Highly efficient glucosylation of flavonoids

Article abstract of DOI:10.1007/s00706-009-0207-6

A highly efficient procedure for glucosylation of flavonoids by acetobromoglucose is described. Glucosylation is carried out in a two-phase system CHCl₃/H₂O over 96 h using tetrabutylammonium bromide as phase-transfer catalyst. A pur

Full text of DOI:10.1007/s00706-009-0207-6

Monatsh Chem (2009) 140:1503–1512
DOI 10.1007/s00706-009-0207-6
ORIGINAL PAPER
Highly efficient glucosylation of flavonoids
•
Volodymyr Semeniuchenko Yana Garazd
•
•
Myroslav Garazd Tetyana Shokol
•
•
Ulrich Groth Volodymyr Khilya
Received: 28 August 2009 / Accepted: 12 October 2009 / Published online: 14 November 2009
Ó Springer-Verlag 2009
Abstract A highly efficient procedure for glucosylation
of flavonoids by acetobromoglucose is described. Glu-
cosylation is carried out in a two-phase system CHCl3/H2O
over 96 h using tetrabutylammonium bromide as phase-
transfer catalyst. A purification procedure can be performed
without column chromatography, and the yields of the
glucosylated flavonoids are mostly quantitative. Acetylated
glucosides were deprotected with sodium methanolate to
afford the desired glucosides of flavonoids.
chromen-2-ones), coumarins (2H-chromen-2-ones), and
related compounds [1]. Many biologically active com-
pounds are found among natural and synthetic flavonoids
[2–7].
3-Heteroarylchromones are isosteric to isoflavones, but
contain two pharmacophoric groups: benzopyrane and a
heteroaryl ring at position C-3. Diverse 3-heteroarylchro-
mones show antiallergic, anti-inflammatory, fungicidal,
antiblastic, and neuroleptic activity [8–10].
The natural flavonoids are generally hydroxylated, and
the hydroxy groups are usually glycosylated by various
sugars [1]. The flavonoids are normally not soluble in
water, and glycosylation enhances their water-solubility.
On the other hand, the flavonoids are insoluble in low-polar
organic solvents, and hence insoluble in the lipid phase of
membranes. Derivatization of flavonoid glycosides (alkyl-
ation or acylation) makes them soluble in solvents such as
toluene. The influence of glucosylation of polyphenols
on their bioavailability is described in a review [11].
Comparison of bactericidal activity of 7-hydroxy-3-pyr-
azolylchromones and their glucosides has shown that the
latter are more active [12].
Keywords Heterocycles ꢀ Phase-transfer catalysis ꢀ
Natural products ꢀ Carbohydrates ꢀ Chromones ꢀ
Coumarins
Introduction
The flavonoids belong to a class of natural heterocyclic
compounds. They are biosynthesized by plants and con-
sumed by humans and by animals, thus being an important
component of nutrition. Flavonoids are represented by
flavones (2-phenyl-4H-chromen-4-ones), isoflavones (3-
phenyl-4H-chromen-4-ones), neoflavones (4-phenyl-2H-
Results and discussion
V. Semeniuchenko (&) ꢀ U. Groth
Fachbereich Chemie und Konstanz Research School Chemical
¨ ¨
Biology, Universitat Konstanz, Universitatsstrasse 10,
Over the last years we have investigated the chemistry
of 6-ethyl-7-hydroxy-3-(4-phenyl-4H-1,2,4-triazol-3-yl)-
chromone (1) [13]. The synthesis of its glucosylated
derivatives should increase the pharmacological profile for
the reasons mentioned above. First we have applied the
technique of Pivovarenko [14–17], which was developed
for the synthesis of isoflavone glycosides. This method
uses acetobromoglucose, which is one of the best reagents
for glucosylation; normally the reaction proceeds with high
Fach 720, 78457 Constance, Germany
e-mail: chem_vova@mail.univ.kiev.ua
V. Semeniuchenko ꢀ T. Shokol ꢀ V. Khilya
Department of Chemistry, National Taras Shevchenko
University, Kiev, Ukraine
Y. Garazd ꢀ M. Garazd
Institute of Bioorganic and Petroleum Chemistry,
National Academy of Sciences of Ukraine, Kiev, Ukraine
123

1504
V. Semeniuchenko et al.
anomeric selectivity. This reagent was widely used for
glucosylation of flavonoids, especially in total synthesis [18].
According to the method of Pivovarenko, 1-(5-ethyl-2,4-
dihydroxyphenyl)-2-(4-phenyl-4H-1,2,4-triazol-3-yl)-
ethanone (2), which is a precursor of 1, should be
deprotonated by KOH and then glucosylated. The product
1-(5-ethyl-4-hydroxy-2-O-(b-D-tetraacetylglucopyranosyl)
phenyl)-2-(4-phenyl-4H-1,2,4-triazol-3-yl)ethanone (3) should
be further cyclized to afford 6-ethyl-3-(4-phenyl-4H-1,2,
4-triazol-3-yl)-7-O-(b-D-tetraacetylglucopyranosyl)-4H-
chromen-4-one (4). Unfortunately, this reaction was too
inefficient. Four peaks could be detected by HPLC. We
were not able to obtain the product 3 after either the usual
silica gel column chromatography or reverse-phase HPLC.
Therefore, this approach was given up (Scheme 1).
tried to apply the glucosylation under phase-transfer con-
ditions in order to synthesize 4.
Firstly, we deprotonated 1 with five equivalents of
K2CO3 by heating. The criterion for complete deprotona-
tion was the formation of a clear solution in water.
Prolonged stirring of this solution at r.t. leads to no traces
of 2, since the carbonate anion is a poor nucleophile but a
rather good base. According to a method found in literature
[19–21], we took CHCl3 and one equivalent each of
tetrabutylammonium bromide (TBAB) and acetobromo-
glucose and let them react with the above-mentioned
solution of deprotonated 1. Although the formation of 4
was detected, the conversion of 1 was not complete. Full
separation of glucoside 4 from aglycone 1 was not possible
by using silica gel column chromatography. Both com-
pounds adsorb too well on silica gel, leading to ‘‘tails’’ on
the column. Only a very small amount of pure 4 could be
obtained, then mixed fractions were eluted.
We investigated the glucosylation of 7-hydroxy-3-
(4-phenyl-4H-1,2,4-triazol-3-yl)-2H-chromen-2-one (5) by
this method following the procedure described in literature
[19]. The glucosylation takes place in aqueous acetone and
proved to be unproblematic. 3-(4-Phenyl-4H-1,2,4-triazol-
3-yl)-7-O-(b-D-tetraacetylglucopyranosyl)-2H-chromen-2-
one (6) was isolated with 50% yield (based on recovered
starting material, 25% raw yield). Since a triazole ring was
not deleterious to this reaction, we speculate that our fail-
ure to convert 2 to 3 is connected with the 6-ethyl group,
which is bulky enough to prevent effective glucosylation.
This speculation is in agreement with the successful glu-
cosylation of other 1-hetaryl-2,4-dihydroxyacetophenones,
bearing structurally similar electron-accepting heterocycles
(1,3-thiazol-4-yl, 2-pyridyl, and 2-quinolyl) and having 6-
CH instead of the ethyl group [14, 15]. The coumarin 5 was
later glucosylated in quantitative yield according to the
general procedure A.
In order to obtain pure 4 a procedure had to be designed
which converted 1 into 4 completely, so that no chro-
matographic purification was necessary.
