Synthesis of S-alkylated sulfonium-ions and their glucosidase inhibitory activities against recombinant human maltase glucoamylase

Article abstract of DOI:10.1016/j.carres.2007.01.018

The syntheses of nine S-alkylated, cyclic sulfonium-ions with varying alkyl chain lengths, as mimics of N-alkylated imino sugars, and their glucosidase inhibitory activities are described. The target compounds were synthesized by alkylation of 2,3,5-tri-O-benzyl-1,4-anhydro-4-thio-d-arabinitol at the ring sulfur atom using various alkyl halides, followed by deprotection using boron trichloride. Enzyme inhibitory assays against recombinant human maltase glucoamylase (MGA), a critical enzyme in the small intestine involved in the breakdown of glucose oligosaccharides into glucose itself, shows that they are effective inhibitors of MGA with K_i values ranging from 6 to 75 μM.

Full text of DOI:10.1016/j.carres.2007.01.018

Carbohydrate Research 342 (2007) 901–912
Synthesis of S-alkylated sulfonium-ions and their glucosidase
inhibitory activities against recombinant
human maltase glucoamylase
Sankar Mohan,a Lyann Sim,b David R. Roseb and B. Mario Pintoa,*
aDepartment of Chemistry, Simon Fraser University, Burnaby, BC, Canada V5A 1S6
bDepartment of Medical Biophysics, University of Toronto and Division of Cancer Genomics and Proteomics,
Ontario Cancer Institute, Toronto, Ont., Canada M5G 1L7
Received 25 October 2006; received in revised form 16 January 2007; accepted 31 January 2007
Available online 7 February 2007
Abstract—The syntheses of nine S-alkylated, cyclic sulfonium-ions with varying alkyl chain lengths, as mimics of N-alkylated imino
sugars, and their glucosidase inhibitory activities are described. The target compounds were synthesized by alkylation of 2,3,5-tri-O-
benzyl-1,4-anhydro-4-thio-D-arabinitol at the ring sulfur atom using various alkyl halides, followed by deprotection using boron
trichloride. Enzyme inhibitory assays against recombinant human maltase glucoamylase (MGA), a critical enzyme in the small intes-
tine involved in the breakdown of glucose oligosaccharides into glucose itself, shows that they are effective inhibitors of MGA with
Ki values ranging from 6 to 75 lM.
ꢀ 2007 Elsevier Ltd. All rights reserved.
Keywords: Glucosidase inhibitors; Maltase glucoamylase; S-Alkylated sulfonium-ions; N-Alkylated imino sugars
1. Introduction
deoxynojirimycin (5) are more potent inhibitors of
porcine liver a-glucosidase I than the parent compound,
1-deoxynojirimycin (DNJ, 1).5 Although the exact role
of the alkyl chain in increasing inhibition is not well
understood, biochemical characterization of N-alkyl-
ated imino sugars indicated that the lipophilic alkyl
chains play a role in the cellular uptake of the inhibitor.6
In a recent study of the molecular requirements of these
compounds for glycosidase inhibition, it was reported
that the protonated imino sugar mimics the charge on
the proposed oxacarbenium-ion transition state formed
during hydrolysis of the natural substrate.7 In addition,
it has been proposed that the deprotonation of the imino
sugars in the slightly basic pH (7.1) of the ER, resulting
in a loss of cationic properties, could be one of the pos-
sible reasons for the much lower in vivo glycosidase
activity exhibited by the N-butyl compound 3 than in
the in vitro studies.7 Hence, it would be of interest to
design inhibitors that incorporate a permanent positive
charge at a suitable position as possible substitutes for
the N-alkylated imino sugars.
Over the past few decades, much research has focused
on understanding the functions of glycosidase and gly-
cosyltransferase enzymes due to their vital roles in living
systems. Such functions can be revealed by modifying or
blocking biological processes using specific inhibitors.
Inhibitors of these two major classes of enzymes have
many therapeutic applications as both the enzyme-cata-
lyzed biosynthesis and hydrolysis of complex carbo-
hydrates are biologically widespread processes in living
systems.1
N-Alkylated imino sugars have been extensively
studied in recent years due to their potential use as
glycosidase inhibitors. A general observation is that
N-alkylation increases the glycosidase inhibitory activity
of the parent imino sugar.2–4 For example, N-methyl-
(2), N-butyl- (3), N-decyl- (4), and N-(7-oxadecyl)-1-
*
Corresponding author. Tel.: +1 604 291 4152; fax: +1 604 291
4860; e-mail: bpinto@sfu.ca
0008-6215/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2007.01.018

902
S. Mohan et al. / Carbohydrate Research 342 (2007) 901–912
substantial oxacarbenium-ion character, by simple anal-
OH OH
OH OH
ogy with the well-studied mechanism of glycosidases,16
our target compounds bearing a permanent positive
charge on the sulfur atom could provide the necessary
electrostatic interactions in the enzyme active site to-
gether with the attached lipophilic alkyl chains required
for substrate recognition.
OH
HO
OH
OH
X
OSO3
NH OSO3
HO
HO
N
R
HO
OH
HO
OH
1 R=H
2 R=methyl
6 X=S
7 X=Se
8
3 R=n-butyl
4 R=n-decyl
5 R=7-oxadecyl
2. Results and discussion
Sulfonium ions A could be synthesized by alkylation of
an appropriately protected anhydrothio-D-arabinitol B
at the ring sulfur atom using alkylating agents (18–23,
25, and 27), corresponding to C (Scheme 1).
Our working hypothesis is to synthesize sulfonium-
ions in order to increase the required electrostatic
interactions between the inhibitor and an active-site car-
boxylate residue. Of relevance here, we8,9 and others10
have reported the synthesis of salacinol (6), a naturally
occurring glucosidase inhibitor isolated from the roots
of Salacia reticulata. Other structure–activity relation-
ship studies of salacinol such as the syntheses and glyco-
sidase inhibitory activities of selenium (7)11–13 and
nitrogen (8)14 analogues of salacinol, and D-lyxitol and
D-ribitol analogues of salacinol,15 indicated that the
D-arabinitol configuration in the heterocyclic ring dis-
played by salacinol (6) is critical for its activity. Hence,
we have chosen the 1,4-anhydro-4-thio-D-arabinitol
moiety as the sugar-based head group in the compounds
of interest in the present study and now report the syn-
theses and glycosidase inhibitory properties of a series of
S-alkylated sulfonium ions (9–17).
The required alkyl bromides 18–21 and alkyl iodides
22 and 23 were commercially available. Alkyl iodides
25 and 27 were synthesized in three steps starting from
commercially available 6-bromohexan-1-ol (24) and 9-
bromononan-1-ol (26), respectively, as shown in Scheme
2. Bromo alcohol 24 was treated with NaOEt in reflux-
ing EtOH for 5 h to produce the ethoxy alcohol that was
subsequently converted into the corresponding mesy-
late. The crude mesylate was then treated with NaI in
dry acetone to produce the corresponding iodide 25 that
was purified by chromatography and used immediately
in the alkylation reaction. Similarly, iodide 27 was pre-
pared from bromo alcohol 26, except that NaOMe in
refluxing MeOH was used in the first step (Scheme 2).
The required 1,4-anhydro-2,3,5-tri-O-benzyl-4-thio-D-
arabinitol (28), corresponding to B, was prepared from
L-xylose, as described by Satoh et al.17 for the synthesis
of its enantiomer.
OR
R
n
n
S
Cl
S
X
Initially, the S-alkylation of compound 28 with
n-tetradecyl bromide 19 was examined in order to opti-
mize the reaction conditions for the alkylation reaction.
At first, the reaction was carried out at room tempera-
ture in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), with
28 and 19 present in a 1:1 ratio. After 24 h of continuous
stirring in a sealed tube at room temperature, there was
no product formation observed, as indicated by TLC.
Increasing the reaction temperature to 90 ꢁC and stirring
the reaction mixture for 24 h in a sealed tube resulted in
30% of the desired product 29 that was purified by col-
umn chromatography. As S-alkylated sulfonium ion 29
formed in this reaction was deemed to be unstable due
to the ring opening reaction by the bromide counterion,
after column chromatographic purification, product 29
was treated immediately with AgOTf (1 equiv) in
CH2Cl2 to exchange the bromide counterion with tri-
flate, resulting in the stable S-alkylated sulfonium ion
30 (Scheme 3).
HO
HO
HO
OH
OH
HO
16 R=CH2CH3; n=5
17 R=CH3; n=8
9 R=CH3; X=OTf; n=12
10 R=CH3; X=Cl; n=2
11 R=CH3; X=Cl; n=4
12 R=CH3; X=Cl; n=6
13 R=CH3; X=Cl; n=12
14 R=CH3; X=Cl; n=16
15 R=CH(CH3)2; X=Cl; n=1
It is worthy of note that the target compounds could
also act as glucosyltransferase inhibitors by analogy with
their N-alkylated imino sugar counterparts. Thus, N-
butyl-1-deoxynojirimycin (3) was found to be not only an
a-glucosidase I inhibitor but also a potent inhibitor of
ceramide-specific glucosyltransferase, a key enzyme
involved in the biosynthesis of glycosphingolipids.7
Increases in alkyl chain lengths have led to increases in
transferase inhibitory activities of these N-alkylated imi-
no sugars, suggesting that a hydrophobic environment is
part of substrate recognition. Since the glycosyl transfer
is also believed to proceed through a transition-state with
Attempts were made to improve the yield of this reac-
tion by the addition of AgOTf (1 equiv with respect to
alkyl bromide) initially to the reaction mixture in HFIP.
Surprisingly, there was no product formation, and

