinflamatory,
antioxidant, and anticancer properties [4e8]. As a result, they are
emerging as a potential therapeutic heterocyclic scaffold for the
design and development of pharmaceuticals.
Unlike other flavonoids, aurones contain a benzofuranone ring
Given the general importance of carbohydrate moieties in bio-
logical activity, recognition, and transport, the ability to readily
access glycosylated aurones via a direct, simple, and general
method would be of considerable value.
* Corresponding author. Department of Chemistry, Middle Tennessee State Uni-
versity, Murfreesboro, TN, 37132, United States.
E-mail address: shandy@mtsu.edu (S.T. Handy).
https://doi.org/10.1016/j.tet.2020.131528
0040-4020/© 2020 Elsevier Ltd. All rights reserved.

2
A. Kafle et al. / Tetrahedron 76 (2020) 131528
Figure 1. Structures of some glucosides aurone derivatives found in various flowering
plants.
Among N-, O-, and C-glycosylations, O-glycosylation is very
common in nature. The formation of a glycosidic bond usually takes
place in the presence of a promotor by nucleophilic substitution of
a leaving group at the anomeric carbon of a glycosyl donor.
Different direct activation-based O-glycosylation methods, as
summarized in Fig. 2, have been developed based on the types of
glycosyl donors and promotors employed in the reaction [18,19].
Glycosylation itself is challenging in that even a subtle change in
electronic and/or steric factors often requires extensive optimiza-
tion of the reaction conditions [18e]. The Lewis acid promoted
methods (Fig. 2), including the Fischer glycosylation, were devel-
oped mostly for alcohols and more typically for oligosaccharide
synthesis. In comparison, the glycosylation of less nucleophilic
phenols has received relatively little attention [19,20].
An electron-deficient phenol, such as those found in aurones is
even more challenging and in reported examples typically requires
acidic conditions employing glycosyl anomeric acetate and chlor-
oacetimidate donors in the presence of the Lewis acid BF3. Et2O,
which in most cases generates side reactions [19,20]. In contrast,
basic medium proves to be advantageous particularly for phenols as
it eliminates the side reactions triggered by Lewis acid promotors.
Additionally, generation of more stable and less basic phenolate
ions in the basic medium greatly discourages 1, 2-elimination in the
donor molecule as well as drives the reaction via an SN2 pathway
providing better stereochemical control of the product [19].
In this context, the Michael protocol, developed back in 1879, is
one of the most effective and frequently utilized methods for O-
glycosylation of phenols [21]. Among various synthetic protocols
that include the use of various types of glycosyl donors such as
acetate esters, trichloroacetimidates, and thioglycosides, Michael
type protocols utilize glycosyl halides [20]. Glycosyl bromides,
Figure 3. Variations in Michael glycosylation.
biphasic reaction conditions have received significant attention for
aromatic O-glycosylation. Tetrabutylammonium bromide (TBAB) is
one of the most commonly employed PCT, particularly with
glycosyl bromide donors.
Both synthetic and natural aurones have been studied for their
possible biological importance. Despite their therapeutic potential,
the carbohydrate derivatives, including the isolated ones, have not
been explored well. Inspired by this gap, we report the first syn-
thesis of 2, 3, 4, 6-tetra-O-acetyl-
ously synthesized, variously substituted aurones using 2, 3, 4, 6-
tetra-O-acetyl- -D glucopyranosyl bromide as a glycosyl donor.
b-D-glucosyl derivatives of previ-
a
2. Results and discussion
To access a library of glycosylated aurones, first we synthesized
various hydroxy substituted aurones via an acid catalyzed Knoe-
venagel type condensation of a benzofuranone with an aldehyde in
glacial acetic acid medium (Scheme 1). The reaction generally re-
sults in precipitation of the desired product which can be simply
isolated by filtration, thus avoiding the necessity of chromato-
graphic separation. The ease of separation as well as the relatively
fast reaction times allowed us to access the desired hydroxyaurones
quickly.
particularly the thermodynamically favored a-anomers, have been
Following initial failures to glycosylate aurone 1 with the
glycosyl bromide under Koenigs-Knorr (using Ag2O) and original
Michael conditions (employing 1 M NaOH) we utilized tetrabuty-
lammonium bromide (TBAB) as a phase transfer catalyst in a
biphasic basic medium of chloroform and 5% aqueous Na2CO3. The
the frontrunner as they are more reactive than the chlorides and
more stable than the iodides. Influenced by their anomeric ste-
reochemistry, the O-glycosylation generally results in a
linkage irrespective of solvent effects [19,20].
b-glycosidic
This method has evolved with variations in the types of solvent
and catalysts employed (Fig. 3) [22]. Particularly the use of qua-
ternary ammonium salts as a phase transfer catalyst (PCT) in
reaction successfully afforded 68% of the corresponding b-glycoside
(1a) utilizing an excess (2 equivalents) of glycosyl donor to main-
tain its concentration, as it readily undergoes hydrolysis in an
aqueous medium (Scheme 2).
Both electron withdrawing and electron donating groups in the
phenyl moiety of the aurone molecule were tolerated well yielding
Figure 2. Methods of O-glycosylation.
Scheme 1. Synthesis of Aurones.

A. Kafle et al. / Tetrahedron 76 (2020) 131528
3
60e92% of the corresponding peracetylated
(Scheme 3).
As expected, the stereochemistry of the anomeric carbon of the
donor changed creating a -glycosidic linkage with the aglycon
(hydroxyaurone) in accordance with the likelihood of the reaction
proceeding via SN2 mechanism in the basic medium. The -ste-
b-
D-glycosyl aurones
b
b
reochemistry of the glycosidic linkage is established from the
magnitude of coupling constant (J1,2), with values 7e9 Hz observed
for the anomeric hydrogens of the synthesized compounds in
Scheme 2. Glycosylation of Aurone.
contrast to the J-values of 2e4 Hz for a-anomers [23]. While the
alkene geometry of aurones is generally observed to be the ther-
modynamically favored Z geometry, this was also confirmed by the
highly characteristic chemical shift of the exocyclic alkene proton
signal in the as a singlet below 6.9 ppm, while the E isomer would
have a signal above 6.95 ppm [24].
Similarly, reactions with aurone analogs containing different
heterocyclic moieties attached to the exocyclic double bond also
afforded good yield reflecting the generality of the reaction
(Scheme 4). Since naturally occurring glycosylated aurones exist
mostly as glucosides, we took some of the peracetylated glycosyl
aurone derivatives and subjected them to deacetylation using so-
dium methoxide to obtain the corresponding aurones glucosides in
good (ꢀ72%) yield (Scheme 5).
In conclusion, we report the first convenient and efficient O-
glycosylation of variously substituted synthetic hydroxyaurones
and their analogs with 2, 3, 4, 6-tetra-O-acetyl-a-D glucopyranosyl
bromide using a readily available phase transfer catalyst tetrabu-
tylammonium bromide (TBAB) in a basic biphasic medium. This
will eventually provide us with an opportunity to access syntheti-
cally diverse glycosides and glucosides of aurones and their analogs
for further biological screening against both metabolic and infec-
tive diseases.
3. Experimental section
General Information. All the reactions were done under an air
atmosphere. 1H and 13C NMR of all the compounds were recorded
on JEOL AS (500 and 300 MHz) NMR instruments and chemical
shifts were recorded in ppm. All the chemical shifts were recorded
taking CDCl3, DMSO, methanol, or acetone as a standard reference.
[25] The following conventions are used for multiplicities: s,
singlet; d, doublet; t, triplet; m, multiplet; dd, doublet of doublet; tt,
triplet of triplet; dt, doublet of triplet; ddd, doublet of doublet of
Scheme 3. Glycosylation of Aurone Analogs.
Scheme 4. Glycosylation of Aurone Analogs Containing Heterocyclic Moiety.

4
A. Kafle et al. / Tetrahedron 76 (2020) 131528
dichloromethane (DCM ~ 50 mL). The organic layer was concen-
trated in vacuo. The crude material thus obtained was purified by
flash column chromatography using a mixture of hexane and ethyl
acetate.
3.3. General procedure for de-acetylation of peracetyl glycosyl
aurones
In a 1-dram glass vial, 0.051 mmol of peracetylated glycosyl
aurone was dissolved in 1 mL MeOH. To this solution 10 mol% of
NaOMe was added (5 M in MeOH) and stirred at room temperature
for 2 h. After completion of the reaction, solvent was removed. The
crude material was purified using column chromatography, eluting
with ethyl acetate followed by 5e7% MeOH in DCM.
3.4. Characterization data for isolated compounds
Peracetylated Glycosyl Derivatives of Aurones
[(Z)-2-(4ʹ-cyanobenzylidene)benzofuran-3(2H)-one]-[(2ʺ,3ʺ,
4ʺ,6ʺ-tetra-O-acetyl)-6-O-b-D-glucopyranoside] (1a): Reaction
Scheme 5. Deacetylation of Glycosylated Aurones.
mixture of aurone 1 (0.26 mmol, 68.4 mg) and glycosyl donor
(0.52 mmol, 214 mg) in 4 mL chloroform was stirred for 72 h in the
presence of TBAB (0.2 equiv., 17.12 mg), potassium carbonate (6
equiv., 213 mg) and 3 mL DI water under the standard condition.
Eluent 40% ethyl acetate in hexane. Yield: 106 mg, 68%; yellow
doublet; br, broad. Cary 630 FT-IR (Agilent Technologies) was used
to collect IR spectra. All extracts were concentrated under reduced
pressure using a Buchi Rotary Evaporator. During purification and
identification of compounds, Thin Layer Chromatography (TLC) was
performed on silica coated TLC plates and monitored by short
wavelength (254 nm) UV light. Products were purified by silica gel
column chromatography. ACS grade reagents were employed dur-
ing the experiments.
solid, mp 239e240 ꢁC. 1H NMR (500 MHz, DMSO-D6)
d
¼ 8.12 (d,
J ¼ 8.5 Hz, 2H), 7.98 (d, J ¼ 8.4 Hz, 2H), 7.80 (d, J ¼ 8.5 Hz, 1H), 7.24
(d, J ¼ 2.0 Hz, 1H), 6.99 (s, 1H), 6.91 (dd, J ¼ 8.5, 1.9 Hz, 1H), 5.82 (d,
J ¼ 7.9 Hz, 1H), 5.40 (t, J ¼ 9.6 Hz, 1H), 5.15 (dd, J ¼ 9.7, 8.0 Hz, 1H),
5.05 (t, J ¼ 9.8 Hz, 1H), 4.41e4.33 (m, 1H), 4.18 (ddd, J ¼ 14.9, 12.5,
4.2 Hz,1H), 2.05 (s, 3H), 2.03 (s, 6H),1.99 (s, 3H). 13C NMR (126 MHz,
CDCl3)
d 182.78, 170.48, 170.27, 169.48, 169.28, 167.99, 164.15,
3.1. General procedure for the Synthesis of Aurones
148.86, 136.75, 132.55, 131.51, 126.48, 118.61, 116.43, 113.72, 112.70,
109.81, 100.49, 98.24, 72.56, 72.50, 70.98, 68.10, 61.97, 20.76, 20.70.