The NMR spectrum of the organic layer of the reaction
mixture showed one equivalent of acetobromoglucose at
the beginning. After stirring for 8 h, only 20% of 1 was
converted to 4. The glucosylation seemed to be only a side-
reaction of acetobromoglucose accompanied by decompo-
sition. The products of the decomposition were glucals [15,
19], which were also seen by NMR. On the other hand,
acetobromoglucose was still detected, which indicated a
slow reaction rate.
A breakthrough was the use of five equivalents of
acetobromoglucose and running the reaction for 96 h
instead of 8 h. Continuous stirring during 96 h was found
to be absolutely necessary for full conversion of substrate.
On the other hand, prolonged stirring (1 week) resulted in
decomposition of the product. For each equivalent of
acetobromoglucose one equivalent of K2CO3 had to be
Chromones are unstable towards nucleophiles [10], e.g.,
1 is decomposed to 2 under the influence of KOH. This is
the reason why the above-mentioned procedure [19] is not
applicable for the direct glucosylation of 1. Instead, we
Scheme 1
OAc
O
HO
OH
O
AcO
KOH
Ph
N
AcO
O
OH
O
Acetobromoglucose
OAc
Ph
N
acetone/H2O
N
N
N
2
3
N
OAc
Vilsmeier-Haack Reaction
O
Vilsmeier-Haack
Reaction
O
HO
K2CO3, TBABr
AcO
AcO
Ph
O
O
Acetobromoglucose
OAc
Ph
N
N
CHCl3/H2O
O
N
N
1
O
N
N
4
123

Highly efficient glucosylation of flavonoids
1505
added, since the products of decomposition are glucals and
HBr. Using a chloroform extraction (one should closely
adhere to this protocol) with subsequent washing of
extracts with hexane and further with water, chromato-
graphic purification could be avoided. Compound 4 could
be isolated in quantitative yield and in anomerically pure
form.
(12). The freshly prepared solution in DMSO-d6 of
both compounds showed broad peaks in the 1H NMR
spectra, as if paramagnetically broadened. Careful repro-
duction of deprotection reaction without using a metal
spatula, however, reproduced this broadening. By heating
to 90 °C the peaks became sharp, and multiplets appeared.
After cooling to r.t. the peaks remained sharp. We suppose
that a polymeric structure was formed with hydrogen
bonds between nitrogen atoms of the triazole ring and OH
groups of glucosyl. By heating, the polymeric structure
was destroyed, and the molecules of glucoside were sol-
vated by DMSO-d6. Parent acetylated glucosides 4 and 6
and the other deprotected glucosides have not shown this
effect. The signals of the CH protons of the glucosyl
moiety of compound 11 were found to be different in
‘‘polymeric’’ and in ‘‘solvated’’ state, e.g., the anomeric
proton of 11 resonated at d = 4.88 ppm as a broad singlet
at r.t. in the spectrum with broad peaks. After heating to
90 °C it was shifted to d = 5.07 ppm (broad doublet,
J = 7.4 Hz) and remained at this position after cooling.
The signals of OH groups were found to be temperature
dependent, and in the Experimental Section we provide the
chemical shifts for both r.t. (after preheating and cooling)
and 90 °C.
The use of excess glycosylating reagent was suggested
previously for solid/solution PTC glucosylation of other
isoflavones (threefold excess) [22], flavones (twofold
excess) [23], chalcones (1.2-fold excess) [24], and simple
phenols (twofold excess) [25]. In conditions of solution-
solution PTC, chalcones (2- or 1.2-fold excess) [24] and
various flavones and flavonols (1.2-fold excess) [26] were
glycosylated. One phenol was glucosylated using an excess
of acetobromoglucose with help of autotitration by NaOH
solution [27]. Generally the purification required flash
chromatography; only two articles report recrystallization
of the peracetylated glycosides from MeOH [25] or EtOH
[23]. However recrystallization of crude compounds 4, 6,
and of 2-amino-6-ethyl-3-(4-phenyl-4H-1,2,4-triazol-3-yl)-
7-O-(b-D-tetraacetylglucopyranosyl)-4H-chromen-4-one(22)
was not applicable because of fair solubility in alcohols,
which was obviously caused by contaminants (in contrast,
pure 6 can be recrystallized from i-PrOH).
We have studied the glucosylation of 2-amino-6-ethyl-
7-hydroxy-3-(4-phenyl-4H-1,2,4-triazol-3-yl)-4H-chromen-
4-one (21) and found it to form 22 readily in the presence
of ten equivalents of acetobromoglucose. Its 1H NMR
spectrum showed broad signals, which became sharp after
storage of the sample for 1 month or more in DMSO-d6 at
r.t. Surprisingly, the peaks remained broad even at heating
to 160 °C. Probably this compound has strong hydrogen
bonds between the NH2 groups and the triazole ring, thus
having a polymeric structure. The purity of crude com-
pound could be estimated to be 90% or even higher
The above-mentioned procedure was successfully applied
for the other flavonoids 7-10 (Scheme 2). 3-Phenyl-7-
O-(b-D-tetraacetylglucopyranosyl)-4H-chromen-4-one (13),
2-phenyl-7-O-(b-D-tetraacetylglucopyranosyl)-4H-chromen-
4-one (15), 3-phenyl-7-O-(b-D-tetraacetylglucopyranosyl)-
2H-chromen-2-one (17), and 4-phenyl-7-O-(b-D-tetraace-
tylglucopyranosyl)-2H-chromen-2-one (19) are very well
soluble in toluene and do not tend to adsorb irreversibly on
silica gel, which makes purification simpler, since filtration
through silica gel is sufficient (see general procedure B).
The protected glucosides were deacetylated using a very
mild modification of Zemplen’s protocol [28], which
allowed free glucosides to be obtained in quantitative yield
without decomposition of the chromone/coumarin ring.
The structures of the synthesized compounds were
1
according to H NMR. It could not be further purified by
silica gel column chromatography, because of its irre-
versible adsorption, even in presence of triethylamine in
the eluent. Deacetylation of 22 gave crude 2-amino-6-
ethyl-7-O-(b-D-glucopyranosyl)-3-(4-phenyl-4H-1,2,4-tria-
zol-3-yl)-4H-chromen-4-one (23) with a yield of 85%,
which was very well soluble in water (Scheme 3). It could
not be purified further without the use of HPLC.
1
proven by H and 13C NMR spectra and by mass spectra.
The use of 2D NMR techniques (COSY, HSQC, and
HMBC spectra) allowed us to perform a full assignment of
signals for each compound.
Compounds 13 and 14 [29], 15 and 16 [30], and 19 and
20 [31] are already known, but spectral information (1H
NMR) has been given only for 19 and 7-O-(b-D-gluco-
pyranosyl)-4-phenyl-2H-chromen-2-one (20).
Conclusion
In summary, we have developed a highly efficient proce-
dure for glucosylation of flavonoids (with respect to the
efficiency of utilization of such expensive compounds).
This has been demonstrated on four model flavonoids and
on two 3-heteroarylflavonoids.
A few words should be said about the NMR spectra of
6-ethyl-7-O-(b-D-glucopyranosyl)-3-(4-phenyl-4H-1,2,4-triaz-
ol-3-yl)-4H-chromen-4-one (11) and 7-O-(b-D-glucopy-
ranosyl)-3-(4-phenyl-4H-1,2,4-triazol-3-yl)-2H-chromen-2-one
123

1506
V. Semeniuchenko et al.
Scheme 2
HO
O
O
HO
O
O
N
Ph
Ph
N
N
N
5
1
N
OR
OR
N
O
O
RO
RO
RO
RO
O
O
O
N
O
O
OR
Ph
N
OR
Ph
N
6, R = COCH3
12, R = H
O
N
N
N
4, R = COCH3
11, R = H
HO
O
O
Ph
HO
O
Ph
O
8
7
OR
OR
O
O
RO
RO
RO
RO
O
O
O
O
O
Ph
OR
OR
Ph
13, R = COCH3
14, R = H
15, R = COCH
16, R = H
3O
HO
O
O
HO
O
O
Ph
9
Ph
OR
10
OR
O
O
RO
RO
RO
RO
O
O
O
O
O
O
OR
OR
Ph
17, R = COCH3
18, R = H
19
20
, R = COCH3
, R = H
Ph
All reactions gave quantitative yield. Glucosylation in PTC
conditions, deacetylation by NaOMe in MeOH.
