Knoevenagel condensation between C-glycoside and active methylene compounds without catalysts

Article abstract of DOI:10.3184/174751916X14762012580355

A Knoevenagel condensation reaction between a C-glycoside based aromatic aldehyde and cyclic active methylene compounds such as barbituric acid, thiobarbituric acid, 1,3-dimethylbarbituric acid, 5,5-dimethyl-1,3-cyclohexanedione, 2,2-dimethyl-1,3-dioxane-

Full text of DOI:10.3184/174751916X14762012580355

JOURNAL OF CHEMICAL RESEARCH 2016
VOL. 40 NOVEMBER, 683–686
RESEARCH PAPER 683
Knoevenagel condensation between C-glycoside and active methylene
compounds without catalysts
Xiaomin Gu and Zhijie Fang*
School of Chemical Engineering, Nanjing University of Science and Technology, 200 Xiaolingwei St, Nanjing, JiangSu 210 094, P.R. China
A Knoevenagel condensation reaction between a C-glycoside based aromatic aldehyde and cyclic active methylene compounds such as
barbituric acid, thiobarbituric acid, 1,3-dimethylbarbituric acid, 5,5-dimethyl-1,3-cyclohexanedione, 2,2-dimethyl-1,3-dioxane-4,6-dione
and 3-methyl-1-phenyl-2-pyrazolin-5-one has been developed, to give a series of unusual fused heterocyclic compounds. The structures
of all the new compounds were established by the spectral data. This method which did not use any catalysts, has the advantages of
operational simplicity and minimal environmental impact.
Keywords: Knoevenagel condensation, C-glycoside, active methylene compounds
The Knoevenagel condensation reaction between carbonyl
compounds and active methylene compounds has largely been
studied in heterogeneous media. It is a simple and effective
method for forming carbon–carbon bonds.1,2 Heterocyclic ring
systems remain part of many powerful scaffolds holding several
pharmacophores, which can act as potent and selective drugs
for many diseases.3,4 Furthermore, Knoevenagel adducts, are
also useful intermediates for further transformations, such as
Diels–Alder and Michael additions.5
the reaction proceeded under reflux in ethanol without a catalyst
to give the desired product 5a in 85% yield. Next, different
catalysts including PTSA, CH3COOH, NEt3, and piperidine were
examined in the reaction. However, to our surprise, they did not
improve the yield. In addition, other solvents, such as dioxane,
CH3OH, CH3CN, and THF (Table 1, entries 3, 8–11), were also
tested but EtOH proved to be superior. Furthermore, the product
was collected by filtration when the EtOH solution was cooled to
room temperature after completion of the reaction.
C-glycosylation is a rare structural modification of natural
With optimised conditions established, we next extended
the process to four different cyclic 1,3-dicarbonyl compounds
including thiobarbituric acid, 1,3-dimethylbarbituric acid,
5,5-dimethyl-1,3-cyclohexanedione and 2,2-dimethyl-1,3-
dioxane-4,6-dione. By selecting the different materials, a new
class of compounds was synthesised which may show interesting
properties. The results in Table 2 showed that all the reactions
proceeded smoothly to afford the derivatives in moderate to
excellent yields. The structures of the products were deduced
from their 1H NMR, and 13C NMR and elemental analysis.
Next, we planned to utilise 3-methyl-1-phenyl-2-pyrazolin-
5-one as the active methylene compound in the above
reaction. In this case, an unexpected product namely the
4,4’-(arylmethylene)bis(1H-pyrazol-5-ol) derivative 5f was
obtained as a Knoevenagel–Michael adduct in 73% yield instead
of a benzylidene–pyrazolinone derivative (Scheme 2). In the 1H
NMR spectrum, one singlet appeared at δ 4.72 ppm for methine
proton (–CH) and another singlet at δ 1.97 ppm for two methyl
protons (–CH3), supporting the formation of compound 5f.
