Improved synthesis of dicyclohexylidene protected quebrachitol and its use in the synthesis of l-chiro-inositol derivatives

Article abstract of DOI:10.1016/j.carres.2006.04.030

A modified synthesis of 1l-1,2:3,4-di-O-cyclohexylidene-5-O-methyl-chiro-inositol has been accomplished that improves the overall procedure, yield, and environmental aspects of its formation. Several inositol analogues have been prepared from this intermediate for testing as biosynthetic inhibitors of glycosyl-phosphatidylinositol (GPI) anchor formation.

Full text of DOI:10.1016/j.carres.2006.04.030

Carbohydrate Research 341 (2006) 1680–1684
Note
Improved synthesis of dicyclohexylidene protected quebrachitol
and its use in the synthesis of L-chiro-inositol derivatives
Sylvia M. Baarsa and John O. Hobergb,*
aSchool of Chemical and Physical Sciences, Victoria University of Wellington, Wellington, New Zealand
bDepartment of Chemistry, University of Wyoming, Laramie, WY, USA
Received 17 February 2006; received in revised form 12 April 2006; accepted 14 April 2006
Available online 15 May 2006
Abstract—A modified synthesis of 1L-1,2:3,4-di-O-cyclohexylidene-5-O-methyl-chiro-inositol has been accomplished that improves
the overall procedure, yield, and environmental aspects of its formation. Several inositol analogues have been prepared from this
intermediate for testing as biosynthetic inhibitors of glycosyl-phosphatidylinositol (GPI) anchor formation.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Keywords: Inositol protection; Quebrachitol; 1L-1,2:3,4-Di-O-cyclohexylidene-5-O-methyl-chiro-inositol; chiro-Inositol derivatives
Quebrachitol is a versatile cyclitol from the chiral pool
that has received considerable attention as a starting
material for the synthesis of natural products and bioac-
tive materials.1,2 An important derivative of quebrachi-
tol is dicyclohexylidene acetal 1, which has been used
in the synthesis of inositol phosphates,3,4 natural prod-
ucts,5–7 and as a chiral auxiliary.8 However, the usual
preparation of 1 from quebrachitol is an unattractive
procedure involving treatment with cyclohexanone in
benzene followed by extraction with chloroform.9–11
The yield for this procedure is a reported 55–72% using
recrystallized quebrachitol, and in the course of our
work yields below this range were obtained. Large
amounts of the cyclohexanone aldol condensation
by-product were also formed,10 complicating the purifica-
tion. Because we required a significant amount of 1 for
subsequent use, we began by designing a more environ-
mentally friendly synthesis involving treatment of queb-
rachitol, without prior recrystallization, with dimethoxy
cyclohexane acetal (Scheme 1). A 24 h reaction time was
followed by dilution in ethyl acetate, washing with
water, and crystallization of the crude material from
hexanes to give pure 1 in good yield. The mono-cyclo-
hexylidene derivative 2, formed as a by-product, was
found to be isolable by simple concentration of the
aqueous fractions followed by purification. This prepa-
ration of 1 is a highly robust procedure that has been
reproduced on the 65 g scale (isolated 1), thus allowing
for large-scale formation of this important intermediate.
Inositol is an essential precursor for the formation of
glycosyl-phosphatidylinositol (GPI) anchors found in
the majority of surface molecules in organisms. In addi-
tion, it has an essential role in the phoshatidylinositol
signal transduction pathways that controls many cell
cycle events. Examples that we are interested in include
protozoan flagellates12,13 and yeast cells such as Candida
albicans.14 Quebrachitol derivatives have been shown to
have small substrate recognition activity in these two
species,15,16 therefore, the synthesis of several new sub-
strates from inositol 1 were undertaken for additional
studies. Synthesis of inositols 5 and 617 involved stan-
dard chemistry. Initial protection of the remaining
hydroxyl in 1 as either the methyl ether or the benzoyl
ester gave 3 and 4, respectively, in excellent yields.
Subsequent removal of the cyclohexylidene protecting
groups under typical conditions18,19 gave 5 and 6 as
diprotected chiro-inositol derivatives (Scheme 2).