S. Mohan et al. / Carbohydrate Research 342 (2007) 901–912
903
R
n
S
L
S
R
PO
PO
L
n
OP
PO
OP
PO
C
B
A
L = leaving group
P = protecting group
18 R=CH3; L=Br; n=6
19 R=CH3; L=Br; n=12
20 R=CH3; L=Br; n=16
21 R=CH(CH3)2; L=Br; n=1
22 R=CH3; L=I; n=2
23 R=CH3; L=I; n=4
25 R=OCH2CH3; L=I; n=5
27 R=OCH3; L=I; n=8
Scheme 1.
i) NaOEt / EtOH / reflux
ii) MsCl / Et3N /
CH2Cl2
HO
I
Br
OEt
iii) NaI / dry acetone /
60 °C
24
25
60% (3 steps)
i) NaOMe / MeOH / reflux
ii) MsCl / Et3N /
CH2Cl2
HO
Br
I
OMe
iii) NaI / dry acetone /
60 °C
27
26
59% (3 steps)
Scheme 2.
rt / 24 h
No reaction
S
HFIP
Br
12
BnO
12
12
90 °C / 24 h
AgOTf / CH2Cl2
OBn
BnO
Br
OTf
S
S
19
BnO
28
BnO
30%
OBn
BnO
BnO
OBn
29
30
Scheme 3.
decomposition of the starting material 28 was observed
after stirring at 90 ꢁC for 24 h, as indicated by TLC.
Based on a literature precedent,18 the reaction was
repeated with AgBF4 (1 equiv with respect to alkyl
bromide), instead of AgOTf, in refluxing CH3CN;
alkylated product 31 was obtained in 74% yield, with
15% of the unreacted starting material 28 being recov-
ered. After optimizing the reaction conditions with com-
pound 28 and bromide 19, a series of S-alkylated
sulfonium ions (32–34) were synthesized analogously
in 65–79% yield using alkyl bromides 18, 20, and 21
(Scheme 4).
It was also observed that alkyl iodides 22 and 23
reacted with compound 28 smoothly to produce the cor-
responding S-alkylated sulfonium ions 35 and 36 in 90%
and 95% yield, respectively. Similarly, sulfonium ions 37
and 38 with alkoxy substitutions at the end of the alkyl
chain were synthesized in 90% and 89% yield, respec-
tively, using the corresponding iodides 25 and 27 as
the alkylating agents (Scheme 5).

904
S. Mohan et al. / Carbohydrate Research 342 (2007) 901–912
AgOTf / HFIP /
90 °C / 24 h
No product
S
Br
12
BnO
12
OBn
BnO
AgBF4 / dry CH3CN /
65 °C / 17 h
S
BF4
19
28
BnO
74%
OBn
R
BnO
31
n
AgBF4 / dry CH3CN /
65 °C / 17 h
S
BF4
S
R
BnO
BnO
Br
n
65-79%
OBn
BnO
BnO
OBn
28
18 R=CH3; n=6
20 R=CH3; n=16
21 R=CH(CH3)2; n=1
32 R=CH3; n=6
33 R=CH3; n=16
34 R=CH(CH3)2; n=1
Scheme 4.
n
AgBF4 / dry CH3CN /
65 °C / 17 h
S
S
BF4
BnO
I
n
BnO
OBn
BnO
OBn
BnO
28
22 n=2
23 n=4
35 n=2 90%
36 n=4 95%
OR
n
AgBF4 / dry CH3CN /
65 °C / 17 h
S
S
BF4
OR
BnO
I
n
BnO
OBn
BnO
OBn
BnO
28
25 R=CH2CH3; n=5
27 R=CH3; n=8
37 R=CH2CH3; n=5 90%
38 R=CH3; n=8 89%
Scheme 5.
The alkylation reactions proceeded stereoselectively
and we did not observe (by TLC) the formation of the
diastereomers at the stereogenic sulfur atom in any
detectable amounts; the purified products were found
(Fig. 1). The stereochemistry at the stereogenic sulfo-
nium center in sulfonium ions 30–35 and 37 was also as-
signed to have an anti relationship between the alkyl side
chain and the C-4 substituent on the anhydroarabinitol
moiety, by analogy with compounds 36 and 38, and
based on our previous, extensive work with alkylation
of anhydrothio-D-arabinitol derivatives.
Initial attempts to remove the benzyl protecting
groups on the S-alkylated sulfonium ions using 10%
Pd/C in MeOH and also in a 1:1 mixture of AcOH/
MeOH were not successful. The benzyl groups of
2,3,5-tri-O-benzylsulfonium-ions (30–38) were therefore
1
to be only one isomer, as indicated by H NMR spec-
troscopy. The absolute stereochemistry at the stereo-
genic sulfur center in 36 and 38 was established by
means of 1D-NOESY experiments (Fig. 1). Correlation
between H-10 and H-4 and also a correlation between
H-20 and H-4 confirmed the anti relationship between
the alkyl side chain and the C-4 substituent on the anhy-
droarabinitol moiety in both of these compounds

S. Mohan et al. / Carbohydrate Research 342 (2007) 901–912
905
2'
2'
6'
4'
4'
6'
8'
1'
H2C
1'
H2C
CH2
CH2
O
3'
5'
3'
5'
7'
9'
H
H
BF4
BF4
S
S
1
1
5
5
4
4
2
2
BnO
BnO
3
3
OBn
BnO
OBn
BnO
36
38
Figure 1. NOE correlations observed in the 1D-NOESY spectra of compounds 36 and 38.
removed by treatment with boron trichloride at ꢀ78 ꢁC
in CH2Cl2. During the course of deprotection, some of
the tetrafluoroborate counterion was exchanged with
chloride ion. Similar results were also observed in previ-
ous work from our laboratory.19 Hence, in the cases of
sulfonium ions 31–38, after removal of the benzyl
groups, the products were subsequently treated with
Amberlyst A-26 resin (chloride form) to completely
exchange the tetrafluoroborate counterion with chloride
ion to give compounds 10–17, respectively (Scheme 6).
In the case of compound 30, the deprotected sulfonium
ion 9 was obtained without any counterion exchange,
probably due to the shorter reaction time.
R
R
n
n
i) BCl3/CH2Cl2/
BF4
S
S
Cl
-78 °C
BnO
HO
ii) Ion Exchange
(Amberlyst A-26)
OBn
OH
BnO
HO
Finally, we comment on the inhibitory properties of
9–17 against recombinant human maltase glucoamylase
(MGA), a critical intestinal glucosidase involved in the
breakdown of oligosaccharides of D-glucose into D-glu-
cose itself. All of the synthesized compounds were inhib-
itors of MGA with Ki values ranging from 6 to 75 lM
(Table 1). However, these compounds are less active
10 R=CH3; n=2 96%
11 R=CH3; n=4 93%
12 R=CH3; n=6 99%
13 R=CH3; n=12 98%
14 R=CH3; n=16 98%
15 R=CH(CH3)2; n=1 95%
35 R=CH3; n=2
36 R=CH3; n=4
32 R=CH3; n=6
31 R=CH3; n=12
33 R=CH3; n=16
34 R=CH(CH3)2; n=1
OR
n
OR
n
i) BCl3/CH2Cl2/
-78 °C
S
S
BF4
Cl
Table 1. Experimentally determined Ki valuesa
BnO
HO
ii) Ion Exchange
(Amberlyst A-26)
OBn
HO
OH
BnO
Inhibitor
Alkyl chain
Ki (lM)
16 R=CH2CH3; n=5 97%
17 R=CH3; n=8 94%
9
10
Tetradecyl
Butyl
10
32
2
4
37 R=CH2CH3; n=5
38 R=CH3; n=8
11
12
Hexyl
Octyl
75 13
51
6
19
8
1
4
13
14
Tetradecyl
Octadecyl
2-Methylbutyl
1-Ethoxyhexyl
1-Methoxynonyl
—
12
12
BCl3/CH2Cl2/
15
16
67 11
OTf
S
-78 °C
S
OTf
OH
52
33
9
2
BnO
HO
17
Salacinol (6)
93%
0.19 0.02b
OBn
BnO
HO
a Analysis of MGA inhibition was performed using p-nitrophenyl a-D-
glucopyranoside as the substrate.
b Ref. 13.
30
9
Scheme 6.
2
OH
HO
2
OH
OH
N
N
R
HO
HO
N
R
HO
OH
HO
OH
1 R=H; IC50=1.44 μM
3 R=n-butyl; IC50=0.57 μM
4 R=n-decyl; IC50=0.48 μM
5 R=7-oxadecyl; IC50=0.29 μM
39 R=CH2OH; IC50=50.4 μM
40 R=CH3; IC50=190.3 μM
41 R=H; IC50=319.0 μM
42 IC50=769.4 μM
Figure 2. IC50 Values for various N-alkylated imino sugars against porcine liver a-glucosidase I.7

