Synthesis of Salicaceae Acetyl Salicins Using Selective Deacetylation and Acetyl Group Migration

Article abstract of DOI:10.1021/acs.jnatprod.9b00570

In the present work, the synthesis of acetylated salicins, which occur naturally in many Salicaceae species, is reported. The preparation of 2-O-acetylsalicin, 2-O-acetylchlorosalicin, and 2-O-acetylethylsalicin from peracetylated bromosalicin with selective acid-catalyzed deacetylation and one-pot nucleophilic substitution of bromine as the key steps is described. The base-catalyzed O-2 → O-6 acetyl migration afforded 6-O-acetylsalicin derivatives in good yields. Thus, the first synthesis of 6-O-acetylsalicin (fragilin) using acetyl group migration is reported as well as the synthesis of 6-O-acetylchlorosalicin and 6-O-acetylethylsalicin. The NaOMe-catalyzed deacetylation of acetylated glycosides gave salicin, chlorosalicin, and ethylsalicin recently reported from Alangium chinense.

Full text of DOI:10.1021/acs.jnatprod.9b00570

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Article
Synthesis of Salicaceae Acetyl Salicins Using Selective Deacetylation
and Acetyl Group Migration
Dariya A. Romanova, David L. Avetyan, Maxim L. Belyanin, and Elena V. Stepanova*
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ABSTRACT: In the present work, the synthesis of acetylated
salicins, which occur naturally in many Salicaceae species, is
reported. The preparation of 2-O-acetylsalicin, 2-O-acetylchlor-
osalicin, and 2-O-acetylethylsalicin from peracetylated bromosali-
cin with selective acid-catalyzed deacetylation and one-pot
nucleophilic substitution of bromine as the key steps is described.
The base-catalyzed O-2 → O-6 acetyl migration afforded 6-O-
acetylsalicin derivatives in good yields. Thus, the first synthesis of
6-O-acetylsalicin (fragilin) using acetyl group migration is reported
as well as the synthesis of 6-O-acetylchlorosalicin and 6-O-
acetylethylsalicin. The NaOMe-catalyzed deacetylation of acety-
lated glycosides gave salicin, chlorosalicin, and ethylsalicin recently
reported from Alangium chinense.
alicin is the glucoside of salicylic alcohol and the first
The semisynthesis of 2-O- and 3-O-acetylsalicins was
recently performed via the organotin-mediated acetylation of
4,6-benzylidene-ω-tritylsalicin.32 Herein the synthesis of 2-O-
acetylsalicins using peracetylated bromosalicin as the key
intermediate is described. An additional acetyl group migration
is the key step for the preparation of 6-O-acetylsalicins from 2-
O-acetylsalicins.
S
isolated and well-studied natural arylglycoside.1 It is one of
the most abundant secondary metabolites of Salicaceae and
other plants2 and is a valuable human resource in both native
form3−5 and as the precursor of aspirin.6−8 Many partially
acetylated salicin-like glycosides bearing different aglycones
have been isolated from natural sources.9−12 Fragilin was
isolated from Salix fragilis L. in the 1960s13,14 and identified as
6-O-acetylsalicin (also referred to as 6′-O-acetylsalicin),
although the position of the acetyl group was not
unequivocally known. The isolation of fragilin in the early
studies was likely enabled by a process of acetyl group
migration in the 2-O- and 3-O-acetylsalicins during plant
material treatment.15 For instance, the migration of the
benzoyl group occurred readily during the isolation of
benzoylated salicins from aspen leaves.16 2-O-Acetylsalicin
(also referred to as 2′-O-acetylsalicin) was first described in
1991 and17 3-O-acetylsalicin was described in 2013,11 and
since then, both were found in Salicaceae plants, as a rule, along
with other partially acetylated salicins including fragilin.18−26
Therefore, the possibility for acetyl migration should be
considered during the isolation of the acetylated glucosides
from plants. Thus, acetyl group migration should not only be
seen as an unwanted side process but also as a preparative
reaction to yield value-added products.27,28
RESULTS AND DISCUSSION
■
The starting material for the transformations was the known 2-
methylphenyl-(2,3,4,6-tetra-O-acetyl)-β-D-glucopyranoside
(1),33 which was converted to bromide 2 using photo-
generated bromine radicals (Scheme 1). A small amount of
dibromide 2a (∼5%) was also produced but could be removed
by recrystallization of the product mixture from EtOH. We and
others have found that bromide 2 is highly labile due to its
reactive benzylic C−Br bond.34,35 Thus, recrystallization of the
2/2a mixture from EtOH permitted the isolation of 2a;
however, partial substitution of the bromo substituent with an
ethoxy group occurred. To decrease the reactivity of 2, it was
converted to chloride 3 using a halogen-exchange reaction.36
However, the high reactivity of bromide 2 indicated that
deacetylation and the bromo-substitution may be carried out in
Received: June 20, 2019
It was demonstrated that the acetyl groups at different
positions of the sugar moiety may have a significant effect on
the biological activity.29,30 As an example, 2-acylated glycosides
are not decomposed by β-glucosidase and are more stable in
acidic medium9 and at elevated temperatures31 compared to
the nonacylated analogues.
