S.M. Khersonsky, Y.-T. Chang / Carbohydrate Research 337 (2002) 75–78
77
further purification. NMR spectra were recorded on a
Gemini 300 MHz spectrometer. GC–MS data were
obtained on a Hewlett–Packard HP5971 GC–MS spec-
trometer (HP–5MS ultra low bleed 5%-diphenyl–95%-
dimethylsiloxane copolymer column, oven temperature
range 80–310 °C). HPLC–MS data were obtained on a
Hewlett–Packard HP1100 spectrometer equipped with
a C18 column (20×4 mm, 3 mm) using 5–95% MeCN
(over water) gradient. The identities of the compounds
were confirmed by electrospray-ionization mass spectra
(ESIMS), and the relative quantities were measured by
UV absorption at 230 nm. Silica filtrations were per-
off-white solid was thoroughly washed with 1:5
EtOAc–hexanes solvent mixture to remove methyl ben-
zoate. The white solid 5 was obtained in 91% yield (5.03
g). 1H NMR data were in agreement with those re-
ported in the literature.5 ESIMS: [M+H]+ Calcd,
261.1; Found, 261.1.
Preparation of (9)-1,2:4,5-di-O-isopropylidene-myo-
inositol (6).—Compound 3 (10 g, 21.4 mmol) was
suspended in 300 mL of MeOH and treated with
NaOMe (1.38 g, 25.6 mmol). The reaction mixture was
allowed to stir at reflux until all starting material had
reacted (solution turned clear). After an additional 30
min of stirring under reflux, the reaction mixture was
cooled to rt and diluted with CH2Cl2 (1500 mL). The
solution was then filtered through a plug of silica (4 cm
in height, 7 cm in diameter, 50 g). The silica was
washed with 150 mL of EtOAc, and the solvents were
evaporated in vacuo. The off-white solid was thor-
oughly washed with 1:5 EtOAc–hexanes solvent mix-
ture to remove methyl benzoate. The white solid 6 was
,
formed on Sorbent Technologies, 60 A silica gel (63–
200 mesh). TLC was done on SAI F254 precoated silica
gel plates (250-mm layer thickness).
Preparation of (9)-3,6-di-O-benzoyl-1,2:4,5-di-O-
isopropylidene-myo-inositol (3).—A mixture of myo-
inositol (25 g, 139 mmol), 2,2-dimethoxypropane (75
mL, 600 mmol), and p-toluenesulfonic acid monohy-
drate (0.5 g, 2.6 mmol) in DMF (100 mL) was heated
to 120 °C for 3 h until no more solid remained. The
reaction mixture was concentrated by vacuum distilla-
tion (50 °C at 20 barr), and Et3N (0.36 mL) was added
to the residual oil. The oil was diluted with 100 mL of
EtOAc and vacuum evaporated together with silica (40
g) to complete dryness. The resulting powder was
loaded on top of a plug of silica (5.5 cm in height, 8.5
cm in diameter, 120 g) and washed thoroughly with
EtOAc (700 mL). After the solvent was removed in
vacuo, pyridine (70 mL) and PhCOCl (50 mL, 0.42
mol) were added to the residual oil at 0 °C. The reac-
tion mixture was then allowed to stir at rt for 2 h. The
precipitate was collected (the initial filtrate was set aside
for further use) and washed with pyridine, water,
Me2CO, and Et2O to give 3 as a white solid in 26%
1
obtained in 94% yield (5.2 g). H NMR data were in
agreement with those reported in the literature.5 ES-
IMS: [M+H]+ Calcd, 261.1; Found, 261.1.
Preparation of (9)-6-O-benzoyl-1,2:4,5-di-O-iso-
propylidene-myo-inositol (7).—Compound 3 (5 g, 10.7
mmol) was completely dissolved in CH2Cl2 (350 mL)
and MeOH (200 mL). NaOH (0.17 g, 4.27 mmol) in
water (50 mL) was diluted with MeOH (100 mL) and
added to the reaction mixture over 20 min. The reac-
tion mixture was stirred overnight at rt, and the sol-
vents were removed in vacuo. The solid was dissolved
in EtOAc and vacuum evaporated together with silica
(10 g) to complete dryness. The resulting powder was
loaded on top of a plug of silica (4 cm in height, 7 cm
in diameter, 50 g) and washed with 5:1 hexanes–EtOAc
to elute methyl benzoate and starting material 3. The
silica gel was further washed with 1:1:1 solvent mixture
of hexanes–EtOAc–CH2Cl2 to elute 7, that, after evap-
oration of solvents, was obtained in 49% yield (1.9 g).
1
yield (16.9 g). H NMR data were in agreement with
those reported in the literature.5 ESIMS: [M+H]+
Calcd, 469.2; Found, 469.0.
Preparation of (9)-3,4-di-O-benzoyl-1,2:5,6-di-O-
isopropylidene-myo-inositol (2).—The initial pyridine
filtrate from the preparation of 3 was diluted with an
excess of water (1 L) and stirred at rt for 48 h. The
precipitate was collected, thoroughly washed with wa-
ter, and recrystallized from acetone to give 2 as a white
solid in 22% yield (14.2 g). 1H NMR data were in
agreement with those reported in the literature.5 ES-
IMS: [M+H]+ Calcd, 469.2; Found, 469.0.
Preparation of (9)-1,2:5,6-di-O-isopropylidene-myo-
inositol (5).—Compound 2 (10 g, 21.4 mmol) was
dissolved in MeOH (150 mL) and treated with NaOMe
(1.38 g, 25.6 mmol). The reaction mixture was allowed
to stir at reflux for 1.5 h, cooled down to rt, and diluted
with CH2Cl2 (750 mL). The solution was then filtered
through a plug of silica (4 cm in height, 7 cm in
diameter, 50 g). The silica was washed with EtOAc (150
mL), and the solvents were removed in vacuo. The
1
No trace of 8 was detected by GC–MS analysis. H
NMR (CDCl3): l 1.31, 1.38, 1.43, 1.59 (4s, each 3 H, 2
CMe2), 2.47 (d, 1 H, J 8.5 Hz, 3-OH), 3.51 (dd, 1 H,
J5,4 9.0 Hz, H-5), 3.98 (dd, 1 H, J4,3 10.0, H-4), 4.08
(ddd, 1 H, J3,2 4.5 Hz, H-3), 4.29 (dd, 1 H, J1,6 6.7 Hz,
H-1), 4.48 (dd, 1 H, J2,1 4.8 Hz, H-2), 5.47 (dd, 1 H, J6,5
11.0 Hz, H-6), 6.37 (dd, 2 H, Ph), 7.51 (dd, 1 H, Ph),
8.03 (d, 2 H, Ph); ESIMS: [M+H]+ Calcd, 365.2;
Found, 365.0; Anal. Calcd for C19H24O7: C, 62.63; H,
6.64. Found: C, 62.48; H, 6.73.
Acknowledgements
This project was supported by a New York Univer-
sity Research Challenge Fund Grant.