A simple and efficient method for synthesis of fluorine-containing saccharide esters and antiviral activity

Article abstract of DOI:10.1016/j.jfluchem.2006.06.002

Sixteen new fluorine-containing saccharide esters from fluorine-containing benzoic acids and α-O-acetylglycosyl bromide were synthesized in the presence of 4-dimethylaminopyridine (DMAP) and triethylamine (Et₃N) under mild conditions in good yi

Full text of DOI:10.1016/j.jfluchem.2006.06.002

Journal of Fluorine Chemistry 127 (2006) 1130–1136
www.elsevier.com/locate/fluor
A simple and efficient method for synthesis of fluorine-containing
saccharide esters and antiviral activity
*
Hong Chen, Si-Qing Huang , Jian-Ying Xie
Department of Applied Chemistry, Guangdong Ocean University, Zhanjiang 524088, PR China
Received 19 April 2006; received in revised form 1 June 2006; accepted 2 June 2006
Available online 7 June 2006
Abstract
Sixteen new fluorine-containing saccharide esters from fluorine-containing benzoic acids and a-O-acetylglycosyl bromide were synthesized in
the presence of 4-dimethylaminopyridine (DMAP) and triethylamine (Et3N) under mild conditions in good yields and their structures were clearly
1
verified by IR, H NMR, MS and elemental analysis. This method has high stereospecificity, the configuration is unitary, the new synthesized
compounds are all of b-configuration. The results of bioassay showed that these title compounds possess potential antiviral activities against
tobacco mosaic virus (TMV).
# 2006 Elsevier B.V. All rights reserved.
Keywords: Fluorine-containing benzoic acid; O-Acetylglycosyl saccharide esters; TMV; DMAP/Et3N
1. Introduction
pesticides and effective medicine. In addition, saccharide ester
compounds possess broad biological activities [22]. Recently,
much attention has been focused on their antiviral and
antitumor agents after the discovery of the trifluoromethyl
substituted pyrazole C-glycoside pyrazofurin [23,24].
Recently, much interest has been focused on organofluorine
compounds as pharmaceutical and agrochemical agents
because the fluorine atom often alters the physiochemical
properties of organic compounds, thereby modifying biological
activities [1–3]. A variety of pharmacological agents bearing a
trifluoromethyl group are of special interest as they exhibit
broad biological properties [4,5]. The fluorine atom, trifluor-
omethyl substituted compounds have been reported to possess
biological activities as herbicides [6], fungicides [7], analgesic
agents [8], antipyretic agents [9] and inhibitors for platelet
aggregation [10]. Fluorinated pesticides received more and
more recognization as well, because of its high activity, low
toxicity and less residua [11]. Accordingly, the development of
novel and convenient methods for the synthesis of fluorine-
containing molecules has been becoming more and more
important in fluorine chemistry [12–18].
In order to find new plant virucides, we had designed and
synthesized a series of nitro-containing, trifluoromethyl benzi-
midazolyl phenoxyacetic acid O-acetylglycosyl saccharide
esters, some of which displayed improved anti-TMV activity
[25]. Tobacco mosaic virus is a kind of familiar phytovirus, the
virus can do a lot of harm to plants. Considering the wide
application of these fluorinated compounds and potential to serve
as antiviral agents, in view of the above, and in conjunction with
our recent work on search for new phytoantiviral agents [25–27],
we decided to reserve of bioactivity unit and replace of phenyl
group by 3-trifluoromethylphenyl or 2-fluorophenyl, 4-fluor-
ophenyl, 2,3,4,5-tetrafluorophenyl. Thus, we designed a series of
novel fluorine-containing benzoic acid saccharide esters.
DMAP (4-dimethylaminopyridine) has light straw coloured
or colourless crystals, which were discovered in the 1960’s as a
new type of nucleophilic reaction catalyst. They have been
applied widely in organic synthesis [28,29]. DMAP can
efficiently catalyse esterification reactions, but it has been rarely
reported as catalyst for the synthesis of fluorine-containing
saccharide esters by using a-O-acetylglycosyl bromide as the
active group and fluorine atom or trifluoromethyl substituted
benzoic acids as lead compounds.
In summary, many compounds are of biological activities
because of containing fluorine or trifluoromethyl [19–21].
Therefore, leading the fluorine or trifluoromethyl into the
molecules is a common way to design new agricultural
* Corresponding author. Tel.: +86 759 3865629; fax: +86 759 2383001.
E-mail addresses: chenh@gdou.edu.cn (H. Chen), huangsq2005@sina.com
(S.-Q. Huang).
0022-1139/$ – see front matter # 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2006.06.002

H. Chen et al. / Journal of Fluorine Chemistry 127 (2006) 1130–1136
1131
reach 89%, the biological test results indicate that the antiviral
activities of the synthesized compounds against tobacco mosaic
virus are up to 85.8%. The synthetic route is as follows (Scheme
1 and Table 1).
Scheme 1. The synthetic route of compounds 1–16.