IR (neat) 2231, 1754, 1709, 1607, 1445, 1372, 1238, 1218, 1086, 1065,
1035, 910, 886, 829 cmꢂ1. HRMS (ESI): [M þ H], calcd for
All the aurones utilized for the glycosylation were synthesized
based on the literature [10]. 0.57 mmol of benzofuranone was
dissolved in 5 mL of glacial acetic acid in a 3-dram glass vial con-
taining a magnetic stir bar in it. To this solution, 1.1 equivalent of
aldehyde and 3 drops (0.1 mL) of concentrated HCl were added and
stirred at room temperature for 30 min to 4 h. In most cases the
reaction resulted in the precipitation of the desired product indi-
cating completion of the reaction. After the reaction was complete,
it was poured into ice-cold DI water. The precipitate obtained was
filtered and washed multiple times with DI water and air dried. The
resulting aurones were characterized and directly used for the
glycosylation reaction. For some of the aurones which did not
precipitate out efficiently, the water diluted reaction mixture was
neutralized with saturated NaHCO3 and extracted with ethyl
acetate.
C30H28NO12, 594.1612, found 594.1604.
[(Z)-2-(4ʹ-cyanobenzylidene)-7-methylbenzofuran-3(2H)-
one]
-[(2ʺ,3ʺ,4ʺ,6ʺ-tetra-O-acetyl)-6-O-b-D-glucopyranoside]
(2a): Reaction mixture of aurone 2 (0.26 mmol, 72 mg) and glycosyl
donor (0.52 mmol, 214 mg) in 4 mL chloroform was stirred for 48 h
in the presence of TBAB (0.2 equiv., 17.12 mg), potassium carbonate
(6 equiv., 213 mg) and 3 mL DI water under the standard condition
Eluent 40% ethyl acetate in hexane. Yield: 112 mg, 72%; yellow solid,
mp 226e228 ꢁC. 1H NMR (500 MHz, DMSO-D6)
d
8.14 (d, J ¼ 8.3 Hz,
2H), 7.97 (d, J ¼ 8.2 Hz, 2H), 7.74 (d, J ¼ 8.5 Hz, 1H), 7.04 (d,
J ¼ 8.6 Hz,1H), 6.97 (s, 1H), 5.74 (d, J ¼ 7.9 Hz, 1H), 5.47 (t, J ¼ 9.6 Hz,
1H), 5.24e5.16 (m, 1H), 5.05 (t, J ¼ 9.7 Hz, 1H), 4.34 (d, J ¼ 7.4 Hz,
1H), 4.23 (dd, J ¼ 12.4, 5.5 Hz, 1H), 4.11 (d, J ¼ 10.6 Hz, 1H), 2.42 (s,
3H), 2.05 (s, 3H), 2.03 (s, 6H),1.99 (s, 3H). 13C NMR (126 MHz, CDCl3)
The characterization of the isolated aurones is available in the
supporting information.
d
183.63, 170.57, 170.27, 169.51, 169.24, 166.00, 161.92, 149.02,
136.98, 132.63, 131.50, 123.38, 118.67, 116.16, 112.69, 112.57, 110.62,
109.51, 98.67, 72.47, 72.44, 70.92, 68.21, 61.91, 20.79, 20.73, 8.15. IR
(neat) 2959, 2926, 2229, 1750, 1706, 1657, 1603, 1369, 1208, 1037,
3.2. General procedure for Glycosylation of Aurones
In a 6-dram glass vial, aurone 1 (0.26 mmol, 65.6 mg) and
glycosyl donor peracetylglycosyl bromide (212 mg, 2 equiv.) were
dissolved in 4 mL chloroform. After stirring for 5 min, a solution of
tetrabutylammonium bromide (TBAB) (17.3 mg, 0.2 equiv.) and
potassium carbonate (213 mg, 6 equiv.) in water (3 mL) was added.
The reaction vial was then wrapped with Al-foil as the glycosyl
donor is light sensitive. The reaction mixture was then stirred for
next 72 h at room temperature. The reaction was monitored by thin
layer chromatography followed by p-anisaldehyde staining. After
completion of the reaction, the mixture was transferred to a 50 mL
centrifuge tube, diluted with distilled water, and extracted with
910, 875, 775, 685 cmꢂ1. HRMS (ESI): [M þ H], calcd for C31H30NO12
,
608.1768, found 608.1775.
[(Z)-2-(4ʹ-nitrobenzylidene)benzofuran-3(2H)-one]-[(2ʺ, 3ʺ,
4ʺ, 6ʺ-tetra-O-acetyl)-6-O- -glucopyranoside](3a): Reaction
b-D
mixture of aurone 3 (0.26 mmol, 74 mg) and glycosyl donor
(0.52 mmol, 214 mg) in 4 mL chloroform was stirred for 48 h in the
presence of TBAB (0.2 equiv., 17.12 mg), potassium carbonate (6
equiv., 213 mg) and 3 mL DI water under the standard condition.
Eluent 40% ethyl acetate in hexane. Yield: 147.5 mg, 92%; yellow
solid, mp 218e221 ꢁC. 1H NMR (500 MHz, DMSO-D6)
d
8.34 (d,
J ¼ 8.8 Hz, 2H), 8.20 (d, J ¼ 8.9 Hz, 2H), 7.81 (d, J ¼ 8.5 Hz, 1H), 7.22

A. Kafle et al. / Tetrahedron 76 (2020) 131528
5
(d, J ¼ 2.0 Hz, 1H), 7.04 (s, 1H), 6.93 (dd, J ¼ 8.5, 2.0 Hz, 1H), 5.84 (d,
J ¼ 7.9 Hz, 1H), 5.42 (t, J ¼ 9.6 Hz, 1H), 5.15 (dd, J ¼ 9.7, 8.0 Hz, 1H),
5.05 (t, J ¼ 9.8 Hz, 1H), 4.40e4.33 (m, 1H), 4.21 (dd, J ¼ 12.3, 5.8 Hz,
1H), 4.15 (dd, J ¼ 12.3, 2.3 Hz, 1H), 2.05 (s, 3H), 2.04 (s, 6H), 1.99 (s,
HRMS (ESI): [M þ H], calcd for C29H27Cl2O12, 637.0880, found
637.0887.
(Z)-2-(4ʹ-bromobenzylidene)benzofuran-3(2H)-one]- [(2ʺ, 3ʺ,
4ʺ, 6ʺ-tetra-O-acetyl)-6-O-b-D-glucopyranoside](7a): Reaction
3H). 13C NMR (126 MHz, CDCl3)
d
182.71, 170.47, 170.25, 169.47,
mixture of aurone 7 (0.26 mmol, 82 mg) and glycosyl donor
(0.52 mmol, 214 mg) in 4 mL chloroform was stirred for 48 h in the
presence of TBAB (0.2 equiv., 17.12 mg), potassium carbonate (6
equiv., 213 mg) and 3 mL DI water under the standard condition.
Eluent 40% ethyl acetate in hexane. Yield: 149.5 mg, 89%; yellow
169.28, 168.03, 164.20, 149.05, 147.68, 138.64, 131.74, 126.50, 124.05,
116.31, 113.80, 109.17, 100.48, 98.20, 72.53, 72.48, 70.96, 68.08,
61.95, 20.75, 20.68. IR (neat) 2956, 2928, 1752, 1711, 1611, 1594,
1516, 1445, 1341, 1212, 1084, 1045, 910, 864, 852, 773 cmꢂ1. HRMS
(ESI): [M þ H], calcd for C29H28NO14, 614.1510, found 614.1502.
[(Z)-2-(3ʹ-nitrobenzylidene)benzofuran-3(2H)-one]- [(2ʺ, 3ʺ,
solid, mp 224e226 ꢁC. 1H NMR (300 MHz, DMSO-D6)
d 7.90 (d,
J ¼ 8.0 Hz, 2H), 7.77 (d, J ¼ 8.5 Hz,1H), 7.71 (d, J ¼ 8.0 Hz, 2H), 7.20 (s,
1H), 6.90e6.88 (m, 2H), 5.82 (d, J ¼ 7.5 Hz, 1H), 5.41 (t, J ¼ 9.5 Hz,
1H), 5.14 (dd, J ¼ 12.5, 4.9 Hz, 1H), 5.05 (t, J ¼ 9.5 Hz, 1H), 4.41e4.35
(m, 1H), 4.18 (m, 2H), 2.03 (s, 9H), 1.99 (s, 3H). 13C NMR (125 MHz,
4ʺ, 6ʺ-tetra-O-acetyl)-6-O-b-D-glucopyranoside](4a): Reaction
mixture of aurone 4 (0.26 mmol, 74 mg) and glycosyl donor
(0.52 mmol, 214 mg) in 4 mL chloroform was stirred for 48 h in the
presence of TBAB (0.2 equiv., 17.12 mg), potassium carbonate (6
equiv., 213 mg) and 3 mL DI water under the standard condition
Eluent 40% ethyl acetate in hexane. Yield: 118 mg, 74%; yellow solid,
CDCl3) d 182.94,170.51,170.27,169.49,169.30,167.78,163.88,147.78,
132.75, 132.24, 131.19, 126.24, 124.41, 116.83, 113.51, 111.38, 100.37,
98.32, 72.56, 71.02, 68.19, 62.03, 20.77, 20.70. IR (neat) 3097, 3067,
2957,1739,1706,1654,1611,1490,1378,1348,1225,1134,1106,1073,
mp 218e221 ꢁC. 1H NMR (300 MHz, DMSO-D6)
d 8.79 (s, 1H), 8.37
(d, J ¼ 7.7 Hz, 1H), 8.28 (d, J ¼ 8.2 Hz, 1H), 7.82e7.77 (m, 2H), 7.21 (s,
1H), 7.09 (s, 1H), 6.92 (d, J ¼ 8.4 Hz, 1H), 5.86 (d, J ¼ 7.9 Hz, 1H), 5.41
(t, J ¼ 9.5 Hz, 1H), 5.15 (t, J ¼ 8.8 Hz, 1H), 5.05 (t, J ¼ 9.7 Hz, 1H), 4.38
(d, J ¼ 7.2 Hz, 1H), 4.19 (m, 2H), 2.04 (s, 9H), 1.99 (s, 3H). 13C NMR
1050, 1037 821 cmꢂ1. HRMS (ESI): [M þ H], calcd for C29H28BrO12
,
647.0764, found 647.0759.
(Z)-2-(4ʹ-bromobenzylidene)-4-methylbenzofuran-3(2H)
one]- [(2ʺ, 3ʺ, 4ʺ, 6ʺ-tetra-O-acetyl)-6-O-b -D-glucopyranoside]
(125 MHz, CDCl3)
d
182.72, 170.57, 170.25, 169.50, 169.30, 168.05,
(8a): Reaction mixture of aurone 8 (0.26 mmol, 86 mg) and glycosyl
donor (0.52 mmol, 214 mg) in 4 mL chloroform was stirred for 48 h
in the presence of TBAB (0.2 equiv., 17.12 mg), potassium carbonate
(6 equiv., 213 mg) and 3 mL DI water under the standard condition.