906
S. Mohan et al. / Carbohydrate Research 342 (2007) 901–912
than salacinol which was previously shown to have a Ki
value of 0.19 0.02 lM against MGA.13
GraFit 4.0.14 was used to fit the data to the Michae-
lis–Menten equation and estimate the kinetic para-
meters, Km, Kmobs (Km in the presence of inhibitor) and
Vmax of the enzyme. Ki values for each inhibitor were
determined by the equation Ki = [I]/((Kmobs/Km) ꢀ 1).
The Ki reported for each inhibitor was determined by
averaging the Ki values obtained from three different
inhibitor concentrations.
We also note that the Ki values for the sulfonium ions
9–17 against MGA are lower than the IC50 values previ-
ously reported for N-alkylated imino sugars 40–42
(Fig. 2) against porcine liver a-glucosidase I, but are
greater than those for imino sugars 1, 3–5.7
3. Experimental
3.2. 1-Ethoxy-6-iodohexane (25)
3.1. General methods
A solution of 6-bromohexan-1-ol (24) (1 g, 5.5 mmol)
was dissolved in EtOH (20 mL) and NaOEt (3.76 g,
55.2 mmol) was added. The reaction mixture was
refluxed with vigorous stirring for 12 h. The reaction
was monitored by TLC analysis of aliquots (30%
EtOAc/hexanes). When the limiting reagents had been
essentially consumed, the mixture was cooled and the
solvent was evaporated to give a syrupy residue that
was passed through a pad of silica to give the corre-
sponding ethoxy alcohol (800 mg, crude) that was subse-
quently treated with MsCl (0.895 mL, 11.5 mmol) and
Et3N (1.98 mL, 14.3 mmol) in CH2Cl2 (30 mL) at 0 ꢁC.
After the consumption of starting material, as indicated
by TLC after 7 h, the reaction mixture was diluted with
CH2Cl2 (15 mL) and washed with water (2 · 10 mL).
The organic layer was dried over anhydrous Na2SO4
and concentrated to give the corresponding mesylate.
The crude mesylate (800 mg) was dissolved in dry ace-
tone (15 mL), and freshly fused NaI (1.6 g, 10.7 mmol)
was added. The reaction mixture was heated at 55 ꢁC
for 6 h, cooled, and the solvents were removed by evap-
oration at atmospheric pressure (at 25 ꢁC); the residue
was then purified by chromatography to give the title
Optical rotations were measured at 23 ꢁC and reported
in deg dmꢀ1 gꢀ1 cm3. 1H and 13C NMR spectra were re-
corded at frequencies of 500 and 125 MHz, respectively.
All assignments were confirmed with the aid of two-
1
1
1
dimensional H, H (gCOSY) and H, 13C (gHMQC)
experiments using standard Varian pulse programs. Pro-
cessing of the spectra was performed with MestRec soft-
ware. 1D-NOESY experiments were recorded at 295 K
on a 500 MHz spectrometer. For each 1D-NOESY spec-
trum, 512 or 256 scans were acquired with a Q3 Gauss-
ian Cascade pulse. A mixing time of 500 ms or 800 ms
was used in the 1D-NOESY experiments. Matrix-as-
sisted laser desorption ionization time-of-flight (MAL-
DI-TOF) mass spectra were obtained on a PerSeptive
Biosystems Voyager-DE spectrometer, using 2,5-dihydr-
oxybenzoic acid as a matrix. The high-resolution mass
spectrum was recorded in positive-mode with turbo-
ion spray ionization on a Hybrid Quadrupole-TOF
LC/MS/MS mass spectrometer. Analytical thin-layer
chromatography (TLC) was performed on aluminum
plates precoated with silica gel 60F-254 as the adsor-
bent. The developed plates were air-dried, exposed to
UV light and/or sprayed with a solution containing
1% Ce(SO4)2 and 1.5% molybdic acid in 10% aqueous
H2SO4, and heated. Column chromatography was per-
formed with silica gel 60 (230–400 mesh).
1
compound as a colorless oil (850 mg, 60%); H NMR
(CDCl3): d 3.47 (q, 2H, J = 7 Hz, –OCH2CH3), 3.41 (t,
2H, J1,2 = 7 Hz, H-1), 3.19 (t, 2H, J6,5 = 7 Hz, H-6),
1.86–1.80 (m, 2H, H-5), 1.61–1.55 (m, 2H, H-2), 1.45–
1.34 (m, 4H, H-3 and H-4), 1.20 (t, 3H, J = 7 Hz,
–OCH2CH3); 13C NMR (CDCl3): d 70.4 (C-1), 66.1
(–OCH2CH3), 33.4 (C-5), 30.3, 29.6 (2C, C-2 and C-4),
25.2 (C-3), 15.2 (–OCH2CH3), 7.1 (C-6); Anal. Calcd
for C8H17IO: C, 37.52; H, 6.69. Found: C, 37.75; H, 6.89.
3.1.1. Enzyme activity assay and enzyme kinetics.
Kinetic parameters of MGA with compounds 9–17 were
determined using the p-nitrophenyl-D-glucopyranoside
(pNP-glucose, Sigma) assay to follow the production
of p-nitrophenol upon addition of enzyme (500 nM).
The assays were carried out in 96-well microtiter plates
containing 100 mM MES buffer, pH 6.5, inhibitor (at
three different concentrations), and pNP-glucose as sub-
strate (2.5, 3.5, 5, 7.5, 15, and 30 mM), with a final vol-
ume of 50 lL. Reactions were incubated at 37 ꢁC for
35 min and terminated by addition of 50 lL of 0.5 M so-
dium carbonate. The absorbance of the reaction product
was measured at 405 nm in a microtiter plate reader. All
reactions were performed in triplicate and absorbance
measurements were averaged to give a final result. Reac-
tions were linear within this time frame. The program
3.3. 1-Iodo-9-methoxynonane (27)
A solution of 9-bromononan-1-ol (26) (1.1 g, 4.9 mmol)
was dissolved in MeOH (20 mL) and NaOMe (2.66 g,
49.3 mmol) was added. The reaction mixture was
refluxed with vigorous stirring for 12 h. The reaction
was monitored by TLC analysis of aliquots (30%
EtOAc/hexanes). When the limiting reagents had been
essentially consumed, the mixture was cooled and the
solvent was evaporated to give a syrupy residue that
was passed through a pad of silica to give the corre-
sponding methoxy alcohol (830 mg, crude) that was sub-

S. Mohan et al. / Carbohydrate Research 342 (2007) 901–912
907
sequently treated with MsCl (0.775 mL, 10.0 mmol) and
Et3N (1.72 mL, 12.4 mmol) in CH2Cl2 (30 mL) at 0 ꢁC.
After the consumption of starting material, as indicated
by TLC after 7 h, the reaction mixture was diluted with
CH2Cl2 (15 mL) and washed with water (2 · 10 mL).
The organic layer was dried over anhydrous Na2SO4
and concentrated to give the corresponding mesylate.
The crude mesylate (890 mg) was dissolved in dry ace-
tone (15 mL), and freshly fused NaI (3.2 g, 21.2 mmol)
was added. The reaction mixture was heated at 55 ꢁC
for 5 h, cooled, and the solvents were removed by evap-
oration at atmospheric pressure (at 25 ꢁC); the residue
was then purified by chromatography to give the title
compound as a colorless oil (820 mg, 59%). This mate-
rial was identical in all respects to that reported previ-
ously.20 1H NMR (CDCl3): d 3.36 (t, 2H, J9,8 = 7 Hz,
H-9), 3.33 (s, 3H, –OCH3), 3.18 (t, 2H, J1,2 = 7 Hz, H-
1), 1.84–1.78 (m, 2H, H-2), 1.59–1.53 (m, 2H, H-8),
1.41–1.25 (m, 10H, H-3–H-7); 13C NMR (CDCl3): d
72.7 (C-9), 58.3 (–OCH3), 33.4 (C-2), 30.3, 29.4 (2C,
C-3 and C-8), 29.2, 29.1, 28.3 (3C, C-4, C-5 and C-6),
26.0 (C-7), 7.0 (C-1).
(3CH2Ph), 66.9 (C-5), 66.3 (C-4), 47.1 (C-1), 45.7 (C-
10), 31.9–22.7 (11C, C-30–C-130), 25.7 (C-20), 14.1 (C-
140); MALDI-TOF MS: m/z 617.54 [MꢀOTf]+. Anal.
Calcd for C41H57F3O6S2: C, 64.20; H, 7.49. Found: C,
63.91; H, 7.58.
3.5. General procedure for the preparation of sulfonium
ions 31–38
To a mixture of thioarabinitol 28 and the alkyl halide
(18–23, 25 or 27) in dry CH3CN was added AgBF4
(1 equiv with respect to alkyl halide), and the stirred
reaction mixture was heated at 65 ꢁC for 17 h. The pro-
gress of the reaction was monitored by TLC analysis of
aliquots (CHCl3/MeOH, 10:1). When the limiting
reagent had been essentially consumed, the mixture
was cooled and concentrated to give a syrupy residue.
Purification by column chromatography (gradient of
CHCl3/MeOH, 10:1) gave the purified sulfonium ions
31–38.
3.5.1. 2,3,5-Tri-O-benzyl-1,4-dideoxy-1,4-[(1-tetradecyl)-
(R)-episulfoniumylidene]-D-arabinitol tetrafluoroborate
(31). The reaction of thioarabinitol 28 (300 mg,
0.71 mmol) with bromide 19 (0.195 mL, 0.79 mmol)
and AgBF4 (154 mg, 0.79 mmol) in dry CH3CN
3.4. 2,3,5-Tri-O-benzyl-1,4-dideoxy-1,4-[(1-tetradecyl)-
(R)-episulfoniumylidene]-D-arabinitol triflate (30)
A mixture of thioarabinitol 28 (500 mg, 1.19 mmol) and
bromide 19 (0.357 mL, 1.31 mmol) in 1,1,1,3,3,3-hexa-
fluoro-2-propanol (HFIP, 1 mL) was stirred and heated
in a sealed tube at 90 ꢁC for 24 h. The progress of the
reaction was monitored by TLC analysis of aliquots
(CHCl3/MeOH, 10:1) that showed a 30% conversion
of product. Further heating did not improve the conver-
sion rate. Hence, the mixture was cooled and concen-
trated to give a syrupy residue. Purification by column
chromatography (gradient of CHCl3/MeOH, 10:1) gave
the purified sulfonium ion 29 (235 mg, 47%, based on
the isolation of 40% unreacted starting material 28);
treatment with silver triflate (86.6 mg, 0.337 mmol) in
CH2Cl2 at ambient temperature for 5 h gave sulfonium
ion 30 as a colorless syrup (240 mg, 93%): [a]D +4.44
(c 0.2, MeOH); 1H NMR (CDCl3): d 7.36–7.32 (m,
9H, Ar), 7.25–7.18 (m, 6H, Ar), 4.62 and 4.52 (2d, each
1H, Ja,b = 11.9 Hz, CH2Ph), 4.61 and 4.43 (2d, each 1H,
Ja,b = 11.8 Hz, CH2Ph), 4.53 and 4.45 (2d, each 1H,
Ja,b = 11.7 Hz, CH2Ph), 4.53 (br s, 1H, H-2), 4.41 (d,
1H, J1a,1b = 12.9 Hz, H-1a), 4.17 (br s, 1H, H-3), 3.81–
3.76 (m, 2H, H-4 and H-5a), 3.74 (ddd, 1H,
(8 mL) gave compound 31 as a colorless syrup
(370 mg, 74%): [a]D +8.11 (c 0.4, MeOH); 1H NMR
(CDCl3): d 7.37–7.32 (m, 9H, Ar), 7.25–7.18 (m, 6H,
Ar), 4.62 and 4.50 (2d, each 1H, Ja,b = 11.9 Hz, CH2Ph),
4.61 and 4.43 (2d, each 1H, Ja,b = 11.8 Hz, CH2Ph), 4.54
and 4.48 (2d, each 1H, Ja,b = 11.7 Hz, CH2Ph), 4.54 (br
s, 1H, H-2), 4.37 (d, 1H, J1a,1b = 13.2 Hz, H-1a), 4.15
(br s, 1H, H-3), 3.78–3.75 (m, 2H, H-4 and H-5a),
0
0
0
0
0
0
3.68 (ddd, 1H, J1 a;1 b ¼ 13:1 Hz, J1 a;2 a ¼ J1 a;2 b
¼
8:2 Hz, H-10a), 3.64 (dd, 1H, J5b,4 = J5b,5a = 11.9 Hz,
H-5b), 3.64 (dd, 1H, J1b,1a = 13.2 Hz, J1b,2 = 3.1 Hz,
H-1b), 3.28–3.22 (m, 1H, H-10b), 1.78–1.72 (m, 2H, H-
20), 1.50–1.20 (m, 22H, H-30–H-130), 0.88 (dd, 3H,
J14 ;13 a ¼ J14 ;13 b ¼ 6:8 Hz, H-140); 13C NMR (CDCl3):
d 136.6, 136, 135.8 (3Cipso), 128.8–127.8 (15CAr), 82.8
(C-3), 81.8 (C-2), 73.7, 72.6, 71.9 (3CH2Ph), 66.9 (C-
5), 66.6 (C-4), 46.8 (C-1), 45.4 (C-10), 31.9–22.7 (11C,
C-30–C-130), 25.7 (C-20), 14.1 (C-140); MALDI-TOF
MS: m/z 617.86 [MꢀBF4]+. Anal. Calcd for
C40H57BF4O3S: C, 68.17; H, 8.15. Found: C, 68.14; H,
8.29.
0
0
0
0
J1 a;1 b ¼ 12:7 Hz, J1 a;2 a ¼ J1 a;2 b ¼ 8:1 Hz, H-10a), 3.64
(dd, 1H, J5b,4 = J5b,5a = 12.1 Hz, H-5b), 3.64 (dd, 1H,
J1b,1a = 12.9 Hz, J1b,2 = 2.1 Hz, H-1b), 3.30–3.24 (m,
1H, H-10b), 1.78–1.72 (m, 2H, H-20), 1.50–1.20 (m,
3.5.2. 2,3,5-Tri-O-benzyl-1,4-dideoxy-1,4-[(1-octyl)-(R)-
episulfoniumylidene]-D-arabinitol tetrafluoroborate (32).
The reaction of thioarabinitol 28 (500 mg, 1.19 mmol)
with bromide 18 (253 mg, 1.31 mmol) and AgBF4
(255 mg, 1.31 mmol) in dry CH3CN (12 mL) gave com-
pound 32 as a colorless syrup (590 mg, 79%): [a]D +8.16
0
0
0
0
0
0
22H, H-30–H-130), 0.88 (dd, 3H, J14 ;13 a ¼ J14 ;13 b
¼
0
0
0
0
7 Hz, H-140); 13C NMR (CDCl3): d 136.5, 135.9, 135.7
1
(3Cipso), 128.9–127.9 (15CAr), 120.7 (q, 1C, JC,F
=
(c 0.5, MeOH); H NMR (CDCl3): d 7.36–7.31 (m, 9H,
319 Hz, OTf), 83.1 (C-3), 81.7 (C-2), 73.8, 72.7, 71.9
Ar), 7.25–7.18 (m, 6H, Ar), 4.64 and 4.52 (2d, each 1H,

