1
442
Y. Nishida et al. / Tetrahedron: Asymmetry 28 (2017) 1435–1443
5
5
. Experimental
5.1.2. 1,2-Dipalmitoyl-sn-glycerol II
The preceding product I (300 mg) was dissolved in a mixture of
n-hexane and 2-propanol (1:5, 60 mL) and hydrogenated for 3 h
.1. General
with Pd(OH)
the completion of the reaction, the mixture was filtrated with a
pad of celite in a mixture of CHCl and methanol (100:1) and evap-
2 2
under H atmosphere at room temperature. After
All reactions are carried out under a dry argon atmosphere.
Yields refer to chromatographically and spectroscopically homoge-
neous material. Anhydrous solvents are purchased from Wako Pure
Chemical Industries Co., Ltd. All other chemicals for the syntheses
are purchased from Wako Pure Chemical Industries Co., Ltd.
3
orated to give 1,2-dipalmitoyl-sn-glycerol 3 (248 mg, 96%) as a col-
orless powder. A part of this product (100 mg) was recrystallized
1
from hot ethanol. The H NMR spectrum of II matched with the
1
(
Osaka, Japan), Sigma–Aldrich Co., or Tokyo Kasei Kogyo (Tokyo,
H NMR spectrum of an authentic sample (Aldrich, CAS: 30334-
Japan). Reagents purchased at the highest commercial quality are
used without further purification. All reactions are monitored by
thin-layer chromatography (TLC) carried out on silica gel 60-F254
precoated plates (Merck) using UV light and cerium sulfate/molyb-
dic acid solution as visualizing agent. Silica gel BW-80S (average
particle size 100 mesh, Fuji Silicia Chemical Co., Ltd.) or BW-300
71-5).
5.1.3. 1,2-Dipalmitoyl-3-methanesulfonyl-sn-glycerol 13
The preceding crude product II (200 mg, 0.35 mmol) was dis-
solved in dry pyridine (10 mL) and reacted with methanesulfonyl
chloride (MsCl) (61 mg, 1.5 ꢄ 0.35 mmol) for 3 h at room temper-
ature. The reaction mixture was poured into a mixture of crashed
ice and water (100 mL), and the mixture was vigorously stirred.
Precipitates were collected by filtration and dried. TLC (silica gel,
toluene/ethyl acetate = 10:1) showed the presence of two com-
pounds in the crude material (major spot at Rf = 0.59 and minor
spot at Rf = 0.65). Purification with column chromatography on
(
average particle size 60 mesh, Fuji Silicia Chemical Co., Ltd.) is
employed for flash column chromatography.
ESI-HRMS spectra are recorded on a ThermoFisher Exactive.
NMR spectra are recorded with a JEOL ECA 500 spectrometer
equipped with Delta 5.02. Unless otherwise stated, 1H NMR (500
MHz) spectra are recorded at 25 °C using internal tetramethylsi-
13
lane (TMS) at 0 ppm, and
C NMR (125 MHz) spectra were
2
SiO in a mixture of n-hexane and ethyl acetate (10:1) afforded
recorded at 125 MHz using internal CDCl
lowing abbreviations are used to explain the multiplicities: s = sin-
glet, d = doublet, t = triplet, m = multiplet, br = broad.
