Preparation of anhydro-thiohexopyranosides and -thiohexofuranosides with d-fructo-, l-sorbo-, l-psico- and l-tagato-configuration starting from l-sorbose

Article abstract of DOI:10.1080/10426500701340915

Methyl -L-sorbopyranoside is transformed into the bicyclic thiosugar methyl 1,5-anhydro-3,4-di-O-mesyl-1-thio- -D-fructopyranoside in two steps, whereas the corresponding 3-O-benzoate is obtained from methyl 1,3-O-benzylidene-a-L- sorbopyranoside in three

Full text of DOI:10.1080/10426500701340915

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Preparation of Anhydro-
Thiohexopyranosides and -
Thiohexofuranosides with D-
fructo-, L-sorbo-, L-psico- and
L-tagato-Configuration Starting
from L-Sorbose
Kerstin Polchow-Stein a & Jürgen Voss a
a Department of Chemistry, Organic Chemistry,
University of Hamburg, Hamburg, Germany
Published online: 15 Jun 2007.
To cite this article: Kerstin Polchow-Stein & Jürgen Voss (2007): Preparation of
Anhydro-Thiohexopyranosides and -Thiohexofuranosides with D-fructo-, L-sorbo-, L-
psico- and L-tagato-Configuration Starting from L-Sorbose, Phosphorus, Sulfur, and
Silicon and the Related Elements, 182:8, 1871-1891
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Phosphorus, Sulfur, and Silicon, 182:1871–1891, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701340915
Preparation of Anhydro-Thiohexopyranosides and
-Thiohexofuranosides with D-fructo-, L-sorbo-, L-psico-
and L-tagato-Configuration Starting from L-Sorbose
Kerstin Polchow-Stein
¨
Jurgen Voss
University of Hamburg, Department of Chemistry, Organic Chemistry,
Hamburg, Germany
Methyl α-L-sorbopyranoside is transformed into the bicyclic thiosugar methyl
1,5-anhydro-3,4-di-O-mesyl-1-thio-β-D-fructopyranoside in two steps, whereas the
corresponding 3-O-benzoate is obtained from methyl 1,3-O-benzylidene-a-L-
sorbopyranoside in three steps. 2,3-O-Isopropylidenesorbofuranosides, on the other
hand, can be transformed into 6-S-thioacetates by use of the thio-Mitsunobu
reaction. These are suitable precursors for the preparation of 1,6-anhydro-1-
thiosorbofuranosides. Also, methyl 1-S-acetyl-1-thio-L-sorbofuranosides with me-
sylate leaving groups are available by the thio-Mitsunobu reaction. They yield 1,4-
anhydro-1-thio-β-L-tagatofuranosides, 1,3-anhydro-α-L-psicofuranosides and 1,6-
anhydro-1-thio-α-L-sorbofuranosides depending on the configuration of the start-
ing compound. Attempts to prepare azido-thio-sugars by displacement of mesylate
groups with alkali metal azides failed.
Keywords Anhydrothiosugars; intramolecular SN2 reaction; methyl sorbopyranosides;
methyl sorbofuranosides; thio-Mitsunobu reaction
INTRODUCTION
In a recent article in this journal,3 we have described first results on the
synthesis of anhydro-thio-furanosides starting from a ketose, namely
from D-fructose. The key step in these syntheses, i.e., the introduction
of sulfur into the carbohydrate molecule, was achieved by the thio-
Mitsunobu reaction. This method had already turned out earlier to be
Received June 27, 2006; accepted February 23, 2007.
The University of Hamburg and the Fonds der Chemischen Industrie are gratefully
acknowledged for their financial support. K. P.-S. thanks the University of Hamburg for
a Graduate Fellowship.
Address correspondence to Ju¨rgen Voss, Universitat of Hamburg, Department of
Chemistry, Organic Chemistry, Martin-Luther-King-Platz 6, Hamburg D-20146, Ger-
many. E-mail: juergen.voss@chemie.uni-hamburg.de
1871