© XXXX American Chemical Society and
American Society of Pharmacognosy
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Scheme 1. Preparation of Acetylated Salicins
A
Reagents and conditions: (a) Br2 (equimolar), CHCl3, hν, 2 h, 95%; (b) Me4NCl, MeCN, reflux, 4 h, 85%; (c) HBr 36%, CHCl3, EtOH, 30°C, 8
h, 68%; (d) HCl 36%, CHCl3, EtOH, 30°C 8 h; (e) MeCN, H2O, NaHCO3, room temperature (RT), 3−3.5 h; (f) Ag2O, acetone, H2O, HOAc,
RT, 48 h; (g) Ag2O, acetone, H2O, RT, 24 h, 35%.
a one-pot reaction. Indeed, HCl-catalyzed deacetylation37−39
of 2 (HCl, CHCl3, EtOH: 1 M HCl concentration) led to a
bromo/chloro exchange with 2-O-acetyl chloride 5 as the main
product (48%). The same product was obtained from chloride
3 under the same reaction conditions, albeit with a higher yield
(67%). By substituting HBr for HCl in the acidic deacetylation
of 2, only insignificant amounts of the deacetylated bromide
could be detected using HRMS and NMR data, and this
product could not be isolated from the reaction mixture.
Instead, the 2-O-acetylated ethoxymethyl product 4 was
formed. This is the first report of the formation of 4 and the
2-O-acetylated chloromethyl derivative 5.
The conversion of the chloromethyl group in compound 5
to a hydroxymethyl group using Ag2O in acetone−water led to
acetyl group migration to afford 6-O-acetylsalicin (fragilin) (9)
in a mixture with other monoacetates. The unwanted acetyl
group migration was suppressed by adding HOAc to the
reaction mixture and afforded 2-O-acetylsalicin (6) in excellent
yield (95%). This simple procedure may presumably also be
employed to suppress acyl group migration during syntheses of
carbohydrates. Thus, using chloro- and/or bromosalicins as
synthetic intermediates can be considered as a new (compared
with ref 32) method for the preparation of 2-O-acetylsalicin
(6).
acetyl migration instead of hydrolysis and provided 6-O-
acetylated glucosides in good yields. Thus, we converted 2-O-
acetylglucosides 4, 5, and 6 to 6-O-acetylated glucosides 7, 8,
and 9, respectively, in 79−88% yields. Compound 9 was also
obtained from chloromethyl derivative 8 by the chloro/
hydroxy exchange using Ag2O. The 6-O-acetyl derivatives 7−9
were synthesized for the first time.
The deacetylated glucosides 10, 11, and 12 were obtained
by transesterification of compounds 4, 7, 3, 5, 8, and 6, and 9,
respectively, in NaOMe-MeOH (Scheme 2). Small amounts of
Scheme 2. Preparation of O-Ethylsalicin (10), Chlorosalicin
(11), and Salicin (12)
compounds 10 and 11 were also obtained during selective
deacetylation of 2 and 3 (Scheme 1, conditions c and d) as
side products. Although the 2-O-acetyl group is the most stable
among the acetyl groups of peracetates, it can still be cleaved
under prolonged reaction times.38 Therefore, chromatographic
monitoring of the reaction progress is necessary during acid-
catalyzed deacetylation reactions.
However, the migration of acetyl groups is not always an
unwanted process that requires suppression. We made use of
acetyl group migration for target synthetic transformations.
The moderate basification (to pH 7.5−8)40 of the solutions of
2-O-acetylglycosides in a MeCN−water mixture caused rapid
O-Ethylsalicin (10) was recently isolated from Alangium
chinense,41 an herb that is used in traditional Chinese medicine.