908
S. Mohan et al. / Carbohydrate Research 342 (2007) 901–912
Ja,b = 11.9 Hz, CH2Ph), 4.60 and 4.45 (2d, each 1H,
Ja,b = 11.8 Hz, CH2Ph), 4.53 and 4.48 (2d, each 1H,
Ja,b = 11.7 Hz, CH2Ph), 4.58 (br s, 1H, H-2), 4.32 (d,
1H, J1a,1b = 13.2 Hz, H-1a), 4.18 (br s, 1H, H-3), 3.82–
3.77 (m, 2H, H-4 and H-5a), 3.65 (dd, 1H,
J5b,4 = J5b,5a = 11.4 Hz, H-5b), 3.64 (dd, 1H,
J1b,1a = 13.2 Hz, J1b,2 = 3.7 Hz, H-1b), 3.64 (ddd, 1H,
H-2), 4.38 (d, 1H, J1a,1b = 13.1 Hz, H-1a), 4.15 (br s,
1H, H-3), 3.78 (dd, 1H, J4,5a = 5 Hz, J4,5b = 11.5 Hz,
H-4), 3.78 (dd, 1H, J5a,4 = 5 Hz, J5a,5b = 11.5 Hz, H-
0
0
0
0
5a), 3.70 (ddd, 1H, J1 a;1 b ¼ 12:5 Hz, J1 a;2 a ¼ 10:5 Hz,
J1 a;2 b ¼ 6:5 Hz, H-10a), 3.64 (dd, 1H, J5b,4 = J5b,5a
=
0
0
11.5 Hz, H-5b), 3.64 (dd, 1H, J1b,1a = 13.2 Hz,
0
0
J1b,2 = 3.5 Hz, H-1b), 3.24 (ddd, 1H, J1 b;1 a ¼ 12:5 Hz,
J1 a;1 b ¼ 13:1 Hz, J1 a;2 a ¼ J1 a;2 b ¼ 7:5 Hz, H-10a),
J1 b;2 a ¼ 9:5 Hz, J1 b;2 b ¼ 5 Hz, H-10b), 1.75–1.55 (m,
0
0
0
0
0
0
0
0
0
0
3.28–3.21 (m, 1H, H-10b), 1.78–1.71 (m, 2H, H-20),
3H, H-20 and H-30), 0.91 and 0.87 (2d, each 3H,
1.50–1.19 (m, 10H, H-30–H-70), 0.87 (dd, 3H, J8 ;7 a
¼
J4 ;3 ¼ J5 ;3 ¼ 6:5 Hz, H-40 and H-50); 13C NMR
(CDCl3): d 136.6, 136.1, 135.9 (3Cipso), 128.8–127.9
(15CAr), 82.8 (C-3), 82.0 (C-2), 73.6, 72.6, 71.8
(3CH2Ph), 66.9 (C-5), 66.6 (C-4), 46.8 (C-1), 43.5 (C-
10), 33.9 (C-20), 27.1 (C-30), 21.9, 21.5 (2C, C-40 and C-
50); MALDI-TOF MS: m/z 491.18 [MꢀBF4]+. Anal.
Calcd for C31H39BF4O3S: C, 64.36; H, 6.79. Found: C,
64.39; H, 6.99.
0
0
0
0
0
0
J8 ;7 b ¼ 7 Hz, H-80); 13C NMR (CDCl3): d 136.6,
136.1, 135.9 (3Cipso), 128.8–127.9 (15CAr), 82.8 (C-3),
81.9 (C-2), 73.7, 72.6, 71.9 (3CH2Ph), 66.9 (C-5), 66.7
(C-4), 46.8 (C-1), 45.4 (C-10), 31.6–22.5 (5C, C-30–C-
70), 25.6 (C-20), 14.0 (C-80); MALDI-TOF MS: m/z
532.95 [MꢀBF4]+. Anal. Calcd for C34H45BF4O3S: C,
65.80; H, 7.31. Found: C, 65.92; H, 7.26.
0
0
3.5.3. 2,3,5-Tri-O-benzyl-1,4-dideoxy-1,4-[(1-octadecyl)-
(R)-episulfoniumylidene]-D-arabinitol tetrafluoroborate
(33). The reaction of thioarabinitol 28 (500 mg,
1.19 mmol) with bromide 20 (436 mg, 1.31 mmol) and
AgBF4 (255 mg, 1.31 mmol) in dry CH3CN (12 mL)
gave compound 33 as a colorless syrup (465 mg, 73%,
based on the isolation of 30% unreacted starting mate-
3.5.5. 2,3,5-Tri-O-benzyl-1,4-dideoxy-1,4-[(1-butyl)-(R)-
episulfoniumylidene]-D-arabinitol tetrafluoroborate (35).
The reaction of thioarabinitol 28 (500 mg, 1.19 mmol)
with iodide 22 (0.162 mL, 1.43 mmol) and AgBF4
(276 mg, 1.43 mmol) in dry CH3CN (14 mL) gave com-
pound 35 as a colorless syrup (600 mg, 90%): [a]D +4.12
1
(c 0.5, MeOH); H NMR (CDCl3): d 7.35–7.30 (m, 9H,
1
rial 28): [a]D +6.67 (c 0.3, MeOH); H NMR (CDCl3):
Ar), 7.25–7.18 (m, 6H, Ar), 4.64 and 4.55 (2d, each
1H, Ja,b = 11.9 Hz, CH2Ph), 4.58 and 4.45 (2d, each
1H, Ja,b = 11.8 Hz, CH2Ph), 4.52 and 4.49 (2d, each 1H,
Ja,b = 11.8 Hz, CH2Ph), 4.57 (d, 1H, J2,1b = 2.6 Hz, H-
2), 4.27 (d, 1H, J1a,1b = 13.1 Hz, H-1a), 4.24 (br s, 1H,
H-3), 3.83 (dd, 1H, J4,5a = 5 Hz, J4,5b = 11.3 Hz, H-4),
3.83 (dd, 1H, J5a,4 = 5 Hz, J5a,5 b = 11.3 Hz, H-5a),
3.65 (dd, 1H, J5b,4 = J5b,5a = 11.3 Hz, H-5b), 3.62 (dd,
1H, J1b,1a = 13.1 Hz, J1b,2 = 2.7 Hz, H-1b), 3.62 (ddd,
d 7.37–7.29 (m, 9H, Ar), 7.25–7.18 (m, 6H, Ar), 4.63
and 4.52 (2d, each 1H, Ja,b = 11.9 Hz, CH2Ph), 4.60
and 4.44 (2d, each 1H, Ja,b = 11.8 Hz, CH2Ph), 4.58
(br s, 1H, H-2), 4.53 and 4.48 (2d, each 1H,
Ja,b = 11.7 Hz, CH2Ph), 4.32 (d, 1H, J1a,1b = 13.2 Hz,
H-1a), 4.18 (br s, 1H, H-3), 3.81–3.78 (m, 2H, H-4
and H-5a), 3.67–3.62 (m, 1H, H-10a), 3.64 (dd, 1H,
J5b,5a = J5b,4 = 11.0 Hz, H-5b), 3.64 (dd, 1H,
J1b,1a = 13.2 Hz, J1b,2 = 3.6 Hz, H-1b), 3.28–3.20 (m,
1H, H-10b), 1.77–1.71 (m, 2H, H-20), 1.50–1.20 (m,
1H, J1 a;1 b ¼ 13:0 Hz, J1 a;2 a ¼ J1 a;2 b ¼ 7:5 Hz, H-10a),
0
0
0
0
0
0
3.27–3.21 (m, 1H, H-10b), 1.78–1.70 (m, 2H, H-20),
1.49–1.39
0
0
30H,
H-30–H-170),
0.88
(dd,
3H,
J18 ;17 a
¼
(m,
2H,
H-30),
0.85
(dd,
3H,
J18 ;17 b ¼ 6:8 Hz, H-180); 13C NMR (CD3Cl3): d 136.6,
136.1, 135.9 (3Cipso), 128.8–127.8 (15CAr), 82.8 (C-3),
82.0 (C-2), 73.6, 72.6, 71.8 (3CH2Ph), 66.9 (C-5), 66.7
(C-4), 46.8 (C-1), 45.3 (C-10), 31.9–22.6 (15C, C-30–C-
170), 25.6 (C-20), 14.1 (C-180); MALDI-TOF MS: m/z
673.57 [MꢀBF4]+. Anal. Calcd for C44H65BF4O3S: C,
69.46; H, 8.61. Found: C, 69.64; H, 8.53.
J4 ;3 a ¼ J4 ;3 b ¼ 7:5 Hz, H-40); 13C NMR (CDCl3): d
136.7, 136.2, 135.9 (3Cipso), 128.7–127.8 (15CAr), 82.7
(C-3), 82.1 (C-2), 73.6, 72.5, 71.8 (3CH2Ph), 66.8 (C-
5), 66.6 (C-4), 46.7 (C-1), 45.1 (C-10), 27.4 (C-20), 21.1
(C-30), 13.1 (C-40); MALDI-TOF MS: m/z 477.33
[MꢀBF4]+. Anal. Calcd for C30H37BF4O3S: C, 63.83;
H, 6.61. Found: C, 63.50; H, 6.57.
0
0
0
0
0
0
3.5.4. 2,3,5-Tri-O-benzyl-1,4-dideoxy-1,4-[[1-(3-methyl)-
butyl]-(R)-episulfoniumylidene]-D-arabinitol tetrafluoro-
borate (34). The reaction of thioarabinitol 28 (580
mg, 1.38 mmol) with bromide 21 (0.182 mL, 1.52 mmol)
and AgBF4 (296 mg, 1.52 mmol) in dry CH3CN (14 mL)
gave compound 34 as a colorless syrup (518 mg, 65%):
3.5.6. 2,3,5-Tri-O-benzyl-1,4-dideoxy-1,4-[(1-hexyl)-(R)-
episulfoniumylidene]-D-arabinitol tetrafluoroborate (36).
The reaction of thioarabinitol 28 (610 mg, 1.45 mmol)
with iodide 23 (0.211 mL, 1.43 mmol) and AgBF4
(276 mg, 1.43 mmol) in dry CH3CN (14 mL) gave com-
pound 36 as a colorless syrup (810 mg, 95%): [a]D +4.00
1
1
[a]D +6.67 (c 0.5, MeOH); H NMR (CDCl3): d 7.37–
(c 0.8, MeOH); H NMR (CD3OD): d 7.37–7.24 (m,
7.29 (m, 9H, Ar), 7.25–7.18 (m, 6H, Ar), 4.62 and 4.50
(2d, each 1H, Ja,b = 11.9 Hz, CH2Ph), 4.61 and 4.44
(2d, each 1H, Ja,b = 11.8 Hz, CH2Ph), 4.54 and 4.49
(2d, each 1H, Ja,b = 11.7 Hz, CH2Ph), 4.54 (br s, 1H,
15H, Ar), 4.65 and 4.62 (2d, each 1H, Ja,b = 11.7 Hz,
CH2Ph), 4.64 (br s, 1H, H-2), 4.56 and 4.47 (2d, each
1H, Ja,b = 11.6 Hz, CH2Ph), 4.54 and 4.50 (2d, each
1H, Ja,b = 11.7 Hz, CH2Ph), 4.39 (br s, 1H, H-3), 4.13