1872
K. Polchow-Stein and J. Voss
the method of choice in the pentofuranoside4 and glucopyranoside5 se-
ries. In particular, it was possible in most cases to prepare thioacetates
directly from the corresponding methyl glycosides without protection
of the hydroxy groups. We were, therefore, interested in an extension
of the method to further ketoses and have explored its applicability
in the sorbose series. In spite of the fact that L-sorbose is an inexpen-
sive sugar because it is the intermediate in the most important process
for the technical production of L-ascorbic acid,6,7 its chemistry in gen-
eral has been much less studied than that of other monosaccharides.
In particular, thiosorbose derivatives are rather rare. In addition to
the synthesis of compounds of this type, we also wanted to investigate
the stereochemistry of the reactions and, furthermore, of follow-up re-
actions of suitably substituted thiosorbosides such as the nucleophilic
substitution with azides.
RESULTS AND DISCUSSION
Pyranoses
In contrast to the difficulties which one is faced to with the prepa-
ration of methyl fructosides exhibiting a definite structure and
configuration,3,8 methyl α-L-sorbopyranoside 1 is easily available with
good yield.9 Our attempts to introduce an acetylthio group directly into
the primary 1-position of 1 by a thio-Mitsunobu reaction failed, however.
Although we tried various solvents and applied reaction temperatures
between 0◦C and 130◦C, only the starting material 1 was recovered.
Obviously, steric hindrance (the “neopentyl effect”) prevents an attack
of the bulky reagent, which is involved in the Mitsunobu reaction, at
the primary hydroxy group in the 1-position of 1. We have observed the
same effect in the fructose series, where the 1-position is very resistant
to nucleophilic reactions too.3 Therefore, we prepared the tetramesy-
late 2 as a starting compound, which gave the thioacetate 3 on reaction
with potassium thioacetate in DMF (Scheme 1).
Again, the 1-position was not attacked by the nucleophile but instead
the reaction took place at the least hindered secondary 5-position under
inversion. The structure and the resulting β-D-fructo-configuration of
3 were confirmed by its NMR spectra. The structure of a 1-thioacetate
can be excluded on account of the chemical shifts δ = 4.30/4.42 for the
protons at C-1 which agree with the corresponding values (4.33/4.44)
in the precursor 1 in contrast to δ(1-H) = 3.33 in the related 1,6-di-S-
acetyl-1,6-dithio-β-D-fructofuranoside.3 Furthermore, the trans-diaxial
ꢀ
coupling 3 J
= 10.6 Hz and the low vicinal couplings 3 J
=
H3,H4
H5,H6/H5,H6
1.5/2.3 Hz are indicative of the D-fructo-configuration of 3 and exclude

Anhydro-Thiohexopyranosides and -Thiohexofuranosides
1873
SCHEME 1 (1): MsCl, pyridine; (2): AcSK, DMF, 153 ◦C; (3): AcSK,
MeOCH2CH2OH, 125 ◦C; (4): Na2S·9H2O, DMSO, 100◦C.
the alternative SN2 substitution at the 4-position, which would have
led to a 4-thioacetate with D-tagato-configuration.
The intramolecular cyclization of 3 was achieved by reaction with
sodium sulfide. Not unexpectedly, it took place under formation of the
1,5-anhydro-thiosugar 4 since nucleophilic displacement of the mesy-
late group at the primary 1-position is strongly favored over the much
less reactive 3-mesylate group neighboring the anomeric center. Com-
pound 4 can also be obtained directly from 2 and potassium thioacetate
on prolonged refluxing in 2-methoxyethanol. In fact, it is difficult to
isolate the intermediate 3 from reaction mixtures of 2 with potassium
thioacetate (Scheme 1). Unfortunately, the yields are low in both cases
but anyway the one-step procedure starting from 2 is, of course, more
advantageous for the preparation of 4.
As expected, 4 retains the β-D-fructo-configuration of 3 and exhibits
a boat-conformation of the hexose ring, i.e., a bicyclo[2.2.2]octane type
skeleton. This can be clearly deduced from its NMR spectra. The small
coupling constant 3 J
= 3.5 Hz, in contrast to 3 J
= 10.6 Hz in
H3,H4
H3,H4
3, is characteristic of a gauche-conformation of the two protons. The 13
C
chemical shifts δ = 29.6, δ = 37.5, and δ = 96.1 for C-1, C-5, and C-2,
respectively, are in agreement with the structure of 4 too.
In a second reaction sequence, we have prepared the related benzoate
8 starting again with 1 (Scheme 2).
The benzylidene derivative 5 and the related dimesylate 6 are de-
scribed in the literature.10 The work-up procedure for 5 is, however,
laborious and involves heavy losses. Large amounts of inorganic salts
have to be removed, since an excess of zinc chloride is used as a catalyst
and condensating agent. We preferred, therefore, to prepare 5 by use of
1,1-dimethoxytoluene with catalytic amounts of camphorsulfonic acid
instead of benzaldehyde. Cleavage of 6 with N-bromosuccinimide11 led
to the 1-bromo derivative 7 with 80% yield. Finally, the reaction with