3
at 77.16 ppm. The fol-
13 as a waxy solid (163 mg, 72%). 13: mp = 57.8–59.2 °C (softening
1
temperature = 45.7 °C). H NMR (CDCl
CH
), 1.25–1.35 (48H, m, 2 ꢄ pal-(CH
3
), d
H
0.88 (6H, t, 2 ꢄ pal-
3
2
)
12), 1.62 (4H, m, 2 ꢄ pal-C
CH OR
CH OBn
2
2
i
H
OOCO(CH ) CH3
2 14
H
C
OOCO(CH )14CH
2 3
C
CH OCO(CH ) CH3
CH OCO(CH ) CH3
2
2 14
2
2 14
II : R =
H
I
ii
1
1
3: R = -SO CH
4: R = -SO PhCH
iii
2
3
2
3
(
i) H
rt, 96%, (ii) methanesulfonyl chloride (1.5 mol. equiv) in a mixture
of pyridine and CH Cl (1:5, v/v), 0 °C ? rt, 72%, (iii) p-toluenesul-
fonyl chloride (1.5 mol. equiv) in a mixture of pyridine and CH Cl
1:5, v/v), 0 °C ? rt, 80%
2
, Pd(OH)
2
in a mixture of n-hexane and 2-propanol (1:4, v/v),
b H ,), 2.32ꢃ2.36 (4H, t, 2 ꢄ pal-C H ), 3.06 (3H, s, OSO CH ),
2
a
2
2
3
4.19 (1H, dd, 5.6 and 11.9 Hz, glycerol H1proR), 4.33 (1H, dd, 4.6
and 11.9 Hz, glycerol H1proS), 4.33 (1H, dd, 5.3 and 11.2 Hz, glyc-
erol H3proS or H3proR), 4.39 (1H, dd, 3.9 and 11.2 Hz, glycerol
2
2
2
2
1
3
(
3 C
H3proR or H3proS), 5.28 (1H, m, glycerol H2). C NMR (CDCl ) d
1
3 2 3
4.1 (pal-CH ), 22.7 (pal-CH CH ), 24.79 (pal-C b), 24.84 (pal-C
5
.1.1. 3-Benzyl-1,2-dipalmitoyl-sn-glycerol I
A purified syrup of 3-benzyl-sn-glycerol (250 mg, 1.37 mmol)
was dissolved in dry pyridine (15 mL) containing 4-(dimety-
lamino)pyridine (50 mg). To the stirred solution was added a CH
Cl
b), 29.1ꢃ29.7 (pal-(CH ) ꢄ 2), 31.9 (pal-CH ꢄ 2), 34.0 (pal-C ),
2
10
2
a
34.1 (pal-C ), 37.8 (-OSO CH ), 61.5 (glycerol sn-1), 66. 9 (glycerol
a
2
3
sn-3), 68.6 (glycerol sn-2), 172.9 (–C@O), 173.3 (–C@O). ESI-HRMS
+
4
2
-
(positive mode): 664.5181 (M+NH ). Elementary analysis calcu-
2
solution (5 mL) of palmitoyl chloride (942 mg, 2.5 ꢄ 1.37
lated for C36H74O NS = 664.518.
7
mmol), and the reaction mixture was stirred at room temperature
until the reaction was completed (2–6 h). The mixture was treated
5.1.4. 1,2-Dipalmitoyl-3-tosyl-sn-glycerol 14
with sat. NaHCO
3
aq. solution (1 mL), stirred at room temperature
The preceding crude product II (100 mg, 0.18 mmol) was dis-
solved in dry pyridine (1 mL) and reacted with p-toluenesulfonyl
chloride (71 mg, 1.5 ꢄ 0.37 mmol) for 22 h at room temperature.
Water was poured into the reaction mixture, and chloroform was
added. The mixture was washed with water and saturated brine.
for 3 h, and evaporated. The residue was diluted with a 10:1 (v/v)
mixture of toluene and ethyl acetate (60 mL), and the organic layer
washed with aqueous solutions of sat. NaCl, sat. NaHCO
3
, and again
sat. NaCl. After dried over MgSO , the organic layer was evaporated
4
to afford a solid (912 mg). Part of the crude solid (500 mg) was
recrystallized from hot ethanol and hexane, and the purified pro-
duct (378 mg) was identified as 3-benzyl-1,2-dipalmitoyl-sn-glyc-
erol I with the H NMR spectrum of an authentic sample (Aldrich,
CAS: 30403-51-1).
The organic phase was dried over MgSO , and concentrated. TLC
(silica gel, toluene/ethyl acetate = 10:1) showed the presence of
two compounds in the crude material (a major spot at Rf = 0.65
and a minor spot at Rf = 0.68). Purification with column chro-
matography on SiO2 in a mixture of toluene and ethyl acetate
4
1