Eluent 40% ethyl acetate in hexane. Yield: 138 mg, 82%; yellow
164.18, 148.75, 148.63, 136.80, 133.97, 129.92, 126.42, 125.41, 124.10,
116.41, 113.91, 109.36, 100.34, 98.16, 72.60, 72.55, 71.01, 68.14, 62.01,
20.71, 20.70. IR (neat) 2962, 2924, 1747, 1709, 1665, 1613, 1527, 1447,
1352, 1236, 1220, 1037, 914, 905, 773, 739, 681 cmꢂ1. HRMS (ESI):
[M þ H], calcd for C29H28NO14, 614.1510, found 614.1513.
solid, mp 99e102 ꢁC. 1H NMR (300 MHz, DMSO-D6)
d 7.89 (d,
[(Z)-2-(2ʹ-chlorobenzylidene)-7-methylbenzofuran-3(2H)-
J ¼ 8.5 Hz, 2H), 7.71 (d, J ¼ 8.5 Hz, 2H), 7.00 (d, J ¼ 1.8 Hz, 1H), 6.82
(s, 1H), 6.69 (dd, J ¼ 1.8, 0.9 Hz, 1H), 5.79 (d, J ¼ 7.8 Hz, 1H), 5.39 (t,
J ¼ 9.6 Hz, 1H), 5.12 (dd, J ¼ 9.6, 7.8 Hz, 1H), 5.03 (t, J ¼ 9.6 Hz, 1H),
4.40e4.31 (m, 1H), 4.22e4.13 (m, 2H), 2.55 (s, 3H), 2.05 (s, 3H), 2.03
one]-[(2ʺ,3ʺ,4ʺ,6ʺ-tetra-O-acetyl)-6-O-b-D-glucopyranoside] (5a):
Reaction mixture of aurone 5 (0.26 mmol, 74.5 mg) and glycosyl
donor (0.52 mmol, 214 mg) in 4 mL chloroform was stirred for 48 h
in the presence of TBAB (0.2 equiv., 17.12 mg), potassium carbonate
(6 equiv., 213 mg) and 3 mL DI water under the standard condition.
Eluent 40% ethyl acetate in hexane. Yield: 109 mg, 68%; yellow
(s, 6H), 1.98 (s, 3H). 13C NMR (125 MHz, CDCl3)
d 183.58, 170.50,
170.26, 169.50, 169.30, 168.02, 163.19, 147.95, 142.00, 132.60, 132.14,
131.37, 124.05, 115.17,114.40,110.25, 98.19, 97.54, 72.58, 72.51, 71.03,
68.25, 62.10, 20.76, 20.73, 20.69, 18.15. IR (neat) 2957, 1747, 1704,
1667, 1596, 1488, 1367, 1214, 1171, 1138, 1037, 1013, 909, 821,
732 cmꢂ1. HRMS (ESI): [M þ H], calcd for C30H30BrO12, 661.0920,
found 661.0923.
solid, mp 195e197 ꢁC. 1H NMR (500 MHz, DMSO-D6)
d 8.31 (dd,
J ¼ 7.8, 1.4 Hz, 1H), 7.74 (d, J ¼ 8.5 Hz, 1H), 7.62 (dd, J ¼ 8.0, 0.9 Hz,
1H), 7.54 (t, J ¼ 7.3 Hz,1H), 7.47 (td, J ¼ 7.8,1.6 Hz,1H), 7.07e7.01 (m,
2H), 5.74 (d, J ¼ 7.9 Hz, 1H), 5.47 (t, J ¼ 9.6 Hz, 1H), 5.19 (dd, J ¼ 9.8,
8.0 Hz,1H), 5.05 (t, J ¼ 9.7 Hz,1H), 4.35 (ddd, J ¼ 9.9, 5.6, 2.3 Hz,1H),
4.23 (dd, J ¼ 12.3, 5.7 Hz, 1H), 4.11 (dd, J ¼ 12.2, 2.1 Hz, 1H), 2.16 (s,
3H), 2.06 (s, 3H), 2.03 (s, 3H), 2.02 (s, 3H), 2.00 (s, 3H). 13C NMR
[(Z)-2-(4ʹ-bromobenzylidene)-7-methylbenzofuran-3(2H)-
one]-[(2ʺ,3ʺ,4ʺ,6ʺ-tetra-O-acetyl)-6-O-b-D-glucopyranoside] (9a):
Reaction mixture of aurone 9 (0.26 mmol, 86 mg) and glycosyl
donor (0.52 mmol, 214 mg) in 4 mL chloroform was stirred for 48 h
in the presence of TBAB (0.2 equiv., 17.12 mg), potassium carbonate
(6 equiv., 213 mg) and 3 mL DI water under the standard condition.
Eluent 30% ethyl acetate in hexane. Yield: 120.5 mg, 70%; yellow
(125 MHz, CDCl3)
d 183.68, 170.57, 170.23, 169.51, 169.25, 165.85,
161.59, 148.39, 135.95, 132.09, 130.60, 130.50, 130.11, 127.21, 123.19,
116.49, 112.54, 110.35, 107.41, 98.70, 72.47, 72.40, 70.91, 68.23, 61.92,
20.76, 20.70, 8.05. IR (neat) 2961, 2935, 1737, 1709, 1657, 1607, 1426,
1378, 1214, 1035, 914, 782, 758 732 cmꢂ1. HRMS (ESI): [M þ H],
calcd for C30H30ClO12, 617.1426, found 617.1433.
solid, mp 218e219 ꢁC. 1H NMR (300 MHz, DMSO-D6)
d 7.92 (d,
J ¼ 8.5 Hz, 2H), 7.73e7.70 (m, 3H), 7.03 (d, J ¼ 8.5 Hz, 1H), 6.89 (s,
1H), 5.73 (d, J ¼ 7.9 Hz, 1H), 5.47 (t, J ¼ 9.6 Hz, 1H), 5.26e5.14 (m,
1H), 5.05 (t, J ¼ 9.7 Hz, 1H), 4.34 (d, J ¼ 9.9 Hz, 1H), 4.23 (dd, J ¼ 12.1,
5.4 Hz, 1H), 4.11 (d, J ¼ 11.7 Hz, 1H), 2.18 (s, 3H), 2.06 (s, 3H), 2.03 (s,
[(Z)-2-(3ʹ,5ʹ-dichlorobenzylidene)benzofuran-3(2H)-one]-
[(2ʺ, 3ʺ, 4ʺ, 6ʺ-tetra-O-acetyl)-6-O-b-D-glucopyranoside] (6a):
Reaction mixture of aurone 6 (0.26 mmol, 79.8 mg) and glycosyl
donor (0.52 mmol, 214 mg) in 4 mL chloroform was stirred for 48 h
in the presence of TBAB (0.2 equiv., 17.12 mg), potassium carbonate
(6 equiv., 213 mg) and 3 mL DI water under the standard condition.
Eluent 30% ethyl acetate in hexane. Yield: 124.5 mg, 65%; yellow
6H), 2.00 (s, 3H). 13C NMR (125 MHz, CDCl3)
d 183.81,170.59, 170.28,
169.52, 169.26, 165.84, 161.62, 147.95, 132.78, 132.34, 131.42, 124.30,
123.13,116.59,112.60,111.11,110.41, 98.78, 72.52, 72.47, 70.97, 68.28,
61.96, 20.79, 20.74, 8.11. IR (neat) 2957, 2263, 1745, 1706, 1657, 1605,
1490, 1371, 1223, 1041, 1013, 918, 905, 888, 823, 734 cmꢂ1. HRMS
(ESI): [M þ H], calcd for C30H30BrO12, 661.0920, found 661.0918.
(Z)-2-(4ʹ-fluorobenzylidene)benzofuran-3(2H)-one]- [(2ʺ, 3ʺ,
solid, mp 109e110 ꢁC. 1H NMR (500 MHz, DMSO-D6)
d 7.99 (d,
J ¼ 1.5 Hz, 2H), 7.79 (d, J ¼ 8.5 Hz, 1H), 7.71 (t, J ¼ 1.5 Hz, 1H), 7.25 (d,
J ¼ 1.5 Hz, 1H), 6.92e6.89 (m, 2H), 5.84 (d, J ¼ 8.0 Hz, 1H), 5.38 (t,
J ¼ 9.5 Hz, 1H), 5.15 (dd, J ¼ 9.5, 8.0 Hz, 1H), 5.04 (t, J ¼ 9.5 Hz, 1H),
4.42e4.36 (m, 1H), 4.19 (dd, J ¼ 12.0, 6.0 Hz, 1H), 4.14 (dd, J ¼ 12.0,
2.5 Hz, 1H), 2.05 (s, 3H), 2.03 (s, 6H), 1.99 (s, 3H). 13C NMR (125 MHz
4ʺ,6ʺ-tetra-O-acetyl)-6-O-
b-
D-glucopyranoside](10a):
Reaction
mixture of aurone 10 (0.26 mmol, 67 mg) and glycosyl donor
(0.52 mmol, 214 mg) in 4 mL chloroform was stirred for 48 h in the
presence of TBAB (0.2 equiv., 17.12 mg), potassium carbonate (6
equiv., 213 mg) and 3 mL DI water under the standard condition.
Eluent 40% ethyl acetate in hexane. Yield: 130 mg, 85%; off-white
CDCl3)
d 182.46, 170.45, 170.15, 169.43, 169.19, 167.83, 164.02,
148.32, 135.33, 134.99, 129.32, 128.99, 126.19, 116.23, 113.89, 109.05,
100.09, 98.09, 72.51, 72.45, 70.89, 68.13, 62.03, 20.80, 20.60. IR
(neat) 1749, 1709, 1611, 1447, 1369, 1216, 1035, 961, 907, 674 cmꢂ1
.
solid, mp 191e194 ꢁC. 1H NMR (500 MHz, DMSO-D6)
d 8.04 (dd,

6
A. Kafle et al. / Tetrahedron 76 (2020) 131528
J ¼ 9.0, 6.0 Hz, 2H), 7.78 (d, J ¼ 8.5 Hz, 1H), 7.37 (t, J ¼ 9.0 Hz, 2H),
7.21 (d, J ¼ 2.0 Hz,1H), 6.95 (s,1H), 6.90 (dd, J ¼ 8.5, 2.0 Hz,1H), 5.81
(d, J ¼ 7.5 Hz, 1H), 5.41 (t, J ¼ 10.0 Hz, 1H), 5.15 (dd, J ¼ 9.5, 8.0 Hz,
1H), 5.05 (t, J ¼ 10.0 Hz,1H), 4.37 (ddd, J ¼ 10.0, 5.5, 2.5 Hz,1H), 4.20
(dd, J ¼ 12.5, 6.0 Hz, 1H), 4.15 (dd, J ¼ 12.5, 2.5 Hz, 1H), 2.05 (s, 3H),
J ¼ 8.0 Hz, 1H), 5.40 (t, J ¼ 9.5 Hz, 1H), 5.14 (dd, J ¼ 10.0, 8.0 Hz, 1H),
5.04 (t, J ¼ 10.0 Hz,1H), 4.43e4.33 (m, 1H), 4.20 (dd, J ¼ 12.0, 6.0 Hz,
1H), 4.16 (dd, J ¼ 12.0, 2.5 Hz, 1H), 2.37 (s, 3H), 2.07e2.03 (m, 9H),
1.99 (s, 3H). 13C NMR (125 MHz, DMSO-D6)
d 181.84, 169.95, 169.64,
169.38, 169.13, 167.16, 163.41, 146.64, 140.28, 131.30, 129.71, 129.10,
125.89, 115.91, 113.49, 111.91, 99.85, 96.50, 71.87, 71.22, 70.45, 67.91,
61.68, 21.18, 20.46, 20.44, 20.35, 20.31. IR (neat) 2957, 2918, 1737,
1700, 1652, 1607, 1596, 1443, 1378, 1348, 1246, 1052 cmꢂ1. HRMS
(ESI): [M þ H], calcd for C30H31O12, 583.1816, found 583.1810.