1874
K. Polchow-Stein and J. Voss
SCHEME 2 (1): PhCH(OMe)2, DMF, H+; (2): MsCl, pyridine; (3): NBS, CCl4;
(4): AcSK, DMF, 153◦C.
potassium thioacetate gave the 3-O-benzoyl-anhydrothiosugar 8 in a
nucleophilic substitution and concomitant base-promoted intramolec-
ular cyclization (Scheme 2). The moderate yield of 26% is due to the
several steps involved in the transformation of 7 to 8. In this case, none
of the expected intermediates, the 1-thioacetate or the 5-thioacetate,
could be detected.
1
The H NMR spectrum of 7 closely resembles that of the related 2.
Only the signals of 1-H, 1ꢀ-H and 3-H in 7 are shifted downfield as
compared with 2 due to the 1-bromo substituent and the anisotropic
effect of the 3-benzoyl group, whereas all coupling constants are nearly
identical. The same holds for 8, which even more resembles its ana-
log 4. The expected downfield shift of the signal of 3-H from δ = 4.93
(4) to δ = 5.53 (8) is the only significant difference observed (Table I).
The structural assignments of 7 and 8 are also corroborated by the
TABLE I Relevant Chemical Shifts δ [ppm] and Vicinal Coupling
Constants 3 J [Hz] in the 1H NMR Spectra of Thioanhydrosugars
Compound 1-H/1ꢀ-H 3-H
J
3H,4H
4-H
J
4H,5H
5-H
J
5H,6H
J
6-H/6ꢀ-H
ꢀ
5H,6 H
4
8
2.71/3.48 4.93
2.82/3.45 5.53
2.42/3.31 5.05
2.36/3.02 4.65
2.25/3.35 4.76
2.25/3.36 4.28
2.48/3.05 3.63a
3.02/3.02 4.44
3.10/3.14 3.53
2.25/3.36 4.77
3.6
3.4
1.8
3.1
3.1
2.3
3.1
2.5
2.5
3.1
5.17
5.26
5.15
4.94
4.99
4.41
3.71a
3.26
5.25
5.00
3.4
3.4
6.9
7.3
7.2
7.4
3.1
0.0
0.0
7.2
3.08
3.11
5.1
4.7
4.8
4.70
4.51
4.61
4.69
4.84
1.6
1.7
0.7
1.0
1.0
2.2
1.8
5.7
4.6
1.0
3.0
3.0
3.2
3.2
3.1
2.8
3.2
5.0
4.2
3.1
4.47/4.50
4.52/4.56
2.36/3.03
2.28/2.87
2.35/2.94
2.34/2.91
2.30/3.15
4.22/4.23
4.23/4.32
2.35/2.95
13
14
15
16
17
23
26
27
aAn unequivocal assignment to 3-H or 4-H is not possible