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We trust that the chemical synthesis of such compounds will
contribute to their phytochemical study.
The NMR data of monoacetylated and deacetylated
1
compounds are summarized in Tables 1 (for H NMR) and
2 (for 13C NMR). Notably, the acetylation of HO-2 leads to a
1
downfield shift of the H-2 signal in the H NMR spectra but
does not significantly affect the 13C NMR chemical shift of C-
2. Acetylation of HO-6 shifts both H-6 and C-6 resonances
downfield.
In conclusion, acetyl groups in glucosides behave differently
depending on the pH of the reaction medium. Acidic catalysis
prompted selective deacetylation, providing several 2-O-
acetylsalicin derivatives from peracetylated bromosalicin. The
moderately basic conditions favored O-2 → O-6 acetyl group
migration, providing 6-O-acetylsalicins from 2-O-acetylsalicins.
Finally, the classic methanolysis with a strong base (NaOMe)
caused complete acetyl group cleavage to yield deacetylated
products.
EXPERIMENTAL SECTION
■
General Experimental Procedures. The reactions were
performed in commercial reagents (Aldrich, Fluka, Acros Organics).
Anhydrous solvents were purified and dried according to standard
procedures. Melting points, which are uncorrected, were determined
using an MP50 melting point system (Mettler Toledo). UV spectra
were recorded on an Evolution 600 UV−visible spectrophotometer.
Optical rotations were measured on an automatic compact polar-
imeter POP-1/2. IR spectra were recorded on an Agilent Cary 630
FTIR spectrometer equipped with a diamond ATR. 1H and 13C NMR
spectra were acquired for solutions in CDCl3, DMSO-d6, or methanol-
d4 on a Bruker AVANCE III HD instrument (400 and 101 MHz for
1
1H and 13C, respectively). The H NMR chemical shifts are referred
to the residual signal of CHCl3 (δH 7.26), DMSO-d5 (δH 2.50),
methanol-d3 (δH 3.31), or HDO (δH 4.79 ), and the 13C NMR shifts,
to the central line of CDCl3 signal (δC 77.00), DMSO-d6 signal (δC
39.52), and methanol-d4 signal (δC 49.00). Assignments of the signals
in the NMR spectra were performed using 2D-spectroscopy (COSY,
HSQC, and HMBC) experiments. High resolution mass spectra
(electrospray ionization, ESI-HRMS) were recorded in a positive ion
mode on a Bruker micrOTOF II mass spectrometer for 2 × 10−5 M
solutions in MeCN. Column chromatography was performed on silica
gel 60 (40−63 μm, Merck). Flash chromatography was carried out on
Reveleris X2 Buchi chromatographer using FlashPure Select C18 30
̈
μm columns. Thin-layer chromatography was carried out on silica gel
60 F254 plates on aluminum foil (Merck). Spots of compounds were
visualized under UV light (254 nm) and by heating the plates (at ca.
150 °C) after immersion in a 1:10 (v/v) mixture of 85% aqueous
H3PO4 and 95% EtOH.
2-(Bromomethyl)phenyl-2,3,4,6-tetra-O-acetyl-β-D-glucopyrano-
side (2). To a stirred suspension of 2-methylphenyl-(2,3,4,6-tetra-O-
acetyl)-β-D-glucopyranose (1) (1 g, 2.28 mmol) and NaHCO3 (3 g,
35.70 mmol) in CHCl3 (120 mL), the solution of bromine (118 μL,
2.28 mmol) in CHCl3 (5.8 mL) was added dropwise, and the reaction
mixture was irradiated with an incandescent lamp (200 W) until all
bromine reacted (red color disappeared). Solids were filtered off and
washed with CHCl3 (100 mL). The filtrate was concentrated under
reduced pressure, and the residue was purified by flash-chromatog-
raphy on a C18 column to give 1.12 g (95%) of the title compound as
colorless crystals, Rf 0.33 (toluene−acetone 10:1). Mp: 150−151 °C.