Synthesis of mono-methoxy inositol 7 was achieved as
shown in Scheme 3 via demethylation of 1, using a slight
*
Corresponding author. Tel.: +1 307 766 2795; fax: +1 307 766
2807; e-mail: hoberg@uwyo.edu
0008-6215/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2006.04.030

S. M. Baars, J. O. Hoberg / Carbohydrate Research 341 (2006) 1680–1684
1681
OH
OH
CH3O OCH3
OH
OCH3
OCH3
OH
OCH3
OH
p
TsOH
O
+
+
O
OH
OH
DMF
O
O
OH
O
O
HO
Quebrachitol
9%
71%
1
2
Scheme 1.
OR
O
OR
approximately 20% of 10 still present, which could be
completely removed following the subsequent transfor-
mation. Alternative mono-protection using tin chemis-
try, for example, has not been attempted to date.
Inositol 7 was obtained by methylation of 9 followed
by removal of the silyl and cyclohexylidene protecting
groups. Comparison of the 1H NMR spectrum of 7,
which contains an axial methoxy group, to that of queb-
rachitol containing an equatorial methoxy, further
established the regioselectivity in the formation of 9.
Improving the yield of the methylation reaction with
alternative reagents has also not been attempted at this
point.
In conclusion, an improved synthesis of 1L-1,2:3,4-
di-O-cyclohexylidene-5-O-methyl-chiro-inositol (1) has
been achieved involving benign reagents and a straight-
forward purification. This procedure would be amenable
to the large-scale preparation of 1. Using inositol 1, sev-
eral new derivatives of quebrachitol have been synthe-
sized for biological testing. Results of the biological
activity will be presented elsewhere.
OCH3
OCH3
OH
O
BzCl, Et3N, DMAP
HCl
O
OH
1
or
OH
HO
O
CH3I, NaH, DMF
5 R = CH3 71%
6 R = Bz 88%
3 R = CH3 94%
4 R = Bz 98%
Scheme 2.
modification of Shima’s procedure.4,6,7 It was envi-
sioned that subsequent treatment of diol 8 with tert-
butyldimethylsilyl chloride (TBSCl) would preferentially
give 9. Although an acceptable yield of 9 was obtained, a
2:1 ratio of isomers 9 and 10 was generated. The regio-
chemistry of this reaction was determined by benzoyl-
ation of a portion of the product mixture to give a
mixture of 11 and 12, which simplified the determination
of the regioisomeric ratio due to a downfield shift of the
signal attributed to the proton adjacent to the OBz
1
group. In the H NMR spectrum of the product mix-
ture, a doublet of doublets at 5.58 ppm (Jeq–eq = 4.94,
Jax–eq = 3.5 Hz) was attributed to the equatorial proton
vicinal to the OBz group in the major product 11, and a
1. Experimental
doublet of doublets at 5.41 ppm (Jax–ax = 9.6, Jax–eq
=
4.4 Hz) was attributed to the axial proton vicinal to
the OBz group in the isomeric product 12. The 2:1 ratio
of 11:12, and hence 2:1 ratio of 9:10 was obtained from
the ratio of the integrals of those two signals. Separation
via flash chromatography gave predominantly 9 with
1.1. General methods
Unless otherwise stated, the following conditions apply:
All reactions were performed under argon in oven-dried
1
AlCl3,
n-Bu4NI
Py, CH3CN, 65%
OH
O
OH
2
OH
OTBS
3
CH3O
O
O
OH
i. CH3I, NaH, 46%
OH
O
TBSCl,DMF
imidazole
75%
O
O
OH
O
ii.HCl, CH3OH, 89%
O
OH
HO
7
8
9
BzCl
DMAP
86%
OBz
TBSO
OR
OTBS
O
O
O
O
O
O
O
O
10 R=OH
12 R= Bz
11
Scheme 3.

1682
S. M. Baars, J. O. Hoberg / Carbohydrate Research 341 (2006) 1680–1684
glassware using standard syringe techniques. CH2Cl2,
Et3N, CH3CN, and CH3OH were distilled from calcium
hydride. Anhydrous N,N-dimethylformamide (DMF)
was purchased from Aldrich Chemical company and
used without further purification. All other reagents
were of commercial quality and distilled prior to use if
necessary. Reaction progress was monitored using alu-
minum-backed TLC plates pre-coated with silica
UV254 and visualized by UV radiation (254 nm), ceric
ammonium molybdate dip or anisaldehyde dip. Purifica-
tion of products via flash column chromatography was
conducted using a column packed with Silica Gel 60
(220–240 mesh) with the solvent systems as indicated.
