Design and synthesis of selenonium and sulfonium ions related to the naturally occurring glucosidase inhibitor salacinol

Article abstract of DOI:10.1139/V06-100

Four series of analogues of the naturally occurring glucosidase inhibitor salacinol were synthesized for structure-activity studies with different glycosidase enzymes. The target zwitterionic compounds were synthesized by means of nucleophilic attack at t

Full text of DOI:10.1139/V06-100

1351
Design and synthesis of selenonium and
sulfonium ions related to the naturally occurring
glucosidase inhibitor salacinol1
Hui Liu and B. Mario Pinto
Abstract: Four series of analogues of the naturally occurring glucosidase inhibitor salacinol were synthesized for
structure–activity studies with different glycosidase enzymes. The target zwitterionic compounds were synthesized by
means of nucleophilic attack at the least-hindered carbon atom of the 1,3-cyclic sulfates derived from D-glucose and
D-mannose by the isopropylidene-protected 1,4-anhydro-4-thio- and seleno-D-allitols and the 4-thio- and seleno-L-
allitols. Deprotection of the coupled products afforded the novel sulfonium and selenonium ions containing polyhy-
droxylated acyclic chains of four and six carbons, with different stereochemistry at the stereogenic centers and with
1,4-anhydro-4-seleno or 4-thio-D- or L- alditol heterocyclic rings. The compounds showed no significant activity against
recombinant human maltase glucoamylase (MGA), a critical intestinal glucosidase involved in the processing of oligo-
saccharides of glucose into glucose itself.
Key words: glycosidase inhibitors, zwitterionic, selenonium salts, sulfonium salts, cyclic sulfates, L-ascorbic acid,
D-gulonic-γ-lactone.
Résumé : Afin de pouvoir faire des études de structure–activité avec divers enzymes glycosides, on a réalisé la syn-
thèse de quatre séries d’analogues du salacinol, un inhibiteur naturel de glucosidase. Les composés zwitterioniques ci-
bles ont été synthétisés par le biais d’une attaque nucléophile au niveau de l’atome de carbone le moins encombré de
sulfates 1,3-cycliques obtenus à partir du D-glucose et du D-mannose par des 1,4-anhydro-4-thio- et 1,4-anhydro-4-
séléno-D-allitols et des 4-thio- et 4-séléno-L-allitols. La déprotection des produits de couplage fournit des nouveaux ions
sulfonium et sélénonium qui contiennent des chaînes acycliques polyhydroxylées de quatre et de six carbones, avec des
stéréochimies différentes au niveau des centres stéréogènes et hétérocycles 1,4-anhydro-4-séléno- et 1,4-anhydro-4-thio-
D- ou L-alditols. Ces composés ne présentent aucune activité significative contre la maltase glucoamylase humaine
recombinante (MGA), une glucosidase intestinale critique dans la transformation des oligosaccharides du glucose en glucose.
Mots clés : inhibiteurs de glycosidase, zwitterion, sels de sélénonium, sels de sulfonium, sulfates cycliques, acide L-as-
corbique, γ-lactone de l’acide D-gulonique.
[Traduit par la Rédaction] Liu and Pinto 1362
Introduction
agement of blood glucose levels is crucial since their insulin
secretion may be normal, but the entry into cells of glucose
(normally mediated by insulin) is compromised (3).
Glycosidase inhibitors can be used to inhibit the activity of
intestinal glucosidases that break down oligosaccharides to
glucose. This enzyme inhibition delays glucose absorption
into the blood and results in a lowering or smoothing of the
blood glucose levels (4, 5).
There are two generally accepted mechanisms for the en-
zymatic hydrolysis of a glycosidic bond, proceeding either
with the inversion or retention of configuration at the
anomeric center (6, 7). In either case, protonation of the
exocyclic oxygen leads to cleavage of the glycosidic bond
with subsequent formation of an oxacarbenium ion. To gen-
erate potent glycosidase inhibitors, an attractive approach is
to create compounds that mimic the oxacarbenium ion tran-
sition state in the enzyme-catalyzed reaction. Some naturally
occurring compounds, such as acarbose (1) and voglibose
(2) (Chart 1), are potent glycosidase inhibitors and presum-
ably mimic the oxacarbenium ion, at least in binding to ac-
tive site carboxylate residues via the protonated nitrogen
atom (8, 9).
Glycosidases are responsible for the hydrolysis of poly-
and oligo-saccharides into monomers or the cleavage of
bonds between sugars and non-carbohydrate aglycons. In re-
cent years, much attention has focused on the synthesis and
development of glycosidase inhibitors because of an increas-
ing awareness of the vital role played by sugars in biological
processes and because of their therapeutic potential (1, 2). In
the case of patients suffering from Type II diabetes, the man-
Received 11 November 2005. Accepted 21 December 2005.
Published on the NRC Research Press Web site at
http://canjchem.nrc.ca on 19 September 2006.
Dedicated, with respect, to Dr. Alfred Bader for his impact
on the field of chemistry.
H. Liu and B.M. Pinto.2 Department of Chemistry, Simon
Fraser University, Burnaby, BC V5A 1S6, Canada.
1This article is part of a Special Issue dedicated to Dr. Alfred
Bader.
2Corresponding author (e-mail: bpinto@sfu.ca).
Can. J. Chem. 84: 1351–1362 (2006)
doi:10.1139/V06-100
© 2006 NRC Canada

1352
Can. J. Chem. Vol. 84, 2006
Chart 1.
Chart 3.
OH
OH
OH
OH
2'
3'
1'
HO
HO
HO
HO
OH
OH
4'
HO
HO
H
HO
O
X
OSO3
OH
X
4
OSO3
HN
5
HO
OH
HN
1
6
OH
O
O
HO
OH
H
OH
3
2
OH
HO
O
O
HO
OH
OHOH
OH
OH
OH
7 X = Se
8 X = S
9 X = Se
10 X = S
acarbose (1)
voglibose (2)
OH OH
OH OH
5'
Chart 2.
OH
3'
1'
HO
5
OH
OH OH
OH
H
X
2'
4'
6'
OH
OSO3 OH
HO
X
4
OSO3
OH
HO
OH
1
6
H
HO
3
S
OSO3
2
S
OSO3OH
HO
OH
HO
HO
OHOH
13 X = Se
14 X = S
11 X = Se
12 X = S
HO
OH
HO
OH
kotalanol (4)
salacinol (3)
ysis by NMR techniques (23) and X-ray crystallography
(24).
To further understand the enzyme discrimination of
related compounds, we now describe the synthesis of new
analogues of salacinol analogues 7–14 based on novel
seleno- and thio-alditols derived from D-gulonic-γ-lactone
and L-ascorbic acid (Chart 3).
OH
OH
OH
OH
Se
OSO3
NH OSO3
HO
HO
HO
OH
blintol (5)
HO
OH
ghavaminol (6)
Results and discussion
Recently, a new class of glycosidase inhibitors, including
salacinol (3) and kotalanol (4) (Chart 2), with an intriguing
inner-salt sulfonium sulfate structure was isolated from the
roots and stems of the plant Salacia reticulata (10–12). The
compounds were shown to be inhibitors of intestinal
glucosidase enzymes that attenuate the undesirable spike in
blood glucose that is experienced by diabetics after consum-
ing a meal rich in carbohydrates. It is postulated that the in-
hibition of glucosidases by salacinol and kotalanol is due to
their ability to mimic both the shape and charge of the
oxocarbenium ion-like transition state involved in the enzy-
matic reactions.
In our current research program, we have undertaken a
limited structure–activity study of salacinol and related com-
pounds. The synthesis of salacinol and its ammonium and
selenonium analogues have been reported by us and others
(13–17). Analogues containing six-membered heterocyclic
rings and some chain-extended analogues of salacinol have
also been synthesized (18–21). Some of these analogues ex-
hibited inhibitory activities in the micromolar range for re-
combinant human maltase glucoamylase, an intestinal
glucosidase (20, 21). The studies also showed an interesting
variation in the inhibitory power of these compounds against
glycosidase enzymes of different origin (14–17, 22). In par-
ticular, the stereochemistry at the different stereogenic cen-
ters as well as the nature of the heteroatom play significant
roles in discrimination between glycosidase enzymes. The
molecular basis for this selectivity is being investigated
through structural studies of the enzyme-bound inhibitors using
molecular modeling in conjunction with conformational anal-
The analogues 7–14 can be synthesized by alkylation of a
protected anhydroalditol at the ring heteroatom with termi-
nal 1,3-cyclic sulfates. The protected anhydroalditols and the
cyclic sulfates can be synthesized from the appropriate car-
bohydrate starting materials (Scheme 1).
The choice of protecting groups for the thio- and seleno-
anhydroalditols and the cyclic sulfates, however, merited
careful consideration, especially in the case of the selenonium
analogues. Hydrogenolysis and strongly basic conditions
proved to be problematic deprotection steps for similar
selenonium analogues; thus, these conditions needed to be
avoided (15–17). Therefore, we chose to use isopropylidene
and benzylidene acetals as the protecting groups for the thio-
and seleno-anhydroalditols 15–18 and the cyclic sulfates 19
and 20 since these acetals are both labile to acidic hydrolysis
(Chart 4).
Our previous work also suggested that the release of ring
strain in the opening of bicyclic sulfates was beneficial (14–
17). Therefore, the benzylidene acetal at the 2,4-positions of
the cyclic sulfates 19 and 20 played dual roles as protecting
groups and reaction facilitators for the coupling reactions
with compounds 15–18. After the coupling reactions, the
products could then be readily deprotected by simple treat-
ment with trifluoroacetic acid.
The synthesis of the isopropylidene-protected 1,4-
anhydro-4-seleno-D-allitol (15) and 1,4-anhydro-4-thio-D-
allitol (16) started from the commercially available D-gulonic-
γ-lactone (21, Scheme 2). 2,3,5,6-Di-O-isopropylidene-D-
gulonic-γ-lactone (22) (25) was reduced with sodium
borohydride to afford the corresponding diol 23. Compound
© 2006 NRC Canada