[(Z)-2-(3ʹ, 5ʹ-dimethoxybenzylidene)benzofuran-3(2H)-one]-
2.03 (s, 6H), 1.99 (s, 3H). 13C NMR (125 MHz, CDCl3)
d 183.01, 170.53,
170.29, 169.50, 169.31, 167.77, 163.80, 163.5 (d, [1]JC-F ¼ 252.5 Hz),
147.21, 133.5 (d, [3]JC-F ¼ 8.3 Hz), 128.58 (d, [4]JC-F ¼ 2.0 Hz), 126.21,
116.96, 116.31 (d, [2]JC-F ¼ 21.7 Hz), 113.42, 111.62, 100.34, 98.34,
72.57, 71.01, 68.18, 62.02, 20.77, 20.71. IR (neat) 2950, 1745 1706,
1657, 1600, 1449, 1369, 1216, 1071 1033, 892, 830, 702, 685 cmꢂ1
.
[(2ʺ,3ʺ,4ʺ,6ʺ-tetra-O-acetyl)-6-O-
b
-D
-
glucopyranoside] (14a):
HRMS (ESI): [M þ H], calcd for C29H28FO12, 587.1565, found
Reaction mixture of aurone 14 (0.26 mmol, 79 mg) and glycosyl
donor (0.52 mmol, 214 mg) in 4 mL chloroform was stirred for 48 h
in the presence of TBAB (0.2 equiv., 17.12 mg), potassium carbonate
(6 equiv., 213 mg) and 3 mL DI water under the standard con-
ditionEluent 50% ethyl acetate in hexane. Yield: 100 mg, 61%; off-
587.1560.
(Z)-4-methyl-2-(4ʹ-(trifluoromethyl)benzylidene)benzo-
furan-3(2H)-one]-[(2ʺ,3ʺ,4ʺ,6ʺ-tetra-O-acetyl)-6-O-b-D-gluco-
pyra- noside (11a): Reaction mixture of aurone 11 (0.13 mmol,
42 mg) and glycosyl donor (0.26 mmol, 107 mg) in 4 mL chloroform
was stirred for 48 h in the presence of TBAB (0.2 equiv., 8.6 mg),
potassium carbonate (6 equiv., 106.5 mg) and 3 mL DI water under
the standard condition. Eluent 40% ethyl acetate in hexane. Yield:
51 mg, 60%; off-white solid, mp 201e203 ꢁC. 1H NMR (500 MHz,
white solid, mp 192e193 ꢁC. 1H NMR (500 MHz, DMSO-D6)
d 7.77
(d, J ¼ 8.5 Hz, 1H), 7.23 (d, J ¼ 2.0 Hz, 1H), 7.16 (d, J ¼ 2.0 Hz, 2H),
6.90 (dd, J ¼ 8.5, 2.0 Hz,1H), 6.83 (s, 1H), 6.63 (t, J ¼ 2.0 Hz, 1H), 5.83
(d, J ¼ 8.0 Hz, 1H), 5.39 (t, J ¼ 9.5 Hz, 1H), 5.14 (dd, J ¼ 10.0, 8.0 Hz,
1H), 5.04 (t, J ¼ 10.0 Hz, 1H), 4.42e4.34 (m, 1H), 4.19 (dd, J ¼ 12.5,
6.0 Hz, 1H), 4.14 (dd, J ¼ 12.0, 2.5 Hz, 1H), 3.80 (s, 6H), 2.03 (s, 9H),
DMSO-D6)
d
8.14 (d, J ¼ 8.0 Hz, 2H), 7.86 (d, J ¼ 8.0 Hz, 2H), 7.01 (s,
1H), 6.92 (s, 1H), 6.72 (s, 1H), 5.80 (d, J ¼ 8.0 Hz, 1H), 5.40 (t,
J ¼ 10.0 Hz, 1H), 5.13 (dd, J ¼ 10.0, 8.0 Hz, 1H), 5.04 (t, J ¼ 10.0 Hz,
1H), 4.38e4.33 (m, 1H), 4.19 (dd, J ¼ 12.0, 6.0 Hz, 1H), 4.15 (dd,
J ¼ 12.0, 2.5 Hz, 1H), 2.56 (s, 3H), 2.05 (s, 3H), 2.03 (s, 6H), 1.98 (s,
1.99 (s, 3H). 13C NMR (125 MHz, DMSO-D6)
d 181.94, 169.98, 169.64,
169.38, 169.13, 167.28, 163.53, 160.66, 147.20, 133.40, 126.01, 115.73,
113.39, 111.63, 109.49, 101.70, 99.98, 96.35, 71.86, 71.21, 70.41, 67.91,
61.68, 55.41, 20.48, 20.43, 20.36, 20.31. IR (neat) 2950, 2922, 2853,
1749,1739,1704,1657,1607,1590,1449,1367,1318,1249,1223,1091,
3H). 13C NMR (125 MHz, CDCl3)
d 183.65, 170.55, 170.31, 169.53,
2
169.35, 168.28, 163.40, 148.70, 142.25, 135.93, 131.27 (q, JC-
1974, 843, 776 cmꢂ1. HRMS (ESI): [M þ H], calcd for C31H33O14
,
¼ 32.8 Hz), 125.74, 123.9 (q, 1JC-F ¼ 272.2 Hz) 115.02,114.55, 109.51,
629.1870, found 629.1875.
F
98.18, 97.63, 72.57, 72.55, 71.04, 68.22, 62.10, 20.78, 20.75, 20.72,
18.22. IR (neat) 2941, 1749, 1708, 1598, 1326, 1216, 1123, 1052, 1035,
1020, 910, 702, 687 cmꢂ1. HRMS (ESI): [M þ H], calcd for
[(Z)-2-(3 ʹ, 4 ʹ, 5 ʹ-trimethoxybenzylidene)benzofuran-3(2H)-
one]-[(2ʺ,3ʺ,4ʺ, 6ʺ-tetra-O-acetyl)-6-O- glucopyranoside]
b
-D-
(15a): Reaction mixture of aurone 15 (0.26 mmol, 85 mg) and
glycosyl donor (0.52 mmol, 214 mg) in 4 mL chloroform was stirred
for 48 h in the presence of TBAB (0.2 equiv., 17.12 mg), potassium
carbonate (6 equiv., 213 mg) and 3 mL DI water under the standard
condition. Eluent 50% ethyl acetate in hexane. Yield: 156 mg, 91%;
C
29H28F3O12, 651.1689, found 651.1684.
[(Z)-2-(2ʹ-fluoro-3ʹ-methoxybenzylidene)benzofuran-3(2H)-
one]-[(2ʺ,3ʺ, 4ʺ, 6ʺ-tetra-O-acetyl)-6-O-b-D- glucopyranoside]
(12a): Reaction mixture of aurone 12 (0.26 mmol, 74 mg) and
glycosyl donor (0.52 mmol, 214 mg) in 4 mL chloroform was stirred
for 48 h in the presence of TBAB (0.2 equiv., 17.12 mg), potassium
carbonate (6 equiv., 213 mg) and 3 mL DI water under the standard
condition. Eluent 40% ethyl acetate in hexane. Yield: 141 mg, 88%;
off-white solid, mp 220e222 ꢁC. 1H NMR (500 MHz, DMSO-D6)
yellow solid, mp 113e116 ꢁC. 1H NMR (500 MHz, DMSO-D6)
d 7.79
(d, J ¼ 8.6 Hz, 1H), 7.35 (s, 2H), 7.19 (d, J ¼ 2.1 Hz, 1H), 6.93 (dd,
J ¼ 8.6, 2.2 Hz, 1H), 6.87 (s, 1H), 5.86 (d, J ¼ 8.0 Hz, 1H), 5.42 (t,
J ¼ 9.6 Hz, 1H), 5.14 (dd, J ¼ 9.7, 7.9 Hz, 1H), 5.05 (t, J ¼ 9.7 Hz, 1H),
4.36 (ddd, J ¼ 10.1, 5.7, 2.5 Hz,1H), 4.21 (dd, J ¼ 12.4, 5.7 Hz,1H), 4.11
(dd, J ¼ 12.4, 2.3 Hz, 1H), 3.86 (s, 6H), 3.74 (s, 3H), 2.03 (s, 3H), 2.02
d
7.79 (d, J ¼ 8.5 Hz, 1H), 7.77e7.71 (m, 1H), 7.33e7.26 (m, 2H),
7.21 (d, J ¼ 2.0 Hz,1H), 6.90 (dd, J ¼ 8.5, 2.0 Hz,1H), 6.85 (s,1H), 5.81
(d, J ¼ 8.0 Hz, 1H), 5.40 (t, J ¼ 9.5 Hz, 1H), 5.14 (dd, J ¼ 9.5, 8.0 Hz,
1H), 5.04 (t, J ¼ 10.0 Hz, 1H), 4.40e4.38e4.35 (m, 1H), 4.19 (dd,
J ¼ 12.0, 6.0 Hz, 1H), 4.15 (dd, J ¼ 12.0, 2.5 Hz, 1H), 3.88 (s, 3H), 2.04
(s, 3H), 2.01 (s, 3H), 1.98 (s, 3H). 13C NMR (125 MHz, CDCl3)
d 182.85,
170.50, 170.20, 169.44, 169.30, 167.41, 163.54, 153.37, 146.99, 140.18,
127.57, 126.11, 117.04, 113.09, 112.63, 109.05, 100.66, 98.06, 72.46,
72.34, 71.00, 68.17, 61.92, 61.05, 56.35, 20.70, 20.64. IR (neat) 1754,
1732,1652,1605,1506,1447,1423,1372,1350,1339,1240,1214,1074,
(s, 3H), 2.03 (s, 6H), 1.99 (s, 3H). 13C NMR (125 MHz, CDCl3)
d 182.77,
1
170.54, 170.25, 169.49, 169.31, 167.83, 163.87, 151.58 (d, JC-
1035, 843, 910, 691 cmꢂ1. HRMS (ESI): [M þ H], calcd for C32H35O15
,
2
¼ 254.8 Hz), 148.43, 147.91 (d, JC-F ¼ 10.6 Hz), 126.25, 124.09 (d,
659.1976, found 659.1971.
F
4JC-F ¼ 4.1 Hz), 122.71, 121.17 (d, JC-F ¼ 9.2 Hz), 116.78, 114.72,
(Z)-7-methyl-2-(3 ʹ,
furan-3(2H)-one]-[(2ʺ,3ʺ,4ʺ,6ʺ-tetra-O-acetyl)-6-O-b-D
4
ʹ, 5ʹ-trimethoxybenzylidene)benzo-
-glucopyr-
2
113.49, 103.81 (d, 3JC-F ¼ 8.0 Hz), 100.33, 98.34, 72.56, 72.53, 70.97,
68.19, 62.02, 56.43, 20.75, 20.69. IR (neat) 2969, 1747, 1737, 1708,
1657, 1613, 1449, 1253, 1223, 1132, 1087, 1035, 842, 834,
782 722 cmꢂ1. HRMS (ESI): [M þ H], calcd for C30H29FO13, 616.1592,
found 616.1587.
anoside] (16a): Reaction mixture of aurone 16 (0.26 mmol, 89 mg)
and glycosyl donor (0.52 mmol, 214 mg) in 4 mL chloroform was
stirred for 48 h in the presence of TBAB (0.2 equiv., 17.12 mg), po-
tassium carbonate (6 equiv., 213 mg) and 3 mL DI water under the
standard condition. Eluent 50% ethyl acetate in hexane. Yield:
150.7 mg, 87%; yellow solid, mp 127e130 ꢁC. 1H NMR (500 MHz,
[(Z)-2-(4ʹ-methylbenzylidene)benzofuran-3(2H)-one]-[(2ʺ,
3ʺ, 4ʺ,6ʺ-tetra-O-acetyl)-6-O-b-D-glucopyranoside](13a): Reac-
tion mixture of aurone 13 (0.26 mmol, 66 mg) and glycosyl donor
(0.52 mmol, 214 mg) in 4 mL chloroform was stirred for 48 h in the
presence of TBAB (0.2 equiv., 17.12 mg), potassium carbonate (6
equiv., 213 mg) and 3 mL DI water under the standard condition.