Scheme 3
OAc
HO
O
NH2
N
O
AcO
AcO
Ph
O
O
O
O
NH2
OAc
Ph
92.3%
N
O
21
N
N
N
22
N
OH
85%
crude yield
O
HO
HO
O
NH2
OH
Ph
N
N
O
N
23, not isolated in pure form
123

Highly efficient glucosylation of flavonoids
1507
General procedure A for glucosylation of 1, 5, and 21
Experimental
Substrate (2.5 mmol) and K2CO3 (25 mmol) were added to
50 cm3 water and dissolved with heating, filtered, and more
K2CO3 (12.5 mmol) was added to the filtrate. Chloroform
(50 cm3) was added to this aqueous solution, followed by
acetobromoglucose (12.5 mmol) and tetrabutylammonium
bromide (2.5 mmol). The resulting mixture was vigorously
stirred for 96 h and then heated to reflux for 1 h
(destroying the excess of acetobromoglucose). After cool-
ing to r.t. the two-phase system was separated, and the
aqueous phase was washed repeatedly with chloroform
(emulsion was always combined with organic extracts).
The combined organic extracts were shaken with a satu-
rated solution of K2CO3 and diluted with water, and the
organic phase was separated. The remaining aqueous phase
was reextracted with chloroform, and the combined organic
extracts were washed with brine. The chloroform layer was
separated, dried with Na2SO4, filtered, and evaporated in
vacuum. The remaining resin was dissolved or suspended
in 20 cm3 toluene under reflux; after cooling, exactly
100 cm3 n-hexane were added, which resulted in the for-
mation of a brown resin. The solvent was decanted and the
residue was washed with hexane and again refluxed in
20 cm3 of toluene, cooled, treated with 100 cm3 of hexane,
and decanted. The resting gum was dissolved in a mini-
mum amount of acetone and poured into 200 cm3 water.
After 10 min, 200 cm3 brine was added; this resulted in
coagulation and formation of the crude glucoside. It was
separated by filtration or decantation, redissolved in ace-
tone and the precipitation described above was repeated
(with brine-induced coagulation). Usually after the fourth
cycle of such precipitation, a crystalline sediment was
formed, which was collected by filtration, washed with
distilled water, dried in vacuum, and redissolved in acetone
(washed off from the frit, NaCl stays undissolved). The
acetone was evaporated and the residue was dried in vac-
uum (10-2 mbar), resulting in a voluminous crystalline
mass of the acetylated glucoside. The yield was
quantitative.
NMR spectra were recorded on Bruker Avance 400 or
JEOL JNM-LA 400 with TMS as internal standard. Atom
numbers with one prime correspond to atoms of the phenyl
ring, with two primes to atoms of the glucosyl moiety.
HRMS ESI/TOF were measured on a Bruker Daltonics
microTOF II, using Agilent Tune mix for LC/MSD ion trap
as external standard, in positive polarization. HRMS ESI/
Fourier-transform ion-cyclotrone resonance (FT-ICR) were
measured on a Bruker APEX II FT/ICR instrument with a 7-
T magnet in positive polarization. Analytical HPLC was
performed on Merck RP-18 columns (250 9 4.1 mm) using
gradient or isocratic elution by an acetonitrile–water mix-
ture (UV detection at 254 nm). IR spectra were measured
on Perkin-Elmer Spectrum 100 IR spectrometer with an
attenuated total reflectance (ATR) element. Rotation angles
were measured on a Perkin-Elmer 241 polarimeter with 5 s
integration time. Syntheses of 1 [13] and 21 [32] have been
described previously. 2-(4-Phenyl-4H-1,2,4-triazol-3-
yl)acetonitrile was synthesized according to the published
procedure [33]. Acetobromoglucose was synthesized
according to the known procedure [34], stabilized with 2%
of CaCO3, precipitated from benzene with hexane (20 cm3
benzene and 100 cm3 hexane per 100 g acetobromoglu-
cose) and stored at -20 °C. Methanol was allowed to react
with metallic sodium and distilled in nitrogen atmosphere.
7-Hydroxy-3-(4-phenyl-4H-1,2,4-triazol-3-yl)-
2H-chromen-2-one (5, C17H11N3O3) [35]
A mixture containing 1.842 g 2-(4-phenyl-4H-1,2,4-tria-
zol-3-yl)acetonitrile (10 mmol), 1.381 g 2,4-dihydroxy-
benzaldehyde (10 mmol), 0.1 cm3 piperidine, and 40 cm3
2-propanol was refluxed for 3 min and allowed to stand for
5 h. All volatiles were evaporated in vacuum; 100 cm3
aqueous 3% H2SO4 was added and refluxed for 12 h. The
formed precipitate was filtered, washed with water, and
1
dried to give 2.52 g (82%) of 5. M.p.: 299 °C; H NMR
(400 MHz, DMSO-d6): d = 6.73 (d, J = 2.2 Hz, 1H, 8-H),
6.87 (dd, J = 8.8 Hz, J = 2.2 Hz, 1H, 6-H), 7.39–7.50 (m,
5H, Ph), 7.70 (d, J = 8.8 Hz, 1H, 5-H), 8.48 (s, 1H, 4-H),
8.97 (s, 1H, 5-Htriazole), 10.92 (s, 1H, OH) ppm; 13C NMR
(100 MHz, DMSO-d6): d = 102.1 (8-CH), 110.18 (3-C),
110.82 (10-C), 113.92 (6-CH), 124.12 (20-CHPh), 128.64
(40-CHPh), 129.58 (30-CHPh), 130.96 (5-CH), 134.53 (10-
CPh), 144.95 (5-CHtriazole), 147.41 (4-CH), 148.61 (3-
6-Ethyl-3-(4-phenyl-4H-1,2,4-triazol-3-yl)-7-O-(b-D-tetra-
acetylglucopyranosyl)-4H-chromen-4-one
(4, C33H33N3O12)
1
M.p.: 117 °C; H NMR (400 MHz, DMSO-d6): d = 1.04
(t, J = 7.3 Hz, 3H, CH3CH2), 1.99–2.04 (m, 12H, OAc),
2.5 (q, J = 7.3 Hz, 2H, CH3CH2), 4.15 (d, J = 11 Hz, 1H,
600-CH2), 4.22 (dd, J = 12.3 Hz, J = 5.8 Hz, 1H, 600-CH2),
4.41 (br m, 1H, 500-CH), 5.06 (t, J = 9.6 Hz, 1H, 400-CH),
5.19 (dd, J = 8.3 Hz, J = 9.3 Hz, 1H, 200-CH), 5.44 (d,
J = 9.6 Hz, 1H, 300-CH), 5.76 (d, J = 7.8 Hz, 1H, 100-CH),
7.29 (s, 1H, 8-H), 7.42 (m, 5H, Ph), 7.68 (s, 1H, 5-H), 8.79
(s, 1H, 2-H), 8.99 (s, 1H, 5-Htriazole) ppm; 13C NMR
Ctriazole), 156.01 (9-C), 158.00 (2-C), 162.75 (7-C) ppm; IR
(ATR): vꢀ = 688, 693, 751, 763, 772, 812, 837, 853, 939,
1,117, 1,134, 1,172, 1,205, 1,236, 1,250, 1,274, 1,332,
1,367, 1,393, 1,453, 1,460, 1,501, 1,557, 1,582, 1,597,
1,609, 1,700, 1,724, 3,100–3130 (broad dCH), 3540 (dOH
)
cm-1; HRMS (ESI/TOF): [M ? H?] found (calculated):
306.0887 (306.0873).