[α]20 +7 (c 1, CH2Cl2). UV (EtOH): λmax 277 nm. FTIR (ATR):
D
1
νmax 2960, 1749, 1602, 1488, 1368, 1225, 1038, 908, 731 cm−1. H
NMR (400 MHz, CDCl3, δ, ppm, J, Hz): 2.05 (s, 3H), 2.06 (s, 3H),
2.08 (s, 3H), 2.12 (s, 3H, COOCH3), 3.91 (ddd, 1H, J 2.4, J 5.4, J 9.8,
H-5), 4.19 (dd, 1H, J 2.4, J 12.3, H-6a), 4.30 (dd, 1H, J 5.4, J 12.3, H-
6b), 4.35 (d, 1H, J 9.8, CH2Br), 4.64 (d, 1H, J 9.8, CH2Br), 5.16 (d,
1H, J 7.6, H-1), 5.19 (dd, 1H, J 9.2, J 9.8, H-4), 5.33 (dd∼t, 1H, J 9.2,
H-3), 5.39 (dd, 1H, J 7.6, J 9.2, H-2), 7.01 (d, 1H, J 8.3, C6H4), 7.06
D
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(t, 1H, J 7.5, C6H4), 7.24−7.30 (m, 1H, C6H4), 7.37 (dd, 1H, J 1.3, J
7.5, C6H4). 13C NMR (101 MHz, CDCl3, δ, ppm): 20.6, 20.6, 20.7,
21.0 (4 × COOCH3), 27.9 (CH2Br), 61.9 (C-6), 68.3 (C-4), 70.7 (C-
2), 72.0 (C-5), 72.6 (C-3), 98.5 (C-1), 115.0, 123.5, 127.5, 130.1,
131.3, 154.2 (6 × C6H4), 169.4, 169.5, 170.2, 170.6 (4 × COOCH3).
HRESIMS: m/z 539.0531 [M + Na]+ (calcd for C21H25BrO10Na,
539.0529).
reaction mixture was stirred at RT (∼20 °C) for 48 h and
concentrated in vacuo, and the residue was directly purified by silica
gel column chromatography CHCl3−EtOH 14% to give 18 mg (95%)
of the title compound as a white solid, Rf 0.45 (CHCl3−EtOH 3:1).
Mp: 191−193 °C (lit. 189−191 °C).18 [α]20D −34 (c 1 MeOH). UV
(EtOH): λmax 215, 267 nm. FTIR (ATR): νmax 3307 (br), 2919, 1735,
1
1637, 1491, 1374, 1230, 1072, 1022, 991, 759 cm−1. H and 13C
2-(Chloromethyl)phenyl-2,3,4,6-tetra-O-acetyl-β-D-glucopyrano-
side (3). Bromide 2 (200 mg, 0.35 mmol) and Me4NCl (423 mg, 3.86
mmol) were dissolved in dry MeCN (20 mL) and refluxed under
stirring for 4 h. MeCN was distilled off in vacuo, and the residue was
dissolved in CHCl3 (30 mL), washed with 5% aq HCl (3 × 30 mL),
water (2 × 30 mL), dried over Na2SO4, and concentrated in vacuo.
The solid residue was recrystallized from EtOH (4 mL) to give 185
mg (85%) of the title compound as white crystals, Rf 0.33 (toluene−
NMR data are given in Tables 1 and 2, respectively. HRESIMS: m/z
351.1038 [M + Na]+ (calcd for C15H20O8Na, 351.1050). The
spectroscopic data are in agreement with the literature.18
General Procedure For O-2 → O-6 Acetyl Group Migration.
2-O-Acetylglucoside 4, 5, or 6 (0.06 mmol) was dissolved in a mixture
of CH3CN (1.5 mL) and H2O (1 mL), and saturated aqueous
NaHCO3 (100 μL) was added. The reaction mixture was stirred at
RT (∼20 °C) for 3−3.5 h (TLC control), HOAc (100 μL) was
added, and solvents were distilled under reduced pressure. The
residue was dissolved in water (3 mL), and extracted with EtOAc (3
× 3 mL). The EtOAc extracts were combined, dried over Na2SO4,
filtered, and concentrated in vacuo. The residue was purified on silica
gel column chromatography using CHCl3−EtOH 20:1 → 10:1.
2-(Ethoxymethyl)phenyl-6-O-acetyl-β-D-glucopyranoside (7).