2. Results and discussion
We selected DMAP as catalyst, Et3N (triethylamine) was
used as deacidification reagent, 16 new saccharide esters were
synthesized using the system of DMAP/Et3N. Experimental
results show that DMAP is an efficient catalyst, the yield can
2.1. Synthesis
The reactions are shown in Scheme 1 and Table 1, and results
are summarized in Tables 2 and 3. From the result of the
Table 1
Preparation and structure of the compounds 1–16
Compounds
Substituent
GL-Br
Product
R1
R2
R3
R4
1
2
3
4
F
H
H
F
H
H
H
F
H
H
F
H
CF3
F
H
F
5
6
7
8
F
H
H
F
H
H
H
F
H
H
F
H
CF3
F
H
F
9
10
11
12
H
F
H
F
H
H
H
F
H
H
H
F
H
F
CF3
F
13
14
15
16
H
F
H
F
H
H
H
F
H
H
H
F
H
F
CF3
F
Table 2
Characterization data for newly synthesized compounds
Compounds
Molecular formula
Melting point (8C)
Recrystallization solvent
Yield (%)a
Yield (%)b
Reaction time (h)
Activity (%)
Method a
Method b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
C21H23O11
F
F
127–128
163–165
137–139
123–125
105–107
97–99
C2H5OH
71
84
86
79
82
89
76
77
73
75
67
80
75
73
70
88
43
61
57
62
62
70
42
57
41
42
41
43
62
43
48
61
2.5
1.5
2.5
2.5
2.0
2.5
2.0
2.0
1.5
1.5
1.5
1.5
2.0
2.0
1.5
1.5
5
61.0
62.5
77.3
79.1
72.6
79.2
81.8
83.9
80.7
80.9
84.8
85.8
74.2
75.6
83.7
85.1
C21H23O11
C2H5OH
3.5
5
C22H23O11F3
C2H5OH
C21H20O11F4
C2H5OH
5.5
3.5
4.0
4.0
4.0
4.5
4.0
4.0
4.5
5.0
5.5
4.5
4.5
C
21H23O11
F
F
C2H5OC2H5
C2H5OC2H5
CH3CH(CH3)OH
C2H5OC2H5
C21H23O11
C
22H23O11F3
21H20O11F4
91–92
C
94–96
C18H19O9F
18H19O9F
C
C19H19O9F3
C18H16O9F4
C33H39O19
F
F
145–147
113–115
115–117
137–139
C2H5OC2H5
C33H39O19
CH3CH(CH3)OH
C2H5OC2H5
C34H39O19F3
33H36O19F4
C
C2H5OC2H5
Activity (%) is antiviral activity against tobacco mosaic virus.
a
Yield obtained using DMAP/Et3N method.
b
Yield obtained using the phase transfer catalyst (Bu4NBr) method.

1132
H. Chen et al. / Journal of Fluorine Chemistry 127 (2006) 1130–1136
Table 3
fluorine-containing benzoic acid compounds is 25.6–35.1%,
Optimum reaction conditions and yield
the anti-TMV activities of the saccharide esters containing no
fluorine atom are 40% or so [33], but the extent of inhibition of
the synthesized compounds anti-TMV is 61.0–85.8% at dosage
of 0.001%.
Item
Optimum conditions
Reactant molar ratio
Acid (mmol)
1:1
1.25
Amount of catalyst (mmol)
Et3N (mL)
0.10
The preliminary biological tests showed that antiviral
activities of the products are moderate. For example, the
antiviral activities of the synthesized compounds are up to
85.8%. It is listed in Table 2. The results showed that these
compounds exhibit certain activities against TMV. The anti-
TMV data given in Table 2 indicate that the nature of fluorine
and O-acetylglycosyl affect anti-TMV activity of the com-
pounds. For example, the inhibition rate of compound 15 with
R2 being 3-CF3 group attains 83.7%, compound 16 with R2, R3,
R4 being F group attains 85.1%, the inhibition rate of O-
acetylxylopyranosyl saccharide esters is higher than the O-
tetra-acetylglucopyranosyl saccharide esters.
0.25
Reaction temperature (8C)
Reaction time (h)
Yield (%)
20–25
1.5–2.5
67–89
The reaction temperature using a phase transfer catalytic method (used Bu4NBr
catalyst) is 30–60 8C.
experiment in the system of DMAP/Et3N, we found that the
advantages of the procedure are short reaction period, high
yield and simple working up, amount of catalyst DMAP is little
and with a substantially increased yields and decrease in the
reaction time compared with the phase transfer catalytic
(Bu4NBr) method. Optimum reaction conditions and yield were
obtained (Table 3).
2.3. The configuration of compounds 1–16
The configuration is unitary. In the IR spectra of compounds
1–16, two strong and wide bi-shoulder peaks of pyranoid ring,
appear at 1000–1100 and 1200–1300 cmꢀ1, and the absorbance
at 1750 cmꢀ1 or so is attributed to the carbonyl group; in the 1H
NMR spectra, the assignments of the hydrogen atoms in peaks
are very obvious, the coupling constant J1–2 between C1–H1 and
C2–H2 is 7.2–7.6 Hz. Generally, the structures of saccharide
esters can be determined according to chemical shift of C1
proton (H1) NMR of pyranose and coupling constant of H1–H2.