The literature survey showed that the synthesis of
4,4’-(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ols) can
be achieved by two methods: (i) successive Knoevenagel synthesis
of the corresponding arylidenepyrazolones and its base-promoted
Michael reaction;18,19 and (ii) one-pot tandem Knoevenagel–
Michael reaction of aldehydes with two equivalents of 3-methyl-
1-phenyl-1H-pyrazol-5(4H)-one performed under various reaction
conditions.20 This is an example of the second case.
products found in microorganisms and higher plants.6
A
major modification of natural products has been focused
on glycosylation methods to diversify the functionality of
natural products.7 C-glycosides as subunits occur in a variety
of biologically important natural products and synthetic
compounds.8–10 Consequently the development of new routes for
the synthesis of C-glycosides has attracted attention.
In continuation of our research on C-glycosides,11–14 in this
paper, we describe the synthesis of novel C-glycoside derivatives
by a Knoevenagel condensation. The target C-glycoside-derived
heterocyclic compounds were composed of a sugar ring and a
rigid ring-framework.
Results and discussion
Firstly, we needed to synthesise the novel key intermediate of
C-glycoside 4. The route is shown in Scheme 1. Starting from
D-glucose the β-C-glycosidic aryl ketone was synthesised in
a one step process.11 In the next steps, the hydroxyl groups of
the sugar were protected as their acetate esters,15 the carbonyl
group was reduced to a methylene16 and a formyl group was
then introduced onto the aromatic ring17 to give 1-(2,3,4,6-tetra-
O-acetyl-1-β-D-glucopyranose)-2-(4-formylphenyl)-ethane
in an overall yield of 60%.
4
Initially, we chose the reaction of pyrimidine-
2,4,6(1H,3H,5H)-trione(barbituric acid) with 1-(2,3,4,6-tetra-
O-acetyl-1-β-D-glucopyranose)-2-(4-formylphenyl)-ethane
(4) as a model system for an optimisation study. The reaction
rate was investigated by measuring the isolated yield of the
product, using identical amounts of reactants. It was found that
Several solvents (MeOH, CH3CN, acetone, THF, DCM) were
also examined with two equivalents of 3-methyl-1-phenyl-2-
pyrazolin-5-one. This revealed that DCM was the solvent of
OAc
O
OAc
O
OAc
O
a
OH
O
c
CHO
b
AcO
AcO
AcO
AcO
AcO
AcO
HO
HO
Ph
OH
OH
OAc
OAc
OAc
O
1
2
3
4
Scheme 1 Synthetic route to the key intermediate 4.
* Correspondent. E-mail: zjfang@njust.edu.cn

684 JOURNAL OF CHEMICAL RESEARCH 2016
Table 1 Synthetic results of 5a under different reaction conditionsa
O
O
OAc
O
OAc
O
NH
NH
AcO
AcO
CHO
AcO
AcO
O
O
OAc
NH
N
OAc
O
H
O
4
5a
Entry
1
2
3
4
5
6
7
8
Temperature/°C
r.t.
50 °C
Catalyst
–
–
–
PTSA
CH3COOH
NEt3
Piperidine
–
–
–
–
Time/h
10
10
10
10
8
10
10
8
Solvent
Yield/%b
Trace
53
85
71
57
80
75
80
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
Dioxane
CH3OH
CH3CN
THF
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
9
10
11
16
12
14
82
84
82
aReagents and conditions: (0.046 g, 0.1 mmol); barbituric acid (0.026 g, 0.2 mmol); and solvent (5 mL).
bIsolated yield.
N
N
OH
OAc
O
OAc
O
EtOH
73%
N
N
OH
N
AcO
AcO
CHO
AcO
AcO
OAc
OAc
O
N
4
5f
Scheme 2 Knoevenagel–Michael condensation of 1-(2,3,4,6-tetra-O-acetyl-1-β-D-glucopyranose)-2-(4-formylphenyl)-ethane and
3-methyl-1-phenyl-1H-pyrazol-5(4H)-one.