The title compound was obtained from compound 4 as an amorphous
powder. Yield: 88%. Rf 0.69 (CHCl3−EtOH 8:1). [α]20D −94 (c 0.4,
MeOH). UV (EtOH): λmax 215, 269 nm. FTIR (ATR): νmax 3428
acetone 10:1). Mp: 148−149 °C. [α]20 +7 (c 1, CH2Cl2). UV
D
(EtOH): λmax 219, 275 nm. FTIR (ATR): νmax 2958, 2877, 1742,
1
1605, 1494, 1366, 1227, 1209, 1035, 908, 752 cm−1. H NMR (400
MHz, CDCl3, δ, ppm, J, Hz): 2.05 (s, 3H), 2.05 (s, 3H), 2.08 (s, 3H),
2.09 (s, 3H, COOCH3), 3.90 (ddd, 1H, J 2.0, J 5.3, J 9.3, H-5), 4.19
(dd, 1H, J 2.0, J 12.3, H-6a), 4.30 (dd, 1H, J 5.3, J 12.3, H-6b), 4.43
(d, 1H, J 11.2, CH2Cl), 4.73 (d, 1H, J 11.2, CH2Cl), 5.12 (d, 1H, J
7.9, H-1), 5.19 (dd∼t, 1H, J 9.3, H-4), 5.32 (dd∼t, 1H, J 9.3, H-3),
5.37 (dd, 1H, J 7.8, J 9.3, H-2), 7.03 (d, 1H, J 8.3), 7.08 (t, 1H, J 7.5),
7.29 (t, 1H, J 7.9), 7.38 (d, 1H, J 7.5, C6H4). 13C NMR (101 MHz,
CDCl3, δ, ppm): 20.6, 20.6, 20.7, 20.8 (4 × COOCH3), 40.8
(CH2Cl), 61.9 (C-6), 68.3 (C-4), 70.7 (C-2), 72.0 (C-5), 72.6 (C-3),
98.9 (C-1), 115.1, 123.5, 127.2, 130.0, 131.0, 154.4 (6 × C6H4),
169.4, 169.4, 170.2, 170.6 (4 × COOCH3). HRESIMS: m/z 495.1041
[M + Na]+ (calcd for C21H25ClO10Na, 495.1034).
1
(br), 3092, 1735, 1654, 1624, 1458 1235, 1000, 821, 759 cm−1. H
and 13C NMR data are given in Tables 1 and 2, respectively.
HRESIMS: m/z 379.1359 [M + Na]+ (calcd for C17H24O8Na,
379.1369).
2-(Chloromethyl)phenyl-6-O-acetyl-β-D-glucopyranoside (8).
The title compound was obtained from compound 6 as an amorphous
powder. Yield: 85%. Rf 0.70 (CHCl3−EtOH 4:1). [α]20D −52 (c 0.2,
MeOH). UV (EtOH): λmax 220, 275 nm. FTIR (ATR): νmax 3367
(br), 2917, 1718, 1603, 1492, 1368, 1235, 1068, 1035, 749 cm−1. 1H
and 13C NMR data are given in Tables 1 and 2, respectively.
HRESIMS: m/z 369.0720 [M + Na]+ (calcd for C15H19ClO7Na,
369.0712).
2-(Ethoxymethyl)phenyl-2-O-acetyl-β-D-glucopyranoside (4).
Peracetylated bromide 2 (330 mg,0.64 mmol) was dissolved in a
mixture of CHCl3 (1.5 mL) and EtOH (3 mL), and 36% aqueous
HBr (1 mL) was added. The reaction mixture was kept at 30 °C for 8
h (TLC showed the formation of the major component and one
lower-running spot), and anion-exchange resin AB-17 (OH− form)
was added until pH ∼ 7, then was filtered off, and the mixture was
thoroughly washed with EtOH (80 mL). The solvents were combined
and evaporated under reduced pressure. The residue was purified on
silica gel column chromatography CHCl3−EtOH 13% and recrystal-
lized from EtOH (4 mL) to give 0.155 g (68%) of the title compound
as a white solid, Rf 0.66 (CHCl3−EtOH 8:1). Mp: 141−143 °C.
2-(Hydroxymethyl)phenyl-6-O-acetyl-β-D-glucopyranoside (Fra-
gilin) (9). The title compound wasobtained from compound 5 as
colorless crystals. Yield: 79%; Rf 0.47 (CHCl3−EtOH 4:1). Mp: 179−
180 °C (lit. 177−179 °C,14 178−180 °C).29 [α]20 −57 (c 0.6,
D
MeOH). UV (EtOH): λmax 212, 268 nm. FTIR (ATR): νmax 3429
(br), 3099, 3074, 2970, 1701, 1654, 1161, 1358, 1182, 1000, 763
cm−1. 1H and 13C NMR data are given in Tables 1 and 2, respectively.