Eluent 40% ethyl acetate in hexane. Yield: 129 mg, 86%; off-white
DMSO-D6)
d
7.69 (d, J ¼ 8.5 Hz, 1H), 7.39 (s, 2H), 7.02 (d, J ¼ 8.5 Hz,
1H), 6.87 (s, 1H), 5.72 (d, J ¼ 8.0 Hz, 1H), 5.47 (t, J ¼ 9.5 Hz, 1H), 5.19
(dd, J ¼ 9.5, 8.0 Hz, 1H), 5.05 (t, J ¼ 9.5 Hz, 1H), 4.39e4.31 (m, 1H),
4.23 (dd, J ¼ 12.5, 5.5 Hz, 1H), 4.11 (d, J ¼ 10.0 Hz, 1H), 3.86 (s, 6H),
3.73 (s, 3H), 2.17 (s, 3H), 2.06 (s, 3H), 2.03 (s, 6H), 1.99 (s, 3H). 13
C
solid, mp 210e211 ꢁC. 1H NMR (500 MHz, DMSO-D6)
d
7.87 (d,
NMR (125 MHz CDCl3) d 183.62, 170.56, 170.23, 169.50, 169.25,
J ¼ 8.0 Hz, 2H), 7.77 (d, J ¼ 8.5 Hz, 1H), 7.33 (d, J ¼ 8.0 Hz, 2H), 7.22
165.53, 161.32, 153.33, 147.27, 139.84, 127.82, 123.04, 116.68, 112.80,
112.09, 110.13, 108.68, 98.66, 72.44, 72.39, 70.93, 68.24, 61.92, 61.09,
(d, J ¼ 2.0 Hz, 1H), 6.89 (dd, J ¼ 8.0, 2.5 Hz, 2H), 6.87 (s, 1H), 5.81 (d,

A. Kafle et al. / Tetrahedron 76 (2020) 131528
7
56.07, 20.75, 20.68, 7.90. IR (neat) 2942, 2844, 1752, 1730, 1655,
1611, 1506, 1426, 1214, 1037, 910, 775 cmꢂ1. HRMS (ESI): [M þ H],
calcd for C33H37O15, 673.2133, found 673.2135.
donor (0.52 mmol, 214 mg) in 4 mL chloroform was stirred for 48 h
in the presence of TBAB (0.2 equiv., 17.12 mg), potassium carbonate
(6 equiv., 213 mg) and 3 mL DI water under the standard condition.
Eluent 40% ethyl acetate in hexane. Yield: 136 mg, 87%; yellow
(Z)-2-(4ʹ-(dimethylamino)benzylidene)benzofuran-3(2H)
one]-[(2ʺ,3ʺ,4ʺ,6ʺ-tetra-O-acetyl)-6-O-
b
-D-
glucopyranoside]
solid, mp 78e79 ꢁC. 1H NMR (500 MHz, DMSO-D6)
d 7.81
(17a): Reaction mixture of aurone 17 (0.26 mmol, 73 mg) and
glycosyl donor (0.52 mmol, 214 mg) in 4 mL chloroform was stirred
for 48 h in the presence of TBAB (0.2 equiv., 17.12 mg), potassium
carbonate (6 equiv., 213 mg) and 3 mL DI water under the standard
condition. Eluent 40% ethyl acetate in hexane. Yield: 141 mg, 89%;
(d ¼ 7.0 Hz, 2H), 7.69 (d, J ¼ 2.0 Hz, 1H), 7.66 (dd, J ¼ 8.5, 2.0 Hz, 1H),
7.59 (d, J ¼ 8.0 Hz, 1H), 7.33 (t, J ¼ 8.0 Hz,1H), 7.23 (d, J ¼ 8.5 Hz,1H),
6.96 (s, 1H), 5.54 (d, J ¼ 8.0 Hz, 1H), 5.41 (t, J ¼ 9.5 Hz, 1H), 5.09 (dd,
J ¼ 10.0, 8.0 Hz, 1H), 5.02 (t, J ¼ 9.5 Hz, 1H), 4.23 (dt, J ¼ 9.0, 6.0 Hz,
2H), 4.10 (t, J ¼ 7.0 Hz, 1H), 3.84 (s, 3H), 2.03 (s, 6H), 2.01 (s, 3H), 1.98
orange solid, mp 140e142 ꢁC. 1H NMR (500 MHz, DMSO-D6)
d
7.82
(s, 3H). 13C NMR (125 MHz, CDCl3)
d 184.71, 170.73, 170.41, 169.54,
(d, J ¼ 9.0 Hz, 2H), 7.72 (d, J ¼ 8.5 Hz,1H), 7.17 (d, J ¼ 2.0 Hz,1H), 6.86
(dd, J ¼ 8.5, 2.0 Hz, 1H), 6.83 (s, 1H), 6.79 (d, J ¼ 9.0 Hz, 2H), 5.79 (d,
J ¼ 8.0 Hz, 1H), 5.41 (t, J ¼ 9.5 Hz, 1H), 5.14 (dd, J ¼ 9.5, 8.0 Hz, 1H),
5.04 (t, J ¼ 10.0 Hz, 1H), 4.40e4.33 (m, 1H), 4.21 (dd, J ¼ 12.0, 6.0 Hz,
1H), 4.16 (dd, J ¼ 12.0, 2.5 Hz, 1H), 3.02 (s, 6H), 2.06 (s, 3H), 2.04 (s,
3H), 2.03 (s, 3H), 1.99 (s, 3H). 13C NMR (125 MHz, DMSO-D6)
169.47, 166.06, 150.68, 147.62, 146.57, 136.97, 128.88, 125.30, 124.82,
123.68, 121.78, 119.51, 115.40, 113.00, 112.79, 100.33, 72.60, 72.23,
71.21, 68.40, 61.97, 56.25, 20.85, 20.78, 20.73. IR (neat) 2924, 1745,
1648, 1600, 1514, 1369, 1216, 1067, 1035, 884, 758, 702 cmꢂ1. HRMS
(ESI): [M þ H], calcd for C30H31O13, 599.1796, found 599.1800.
(Z)-2-(3ʹ-methoxybenzylidene)benzofuran-3(2H)-one]-
d
180.86, 169.96, 169.65, 169.38, 169.14, 166.17, 162.74, 151.33,
[(2ʺ,3ʺ, 4ʺ,6ʺ-tetra-O-acetyl)-2ʹ-O-b-D-glucopyranoside] (21a):
144.71, 133.29, 125.40, 118.81, 116.65, 114.04, 113.09, 111.94, 99.73,
96.59, 71.88, 71.17, 70.50, 67.94, 61.67, 20.45, 20.35, 20.32. IR (neat)
2920, 2117, 1747, 1698, 1644, 1588, 1527, 1369, 1222, 1037, 951, 814,
732 cmꢂ1. HRMS (ESI): [M þ H], calcd for C31H34NO12, 612.2081,
found 612.2077.
Reaction mixture of aurone 21 (0.26 mmol, 69.5 mg) and glycosyl
donor (0.52 mmol, 214 mg) in 4 mL chloroform was stirred for 48 h
in the presence of TBAB (0.2 equiv., 17.12 mg), potassium carbonate
(6 equiv., 213 mg) and 3 mL DI water under the standard condition.
Eluent 40% ethyl acetate in hexane. Yield: 98.5 mg, 64%; yellow
[(Z)-2-(4ʹ-(dimethylamino)
methylbenzofuran-3(2H)-one]-[(2ʺ,3ʺ,4ʺ,6ʺ-tetra-O-acetyl)-6-O-
- glucopyranoside] (18a): Reaction mixture of aurone 18
benzylidene)-7-
solid, mp 105e107 ꢁC. 1H NMR (500 MHz, CHLOROFORM-D)
d 7.92
(dd, J ¼ 8.0, 1.5 Hz, 1H), 7.80 (dd, J ¼ 8.0, 1.5 Hz, 1H), 7.64 (ddd,
J ¼ 8.5, 7.5, 1.5 Hz, 1H), 7.44 (s, 1H), 7.29 (d, J ¼ 8.0 Hz, 1H), 7.26e7.19
(m, 2H), 6.99 (dd, J ¼ 8.0, 1.5 Hz, 1H), 5.40 (dd, J ¼ 9.5, 8.0 Hz, 1H),
5.31 (t, J ¼ 9.5 Hz,1H), 5.25 (t, J ¼ 9.5 Hz, 1H), 5.05 (d, J ¼ 7.5 Hz, 1H),
2.14 (s, 3H), 2.06 (s, 3H), 2.01 (s, 3H),1.99 (s, 3H). 13C NMR (125 MHz,
b-D
(0.26 mmol, 77 mg) and glycosyl donor (0.52 mmol, 214 mg) in
4 mL chloroform was stirred for 48 h in the presence of TBAB (0.2
equiv., 17.12 mg), potassium carbonate (6 equiv., 213 mg) and 3 mL
DI water under the standard condition. Eluent 40% ethyl acetate in
hexane. Yield: 137 mg, 84%; red solid, mp 107e109 ꢁC. 1H NMR
CDCl3) d 184.49,170.95,170.58,169.64,169.44,166.11,152.16,147.33,
144.64, 136.81, 128.40, 125.66, 124.79, 123.49, 121.86, 113.85, 112.91,
108.00, 101.58, 72.88, 71.80, 71.71, 68.48, 61.58, 56.05, 20.85, 20.79,
20.70, 20.57. IR (neat) 3613, 2952,1745,1704,1652,1603,1462,1367,
1218, 1190, 1035, 886, 761, 737, 702 cmꢂ1. HRMS (ESI): [M þ H],
calcd for C30H31O13, 599.1796, found 599.1893.