123

1508
V. Semeniuchenko et al.
(100 MHz, DMSO-d6): d = 13.76 (CH3CH2), 20.25 (2C,
CH3CO), 20.37 (CH3CO), 20.42 (CH3CO), 22.19
(CH3CH2), 61.64 (600-CH2), 67.98 (400-CH), 70.23 (200-
CH), 71.14 (500-CH), 71.64 (300-CH), 96.63 (100-CH), 102.83
(8-CH), 113.28 (3-C), 117.97 (10-C), 124.11 (20-CHPh),
124.95 (5-CH), 128.60 (40-CHPh), 129.45 (30-CHPh),
132.07 (6-C), 134.48 (10-CPh), 145.28 (5-CHtriazole),
146.34 (3-Ctriazole), 155.56 (9-C), 158.33 (2-CH), 158.58
(7-C), 169.03 (200-OAc), 169.30 (400-OAc), 169.58 (300-
OAc), 169.95 (600-OAc), 172.71 (4-C) ppm; IR (ATR):
vꢀ = 695, 766, 890, 1,035, 1,066, 1,206, 1,367, 1,454,
1,480, 1,505, 1,616, 1,627, 1,657, 1,746, 2,850–3,000
(broad dCH) cm-1; [a]D25 = -20° g-1 cm3 dm-1 (c = 0.25,
DMF); HRMS (ESI/TOF): [M ? H?] found (calculated):
664.2138 (664.2137).
1.7 g product correspond to 92.3% yield. M.p.: 143 °C; 1H
NMR (400 MHz, DMSO-d6): d = 1.05 (t, J = 7.3 Hz, 3H,
CH3CH2), 1.91–2.07 (br m, 12H, OAc), 2.08 (acetone), 2.5
(CH2CH3 and DMSO), 4.08 (d, J = 12.1 Hz, 1H, 600-CH2),
4.23 (dd, J = 12.1 Hz, J = 6.3 Hz, 1H, 600-CH2), 4.33 (m,
1H, 500-CH), 5.03 (t, J = 9.5 Hz, 1H, 400-CH), 5.17 (dd,
J = 9.5 Hz, J = 8.0 Hz, 1H, 200-CH), 5.45 (t, J = 9.5 Hz,
1H, 300-CH), 5.73 (d, J = 7.8 Hz, 1H, 100-CH), 6.94 (s, 1H,
8-H), 7.12–7.53 (br m, 5H, Ph), 7.61 (s, 1H, 5-CH), 7.70
(br s, 2H, NH2), 8.90 (s, 1H, 5-CHtriazole) ppm; 13C NMR
(100 MHz, DMSO-d6): d = 14.01 (CH3CH2), 20.30 (2C,
OAc), 20.41 (OAc), 20.47 (OAc), 22.13 (CH3CH2), 30.68
(acetone), 61.75 (600-CH2), 68.15 (400-CH), 70.37 (200-CH),
71.03 (500-CH), 71.63 (300-CH), 85.19 (3-C), 96.71 (100-CH),
101.75 (8-CH), 116.36 (10-C), 124.28 (20-CHPh), 124.97
(5-CH), 128.46 (40-CHPh), 129.25 (30-CHPh), 130.00 (6-C),
134.70 (10-CPh), 144.65 (5-CHtriazole), 147.00 (3-Ctriazole),
152.11 (9-C), 157.10 (7-C), 163.78 (2-CNH2), 169.05 (200-
OAc), 169.35 (400-OAc), 169.63 (300-OAc), 170.06 (600-
OAc), 172.49 (4-C), 206.51 (acetone) ppm; IR (ATR):
vꢀ = 693, 763, 908, 1,033, 1,062, 1,213, 1,367, 1,460,
1,505, 1,520, 1,562, 1,618, 1,743, 2,910–3,000 (broad
3-(4-Phenyl-4H-1,2,4-triazol-3-yl)-7-O-(b-D-tetra-
acetylglucopyranosyl)-2H-chromen-2-one
(6, C31H29N3O12)
1
M.p.: 113 °C; H NMR (400 MHz, DMSO-d6): d = 1.97
(s, 3H, 600-OAc), 1.98 (s, 3H, 300-OAc), 2.01 (s, 3H, 400-
OAc), 2.02 (s, 3H, 200-OAc), 4.10 (dd, J = 12.0 Hz,
J = 1.8 Hz, 1H, 600-CH), 4.19 (dd, J = 12.0 Hz,
J = 5.8 Hz, 1H, 600-CH), 4.33 (m, 1H, 500-CH), 5.03 (t,
J = 9.5 Hz, 1H, 400-CH), 5.12 (dd, J = 8.5 Hz,
J = 8.0 Hz, 1H, 200-CH), 5.40 (t, J = 9.5 Hz, 1H, 300-
CH), 5.77 (d, J = 8.0 Hz, 1H, 100-CH), 7.06 (dd,
J = 8.8 Hz, J = 2.2 Hz, 1H, 6-CH), 7.08 (d, J = 2.2 Hz,
1H, 8-CH), 7.39–7.50 (m, 5H, Ph), 7.87 (d. J = 8.3 Hz,
d
CH), 3,000–3,670 (broad dNH
)
cm-1
;
[a]2D5 = 08
g-1 cm3 dm-1, [a] = -20.0° g-1 cm3 dm-1 (c = 0.1,
25
546
acetone); HRMS (ESI/TOF): [M ? H?] found (calcu-
lated): 679.2237 (679.2246).
General procedure B for glucosylation of 7-10
1H, 5-CH), 8.58 (s, 1H, 4-CH), 9.00 (s, 1H, 5-CHtriazole
)
The reaction and extraction was performed according to the
general procedure A; the chloroform extracts were evapo-
rated without prior drying and 150 cm3 toluene was added.
The obtained heterogeneous mixture was refluxed for
5 min, cooled, and treated with solid Na2SO4 to absorb the
remaining water, tetrabutylammonium bromide, and some
black by-products. The mixture was filtered and washed
thoroughly with toluene. The toluene was evaporated, and
the remaining gum was dissolved in 10 cm3 toluene (if
necessary, with heating). After cooling, to this solution
exactly 50 cm3 n-hexane was added, which resulted in the
formation of a brown resin. This was decanted and washed
with hexane, and the remaining resin was dissolved in some
appropriate solvent (ethyl acetate, acetone, etc.) and
adsorbed on 5 g silica gel. Then the silica with the adsorbed
peracetylated glucoside was placed on top of a short column
(60 g silica) and eluted by ethyl acetate (ca. 0.5 dm3). The
eluate was evaporated and dried in vacuum (10-2 mbar),
giving pure 15 or not pure 13, 17 or 19 (more than quan-
titative yield). The latter were purified by precipitation with
water from the acetone solution with brine-induced coag-
ulation (according to the general procedure A). Pure
crystalline glucoside came after one (13, 17) or two (19)
cycles of precipitation. The yield was quantitative.
ppm; 13C NMR (100 MHz, DMSO-d6): d = 20.23 (CH3),
20.28 (CH3), 20.31 (CH3), 20.33 (CH3), 61.53 (600-CH2),
67.85 (400-CH), 70.38 (200-CH), 71.07 (500-CH), 71.85 (300-
CH), 96.34 (100-CH), 103.13 (8-CH), 112.73 (3-C), 113.60
(10-C), 114.21 (6-CH), 124.04 (20-CHPh), 128.66 (40-
CHPh), 129.60 (30-CHPh), 130.90 (5-CH), 134.45 (10-CPh),
145.05 (5-CHtriazole), 146.97 (4-CH), 148.28 (3-Ctriazole),
155.32 (9-C), 157.57 (2-C), 159.83 (7-C), 169.07 (200-
OAc), 169.29 (400-OAc), 169.58 (300-OAc), 169.88 (600-
OAc) ppm; IR (ATR): vꢀ = 691, 753, 765, 907, 934, 991,
1,033, 1,066, 1,131, 1,181, 1,214, 1,366, 1,504, 1,576,
1,613, 1,738, 2,830–3,150 (broad dCH) cm-1; [a]D25
=
-24° g-1 cm3 dm-1 (c = 0.25, acetone); HRMS (ESI/
TOF): [M ? H?] found (calculated): 636.1826 (636.1824).