Anhydro-Thiohexopyranosides and -Thiohexofuranosides
1875
TABLE II Chemical Shifts δ [ppm] of Relevant Carbon Atoms
in the 13C NMR Spectra of Thioanhydrosugars
Compound
C-1
C-2
C-3
C-4
C-5
C-6
4
8
29.6
29.7
30.6
33.4
30.4
30.0
30.1
33.0
34.1
30.4
96.1
96.4
110.4
99.7
102.4
100.7
101.6
111.8
110.2
100.4
83.3
76.7
86.4
75.8
76.6
81.0
52.8a
70.3
45.5
76.6
83.6
82.8
82.2
87.1
86.0
80.8
53.0a
48.1
74.8
86.1
37.5
37.3
81.0
75.8
76.9
78.0
74.3
82.6
84.0
76.9
70.9
70.8
24.1
23.9
23.8
24.2
25.7
69.1
68.2
23.8
13
14
15
16
17
23
26
27
aAn unequivocal assignment to C-3 or C-4 is not possible.
agreement of their 13C NMR spectra with those of 2 and 4, respectively.
Only the C-1 signal of 7 at δ = 29.3 appears with a considerable upfield
shift as compared with δ = 66.0 for 2 according to the bromo substituent.
Also the C-3 signals at δ = 70.9 (7) and δ = 76.7 (8) are slightly but sig-
nificantly shifted with respect to δ = 73.8 (2) and δ = 83.3 (4) (Table
II).
Attempts to replace the mesylate group in 8 by an azido substituent
failed. Debenzoylation of 8 with sodium methoxide and subsequent re-
action with sodium azide and ammonium chloride led to decomposition
without the formation of any azido derivative.
Furanoses
The preparation of sorbofuranosides is not as easy since the forma-
tion of the corresponding pyranosides is absolutely prevalent. There-
fore, we started from 2,3-O-isopropylidene-α-L-sorbose 9 with a fixed
furanose structure in order to synthesize anhydrothio-sorbofuranosides
(Scheme 3).
Compound 9 is easily available from L-sorbose via the 2,3:4,6-di-O-
isopropylidene-α-L-sorbose.7,12−14 In contrast to 1, the isopropylidene-
sorbofuranose 9 formed a thioacetate 10 by a direct thio-Mitsunobu
reaction with thioacetic acid in the presence of diisopropyl azodicar-
boxylate (DIAD) and triphenylphosphine. As expected, only the primary
hydroxy group in the 6-position was attacked when equivalent amounts
of the reagents were used. The yield of 10 was, however, low (26%). It
could be considerably increased to 62% by applying the reagents in ex-
cess. Under these conditions, also 11% of the 1,6-bis-thioacetate 11 was

1876
K. Polchow-Stein and J. Voss
SCHEME 3 (1): Ph3P, DIAD, AcSH, THF; (2): MsCl, pyridine; (3): NaHCO3,
MeOCH2CH2OH; (4): AcOH.
formed as by-product. The structures of the 6-thioacetate 10 and the
1
1,6-bis-thioacetate 11 are obvious from their H and 13C NMR spec-
tra. Mesylation of 10 gave the dimesylate 12. Cyclization of 12 with
sodium hydrogencarbonate in boiling 2-methoxyethanol finally led to
the 1,6-anhydro-thiosorbose 13 by cleavage of the thioacetate group
and subsequent intramolecular nucleophilic attack of the thiolate at
C-1 (Scheme 3).15 Small amounts of diisopropyl hydrazodicarboxylate
(DIHD) could not be completely removed from 10, 12, and 13 despite of
repeated column chromatography. Irrespective of this contamination,
13 was deprotected with aqueous acetic acid to yield pure 1,6-anhydro-
4-O-mesyl-1-thio-α-L-sorbofuranose 14 (Scheme 3). The interesting 1,6-
anhydrothio (oxa-thia-bicyclo[3,2,1]octane) skeleton of 13 (and, conse-
quently, of 14) represents the only reasonable outcome of the cyclization
of 12, due to the stereochemical situation, i.e., the syn-configuration
of the thioacetate substituent and the mesylate leaving group in the
4-position, the alternative formation of a 4,6-anhydrothio derivative
through intramolecular SN2 displacement is not possible. The struc-
tures are of course in agreement with the NMR spectra. The chemical
shifts of 4-H in 12 and 13 are nearly identical, whereas the 1-H and
1-H signals of 13 are shifted up-field as one would expect (Table I).
The only significant difference between the 13C NMR spectra of 12 and
13 consists in a considerable shift of the C-1 signal from 67.5 ppm in
12 to 30.6 ppm in 13 (33.4 in 14). Again, the chemical shifts of the C-
4 signals are virtually the same for 12 (80.7 ppm) and 13 (81.2 ppm)
(Table II).