(500 MHz, DMSO-D6)
d
7.85 (d, J ¼ 9.0 Hz, 2H), 7.65 (d, J ¼ 8.5 Hz,
1H), 7.00 (d, J ¼ 8.5 Hz, 1H), 6.83 (s, 1H), 6.82 (d, J ¼ 7.5 Hz, 2H), 5.70
(d, J ¼ 8.0 Hz, 1H), 5.47 (t, J ¼ 9.5 Hz, 1H), 5.18 (dd, J ¼ 9.5, 8.0 Hz,
1H), 5.04 (t, J ¼ 9.5 Hz, 1H), 4.36e4.30 (m, 1H), 4.23 (dd, J ¼ 12.5,
5.6 Hz, 1H), 4.11 (dd, J ¼ 12.0, 2.0 Hz, 1H), 3.03 (s, 6H), 2.19 (s, 3H),
2.06 (s, 3H), 2.03 (s, 3H), 2.02 (s, 3H), 1.99 (s, 3H). 13C NMR
[(Z)-4-methyl-2-(4ʹ-(pyrrolidin-1-yl)benzylidene)benzo-
furan-3(2H)-one]-[(2ʺ,3ʺ,4ʺ,6ʺ-tetra-O-acetyl)-6-O-b-D-gluco-
(125 MHz, CDCl3)
d
183.25, 170.59, 170.23, 169.52, 169.29, 164.97,
pyran-oside (22a): Reaction mixture of aurone 22 (0.093 mmol,
30 mg) and glycosyl donor (0.187 mmol, 76.8 mg) in 2.5 mL chlo-
roform was stirred for 48 h in the presence of TBAB (0.2 equiv.,
6.2 mg), potassium carbonate (6 equiv., 77 mg) and 1.5 mL DI water
under the standard condition. Eluent 40% ethyl acetate in hexane.
Yield: 50 mg, 82%; red solid, mp 113e116 ꢁC. 1H NMR (500 MHz,
160.72, 151.30, 145.77, 133.58, 122.49, 120.09, 117.54, 114.73, 112.26,
112.06, 109.96, 98.91, 72.57, 72.31, 70.98, 68.30, 61.95, 40.14, 20.76,
20.72, 8.07. IR (neat) 2926, 2861, 1749, 1581, 1527, 1428, 1367, 1212,
1113, 1035, 815, 778, 685 cmꢂ1. HRMS (ESI): [M þ H], calcd for
C
32H36NO12, 626.2238, found 626.2241.
[(Z)-2-benzylidenebenzofuran-3(2H)-one]-[(2ʺ,3ʺ,4ʺ,6ʺ-tetra-
DMSO-D6)
d
7.80 (d, J ¼ 9.0 Hz, 2H), 6.97 (d, J ¼ 1.6 Hz, 1H), 6.74 (s,
O-acetyl)-4ʹ-O-
b
-
D-glucopyranoside] (19a): Reaction mixture of
1H), 6.64e6.62 (m, 3H), 5.76 (d, J ¼ 8.0 Hz, 1H), 5.39 (t, J ¼ 9.5 Hz,
1H), 5.12 (dd, J ¼ 9.5, 8.0 Hz, 1H), 5.03 (t, J ¼ 10.0 Hz, 1H), 4.39e4.32
(m, 1H), 4.23e4.11 (m, 2H), 3.36e3.33 (m, 4H, overlapped with H2O
signal) 2.56 (s, 3H), 2.06 (s, 3H), 2.04 (s, 3H), 2.03 (s, 3H), 1.99e1.96
aurone 19 (0.26 mmol, 62 mg) and glycosyl donor (0.52 mmol,
214 mg) in 4 mL chloroform was stirred for 48 h in the presence of
TBAB (0.2 equiv., 17.12 mg), potassium carbonate (6 equiv., 213 mg)
and 3 mL DI water under the standard condition. Eluent 40% ethyl
acetate in hexane. Yield: 125.7 mg, 85%; yellow solid, mp 77e79 ꢁC.
(m, 7H). 13C NMR (125 MHz, CDCl3)
d 183.28, 170.66, 170.31, 169.54,
169.39, 167.11, 162.37, 148.87, 145.65, 141.28, 133.57, 119.56, 116.23,
114.30, 113.84, 111.96, 98.41, 97.40, 72.71, 72.44, 71.10, 68.38, 62.16,
47.66, 25.57, 20.83, 20.76, 20.72, 18.13. IR (neat)) 2959, 2928, 2855,
1H NMR (500 MHz, DMSO-D6)
d
8.02 (d, J ¼ 9.0 Hz, 2H), 7.83e7.79
(m, 2H), 7.57 (d, J ¼ 8.5 Hz, 1H), 7.33 (t, J ¼ 7.5 Hz, 1H), 7.14 (d,
J ¼ 9.0 Hz, 2H), 6.98 (s,1H), 5.71 (d, J ¼ 8.0 Hz,1H), 5.43 (t, J ¼ 9.5 Hz,
1H), 5.10 (dd, J ¼ 9.5, 8.0 Hz, 1H), 5.03 (t, J ¼ 9.5 Hz, 1H), 4.30 (ddd,
J ¼ 10.0, 5.0, 2.5 Hz, 1H), 4.22 (dd, J ¼ 12.0, 5.0 Hz, 1H), 4.10 (dd,
J ¼ 12.0, 2.5 Hz, 1H), 2.03 (s, 3H), 2.02 (s, 6H), 1.98 (s, 3H). 13C NMR
1747, 1581, 1525, 1378, 1346, 1214, 1171, 1138, 1037, 815, 698 cmꢂ1
.
HRMS (ESI): [M þ H], calcd for C34H38NO12, 652.2394, found
652.2395.
[(Z)-2-(4ʹ-(diphenylamino)benzylidene)-4-
methylbenzofuran-3(2H)-one]-[(2ʺ,3ʺ,4ʺ,6ʺ-tetra-O-acetyl)-6-O-
(125 MHz, CDCl3)
d 184.74, 170.67, 170.34, 169.50, 169.40, 166.06,
157.86, 146.44, 136.94, 133.32, 127.59, 124.76, 123.58, 121.80, 117.18,
112.99, 112.51, 98.54, 72.71, 72.25, 71.15, 68.25, 61.95, 20.80, 20.73.
IR (near) 1745, 1706, 1600, 1510, 1369, 1210, 1182, 1035, 888, 758,
702 cmꢂ1. HRMS (ESI): [M þ H], calcd for C29H29O12, 569.1659,
found 569.1664.
b-D-glucopyran-oside] (23a): Reaction mixture of aurone 23
(0.26 mmol, 109 mg) and glycosyl donor (0.52 mmol, 214 mg) in
4 mL chloroform was stirred for 48 h in the presence of TBAB (0.2
equiv., 17.12 mg), potassium carbonate (6 equiv., 213 mg) and 3 mL
DI water under the standard condition. Eluent 40% ethyl acetate in
hexane. Yield: 129 mg, 67%; orange-yellow solid, mp 103e105 ꢁC.
(Z)-2-(3ʹ-methoxybenzylidene)benzofuran-3(2H)-one]-
[(2ʺ,3ʺ,
4ʺ,6ʺ-tetra-O-acetyl)-4ʹ-O-
b
-D
-glucopyranoside](20a):
1H NMR (500 MHz, DMSO-D6)
J ¼ 11.0, 5.0 Hz, 4H), 7.20e7.10 (m, 6H), 6.97e6.90 (m, 3H), 6.75 (s,
d
7.83 (d, J ¼ 9.0 Hz, 2H), 7.38 (dd,
Reaction mixture of aurone 20 (0.26 mmol, 70 mg) and glycosyl

8
A. Kafle et al. / Tetrahedron 76 (2020) 131528
1H), 6.67 (d, J ¼ 1.0 Hz, 1H), 5.75 (d, J ¼ 8.0 Hz, 1H), 5.39 (t,
J ¼ 9.5 Hz, 1H), 5.11 (dd, J ¼ 9.5, 8.0 Hz, 1H), 5.02 (t, J ¼ 9.5 Hz, 1H),
4.34e4.30 (m, 1H), 4.19e4.11 (m, 2H), 2.55 (s, 3H), 2.03 (s, 3H), 2.02
(ESI): [M þ H], calcd for C29H28NSO12, 614.1332, found 614.1330.
[(Z)-2-((4ʹ-bromothiophen-2ʹ-yl)methylene)-4-methylbenzo
furan-3(2H)-one]-[(2ʺ,3ʺ,4ʺ,6ʺ-tetra-O-acetyl)-6-O-
b
-D
-
gluco-
(s, 3H), 2.00 (s, 3H), 1.98 (s, 3H). 13C NMR (125 MHz, CDCl3)
d
170.52,
pyranoside (27a): Reaction mixture of aurone 27 (0.26 mmol,
84 mg) and glycosyl donor (0.52 mmol, 214 mg) in 4 mL chloroform
was stirred for 48 h in the presence of TBAB (0.2 equiv., 17.12 mg),
potassium carbonate (6 equiv., 213 mg) and 3 mL DI water under
the standard condition. Eluent 30% ethyl acetate in hexane. Yield:
146 mg, 86%; yellow solid, mp 139e140 ꢁC. 1H NMR (300 MHz,
170.22, 169.44, 169.28, 167.50, 162.68, 149.31, 146.72, 141.47, 132.60,
129.56, 125.61, 125.22, 124.28, 121.33, 114.15, 112.21, 98.20, 97.32,
72.59, 72.39, 70.96, 68.20, 62.04, 20.70, 20.66, 18.10. IR (neat) 1749,
1695, 1650, 1587, 1510, 1492, 1214, 1138, 1035, 907, 758, 698 cmꢂ1
.
HRMS (ESI): [M þ H], calcd for C42H40NO12, 750.2550, found
750.2547.
DMSO-D6)
d
8.08e8.01 (m, 1H), 7.76 (d, J ¼ 8.5 Hz, 1H), 7.74e7.70
[(Z)-4-methyl-2-(thiophen-2-ylmethylene)benzofuran-
3(2H)-one]- [(2ʺ, 3ʺ, 4ʺ, 6ʺ-tetra-O-acetyl)-6-O-b-D-glucopyrano-
(m, 1H), 7.27 (s, 1H), 7.17 (d, J ¼ 2.0 Hz, 1H), 6.90 (dd, J ¼ 8.5, 2.0 Hz,
1H), 5.84 (d, J ¼ 8.0 Hz, 1H), 5.40 (t, J ¼ 9.5 Hz, 1H), 5.14 (dd, J ¼ 9.5,
8.0 Hz,1H), 5.04 (t, J ¼ 9.5 Hz,1H), 4.43e4.32 (m,1H), 4.24e4.09 (m,
2H), 2.05 (s, 3H), 2.03 (s, 6H),1.99 (s, 3H). 13C NMR (125 MHz, CDCl3)
side (24a): Reaction mixture of aurone 24 (0.26 mmol, 67 mg) and
glycosyl donor (0.52 mmol, 214 mg) in 4 mL chloroform was stirred
for 48 h in the presence of TBAB (0.2 equiv., 17.12 mg), potassium
carbonate (6 equiv., 213 mg) and 3 mL DI water under the standard
condition. Eluent 40% ethyl acetate in hexane. Yield: 143 mg, 87%;
d
182.01, 170.52, 170.21, 169.47, 169.26, 167.31, 163.79, 146.59,
136.38, 134.20, 128.03, 126.06, 117.08, 113.65, 111.41, 104.83, 100.22,
98.17, 72.49, 70.95, 68.17, 62.02, 20.84, 20.66, 20.63. IR (neat) 3093,
1745, 1650, 1605, 1447, 1411, 1371, 1216, 1035, 910, 875, 732,
696 cmꢂ1. HRMS (ESI): [M þ H], calcd for C28H27BrSO12, 667.0485,
found 667.0489.