S. Mohan et al. / Carbohydrate Research 342 (2007) 901–912
909
(dd, 1H, J4,5a = 5 Hz, J4,5b = 11.0 Hz, H-4), 4.04 (d, 1H,
J1a,1b = 12.5 Hz, H-1a), 3.88 (dd, 1H, J5a,4 = 5 Hz,
J5a,5b = 10.5 Hz, H-5a), 3.67 (dd, 1H, J1b,1a = 12.5 Hz,
J1b,2 = 3 Hz, H-1b), 3.64 (dd, 1H, J5b,5a = 10.5 Hz,
(2d, each 1H, Ja,b = 11.8 Hz, CH2Ph), 4.54 and 4.48
(2d, each 1H, Ja,b = 11.5 Hz, CH2Ph), 4.54 (br s, 1H,
H-2), 4.37 (d, 1H, J1a,1b = 13.0 Hz, H-1a), 4.14 (br s,
1H, H-3), 3.80–3.75 (m, 2H, H-4 and H-5a), 3.68
0
0
0
0
0
0
0
0
J5b,4 = 11.0 Hz, H-5b), 3.41 (ddd, 1H, J1 a;1 b
¼
(ddd, 1H, J1 a;1 b ¼ 13:0 Hz, J1 a;2 a ¼ J1 a;2 b ¼ 8:0 Hz,
H-10a), 3.64 (dd, 1H, J5b,4 = J5b,5a = 12.0 Hz, H-5b),
3.64 (dd, 1H, J1b,1a = 13.0 Hz, J1b,2 = 2.8 Hz, H-1b),
12:5 Hz, J1 a;2 a ¼ J1 a;2 b ¼ 8:0 Hz, H-10a), 3.31 (ddd,
0
0
0
0
0
0
0
0
0
0
1H, J1 b;1 a ¼ 12:5 Hz, J1 b;2 a ¼ 5:5 Hz, J1 b;2 b ¼ 8:5 Hz,
H-10b), 1.82–1.68 (m, 2H, H-20), 1.43–1.40 (m, 2H, H-
30), 1.21–1.18 (m, 4H, H-40 and H-50), 0.85 (dd, 3H,
3.36 (dd, 2H, J9 ;8 a ¼ J9 ;8 b ¼ 6:8 Hz, H-90), 3.33 (s,
3H, –OCH3), 3.28–3.23 (m, 1H, H-10b), 1.78–1.72 (m,
2H, H-20), 1.56–1.52 (m, 2H, H-80), 1.49–1.37 (m, 2H,
H-30), 1.34–1.18 (m, 8H, H-40, H-50, H-60 and H-70);
13C NMR (CDCl3): d 136.6, 136.1, 135.9 (3Cipso),
128.8–127.9 (15CAr), 82.8 (C-3), 81.9 (C-2), 73.6, 72.6,
71.8 (3CH2Ph), 72.8 (C-90), 66.8 (C-5), 66.7 (C-4), 58.5
(–OCH3), 46.7 (C-1), 45.3 (C-10), 29.5 (C-80), 29.2,
29.1, 28.7, 26.0 (4C, C-40–C-70), 27.9 (C-30), 25.6 (C-
20); MALDI-TOF MS: m/z 577.04 [MꢀBF4]+. Anal.
Calcd for C36H49BF4O4S: C, 65.06; H, 7.43. Found: C,
65.13; H, 7.53.
0
0
0
0
J6 ;5 a ¼ J6 ;5 b ¼ 7:0 Hz, H-60); 13C NMR (CD3OD): d
138.5, 138.3, 138.0 (3Cipso), 129.8–129.2 (15CAr), 84.3
(C-3), 84.2 (C-2), 74.6, 73.6, 73.1 (3CH2Ph), 68.2 (C-
5), 67.7 (C-4), 47.9 (C-1), 46.7 (C-10), 32.2, 23.4 (C-40
and C-50), 28.8 (C-30), 26.7 (C-20), 14.3 (C-60); MAL-
DI-TOF MS: m/z 505.34 [MꢀBF4]+. Anal. Calcd for
C32H41BF4O3S: C, 64.86; H, 6.97. Found: C, 64.78; H,
7.10.
0
0
0
0
3.5.7. 2,3,5-Tri-O-benzyl-1,4-dideoxy-1,4-[[1-(6-ethoxy)-
hexyl]-(R)-episulfoniumylidene]-D-arabinitol tetrafluoro-
borate (37). The reaction of thioarabinitol 28
(500 mg, 1.19 mmol) with iodide 25 (363 mg, 1.42 mmol)
and AgBF4 (276 mg, 1.43 mmol) in dry CH3CN (14 mL)
gave compound 37 as a colorless syrup (680 mg, 90%):
3.6. 1,4-Dideoxy-1,4-[(1-tetradecyl)-(R)-episulfoniumyl-
idene]-D-arabinitol triflate (9)
BCl3 gas was bubbled vigorously through a solution of
sulfonium ion 30 (200 mg, 0.26 mmol) in CH2Cl2
(5 mL) at ꢀ78 ꢁC under N2 atmosphere for 5 min. The
mixture was stirred at ꢀ78 ꢁC for 1.5 h and a stream
of dry air was blown vigorously over the solution to
remove excess BCl3. The reaction was quenched with
MeOH (3 mL), and the solvents were removed. The res-
idue was co-evaporated with MeOH (2 · 4 mL) to give
final product 9, as a colorless, amorphous solid
(120 mg, 93%): mp 69–71 ꢁC; [a]D +19.5 (c 0.2, MeOH);
1H NMR (CD3OD): d 4.60 (br s, 1H, H-2), 4.31 (d, 1H,
J3,2 = 1.5 Hz, H-3), 4.03–4.0 (m, 1H, H-5a), 3.86–3.80
(m, 2H, H-4 and H-5b), 3.81 (d, 1H, J1a,1b = 12.5 Hz,
H-1a), 3.70 (dd, 1H, J1b,1a = 12.5 Hz, J1b,2 = 3 Hz, H-
1
[a]D +8.1 (c 0.6, MeOH); H NMR (CDCl3): d 7.38–
7.33 (m, 9H, Ar), 7.25–7.18 (m, 6H, Ar), 4.61 and 4.50
(2d, each 1H, Ja,b = 11.9 Hz, CH2Ph), 4.60 and 4.43
(2d, each 1H, Ja,b = 11.8 Hz, CH2Ph), 4.54 and 4.48
(2d, each 1H, Ja,b = 11.7 Hz, CH2Ph), 4.54 (br s, 1H,
H-2), 4.37 (d, 1H, J1a,1b = 13.2 Hz, H-1a), 4.14 (br s,
1H, H-3), 3.79–3.74 (m, 2H, H-4 and H-5a), 3.70
(ddd, 1H, J1 a;1 b ¼ 12:5 Hz, J1 a;2 a ¼ J1 a;2 b ¼ 8:0 Hz,
H-10a), 3.63 (dd, 1H, J5b,4 = J5b,5a = 12.5 Hz, H-5b),
3.63 (dd, 1H, J1b,1a = 13.2 Hz, J1b,2 = 3.0 Hz, H-1b),
3.45 (q, 2H, J = 7 Hz, –OCH2CH3), 3.36 (dd, 2H,
J6 ;5 a ¼ J6 ;5 b ¼ 6:5 Hz, H-60), 3.29–3.23 (m, 1H, H-
10b), 1.80–1.74 (m, 2H, H-20), 1.53–1.40 (m, 4H, H-30
and H-50), 1.39–1.27 (m, 2H, H-40), 1.18 (t, 3H,
J = 7 Hz, –OCH2CH3); 13C NMR (CDCl3): d 136.6,
136.1, 135.9 (3Cipso), 128.8–127.9 (15CAr), 82.7 (C-3),
82.0 (C-2), 73.6, 72.6, 71.8 (3CH2Ph), 70.1 (C-60), 66.8
(C-5), 66.7 (C-4), 66.0 (–OCH2CH3), 46.8 (C-1), 45.2
(C-10), 29.2 (C-50), 27.7 (C-30), 25.5 (C-20), 25.4 (C-40),
15.2 (–OCH2CH3); MALDI-TOF MS: m/z 549.49
[MꢀBF4]+. Anal. Calcd for C34H45BF4O4S: C, 64.15;
H, 7.13. Found: C, 64.36; H, 7.33.
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1b), 3.50 (ddd, 1H, J1 a;1 b ¼ 12:5 Hz, J1 a;2 a ¼ J1 a;2 b
¼
8:0 Hz, H-10a), 3.40 (ddd, 1H, J1 b;1 a ¼ 12:5 Hz,
0
0
J1 b;2 a ¼ 8:5 Hz, J1 b;2 b ¼ 5:5 Hz, H-10b), 1.91–1.80 (m,
0
0
0
0
2H, H-20), 1.55–1.42 (m, 2H, H-30), 1.41–1.22 (m,
20H, H-40–H-130), 0.87 (dd, 3H, J14 ;13 a ¼ J14 ;13 b
¼
0
0
0
0
7:0 Hz, H-140); 13C NMR (CD3OD): d 121.8 (q, 1C,
JC,F = 316.3 Hz, OTf), 79.6 (C-3), 79.5 (C-2), 73.6 (C-
4), 61.0 (C-5), 50.1 (C-1), 46.7 (C-10), 33.1–23.8 (10C,
C-40–C-130), 29.2 (C-30), 26.8 (C-20), 14.5 (C-140); MAL-
DI-TOF MS: m/z 347.25 [MꢀOTf]+. Anal. Calcd for
C20H39F3O6S2: C, 48.37; H, 7.92. Found: C, 47.97; H,
7.77.
3.5.8.
2,3,5-Tri-O-benzyl-1,4-dideoxy-1,4-[[1-(9-meth-
oxy)-nonyl]-(R)-episulfoniumylidene]-D-arabinitol tetra-
fluoroborate (38). The reaction of thioarabinitol 28
(740 mg, 1.76 mmol) with iodide 27 (600 mg, 2.11 mmol)
and AgBF4 (411 mg, 2.11 mmol) in dry CH3CN (12 mL)
gave compound 38 as a colorless syrup (1.05 g, 89%):
[a]D +7.30 (c 0.3, MeOH); H NMR (CDCl3): d 7.37–
7.33 (m, 9H, Ar), 7.25–7.18 (m, 6H, Ar), 4.61 and 4.50
(2d, each 1H, Ja,b = 12.0 Hz, CH2Ph), 4.60 and 4.43
3.7. General procedure for the deprotection of the
S-alkylated sulfonium ions (31–38)
1
BCl3 gas was bubbled vigorously through a solution of
sulfonium ion (31–38) in CH2Cl2 at ꢀ78 ꢁC under N2
atmosphere for 10 min. The mixture was stirred at