1H and 13C spectra were recorded on a Varian Inova
at 300 and 75 MHz, respectively. Spectra were refer-
enced to solvent peaks (1H: residual CHCl3, DMSO,
or acetone; 13C: CDCl3, DMSO-d6, or acetone-d6).
Infrared spectra were obtained on a Biorad FTS-7 or
a Bruker Tensor 27 FTIR spectrometer. High-resolution
mass spectroscopy was recorded using a Mariner
electrospray time of flight spectrometer. Optical
rotations were measured using a Perkin–Elmer 241
polarimeter.
1.3. 1L-3,4:5,6-Di-O-cyclohexylidene-1,2-di-O-methyl-
chiro-inositol (3)
To a solution of 1 (460 mg, 1.30 mmol) in anhydrous
DMF (6 mL) at 0 ꢁC under argon was added NaH
(80% in mineral oil, 60 mg, 1.95 mmol). The resulting
suspension was stirred for 30 min after which time
CH3I (405 lL, 6.5 mmol) was added. The solution was
then warmed to rt and allowed to stir overnight. The
reaction was quenched by the addition of H2O, and
the mixture was extracted with Et2O (2·). The combined
organic fractions were then washed with 5% NaHCO3,
H2O, and brine, dried (MgSO4), and the solvents
removed under reduced pressure. The residues were
purified by gradient flash column chromatography
(1:10!1:5, EtOAc/petroleum ether) to yield 3 as an oil
that solidified upon standing, 450 mg (94%): [a]D ꢀ50
1
(c 0.18, CH2Cl2); H NMR (300 MHz, CDCl3) d 4.39–
4.26 (m, 2H), 3.83 (dd, 1H, J = 4.1, 3.8 Hz), 3.74–3.68
(m, 2H), 3.59 (dd, 1H, J = 8.0, 1.5 Hz), 3.54 (s, 3H),
3.52 (s, 3H), 1.84–1.32 (m, 20H); 13C NMR (75 MHz,
CDCl3) d 112.0, 110.4, 79.0, 78.6, 78.2, 76.2, 76.1,
75.6, 59.5, 57.8, 37.6, 36.3, 36.2, 34.5, 24.8 (2C), 23.7,
23.5, 23.4, 23.3; IR (neat) 2934, 2860, 1449, 1279,
1100, 907, 830, 727 cmꢀ1; ESIMS m/z calcd for
C20H33O6 [M+H+]: 369.2272. Found: 369.2267.
1.2. 1L-1,2:3,4-di-O-cyclohexylidene-5-O-methyl-chiro-
inositol (1)
To a stirred suspension of quebrachitol (50 g, 0.25 mol)
in DMF (400 mL) and dimethoxycyclohexane (320 mL,
2.06 mol), under argon, was added p-TsOHÆH2O (8.0 g,
0.04 mol) at rt. The mixture was then heated to 85 ꢁC
and stirred for 18 h, and then to 105 ꢁC for a further
4.5 h. The reaction was cooled, treated with Et3N
(7 mL, 0.05 mol), and diluted with EtOAc (1 L). The
solution was washed with H2O (3 · 500 mL), and the
combined H2O washings were extracted with Et2O
(2 · 300 mL). The combined organic fractions were
washed with brine, dried (MgSO4), and the solvents re-
moved in vacuo to yield a yellow solid, which was
recrystallized from petroleum ether (ca. 500 mL) to yield
a first crop of 1 as white crystals (45.5 g). Two further
crystallizations from petroleum ether gave a total yield
of 64.8 g (71%) of 1: mp 117–119 ꢁC (lit.:9 mp 117–
119 ꢁC); [a]D ꢀ18 (c 0.1, CH2Cl2, lit.:9 [a]D ꢀ18 (c 0.1,
CH2Cl2)); 1H NMR (300 MHz, CDCl3) d 3.80–4.24
(m, 3H), 3.71–3.56 (m, 3H), 3.56 (s, 3H), 2.80 (s, 1H)
1.76–1.32 (m, 20H); 13C NMR (75 MHz, CDCl3) d
112.7, 110.6, 79.3, 79.0, 78.3, 76.4, 75.9, 69.5, 58.2,
38.0, 36.7, 34.9, 25.2, 24.1, 23.9, 23.8, 23.7; IR (neat)
3499, 2940, 1468, 1336, 1098, 1040, 973, 902, 769,
648 cmꢀ1; ESIMS m/z calcd for C19H31O6 [M+H+]:
355.2115. Found: 355.2106.
1.4. 1L-1,2-Di-O-methyl-chiro-inositol (5)
A solution of 3 (250 mg, 0.68 mmol) was stirred over-
night at rt under air in 3 mL of 10% aq HCl in CH3OH.
After this time, solid NaHCO3 was added until efferves-
cence was no longer observed, and the solvents then re-
moved under reduced pressure. The residue was purified
by flash column chromatography (1:6, CH3OH/CH2Cl2)
to yield 5, 120 mg (71%), as an oil which crystallized
upon standing: mp 138–140 ꢁC; [a]D ꢀ56 (c 0.06,
CH3OH);20 1H NMR (300 MHz, DMSO) d 4.86 (d,
1H, J = 3.9 Hz), 4.60 (d, 1H, J = 4.2 Hz), 4.55 (d, 1H,
J = 3.7 Hz), 4.45 (d, 1H, J = 4.7 Hz), 3.80 (m, 1H),
3.53 (m, 1H), 3.30 (s, 3H), 3.29 (s, 3H), 3.26 (m, 3H),
3.15 (dd, 1H, J = 9.3, 2.7 Hz); 13C NMR (75 MHz,
DMSO) d 81.3, 78.6, 73.5, 72.7, 71.0, 69.1, 58.9, 57.7;
IR (neat) 1340, 2932, 2854, 1448, 1365, 1278, 1105,
1026, 927, 907 cmꢀ1; ESIMS m/z calcd for C8H17O6
[M+H+]: 209.1019. Found: 209.1009.
1.5. 1L-1-O-Benzoyl-3,4:5,6-di-O-cyclohexylidene-2-O-
methyl-chiro-inositol (4)
Benzoyl chloride (260 lL, 2.32 mmol) and DMAP (7 mg,
0.06 mmol) were added to a solution of 1 (412 mg,
1.16 mmol) in CH2Cl2 (5.5 mL) and Et3N (645 lL,
4.66 mmol) at 0 ꢁC under argon, and then stirred for five
days at rt. H2O was then added and the mixture extracted
with CH2Cl2 (3·). The combined organic fractions were
Also isolated, by concentration of the aqueous por-
tions, EtOAc extraction, and crystallization, was 9% of
the mono-acetal 1L-1,2-O-cyclohexylidene-5-O-methyl-
chiro-inositol 2.

S. M. Baars, J. O. Hoberg / Carbohydrate Research 341 (2006) 1680–1684
1683
washed with brine, dried (MgSO4), and the solvents re-
moved under reduced pressure to yield an orange oil that
was purified by flash chromatography (1:15, EtOAc/
petroleum ether) to yield 4 as a white solid, 522 mg
(98%): mp 79–81 ꢁC; [a]D ꢀ8.3 (c 0.1, CH2Cl2); 1H
NMR (300 MHz, CDCl3) d 8.04 (m, 2H), 7.59 (m, 1H),
7.46 (m, 2H), 5.82 (dd, 1H, J = 3.7, 3.2 Hz), 4.42 (m,
2H), 3.90–3.68 (m, 3H), 3.46 (s, 3H), 1.85–1.35 (m,
20H); 13C NMR (75 MHz, CDCl3) d 165.5, 133.3, 129.9,
129.5, 128.4, 112.6, 111.0, 79.2, 77.9, 76.4, 76.0, 75.7,
70.0, 58.2, 37.9, 36.5, 36.3, 34.8, 25.0, 24.9, 23.9, 23.6
(2C), 23.5; IR (neat) 2936, 2860, 1724, 1450, 1269, 1107,
1070, 908, 731 cmꢀ1; ESIMS m/z calcd for C26H35O7
[M+H+]: 459.2377. Found: 459.2383.