HRESIMS: m/z 351.1044 [M + Na]+ (calcd for C15H20O8Na,
351.1050). The spectroscopic data are in agreement with the
literature.29
[α]28 −40 (c 2, MeOH). UV (EtOH): λmax 218, 269 nm. FTIR
D
(ATR): νmax 3405 (br), 2970, 2923, 2875, 1743, 1492, 1228, 1075,
1
1031, 756 cm−1. H and 13C NMR data are given in Tables 1 and 2,
respectively. HRESIMS: m/z 379.1361 [M + Na]+ (calcd for
C17H24O8Na, 379.1369).
General Procedure For Nonselective Deacetylation. Acety-
lated glucosides 3, 4, 5, 6, 7, 8, or 9 (0.120 mmol) were separately
dissolved or suspended in MeOH (6 mL), and solid NaOMe (5 mg)
was added. The reaction mixture was stirred at RT (∼20 °C) for 2 h,
neutralized by adding cation-exchange resin KU-2-8, which was
filtered off, and washed with MeOH (30 mL). The methanolic
solution was concentrated under reduced pressure and dried in vacuo
to produce deacetylated glucosides.
2-(Chloromethyl)phenyl-2-O-acetyl-β-D-glucopyranoside (5).
Peracetylated bromide 2 (2 g, 3.80 mmol) or chloride 3 (1.83 g,
3.80 mmol) was dissolved in a mixture of CHCl3 (4 mL) and EtOH
(6 mL), and 36% aqueous HCl (1.5 mL) was added. The reaction
mixture was kept at 30 °C for 8 h (TLC showed the formation of
major component and one lower-running spot), and anion-exchange
resin AB-17 (OH− form) was added until pH ∼ 7, then was filtered
off, and the mixture was thoroughly washed with EtOH (130 mL).
The solvents were combined and evaporated under reduced pressure.
The residue was purified on silica gel column chromatography
CHCl3−EtOH 20:1 → 4:1 and recrystallized from EtOH (7 mL) to
give the title compound as a white solid. The yield was 0.640 g (48%)
from 2 and 0.898 g (67%) from 3, Rf 0.67 (CHCl3−EtOH 4:1). Mp:
187−188 °C. [α]20D −12 (c 0.6, Me2CO). UV (EtOH): λmax 212, 275
nm. FTIR (ATR): νmax 3515, 3240 (br), 2972, 2902, 1726, 1605,
2-(Ethoxymethyl)phenyl-β-D-glucopyranoside (Ethylsalicin) (10).
The title compound was obtained from compounds 4 or 7 as an
amorphous powder. Yield: 99% in both cases. Rf 0.70 (CHCl3−EtOH
4:1). [α]20 −35 (c 0.8, MeOH). UV (EtOH): λmax 211, 269 nm.
D
FTIR (ATR): νmax 3449 (br), 2974, 2872, 1603, 1491, 1389, 1232,
1
1020, 751 cm−1. H and 13C NMR data are given in Tables 1 and 2,
respectively. HRESIMS: m/z 337.1255 [M + Na]+ (calcd for
C15H22O7Na,337.1263). The spectroscopic data are in agreement
with the published data.41
1
1497, 1259, 1236, 1077, 1035, 748 cm−1. H and 13C NMR data are
given in Tables 1 and 2, respectively. HRESIMS: m/z 369.0726 [M +
Na]+ (calcd for C15H19ClO7Na, 369.0712).
2-(Chloromethyl)phenyl-β-D-glucopyranoside (Chlorosalicin)
(11). The title compound was obtained from compounds 5, 8, or 3
as colorless crystals. Yield: 99% in both cases. Rf 0.34 (CHCl3−EtOH
2-(Hydroxymethyl)phenyl-2-O-acetyl-β-D-glucopyranoside (2-O-
acetylsalicin) (6). Chloride 5 (20 mg, 57.80 μmol) was dissolved in a
mixture of acetone (2 mL) and water (2 mL), and grounded Ag2O
(20 mg, 86.60 μmol) was added followed by HOAc (0.5 mL).
Whereupon the black Ag2O suspension changed color to gray. The
4:1). Mp: 120 °C (decomp). [α]20 −82 (c 0.3, MeOH). UV
D
(EtOH): λmax 221, 275 nm. FTIR (ATR): νmax 3380 (br), 2921, 2877,
1
1604, 1492, 1241, 1072, 1043, 751 cm−1. H and 13C NMR data are
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given in Tables 1 and 2, respectively. HRESIMS: m/z 327.0609 [M +
Na]+ (calcd for C13H17ClO6Na, 327.0611).