Liu and Pinto
1353
Scheme 1.
OP OP
OP OP
OSO3
OP
OP
OP
X
O
O
O
OP
S
RO
X
O
RO
RO
RO OR
X = S, Se
RO
OR
R, P = protecting groups
RO
Scheme 2.
OH
O
H
OH
O
MeO
OMe
H
O
O
1.NaBH4,
MeOH
O
O
O
HO
O
O
O
O
O
OH
Acetone, p-TSA
OHOH
23, 77%
21
22, 90%
O
O
Se
Se, NaBH4
EtOH
15, 62%
H
OMs
OMs
MsCl, pyr.
CH2Cl2
O
O
O
O
O
O
O
Na2S, DMF
S
O
16, 92%
24, 75%
H
O
O
Chart 4.
L-allitol (18) could, in principle, be prepared from L-gulonic-
γ-lactone, the high cost of this starting material made these
syntheses unrealistic. Thus, inexpensive and commercially
available L-ascorbic acid (25) was used as the starting mate-
rial to give the L-gulonic-γ-lactone (26) in 71% yield (27)
(Scheme 3). Compound 26 was then treated with 2,2-
dimethoxypropane in dry acetone containing p-toluene-
sulfonic acid as a catalyst to give 2,3,5,6-di-O-isopropyli-
dene-L-gulonic-γ-lactone (27) (25). The lactone 27 was
subsequently reduced with sodium borohydride to afford the
corresponding diol that was, in turn, converted to the
dimesylate 28 by treatment with methanesulfonyl chloride
and pyridine. When the dimesylate 28 was reacted with sele-
nium metal and sodium borohydride in EtOH at 60–65 °C,
the isopropylidene-protected 1,4-anhydro-4-seleno-L-allitol
17 was obtained in 67% yield. The isopropylidene-protected
1,4-anhydro-4-thio-L-allitol 18 was prepared in 82% yield by
treatment of the dimesylate 28 with sodium sulfide in DMF.
O
H
O
X
X
O
H
O
O
O
O
O
17 X = Se
18 X = S
15 X = Se
16 X = S
O
O
Ph
S
O
O
O
S
O
O
O
O
O
O
O
O
O
Ph
19
20
Since salacinol 3 and its selenonium analogue, blintol (5)
(Chart 2), are the most active, so far, of this class of glyco-
sidase inhibitors against human maltase glucoamylase, we
first concentrated on the coupling reactions of 15 and 16
with the cyclic sulfate 19, which would yield the identical
side chain present in salacinol and blintol (Scheme 4). The
solvent chosen for the coupling reactions was the unusual
solvent 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), which of-
fers significant advantage in these types of coupling reac-
tions compared with other solvents (15–17). The cyclic
sulfates 19, prepared as described previously (16), were re-
acted with 15 and 16, to give the corresponding protected
23 was then converted to the dimesylate 24 by treatment
with methanesulfonyl chloride and pyridine in 80% yield
(26). When the dimesylate 24 was reacted with selenium
metal and sodium borohydride in EtOH at 60–65 °C, the
isopropylidene-protected 1,4-anhydro-4-seleno-D-allitol 15
was obtained in 62% yield. The isopropylidene-protected
1,4-anhydro-4-thio-D-allitol 16 was prepared in 92% yield
by treatment of the dimesylate 24 with sodium sulfide in
DMF (Scheme 2).
Although the enantiomeric isopropylidene-protected
1,4-anhydro-4-seleno-L-allitol (17) and 1,4-anhydro-4-thio-
© 2006 NRC Canada

1354
Can. J. Chem. Vol. 84, 2006
Scheme 3.
O
H
O
OH
OH
MeO
O
OMe
HO
HO
O
O
O
Pd/C, H2
O
O
H
H
O
O
Acetone, p-TSA
HO
OH
HO
OH
25
26, 71%
27, 90%
H
Se, NaBH4
EtOH
Se
O
O
17, 67%
O
O
O
O
O
O
1. NaBH4, MeOH
2. MsCl, pyr.
O
H
S
OMs
OMs
Na2S, DMF
28, 45%
in two steps
O
18, 82%
O
O
Scheme 4.
Ph
O
O
O
O
S
O
O
O
O
X
O
HFIP/K2CO3
X
OSO3
+
O
H
O
O
H
X = Se, 65–70 °C
X = S, 70–75 °C
O
O
O
O
Ph
15 X = Se
16 X = S
19
29 X = Se, 90%
30 X = S, 94%
selenonium and sulfonium sulfates 29 and 30, respectively
(Scheme 4).
The coupling reactions of enantiomeric 17 and 18 with the
cyclic sulfate 19 were carried out analogously, to give the
corresponding protected selenonium and sulfonium sulfates
31 and 32, respectively (Scheme 5).
ing in higher yields of the coupling reactions. Thus, the cou-
pling reactions with the cyclic sulfate 19 usually proceeded
in yields of 90%–95%, while the cyclic sulfate 20 typically
gave yields of 70%–80%, with the remainder consisting of
starting materials and a small amount of decomposition
products. With the same cyclic sulfate, the selenoalditols
were slightly more reactive than their sulfur counterparts, as
demonstrated by the different reaction temperatures required
in the coupling reactions. The reactivities of the enantio-
meric pairs, compounds 15–17 and 16–18 with the cyclic
sulfates 19 and 20 were virtually the same. Selectivity for at-
tack at the primary center of the cyclic sulfates 19 and 20
over possible alternative attack at the secondary center by
compounds 15–18 was invariably excellent, and in no case
were isolable quantities of the regioisomers detected. In the
case of the coupling reaction of 15 and L-allitol 17 with the
cyclic sulfates 19 and 20, there was a small amount (5%–
10%) of the stereoisomer formed through electrophilic at-
tack on the β face of the seleno-D-allitol 15 and the α face of
the seleno-L-allitol 17 to give products that were diastereo-
meric at the selenonium center, but could not be isolated in
pure form. However, this type of minor product was not de-
tected in the reactions of the corresponding thioallitols.
We next turned our attention to the possibility of attaching
longer side chains to the anhydroalditols 15–18. Our interest
in longer side chains stemmed from the fact that kotalanol 4,
which has a seven-carbon side chain instead of four-carbon
side chain of the salacinol, exhibits stronger inhibitory activ-
ities toward certain glycosidase enzymes. Since the exact
stereochemistry of kotalanol 4 is not yet known, it is neces-
sary and important to study the structure–activity relation-
ships of these types of compounds systematically by
attaching side chains with different chain lengths and differ-
ent stereochemistry at the stereogenic centers to the
heterocyclic rings of the anhydroheteroalditols. The cyclic
sulfate 20, which consisted of a protected polyhydroxylated
six-carbon chain (19), was chosen for this purpose. The cy-
clic sulfate 20 reacted with 15 and 16 and their enantiomers
17 and 18 in HFIP to give the corresponding protected
selenonium and sulfonium compounds 33–36, respectively
(Scheme 6).
The deprotection of the coupled products 29–36 was car-
ried out by treatment with trifluoroacetic acid (Scheme 7).
After rinsing away the cleaved protecting groups with di-
chloromethane, the resulting residues were purified by flash
The reactivity of 15–18 with cyclic sulfates 19 and 20 var-
ied slightly. With the same anhydroalditols, the cyclic sulfate
19 was more reactive than the cyclic sulfate 20, also result-
© 2006 NRC Canada

Liu and Pinto
1355
Scheme 5.
Ph
O
O
O
O
O
S
O
O
H
X
H
HFIP/K2CO3
X
OSO3
+
O
O
O
X = Se, 65–70 °C
X = S, 70–75 °C
O
O
O
O
O
O
Ph
17 X = Se
18 X = S
31 X = Se, 90%
32 X = S, 92%
19
Scheme 6.
Ph
O
O
Ph
O
O
O
O
S
O
O
X
O
O
X
OSO3
HFIP/K2CO3
+
O
H
H
O
O
O
X = Se, 80–85 °C
X = S, 90–95 °C
O
O
O
O
O
O
33 X = Se, 70%
34 X = S, 82%
15 X = Se
16 X = S
20
Ph
O
O
Ph
O
O
O
H
X
H
O
OSO3
X
HFIP/K2CO3
+
O
O
O
O
O
O
O
O
X = Se, 80–85 °C
X = S, 90–95 °C
O
O
S
O
O
O
O
17 X = Se
18 X = S
35 X = Se, 67%
36X = S, 79%
20
chromatography to yield compounds 7–10 as amorphous,
hygroscopic solids. In the cases of compounds 33–36, how-
ever, some of the benzylidene acetal protecting group (up to
30% by NMR measurements) remained even after prolonged
(up to 48 h) treatment with TFA. The remaining benzylidene
acetal was eventually cleaved by hydrogenolysis in 80%
acetic acid to give the corresponding deprotected products
11–14 as amorphous, hygroscopic solids. The yields of com-
pounds 11–14 were low, partly because of the adsorption of
the products on the Pd–C catalyst. Compounds 7–14 were
characterized by spectroscopic methods. The MALDI-TOF
mass spectra of compounds 7–14 showed major fragmenta-
tion peaks (M + Na+ – SO3) together with the molecular ion
peaks (M + Na+) of much lower intensities.
The absolute stereochemistry at the heteroatom center of
compounds 7–14 was established by 1D-NOE NMR spec-
troscopy. For example, in the 1D-NOE spectrum of com-
pound 8 (Fig. 1), the H-4 to H-1′b correlation was clearly
exhibited, implying that these two hydrogens are syn-facial.
Therefore, C-1′ of the side chain must be anti to C-5 of the
sulfonium salt ring.
(MGA), a critical intestinal glucosidase involved in the pro-
cessing of oligosaccharides of glucose into glucose itself.
The compounds showed no significant activity.3
Conclusions
Four series of analogues of the naturally occurring
glucosidase inhibitor salacinol were synthesized. These ana-
logues contained the acyclic chains of salacinol and ex-
tended acyclic chains of six carbons, as well as ring
heteroatom substitution (Se, S). In addition, the heterocyclic
ring bore the D- or L-allitol configuration. These syntheses
utilized the 1,3-cyclic sulfates derived from commercially
available D-glucose and D-mannose. The isopropylidene and
benzylidene acetal protecting groups on the coupled prod-
ucts ensured facile deprotection with TFA to yield the final
compounds 7–14. The compounds showed no inhibitory ac-
tivity against human maltase glucoamylase.
Experimental section
As a final point of interest, compounds 7–14 were
screened against recombinant human maltase glucoamylase
General
1
Optical rotations were measured at 23 °C. H and 13C
3 L. Sim and D.R. Rose. Unpublished data.
© 2006 NRC Canada