2-Amino-6-ethyl-3-(4-phenyl-4H-1,2,4-triazol-3-yl)-7-O-
(b-D-tetraacetylglucopyranosyl)-4H-chromen-4-one
(22, C33H34N4O12)
Synthesized according to the general procedure A from
871 mg 21 (2.5 mmol), K2CO3 (37.5 ? 12.5 mmol), and
acetobromoglucose (25 mmol). The crystalline product
was found to occlude resting acetone, not removable in
vacuum of oil pump (10-2 mbar). The product-to-acetone
ratio was found to be approximately 1:1 (by NMR). Hence
123

Highly efficient glucosylation of flavonoids
1509
3-Phenyl-7-O-(b-D-tetraacetylglucopyranosyl)-
4H-chromen-4-one (13, C29H28O12)
3-Phenyl-7-O-(b-D-tetraacetylglucopyranosyl)-
2H-chromen-2-one (17, C29H28O12)
M.p.: 145 °C; 1H NMR (400 MHz, DMSO-d6): d = 1.99 (s,
3H, 300-OAc), 2.03 (s, 6H, 400- and 500-OAc), 2.04 (s, 3H, 200-
OAc), 4.12 (dd, J = 12.3 Hz, J = 2.3 Hz, 1H, 600-CH2),
4.22 (dd, J = 12.3 Hz, J = 5.8 Hz, 1H, 600-CH2), 4.36 (m,
1H, 500-CH), 5.06 (t, J = 9.5 Hz, 1H, 400-CH), 5.15 (dd,
J = 9.5 Hz, J = 8.0 Hz, 1H, 200-CH), 5.43 (t, J = 9.5 Hz,
1H, 300-CH), 5.83 (d, J = 8.0 Hz, 1H, 100-CH), 7.13 (dd,
J = 8.8 Hz, J = 2.3 Hz, 1H, 6-H), 7.27 (d, J = 2.3 Hz, 1H,
8-H), 7.35–7.46 (m, 5H, Ph), 8.10 (d, J = 8.8 Hz, 1H, 5-H),
8.51 (s, 1H, 2-H) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 20.24 (OAc), 20.30 (OAc), 20.35 (OAc), 20.41 (OAc),
61.56 (600-CH2), 67.87 (400-CH), 70.45 (200-CH), 71.10 (500-
CH), 71.85 (300-CH), 96.44 (100-CH), 103.77 (8-CH), 115.35
(6-CH), 119.24 (10-C), 123.85 (3-C), 127.43 (5-CH), 127.86
(40-CHPh), 128.12 (30-CHPh), 128.89 (20-CHPh), 131.73 (10-
CPh), 154.47 (2-CH), 156.86 (9-C), 160.13 (7-C), 169.08
(200-OAc), 169.30 (400-OAc), 169.59 (300-OAc), 169.94 (600-
OAc), 174.37 (4-C) ppm; IR (ATR): vꢀ = 694, 752, 784, 858,
884, 905, 948, 980, 1,031, 1,055, 1,080, 1,100, 1,124, 1,150,
1,220, 1,371, 1,444, 1,497, 1,620, 1,638, 1,739, 1,750,
M.p.: 152 °C; H NMR (400 MHz, DMSO-d6): d = 1.98
(s, 3H, OAc), 2.02 (s, 3H, OAc), 2.03 (s, 6H, OAc), 4.15
(dd, J = 12.3 Hz, J = 2.3 Hz, 1H, 600-CH2), 4.21 (dd,
J = 12.3 Hz, J = 5.6 Hz, 1H, 600-CH2), 4.34 (m, 1H, 500-
CH), 5.04 (t, J = 9.5 Hz, 1H, 400-CH), 5.12 (dd,
J = 9.8 Hz, J = 8.0 Hz, 1H, 200-CH), 5.42 (t,
J = 9.5 Hz, 1H, 300-CH), 5.75 (d, J = 8.0 Hz, 1H, 100-
CH), 7.01 (dd, J = 8.5 Hz, J = 2.3 Hz, 1H, 6-H), 7.10 (d,
J = 2.3 Hz, 1H, 8-H), 7.37–7.78 (m, 3H, 30- and 40-HPh),
7.71 (m, 2H, 20-HPh), 7.75 (d, J = 8.5 Hz, 1H, 5-H), 8.23
(s, 1H, 4-H) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 20.25 (OAc), 20.31 (OAc), 20.37 (OAc), 20.41 (OAc),
61.58 (600-CH2), 67.90 (400-CH), 70.48 (200-CH), 71.04 (500-
CH), 71.89 (300-CH), 96.54 (100-CH), 102.79 (8-CH),
113.76 (6-CH), 114.79 (10-C), 124.47 (3-C), 128.19 (30-
CHPh), 128.34 (3C, 20- and 40-CHPh), 129.90 (5-CH),
134.69 (10-CPh), 140.41 (4-CH), 154.25 (9-C), 158.65 (7-
C), 159.68 (2-C), 169.08 (200-OAc), 169.30 (400-OAc),
169.58 (300-OAc), 169.93 (600-OAc) ppm; IR (ATR):
vꢀ = 698, 737, 786, 865, 899, 931, 997, 1,028, 1,044,
1,073, 1,110, 1,127, 1,177, 1,209, 1,241, 1,367, 1,430,
1
2,861–3,120 (broad dCH
)
cm-1
;
[a]2D5 = -15.0°
g-1 cm3 dm-1 (c = 1.03, acetone); HRMS (ESI/TOF):
[M ? H?] found (calculated): 569.1652 (569.1654).
1,502, 1,612, 1,727, 1,741, 2,850–3,120 (broad dCH) cm-1
;
[a]D25 = -18.4° g-1 cm3 dm-1 (c = 1, acetone); HRMS
(ESI/TOF): [M ? H?] found (calculated): 569.1645
(569.1654).