Anhydro-Thiohexopyranosides and -Thiohexofuranosides
1877
SCHEME 4 (1): HCl, MeOH; (2): LiN3 (LiOH, cf. text), DMF.
The isopropylidene derivative 13 was glycosylated with methanolic
hydrogen chloride. Besides a 61% yield of 15, also 4% of the solvolysis
product 16 was obtained (Scheme 4).
When we tried to replace the mesylate group of 15 by an azide
substituent we failed again. Only the starting material was recov-
ered after refluxing 15 with sodium azide in DMF for 22 h. The cor-
responding reaction with lithium azide, on the other hand, unexpect-
edly led to the 3,4-anhydro derivative 17 with 92% yield. Obviously, the
reagent was contaminated with lithium hydroxide, which set off a base-
catalyzed epoxide formation under elimination of the mesylate group
(Scheme 4).
The NMR spectra of 15 and 16 are in agreement with their struc-
tures. The proton signals of 3-H and 4-H (3.63 and 3.71 ppm or vice
versa) in 17 exhibit the typical high-field shifts as compared with 3-H
(4.76 ppm) and 4-H (4.99 ppm) in the precursor 15, which is charac-
teristic of epoxide protons.1,4,16,17 Also the vicinal coupling constant
3 J
= 3.2 Hz in 17 is indicative of the L-psico configuration with
H4,H5
gauche conformation of 4-H and 5-H, as compared with 3 J
= 7.2
H4,H5
Hz in the precursor 15 with eclipsed conformation and L-sorbo configu-
ration (Table I). Accordingly, the 13C NMR signals of C-3 and C-4 in 17
appear in the typical epoxide range at 52.8/53.0 ppm1,4,16,17 in contrast
to C-3 (77 ppm) and C-4 (86 ppm) in 15 (Table II).

1878
K. Polchow-Stein and J. Voss
SCHEME 5 (1): MsCl, pyridine; (2): HCl, MeOH; (3): Ph3P, DIAD, AcSH, THF;
(4): NaHCO3, MeOCH2CH2OH.
In order to further explore the selectivity of the cyclization reactions,
i.e., the formation of thietano (1,3-thioanhydro) versus thiolano (1,4-
thioanhydro), or thiepano (1,6-thioanhydro) sugars we have prepared
the anomeric thioacetates 22 and 24 as starting compounds (Scheme 5).
The β-anomer 22 was obtained from the known 1-O-acetyl-2,3-O-
isopropylidene-α-L-sorbose 1818 in three steps. Mesylation to form 19
and deprotection under acidic conditions led to the two anomeric dime-
sylates 20 (12%) and 21 (19%). Their configuration could be assigned
based on NOESY NMR spectra. The β-anomer 20 exhibits the expected
interaction between 3-H and the glycosidic OCH3 group whereas the
α-anomer 21 shows an interaction between 3-H and the protons of the
1-CH2 group. After separation, the β-anomer 20 was subjected to a thio-
Mitsunobu reaction to yield 22 (35%). Reaction of 22 with sodium hydro-
gencarbonate in boiling 2-methoxyethanol led to the 1,4-thioanhydro-
glycoside 23 (71%) with β-L-tagato-configuration under intramolecular