yellow solid, mp 93e94 ꢁC. 1H NMR (500 MHz, DMSO-D6)
d 7.94 (d,
J ¼ 5.0 Hz, 1H), 7.71 (d, J ¼ 3.5 Hz, 1H), 7.23 (dd, J ¼ 4.0, 3.0 Hz, 2H),
6.95 (d, J ¼ 2.0 Hz, 1H), 6.71e6.67 (m, 1H), 5.81 (d, J ¼ 8.0 Hz, 1H),
5.39 (t, J ¼ 9.5 Hz, 1H), 5.13 (dd, J ¼ 9.5, 8.0 Hz, 1H), 5.02 (t,
J ¼ 9.5 Hz, 1H), 4.41e4.34 (m, 1H), 4.19 (dd, J ¼ 12.0, 6.0 Hz, 1H), 4.14
(dd, J ¼ 12.0, 2.5 Hz, 1H), 2.55 (s, 3H), 2.06 (s, 3H), 2.03 (s, 6H), 1.98
(Z)-4-methyl-2-((5ʹ-methylfuran-2ʹyl)methylene)benzo-
furan-3(2H)-one]-[(2ʺ,3ʺ,4ʺ,6ʺ-tetra-O-acetyl)-6-O-
b
-D
-
gluco-
pyranoside (28a): Reaction mixture of aurone 28 (0.26 mmol,
67 mg) and glycosyl donor (0.52 mmol, 214 mg) in 4 mL chloroform
was stirred for 48 h in the presence of TBAB (0.2 equiv., 17.12 mg),
potassium carbonate (6 equiv., 213 mg) and 3 mL DI water under
the standard condition. Eluent 40% ethyl acetate in hexane. Yield:
109 mg, 72%; yellow solid, mp 83e85 ꢁC. 1H NMR (500 MHz, DMSO-
(s, 3H). 13C NMR (125 MHz, CDCl3)
d 182.85, 170.52, 170.18, 169.45,
169.26, 167.48, 162.87, 146.07, 141.59, 135.48, 132.67, 131.16, 127.97,
115.74, 114.29, 105.63, 98.02, 97.36, 72.53, 72.37, 70.95, 68.24, 62.06,
20.82, 20.67, 20.62, 18.01. IR (neat) 2956, 1749, 1698, 1650, 1605,
1423, 1367, 1216, 1171, 1134, 1037, 909 717, 698 cmꢂ1. HRMS (ESI):
[M þ H], calcd for C28H28SO12, 589.1380, found 589.1385.
D6)
d
7.07 (d, J ¼ 3.0 Hz,1H), 6.95 (d, J ¼ 2.0 Hz,1H), 6.70 (s,1H), 6.67
[(Z)-4-methyl-2-(thiophen-3ʹ-ylmethylene)benzofuran-
(d, J ¼ 1.0 Hz, 1H), 6.41 (d, J ¼ 3.0 Hz, 1H), 5.78 (d, J ¼ 8.0 Hz, 1H),
5.39 (t, J ¼ 9.5 Hz, 1H), 5.12 (dd, J ¼ 9.5, 8.0 Hz, 1H), 5.03 (t,
J ¼ 10.0 Hz, 1H), 4.38e4.33 (m, 1H), 4.19e4.11 (m, 2H), 2.54 (s, 3H),
3(2H)-one]-[(2ʺ, 3ʺ, 4ʺ, 6ʺ-tetra-O-acetyl)-6-O-b-D-glucopyrano-
side (25a): Reaction mixture of aurone 25 (0.26 mmol, 67 mg) and
glycosyl donor (0.52 mmol, 214 mg) in 4 mL chloroform was stirred
for 48 h in the presence of TBAB (0.2 equiv., 17.12 mg), potassium
carbonate (6 equiv., 213 mg) and 3 mL DI water under the standard
condition. Eluent 40% ethyl acetate in hexane. Yield: 115 mg, 75%;
yellow solid, mp 94e96 ꢁC. 1H NMR (300 MHz, DMSO-D6)
2.39 (s, 3H), 2.04 (s, 3H), 2.03 (s, 3H), 2.02 (s, 3H), 1.98 (s, 3H). 13
C
NMR (125 MHz, CDCl3)
d 183.04, 170.59, 170.26, 169.50, 169.34,
167.41, 162.75, 156.07, 147.39, 145.12, 141.49, 118.48, 115.86, 114.09,
109.88, 100.91, 98.18, 97.48, 72.60, 72.41, 71.01, 68.27, 62.08, 20.79,
20.72, 20.68, 18.07, 14.13. IR (neat) 1747, 1695, 1648, 1600, 1521,
1369, 1210, 1171, 1132, 1033, 909, 791, 698 cmꢂ1. HRMS (ESI): [M þ
H], calcd for C29H28NSO12, 587.1765, found 587.1767.
Glucosides
d
8.20e8.15 (m, 1H), 7.73 (dd, J ¼ 5.0, 3.0 Hz, 1H), 7.68 (dd,
J ¼ 5.0, 1.0 Hz, 1H), 6.98 (d, J ¼ 2.0 Hz, 1H), 6.94 (s, 1H), 6.68 (d,
J ¼ 1.0 Hz, 1H), 5.77 (d, J ¼ 8.0 Hz, 1H), 5.41 (t, J ¼ 9.5 Hz, 1H), 5.12
(dd, J ¼ 9.5, 8.0 Hz, 1H), 5.04 (t, J ¼ 9.5 Hz, 1H), 4.41e4.29 (m, 1H),
4.26e4.09 (m, 2H), 2.55 (s, 3H), 2.04 (s, 3H), 2.03 (s, 6H),1.98 (s, 3H).
[(Z)-2-(4-methylbenzylidene)benzofuran-3(2H)-one]-6-O-
b-
D- glucopyranoside (29a): 0.051 mmol (30 mg) 13a was stirred in
13C NMR (75 MHz, CDCl3)
d
183.63, 170.53, 170.25, 169.48, 169.31,
1 mL MeOH in the presence of 10 mol% NaOMe (5 M in MeOH) for
2 h under standard condition. Eluent 5% MeOH in DCM. Yield:
18 mg, 84%; off-white solid, mp 158e160 ꢁC. 1H NMR (500 MHz,
167.74, 162.97, 146.94, 141.74, 133.82, 129.86, 129.13, 126.32, 115.65,
114.13, 105.91, 98.13, 97.41, 72.56, 72.41, 70.98, 68.20, 62.05, 20.76,
20.71, 20.67, 18.10. IR (neat) 2956, 1747, 1700, 1652, 1601, 1369, 1212,
1171, 1130, 1035, 909, 791, 698 cmꢂ1. HRMS (ESI): [M þ H], calcd for
ACETONE-D6)
d
7.88 (d, J ¼ 8.0 Hz, 2H), 7.69 (d, J ¼ 8.5 Hz, 1H), 7.33
(d, J ¼ 8.0 Hz, 2H), 7.16 (s, 1H), 6.95 (d, J ¼ 8.5 Hz, 1H), 6.76 (s, 1H),
C
28H29SO12, 589.1380, found 589.1379.
5.25 (d, J ¼ 7.5 Hz, 1H), 3.92 (d, J ¼ 12.0 Hz, 1H), 3.76e3.70 (m, 1H),
[(Z)-2-((5ʹ-cyanothiophen-2ʹ-yl)methylene)-4-methylbenzo
3.67 (s, 1H), 3.58e3.53 (m, 2H), 3.52e3.47 (m, 1H), 2.39 (s, 3H). 13
C
furan-3(2H)-2ʺ,3ʺ,4ʺ,6ʺ-tetra-O-acetyl)-6-O-
b
-D
-glucopyrano-
NMR (75 MHz, METHANOL-D3) d 184.74, 169.53, 166.95, 148.62,
side] (26a): Reaction mixture of aurone 26 (0.26 mmol, 74 mg) and
glycosyl donor (0.52 mmol, 214 mg) in 4 mL chloroform was stirred
for 48 h in the presence of TBAB (0.2 equiv., 17.12 mg), potassium
carbonate (6 equiv., 213 mg) and 3 mL DI water under the standard
condition. Yield: 135 mg, 85%; yellow solid, mp 139e140 ꢁC. 1H
141.98, 132.69, 130.73, 126.56, 116.88, 114.99, 113.95, 101.68, 100.84,
78.43, 77.82, 74.70, 71.21, 62.45, 21.59. HRMS (ESI): [M þ H], calcd
for C22H23O8, 415.1393, found 415.1397.
[(Z)-2-(4ʹ-cyanobenzylidene)-7-methylbenzofuran-3(2H)-
one] -6-O-b-D-glucopyranoside] (30a): 0.051 mmol (31 mg) 2a
NMR (500 MHz, DMSO-D6)
d
8.02 (d, J ¼ 4.0 Hz, 1H), 7.76 (d,
was stirred in 1 mL MeOH in the presence of 10 mol% NaOMe (5 M
in MeOH) for 2 h under standard condition. Eluent 5% MeOH in
DCM. Yield: 18.3 mg, 80%; off-white solid, mp 230e233 ꢁC. 1H NMR
J ¼ 4.0 Hz,1H), 7.31 (s,1H), 6.99 (d, J ¼ 2.0 Hz,1H), 6.71 (d, J ¼ 1.0 Hz,
1H), 5.80 (d, J ¼ 8.0 Hz, 1H), 5.40 (t, J ¼ 9.5 Hz, 1H), 5.13 (dd, J ¼ 9.5,
8.0 Hz, 1H), 5.04 (t, J ¼ 9.5 Hz, 1H), 4.37 (ddd, J ¼ 10.0, 5.5, 2.5 Hz,
1H), 4.17 (m, 2H), 2.54 (s, 3H), 2.05 (s, 3H), 2.04 (s, 3H), 2.03 (s, 3H),
(300 MHz, DMSO-D6)
d
8.14 (d, J ¼ 8.5 Hz, 2H), 7.97 (d, J ¼ 8.5 Hz,
2H), 7.63 (d, J ¼ 8.5 Hz, 1H), 7.08 (d, J ¼ 8.5 Hz, 1H), 6.93 (s, 1H), 5.59
(s, 1H, eOH), 5.45 (s, 1H, eOH), 5.31 (s, 1H, eOH), 5.08 (d, J ¼ 7.0 Hz,
1H), 4.67 (s, 1H, eOH), 3.69 (d, J ¼ 11.0 Hz, 1H), 3.54e3.45 (m, 2H),
3.42 (m, 2H), 3.22 (m, 1H), 2.32 (s, 3H). 13C NMR (125 MHz, DMSO-
1.99 (s, 3H). 13C NMR (125 MHz, CDCl3)
d 182.26, 170.39, 170.13,
169.42, 169.20, 167.65, 163.39, 147.81, 142.08, 137.42, 131.32, 115.09,
114.85, 113.95, 112.82, 102.85, 97.93, 97.49, 72.42, 70.88, 68.09,
62.02, 20.78, 20.63, 20.59, 18.01. IR (neat) 2218, 1745, 1704, 1655,
1596, 1439, 1369, 1214, 1173, 1134, 1033, 909, 810, 698 cmꢂ1. HRMS
D6)
d 182.53, 165.24, 162.92, 148.65, 136.89, 132.80, 131.52, 123.05,
118.73, 114.25, 111.34, 111.00, 110.90, 108.58, 100.35, 77.28, 76.39,

A. Kafle et al. / Tetrahedron 76 (2020) 131528
9
73.24, 69.48, 60.54, 7.94. IR (neat) 3313, 2924, 2227, 1693, 1654,
Acknowledgments
1600, 1428, 1397, 1264, 1102, 1080, 1043, 991, 778, 681 cmꢂ1. HRMS
(ESI): [M þ H], calcd for C23H22NO8, 440.1345, found 440.1339.