2-Phenyl-7-O-(b-D-tetraacetylglucopyranosyl)-
4H-chromen-4-one (15, C29H28O12)
1
M.p.: 180 °C; H NMR (400 MHz, DMSO-d6): d = 1.99
4-Phenyl-7-O-(b-D-tetraacetylglucopyranosyl)-
2H-chromen-2-one (19, C29H28O12)
(s, 3H, OAc), 2.01 (s, 3H, OAc), 2.03 (s, 3H, OAc), 2.04 (s,
3H, OAc), 4.15 (dd, J = 12.3 Hz, J = 2.5 Hz, 1H, 600-
CH2), 4.21 (dd, J = 12.3 Hz, J = 5.8 Hz, 1H, 600-CH2),
4.37 (m, 1H, 500-CH), 5.05 (t, J = 9.5 Hz, 1H, 400-CH),
5.15 (dd, J = 9.5 Hz, J = 8.0 Hz, 1H, 200-CH), 5.43 (t,
J = 9.5 Hz, 1H, 300-CH), 5.82 (d, J = 8.0 Hz, 1H, 100-CH),
7.00 (s, 1H, 3-H), 7.13 (dd, J = 8.8 Hz, J = 2.3 Hz, 1H, 6-
H), 7.39 (d, J = 2.3 Hz, 1H, 8-H), 7.55–7.64 (m, 3H, 30-
and 40-HPh), 8.0 (d, J = 8.8 Hz, 1H, 5-H), 8.08 (m, 2H, 20-
HPh) ppm; 13C NMR (100 MHz, DMSO-d6): d = 20.26
(OAc), 20.31 (OAc), 20.37 (OAc), 20.40 (OAc), 61.63 (600-
CH2), 67.89 (400-CH), 70.48 (200-CH), 71.14 (500-CH), 71.82
(300-CH), 96.58 (100-CH), 104.28 (8-CH), 106.94 (3-CH),
115.15 (6-CH), 118.80 (10-C), 126.22 (20-CHPh), 126.68
(5-CH), 129.07 (30-CHPh), 131.01 (10-CPh), 131.78 (40-
CHPh), 156.92 (9-C), 160.31 (7-C), 162.49 (2-C), 169.09
(200-OAc), 169.31 (400-OAc), 169.57 (300-OAc), 169.92 (600-
OAc), 176.33 (4-C) ppm; IR (ATR): vꢀ = 667, 694, 782,
816, 836, 909, 956, 979, 1,032, 1,062, 1,081, 1,129, 1,157,
1,182, 1,216, 1,233, 1,351, 1,370, 1,448, 1,494, 1,571,
This compound tends to form a resin, which solidifies when
staying in water for 24 h. 1H NMR data recorded in CDCl3
1
are reported in Ref. [31]. The H NMR spectrum recorded
1
in DMSO-d6 differs from that mentioned above. H NMR
(400 MHz, DMSO-d6): d = 1.98 (s, 3H, OAc), 2.02 (s, 3H,
OAc), 2.03 (s, 3H, OAc), 2.08 (s, 3H, OAc), 4.11 (dd,
J = 12.3 Hz, J = 2.1 Hz, 1H, 600-CH2), 4.20 (dd,
J = 12.3 Hz, J = 5.6 Hz, 1H, 600-CH2), 4.34 (m, 1H, 500-
CH), 5.04 (t, J = 9.8 Hz, 1H, 400-CH), 5.12 (dd,
J = 9.8 Hz, J = 8.0 Hz, 1H, 200-CH), 5.42 (t,
J = 9.8 Hz, 1H, 300-CH), 5.76 (d, J = 8.0 Hz, 1H, 100-
CH), 6.31 (s, 1H, 3-H), 6.96 (dd, J = 8.8 Hz, J = 2.5 Hz,
1H, 6-H), 7.17 (d, J = 2.5 Hz, 1H, 8-H), 7.39 (d,
J = 8.8 Hz, 1H, 5-H), 7.51–7.59 (m, 5H, Ph) ppm; 13C
NMR (100 MHz, DMSO-d6): d = 20.23 (OAc), 20.27
(OAc), 20.34 (OAc), 20.37 (OAc), 61.57 (600-CH2), 67.90
(400-CH), 70.46 (200-CH), 71.06 (500-CH), 71.87 (300-CH),
96.48 (100-CH), 103.57 (8-CH), 112.50 (3-CH), 113.58 (10-
C), 113.70 (6-CH), 128.10 (5-CH), 128.42 (20-CHPh),
128.86 (30-CHPh), 129.71 (40-CHPh), 134.75 (10-CPh),
154.79 (4-C), 154.99 (9-C), 158.84 (7-C), 159.69 (2-C),
169.06 (200-OAc), 169.29 (400-OAc), 169.57 (300-OAc),
169.93 (600-OAc) ppm; IR (ATR): vꢀ = 701, 774, 859,
1,610, 1,627, 1,653, 1,730, 1,755, 2,860–3,100 (broad dCH
)
cm-1; [a]2D5 = -22.3° g-1 cm3 dm-1 (c = 1.03, acetone);
HRMS (ESI/TOF): [M ? H?] found (calculated):
569.1653 (569.1654).
123

1510
V. Semeniuchenko et al.
907, 999, 1,032, 1,068, 1,118, 1,158, 1,210, 1,371, 1,610,
1,734, 2,880–3,120 (broad dCH) cm-1; [a]D25 = -18.0°
g-1 cm3 dm-1 (c = 0.5, acetone); HRMS (ESI/TOF):
[M ? H?] found (calculated): 569.1640 (569.1654).
1,000, 1,041, 1,077, 1,091, 1,207, 1,243, 1,257, 1,284,
1,315, 1,371, 1,429, 1,459, 1,479, 1,506, 1,625, 1,650,
2,850–3,000 (broad dCH), 3,000–3,600 (broad dOH) cm-1
;
[a]2D5 = -41.6° g-1 cm3 dm-1 (c = 0.084, MeOH);
HRMS (ESI/FT-ICR): [M ? H?] found (calculated):
496.1727 (496.1720).
General procedure C for the deacetylation of protected
glucosides
7-O-(b-D-Glucopyranosyl)-3-(4-phenyl-4H-1,2,4-triazol-3-
yl)-2H-chromen-2-one (12, C23H21N3O8)
M.p.: 180 °C; 1H NMR (400 MHz, DMSO-d6, r.t.):
d = 3.16 (br s, 1H, 400-CH), 3.28 (br s, 2H, 200-CH and
500-CH), 3.43 (br m, 2H, 300-CH and 600-CH2), 3.69 (br m,
1H, 600-CH2), 4.60 (br t, J = 5.5 Hz, 1H, 600-OH), 5.06 (d,
J = 7.0 Hz, 1H, 100-CH), 5.08 (br d, J = 4.5 Hz, 1H, 400-
OH), 5.17 (br s, 1H, 300-OH), 5.44 (br s, 1H, 200-OH), 7.08
(br s, 1H, 8-CH), 7.09 (br d, J = 8.3 Hz, 6-H), 7.37–7.50
(m, 5H, Ph), 7.82 (d, J = 8.3 Hz, 5-CH), 8.57 (s, 1H, 4-
The reaction should be carried out strictly under inert
atmosphere. Peracetylated glucoside (0.5 g), 20 cm3 abso-
lute methanol, and NaOMe (0.1 cm3, 0.5 N MeOH
solution, Fluka) were placed in a weighed flask. The reac-
tion was stirred at r.t. for 24 h and evaporated in vacuum.
Conversion was calculated by the difference of mass; in
case of insufficient conversion, the procedure was repeated
(e.g., for 20, three cycles of deacetylation were needed).
Water was added, and the mixture was filtrated, affording
crystalline deprotected glucoside after drying. Ion exchan-
ger DowexÒ 50WX8 100–200 mesh (0.5 g) was added to
the filtrate and the mixture was stirred for 5 min (controlled
by pH), filtrated, and washed with water. Evaporation and
drying of the filtrate (in vacuum, 10-2 mbar) gave an
additional portion of the crystalline glucoside. Yield of the
combined fractions was quantitative.