fied by gradient flash chromatography (1:10!1:3,
EtOAc/petroleum ether,) to give 624 mg (65%) of 8 as
an amorphous white solid: 1H NMR (300 MHz, CDCl3)
d 4.39 (m, 2H), 4.19 (m, 1H), 4.13 (m, 1H), 3.78–3.63
(m, 2H), 2.77 (d, 1H, J = 2.9 Hz), 2.73 (d, 1H,
J = 2.4 Hz), 1.85–1.36 (m, 20H); 13C NMR (75 MHz,
CDCl3) d 113.1, 110.9, 78.7, 78.1, 77.3, 75.9, 71.0, 70.1,
38.0, 36.7 (2C), 34.8, 25.2, 25.1, 24.2, 23.9, 23.8, 23.7; IR
(neat) 3460, 2937, 2857, 1368, 1270, 1095, 1046, 909,
730 cmꢀ1; ESIMS m/z calcd for C18H29O6 [M+H+]:
341.1959. Found: 341.1973.
1.8. 1L-1,2:3,4-Di-O-cyclohexylidene-5-O-(tert-butyldi-
methylsilyloxy)-chiro-inositol (9)
1.6. 1L-1-O-Benzoyl-2-O-methyl-chiro-inositol (6)
To a solution of the diol 8 (130 mg, 0.38 mmol) in DMF
(650 lL) at 0 ꢁC were added imidazole (52 mg,
0.76 mmol) and TBSCl (63 mg, 0.42 mmol). The solu-
tion was then allowed to warm to rt and stir overnight,
after which it was diluted with Et2O, washed with satd
aq NaHCO3, H2O, and brine, dried (MgSO4), and the
solvents removed under reduced pressure. The product
9 was isolated by flash column chromatography (1:5,
EtOAc/petroleum ether) as an oil, 130 mg (75%, as a
mixture of 9 and 10). Further gradient flash chromatog-
raphy (1:20!1:5, EtOAc/petroleum ether) allowed par-
tial separation of the isomers, to yield 9 contaminated
To a solution of 4 (80 mg, 0.18 mmol) in wet acetone
(1 mL) at rt under air was added aqueous HCl (four
drops) and the reaction stirred for 2 days, when TLC
analysis revealed 100% conversion. Solid NaHCO3
(50 mg) was added, and the solvents removed under
reduced pressure. The residue was purified by flash col-
umn chromatography (1:10, CH3OH/CH2Cl2) to yield
6, 46 mg (88%) as a crystalline solid: mp 144–149 ꢁC.
[a]D ꢀ48 (c 0.06, CH3OH or acetone);ꢀ 1H NMR
(300 MHz, (CD3)2CO) d 8.00 (m, 2H), 7.64 (m, 1H),
7.51 (m, 2H), 5.63 (m, 1H), 4.65 (d, 1H, J = 3.4 Hz),
4.32 (br s, 1H), 4.24 (br s, 1H), 4.15 (br s, 1H), 4.06
(m, 1H), 3.66 (m, 3H), 3.47 (dd, 1H, J = 9.5, 3.2 Hz),
3.38 (s, 3H); 13C NMR (75 MHz, (CD3)2CO) d 165.6,
133.9, 130.8, 130.2, 129.3, 80.5, 74.1, 73.8, 72.4, 70.6,
70.5, 58.1; IR (neat) 3336, 2928, 1699, 1450, 1178,
1096, 1070, 1025, 751, 708 cmꢀ1; ESIMS m/z calcd for
C14H19O7 [M+H+]: 299.1125. Found: 299.1133.
1
with 20% of the isomer: H NMR (300 MHz, CDCl3)
d 4.38–4.28 (m, 2H), 4.11 (m, 1H), 4.01 (dd, 1H,
J = 8.3, 5.6 Hz), 3.60–3.53 (m, 2H), 2.99 (br s, 1H),
1.72–1.35 (m, 20H), 1.91 (s, 9H), 1.18 (s, 3H), 0.16 (s,
3H); 13C NMR (75 MHz, CDCl3) d 112.0, 110.1, 78.7,
78.0, 76.5, 75.7, 71.6, 71.2, 37.8, 36.8, 36.0, 34.6, 25.7
(3C), 25.0, 24.9, 23.8, 23.7, 23.5, 23.4, 18.4, ꢀ3.9,
ꢀ4.6; IR (neat) 3544, 2932, 2856, 1449, 1211, 1099,
1084, 935, 907, 837, 779, 731 cmꢀ1; ESIMS m/z calcd
for C24H43O6Si [M+H+]: 455.2829. Found: 455.2822.