910
S. Mohan et al. / Carbohydrate Research 342 (2007) 901–912
ꢀ78 ꢁC for 2 h and a stream of dry air was blown vigor-
ously over the solution to remove excess BCl3. The reac-
tion was quenched with MeOH (3–4 mL), and the
solvents were removed. The residue was co-evaporated
with MeOH (2 · 4 mL) to give the deprotected products,
which were subsequently dissolved in MeOH and a
freshly washed ion-exchange resin Amberlyst A-26
(chloride form) was added. The mixture was stirred at
room temperature for 2 h and filtered. The filtrate was
concentrated to give final products 10–17.
(10 mL), followed by treatment with Amberlyst A-26
resin (250 mg), gave final product 12 as a colorless syrup
1
(238 mg, 99%): [a]D +22.22 (c 0.3, MeOH); H NMR
(CD3OD): d 4.62 (br s, 1H, H-2), 4.34 (br s, 1H, H-3),
4.06–4.01 (m, 1H, H-5a), 3.89–3.83 (m, 2H, H-4 and
H-5b), 3.85 (d, 1H, J1a,1b = 12.5 Hz, H-1a), 3.71 (dd,
1H, J1b,1a = 12.5 Hz, J1b,2 = 2.5 Hz, H-1b), 3.50 (ddd,
1H, J1 a;1 b ¼ 12:5 Hz, J1 a;2 a ¼ J1 a;2 b ¼ 8:0 Hz, H-10a),
0
0
0
0
0
0
0
0
0
0
3.43 (ddd, 1H, J1 b;1 a ¼ 12:5 Hz, J1 b;2 a ¼ 8:0 Hz,
J1 b;2 b ¼ 6:0 Hz, H-10b), 1.91–1.83 (m, 2H, H-20), 1.56–
0
0
1.49 (m, 2H, H-30), 1.46–1.32 (m, 8H, H-40 – H-70)
0.90 (dd, 3H, J8 ;7 a ¼ J8 ;7 b ¼ 6:0 Hz, H-80); 13C NMR
(CD3OD): d 79.6 (C-3), 79.4 (C-2), 73.6 (C-4), 61.0 (C-
5), 50.1 (C-1), 46.7 (C-10), 32.9, 30.1, 30.0 and 23.7
(4C, C-40–C-70), 29.2 (C-30), 26.8 (C-20), 14.5 (C-80);
MALDI-TOF MS: m/z 263.33 [MꢀCl]+. Anal. Calcd
for C13H27ClO3S: C, 52.24; H, 9.11. Found: C, 52.55;
H, 8.89.
0
0
0
0
3.7.1. 1,4-Dideoxy-1,4-[(1-butyl)-(R)-episulfoniumylidene]-
D-arabinitol chloride (10). Treatment of sulfonium
ion 35 (560 mg, 0.99 mmol) with BCl3 in CH2Cl2
(12 mL), followed by treatment with Amberlyst A-26
resin (250 mg) gave final product 10 as a colorless syrup
1
(230 mg, 96%): [a]D +21.05 (c 0.2, MeOH); H NMR
(CD3OD): d 4.62 (br s, 1H, H-2), 4.33 (br s, 1H, H-3),
4.10–4.0 (m, 1H, H-5a), 3.90–3.83 (m, 2H, H-4 and H-
5b), 3.84 (d, 1H, J1a,1b = 12.5 Hz, H-1a), 3.71 (dd, 1H,
J1b,1a = 12.5 Hz, J1b,2 = 3.0 Hz, H-1b), 3.50 (ddd, 1H,
3.7.4. 1,4-Dideoxy-1,4-[(1-tetradecyl)-(R)-episulfoniumyl-
idene]-D-arabinitol chloride (13). Treatment of sulfo-
nium ion 31 (200 mg, 0.28 mmol) with BCl3 in CH2Cl2
(5 mL), followed by treatment with Amberlyst A-26
resin (150 mg), gave final product 13 as a colorless,
amorphous solid (120 mg, 98%): mp 86–88 ꢁC; [a]D +10.87
(c 0.2, MeOH); 1H NMR (CD3OD): d 4.62 (br s, 1H, H-2),
4.34 (br s, 1H, H-3), 4.10–4.0 (m, 1H, H-5a), 3.90–3.83
(m, 2H, H-4 and H-5b), 3.84 (d, 1H, J1a,1b = 12.5 Hz,
H-1a), 3.71 (dd, 1H, J1b,1a = 12.5 Hz, J1b,2 = 3 Hz,
J1 a;1 b ¼ 12:5 Hz, J1 a;2 a ¼ J1 a;2 b ¼ 8:0 Hz, H-10a), 3.42
0
0
0
0
0
0
0
0
0
0
0
0
(ddd, 1H, J1 b;1 a ¼ 12:5 Hz, J1 b;2 a ¼ 8:5 Hz, J1 b;2 b
¼
6:2 Hz, H-10b), 1.90–1.80 (m, 2H, H-20), 1.60–1.48 (m,
2H, H-30), 1.0 (dd, 3H, J4 ;3 a ¼ J4 ;3 b ¼ 7:0 Hz, H-40);
13C NMR (CD3OD): d 79.6 (C-3), 79.4 (C-2), 73.6 (C-
4), 61.0 (C-5), 50.2 (C-1), 46.4 (C-10), 28.7 (C-20), 22.5
(C-30), 13.7 (C-40); MALDI-TOF MS: m/z 207.36
[MꢀCl]+. Anal. Calcd for C9H19ClO3S: C, 44.53; H,
7.89. Found: C, 44.28; H, 8.11.
0
0
0
0
0
0
0
0
0
0
H-1b), 3.50 (ddd, 1H, J1 a;1 b ¼ 12:5 Hz, J1 a;2 a ¼ J1 a;2 b
¼
8:0 Hz, H-10a), 3.42 (ddd, 1H, J1 b;1 a ¼ 12:5 Hz,
0
0
3.7.2. 1,4-Dideoxy-1,4-[(1-hexyl)-(R)-episulfoniumylidene]-
D-arabinitol chloride (11). Treatment of sulfonium
ion 36 (425 mg, 0.72 mmol) with BCl3 in CH2Cl2
(9 mL), followed by treatment with Amberlyst A-26 re-
sin (200 mg), gave final product 11 as a colorless syrup
J1 b;2 a ¼ 8:5 Hz, J1 b;2 b ¼ 5:5 Hz, H-10b), 1.91–1.81 (m,
0
0
0
0
2H, H-20), 1.58–1.45 (m, 2H, H-30), 1.43–1.28 (m,
20H, H-40–H-130), 0.89 (dd, 3H, J14 ;13 a ¼ J14 ;13 b
¼
0
0
0
0
7:0 Hz, H-140); 13C NMR (CD3OD): d 79.6 (C-3), 79.3
(C-2), 73.6 (C-4), 61.0 (C-5), 50.1 (C-1), 46.7 (C-10),
33.1–23.8 (10C, C-40–C-130), 29.2 (C-30), 26.8 (C-20),
14.5 (C-140); MALDI-TOF MS: m/z 347.12 [MꢀCl]+.
Anal. Calcd for C19H39ClO3S: C, 59.58; H, 10.26.
Found: C, 59.26; H, 10.33.
1
(180 mg, 93%): [a]D +19.05 (c 0.3, MeOH); H NMR
(CD3OD): d 4.59 (br s, 1H, H-2), 4.31 (d, 1H,
J3,2 = 1.5 Hz, H-3), 4.03–3.97 (m, 1H, H-5a), 3.86–3.80
(m, 2H, H-4 and H-5b), 3.82 (d, 1H, J1a,1b = 12.0 Hz,
H-1a), 3.68 (dd, 1H, J1b,1a = 12.0 Hz, J1b,2 = 3.5 Hz,
0
0
0
0
H-1b), 3.48 (ddd, 1H, J1 a;1 b ¼ 12:5 Hz, J1 a;2 a
¼
3.7.5. 1,4-Dideoxy-1,4-[(1-octadecyl)-(R)-episulfoniumyl-
idene]-D-arabinitol chloride (14). Treatment of sulfo-
nium ion 33 (450 mg, 0.59 mmol) with BCl3 in CH2Cl2
(10 mL), followed by treatment with Amberlyst A-26
resin (280 mg), gave final product 14 as a colorless amor-
phous solid (256 mg, 98%): mp 95–97 ꢁC; [a]D +12.92 (c
0.5, MeOH); 1H NMR (CD3OD): d 4.61 (br s, 1H, H-2),
4.33 (br s, 1H, H-3), 4.05–3.99 (m, 1H, H-5a), 3.88–3.82
(m, 2H, H-4 and H-5b), 3.83 (d, 1H, J1a,1b = 12.5 Hz, H-
1a), 3.70 (dd, 1H, J1b,1a = 12.5 Hz, J1b,2 = 3.2 Hz, H-
J1 a;2 b ¼ 8:0 Hz, H-10a), 3.40 (ddd, 1H, J1 b;1 a
¼
0
0
0
0
12:5 Hz, J1 b;2 a ¼ 8:5 Hz, J1 b;2 b ¼ 6:0 Hz, H-10b), 1.91–
0
0
0
0
1.78 (m, 2H, H-20), 1.55–1.42 (m, 2H, H-30), 1.39–1.32
(m, 4H, H-40 and H-50), 0.90 (dd, 3H, J6 ;5 a
¼
0
0
J6 ;5 b ¼ 7:5 Hz, H-60); 13C NMR (CD3OD): d 79.6 (C-
3), 79.4 (C-2), 73.6 (C-4), 61.0 (C-5), 50.2 (C-1), 46.7
(C-10), 32.3 (1C, C-40 or C-50), 28.9 (C-30), 26.8 (C-20),
23.5 (1C, C-40 or C-50), 14.3 (C-60); MALDI-TOF MS:
m/z 235.21 [MꢀCl]+. Anal. Calcd for C11H23ClO3S: C,
48.78; H, 8.56. Found: C, 48.50; H, 8.76.
0
0
0
0
0
0
0
0
1b), 3.49 (ddd, 1H, J1 a;1 b ¼ 12:5 Hz, J1 a;2 a ¼ J1 a;2 b
¼
8:0 Hz, H-10a), 3.41 (ddd, 1H, J1 b;1 a ¼ 12:5 Hz,
0
0
J1 b;2 a ¼ 8:5 Hz, J1 b;2 b ¼ 6:0 Hz, H-10b), 1.92–1.81 (m,
0
0
0
0
3.7.3. 1,4-Dideoxy-1,4-[(1-octyl)-(R)-episulfoniumylidene]-
D-arabinitol chloride (12). Treatment of sulfonium
ion 32 (500 mg, 0.81 mmol) with BCl3 in CH2Cl2
2H, H-20), 1.56–1.42 (m, 2H, H-30), 1.41–1.27 (m,
28H, H-40–H-170), 0.88 (dd, 3H, J18 ;17 a ¼ J18 ;17 b
¼
0
0
0
0