Because the coupling constant between C1–H1 and C2–H2 of b-
configuration of saccharide ester is 7–10 Hz [34], therefore, the
2.2. Biological activity
The anti-TMV activity is assayed by the Reference [30,31]
method. The inhibition rate of anti-TMV was expressed by
calculating the withered spot number in the tobacco leaf, with a
dosage of 0.001% and NS-83 [32] as control.
Fluorine-containing benzoic acid saccharide esters have
relatively higher anti-TMV activity than those fluorine-
containing benzoic acid compounds and the saccharide esters
containing no fluorine atom. The extent of inhibition of
Scheme 2. The cleaving of compounds 5–8.

H. Chen et al. / Journal of Fluorine Chemistry 127 (2006) 1130–1136
1133
Scheme 3. The catalytic mechanism of DMAP/Et3N.
synthesized compounds 1–16 have b-configuration in the
system of DMAP/Et3N. Their structure is same as
obtained using a phase transfer catalytic method (used Bu4NBr
catalyst).
can approach to 61.0–85.8%. The experimental results show
that some of the compounds exhibit potential antiviral activity
against TMV.
Their structure were firmly established by well-defined IR,
19F NMR, 1H NMR, MS and elemental analysis, According to
1
the H NMR chemical shift of C1–H1 proton of pyranoid ring
2.4. Mass spectral analysis for compounds 1–16
and coupling constant of H1–H2, this method has high
stereospecificity, the configuration is unitary, the new
synthesized compounds are all of b-configuration, their
structure is same as compared with a phase transfer catalytic
method.
The molecular ions (M + H)+ peak were obtained by FAB
(fast atom bombardment) of the saccharide ester, whereas by
the EI (electron impact) method, no molecular ion peaks were
obtained exception of a 331 (m/z) fragment peak, which
corresponding to a O-tetra-acetylglucopyranosyl fragment, or
O-tetra-acetylgalactopyranosyl fragment, and a 259 (m/z)
fragment peak, which corresponding to a O-acetylxylopyr-
anosyl fragment and a 619 (m/z) fragment peak, which
corresponding to the O-octa-acetyllactosyl fragment. Some of
fragment peaks of fluorine-containing benzoic acid were
obtained by both FAB and EI methods. The cleavage of
compounds 5–8 is shown as Scheme 2.
In summary, this work demonstrated a simple and useful
method for the synthesis of new fluorine-containing benzoic
acid saccharide esters from the reaction of a-O-acetylglycosyl
bromide and fluorine atom, trifluoromethyl substituted benzoic
acids at room temperature under mild conditions and good
yields, the yields can reach 89%. DMAP/Et3N method has
many advantages compared with the phase transfer catalytic
method, for example, it can increase yields of fluorine-
containing benzoic acid saccharide esters obviously, shortening
reaction time, reducing reaction temperature.
2.5. The catalytic mechanism of DMAP/Et3N
As far as we know, this is the first example of fluorine-
containing benzoic acids saccharide esters synthesized using
DMAP/Et3N method. According to the structure character of
DMAP and uses in the reaction, its mechanism is put forward.
The mechanism of the reaction may belong to nucleophilic
substitution reaction (Scheme 3).
4. Experimental
4.1. Instruments
IR spectra were obtained using a Shimadzu IR-435 IR
spectrometer. The elemental analysis were recorded on an
Immunomedia MT-3 elemental analyzer. 1H NMR spectra were
recorded in acetone-d6 on a Varian Mercury-VX300 (300 MHz)
NMR instrument, using TMS, as internal standard. FAB mass
spectra of the complexes were recorded using a JEOL SX-120
instrument. 19F NMR spectra were obtained on a Varian EM-
360A Spectrometer using CF3COOH (TFA) as an external
standard, positive for downfield shift. The melting points of the
3. Conclusions
The activities of fluorine-containing benzoic acid saccharide
esters are higher than those fluorine-containing benzoic acid
compounds and the saccharide esters containing no fluorine
atom [33], the antiviral activities of the synthesized compounds

1134
H. Chen et al. / Journal of Fluorine Chemistry 127 (2006) 1130–1136
products were determined on an XT-4 binocular microscope
and are not corrected.
1224 cmꢀ1 (bi-shoulder peaks of pyranoid ring). 19F NMR
(CDCl3, TFA): d ꢀ62.76; 1H NMR (CD3COCD3/TMS): d 7.60–
7.80 (m, 4H) (Ar–H), 5.82–5.90 (d, J = 7.2 Hz, 1H) (C1–H1 of
pyranoid ring). 4.70–5.53 (m, 3H) (C2-4–H2-4 of pyranoid ring);
3.43–4.18 (m, 1H) (C5–H5 of pyranoid ring); 4.02–4.36 (d, J5-
6 = 2.0–6.5 Hz, J6-6 = 12.0–12.5 Hz, 2H); 1.23–2.09 (m, 12H)
(CH3). Anal. Calcd. for C22H23O11F3: C, 50.77; H, 4.42%.
Found: C, 50.72; H, 4.38%. FAB-MS, m/z (%): 521 ([M + H]+).