Table 2 The reaction time and yields of the products
Table 3 Condensation of 4 and 3-methyl-1-phenyl-2-pyrazolin-5-one
under different solvents
Entry 1,3-Dicarbohyla
Time/h
Products
Yield/%
87
Entry
Solvents
MeOH
CH3CN
Acetone
THF
Time/h
Yield/%
72
66
60
65
O
1
2
3
4
5
6
7
8
8
8
8
NH
1
10
5b
O
N
H
S
O
8
DCM
8
85
N
2
12
5c
92
DCM
6
90
O
N
O
DCM
4
77
O
DCM
10
78
3
4
14
13
5d
5e
76
80
O
and several methylene active compounds. The easy availability of
the starting materials and the simplicity of the procedure make it
a promising approach for the synthesis of heterocyclic compounds
containing sugar rings. The synthetic benzylidene derivatives are
promising building blocks for drug design, advanced materials,
and agricultural chemistry. Further investigations into the scope
and synthetic applications of this new approach to complex
molecules are now in progress in our laboratory.
O
O
O
O
aReagents and conditions: (0.046 g, 0.1 mmol); 1,3-dicarbohyl (0.2 mmol); EtOH(5 mL);
and reflux.
choice. Incomplete conversion was observed in the other solvents.
Decreasing the reaction time to 6 h led to complete conversion in
dichloromethane (yield 90%). Good solubility in dichloromethane
may be responsible for the higher yields.
Experimental
Melting points were determined in open glass capillaries using a
Griffin melting point apparatus. Solvents were distilled and dried by
standard methods. All the chemicals used were of analytical grade and
used without further purification. The progress of the reactions was
monitored by thin-layer chromatography (TLC) on silica gel, and spots
Conclusion
In this paper, we have described a strategy for the synthesis of a rigid
ring-framework from an aromatic aldehyde containing a sugar unit

JOURNAL OF CHEMICAL RESEARCH 2016 685
1
were visualised with UV light or iodine. H, 13C NMR and NOESY
ether (2 mL, 2.1 mmol) was dissolved in dry dichloromethane (10 mL),
and the solution was cooled to 0 °C under a nitrogen atmosphere. The
solution was stirred vigorously as a solution of titanium tetrachloride
(2.3 mL, 2.1 mmol) in dry dichloromethane (10 mL) was added via
syringe pump over a period of 45 min. The dark green mixture was
warmed to room temperature and stirred for an additional 2 h. The
reaction mixture was poured into ice water (50 mL) and the aqueous
layer thoroughly extracted with ether (3 × 15 mL). The combined
ether layers were washed with saturated sodium bicarbonate (50 mL),
water (60 mL), and saturated sodium chloride (50 mL) and dried
over anhydrous magnesium sulfate and the volatile material was
evaporated in vacuo. The residual blue–green solid was purified by
flash chromatography to give the aldehyde 4 (5.56 g, 80%) as white
powder, m.p.: 126–128 ºC. 1H NMR (500 MHz, CDCl3) δ 9.98 (s, 1H,
CHO), 7.80 (d, J = 8.0 Hz, 2H, Ph), 7.33 (d, J = 8.0 Hz, 2H, Ph), 5.13 (t,
J = 9.3 Hz, 1H, H3’), 5.05 (t, J = 9.3 Hz, 1H, H4’), 4.92 (t, J = 9.3 Hz,
1H, H2’), 4.25 (dd, J = 12.3, 5.2 Hz, 1H, H6’b), 4.14 (dd, J = 12.3, 2.0
Hz, 1H, H6’a), 3.60 (ddd, J = 9.3, 8.4, 7.0 Hz, 1H, H1’), 3.42–3.28 (m,
1H, H5’), 2.93 (dt, J = 13.8, 7.0 Hz, 1H, H1’a), 2.75 (dt, J = 13.8, 8.4 Hz,
1H, H1’b), 2.11 (s, 3H, CH3), 2.07–1.94 (m, 9H, CH3), 1.86–1.76 (m,
2H, CH2) ppm. 13C NMR (125 MHz, CDCl3), δ 20.6, 20.7, 30.1, 31.1,
32.4, 62.4, 68.7, 71.7, 74.2, 75.7, 76.3, 129.1, 130.0, 134.7, 148.6, 169.5,
169.6, 170.3, 170.6, 191.8 ppm. Anal. calcd for C23H28O10: C, 59.48; H,
6.08; found: C, 59.45; H, 6.04%.