S. Mohan et al. / Carbohydrate Research 342 (2007) 901–912
911
7:0 Hz, H-180); 13C NMR (CD3OD): d 79.6 (C-3), 79.4
(C-2), 73.6 (C-4), 61.0 (C-5), 50.2 (C-1), 46.7 (C-10),
33.1-23.8 (14C, C-40–C-170), 29.3 (C-30), 26.8 (C-20),
14.5 (C-180); MALDI-TOF MS: m/z 403.47 [MꢀCl]+.
Anal. Calcd for C23H47ClO3S: C, 62.91; H, 10.79.
Found: C, 62.57; H, 10.41.
A-26 resin (150 mg), gave final product 17 as a colorless
syrup (120 mg, 94%): [a]D +20.34 (c 0.5, MeOH); H
NMR (CD3OD): d 4.59 (br s, 1H, H-2), 4.31 (d, 1H,
J3,2 = 2.0 Hz, H-3), 4.03–3.97 (m, 1H, H-5a), 3.86–3.80
(m, 2H, H-4 and H-5b), 3.82 (d, 1H, J1a,1b = 12.5 Hz,
H-1a), 3.68 (dd, 1H, J1b,1a = 12.0 Hz, J1b,2 = 3.0 Hz, H-
1
0
0
0
0
0
0
1b), 3.48 (ddd, 1H, J1 a;1 b ¼ 12:5 Hz, J1 a;2 a ¼ J1 a;2 b
¼
0
0
3.7.6. 1,4-Dideoxy-1,4-[[1-(3-methyl)-butyl]-(R)-episulfon-
iumylidene]-D-arabinitol chloride (15). Treatment of
sulfonium ion 34 (340 mg, 0.59 mmol) with BCl3 in
CH2Cl2 (8 mL), followed by treatment with Amberlyst
A-26 resin (160 mg), gave final product 15 as a colorless
8:0 Hz, H-10a), 3.40 (ddd, 1H, J1 b;1 a ¼12.5 Hz,
J1 b;2 a ¼ 8:5 Hz, J1 b;2 b ¼ 5:5 Hz, H-10b), 3.35 (dd, 2H,
0
0
0
0
J9 ;8 a ¼ J9 ;8 b ¼ 6:5 Hz, H-90), 3.33 (s, 3H, –OCH3),
1.91–1.78 (m, 2H, H-20), 1.53–1.47 (m, 4H, H30 and
H-80), 1.37–1.31 (m, 8H, H-40–H-70); 13C NMR
(CD3OD): d 79.6 (C-3), 79.4 (C-2), 73.9 (C-90), 73.5
(C-4), 61.0 (C-5), 58.8 (1C, –OCH3), 50.2 (C-1), 46.7
(C-10), 30.6, 30.4, 30.3, 30.0, 29.2, 27.1 (6C, C-30–C-
80), 26.8 (C-20); MALDI-TOF MS: m/z 307.30 [MꢀCl]+.
Anal. Calcd for C15H31ClO4S: C, 52.54; H, 9.11. Found:
C, 52.75; H, 9.07.
0
0
0
0
1
syrup (144 mg, 95%): [a]D +21.15 (c 0.4, MeOH); H
NMR (CD3OD): d 4.59 (br s, 1H, H-2), 4.31 (d, 1H,
J3,2 = 2.0 Hz, H-3), 4.03–3.97 (m, 1H, H-5a), 3.85–3.80
(m, 2H, H-4 and H-5b), 3.81 (d, 1H, J1a,1b = 12.0 Hz,
H-1a), 3.67 (dd, 1H, J1b,1a = 12.0 Hz, J1b,2 = 3.0 Hz,
0
0
0
0
H-1b), 3.49 (ddd, 1H, J1 a;1 b ¼ 12:5 Hz, J1 a;2 a
¼
J1 a;2 b ¼ 8:0 Hz, H-10a), 3.38 (ddd, 1H, J1 b;1 a
¼
0
0
0
0
12:5 Hz, J1 b;2 a ¼ J1 b;2 b ¼ 7:5 Hz, H-10b), 1.79–1.70
0
0
0
0
(m, 3H, H-20 and H-30), 0.96 (2d, each 3H, J4 ;3
¼
Acknowledgments
0
0
J5 ;3 ¼ 6:5 Hz, H-40 and H-50); 13C NMR (CD3OD): d
79.6 (C-3), 79.4 (C-2), 73.6 (C-4), 61.0 (C-5), 50.2 (C-
1), 44.8 (C-10), 35.3 (C-20), 28.6 (C-30), 22.5, 22.2 (2C,
C-40 and C-50); MALDI-TOF MS: m/z 221.14 [MꢀCl]+.
Anal. Calcd for C10H21ClO3S: C, 46.77; H, 8.24. Found:
C, 46.43; H, 8.09.
0
0
We thank Dr. B. D. Johnston for helpful discussion and
the Canadian Institutes of Health Research for financial
support.
References
3.7.7. 1,4-Dideoxy-1,4-[[1-(6-ethoxy)-hexyl]-(R)-episulfon-
iumylidene]-D-arabinitol chloride (16). Treatment of
sulfonium ion 37 (230 mg, 0.36 mmol) with BCl3 in
CH2Cl2 (7 mL), followed by treatment with Amberlyst
A-26 resin (150 mg), gave final product 16 as a colorless
1. For leading references: (a) Herscovics, A. In Comprehen-
sive Natural Products Chemistry; Pinto, B. M., Ed.;
Barton, D. H. R., Nakanishi, K., Meth-Cohn, O., Eds.;
Elsevier: UK, 1999; Vol. 3, Chapter 2; (b) McCarter, J.;
Withers, S. G. Curr. Opin. Struct. Biol 1994, 4, 885–892;
(c) Ly, H. D.; Withers, S. G. Annu. Rev. Biochem. 1999,
68, 487–522; (d) Lillelund, V. H.; Jensen, H. H.; Liang, X.;
Bols, M. Chem. Rev. 2002, 102, 515–553.
2. (a) Fleet, G. W. J.; Karpus, A.; Dwek, R. A.; Fellows, L.
E.; Tyms, A. S.; Petursson, S.; Namgoong, S. K.;
Ramsden, N. G.; Smith, P. W.; Son, J. C.; Wilson, F.;
Witty, D. R.; Jacob, G. S.; Rademacher, T. W. FEBS Lett.
1988, 237, 128–132; (b) Karpas, A.; Fleet, G. W. J.; Dwek,
R. A.; Petursson, S.; Namgoong, S. K.; Ramsden, N. G.;
Jacob, G. S.; Rademacher, T. W. Proc. Natl. Acad. Sci.
USA 1988, 85, 9229.
1
syrup (110 mg, 97%): [a]D +18.56 (c 0.3, MeOH); H
NMR (CD3OD): d 4.59 (br s, 1H, H-2), 4.30 (d, 1H,
J3,2 = 2.0 Hz, H-3), 4.03–3.97 (m, 1H, H-5a), 3.85–3.80
(m, 2H, H-4 and H-5b), 3.81 (d, 1H, J1a,1b = 12.5 Hz,
H-1a), 3.68 (dd, 1H, J1b,1a = 12.5 Hz, J1b,2 = 3.2 Hz,
0
0
0
0
H-1b), 3.47 (ddd, 1H, J1 a;1 b ¼ 12:5 Hz, J1 a;2 a
¼
J1 a;2 b ¼ 8:0 Hz, H-10a), 3.44 (q, 2H, J = 7.0 Hz,
0
0
0
0
0
0
–OCH2CH3), 3.41 (dd, 2H, J6 ;5 a ¼ J6 ;5 b ¼ 6:5 Hz,
H-60), 3.40 (ddd, 1H, J1 b;1 a ¼ 12:5 Hz, J1 b;2 a ¼ 8:5 Hz,
0
0
0
0
3. Schweden, J.; Borgmann, C.; Legler, G.; Bause, E. Arch.
Biochem. Biophys. 1986, 248, 335–340.
J1 b;2 b ¼ 6:0 Hz, H-10b), 1.91–1.79 (m, 2H, H-20), 1.59–
1.52 (m, 2H, H-50), 1.52–1.47 (m, 2H, H-30), 1.44–1.39
(m, 2H, H-40), 1.14 (t, 3H, J = 7.0 Hz, –OCH2CH3);
13C NMR (CD3OD): d 79.6 (C-3), 79.5 (C-2), 73.7 (C-
4), 71.5 (C-60), 67.3 (1C, –OCH2CH3), 61.0 (C-5), 50.1
(C-1), 46.6 (C-10), 30.4 (C-50), 29.0 (C-30), 26.8 (C-20),
26.7 (C-40), 15.5 (1C, –OCH2CH3); MALDI-TOF MS:
m/z 279.20 [MꢀCl]+. HRMS Calcd for C13H27ClO4S:
279.1630 [MꢀCl]+. Found: 279.1629.
0
0
4. van den Broek, L. A. G. M.; Vermaas, D. J.; Heskamp, B.
M.; van Boeckel, C. A. A.; Tan, M. C. A. A.; Bolscher, J.
G. M.; Ploegh, H. L.; van Kemenade, F. J.; de Goede, R.
E. Y.; Miedema, F. Rec. Trav. Chim. Pays-Bas 1993, 112,
82–94.
5. van den Broek, L. A. G. M.; Vermaas, D. J.; van
Kemenade, F. J.; Tan, M. C. A. A.; Rotteveel, F. T. M.;
Zandberg, P.; Butters, T. D.; Miedema, F.; Ploegh, H. L.;
van Boeckel, C. A. A. Rec. Trav. Chim. Pays-Bas 1994,
113, 507–516.
6. Mellor, H. R.; Nolan, J.; Pickering, L.; Wormald, M. R.;
Platt, F. M.; Dwek, R. A.; Fleet, G. W. J.; Butters, T. D.
Biochem. J. 2002, 366, 225–233.
7. Butters, T. D.; Van den Broek, L. A. G. M.; Fleet, G.
W. J.; Krulle, T. M.; Wormald, M. R.; Dwek, R. A.;
3.7.8.
1,4-Dideoxy-1,4-[[1-(9-methoxy)-nonyl]-(R)-epi-
sulfoniumylidene]-D-arabinitol chloride (17). Treatment
of sulfonium ion 38 (248 mg, 0.37 mmol) with BCl3 in
CH2Cl2 (7 mL), followed by treatment with Amberlyst