(12) Keefover-Ring, K.; Ahnlund, M.; Abreu, I. N.; Jansson, S.;
Moritz, T.; Albrectsen, B. R. PLoS One 2014, 9, No. e107189.
(13) Thieme, H. Naturwissenschaften 1964, 51, 310−310.
(14) Thieme, H. Naturwissenschaften 1963, 50, 477−477.
(15) Julkunen-Tiitto, R.; Tahvanainen, J. Planta Med. 1989, 55, 55−
58.
2-(Hydroxymethyl)phenyl-β-D-glucopyranoside (Salicin) (12).
The title compound was obtained from compounds 6 and 9 as
colorless crystals. Yield: 99% in both cases. Rf 0.25 (CHCl3−EtOH
4:1). Mp: 201−202 °C (lit. 198−200 °C).42,43 [α]20 −58 (c 1,
D
MeOH). UV (EtOH): λmax 213, 268 nm. FTIR (ATR): νmax 3345
(br), 3077, 2972, 2932, 1603, 1494, 1238, 1079, 1038, 1012, 755
cm−1. 1H and 13C NMR data are given in Tables 1 and 2, respectively.
The spectroscopic data are in agreement with the published data.42,44
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
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AUTHOR INFORMATION
Corresponding Author
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(23) Foerster, N.; Ulrichs, C.; Zander, M.; Katzel, R.; Mewis, I.
Gesunde Pflanz. 2009, 61, 129−134.
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(25) Abreu, I. N.; Ahnlund, M.; Moritz, T.; Albrectsen, B. R. J.
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Elena V. Stepanova − Tomsk Polytechnic University, Tomsk
634050, Russian Federation; N. D. Zelinsky Institute of Organic
Chemistry of the Russian Academy of Sciences, Moscow 119991,
Russian Federation; orcid.org/0000-0001-9617-9110;
Phone: +7 (3822) 563861; Email: eline_m@mail.ru,
glycoside.m@gmail.com
(26) Nybakken, L.; Julkunen-Tiitto, R. Physiol. Plant. 2013, 147,
465−476.
(27) Lassfolk, R.; Rahkila, J.; Johansson, M. P.; Ekholm, F. S.;
Warna, J.; Leino, R. J. Am. Chem. Soc. 2019, 141, 1646−1654.
(28) Terreni, M.; Salvetti, R.; Linati, L.; Fernandez-Lafuente, R.;
Authors
Dariya A. Romanova − Tomsk Polytechnic University, Tomsk
634050, Russian Federation
David L. Avetyan − Tomsk Polytechnic University, Tomsk
634050, Russian Federation; Siberian State Medical University,
Tomsk 634050, Russian Federation
Maxim L. Belyanin − Tomsk Polytechnic University, Tomsk
634050, Russian Federation
́
Fernandez-Lorente, G.; Bastida, A.; Guisan, J. M. Carbohydr. Res.
2002, 337, 1615−1621.
(29) Kim, C. S.; Subedi, L.; Park, K. J.; Kim, S. Y.; Choi, S. U.; Kim,
K. H.; Lee, K. R. Fitoterapia 2015, 106, 147−152.
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Matsumoto, M.; Yamakita, H.; Tsujihara, K. Chem. Pharm. Bull. 1998,
46, 1545−1555.
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Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.jnatprod.9b00570
(32) Shao, C.; Pei, Y.; Borg-Karlson, A.-K.; Pei, Z. Chem. Res. Chin.
Univ. 2014, 30, 774−777.
(33) Stepanova, E.; Nagornaya, M.; Belyanin, M.; Filimonov, V.
Curr. Org. Synth. 2017, 14, 394−397.
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
(35) Stepanova, E. V.; Belyanin, M. L.; Filimonov, V. D. Carbohydr.
Res. 2014, 388, 105−111.
This work was financially supported by the Tomsk Polytechnic
University Competitiveness Enhancement Program grant. The
authors would like to thank TPU Shared Knowledge Center −
Physical and Chemical Methods and Aleksey Ivanov for the
help with UV experiments.
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(37) Stepanova, E. V.; Nagornaya, M. O.; Filimonov, V. D.; Valiev,
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