1356
Can. J. Chem. Vol. 84, 2006
Scheme 7.
were obtained by the electrospray ionization (ESI) technique,
using a ZabSpec oaTOF mass spectrometer at 10 000 RP.
OH
HO
OH
OSO3
2,3,5,6-Di-O-isopropylidene-1,4-di-O-methanesulfonyl-D-
gulitol (24)
HO
X
H
2,3,5,6-Di-O-isopropylidene-1,4-di-O-methanesulfonyl-D-
gulitol (24) was prepared by the literature method (26) with
slight variations. To a solution of commercially available D-
gulonic-γ-lactone 21 (10.0 g, 56.1 mmol) in dry acetone
(200 mL), 2,2-dimethoxypropane (40 mL, 0.32 mmol) was
added at RT. To this solution, p-toluenesulfonic acid (200 mg)
was added as a catalyst. The progress of the reaction was
followed by TLC analysis of the aliquots (hexane–EtOAc,
1:1). When the starting material 21 had been essentially con-
sumed, the reaction was stopped by addition of triethylamine
(1 mL) to the reaction mixture. The solvent was then evapo-
rated under reduced pressure and the residue was purified by
column chromatography (hexane–EtOAc, 1:1) to give com-
pound 22 as a white solid (13.1 g, 90%). The NMR spec-
trum of compound 22 matched that of the published data
(25). The lactone 22 (5.0 g, 19.3 mmol) was dissolved in
THF (20 mL) and MeOH (50 mL) was then added. To this
solution, NaBH4 was added portionwise at 0 °C. The prog-
ress of the reaction was followed by TLC analysis of the
aliquots (hexane–EtOAc, 1:1). When the starting material 22
had been consumed, the solvent was evaporated under re-
duced pressure. The residue was redissolved in EtOAc
(50 mL), washed with aqueous tartaric acid solution (2 ×
10 mL) and brine (50 mL), and dried over Na2SO4. Purifica-
tion by column chromatography (hexane–EtOAc, 2:1)
yielded compound 23 as a colourless syrup (3.9 g, 77%).
The NMR spectrum of compound 23 matched that of the
published data (26). The diol 23 (5.0 g, 19.1 mmol) was dis-
solved in CH2Cl2 (50 mL) and the solution was added
HO
OH
7 X = Se, 57%
8 X = S, 69%
OH
OH
OSO3
H
X
HO
HO
HO
OH
9 X = Se, 61%
10 X = S, 65%
TFA
29–36
OH OH
HO
OH
HO
OH
OSO3
X
H
HO
OH
11 X = Se, 38%
12 X = S, 42%
OH OH
OSO3
OH
H
OH
X
HO
HO
HO
OH
dropwise to a mixture of pyridine (100 mL) and
methanesulfonyl chloride (6 mL, 77.5 mmol) and cooled to
0 °C. The reaction mixture was stirred at 0 °C for 30 min
and then allowed to warm to RT for 6 h. When TLC analysis
of the aliquots (hexane–EtOAc, 1:1) showed total consump-
tion of the starting material, the reaction mixture was poured
into ice water, extracted with CH2Cl2 (3 × 100 mL), washed
with brine (50 mL), and dried over Na2SO4. Purification by
column chromatography (hexane–EtOAc, 2:1) yielded com-
13 X = Se, 47%
14X = S, 41%
Fig. 1. NOE correlation observed in the 1D-NOE spectrum of
compound 8.
pound 24 as a colourless syrup (5.9 g, 75%). [α]22 –46° (c
D
1, CH2Cl2). 1H NMR ((CD3)2O) δ: 4.87 (dd, 1H, J3,4
=
5.8 Hz, J4,5 = 4.7 Hz, H-4), 4.56 (ddd, 1H, J1b,2 = 6.0 Hz,
J1a,1b = 12.0 Hz, H-1b), 4.56–4.48 (m, 2H, H-2, H-3, H-1a),
4.48 (dd, 1H, H-1a), 4.46 (ddd, 1H, H-5), 4.14 (dd, 1H,
J5,6b = 6.8 Hz, J6a,6b = 8.7 Hz, H-6b), 4.02 (dd, 1H, J5,6a
=
6.7 Hz, H-6a), 3.23, 3.14 (2 s, 6H, 2 × OSO2CH3), 1.51,
1.41, 1.38, 1.34 (4 s, 12H, 4 × CH3). 13C NMR ((CD3)2O) δ:
110.1, 109.6 ((CH3)2C(OR)2), 79.1 (C-4), 75.6 (C-3), 75.0
(C-2), 74.9 (C-1), 68.7 (C-5), 65.4 (C-6), 38.8, 36.7 (2 ×
OSO2CH3), 26.9, 25.6, 25.1, 25.0 (4 × CH3). Anal. calcd. for
C14H26O10S2: C 40.18, H 6.26; found: C 40.35, H 6.14.
NMR spectra were recorded at 500 and 125 MHz, respec-
tively. All assignments were confirmed with the aid of two-
dimensional 1H and 1H (COSYDFTP) or 1H and 13C
(INVBTP) experiments using standard Bruker pulse pro-
grams. Column chromatography was performed with Merck
silica gel 60 (230–400 mesh). MALDI mass spectra were
obtained on a PerSeptive Biosystems Voyager DE time-of-
2,3,5,6-Di-O-isopropylidene-1,4-di-O-methanesulfonyl-L-
gulitol (28)
flight spectrometer for samples dispersed in
dihydroxybenzoic acid matrix. High-resolution mass spectra
a
2,5-
To a solution of commercially available L-ascorbic acid 25
(30.0 g, 0.17 mmol) in distilled water (200 mL), palladium
© 2006 NRC Canada