spectra were recorded in CDCl3 or DMSO-d6 on a Bruker Avance III
500 MHz spectrometer. Proton chemical shifts are reported in ppm
relative to the internal standard tetramethylsilane (δTMS = 0 ppm) and
carbon chemical shifts are reported in ppm relative to the solvents
(δCDCl3 = 77.00 ppm). Data were recorded and evaluated using
TOPSPIN 3.1 (Bruker Biospin). All chemical shifts are given in ppm
relative to tetramethylsilane. The resonance multiplicity is indicated
as s (singlet), d (doublet), t (triplet), q (quartet), quin (quintet), m
(multiplet), or a combination of these. Elemental analyses were
performed on a Vario EL III elemental analyser.
2,3,4,6-O-tetra-acety-1-deoxy-1-(2-oxo-2-phenylethyl)-β-D-
glucopyranose (2)
D-Glucose (50 mmol), dibenzoylmethane (16.8 g, 75 mmol), sodium
bicarbonate (6.3 g, 75 mmol), and EtOH–H2O (4:1, v/v) 100 mL were
introduced and microwave irradiation started, the EtOH–H2O (4:1)
began to reflux within 1 h. After the microwave reactor was turned off,
the solutions were allowed to cool to room temperature and treated with
cation exchange resin (sodium form) to reach pH = 5. The resin was
filtered and EtOH was evaporated. The aqueous solution was washed
with CH2Cl2 and concentrated. The product was used directly without
further purification. Sodium acetate (2.46 g, 30 mmol) was added to a
solution of 1-phenyl-2-C-(β-D-glucopyranosyl) ethanone in acetic
anhydride (20 mL, 200 mmol) and the reaction was heated to 135 °C for
4 h. After completion of the reaction (TLC (AcOEt/PE) monitoring),
the mixture was cooled to room temperature and ethyl acetate (100 mL)
and water (80 mL) were added to the reaction, which was neutralised
to pH = 7 by adding sodium carbonate. The extract was then washed
with saturated sodium chloride solution three times. Evaporation of the
solvent followed by recrystallisation from EtOH gave the crystalline
product 2 (8.1 g, 90%), m.p.: 105.5–107 ºC (lit.21 104–106 ºC), 1H NMR
(500 MHz, CDCl3) δ 7.91 (d, J = 8.0 Hz, 2H, Ph), 7.56 (t, J = 7.3 Hz, 1H,
Ph), 7.45 (t, J = 7.6 Hz, 2H, Ph), 5.23 (t, J = 9.5 Hz, 1H, H3’), 5.07 (t,
J = 9.5 Hz, 1H, H4’), 5.01 (t, J = 9.6 Hz, 1H, H2’), 4.22 (dt, J = 10.4, 5.1
Hz, 2H, H1’, H6’a), 3.98 (d, J = 12.2 Hz, 1H, H6’b), 3.72 (dd, J = 9.8, 2.9
Hz, 1H, H5’), 3.33 (dd, J = 16.7, 8.3 Hz, 1H, H1’a), 2.93 (dd, J = 16.7, 2.7
Hz, 1H, H1’b), 1.98 (dd, J = 14.1, 10.0 Hz, 12H, CH3CO) ppm. 13C NMR
(125 MHz, CDCl3), δ 196.1, 170.8, 170.6, 170.1, 169.9, 136.7, 133.6,
128.8, 128.3, 76.4, 73.3, 72.4, 70.3, 66.3, 62.8, 39.5, 20.9 ppm. Anal.
calcd for C22H26O10: C, 58.66; H, 5.82; found: C, 58.62; H, 6.85%.