1
CH), 9.00 (s, 1H, 5-CHtriazole) ppm; H NMR (400 MHz,
DMSO-d6, 90 °C): d = 3.04 (br s, OH ? H2O), 3.22 (t,
J = 8.4 Hz, 1H, 400-CH), 3.33 (m, 2H, 200-CH and 500-CH),
3.43 (t, J = 7.0 Hz, 1H, 300-CH), 3.51 (dd, J = 11.7 Hz,
J = 5.9 Hz, 1H, 600-CH2), 3.73 (d, J = 11.3 Hz, 1H, 600-
CH2), 4.25 (br s, 1H, OH), 4.71 (br s, 1H, OH), 5.04 (br d,
J = 7.0 Hz, 2H, 100-CH and OH), 7.06 (d, J = 2.0 Hz, 1H,
8-H), 7.09 (dd, J = 8.6 Hz, J = 2.0 Hz, 6-H), 7.36–7.52
(m, 5H, Ph), 7.76 (d, J = 8.6 Hz, 1H, 5-CH), 8.45 (s, 1H,
6-Ethyl-7-O-(b-D-glucopyranosyl)-3-(4-phenyl-4H-1,2,4-
triazol-3-yl)-4H-chromen-4-one
4-CH), 8.85 (s, 1H, 5-CHtriazole
)
ppm; 13C NMR
(100 MHz, DMSO-d6, r.t.): d = 60.57 (600-CH2), 69.55
(400-CH), 73.03 (200-CH), 76.42 (500-CH), 77.14 (300-CH),
99.89 (100-CH), 103.05 (8-CH), 111.96 (3-C), 112.77 (10-
C), 114.41 (6-CH), 124.06 (20-CHPh), 128.69 (40-CHPh),
129.62 (300-CHPh), 130.60 (5-CH), 134.47 (10-CPh), 145.05
(5-CHtriazole), 147.20 (4-CH), 148.39 (3-Ctriazole), 155.50
(9-C), 157.81 (2-C), 161.36 (7-C) ppm; IR (ATR):
vꢀ = 690, 753, 767, 827, 841, 892, 941, 979, 990, 1,021,
1,077, 1,114, 1,128, 1,182, 1,226, 1,250, 1,273, 1,348,
1,364, 1,394, 1,503, 1,612, 1,736, 2,830–2,950 (broad
(11, C25H25N3O8)
M.p.: 203 °C; 1H NMR (400 MHz, DMSO-d6, r.t.):
d = 1.13 (t, J = 7.4 Hz, 3H, CH3CH2), 2.66 (q,
J = 7.4 Hz, 2H, CH3CH2), 3.19 (m, 1H, 400-CH), 3.33
(m, 2H, 200- and 300-CH), 3.48 (m, 2H, 500-CH and 600-CH2),
3.72 (m, 1H, 600-CH2), 4.68 (br t, J = 5.5 Hz, 1H, 600-OH),
5.08 (br d, J = 7.5 Hz, 1H, 100-CH), 5.16 (d, J = 4.8 Hz,
1H, 400-OH), 5.22 (br s, 1H, 300-OH), 5.44 (br s, 1H, 200-
OH), 7.29 (s, 1H, 8-H), 7.35–7.45 (m, 5H, Ph), 7.65 (s, 1H,
1
5-H), 8.76 (s, 1H, 2-H), 8.99 (s, 1H, 5-Htriazole) ppm; H
d
CH), 3,000–3,500 (broad dOH) cm-1; [a]D25 = -24.5°
NMR (400 MHz, DMSO-d6, 90 °C): d = 1.17 (t,
J = 7.4 Hz, 3H, CH3CH2), 2.70 (q, J = 7.4 Hz, 2H,
CH3CH2), 3.06 (br s, OH ? H2O), 3.27 (m, 1H, 400-CH),
3.39 (m, 2H, 200- and 300-CH), 3.45–3.55 (m, 2H, 500-CH and
600-CH2), 3.77 (br d, J = 11.3 Hz, 600-CH2), 4.34 (br s, 1H,
OH), 4.84 (br s, 1H, OH), 5.06 (m, 2H, 100-CH and OH),
7.30 (s, 1H, 8-H), 7.36–7.46 (m, 5H, Ph), 7.69 (s, 1H, 5-H),
8.64 (s, 1H, 2-H), 8.85 (s, 1H, 5-Htriazole) ppm; 13C NMR
(100 MHz, DMSO-d6): d = 13.64 (CH3CH2), 22.36
(CH3CH2), 60.66 (600-CH2), 69.68 (400-CH), 73.17 (200-
CH), 76.53 (300-CH), 77.26 (500-CH), 100.21 (100-CH),
102.68 (8-CH), 113.15 (3-C), 117.14 (10-C), 124.15 (3C,
5-CH and 20-CHPh), 128.60 (40-CHPh), 129.45 (30-CHPh),
132.24 (6-C), 134.47 (10-CPh), 145.22 (5-CHtriazole), 146.46
(3-Ctriazole), 155.81 (9-C), 158.09 (2-CH), 160.03 (7-C),
172.83 (4-C) ppm; IR (ATR): vꢀ = 692, 761, 794, 894,
g-1 cm3 dm-1 (c = 1.02, DMF); HRMS (ESI/FT-ICR):
[M ? H?] found (calculated): 468.1422 (468.1407),
[M ? Na?] found (calculated): 490.1194 (490.1226).
7-O-(b-D-Glucopyranosyl)-3-phenyl-4H-chromen-4-one
(14, C21H20O8)
1
M.p.: 170 °C; H NMR (400 MHz, DMSO-d6): d = 3.19
(br m, 1H, 400-CH), 3.31 (br m, 2H, 200- and 300-CH), 3.44–
3.51 (m, 2H, 500-CH and 600-CH2), 3.71 (dd, J = 10.0 Hz,
J = 5.5 Hz, 1H, 600-CH2), 4.62 (t, J = 5.5 Hz, 1H, 600-OH),
5.10 (d, J = 4.7 Hz, 1H, 400-OH), 5.11 (d, J = 7.0 Hz, 1H,
100-CH), 5.16 (br d, J = 4.3 Hz, 1H, 300-OH), 5.45 (br d,
J = 4.3 Hz, 1H, 200-OH), 7.16 (dd, J = 8.8 Hz,
J = 2.3 Hz, 1H, 6-H), 7.26 (d, J = 2.3 Hz, 1H, 8-H),
7.35–7.46 (m, 3H, 30- and 40-CHPh), 7.59 (m, 2H, 20-CHPh),
8.06 (d, J = 8.8 Hz, 1H, 5-H), 8.49 (s, 1H, 2-H) ppm; 13C
123

Highly efficient glucosylation of flavonoids
1511
NMR (100 MHz, DMSO-d6): d = 60.60 (600-CH2), 69.59
(400-CH), 73.09 (200-CH), 76.45 (300-CH), 77.19 (500-CH),
99.95 (100-CH), 103.43 (8-CH), 115.70 (6-CH), 118.45 (10-
C), 123.73 (3-C), 126.95 (5-CH), 127.82 (40-CHPh), 128.12
(30-CHPh), 128.91 (20-CHPh), 131.87 (10-CPh), 154.32 (2-
CH), 157.04 (9-C), 161.50 (7-C), 174.43 (4-C) ppm; IR
(ATR): vꢀ = 689, 697, 756, 780, 831, 840, 883, 898, 954,
1,012, 1,025, 1,044, 1,053, 1,070, 1,105, 1,198, 1,223,
1,236, 1,308, 1,310, 1,329, 1,349, 1,373, 1,381, 1,442,
1,496, 1,600, 1,602, 1,605, 1,623, 1,636, 2,850–2,950
(6-CH), 113.96 (10-C), 123.79 (3-C), 128.17 (30-CHPh),
128.24 (40-CHPh), 128.31 (20-CHPh), 129.62 (5-CH),
134.82 (10-CPh), 140.67 (4-C), 154.39 (9-C), 159.90
(2-C), 160.09 (7-C) ppm; IR (ATR): = 690, 783, 837,
1,019, 1,042, 1,071, 1,099, 1,113, 1,172, 1,255, 1,363,
1,505, 1,611, 1,622, 1,714, 2,840–2,940 (broad dCH),
3,000–3,600 (broad dOH) cm-1; [a]D25 = -34.6° g-1 cm3
dm-1 (c = 1.01, DMF); HRMS (ESI/FT-ICR): [M ? H?]
found (calculated): 401.1242 (401.1236), [M ? Na?]
found (calculated): 423.1019 (423.1056).