4.2. General procedure for the preparation of fluorine-
containing saccharide esters (compounds 1–16)
A 1.25 mmol fluorine-containing benzoic acids, 1.25 mmol
a-O-acetylglycosyl bromide, 0.10 mmol DMAP, 40 mL DMF
were added into a four-necked, round-bottomed flask. The
temperature was kept constant at 0 8C, 0.25 mL triethylamine
were slowly dropped into reaction system under stirring, then
kept reaction at 20–25 8C for 1.5–2.5 h. As soon as the reaction
finished, the solution was filtrated. After separation, organic
phase was washed to neutrality with water and dried with
anhydrous magnesium sulfate. The dense liquid was obtained
by the vaporization of solvent under condition of vacuum
distillation. (1) After recrystallized from different solvent
(Table 2), white solid products (compounds 1–8, 13–16) were
obtained. (2) After semifinished product dissolve in ethyl
acetate and separation through silica gel chromatography by
using ethyl acetate as eluant, 4-fluorobenzoic acid O-
acetylxylopyranosyl saccharide ester (compound 9) was
obtained by the vaporization of the solvent. Compounds 10–
12 were prepared similarly.
4.2.4. 2,3,4,5-Tetrafluorobenzoic acid O-
acetylglucopyranosyl saccharide ester (4)
White solid; yield: 79%; mp, 123–125 8C. IR (KBr): 1745
(C O), 1612 (Ph-), 1093, 891 (C–F), 1035, 1234 cmꢀ1 (bi-
shoulder peaks of pyranoid ring). 19F NMR (CDCl3, TFA): d
1
ꢀ134.54; H NMR (CD3COCD3/TMS): d 7.50–7.60 (m, 1H)
(Ar–H), 5.92–5.89 (d, J = 7.2 Hz, 1H) (C1–H1 of pyranoid
ring). 4.75–5.58 (m, 3H) (C2-4–H2-4 of pyranoid ring); 3.45–
4.20 (m, 1H) (C5–H5 of pyranoid ring); 4.00–4.35 (d, J5-
6 = 2.0–6.5 Hz, J6-6 = 12.0–12.5 Hz, 2H); 1.25–2.10 (m, 12H)
(CH3). Anal. Calcd. for C21H20O11F4: C, 48.09; H, 3.82%.
Found: C, 48.03; H, 3.78%. FAB-MS, m/z (%): 525 ([M + H]+).
4.2.5. 2-Fluorobenzoic acid O-acetylgalactopyranosyl
saccharide ester (5)
White solid; yield: 82%; mp, 105–107 8C. IR (KBr): 1747
(C O), 1604, 1508 (Ph-), 1231 (C–F), 1031–1074, 1200–
1230 cmꢀ1 (bi-shoulder peaks of pyranoid ring). 19F NMR
4.2.1. 2-Fluorobenzoic acid O-acetylglucopyranosyl
saccharide ester (1)
1
White solid; yield: 71%; mp, 127–128 8C. IR (KBr): 1753,
1732 (C O), 1612, 1558 (Ph-), 1234 (C–F), 1033–1085, 1222–
1272 cmꢀ1 (bi-shoulder peaks of pyranoid ring). 19F NMR
(CDCl3, TFA): d ꢀ109.48; H NMR (CD3COCD3/TMS): d
7.16–7.90 (m, 4H) (Ar–H), 6.06–6.15 (d, J = 7.2 Hz, 1H) (C1–
H1 of pyranoid ring), 4.75–5.58 (m, 3H) (C2-4–H2-4 of pyranoid
ring), 3.45–4.20 (m, 1H) (C5–H5 of pyranoid ring), 4.00–4.35
(m, J5-6 = 2.0–6.5 Hz, J6-6 = 12.0–12.5 Hz, 2H) (C6–H6 of
pyranoid ring), 1.29–2.14 (m, 12H) (CH3). Anal. Calcd. for
C21H23O11F: C, 53.62; H, 4.89%. Found: C, 53.65; H, 4.84%.
FAB-MS, m/z (%): 471 ([M + H]+).
1
(CDCl3, TFA): d ꢀ110.10; H NMR (CD3COCD3/TMS): d
7.27–8.11 (m, 4H) (Ar–H), 5.82–5.90 (d, J = 7.2 Hz, 1H) (C1–
H1 of pyranoid ring), 4.75–5.58 (m, 3H) (C2-4–H2-4 of pyranoid
ring), 3.45–4.20 (m, 1H) (C5–H5 of pyranoid ring), 4.00–4.35
(m, J5-6 = 2.0–6.5 Hz, J6-6 = 12.0–12.5 Hz, 2H) (C6–H6 of
pyranoid ring), 1.25–2.10 (m, 12H) (CH3). Anal. Calcd. for
C21H23O11F: C, 53.62; H, 4.89%. Found: C, 53.72; H, 4.88%.
FAB-MS, m/z (%): 471 ([M + H]+).