Liu and Pinto
1357
on activated carbon (10%, 1.0 g) was added as a catalyst at
RT. The reaction mixture was placed in a steel reaction vessel
and underwent hydrogenation (100 psi, 1 psi = 6.894 757 kPa)
at 60 °C for 48 h. The progress of the reaction was followed
by TLC analysis of the aliquots (EtOAc–MeOH–H2O,
10:3:1). When the starting material 25 had been essentially
consumed, the reaction was stopped and the reaction mixture
was filtered under vacuum and washed with water (2 ×
50 mL). The filtrate and the wash were combined and the
water was then evaporated under reduced pressure. The resi-
due was recrystallized from methanol – ethyl acetate to give
compound 26 as a white solid (21.5 g, 71%). The NMR
spectrum of compound 26 matched that of the published lit-
erature (26). To a suspension of the lactone 26 (10.0 g,
56.1 mmol) in dry acetone (200 mL), 2,2-dimethoxypropane
(40 mL, 0.32 mmol) was added at RT. To this mixture, p-
toluenesulfonic acid (200 mg) was added as a catalyst. The
progress of the reaction was followed by TLC analysis of
the aliquots (hexane–EtOAc, 1:1). When the starting mate-
rial 26 had been essentially consumed, the reaction was
stopped by addition of triethylamine (1 mL). The solvent
was then evaporated under reduced pressure and the residue
was purified by column chromatography (hexane–EtOAc,
1:1) to give compound 27 as a white solid. The NMR spec-
trum of compound 26 matched that of the published data
(25). Lactone 27 (5.0 g, 19.3 mmol) was dissolved in THF
(20 mL) and MeOH (50 mL) was then added. To this solu-
tion, NaBH4 was added portionwise at 0 °C. The progress of
the reaction was followed by TLC analysis of the aliquots
(hexane–EtOAc, 1:1). When the starting material 27 had
been consumed, the solvent was evaporated under reduced
pressure. The residue was redissolved in EtOAc (50 mL),
washed with aqueous tartaric acid solution (2 × 10 mL) and
brine (50 mL), and dried over Na2SO4. After evaporating the
solvent, the crude diol was used directly in the next step.
The crude diol was dissolved in CH2Cl2 (50 mL). The solu-
tion was added dropwise to a mixture of pyridine (100 mL)
and methanesulfonyl chloride (6 mL, 77.5 mmol) and cooled
to 0 °C. The reaction mixture was stirred at 0 °C for 30 min,
then allowed to warm to RT for 6 h. When TLC analysis of
the aliquots (hexane–EtOAc, 1:1) showed total consumption
of the starting material, the reaction mixture was poured into
ice water, extracted with CH2Cl2 (3 × 100 mL), washed with
brine (50 mL), and dried over Na2SO4. Purification by col-
umn chromatography (hexane–EtOAc, 2:1) yielded com-
20.2 mmol) and 95% EtOH (100 mL), NaBH4 was added
portionwise until the black Se color disappeared. To this
mixture, a solution of the dimesylate 24 (7.0 g, 16.8 mmol)
in THF (10 mL) was added and the reaction mixture was
heated at 70 °C for 12 h. The solvent was evaporated under
reduced pressure, the residue was redissolved in EtOAc,
washed with water (20 mL) and brine (20 mL), and dried
over Na2SO4. After evaporating the solvent, the crude prod-
uct was purified by column chromatography (hexane–
EtOAc, 3:1) to give 15 as a colourless oil (3.2 g, 62%).
[α]22 +152° (c 1, CH2Cl2). 1H NMR ((CD3)2O) δ: 4.98
D
(ddd, 1H, J1b,2 = 4.5 Hz, H-2), 4.91 (dd, 1H, J2,3 = 5.6 Hz,
H-3), 4.12 (dd, 1H, J6a,6b = 8.4 Hz, J5,6b = 6.4 Hz, H-6b),
4.04 (ddd, 1H, J5,6a = 5.9 Hz, J4,5 = 5.8 Hz, H-5), 3.71 (dd,
1H, H-6a), 3.18 (m, 1H, H-4), 3.16 (dd, 1H, J1a,1b = 12.8 Hz,
H-1b), 2.78 (dd, 1H, H-1a), 1.42, 1.38, 1.29, 1.28 (4 s, 12H,
4 × CH3). 13C NMR ((CD3)2O) δ: 110.3, 109.8 ((CH3)2C(OR)2),
85.6 (C-3), 83.9 (C-2), 76.4 (C-5), 69.0 (C-6), 57.7 (C-4),
37.4 (C-1), 26.5, 26.0, 25.1, 24.1 (4 × CH3). Anal. calcd. for
C12H20O4Se: C 46.91, H 6.56; found: C 46.67, H 6.37.
1,4-Anhydro-2,3,5,6-di-O-isopropylidene-4-thio-D-allitol (16)
To a solution of the dimesylate 24 (5.0 g, 11.9 mmol) in
DMF (80 mL), Na2S·9H2O (4.0 g, 16.7 mmol) was added
and the reaction mixture was heated at 90 °C for 12 h. The
reaction mixture was poured into water (100 mL), extracted
with Et2O (4 × 50 mL), washed with water (10 × 20 mL),
and dried over Na2SO4. After evaporating the solvent, the
crude product was purified by column chromatography
(hexane–EtOAc, 3:1) to give 16 as a colourless oil (2.9 g,
1
92%). [α]22 +127° (c 1, CH2Cl2). H NMR ((CD3)2O) δ:
D
5.04 (ddd, 1H, J1b,2 = 4.7 Hz, H-2), 4.91 (dd, 1H, J2,3
=
5.6 Hz, H-3), 4.15–4.12 (m, 1H, H-4), 4.13 (dd, 1H, H-6b),
3.68 (ddd, 1H, J5,6a = 6.7 Hz, J4,5 = 9.2 Hz, J5,6b = 8.2 Hz,
H-5), 3.45 (dd, 1H, J6a,6b = 8.5 Hz, H-6a), 3.29 (dd, 1H,
J1a,1b = 11.2 Hz, H-1b), 2.92 (dd, 1H, H-1a), 1.42, 1.38,
1.29, 1.27 (4 s, 12H, 4 × CH3). 13C NMR ((CD3)2O) δ:
109.9, 109.8 ((CH3)2C(OR)2), 87.1 (C-3), 85.3 (C-2), 77.1
(C-5), 69.6 (C-6), 52.6 (C-4), 29.7 (C-1), 26.6, 26.2, 25.2,
24.1 (4 × CH3). Anal. calcd. for C12H20O4S: C 55.36, H
7.74; found: C 55.64, H 7.72.
1,4-Anhydro-2,3,5,6-di-O-isopropylidene-4-seleno-L-
allitol (17)
To
a suspension of grey selenium metal (1.4 g,
pound 28 as a colourless syrup (3.6 g, 45% for two steps).
1
[α]22 +54° (c 4, CH2Cl2). H NMR ((CD3)2O) δ: 4.87 (dd,
18.7 mmol) and EtOH (100 mL, 95%), NaBH4 was added
portionwise until the black Se color disappeared. To this
mixture, a solution of the dimesylate 28 (6.0 g, 14.3 mmol)
in THF (10 mL) was added and the reaction mixture was
heated at 65–70 °C for 12 h. The solvent was evaporated un-
der reduced pressure and the residue was redissolved in
EtOAc, washed with water (20 mL) and brine (20 mL), and
dried over Na2SO4. After evaporating the solvent, the crude
product was purified by column chromatography (hexane–
EtOAc, 3:1) to give 17 as a colourless oil (2.9 g, 67%).
D
1H, J3,4 = 6.1 Hz, J4,5 = 4.8 Hz, H-4), 4.57 (ddd, 1H, J1b,2
=
6.0 Hz, J1a,1b = 12.0 Hz, H-1b), 4.56–4.48 (m, 3H, H-2, H-3,
H-1a), 4.45 (ddd, 1H, H-5), 4.13 (dd, 1H, J5,6b = 6.7 Hz,
J6a,6b = 8.6 Hz, H-6b), 4.03 (dd, 1H, J5,6a = 6.6 Hz, H-6a),
3.24, 3.15 (2 s, 6H, 2 × OSO2CH3), 1.52, 1.41, 1.38, 1.34
(4 s, 12H, 4 × CH3). 13C NMR ((CD3)2O) δ: 114.3, 113.8
((CH3)2C(OR)2), 83.3 (C-4), 79.7 (C-3), 79.0 (C-2), 78.9 (C-
1), 72.9 (C-5), 69.6 (C-6), 43.0, 40.9 (2 × OSO2CH3), 31.3,
29.9, 29.3, 29.2 (4 × CH3). Anal. calcd. for C14H26O10S2: C
40.18, H 6.26; found: C 39.89, H 6.02.
[α]22 –143° (c 1, CH2Cl2). 1H NMR ((CD3)2O) δ: 5.03
D
(ddd, 1H, H-2), 4.91 (dd, 1H, J2,3 = 5.6 Hz, H-3), 4.15–4.10
(m, 2H, H-5, H-6b), 3.68 (dd, 1H, J5,6a = 8.9 Hz, J6a,6b
11.4 Hz, H-6a), 3.45 (dd, 1H, H-4), 3.27 (dd, 1H, J1b,2
4.7 Hz, J1a,1b = 12.0 Hz, H-1b), 2.92 (dd, 1H, J1b,2 = 0.7 Hz,
=
=
1,4-Anhydro-2,3,5,6-di-O-isopropylidene-4-seleno-D-allitol (15)
To
a
suspension of grey selenium metal (1.6 g,
© 2006 NRC Canada

