504 JOURNAL OF CHEMICAL RESEARCH 2007
The precipitate was filtered off and the filtrate was concentrated to
dryness. The residue was purified by column chromatography with
PE/EtOAc (15:1, v/v) to obtain colourless liquid in yield 82%.
[α]20D + 18.63° (c0.8, CHCl3), 1H NMR (CDCl3, 300 MHz) δ: 7.37–
7.31 (m, 5H, ArH), 4.72 (s, 2H, PhCH2), 4.43–4.37 (m, 2H, 1-H,
3-H), 4.16–4.10 (m, 1H, 3-H'), 3.70–3.65 (m, 1H, 2-H), 3.45 (s, 3H,
OCH3), 3.43 (s, 3H, OCH3), 2.32 (t, 2H, J = 7.5 Hz, CH2CO), 1.63
(t, 2H, J = 6.8 Hz, COCH2CH2), 1.27 (s, 16H, (CH2)8), 0.90 (t, 3H,
J = 6.9 Hz, CH3). Anal calcd for C24H40O5: C 70.55, H 9.87; found:
C 70.2, H 9.5
from D-mannitol. Acylation of the primary 1-hydroxyl group
in 3 with lauric acid in the presence of DCC and DMAP
gives 3-O-lauroyl-2-O-benzyl glyceraldehyde dimethylacetal
4 in 82% yield. To deprotect the dimethylacetal, 4 was first
dispersed in 1 M hydrochloric acid and the reactant solution
was stirred vigorously at 70°C, which gave a complex
mixture of inseparable products. Considering mild reaction
conditions and catalyst availability, FeCl3·6H2O, SnCl2·2H2O
or acetone containing molecular iodine were applied to cleave
the dimethylacetal of 4, among which FeCl3·6H2O gave the
best result. Therefore, dimethylacetal 4 was easily converted
into 3-O-lauroyl-2-O-benzyl glycerol 5 in 50% yield by
deacetalisation using FeCl3·6H2O in dichloromethane/
acetone, followed by reduction with sodium borohydride.
In the presence of Et3N, 5 was tosylated by different
sulfonyl chlorides to obtain 3-O-lauroyl-2-O-benzyl-glycerol
sulfonates 6 in yields 40–90%.
3-O-Lauroyl-2-O-benzyl-D-glycerol (5)
To a solution of 4 (5.04 g, 0.012 mol) in 80 ml of CHCl3 was added
FeCl3·6H2O (11.67 g, 0.043 mol) and 20 ml of acetone. The reactant
solution was stirred for 6 h at room temperature. Saturated NaHCO3
solution was added and the water phase was extracted with CH2Cl2
three times. After combination the organic phases were washed with
water until colourless and the solvent was removed. The solution
of the residue in 40 ml of THF was added at 0°C to the solution of
NaBH4 (0.93 g, 0.025 mol) in 10 ml of water. The reactant solution
was stirred for 4 h at room temperature and water was added.
The solution was neutralised with 10% HCOOH and extracted three
times with ether. After combination, drying with magnesium sulfate,
evaporation of the solvent, the product was obtained through column
chromatography with PE/EtOAc (4:1,v/v) as a colourless liquid in
50% yield. [α]20 –2.2° (c1.4, CHCl3), 1H NMR (CDCl3, 300 MHz)
δ: 7.29–7.19 (m,D5H, ArH), 4.65 (d, 1H, J = 12 Hz, PhCHaHb), 4.53
(d, 1H, J = 12 Hz, PhCHaHb), 4.17 (d, J = 4.5 Hz, 2H, 3-H, 3-H'),
3.66–3.52 (m, 3H, 2-H,1-H, 1-H'), 2.25 (t, 2H, J = 7.5 Hz, CH2CO),
1.97 (OH), 1.55 (t, 2H, J = 6.8 Hz, COCH2CH2), 1.29–1.14 (m, 16H,
(CH2)8), 0.81 (t, 3H, J = 6.9 Hz, CH3). Anal calcd for C22H36O4:
C 72.49, H 9.95; found: C 72.1, H 9.9.
Bioactivity
The antifungal activities of the title compounds in vitro
against Gibberella zeae, Alternaria solani, Phoma asparagi,
Physalospora piricola, and Cercospora arachi dicola were
tested. The inhibition percentages in these assays over control
samples without fungicides are listed in Table 1. The results
showed that compounds 6a, 6b, 6f and 6g exhibited some
fungicidal activity against the tested fungi.
Experimental
3-O-Lauroyl-2-O-benzyl-D-glycerol sulfonate (6)
General
To a solution of 5 (1 mmol) and the sulfonyl chloride (1.2 mmol)
in 5 ml of CHCl3 was added dropwise at 0°C a solution of Et3N
(1.2 mmol) in 5 ml of CHCl3. The reactant solution was stirred for
12 h at room temperature. The solution was washed three times
with water and dried with MgSO4. After evaporation of solvent the
product was obtained through column chromatography with PE/
EtOAc (10:1,v/v).
Melting points were determined on a Yanaco melting point
apparatus and are uncorrected. Specific rotation was determined on
a PE MODEL 341 polarimeter. H NMR spectra were recorded on
1
a Bruker Avance 300 M NMR spectrometer in CDCl3 with TMS as
internal standard and coupling constants (J) are expressed in Hz.