4.2.6. 4-Fluorobenzoic acid O-acetylgalactopyranosyl
saccharide ester (6)
White solid; yield: 89%; mp, 97–99 8C. IR (KBr): 1735
(C O), 1610, 1510 (Ph-), 1245 (C–F), 1030–1138, 1210–
1290 cmꢀ1 (bi-shoulder peaks of pyranoid ring). 19F NMR
4.2.2. 4-Fluorobenzoic acid O-acetylglucopyranosyl
saccharide ester (2)
1
White solid; yield: 84%; mp, 163–65 8C IR (KBr): 1739
(C O), 1604, 1508 (Ph-), 1251 (C–F), 1033–1082, 1218–
1260 cmꢀ1 (bi-shoulder peaks of pyranoid ring). 19F NMR
(CDCl3, TFA): d ꢀ119.23; H NMR (CD3COCD3/TMS): d
7.20–8.12 (m, 4H) (Ar–H), 6.04–6.12 (d, J = 7.2 Hz, 1H) (C1–
H1 of pyranoid ring), 4.75–5.58 (m, 3H) (C2-4–H2-4 of pyranoid
ring), 3.45–4.20 (m, 1H) (C5–H5 of pyranoid ring), 4.00–4.35
(m, J5-6 = 2.0–6.5 Hz, J6-6 = 12.0–12.5 Hz, 2H) (C6–H6 of
pyranoid ring), 1.25–2.10 (m, 12H) (CH3). Anal. Calcd. for
C21H23O11F: C, 53.62; H, 4.89%. Found: C, 53.68; H, 4.87%.
FAB-MS, m/z (%): 471 ([M + H]+).
1
(CDCl3, TFA): d ꢀ117.56; H NMR (CD3COCD3/TMS): d
7.31–8.00 (m, 4H) (Ar–H), 5.86–5.94 (d, J = 7.2 Hz, 1H) (C1–
H1 of pyranoid ring), 4.75–5.58 (m, 3H) (C2-4–H2-4 of pyranoid
ring), 3.45–4.20 (m, 1H) (C5–H5 of pyranoid ring), 4.00–4.35
(m, J5-6 = 2.0–6.5 Hz, J6-6 = 12.0–12.5 Hz, 2H) (C6–H6 of
pyranoid ring), 1.25–2.10 (m, 12H) (CH3). Anal. Calcd. for
C21H23O11F: C, 53.62; H, 4.89%; found: C, 53.66; H, 4.85%.
FAB-MS, m/z (%): 471 ([M + H]+).
4.2.7. 3-Trifluoromethyl benzoic acid O-
acetylgalactopyranosyl saccharide ester (7)
White solid; yield: 76%; mp, 91–92 8C. IR (KBr):
1753(C O), 1629, 1520 (Ph-), 1420, 1180, 1250 (C–F),
1074, 1226 cmꢀ1 (bi-shoulder peaks of pyranoid ring). 19F
NMR (CDCl3, TFA): d ꢀ65.13; 1H NMR (CD3COCD3/TMS):
d 7.61–8.00 (m, 4H) (Ar–H), 5.89–5.97 (d, J = 7.2 Hz, 1H)
4.2.3. 3-Trifluoromethyl benzoic acid O-
acetylglucopyranosyl saccharide ester (3)
White solid; yield: 86%; mp, 137–139 8C. IR (KBr): 1747
(C O), 1629, 1527 (Ph-), 1415, 1160, 1140 (C–F), 1039,

H. Chen et al. / Journal of Fluorine Chemistry 127 (2006) 1130–1136
1135
(C1–H1 of pyranoid ring), 4.75–5.58 (m, 3H) (C2-4–H2-4 of
4.2.12. 2,3,4,5-Tetrafluorobenzoic acid
O-acetylxylopyranosyl saccharide ester (12)
pyranoid ring), 3.45–4.20 (m, 1H) (C5–H5 of pyranoid ring),
4.00–4.35 (m, J5-6 = 2.0–6.5 Hz, J6-6 = 12.0–12.5 Hz, 2H) (C6–
H6 of pyranoid ring), 1.27–2.13 (m, 12H) (CH3). Anal. Calcd.
for C22H23O11F3: C, 50.77; H, 4.42%. Found: C, 50.72; H,
4.37%. FAB-MS, m/z (%): 521 ([M + H]+).
Yellow dense liquid; yield: 80%; IR: 1760, 1730 (C O),
1620 (Ph-), 1090, 890 (C–F), 1040, 1250 cmꢀ1 (bi-shoulder
peaks of pyranoid ring). 19F NMR (CDCl3, TFA): d ꢀ138.20;
1H NMR (CD3COCD3/TMS): d 7.50–7.66 (m, 1H) (Ar–H),
5.89–5.97 (d, J = 7.2 Hz, 1H) (C1–H1 of pyranoid ring). 5.45–
4.53 (m, 3H) (C2-4–H2-4 of pyranoid ring); 3.40–3.13 (m, 2H)
(C5–H5 of pyranoid ring); 2.03–2.28 (m, 9H) (CH3). Anal.
Calcd. for C18H16O9F4: C, 47.79; H, 3.54%. Found: C, 47.75;
H, 3.50%. FAB-MS, m/z (%): 453 ([M + H]+).