912
S. Mohan et al. / Carbohydrate Research 342 (2007) 901–912
Platt, F. M. Tetrahedron: Asymmetry 2000, 11, 113–
124.
8. Ghavami, A.; Johnston, B. D.; Pinto, B. M. J. Org. Chem.
2001, 66, 2312–2317.
16. (a) Sinnott, M. L. Chem. Rev. 1990, 90, 1171–1202; (b)
Davies, G.; Sinnott, M. L.; Withers, S. G. In Comprehen-
sive Biological Catalysis; Sinnott, M. L., Ed.; Academic
Press: New York, 1997; Chapter 3, pp 119–208; (c)
Heightman, T. D.; Vasella, A. T. Angew. Chem., Int. Ed.
1999, 38, 750–770; (d) Withers, S. G.; Namchuk, M.;
Mosi, R. In Iminosugars as Glycosidase inhibitors: Nojiri-
mycin and Beyond; Stutz, A. E., Ed.; Wiley-VCH:
Weinheim; New York, 1999; Chapter 9, pp 188–206.
17. Satoh, H.; Yoshi Yoshimura, Y.; Saskata, S.; Miura, S.;
Machida, H. Bioorg. Med. Chem. Lett. 1998, 8, 989–
992.
18. Doi, J. T.; Luehr, G. W. Tetrahedron Lett. 1985, 50, 6143–
6146.
19. (a) Kumar, N. S.; Pinto, B. M. J. Org. Chem. 2006, 71,
1262–1264; (b) Kumar, N. S.; Pinto, B. M. Carbohydr.
Res. 2006, 341, 1685–1691.
9. Ghavami, A.; Sadalapure, K. S.; Johnston, B. D.; Lobera,
M.; Snider, B. B.; Pinto, B. M. Synlett 2003, 9, 1259–1262.
10. Yuasa, H.; Takada, J.; Hashimoto, H. Tetrahedron Lett.
2000, 41, 6615–6618.
11. Johnston, B. D.; Ghavami, A.; Jensen, M. T.; Svensson,
B.; Pinto, B. M. J. Am. Chem. Soc. 2002, 124, 8245–8250.
12. Liu, H.; Pinto, B. M. J. Org. Chem. 2005, 70, 753–755.
13. Rossi, E. J.; Sim, L.; Kuntz, D. A.; Hahn, D.; Johnston, B.
D.; Ghavami, A.; Szczepina, M. D.; Kumar, N. S.;
Strerchi, E. E.; Nichols, B. L.; Pinto, B. M.; Rose, D. R.
FEBS J. 2006, 273, 2673–2683.
14. Ghavami, A.; Johnston, B. D.; Jensen, M. T.; Svensson,
B.; Pinto, B. M. J. Am. Chem. 2001, 123, 6268–6271.
15. Kumar, N. S.; Pinto, B. M. Carbohydr. Res. 2005, 340,
2612–2619.
20. Cox, M.; Prager, R. H.; Svensson, C. E. Aust. J. Chem.
2003, 56, 887–896.