Elemental analyses were done on a Yanaco CHN Corder MT-3 by
Jian-Xin Ma in Nankai University. The reaction progress is followed
with TLC plates run in PE-EtOAc solvent systems. Spots were
visualised by exposure to UV light (254 nm) followed by I2 vapour.
Column chromatographies were carried out with silica gel 200–300
mesh with PE-EtOAc mixtures under positive pressure.
3-O-Lauroyl-2-O-benzyl-D-glycerol benzene sulfonate(6a): Yellow
liquid, [α]20 + 3.63º (c 1.6, CHCl3), yield 69%; H NMR (CDCl3,
1
300 MHz) δD: 7.90 (d, 2H, J = 8.3 Hz, ArH), 7.64 (d, 1H, J = 6.0 Hz,
ArH), 7.53 (t, 2H, J = 7.5 Hz, ArH), 7.33–7.24 (m, 5H, ArH), 4.59
(d, 1H, J = 11 Hz, PhCH2), 4.54 (d, 1H, J = 11 Hz, PhCH2), 4.22–
4.06 (m, 4H, 1-H, 1-H', 3-H, 3-H'), 3.85–3.80 (m, 1H, 2-H), 2.24 (t,
2H, J = 7.5 Hz, CH2CO), 1.56 (t, 2H, J = 6.8 Hz, COCH2CH2), 1.25
(s, 16H, CH2), 0.88 (t, 3H, J = 6.9 Hz, CH3). Anal calcd for
C28H40O6S: C 66.44, H 7.99; found: C 66.4, H 8.0
Biological assay
The fungicidal activities of the title compounds were evaluated using
the mycelium growth rate test. 1 ml solution of the tested compound
in acetone was added to a culture plate and then 9 ml PDA culture
medium was added to obtain the ‘flat' containing 50 ppm of tested
compound. A bacterium tray of 4 mm diameter, cut along the
external edge of the hypase, was added to the ‘flat' containing
the tested compound and put in an equilateral triangular style. Later,
the culture plate was cultured at 24±1°C and the expanded diameter
of the bacterium tray was measured after 48 h and compared with that
treated with sterilised water to estimate the activity. Two replicates
were included in the evaluation.
3-O-Lauroyl-2-O-benzyl-D-glycerol p-methylbenzene sulfonate
(6b): Yellow liquid, [α]20D + 4º (c 0.8, CHCl3), yield 20%; 1H NMR
(CDCl3, 300 MHz) δ: 7.80 (d, 2H, J = 8.3 Hz, ArH), 7.37–7.26
(m, 7H, ArH), 4.61 (d, 1H, J = 12 Hz, PhCH2), 4.57 (d, 1H, J = 12 Hz,
PhCH2), 4.23–4.08 (m, 4H, 1-H, 1-H', 3-H, 3-H'), 3.87–3.80 (m, 1H,
2-H), 2.46 (s, 3H, ArCH3), 2.27 (t, 2H, J = 7.5 Hz, CH2CO), 1.59
(t, 2H, J = 7.5 Hz, COCH2CH2), 1.28 (s, 16H, CH2), 0.90 (t, 3H,
J = 6.9 Hz, CH3). Anal calcd for C29H42O6S: C 67.15, H 8.16; found:
C 66.9, H 8.2
3-O-Lauroyl-2-O-benzyl-D-glyceraldehyde dimethylacetal (4)
To a solution of 3 (5 g, 0.022 mol), lauric acid(5.31 g, 0.027 mol)
and DMAP(0.27 g, 0.002 mol) in 100 ml of CHCl3 was added
dropwise the solution of DCC(5.47 g, 0.027 mol) in 50 ml of CHCl3.
The reactant solution was stirred for 2 h at room temperature.
3-O-Lauroyl-2-O-benzyl-D-glycerol p-fluorobenzene sulfonate
(6c): Yellow liquid, [α]20 + 4º (c 0.4, CHCl3), yield 67%;
D
1H NMR (CDCl3, 300 MHz) δ: 7.92–7.88 (m, 2H, ArH), 7.36–7.15
(m, 7H, ArH), 4.62 (d, 1H, J = 12 Hz, PhCH2), 4.56 (d, 1H, J = 12
Hz, PhCH2), 4.23–4.07 (m, 4H, 1-H, 1-H', 3-H, 3-H'), 3.86–3.79
Table 1 Antifungal activity of title compounds in vitro (%, 50 mg l-1)
Compd
R
Ratio(%)
Gibberella zeae
Alternaria solani
Phoma asparagi
Physalospora
piricola
Cercospora
arachi dicola
6a
6b
6c
6d
6e
6f
C6H5
6.0
12.1
0
34.5
24.1
0
10.7
10.7
0
33.3
28.2
7.7
20.5
15.4
38.5
35.9
13.0
13.0
0
13.0
0
13.0
0
p-CH3C6H4
p-FC6H4
p-ClC6H4
p-BrC6H4
p-NO2C6H4
CH3
0
0
0
9.0
12.1
12.1
10.3
27.6
31.0
0
0
10.7
6g
PAPER: 07/4687