1358
Can. J. Chem. Vol. 84, 2006
H-1a), 1.42, 1.37, 1.29, 1.27 (4 s, 12H, 4 × CH3). 13C NMR
((CD3)2O) δ: 110.0, 109.8 ((CH3)2C(OR)2), 87.1 (C-3), 85.3
(C-2), 77.1 (C-5), 69.6 (C-6), 52.6 (C-4), 29.8 (C-1), 26.6,
26.2, 25.3, 24.1 (4 × CH3). Anal. calcd. for C12H20O4Se: C
46.91, H 6.56; found: C 46.76, H 6.66.
71.5 (C-3), 52.8 (C-1), 50.4 (C-1′), 30.3, 30.1, 28.2, 27.1
(4 × CH3). HRMS calcd. for C23H33O10SSe: 581.0594 (M +
H+); found: 581.0597.
1,4-Anhydro-2,3,5,6-di-O-isopropylidene-1-[(S)-[(2′S,3′S)-
2′,4′-benzylidenedioxy-3′-(sulfooxy)butyl]sulfonio]-D-allitol
inner salt (30)
1,4-Anhydro-2,3,5,6-di-O-isopropylidene-4-thio-L-allitol (18)
To a solution of the dimesylate 28 (5.0 g, 11.9 mmol) in
DMF (80 mL), Na2S·9H2O (4.0 g, 16.7 mmol) was added
and the reaction mixture was heated at 90 °C for 12 h. The
reaction mixture was poured into water (100 mL), extracted
with Et2O (4 × 50 mL), washed with water (10 × 20 mL),
and dried over Na2SO4. After evaporating the solvent, the
crude product was purified by column chromatography
The reaction of compound 16 (500 mg, 1.92 mmol) with
the cyclic sulfate 19 (630 mg, 2.31 mmol) in HFIP (2.0 mL)
for 12 h at 70–75 °C gave compound 30 as a colourless,
amorphous solid (960 mg, 94% based on 16). [α]22 +1.2°
D
1
(c 0.1, CH2Cl2). H NMR ((CD3)2O) δ: 7.56–7.38 (m, 5H,
H-Arom.), 5.74 (s, 1H, CHPh), 5.52 (ddd, 1H, J1b,2
=
5.2 Hz, J2,3 = 5.7 Hz, H-2), 5.26 (dd, 1H, H-3), 4.79 (ddd,
1H, ddd, 1H, J5,6b = 7.4 Hz, J5,6a = 5.1 Hz, J4,5 = 3.9 Hz, H-
5), 4.63 (dd, 1H, H-4), 4.49–4.36 (m, 4H, H-1′b, H-2′, H-3′,
H-4′b), 4.28 (dd, 1H, J1′a,1′b = 13.4 Hz, J1′a,2′ = 3.7 Hz, H-
1′a), 4.25 (dd, 1H, J6a,6b = 9.4 Hz, H-6b), 4.10 (dd, 1H,
J1b,2 = 5.2 Hz, J1a,1b = 14.4 Hz, H-1b), 3.97 (dd, 1H, H-1a),
3.97 (dd, 1H, J5,6a = 5.1 Hz, H-6a), 3.78 (m, 1H, H-4′a),
1.64, 1.42, 1.38, 1.32 (4s, 18H, 4 × CH3). 13C NMR
((CD3)2O) δ: 138.5, 129.3, 128.4, 126.5 (C-Ar), 112.3, 111.1
(2 (CH3)2C(OR)2), 101.4 (CHPh), 85.3 (C-3), 85.2 (C-2),
76.7 (C-2′), 74.4 (C-5), 69.2 (C-4′), 68.8 (C-4), 67.1 (C-6),
67.0 (C-3′), 48.2 (C-1), 45.8 (C-1′), 25.7, 25.5, 23.6, 22.5
(4 × CH3). Anal. calcd. for C23H32O10S2: C 51.86, H 6.06;
found: C 52.06, H 5.87. HRMS calcd. for C23H33O10S2:
533.1510 (M + H+); found: 533.1512.
(hexane–EtOAc, 3:1) to give 18 as a colourless oil (2.5 g,
1
82%). [α]22 –139° (c 1, CH2Cl2). H NMR ((CD3)2O) δ:
D
4.99 (ddd, 1H, H-2), 4.92 (dd, 1H, J2,3 = 5.6 Hz, H-3), 4.12
(dd, 1H, J6a,6b = 8.2 Hz, J5,6b = 6.4 Hz, H-6b), 4.04 (ddd,
1H, H-5), 3.71 (dd, 1H, J5,6a = 5.9 Hz, H-6a), 3.19–3.15 (m,
1H, H-4), 3.17 (dd, 1H, H-1b), 2.80 (dd, 1H, J1a,1b
=
12.9 Hz, H-1a), 1.42, 1.38, 1.29, 1.28 (4 s, 12H, 4 × CH3).
13C NMR ((CD3)2O) δ: 110.3, 109.8 ((CH3)2C(OR)2), 85.6
(C-3), 83.9 (C-2), 76.3 (C-5), 69.0 (C-6), 57.7 (C-4), 37.4
(C-1), 26.5, 26.0, 25.1, 24.1 (4 × CH3). Anal. calcd. for
C12H20O4S: C 55.36, H 7.74; found: C 55.16, H 7.58.
General procedure for the preparation of sulfonium
and selenonium sulfates 29–36
A mixture of 15, 16, 17, or 18, and the cyclic sulfate 19 or
20 in HFIP (1,1,1,3,3,3-hexafluoroisopropanol) was placed
in a reaction vessel and K2CO3 (20 mg) was added. The
stirred reaction mixture was heated in a sealed tube at the in-
dicated temperature for the indicated time, as given later.
The progress of the reaction was followed by TLC analysis
of the aliquots (EtOAc–MeOH, 10:1). When the limiting re-
agent had been essentially consumed, the mixture was
cooled, diluted with CH2Cl2, and evaporated to give a syrupy
residue. Purification by column chromatography (EtOAc to
EtOAc–MeOH, 10:1) gave the purified sulfonium salts and
selenonium salts 29–36.
1,4-Anhydro-2,3,5,6-di-O-isopropylidene-1-[(S)-[(2′S,3′S)-
2′,4 -benzylidenedioxy-3′-(sulfooxy)butyl]selenonio]-L-
allitol inner salt (31)
The reaction of compound 17 (500 mg, 1.63 mmol) with
the cyclic sulfate 19 (530 mg, 1.94 mmol) in HFIP (2.0 mL)
for 12 h at 65–70 °C gave compound 31 as a colourless,
amorphous solid (850 mg, 90% based on 17). [α]22 +18°
D
1
(c 1.0, CH2Cl2). H NMR (CD2Cl2) δ: 7.48–7.38 (m, 5H, H-
Arom.), 5.61 (s, 1H, CHPh), 5.41 (ddd, 1H, H-2), 5.15 (dd,
1H, J2,3 = 5.3 Hz, H-3), 4.81 (ddd, 1H, J4,5 = 2.0 Hz, J5,6a
=
4.6 Hz, J5,6b = 7.8 Hz, H-5), 4.60 (m, 1H, H-4), 4.55 (ddd,
1H, H-3′), 4.52 (dd, 1H, H-4′b), 4.42 (d, 2H, H-1′b, H-1′a),
4.38–4.32 (m, 1H, H-2′), 4.20 (dd, 1H, J5,6b = 7.8 Hz,
J6a,6b = 9.6 Hz, H-6b), 3.95 (dd, 1H, J5,6a = 4.6 Hz, H-6a),
3.85 (dd, 1H, J4′a,4′b = 10.0 Hz, H-4′a), 3.63 (dd, 1H, H-1b),
3.60 (dd, 1H, J1a,2 = 5.1 Hz, J1a,1b = 13.9 Hz, H-1a), 1.60,
1.44, 1.36, 1.32 (4 s, 12H, 4 × CH3). 13C NMR (CD2Cl2) δ:
137.0, 129.5, 128.6, 126.3 (C-Ar), 112.1, 111.2 (2
(CH3)2C(OR)2), 101.8 (CHPh), 87.8 (C-2), 85.7 (C-3), 76.9
(C-3′), 74.7 (C-5), 70.5 (C-4), 69.3 (C-4′), 67.7 (C-2′), 67.2
(C-6), 44.5 (C-1′), 43.2 (C-1), 26.2, 26.0, 23.3, 22.9 (4 ×
CH3). Anal. calcd. for C23H32O10SSe: C 47.67, H 5.57;
found: C 47.89, H 5.67.
1,4-Anhydro-2,3,5,6-di-O-isopropylidene-1-[(S)-[(2′S,3′S)-
2′,4 -benzylidenedioxy-3′-(sulfooxy)butyl]selenonio]-D-
allitol inner salt (29)
The reaction of compound 15 (500 mg, 1.63 mmol) with
the cyclic sulfate 19 (530 mg, 1.94 mmol) in HFIP (2.0 mL)
for 12 h at 80–85 °C gave compound 29 as a colourless,
amorphous solid (850 mg, 90% based on 15). [α]22 +12°
D
1
(c 0.5, CH2Cl2). H NMR ((CD3)2O) δ: 7.56–7.38 (m, 5H,
H-Arom.), 5.74 (s, 1H, CHPh), 5.52 (ddd, 1H, J1b,2
=
5.2 Hz, J2,3 = 5.7, H-2), 5.27 (dd, 1H, H-3), 4.78 (ddd, 1H,
ddd, 1H, J5,6b = 7.3 Hz, J5,6a = 5.2 Hz, J4,5 = 3.8 Hz, H-5),
4.62 (dd, 1H, H-4), 4.46–4.37 (m, 4H, H-1′b, H-2′, H-3′, H-
4′b), 4.28 (dd, 1H, J1′a,1′b = 13.4 Hz, J1′a,2′ = 3.8 Hz, H-1′a),
4.25 (dd, 1H, J6a,6b = 9.5 Hz, J5,6b = 7.3 Hz, H-6b), 4.10 (dd,
1H, J1b,2 = 5.2 Hz, J1a,1b = 15.4 Hz, H-1b), 3.97 (dd, 1H, H-
1a), 3.96 (dd, 1H, J5,6a = 5.2 Hz, H-6a), 3.78 (m, 1H, H-4′a),
1.64, 1.42, 1.38, 1.32 (4 s, 18H, 4 × CH3). 13C NMR
((CD3)2O) δ: 142.3, 133.9, 133.0, 131.1 (C-Ar), 116.9, 115.7
(2 (CH3)2C(OR)2), 106.1 (CHPh), 89.9 (C-3), 89.8 (C-2),
81.3 (C-2′), 79.0 (C-5), 73.9 (C-4), 73.5 (C-4′), 71.8 (C-6),
1,4-Anhydro-2,3,5,6-di-O-isopropylidene-1-[(S)-[(2′S,3′S)-
2′,4′-benzylidenedioxy-3′-(sulfooxy)butyl]sulfonio]-L-allitol
inner salt (32)
The reaction of compound 18 (500 mg, 1.92 mmol) with
the cyclic sulfate 19 (630 mg, 2.31 mmol) in HFIP (2.0 mL)
for 12 h at 80–85 °C gave compound 32 as a colourless,
amorphous solid (940 mg, 92% based on 18). [α]22D +10° (c
1
0.5, CH2Cl2). H NMR ((CD3)2O) δ: 7.48–7.39 (m, 5H, H-
© 2006 NRC Canada