Synthesis of compounds 5a–f; general procedure
A
mixture of 1-(2,3,4,6-tetra-O-acetyl-1-β-D-glucopyranose)-2-
(4-formylphenyl)-ethane (0.046 g, 0.1 mmol), active methylene
compounds (0.026 g, 0.2 mmol), in EtOH (5 mL) was stirred
under reflux for 10 h. After cooling the reaction mixture to room
temperature, the precipitated product was filtered and washed with
ethanol (15 mL). The crude product was recrystallised from EtOH to
afford the pure product or purified by flash chromatography.
1
Compound 5a: Yield 85%, m.p.: 113–115 ºC. H NMR (500 MHz,
DMSO-d6) δ 11.36 (s, 1H, NH), 11.22 (s, 1H, NH), 8.26 (s, 1H, CH=), 8.11
(d, J = 8.0 Hz, 2H, ArH), 7.32 (d, J = 8.0 Hz, 2H, ArH), 5.22 (t, J = 9.6 Hz,
1H, H3’), 4.89 (t, J = 9.6 Hz, 1H, H2’), 4.76 (t, J = 9.6 Hz, 1H, H4’), 4.18
(dd, J = 12.2, 5.4 Hz, 1H, H6’a), 4.04 (d, J = 12.2 Hz, 1H, H6’b), 3.97–3.82
(m, 1H, H1’), 3.63–3.60 (m, 1H, H5’), 2.93–2.75 (m, 1H, H1’a), 2.75–2.59
(m, 1H, H1’b), 2.14–1.88 (m, 12H, CH3), 1.81 (dd, J = 19.0, 9.6 Hz,
1H, CH), 1.64 (dd, J = 9.2, 4.6 Hz, 1H, CH) ppm. 13C NMR (125 MHz,
DMSO-d6) δ 169.5, 19.1, 169.0, 168.8, 163.0, 161.2, 154.3, 149.6, 146.4,
133.5, 129.8, 129.2, 128.7, 127.7, 74.8, 73.9, 72.9, 71.0, 68.1, 61.7, 31.4, 30.0,
20.0, 19.9, 19.9, 19.8 ppm. Anal. calcd for C27H30N2O12: C, 56.44; H, 5.26;
N, 4.88; found: C, 56.40; H, 5.28, N, 4.87%.
2, 3,4,6 - O-Tetra- acet y-1- deox y-1- (2-phenylethyl) - β -D -
glucopyranose (3)15
2,3,4,6-O-Tetra-acety-1-deoxy-1-(2-oxo-2-phenylethyl)-β-D-
glucopyranose (2) (4.5 g, 10 mmol) was dissolved in methanol
(25 mL), trifluoroacetic acid (3 mL) and then Pd/C (0.6 g, 10%) were
added. The reaction vessel was purged three times with hydrogen. The
reaction was stirred at room temperature for 18 h. After completion of
the reaction, it was filtered to recycle the Pd/C, and neutralised with
saturated sodium bicarbonate. Evaporation of the solvent followed
by column chromatography gave the products as white crystals in
92% yield, m.p.: 142–144 ºC. 1H NMR (500 MHz, CDCl3) δ 7.27 (t,
J = 7.5 Hz, 2H, Ph), 7.19 (d, J = 7.2 Hz, 1H, Ph), 7.15 (d, J = 7.5 Hz, 2H,
Ph), 5.11 (t, J = 9.5 Hz, 1H, H3’), 5.04 (t, J = 9.5 Hz, 1H, H4’), 4.90 (t,
J = 9.5 Hz, 1H, H2’), 4.25 (dd, J = 12.2, 5.3 Hz, 1H, H6’b), 4.13 (dd,
J = 12.2, 1.7 Hz, 1H, H6’a), 3.59 (ddd, J = 9.5, 8.4, 6.8 Hz, 1H, H1’),
3.35–3.30 (m, 1H, H5’), 2.83 (dt, J = 13.7, 6.8 Hz, 1H, CH2CH2Ph),
2.66 (dt, J = 13.7, 8.4 Hz, 1H, CH2CH2Ph), 2.10 (s, 3H, CH3CO), 2.01
(s, 3H, CH3CO), 2.00 (s, 3H, CH3CO), 1.97 (s, 3H, CH3CO), 1.77 (dd,
J = 13.9, 7.4 Hz, 2H, CH2CH2Ph) ppm. 13C NMR (125 MHz, CDCl3),
δ 20.5, 30.8, 30.7, 62.4, 68.8, 71.8, 74.3, 75.6, 76.4, 126.0, 128.4, 141.1,
169.4, 169.6, 170.3, 170.6 ppm. Anal. calcd for C22H28O9: C, 60.54; H,
6.47; found: C, 60.58; H, 6.50%.