1.7. 1L-1,2:3,4-Di-O-cyclohexylidene-chiro-inositol (8)
Dicyclohexylidene quebrachitol 1 (1.00 g, 2.82 mmol)
was dissolved in anhydrous CH3CN (25 mL) and cooled
to 0 ꢁC. Pyridine (2.3 mL, 28.2 mmol), n-Bu4NI (7.0 g,
19.0 mmol), and AlCl3 (3.8 g, 28.2 mmol) were then
added in that order. The mixture was heated to 62 ꢁC
overnight, cooled to rt, quenched by careful addition of
H2O (60 mL) and extracted with CH2Cl2 (3 · 60 mL).
The organic fractions were combined and washed with
brine, dried (MgSO4), and the solvents removed under
reduced pressure to yield a white solid, which was subse-
quently re-dissolved in a minimum amount of CH2Cl2.
To this solution was added Et2O (100 mL) and the result-
ing white precipitate removed by vacuum filtration. The
filtrate was reduced in vacuo to yield an oil that was puri-
1.9. 1L-1-O-Methyl-3,4:5,6-di-O-cyclohexylidene-2-O-
(tert-butyldimethylsilyloxy)-chiro-inositol
To a solution of 9 (40 mg, 0.09 mmol, containing ca.
20% of the isomer 10) in DMF (0.5 mL) was added
NaH (80% in mineral oil, 10 mg, 0.29 mmol). The result-
ing suspension was stirred for 10 min after which time
CH3I (50 lL, 0.80 mmol) was added. The solution was
then warmed to rt and allowed to stir for 20 h. H2O
was added and the mixture was extracted with Et2O
(3·). The combined organic fractions were washed with
5% NaHCO3, H2O, and brine, dried (MgSO4), and the
solvents removed under reduced pressure. The residue
was purified by flash column chromatography (1:20,
EtOAc/petroleum ether) to yield 19 mg (46%) of the
1
desired methoxylated inositol an oil: H NMR (300 MHz,
ꢀ The optical rotation for this compound, which has been checked on
multiple occasions, is in disagreement with published data17 (+50.1);
we suggest that the +50.1 is a typographical error.
CDCl3) d 4.32–4.25 (m, 2H), 4.60 (dd, 1 H J = 9.0,
4.2 Hz), 3.68–3.60 (m, 2H), 3.53 (s, 3H), 3.49 (m, 1H),

1684
S. M. Baars, J. O. Hoberg / Carbohydrate Research 341 (2006) 1680–1684
1.70–1.30 (m, 20H), 0.93 (s, 9H), 0.17 (s, 3H), 0.14 (s,
3H); 13C NMR (75 MHz, CDCl3) d 111.6, 110.3, 81.3,
79.3, 77.1, 76.9, 76.4, 75.9, 71.6, 60.6, 37.9, 36.8, 36.0,
34.9, 25.8 (3C), 25.1, 25.0, 23.9, 23.8, 23.6, 23.5, 18.4,
ꢀ4.5, ꢀ5.0; IR (neat) 2933, 2856, 1449, 1366, 1252,
1104, 907, 837, 778, 731 cmꢀ1; ESIMS m/z calcd for
C25H45O6Si [M+H+]: 469.2979. Found: 469.2973.
References
1. Potter, B. V. L.; Lampe, D. Angew. Chem., Int. Ed. Engl.
1995, 34, 1933–1972.
2. Kiddle, J. J. Chem. Rev. 1995, 95, 2189–2202.
3. Akiyama, T.; Takechi, N.; Ozaki, S.; Shiota, K. Bull.
Chem. Soc. Jpn. 1992, 65, 366–372.
4. Akiyama, T.; Takechi, N.; Ozaki, S. Tetrahedron Lett.
1991, 31, 1433–1434.