Liu and Pinto
1359
Arom.), 5.59 (s, 1H, CHPh), 5.26 (ddd, 1H, H-2), 5.10 (dd,
1H, J2,3 = 5.8 Hz, H-3), 4.88 (ddd, 1H, J4,5 = 7.6 Hz, H-5),
1H, J1a,1b = 14.3 Hz, H-1a), 1.61, 1.43, 1.37, 1.30, 1.29, 1.28
(6 s, 18H, 6 × CH3). 13C NMR ((CD3)2O) δ: 138.2, 129.1,
4.68 (ddd, 1H, H-3′), 4.54 (m, 1H, H-4), 4.50 (dd, 1H, J3′,4′
=
128.4, 126.3 (C-Ar), 112.1, 110.9, 107.5 (3
×
1.8 Hz, H-4′), 4.40 (d, 2H, H-1′b, H-1′a), 4.34 (m, 1H, H-2′),
4.32 (dd, 1H, J5,6b = 7.9 Hz, J6a,6b = 9.8 Hz, H-6b), 4.01 (dd,
1H, J5,6a = 4.6 Hz, H-6a), 3.82 (dd, 1H, H-4′a), 3.68 (dd, 1H,
J1b,2 = 5.3 Hz, J1a,1b = 15.0 Hz, H-1b), 3.62 (dd, 1H, H-1a),
1.60, 1.44, 1.36, 1.34 (4 s, 12H, 4 × CH3). 13C NMR
((CD3)2O) δ: 136.9, 129.6, 128.6, 126.3 (C-Ar), 112.8, 111.5
(2 (CH3)2C(OR)2), 101.9 (CHPh), 86.2 (C-2), 84.1 (C-3),
76.9 (C-3′), 74.8 (C-5), 71.4 (C-4), 69.2 (C-2), 67.3 (C-6),
65.7 (C-4′), 47.7 (C-1), 45.9 (C-1′), 26.0, 25.9, 23.3, 22.6 (4
× CH3). HRMS calcd. for C23H33O10S2: 533.1510 (M + H+);
found: 533.1515.
(CH3)2C(OR)2), 100.7 (CHPh), 86.2 (C-2), 84.5 (C-3), 79.0
(C-4), 76.7 (C-5′), 74.7 (C-5), 74.1 (C-2′), 70.3 (C-3′), 70.0
(C-4′), 67.1 (C-6), 64.6 (C-6′), 47.9 (C-1), 46.1 (C-1′), 23.9,
25.6, 25.5, 25.4, 23.4, 22.4 (6 × CH3). Anal. calcd. for
C28H40O12S2: C 53.15, H 6.37; found: C 52.92, H 6.17.
1,4-Anhydro-2,3,5,6-di-O-isopropylidene-1-[(S)-
[(2′R,3′S,4′R,5′R)-2′,4′-benzylidenedioxy-5′,6′-isopro-
pylidenedioxy-3′-(sulfooxy)hexyl]selenonio]-L-allitol inner
salt (35)
The reaction of compound 17 (500 mg, 1.63 mmol) with
the cyclic sulfate 20 (730 mg, 1.96 mmol) in HFIP (2.0 mL)
for 12 h at 80–85 °C gave compound 35 as a colourless,
1,4-Anhydro-2,3,5,6-di-O-isopropylidene-1-[(S)-
[(2′R,3′S,4′R,5′R)-2′,4′-benzylidenedioxy-5′,6′-isopropyli-
denedioxy-3′-(sulfooxy)hexyl]selenonio]-D-allitol inner salt
(33)
amorphous solid (740 mg, 67% based on 17). [α]22 –12°
D
1
(c 1, CH2Cl2). H NMR ((CD3)2O) δ: 7.60–7.38 (m, 5H, H-
Arom.), 5.92 (s, 1H, CHPh), 5.55 (ddd, 1H, H-2), 5.21 (dd,
1H, J2,3 = 5.4 Hz, J3,4 = 1.8 Hz, H-3), 4.96–4.92 (m, 1H, H-
2′), 4.60 (dd, 1H, H-3′), 4.53 (dd, 1H, J1′b,2′ = 6.4 Hz,
J1′b,1′a = 12.2 Hz, H-1′ b), 4.45 (ddd, 1H, J4,5 = 2.3 Hz,
J5,6′a = 9.2 Hz, J5,6′b = 6.9 Hz, H-5′), 4.41 (dd, 1H, H-4′),
4.40–4.36 (m, 1H, H-5), 4.34 (dd, 1H, J6′a,6′b = 8.6 Hz, H-
6′b), 4.24–4.18 (m, 3H, H-4, H-1′a, H-6′a), 3.99 (dd, 1H, 1H,
The reaction of compound 15 (500 mg, 1.63 mmol) with
the cyclic sulfate 20 (730 mg, 1.96 mmol) in HFIP (2.0 mL)
for 12 h at 80–85 °C gave compound 33 as a colourless,
amorphous solid (770 mg, 70% based on 15). [α]22 +8° (c
D
1
0.5, CH2Cl2). H NMR ((CD3)2O) δ: 7.58–7.32 (m, 5H, H-
Arom.), 5.90 (s, 1H, CHPh), 5.63 (ddd, 1H, J2,3 = 5.4 Hz, H-
2), 5.26 (dd, 1H, H-3), 4.92 (m, 1H, H-2′), 4.82 (ddd, 1H,
J5,6b = 7.7 Hz, J5,6a = 4.9 Hz, J4,5 = 3.2 Hz, H-5), 4.62 (dd,
1H, J1′a,1′b = 12.2 Hz, J1′b,2′ = 5.9 Hz, H-1′ b), 4.59–4.57 (m,
2H, H-3′, H-4), 4.46 (ddd, 1H, J4′,5′ = 2.3 Hz, J5′,6′a = 8.1 Hz,
J5′,6′b = 6.8 Hz, H-5′), 4.40 (m, 1H, H-4′), 4.29 (dd, 1H,
J6′a,6′b = 8.5 Hz, H-6′b), 4.28 (dd, 1H, H-6b), 4.18 (dd, 1H,
H-1′a), 4.16 (dd, 1H, H-6′a), 4.08 (dd, 1H, J6a,6b = 9.5 Hz,
H-6a), 3.76 (dd, 1H, J1a,1b = 14.1 Hz, J1b,2 = 5.4 Hz, H-1b),
3.60 (dd, 1H, H-1a), 1.59, 1.43, 1.36, 1.33, 1.31, 1.29, 1.28
(6 s, 18H, 6 × CH3). 13C NMR ((CD3)2O) δ: 138.2, 129.1,
J5,6b = 7.3 Hz, J6a,6b = 9.3 Hz, H-6b), 3.96 (dd, 1H, J1b,2
=
5.2 Hz, H-1b), 3.90 (dd, 1H, J1a,1b = 14.2 Hz, H-1a), 3.76
(dd, 1H, J5,6a = 5.2 Hz, H-6a), 1.59, 1.39, 1.35, 1.30, 1.29,
1.25 (6 s, 18H, 6 × CH3). 13C NMR ((CD3)2O) δ: 142.9,
133.9, 133.1, 131.0 (C-Ar), 116.1, 115.3, 112.1 (3 ×
(CH3)2C(OR)2), 105.0 (CHPh), 91.5 (C-3), 91.0 (C-2), 83.4
(C-4′), 81.2 (C-5′), 78.7 (C-5), 78.5 (C-2′), 75.5 (C-3′), 72.3
(C-4), 71.6 (C-6), 69.3 (C-6′), 49.3 (C-1), 48.0 (C-1′), 30.7,
30.6, 30.3, 30.2, 28.1, 27.5 (6 × CH3). Anal. calcd. for
C28H40O12SSe: C 49.48, H 5.93; found: C 49.31, H 5.90.
128.4 and 126.3 (C-Ar), 111.3, 110.6, 107.5 (3
×
(CH3)2C(OR)2), 100.6 (CHPh), 88.1 (C-2), 85.9 (C-3), 78.9
(C-4′), 76.5 (C-5′), 74.8 (C-5), 74.0 (C-2′), 71.1 (C-3′), 69.1
(C-4), 67.1 (C-6), 64.6 (C-6′), 43.9 (C-1′), 43.6 (C-1), 26.0,
25.7, 25.6, 25.5, 23.4, 22.5 (6 × CH3). Anal. calcd. for
C28H40O12SSe: C 49.48, H 5.93; found: C 49.16, H 6.09.
1,4-Anhydro-2,3,5,6-di-O-isopropylidene-1-[(S)-
[(2′R,3′S,4′R,5′R)-2′,4′-benzylidenedioxy-5′,6′-
isopropylidenedioxy-3′-(sulfooxy)hexyl]sulfonio]-L-allitol
inner salt (36)
The reaction of compound 18 (500 mg, 1.92 mmol) with
the cyclic sulfate 20 (860 mg, 2.30 mmol) in HFIP (2.0 mL)
for 12 h at 90–95 °C gave compound 36 as a colourless,
1,4-Anhydro-2,3,5,6-di-O-isopropylidene-1-[(S)-
[(2′R,3′S,4′R,5′R)-2′,4′-benzylidenedioxy-5′,6′-
isopropylidenedioxy-3′-(sulfooxy)hexyl]sulfonio]-D-allitol
inner salt (34)
amorphous solid (960 mg, 77% based on 18). [α]22 –15° (c
D
1
0.5, CH2Cl2). H NMR (CD2Cl2) δ: 7.56–7.40 (m, 5H, H-
Arom.), 5.76 (s, 1H, CHPh), 5.19 (ddd, 1H, H-2), 4.98 (dd,
1H, J2,3 = 5.7 Hz, H-3), 4.68–4.62 (m, 2H, H-2′, H-3′), 4.51
The reaction of compound 16 (500 mg, 1.92 mmol) with
the cyclic sulfate 20 (860 mg, 2.30 mmol) in HFIP (2.0 mL)
for 12 h at 90–95 °C gave compound 34 as a colourless,
(ddd, 1H, H-5′), 4.42 (dd, 1H, J1′b,2′ = 5.7 Hz, J1′b,1′a
=
13.5 Hz, H-1′b), 4.28 (dd, 1H, J1′a,2′ = 2.3 Hz, H-1′a), 4.28–
4.25 (m, 1H, H-5), 4.25–4.18 (m, 3H, H-6′a, H-6′b, H-4′),
4.14 (m, 1H, H-4), 3.90 (dd, 1H, J1a,1b = 15.4 Hz, H-1b),
amorphous solid (1.0 g, 82% based on 16). [α]22 +5.4°
D
1
(c 0.1, CH2Cl2). H NMR ((CD3)2O) δ: 7.60–7.38 (m, 5H,
H-Arom.), 5.89 (s, 1H, CHPh), 5.50 (ddd, 1H, H-2), 5.26
(dd, 1H, J2,3 = 5.8 Hz, H-3), 4.88 (ddd, 1H, J2′,3′ = 5.0 Hz,
3.86 (dd, 1H, J1a,2 = 4.6 Hz, H-1a), 3.86 (dd, 1H, 1H, J5,6b =
7.8 Hz, H-6b), 3.71 (dd, 1H, J5,6a = 5.1 Hz, J6a,6b = 9.5 Hz,
H-6a), 1.62, 1.39, 1.38, 1.37, 1.34, 1.24 (6 s, 18H, 6 × CH3).
13C NMR (CD2Cl2) δ: 137.4, 129.7, 128.6, 126.3 (C-Ar),
112.7, 111.5, 108.5 (3 × (CH3)2C(OR)2), 100.9 (CHPh), 85.2
(C-2), 84.8 (C-3), 79.1 (C-4′), 75.5 (C-5′), 74.3 (C-5), 74.0
(C-3′), 70.5 (C-2′), 69.8 (C-4), 67.0 (C-6), 65.0 (C-6′), 47.8
(C-1), 45.9 (C-1′), 26.4, 26.1, 25.9, 25.5, 23.3, 22.8 (6 ×
CH3). Anal. calcd. for C28H40O12S2: C 53.15, H 6.37; found:
C 53.36, H 6.41.
J1′b,2′ = 5.0 Hz, J1′a,2′ = 2.1 Hz, H-2′), 4.83 (ddd, 1H, J5,6b
=
2.8 Hz, J5,6a = 5.1 Hz, J4,5 = 7.6 Hz, H-5), 4.59 (dd, 1H,
J3,4 = 2.4 Hz, H-4), 4.57–4.52 (m, 2H, H-1′b, H-3′), 4.50
(ddd, 1H, J4′,5′ = 2.1 Hz, J5′,6′a = 9.1 Hz, J5′,6′b = 7.1 Hz, H-
5′), 4.42 (dd, 1H, J3′,4′ = 1.8 Hz, H-4′), 4.33 (dd, 1H, H-6′b),
4.30 (dd, 1H, J5,6b = 2.8 Hz, H-6b), 4.28 (m, 1H, H-1′a),
4.18 (dd, 1H, J6′a,6′b = 8.4 Hz, H-6′a), 4.11 (dd, 1H, J6a,6b
=
9.6 Hz, H-6a), 3.90 (dd, 1H, J1b,2 = 5.4 Hz, H-1b), 3.75 (dd,
© 2006 NRC Canada