(broad dCH), 3,000–3,500 (broad dOH) cm-1; [a]D25
=
-30.4° g-1 cm3 dm-1 (c = 1.03, DMF); HRMS (ESI/FT-
ICR): [M ? H?] found (calculated): 401.1243 (401.1236),
[M ? Na?] found (calculated): 423.1026 (423.1056).
7-O-(b-D-Glucopyranosyl)-4-phenyl-2H-chromen-2-one
(20)
1H NMR spectrum is consistent with that found in Ref.
13
[31]; C NMR (100 MHz, DMSO-d6): d = 60.61 (600-
7-O-(b-D-Glucopyranosyl)-2-phenyl-4H-chromen-4-one
(16, C21H20O8)
CH2), 69.59 (400-CH), 73.09 (200-CH), 76.47 (300-CH), 77.15
(500-CH), 99.97 (100-CH), 103.63 (8-CH), 111.87 (3-C),
112.72 (10-C), 113.73 (6-C), 127.75 (5-CH), 128.42 (20-
CHPh), 128.85 (300-CHPh), 129.67 (400-CHPh), 134.88 (100-
CPh), 155.00 (9-C), 155.10 (4-C), 159.93 (2-C), 160.27 (7-
C) ppm; IR (ATR): = 707, 781, 796, 816, 893, 991, 1,020,
1,047, 1,071, 1,102, 1,121, 1,161, 1,205, 1,230, 1,257,
1,289, 1,369, 1,382, 1,407, 1,446, 1,552, 1,616, 1,663,
1
M.p.: 281 °C; H NMR (400 MHz, DMSO-d6): d = 3.20
(m, 1H, 400-CH), 3.31 (m, 2H, 200- and 300-CH), 3.48 (m, 2H,
500-CH and 600-CH2), 3.72 (m, 1H, 600-CH2), 4.63 (t,
J = 5.5 Hz, 1H, 600-OH), 5.10 (d, J = 5.3 Hz, 1H, 400-
OH), 5.14 (d, J = 7.0 Hz, 1H, 100-CH), 5.17 (br d,
J = 4.0 Hz, 1H, 300-OH), 5.45 (br d, J = 3.8 Hz, 1H, 200-
OH), 6.99 (s, 1H, 3-H), 7.13 (dd, J = 8.8 Hz, J = 2.3 Hz,
1H, 6-H), 7.41 (d, J = 2.3 Hz, 1H, 8-H), 7.55–7.64 (m,
3H, 30- and 40-HPh), 7.97 (d, J = 8.8 Hz, 1H, 5-H), 8.08
(m, 2H, 20-HPh) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 60.56 (600-CH2), 69.51 (400-CH), 73.11 (200-CH), 76.46
(300-CH), 77.17 (500-CH), 99.95 (100-CH), 103.80 (8-CH),
106.82 (3-CH), 115.53 (6-CH), 117.99 (10-C), 126.33 (3C,
5-CH and 20-CHPh), 129.09 (30-CHPh), 131.14 (10-CPh),
131.72 (40-CHPh), 157.10 (9-C), 161.64 (7-C), 162.33 (2-
C), 176.43 (4-C) ppm; IR (ATR): vꢀ = 673, 774, 823, 861,
870, 910, 1,000, 1,012, 1,065, 1,101, 1,173, 1,248, 1,271,
1,382, 1,450, 1,494, 1,564, 1,571, 1,586, 1,616, 2,830–
2,840–2,970 (broad dCH), 3,000–3,600 (broad dOH) cm-1
;
[a]2D5 = -37.8° g-1 cm3 dm-1 (c = 1, DMF); HRMS
(ESI/FT-ICR): [M ? H?] found (calculated): 401.1238
(401.1236), [M ? Na?] found (calculated): 423.1052
(423.1056).
Attempt to synthesize 2-amino-6-ethyl-7-O-(b-D-glucopyr-
anosyl)-3-(4-phenyl-4H-1,2,4-triazol-3-yl)-4H-chromen-4-
one (23, C25H26N4O8)
Compound 22 (461 mg, 0.679 mmol) and NaOMe
(0.5 cm3, 0.5 N in MeOH) were stirred in 20 cm3 absolute
MeOH for 72 h (nitrogen atmosphere). All volatiles were
removed in vacuum. The difference of mass showed full
conversion of 22. Further operations according to the
general procedure C afforded 296 mg (85%) crude 23,
which showed three major peaks by analytical HPLC and
could not be further purified by washing with boiling
acetone or acetonitrile (23 stays undissolved). HRMS (ESI/
TOF): [M ? H?] found (calculated): 511.1810 (511.1823),
[M ? Na?] found (calculated): 533.1632 (533.1643).
2,970 (broad dCH), 3,030–3,590 (broad dOH) cm-1
;
[a]2D5 = -43.6° g-1 cm3 dm-1 (c = 1.02, DMF); HRMS
(ESI/FT-ICR): [M ? H?] found (calculated): 401.1254
(401.1236).
7-O-(b-D-Glucopyranosyl)-3-phenyl-2H-chromen-2-one
(18, C21H20O8)
1
M.p.: 228 °C; H NMR (400 MHz, DMSO-d6): d = 3.19
(m, 1H, 400-CH), 3.30 (m, 2H, 200- and 300-CH), 3.47 (m, 2H,
500-CH and 600-CH2), 3.72 (m, 1H, 600-CH2), 4.62 (t,
J = 5.5 Hz, 1H, 600-OH), 5.06 (d, J = 7.3 Hz, 1H, 100-
CH), 5.09 (d, J = 5.3 Hz, 1H, 400-OH), 5.16 (br d,
J = 4.5 Hz, 1H, 300-OH), 5.43 (br d, J = 4.5 Hz, 1H, 200-
OH), 7.05 (dd, J = 8.8 Hz, J = 2.3 Hz, 1H, 6-H), 7.09 (d,
J = 2.3 Hz, 1H, 8-H), 7.37–7.48 (m, 3H, 30- and 40-HPh),
7.71 (br d, J = 8.8 Hz, 3H, 5-H and 20-CHPh), 8.21 (s, 1H,
4-H) ppm; 13C NMR (100 MHz, DMSO-d6): d = 60.63
(600-CH2), 69.61 (400-CH), 73.11 (200-CH), 76.48 (300-CH),
77.12 (500-CH), 99.98 (100-CH), 102.69 (8-CH), 113.84
Acknowledgements V.S. thanks the Herbert-Quandt Foundation
and the German Academic Exchange Service (DAAD) for doctoral
fellowships. He also thanks the partnership program between the
University of Konstanz and the NTSU Kiew for the opportunity to
perform his doctoral studies in Konstanz. The authors are thankful
to Kathrin Lindner (Konstanz University) for reproducibility testing,
to Olga Shablykina (Kiev University) for the method for the synthesis
of 5, to Rheinhold Weber, Sascha Keller, and Anna-Lena Steck
(Konstanz University) for measuring of the HRMS, and to Milena
Quentin for helping to prepare the manuscript. We are grateful to
MCAT, Bayer AG, Merck KGaA, and Wacker AG for generous gifts
of reagents.
123

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