4.2.8. 2,3,4,5-Tetrafluorobenzoic acid O-
acetylgalactopyranosyl saccharide ester (8)
White solid; yield: 77%; mp, 94–96 8C. IR (KBr): 1743
(C O), 1615 (Ph-), 1096, 895 (C–F), 1050, 1230 cmꢀ1 (bi-
shoulder peaks of pyranoid ring). 19F NMR (CDCl3, TFA): d
1
ꢀ136.53; H NMR (CD3COCD3/TMS): d 7.55–7.76(m, 1H)
4.2.13. 4-Fluorobenzoic acid O-acetyllactopyranosyl
saccharide ester (13)
(Ar–H), 5.90–5.98 (d, J = 7.2 Hz, 1H) (C1–H1 of pyranoid
ring), 4.75–5.58 (m, 3H) (C2-4–H2-4 of pyranoid ring), 3.45–
4.20 (m, 1H) C5–H5 of pyranoid ring), 4.00–4.35 (m, J5-
6 = 2.0–6.5 Hz, J6-6 = 12.0–12.5 Hz, 2H) (C6–H6 of pyranoid
ring), 1.21–2.10 (m, 12H) (CH3). Anal. Calcd. for
C21H20O11F4: C, 48.09; H, 3.82%. Found: C, 48.06; H,
3.79%. FAB-MS, m/z (%): 525 ([M + H]+).
White solid; yield: 75%; mp, 145–147 8C. IR (KBr): 1747
(C O), 1602, 1508 (Ph-), 1248 (C–F), 1040–1075, 1200–
1240 cmꢀ1 (bi-shoulder peaks of pyranoid ring). 19F NMR
1
(CDCl3, TFA): d ꢀ119.31; H NMR (CD3COCD3/TMS): d
7.28–8.0 (m, 4H) (Ar–H), 4.93–6.02 (d, J = 7.5 Hz, 1H) 5.80–
5.90 (d, J = 7.4 Hz, 1H) (C1–H1 of pyranoid ring), 5.45–5.56 (d,
0
0
J = 9.80 Hz, 1 H) (C1 –H1 of pyranoid ring). 5.18–4.80 (m, 6H)
0
0 0 0 0
(C2 -4 –H2 -4 , C2-4–H2-4 of pyranoid ring), 4.35–4.45 (m, 1H)
4.2.9. 4-Fluorobenzoic acid O-acetylxylopyranosyl
saccharide ester (9)
0
0
(C5 –H5 of pyranoid ring), 3.65–3.80 (m, 1H) (C5–H5 of
0
0
Yellow dense liquid; yield: 73%; IR: 1740, 1720 (C O),
1610, 1520 (Ph-), 1248 (C–F), 1210–1270 cmꢀ1 (bi-shoulder
peaks of pyranoid ring). 19F NMR (CDCl3, TFA): d ꢀ118.57;
1H NMR (CD3COCD3/TMS): d 7.30–8.10 (m, 4H) (Ar–H),
5.92–6.00 (d, J = 7.2 Hz, 1H) (C1–H1 of pyranoid ring). 5.41–
4.52 (m, 3H) (C2-4–H2-4 of pyranoid ring); 3.42–3.14 (m, 2H)
(C5–H5 of pyranoid ring); 2.01–2.21 (m, 9H) (CH3). Anal.
Calcd. for C18H19O9F: C, 54.27; H, 4.77%. Found: C, 54.20; H,
4.72%. FAB-MS, m/z (%): 399 ([M + H]+).
pyranoid ring), 4.01–4.15(m, 4H) (C6 –H6 , C6–H6 of pyranoid
ring), 2.05–2.20 (m, 21H) (CH3). Anal. Calcd. for C33H39O19F:
C, 52.24; H, 5.15%. Found: C, 52.27; H, 5.12%. FAB-MS, m/z
(%): 759 ([M + H]+).
4.2.14. 2-Fluorobenzoic acid O-acetyllactopyranosyl
saccharide ester (14)
White solid; yield: 73%; mp, 113–115 8C. IR (KBr): 1750
(C O), 1585 (Ph-), 1237 (C–F), 1049–1080, 1220–1294 cmꢀ1
(bi-shoulder peaks of pyranoid ring). 19F NMR (CDCl3, TFA): d
1
4.2.10. 2-Fluorobenzoic acid O-acetylxylopyranosyl
saccharide ester (10)
ꢀ109.86; H NMR (CD3COCD3/TMS): d 7.30–7.90 (m, 4H)
(Ar–H), 5.90–5.98 (d, J = 7.2 Hz, 1H) (C1–H1 of pyranoid
0 0
ring), 5.45–5.50 (d, J = 9.50 Hz, 1H) (C1 –H1 of pyranoid
Yellow dense liquid; yield: 75 %; IR: 1740, 1720 (C O),
1620, 1510 (Ph-), 1230 (C–F), 1035–1080, 1200–1290 cmꢀ1
(bi-shoulder peaks of pyranoid ring). 19F NMR (CDCl3,
0
ring). 5.28–4.90 (m, 6H) (C2 -4 –H2 -4 , C2-4–H2-4 of pyranoid
0
ring), 4.30–4.40 (m, 1H) (C5 –H5 of pyranoid ring), 3.70–3.84
0
0
0
0
1
0
0
TFA): d ꢀ111.70; H NMR (CD3COCD3/TMS): d 7.20–8.04
(m, 1H) (C5–H5 of pyranoid ring), 4.07–4.21 (m, 4H) (C6 –H6 ,
C6–H6 of pyranoid ring), 2.07–2.21 (m, 21H) (CH3). Anal.