1360
Can. J. Chem. Vol. 84, 2006
1′), 44.2 (C-1). HRMS calcd. for C10H20O10S2Na: 387.0390
(M + Na); found: 387.0391.
General procedure for the deprotection of the coupled
products to yield the final compounds 7–14
The protected coupled products 29–36 were dissolved in
CH2Cl2 (2 mL), TFA (10 mL) was then added, and the mix-
ture was stirred for 6–8 h at RT. The progress of the reaction
was followed by TLC analysis of the aliquots (EtOAc–
MeOH–H2O, 7:3:1). When the starting material had been
consumed, the TFA and CH2Cl2 were removed under re-
duced pressure. The residue was rinsed with CH2Cl2 (4 ×
2 mL) and the CH2Cl2 was decanted to remove the cleaved
protecting groups. The remaining gum was dissolved in wa-
ter and purified by column chromatography (EtOAc and
EtOAc–MeOH, 2:1) to give the purified compounds 7–10 as
colourless, amorphous, and hygroscopic solids. In the cases
of 33–36, the benzylidene groups were not completely
cleaved. The residue was then dissolved in 80% AcOH
(10 mL) and Pd–C (10%, 200 mg, in two portions) was
added and the reaction mixture was subjected to hydro-
genolysis for 48 h at RT. After filtering the Pd–C, the filtrate
was mixed with water (100 mL) and the solvents were re-
moved under reduced pressure. The remaining gum was dis-
solved in water and purified by column chromatography
(EtOAc and EtOAc–MeOH, 2:1) to give the purified com-
pounds 11–14 as colourless, amorphous, and hygroscopic
solids.
1,4-Anhydro-1-[(S)-[(2′S,3′S)-2′,4′-dihydroxy-3′-
(sufooxy)butyl]selenonio]-L-allitol inner salt (9)
To a solution of 31 (500 mg, 0.86 mmol) in CH2Cl2
(2 mL) was added TFA (10 mL) to yield the compound 9 as
a colourless, amorphous, and hygroscopic solid (216 mg,
1
61%). [α]22 –17° (c 0.5, H2O). H NMR (D2O) δ: 4.77
(ddd, 1H, HD-2), 4.42 (dd, 1H, J2,3 = 8.8 Hz, J3,4 = 3.0 Hz, H-
3), 4.33–4.25 (m, 2H, H-5, H-2′), 4.25–4.30 (ddd, 1H, H-3′),
4.13 (dd, 1H, J4,5 = 8.7 Hz, H-4), 3.97 (dd, 1H, J1′b,2′
=
=
4.0 Hz, J1′a,1′b = 12.4 Hz, H-1′b), 3.94 (dd, 1H, J1′a,2′
8.7 Hz, H-1′a), 3.83 (dd, 1H, J3′,4′b = 3.2 Hz, H-4′b), 3.75
(dd, 1H, J3′,4′a = 3.2 Hz, 1H, J4′a,4′b = 12.8 Hz, H-4′a), 3.68
(d, 2H, H-6a, H-6b), 3.58 (dd, 1H, J1b,2 = 8.5 Hz, H-1b),
3.36 (dd, 1H, J1a,2 = 2.2 Hz, J1a,1b = 13.3 Hz, H-1a). 13C
NMR (D2O) δ: 81.0 (C-3), 75.8 (C-2), 75.5 (C-3), 68.7 (C-
2), 66.5 (C-5), 65.5 (C-4), 63.4 (C-6), 60.0 (C-4), 48.4 (C-
1), 40.4 (C-1). HRMS calcd. for C10H19O10SSe: 410.9859
(M – H); found: 410.9857.
1,4-Anhydro-1-[(S)-[(2′S,3′S)-2′,4′-dihydroxy-3′-
(sufooxy)butyl]sulfonio]-L-allitol inner salt (10)
To a solution of 32 (500 mg, 0.94 mmol) in CH2Cl2
(2 mL) was added TFA (10 mL) to yield the compound 10
1,4-Anhydro-1-[(S)-[(2′S,3′S)-2′,4′-dihydroxy-3′-
(sufooxy)butyl]selenonio]-D-allitol inner salt (7)
To a solution of 29 (500 mg, 0.86 mmol) in CH2Cl2
(2 mL) was added TFA (10 mL) to yield the compound 7 as
as a colourless, amorphous, and hygroscopic solid (223 mg,
1
65%). [α]22 +6° (c 0.5, H2O). H NMR (D2O) δ: 4.60 (m,
D
1H, H-2), 4.47 (dd, 1H, J2,3 = 8.3 Hz, J3,4 = 3.3 Hz, H-3),
4.32 (ddd, 1H, H-5), 4.28–4.24 (m, 1H, H-2′), 4.22 (ddd, 1H,
H-3′), 4.07 (dd, 1H, J4,5 = 8.5 Hz, H-4), 3.98 (dd, 1H,
a colourless, amorphous, and hygroscopic solid (202 mg,
1
57%). [α]22 +54° (c 2, H2O). H NMR (D2O) δ: 4.74 (m,
J
1′b,2′ = 3.5 Hz, H-1′b), 3.92 (dd, 1H, J1′a,2′ = 8.8 Hz, J1′a,1′b =
D
1H, H-2), 4.34 (dd, 1H, J2,3 = 9.1 Hz, J3,4 = 3.1 Hz, H-3),
4.28 (ddd, 1H, H-3′), 4.25–4.18 (m, 2H, H-2′, H-5), 4.05 (dd,
1H, J4,5 = 4.3 Hz, H-4), 3.97 (dd, 1H, J1′b,2′ = 3.6 Hz, J1′a,1′b
13.6 Hz, H-1′a), 3.86 (dd, 1H, J3′,4′b = 9.5 Hz, H-4′b), 3.74
(dd, 1H, J3′,4′a = 3.2 Hz, 1H, J4′a,4′b = 12.8 Hz, H-4′a), 3.66
(d, 2H, H-6a, H-6b), 3.64–3.61 (m, 1H, H-1b), 3.44 (dd, 1H,
J1a,2 = 9.7 Hz, J1a,1b = 14.3 Hz, H-1a). 13C NMR (D2O) δ:
80.5 (C-3′), 74.6 (C-2), 74.5 (C-3), 68.8 (C-5), 66.6 (C-2′),
66.2 (C-4), 63.1 (C-6), 59.9 (C-4′), 50.9 (C-1′), 44.1 (C-1).
HRMS calcd. for C10H20O10S2Na: 387.0390 (M + Na);
found: 387.0389.
=
12.6 Hz, H-1′b), 3.82 (dd, 1H, J3′,4′b = 6.4 Hz, H-4′b), 3.80
(dd, 1H, J1′a,2 ′ = 3.2 Hz, H-1′a), 3.73 (dd, 1H, J3′,4′a = 3.3 Hz,
1H, J4′a,4′b = 12.8 Hz, H-4′a), 3.68 (m, 2H, H-6a, H-6b), 3.55
(dd, 1H, J1b,2 = 3.7 Hz, H-1b), 3.33 (dd, 1H, J1a,2 = 2.1 Hz,
J1a,1b = 13.1 Hz, H-1a). 13C NMR (D2O) δ: 80.8 (C-3′), 76.0
(C-2), 75.9 (C-3), 68.4 (C-5), 66.0 (C-2′), 65.1 (C-4), 63.4
(C-6), 60.1 (C-4′), 48.5 (C-1′), 40.5 (C-1). HRMS calcd. for
C10H19O10SSe: 410.9859 (M – H); found: 410.9861.
1,4-Anhydro-1-[(S)-[(2′R,3′S,4′R,5′R)-2′,4′,5′,6′-
tetrahydroxy-3′-(sufooxy)hexyl]selenonio]-D-allitol inner
salt (11)
1,4-Anhydro-1-[(S)-[(2′S,3′S)-2′,4′-dihydroxy-3′-
(sufooxy)butyl]sulfonio]-D-allitol inner salt (8)
To a solution of 30 (500 mg, 0.94 mmol) in CH2Cl2
(2 mL) was added TFA (10 mL) to yield the compound 8 as
To a solution of 33 (600 mg, 0.88 mmol) in CH2Cl2
(2 mL) was added TFA (10 mL). After removing the cleaved
protecting groups, the remaining gum was then dissolved in
AcOH (10 mL), Pd–C (10%, 100 mg) was added, and the re-
action mixture was subjected to hydrogenolysis to give com-
a colourless, amorphous, and hygroscopic solid (240 mg,
1
69%). [α]22 +39° (c 2, H2O). H NMR (D2O) δ: 4.63 (m,
pound 11 as a colourless, amorphous, and hygroscopic solid
D
1
1H, H-2), 4.48 (dd, 1H, J2,3 = 8.7 Hz, J3,4 = 3.3 Hz, H-3),
4.36–4.30 (m, 2H, H-2′, H-5), 4.27 (ddd, 1H, H-3′), 4.12 (dd,
1H, J1′b,2′ = 3.4 Hz, J1′a,1′b = 13.6 Hz, H-1′ b), 4.05 (dd, 1H,
(157 mg, 38%). [α]22 –8° (c 0.5, H2O). H NMR (D2O) δ:
D
4.80 (m, 1H, H-2), 4.59 (dd, 1H, H-3′), 4.48 (ddd, 1H, H-2′),
4.43 (dd, 1H, J2,3 = 8.9 Hz, J3,4 = 2.8 Hz, H-3), 4.31 (ddd,
1H, H-5), 4.14 (dd, 1H, J4,5 = 8.9 Hz, H-4), 4.08 (dd, 1H,
J1′b,2′ = 9.9 Hz, J1′a,1′b = 12.2 Hz, H-1′b), 3.95 (dd, 1H,
J1′a,2′ = 3.5 Hz, H-1′a), 3.84–3.74 (m, 3H, H-4′, H-5′, H-6′b),
3.72 (d, 2H, H-6a, H-6b), 3.62–3.57 (m, 2H, H-6′a, H-1b),
3.38 (dd, 1H, J1a,2 = 1.9 Hz, J1a,1b = 13.0 Hz, H-1a). 13C
NMR (D2O) δ: 78.5 (C-3′), 75.8 (C-2), 75.7 (C-3), 70.7 (C-
5′), 69.6 (C-4′), 68.8 (C-5), 68.1 (C-2′), 65.5 (C-4), 63.4 (C-
J3,4 = 3.3 Hz, J4,5 = 8.6 Hz, H-4), 3.86 (dd, 1H, J3′,4′b
=
2.8 Hz, H-4′b), 3.85 (dd, 1H, J1′a,2′ = 8.3 Hz, H-1′a), 3.78
(dd, 1H, J3′,4′a = 3.2 Hz, 1H, J4′a,4′b = 12.8 Hz, H-4′a), 3.70
(m, 2H, H-6a, H-6b), 3.69 (dd, 1H, J1b,2 = 3.3 Hz, H-1b),
3.46 (dd, 1H, J1a,2 = 1.6 Hz, J1a,1b = 14.4 Hz, H-1a). 13C
NMR (D2O) δ: 79.8 (C-3′), 74.7 (C-2), 74.4 (C-3), 68.3 (C-
2′), 65.6 (C-4), 65.5 (C-5), 63.0 (C-6), 59.9 (C-4′), 51.1 (C-
© 2006 NRC Canada