1
Compound 5b: Yield 87%, m.p.: 117–119 ºC. H NMR (500 MHz,
DMSO-d6) δ 12.46 (s, 1H, NH), 12.35 (s, 1H, NH), 8.29 (s, 1H, CH=),
8.18 (d, J = 8.2 Hz, 2H, ArH), 7.34 (d, J = 8.2 Hz, 2H, ArH), 5.23
(t, J = 9.5 Hz, 1H, H3’), 4.91 (t, J = 9.5 Hz, 1H, H2’), 4.78 (t, J = 9.5 Hz,
1H, H4’), 4.19 (dd, J = 12.2, 5.5 Hz, 1H, H6’a), 4.05 (d, J = 12.2 Hz, 1H,
H6’b), 3.96–3.78 (m, 1H, H1’), 3.71–3.55 (m, 1H, H5’), 2.91–2.76 (m,
1H, H1’a), 2.76–2.63 (m, 1H, H1’b), 2.05 (d, J = 10.7 Hz, 3H, CH3), 2.01
(d, J = 9.1 Hz, 6H, CH3), 1.95 (s, 3H, CH3), 1.83 (dt, J = 16.9, 7.3 Hz,
1H, CH), 1.66 (dt, J = 9.2, 6.9 Hz, 1H, CH) ppm. 13C NMR (125 MHz,
DMSO-d6) δ 178.0, 169.6, 169.1, 168.8, 161.4, 159.1, 155.2, 147.1, 133.9,
129.9, 127.8, 117.6, 74.7, 73.9, 72.9, 71.0, 68.0, 61.7, 31.4, 30.1, 20.0, 19.9,
19.9, 19.8 ppm. Anal. calcd for C27H30N2O11S: C, 54.91; H, 5.12; N, 4.74;
S, 5.43; found: C, 54.88; H, 5.10; N, 4.76; S, 5.42%.