This work was supported by the Department of Chemistry, the
Molecular Biosciences Program, and the Tennessee Center for
Botanical Medicine at Middle Tennessee State University.
[(Z)-2-(4ʹ-cyanobenzylidene)benzofuran-3(2H)-one]-6-O-b-
D
- glucopyranoside (31a): 0.051 mmol (30.5 mg) 1a was stirred in
1 mL MeOH in the presence of 10 mol% NaOMe (5 M in MeOH) for
2 h under standard condition. Eluent 5% MeOH in DCM. Yield:
20 mg, 88%; off-white solid, mp 188e190 ꢁC. 1H NMR (300 MHz,
Appendix A. Supplementary data
DMSO-D6)
d
8.13 (d, J ¼ 8.5 Hz, 2H), 7.97 (d, J ¼ 8.5 Hz, 2H), 7.75 (d,
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2020.131528.
J ¼ 8.5 Hz, 1H), 7.23 (d, J ¼ 2.0 Hz, 1H), 6.98e6.90 (m, 2H), 5.62 (s,
1H, eOH), 5.52 (s, 1H, eOH), 5.35 (s, 1H, eOH), 5.18 (d, J ¼ 7.0 Hz,
1H), 4.69 (s, 1H, eOH), 3.71 (d, J ¼ 9.0 Hz, 1H), 3.49 (d, J ¼ 8.0 Hz,
2H), 3.29 (d, J ¼ 6.0 Hz, 2H), 3.23e3.12 (m, 1H). 13C NMR (125 MHz,
Supplementary Data
DMSO-D6)
d 181.87, 167.85, 165.39, 148.54, 136.72, 132.75, 131.46,
Supplementary data can be found online at ___.
125.83, 118.68, 114.45, 114.05, 111.47, 108.83, 99.82, 99.66, 77.22,
76.38, 73.12, 69.48, 60.60. IR (neat) 3395, 3326, 2918, 2240, 1704,
1657, 1613, 1600, 1354, 1264, 1080, 1011, 903, 834, 683 cmꢂ1. HRMS
(ESI): [M þ H], calcd for C22H20NO8, 426.1189, found 426.1186.
[(Z)-2-(3ʹ,5ʹ-dimethoxybenzylidene)benzofuran-3(2H)-one]-
References
[1] E. Ono, M. Fukuchi-Mizutani, N. Nakamura, Y. Fukui, K. Yonekura-Sakakibara,
M. Yamaguchi, T. Nakayama, T. Tanaka, T. Kusumi, Y. Tanaka, Proc. Natl. Acad.
Sci. U. S. A 103 (2006) 11075e11080.
[2] B. Boucherle, M. Peuchmaur, A. Boumendjel, R. Haudecoeur, Phytochemistry
142 (2017) 92e111.
[3] B.A. Bohm, The minor flavonoids, in: J.B. Harborne (Ed.), Springer Science,
Dordrecht, 1988, pp. 329e388.
[4] R. Haudecoeur, A. Boumendjel, Curr. Med. Chem. 19 (2012) 2861e2875.
[5] A. Boumendjel, Curr. Med. Chem. 10 (2003) 2621e2630.
[6] B.R. Bandgar, S.A. Patil, B.L. Korbad, S.C. Biradar, S.N. Nile, C.N. Khobragade,
Eur. J. Med. Chem. 45 (2010) 3223e3227.
[7] R. Haudecoeur, A. Ahmed-Belkacem, W. Yi, A. Fortune, R. Brillet, C. Belle,
E. Nicolle, C. Pallier, J.M. Pawlotsky, A. Boumendjel, J. Med. Chem. 54 (2011)
5395e5402.
[8] C. Zwergel, F. Gaascht, M. Diederich, G. Kirsch, Nat. Prod. Commun. 7 (2012)
389e394.
6-O-b-D-glucopyranoside (32a): 0.051 mmol, (32 mg)14a was
stirred in 1 mL MeOH in the presence of 10 mol% NaOMe (5 M in
MeOH) for 2 h under standard condition. Eluent 5% MeOH in DCM.
Yield: 20 mg, 63%; yellow solid, mp 174e177 ꢁC. 1H NMR (500 MHz,
DMSO-D6)
d
7.72 (d, J ¼ 8.5 Hz, 1H), 7.25 (d, J ¼ 2.0 Hz, 1H), 7.17 (d,
J ¼ 2.0 Hz, 2H), 6.92 (dd, J ¼ 8.5, 2.0 Hz, 1H), 6.81 (s, 1H), 6.63 (t,
J ¼ 2.0 Hz,1H), 5.46 (d, J ¼ 3.0 Hz, 1H, OH), 5.17 (d, J ¼ 7.0 Hz, 2H, OH
and anomeric), 5.11 (d, J ¼ 5.0 Hz, 1H, OH), 4.63 (t, J ¼ 5.5 Hz, 1H,
OH), 3.81 (s, 6H), 3.71 (dd, J ¼ 10.0, 5.0 Hz, 1H), 3.53e3.43 (m, 2H),
3.37e3.35 (m, 1H), 3.30e3.28 (m, 2H), 3.18 (m, 1H). 13C NMR
(125 MHz, DMSO-D6)
d 182.01, 167.68, 165.20, 160.71, 147.40,
133.58, 125.69, 114.84, 113.92, 111.35, 109.38, 101.89, 99.91, 99.80,
77.28, 76.49, 73.18, 69.65, 60.70, 55.45. IR (neat) 3604, 3348, 2931,
2885, 2851, 1702, 1654, 1615, 1596, 1445, 1428, 1357, 1346, 1279,
1166, 1089, 1074, 1063, 1039, 853, 685 cmꢂ1. HRMS (ESI): [M þ H],
calcd for C23H25O10, 461.1448, found 461.1451.
(Z)-7-methyl-2-(3 ʹ,4 ʹ,5 ʹ-trimethoxybenzylidene)benzo-
furan-3(2H)-one]-6-O-b-D-glucopyranoside (33a): 0.051 mmol
(34 mg) 16a was stirred in 1 mL MeOH in the presence of 10 mol%
NaOMe (5 M in MeOH) for 2 h under standard condition. Eluent 7%
MeOH in DCM. Yield: 17 mg, 75%; yellow solid, mp 190e192 ꢁC. 1H
[9] R. Atta Ur, M.I. Choudhary, S. Hayat, A.M. Khan, A. Ahmed, Chem. Pharm. Bull.
49 (2001) 105e107.
[10] A.T. Geissman, J.B. Harborne, J. Am. Chem. Soc. 77 (1955) 4622e4624.
[11] K. Thakkar, M. Cushman, Tetrahedron Lett. 35 (1994) 6441e6444.
[12] H. Harkat, A. Blanc, J.M. Weibel, P. Pale, J. Org. Chem. 73 (2008) 1620e1623.
[13] M. Hadjeri, C. Beney, A. Boumendjel, Curr. Org. Chem. 7 (2003) 679e689.
[14] R.S. Varma, M. Varma, Tetrahedron Lett. 33 (1992) 5937e5940.
[15] T. Nakayama, J. Biosci. Bioeng. 94 (2002) 487e491.
[16] T. Nakayama, K. Yonekura-Sakakibara, T. Sato, S. Kikuchi, Y. Fukui, M. Fukuchi-
Mizutani, T. Ueda, M. Nakao, Y. Tanaka, T. Kusumi, T. Nishino, Science 290
(2000) 1163e1166.
[17] T. Tronina, P. Strugala, J. Poplonski, A. Wloch, S. Sordon, A. Bartmanska,
E. Huszcza, Molecules 22 (2017) 1230.
NMR (300 MHz, DMSO-D6) (signals are highly overlapped)
d
7.61
[18] (a) E. Fischer, Chem. Ber. 26 (1893) 2400e2412;
(b) E. Fischer, Chem. Ber. 28 (1895) 1145e1167;
(d, J ¼ 8.5 Hz, 2H), 7.40 (s, 2H), 7.07 (d, J ¼ 8.5 Hz, 2H), 6.85 (s, 2H),
5.53 (s, 1H, OH), 5.23 (s, 1H, OH), 5.05 (d, J ¼ 7.0 Hz, 1H), 4.64 (s, 1H,
OH), 3.87 (s, 6H), 3.74 (s, 3H), 3.68 (m, 1H), 3.49 (dd, J ¼ 5.0, 3.0 Hz,
4H), 3.41 (m, 1H), 3.20 (m, 1H), 2.30 (s, 3H). 13C NMR (125 MHz,
(c) E. Fischer, L. Beesch, Chem. Ber. 27 (1894) 2478e2486;
(d) E. Fischer, L. Beesch, Chem. Ber. 29 (1896) 2927e2931;
(e) W. Koenigs, E. Knorr, Chem. Ber. 34 (1901) 957e981;
(f) H. Paulsen, Angew. Chem., Int. Ed. Engl. 21 (1982) 155e173;
(g) R.R. Schmidt, J.C. Castro-Palomino, O. Retz, Pure Appl. Chem. 71 (1999)
729e744;
DMSO-D6)
d 182.32, 164.84, 162.47, 152.95, 146.78, 139.10, 127.53,
122.68, 114.69, 111.51, 110.91, 110.90, 108.77, 100.54, 77.25, 76.40,
73.23, 69.51, 60.56, 60.21, 55.80, 7.58. IR (neat) 3339, 2931, 1641,
1605, 1587, 1505, 1423, 1352, 1259, 1123, 1099, 1076, 1043, 992,
776 cmꢂ1. HRMS (ESI): [M þ H], calcd for C25H29O11, 505.1710, found
505.1713.
h) A. Kafle, J. Liu, L. Cui, Can. J. Chem. 94 (2016) 894e901.
[19] K.J. Jensen, J. Chem. Soc., Perkin Trans. 1 (2002) 2219e2233.
[20] M. Jacobsson, J. Malmberg, U. Ellervik, Carbohydr. Res. 341 (2006) 1266e1281.
[21] A. Michael, Am. Chem. J. 1 (1879) 305e312.
[22] a) E. Fischer, K. Raske, Chem. Ber. 42 (1909) 1465e1476;
ꢀ
(b) M.C. Courtin-Duchateau, A. Veyrieres, Carbohydr. Res. 65 (1978) 23;
(c) I.J. Talisman, V. Kumar, J.R. Deschamps, M. Frisch, S.V. Malhotra, Carbohydr.
Res. 346 (2011) 2337e2341;
(d) S.H. Jung, S.H. Cho, T.H. Dang, J.H. Lee, J.H. Ju, M.K. Kim, S.H. Lee, J.C. Ryu,
Y. Kim, Eur. J. Med. Chem. 38 (2003) 537e545;
Declaration of competing interest
(e) L. Kroger, J. Thiem, J. Carbohydr. Chem. 22 (2003) 9e23.
[23] W.A. Bubb, Concepts Magn. Reson. A 19A (2003) 1e19.
[24] J.S. Hastings, G.H. Heller, J. Chem. Soc. Perkins Trans. 1 (1972) 2128e2132.
[25] H.E. Gottlieb, V. Lotlyr, J. Org. Chem. 62 (1997) 7512e7515.
The authors declare that they have no known competing
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.