5. Barton, D. H. R.; Bath, S.; Billington, D. C.; Gero, S. D.;
Quiclet-Sire, B.; Samadi, M. J. Chem. Soc., Perkin Trans.
1 1995, 1551–1558.
6. Akiyama, T.; Shima, H.; Ohnare, M.; Okazaki, T.; Ozaki,
S. Bull. Chem. Soc. Jpn. 1993, 66, 3760–3767.
7. Akiyama, T.; Shima, H.; Ozaki, S. Tetrahedron Lett. 1991,
32, 5593–5596.
8. Akiyama, T.; Nishimoto, H.; Kuwata, T. Bull. Chem. Soc.
Jpn. 1994, 67, 180–188.
9. Mercier, D.; Barnett, J. E. G.; Gero, S. D. Tetrahedron
1969, 25, 5681–5687.
10. Angyal, S. J.; Irving, G. C.; Rutherford, D.; Tate, M. E.
J. Chem. Soc. 1965, 6662–6664.
11. Gero, S. D. Tetrahedron Lett. 1966, 6, 591–595.
12. McConville, M. J.; Ferguson, M. A. J. Biochem J. 1993,
294, 305–324.
13. McConville, M. J.; Menon, A. K. Mol. Membr. Biol. 2000,
17, 1–16.
14. Trinel, P.-A.; Plancke, Y.; Gerold, P.; Jouault, T.;
Delplace, F.; Schwarz, R. T.; Strecker, G.; Poulain, D.
J. Biol. Chem. 1999, 274, 30520–30526.
1.10. 1L-1-O-Methyl-chiro-inositol (7)
The fully protected L-chiro-inositol derivative above
(45 mg, 0.10 mmol) was dissolved in 2 mL of 10% HCl
in CH3OH and stirred at rt for 4 h. The solvents were
then removed under reduced pressure and the residue
purified by washing with hexanes and EtOAc and then
purified by flash column chromatography (1:3!1:2,
CH3OH/CH2Cl2) to yield 17 mg (89%) of 7: [a]D ꢀ57
(c 0.05, D2O);21 1H NMR (300 MHz, DMSO-d6) d
4.76 (d, 1H, J = 3.9 Hz), 4.49 (d, 1H, J = 4.1 Hz), 4.47
(d, 1H, J = 3.9 Hz), 4.41 (d, 1H, J = 3.9 Hz), 4.39 (d,
1H, J = 3.4 Hz), 3.77 (dd, 1H, J = 6.7, 3.4 Hz), 3.53–
3.43 (m, 1H), 3.33–3.16 (m, 4H), 3.32 (s, 3H); 13C
NMR (75 MHz, DMSO-d6) d 82.9, 73.5, 73.3, 71.2,
70.8, 69.4, 59.2 cmꢀ1; ESIMS m/z calcd for C7H18O6N
½M þ NH4þꢁ: 212.1129. Found: 212.1126.
15. Mongan, T. P.; Ganapasam, S.; Hobbs, S. B.; Seyfang, A.
Mol. Biochem. Parasitol. 2004, 135, 133–141.
16. Jin, J. H.; Seyfang, A. Microbiology 2003, 149, 3371–3381.
17. Miethchen, R.; Neitzel, K.; Weise, K.; Michalik, M.;
Reinke, H.; Faltin, F. Eur. J. Org. Chem. 2004, 2010–
2018.
Acknowledgments
This work was supported in part by the Foundation for
Research Science and Technology of New Zealand.
18. Cousins, G. S.; Falshaw, A.; Hoberg, J. O. Carbohydr.
Res. 2003, 338, 995–998.
19. Paulsen, H.; von Deyn, W.; Ro¨ben, W. Liebigs Ann.
Chem. 1984, 433–449.
20. Angyal, S. J.; Gallagher, R. T.; Pojer, P. M. Aust. J. Chem.
1976, 29, 219–222.
21. Lit. for the enantiomer, 1D-1-O-methyl-chiro-inositol:
[a]D +59 (c 1.3, D2O); Jaramillo, C.; Chiara, J.-L.;
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.carres.
2006.04.030.
´
Martın-Lomas, M. J. Org. Chem. 1994, 59, 3135–3141.