1
Compound 5c: Yield 92%, m.p.: 128–130 ºC. H NMR (500 MHz,
CDCl3) δ 8.55 (s, 1H, CH=), 8.07 (d, J = 8.2 Hz, 2H, ArH), 7.28 (d,
J = 8.2 Hz, 2H, ArH), 5.15 (t, J = 9.5 Hz, 1H, H3’), 5.06 (t, J = 9.5 Hz,
1H, H2’), 4.93 (t, J = 9.5 Hz, 1H, H4’), 4.26 (dd, J = 12.3, 5.2 Hz, 1H,
H6’a), 4.14 (dd, J = 12.3, 1.9 Hz, 1H, H6’b), 3.68–3.55 (m, 1H, H1’),
3.42 (d, J = 12.5 Hz, 3H, N–CH3), 3.40–3.36 (m, 1H, H5’), 3.40–3.36
(m, 3H, N–CH3), 3.01–2.82 (m, 1H, H1’a), 2.82–2.68 (m, 1H, H1’b),
2.12 (s, 3H, CH3CO), 2.03 (s, 6H, CH3CO), 2.00 (s, 3H, CH3CO), 1.83
(s, 2H, CH2) ppm.13C NMR (125 MHz, CDCl3) δ 168.7, 169.4, 168.7,
168.6, 161.7, 159.6, 158.2, 150.3, 146.7, 133.4, 129.7, 127.5, 115.8, 75.5,
1- (2 , 3,4,6 -tetra- O- acet yl-1- β -D -glucopyranose) -2- (4-
formylphenyl)-ethane (4)
A solution of 2,3,4,6-O-tetra-acety-1-deoxy-1-(2-phenylethyl)-β-D-
glucopyranose 3 (300 mg, 0.69 mmol) and α,α-dichloromethyl methyl

686 JOURNAL OF CHEMICAL RESEARCH 2016
74.8, 73.3, 70.8, 67.8, 61.5, 31.4, 30.2, 28.1, 27.5, 19.8, 19.8, 19.7, 19.7
ppm. Anal. calcd for C29H34N2O12: C, 57.80; H, 5.69; N, 4.65; found: C,
57.85; H, 5.68; N, 4.67%.
Acknowledgement
This work was supported by the Prospective Joint Project of
Production, Education and Research in Jiangsu Province, P.R.
China (grant no. BY2013004-02).
1
Compound 5d: Yield 76%, m.p.: 145–147 ºC. H NMR (500 MHz,
CDCl3) δ 7.38 (d, J = 8.0 Hz, 2H, ArH), 7.16 (d, J = 8.0 Hz, 2H, ArH),
5.48 (s, 1H, CH=), 5.12 (t, J = 9.6 Hz, 1H, H3’), 5.05 (t, J = 9.6 Hz, 1H,
H2’), 4.91 (t, J = 9.6 Hz, 1H, H4’), 4.26 (dd, J = 12.2, 5.3 Hz, 1H, H6’a),
4.14 (dd, J = 12.2, 2.2 Hz, 1H, H6’b), 3.66–3.57 (m, 3H, H5’, CH2),
3.57–3.49 (m, 2H, CH2), 3.39–3.25 (m, 1H, H1’), 2.87–2.81(m, 1H,
H1’a), 2.70–2.64 (m, 1H, H1’b), 2.12 (s, 3H, CH3), 2.04–1.98 (m, 9H,
CH3), 1.90 (s, 6H, CH3), 1.79–1.75 (m, 2H, CH2) ppm.13C NMR (125
MHz, CDCl3) δ 198.6, 190.9, 175.2, 169.7, 169.4, 168.7, 168.5, 147.7,
133.8, 129.1, 128.2, 127.3, 125.8, 100.5, 74.8, 73.3, 70.8, 67.9, 63.3, 61.5,
49.8, 42.0, 31.5, 30.1, 28.7, 28.3, 27.3, 26.2, 19.8, 19.6, 14.2, 13.1 ppm.
Anal. calcd for C31H38O11: C, 63.47; H, 6.53; found: C, 63.44; H, 6.55%.