Anhydro-Thiohexopyranosides and -Thiohexofuranosides
1879
SCHEME 6 (1): Ph3P, DIAD, AcSH, THF; (2): MsCl, pyridine; (3): NaHCO3,
MeOCH2CH2OH.
nucleophilic replacement of the mesylate leaving group at C-4, as ex-
pected (Scheme 5). An attack of the intermediate 1-thiolate at the 6-
position is of course not possible for stereochemical reasons. The struc-
1
ture and configuration of 23 is corroborated by its H and 13C NMR
spectra.
The thio-Mitsunobu reaction of the α-anomer 21, on the other hand,
gave 61% of the 1-thioacetate 24. This compound was nearly quanti-
tatively transformed into the 3,4,5-trimesylate 25, which exhibits two
leaving groups in positions suitable for intramolecular SN2 reactions.
In this case, the cyclization of 25 with sodium hydrogencarbonate led
to a mixture of both of the two possible products 26 (6%) and 27 (8%),
which were separated by chromatography (Scheme 6).
The structures of 26 and 27 could be unequivocally assigned based
on their NMR spectra. Due to the substitution of the mesylate group,
1
the H NMR signal of 3-H in 26 exhibits an up-field shift to δ = 3.53
ppm as compared to δ = 5.17 ppm in the starting compound 25, whereas
no significant difference is observed for the protons in the 6-position.
In 27, on the other hand, the mesylate group at C-6 is displaced. Ac-
cordingly, the signals of 6-H (2.35 ppm) and 6ꢀ-H (2.95 ppm) appear at
higher field as compared with 25 [δ(6-H/6ꢀ-H) = 4.42 ppm] (Table I).
Correspondingly, the C-3 signal of 26 is shifted to 45.5 ppm from 79.9
ppm in 25 and, in contrast, the C-6 signal of 27 is shifted to 23.8 ppm
from 66.5 ppm in 25 (Table II).

1880
K. Polchow-Stein and J. Voss
As an overview and for comparison purposes, the relevant NMR data
of the anhydro-thiosugars, which we have prepared, are compiled in
Tables I and II.
CONCLUSION
Our study has shown that methyl α-L-sorbopyranoside 1 does not re-
act in a thio-Mitsunobu reaction with thioacetic acid. This is probably
due to steric hindrance which prevents an attack of the intermediate
bulky phosphonium cation at the neopentyl position C-1.19 The sor-
bopyranoside 1 can, however, be transformed into the 1,5-thioanhydro-
fructopyranosides 4 and 8 via its tetramesylate 2 or 1,3-O-benzylidene
derivative 5.
The 2,3-O-isopropylidene-sorbofuranosides 9 and 18, on the other
hand, undergo regioselective thio-Mitsunobu reactions in the 6-
position. The resulting thioacetates lead to the 1,6-thioanhydro
(thiepano) sugars 13–16 in two steps. The thiolano sugar methyl 1,4-
anhydro-6-O-mesyl-1-thio-β-L-psicofuranoside 23 is formed from the 1-
thioacetate 22 whereas the corresponding α-anomer 24 yields the 1,3-
thioanhydro (thietano) and 1,6-thioanhydro (thiepano) sugars 26 and
27.
Mesylate leaving groups in the thioanhydrosugars cannot be re-
placed by azido substituents in SN2 reactions. Instead, the 3,4-epoxide
17 is formed from 15.
EXPERIMENTAL
Corrected melting points were determined on an Electrothermal ap-
paratus. Optical rotations were measured on a Perkin Elmer 341 po-
larimeter. Thin layer chromatography (TLC) was performed on Al foils
coated with SiO2 F254 (Merck, Darmstadt). The spots were detected by
the extinction of the fluorescence or, after spraying with 20% H2SO4
in EtOH, by heating. Column chromatography (CC) was performed on
Kieselgel 60 F, 0.063–0.200 mm (Merck, Darmstadt). Eluents [EtOAc,
petroleum ether (PE)] were distilled prior to use. IR (KBr pellets or
films) spectra were measured on an ATI Mattson Instruments Gene-
sis Series FT-IR spectrometer. NMR spectra were measured on Bruker
AMX 400 (1H: 400 MHz; 13C: 100.62 MHz) or DRX 500 (1H: 500 MHz, if
particularly stated) spectrometers. Chemical shifts δ (ppm) are related
to SiMe4 as internal standard in CDCl3. Spectra measured in acetone-
d6 were calibrated to δ(1H)= 2.09 ppm of the CD2H signal and δ(13C)
= 30.56 ppm of the CD3 signal and subsequently related to SiMe4. In
order to enhance the resolution, the 1H NMR spectra were recalculated