Calcd. for C33H39O19F: C, 52.24; H, 5.15%. Found: C, 52.20;
H, 5.12%. FAB-MS, m/z (%): 759 ([M + H]+).
(m, 4H) (Ar–H), 5.94–5.85 (d, J = 7.6 Hz, 1H) (C1–H1 of
pyranoid ring). 5.41–4.62 (m, 3H) (C2-4–H2-4 of pyranoid
ring); 3.42–3.05 (m, 2H) (C5–H5 of pyranoid ring); 2.03–2.31
(m, 9H) (CH3). Anal. Calcd. for C18H19O9F: C, 54.27; H,
4.77%. Found: C, 54.23; H, 4.69%. FAB-MS, m/z (%): 399
([M + H]+).
4.2.15. 3-Trifluoromethyl benzoic acid
O-acetyllactopyranosyl saccharide ester (15)
White solid; yield: 70%; mp, 115–117 8C. IR (KBr): 1751
(C O), 1616, 1420, 1165, 1150 (Ph-), 1234 (C–F), 1051,
1224 cmꢀ1 (bi-shoulder peaks of pyranoid ring). 19F NMR
(CDCl3, TFA): d ꢀ63.18; 1H NMR (CD3COCD3/TMS): d 7.70–
8.10 (m, 4H) (Ar–H), 5.92–6.00 (d, J = 7.2 Hz, 1H) (C1–H1 of
4.2.11. 3-Trifluoromethyl benzoic acid
O-acetylxylopyranosyl saccharide ester (11)
Yellow dense liquid; yield: 67%; IR: 1751(C O), 1616,
1420, 1165, 1150 (Ph-), 1051, 1224 cmꢀ1 (bi-shoulder peaks of
pyranoid ring). 19F NMR (CDCl3, TFA): d ꢀ64.45; H NMR
1
0
pyranoid ring), 5.43–5.55 (d, J = 9.85 Hz, 1H) (C1 –H1 of
0
0 0 0 0
pyranoid ring). 5.10–4.70 (m, 6H) (C2 -4 –H2 -4 , C2-4–H2-4 of
(CD3COCD3/TMS): d 7.10–8.10 (m, 4H) (Ar–H), 5.90–5.98 (d,
J = 7.2 Hz, 1H) (C1–H1 of pyranoid ring). 5.52–4.61 (m, 3H)
(C2-4–H2-4 of pyranoid ring); 3.32–3.03 (m, 2H) (C5–H5 of
pyranoid ring); 2.10–2.31 (m, 9H) (CH3). Anal. Calcd. for
C19H19O9F3: C, 50.89; H, 4.24%. Found: C, 50.85; H, 4.20%.
FAB-MS, m/z (%): 449 ([M + H]+).
0
pyranoid ring), 4.38–4.47 (m, 1H) (C5 –H5 of pyranoid ring),
0
3.68–3.85 (m, 1H) (C5–H5 of pyranoid ring), 4.04–4.20 (m, 4H)
0
0
(C6 –H6 , C6–H6 of pyranoid ring), 2.03–2.18 (m, 21H) (CH3).
Anal. Calcd. for C34H39O19F3: C, 46.36; H, 4.83%. Found: C,
46.31; H, 4.79%. FAB-MS, m/z (%): 809 ([M + H]+).

1136
H. Chen et al. / Journal of Fluorine Chemistry 127 (2006) 1130–1136
[9] S.G. Kucukguzel, S. Rollas, H. Erdeniz, A.C. Kiraz, M. Ekinci, A. Vidin,
Eur. J. Med. Chem. 35 (2000) 761–771.
4.2.16. 2,3,4,5-Tetrafluorobenzoic acid O-
acetyllactopyranosyl saccharide ester (16)
[10] A.E. Mutalib, S.Y. Chen, R.J. Espina, J. Shockcor, S.R. Prakash, L.S. Gan,
Chem. Res. Toxicol. 15 (2002) 63–75.
White solid; yield: 88%; mp, 137–139 8C. IR (KBr): 1747
(C O), 1612 (Ph-), 1102, 892 (C–F), 1047, 1236 cmꢀ1 (bi-
shoulder peaks of pyranoid ring). 19F NMR (CDCl3, TFA): d
[11] Y.J. Zhang, J. Pestic. Transl. 3 (1982) 7–9.
[12] M. Prakesch, D. Gre’e, S. Chandrasekhar, R. Gre’e, Eur. J. Org. Chem.
(2005) 1211–1232.
1
ꢀ135.67; H NMR (CD3COCD3/TMS): d 7.60–7.70 (m, 1H)
[13] K. Mikami, Y. Itoh, M. Yamanaka, Chem. Rev. 104 (2004) 1–16.
[14] R.P. Singh, J.M. Shreeve, Tetrahedron 56 (2000) 7613–7632.