Electronic Supplementary Information
The ESI are available through:
stl.publisher.ingentaconnect.com/content/stl/jcr/supp-data
Received 18 July 2016; accepted 16 September 2016
Paper 1604197 doi: 10.3184/174751916X14762012580355
Published online: 26 October 2016
References
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Compound 5e: Yield 80%, m.p.: 133–135 ºC. H NMR (500 MHz,
CDCl3) δ 8.47 (s, 1H, CH=), 8.10 (d, J = 8.2 Hz, 2H, ArH), 7.35 (d,
J = 8.2 Hz, 2H, ArH), 5.20 (t, J = 9.5 Hz, 1H, H3’), 5.12 (t, J = 9.5 Hz,
1H, H2’), 4.99 (t, J = 9.5 Hz, 1H, H4’), 4.32 (dd, J = 12.2, 5.2 Hz, 1H,
H6’a), 4.20 (dd, J = 12.2, 2.0 Hz, 1H, H6’b), 3.68–3.66 (m, 1H, H1’),
3.47–3.38 (m, 1H, H5’), 2.98 (dt, J = 13.9, 7.1 Hz, 1H, H1’a), 2.88–2.76
(m, 1H, H1’b), 2.18 (s, 3H, CH3), 2.08 (d, J = 8.0 Hz, 6H, CH3), 2.06 (s,
3H, CH3), 1.88 (d, J = 6.9 Hz, 6H, CH3), 1.31 (d, J = 7.2 Hz, 2H, CH2)
ppm.13C NMR (125 MHz, CDCl3) δ 169.7, 169.4, 168.7, 168.5, 162.5,
159.0, 157.0, 147.5, 133.4, 129.1, 128.8, 128.2, 128.0, 112,9, 103.5, 75.4,
74.8, 73.3, 70.8, 67.8, 61.5, 31.3, 30.1, 26.6, 19.8, 19.7, 19.6, 19.6 ppm.
Anal. calcd for C29H34O13: C, 58.98; H, 5.80; found: C, 58.89; H, 5.78%.
3
G. Eren, G. Unlu, M.T. Nunez, L. Labeaga, F. Ledo, A. Entrena, E.B. Lu, G.
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T. Furuta, T. Kimura, S. Kondo, H. Mihara, T. Wakimoto, H. Nukaya, K.
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1
Compound 5f: Yield 90%, m.p.: 118–120 ºC. H NMR (500 MHz,
10 G.L. Yang, J. Schmieg, M. Tsuji and R.W. Franck, Angew. Chem. Int. Ed.,
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CDCl3) δ 7.71 (dd, J = 5.7, 3.3 Hz, 1H, ArH), 7.59 (d, J = 8.0 Hz, 4H,
ArH), 7.52 (dd, J = 5.7, 3.3 Hz, 1H, ArH), 7.26 (dd, J = 8.6, 6.5 Hz, 3H,
ArH), 7.09 (t, J = 7.0 Hz, 3H, ArH), 7.01 (d, J = 8.2 Hz, 2H, ArH), 5.09 (t,
J = 9.6 Hz, 1H, H3’), 5.02 (t, J = 9.6 Hz, 1H, H2’), 4.87 (t, J = 9.6 Hz, 1H,
H4’), 4.72 (s, 1H, CH), 4.23 (dd, J = 12.2, 5.2 Hz, 1H, H6’a), 4.14–4.08
(m, 1H, H6’b), 4.07 (d, J = 6.7 Hz, 2H, OH), 3.57 (ddd, J = 9.6, 5.1, 2.2
Hz, 1H. H1’), 3.38–3.28 (m, 1H, H5’), 2.83–2.70 (m, 1H, H1’a), 2.56 (dt,
J = 13.5, 5.1 Hz, 1H, H1’b), 2.07 (d, J = 2.3 Hz, 6H, CH3), 2.00 (s, 3H,
CH3), 1.97 (s, 6H, CH3), 1.71 (dd, J = 14.8, 7.5 Hz, 2H, CH2), 0.98 (d, J =
6.7 Hz, 3H, CH3) ppm.13C NMR (125 MHz, CDCl3) δ 169.8, 169.4, 168.7,
168.6, 166.8, 157.0, 145.7, 138.2, 137.5, 136.2, 131.4, 130.0, 127.9, 127.5,
126.3, 125.2, 120.3, 105.2, 74.6, 73.4, 70.9, 67.9, 61.5, 32.5, 31.8, 29.4,
26.8, 19.8, 19.7, 18.2, 10.7 ppm. Anal. calcd for C43H46N4O11: C, 64.98; H,
5.83; N, 7.05; found: C, 65.03; H, 5.86; N, 7.02%.
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