Liu and Pinto
1361
6′), 62.8 (C-6), 47.7 (C-1′), 40.2 (C-1). HRMS calcd. for
(dd, 1H, J1′a,2′ = 9.1 Hz, J1′a,1′b = 13.5 Hz, H-1′a), 3.79 (dd,
1H, J4′,5′ = 8.0 Hz, H-4′), 3.68 (dd, 1H, J5′,6′b = 2.4 Hz, H-
6′b), 3.68–3.64 (m, 1H, H-5′), 3.67 (d, 2H, H-6a, H-6b), 3.61
(dd, 1H, J1b,2 = 3.2 Hz, J1a,1b = 14.2 Hz, H-1b), 3.52 (dd,
1H, J5′,6′a = 5.6 Hz, J6′a,6′b = 11.5 Hz, H-6′a), 3.44 (dd, 1H,
J1a,2 = 8.0 Hz, H-1a). 13C NMR (D2O) δ: 77.7 (C-3′), 74.8
(C-3), 74.4 (C-2), 70.5 (C-5′), 69.1 (C-4′), 68.3 (C-5), 67.0
(C-2′), 65.0 (C-4), 62.8 (C-6′), 62.7 (C-6), 49.9 (C-1′), 43.9
(C-1). HRMS calcd. for C12H25O9S: 345.1214 (M + H –
SO3); found: 345.1211.
C12H25O9Se: 393.0658 (M + H – SO3); found: 393.0656.
1,4-Anhydro-1-[(S)-[(2′R,3′S,4′R,5′R)-2′,4′,5′,6′-tetra-
hydroxy-3′-(sufooxy)hexyl]sulfonio]-D-allitol inner salt (12)
To a solution of 34 (500 mg, 0.79 mmol) in CH2Cl2
(2 mL) was added TFA (10 mL). After removing the cleaved
protecting groups, the remaining gum was then dissolved in
AcOH (10 mL), Pd–C (10%, 100 mg) was added, and the re-
action mixture was subjected to hydrogenolysis to give com-
pound 12 as a colourless, amorphous, and hygroscopic solid
1
(140 mg, 42%). [α]22 –32° (c 2, H2O). H NMR (D2O) δ:
D
Acknowledgements
4.53 (m, 1H, H-2), 4.51 (dd, 1H, J2′,3′ = 5.1 Hz, J3′,4′
1.1 Hz, H-3′), 4.44 (ddd, 1H, H-2′), 4.26 (dd, 1H, J2,3
=
=
We are grateful to the Natural Sciences and Engineering
Research Council of Canada (NSERC) for financial support
and to B.D. Johnston for helpful discussions. We are also
grateful to D.R. Bundle for providing access to the high-
resolution mass spectral facilities.
9.6 Hz, J3,4 = 3.1 Hz, H-3), 4.12 (ddd, 1H, H-5), 3.95 (dd,
1H, J1b,2 = 10.8 Hz, J1′a,1′b = 13.4 Hz, H-1′b), 3.88 (dd, 1H,
J1′a,2′ = 2.8 Hz, H-1′a), 3.86 (dd, 1H, J4,5 = 8.2 Hz, H-4),
3.74 (dd, 1H, J4′,5′ = 9.2 Hz, H-4′), 3.72 (dd, 1H, J5,6b
=
3.1 Hz, J6a,6b = 11.9 Hz, H-6b), 3.67 (dd, 1H, J5′,6′b = 2.5 Hz,
J6′a,6′b = 11.8 Hz, H-6′b), 3.66–3.63 (m, 1H, H-5′), 3.59 (dd,
1H, J5,6a = 3.9 Hz, H-6a), 3.52–3.46 (m, 3H, H-1a, H-1b, H-
6′a). 13C NMR (D2O) δ: 77.7 (C-3′), 76.1 (C-3), 72.8 (C-2),
70.4 (C-5′), 68.9 (C-4′), 67.8 (C-2′), 67.4 (C-5), 64.6 (C-6),
64.3 (C-4), 62.7 (C-6′), 49.3 (C-1′), 44.4 (C-1). HRMS calcd.
for C12H25O9S: 345.1214 (M + H – SO3); found: 345.1214.
References
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hydroxy-3′-(sufooxy)hexyl]selenonio]-L-allitol inner salt (13)
To a solution of 35 (600 mg, 0.88 mmol) in CH2Cl2
(2 mL) was added TFA (10 mL). After removing the cleaved
protecting groups, the remaining gum was then dissolved in
AcOH (10 mL), Pd–C (10%, 100 mg) was added, and the re-
action mixture was subjected to hydrogenolysis to give com-
2. (a) A. Varki, R. Cummings, J. Esko, H. Freeze, G. Hart, and J.
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pound 13 as a colourless, amorphous, and hygroscopic solid
1
(197 mg, 47%). [α]22 –22° (c 1, H2O). H NMR (D2O) δ:
D
4.76 (ddd, 1H, H-2), 4.57 (dd, 1H, J2′,3′ = 5.2 Hz, H-3′), 4.50
(ddd, 1H, H-2′), 4.37 (dd, 1H, J2,3 = 9.1 Hz, J3,4 = 3.0 Hz,
H-3), 4.25 (ddd, 1H, H-5), 4.06 (dd, 1H, J4,5 = 7.9 Hz, H-4),
4.00 (dd, 1H, J1′b,2′ = 4.0 Hz, J1′a,1′b = 12.4 Hz, H-1′b), 3.89
(dd, 1H, J1′a,2′ = 9.0 Hz, H-1′a), 3.84–3.79 (m, 1H, H-5′),
3.72 (d, 2H, H-6a, H-6b), 3.63 (dd, 1H, H-4′), 3.60–3.50 (m,
3H, H-6′b, H-6′a, H-1b), 3.34 (dd, 1H, J1a,2 = 2.7 Hz, J1a,1b
=
13.0 Hz, H-1a). 13C NMR (D2O) δ: 78.3 (C-3′), 76.0 (C-3),
75.4 (C-2), 73.1 (C-5′), 69.8 (C-4′), 68.2 (C-5), 67.1 (C-2′),
64.7 (C-4), 62.8 (C-6), 62.6 (C-6′), 47.4 (C-1′), 40.2 (C-1).
HRMS calcd. for C12H25O9Se: 393.0658 (M + H – SO3);
found: 393.0656.
1,4-Anhydro-1-[(S)-[(2′R,3′S,4′R,5′R)-2′,4′,5′,6′-tetra-
hydroxy-3′-(sufooxy)hexyl]sulfonio]-L-allitol inner salt (14)
To a solution of 36 (600 mg, 0.95 mmol) in CH2Cl2
(2 mL) was added TFA (10 mL). After removing the cleaved
protecting groups, the remaining gum was then dissolved in
AcOH (10 mL), Pd–C (10%, 100 mg) was added, and the re-
action mixture was subjected to hydrogenolysis to give com-
pound 14 as a colourless, amorphous, and hygroscopic solid
(165 mg, 41%). [α]22 –32° (c 1, H2O). H NMR (D2O) δ:
1
4.58 (ddd, 1H, H-2),D4.55 (dd, 1H, J2′,3′ = 4.6 Hz, J3′,4′
0.7 Hz, H-3′), 4.49 (ddd, 1H, H-2′), 4.42 (dd, 1H, J2,3
=
=
8.7 Hz, J3,4 = 3.2 Hz, H-3), 4.25 (ddd, 1H, H-5), 4.03 (dd,
1H, J1′b,2′ = 3.8 Hz, H-1′b), 4.04–3.99 (m, 1H, H-4), 3.92
© 2006 NRC Canada

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© 2006 NRC Canada