[15] G.K.S. Prakash, A.K. Yudin, Chem. Rev. 97 (1997) 757–786.
[16] J.H. Steenis, A. Gen, J. Chem. Soc. Perkin Trans. 1 (2002) 2117–
2133.
(Ar–H), 5.98–6.89 (d, J = 7.2 Hz, 1H) (C1–H1 of pyranoid
0
ring), 5.40–5.51 (d, J = 9.65 Hz, 1H) (C1 –H1 of pyranoid
0
0
ring). 5.20–4.86 (m, 6H) (C2 -4 –H2 -4 , C2-4–H2-4 of pyranoid
0
0
0
0
0
ring), 4.37–4.48 (m, 1H) (C5 –H5 of pyranoid ring), 3.60–3.79
[17] M.A. McClinton, D.A. McClinton, Tetrahedron 48 (1992) 6555–6666.
[18] I. Ojima, Chem. Rev. 88 (1988) 1011–1030.
[19] S.A. Jyoti, J. Ind. Chem. Soc. 68 (1991) 103–105.
[20] S. Joel, J. Chem. Indus. (London) 24 (2004) 20–21.
[21] C. Greig, R.K. Alan, B. Laura, B. Eve, J. Acta Crystallogr. C. Cryst. Struct.
Commun. 58 (2002) O645–O648.
0
0
(m, 1H) (C5–H5 of pyranoid ring), 4.03–4.17 (m, 4H) (C6 –H6 ,
C6–H6 of pyranoid ring), 2.08–2.25 (m, 21H) (CH3). Anal.
Calcd. for C33H36O19F4: C, 48.77; H, 4.43%. Found: C, 48.73;
H, 4.39%. FAB-MS, m/z (%): 813 ([M + H]+).
[22] Y. Ohya, H. Kobayashi, T. Ouchi, J. React. Polym. 15 (1991) 153–
163.
Acknowledgements
[23] G. Daidone, B. Maggio, S. Plescia, D. Raffa, C. Musiu, C. Milia, G. Perra,
M.E. Marongiu, Eur. J. Med. Chem. 33 (1998) 375–382.
[24] S.A. Gamage, J.A. Spicer, G.W. Rewcastle, J. Milton, S. Sohal, W.
Dangerfield, P. Mistry, N. Vicker, P.A. Charlton, W.A. Denny, J. Med.
Chem. 45 (2002) 740–743.
We thank the National Natural Science Foundation of China
and the Department of Education of Guangdong Province
Natural Science Foundation of China for financial support.
Helpful discussion with Professor Xiaoling Huang is also
acknowledged.
[25] H. Chen, S.Q. Huang, Y.M. Wen, S.D. Li, J. Chem. Res. 10 (2005) 626–
628.
[26] H. Chen, Z.Q. Dai, F.Q. Qu, X.L. Huang, Chem. J. Chin. Univ. 20 (1999)
1725–1728.
References
[27] H. Chen, S.Q. Huang, X.F. Li, J. Wuhan Univ. (Nat. Sci. Ed.) 47 (6) (2001)
693 (Chapter).
[1] D. O’Hagen, H.S. Rzepa, Chem. Commun. (1997) 645–652.
[2] J.T. Welch, Tetrahedron 43 (1987) 3123–3197.
[28] D.Q. Jiao, X.J. Du, R.B. Wei, J. Spec. Petrochem. 32 (1999) 26–28.
[29] W. Steglish, G. Hofle, Angew Chem. Int. Ed. Engl. 8 (1969) 981.
[30] H.F. Li, X.Y. Lei, W.F. Qiu, Acta Phytopathol. Sin. (in Chinese) 17 (3)
(1987) 147–152.
[3] J. Mann, Chem. Soc. Rev. 16 (1987) 381–436.
[4] L.F. Lee, F.M. Schleppnik, R.W. Schneider, D.H. Campbell, J. Heterocycl.
Chem. 27 (1990) 243–245.
[5] P. Bravo, D. Dillido, G. Resnati, Tetrahedron 50 (1994) 8827–8836.
[6] J.C. Jung, E.B. Watkins, M.A. Avery, Tetrahedron 58 (2002) 3639–3646.
[7] K.L. Kees, J.J. Fitzgerald, K.E. Steimer, J.F. Mattes, B. Mihan, T. Tosi, D.
Mondoro, M.L. McCaleb, J. Med. Chem. 39 (1996) 3920–3928.
[8] T.P. Gregory, C.D. Darlene, M.S. David, Pestic. Biochem. Phys. 60 (1998)
177–185.
[31] X.Y. Lei, H.F. Li, W.F. Qiu, Sci. Agric., Sin. (in Chinese) 20 (4) (1987)
1–6.
[32] W.F. Qiu, X.Y. Lei, H.F. Li, Progr. Nat. Sci. 4 (2) (1994) 173–181.
[33] F.Q. Qu, X.R. Dong, X.X. Luo, J. Wuhan Univ. (Nat. Sci. Ed.) 2 (1998)
201–204.
[34] C.F. Yu, M.S. Cai, L.R. Huang, Chem. Online 3 (1991) 35–38.