Anhydro-Thiohexopyranosides and -Thiohexofuranosides
1881
from the FID by use of the program WinNMR 5.1 (Bruker). Assign-
1
1
ments of the signals were achieved by performing H-1H-COSY-, H-
13C-COSY-, NOESY-, DEPT-135-, or PENDANT experiments. Solvents
were purified and dried by standard laboratory procedures,20 THF was
kept over KOH for several days and subsequently refluxed and dis-
tilled over metallic potassium. Thioacetic acid (Merck, Darmstadt) was
purified by four times distillation at low temp. in vacuum. Removal of
solvents was performed by vacuum distillation in a rotating evaporator.
Methyl 1,3,4,5-Tetra-O-mesyl-α-L-sorbopyranoside (2)
Methyl α-L-sorbopyranoside (1)9 (1.00 g, 5.15 mmol) and methanesul-
fonyl chloride (4.85 mL, 62.27 mmol) were dissolved in dry pyridine (30
mL) under cooling with ice. After stirring at 20◦C for 12 h, the pyridine
was removed. The residue was dissolved in CH2Cl2 (50 mL). The solu-
tion was washed twice with H2O (each 50 mL). The organic layer was
dried over MgSO4 and evaporated until dry. The residue was purified
by CC (EtOAc) to give 2.50 g (96%) 2 as colorless crystals. Mp. 149–
150◦C. [α]D20 –19.6 (1.04, CHCl3). IR: ν 1176 (SO2), 1360 (SO2) cm
.
–1
1H NMR (CDCl3): δ 3.11 (s, 3H, SO2CH3), 3.16 (s, 3H, SO2CH3), 3.21
(s, 3H, SO2CH3), 3.25 (s, 3H, SO2CH3), 3.40 (s, 3H, OCH3), 3.65 (d,
1H, 6-H), 4.19 (dd, 1H, 6-H), 4.33 (d, 1H, 1-H), 4.44 (d, 1H, 1-H), 4.78
ꢀ
(ddd, 1H, 5-H), 4.87 (d, 1H, 3-H), 5.11 (vt, 1H, 4-H). 2 J
= 10.3 Hz,
H1,H1
3
3
3
3 J
= 9.5 Hz, J
= 9.3 Hz, J
= 1.4 Hz, J
= 6.2 Hz,
ꢀ
H3,H4
H4,H5
H5,H6
H5,H6
2 J
= 11.1 Hz. 13C NMR (CDCl3): δ 37.9 (SO2CH3), 38.7 (SO2CH3),
ꢀ
H6,H6
39.1 (SO2CH3), 39.3 (SO2CH3), 49.7 (OCH3), 60.3 (C-6), 66.0 (C-1), 73.2
(C-5), 73.8 (C-3), 75.6 (C-4), 98.1 (C-2).
Methyl 5-S-Acetyl-1,3,4-tri-O-mesyl-5-thio-β-D-
fructopyranoside (3)
AcSK (0.71 g, 6.22 mmol) and 2 (2.10 g, 4.15 mmol) were dissolved in
dry DMF (16 mL) and stirred under N2 at 20◦C for 24 h. After addition
of another portion of AcSK (0.57 g, 4.99 mmol) in DMF (12.5 mL), the
solution was heated to reflux under N2 for 6 h. The DMF was removed.
The residue was extracted with EtOAc and the extract was evaporated
until dry. The product was purified by CC (EtOAc/PE 3:1) to yield 3 (0.45
g, 22%) as a syrup. IR: ν 1176 (SO2), 1360 (SO2), 1734 (C O) cm–1. 1H
NMR (CDCl3): δ 2.49 (s, 3H, CH3CO), 3.11 (s, 3H, SO2CH3), 3.14 (s, 3H,
SO2CH3), 3.20 (s, 3H, SO2CH3), 3.39 (s, 3H, OCH3), 3.82 (dd, 1H, 6-H),
4.14 (dd, 1H, 6-H), 4.30 (d, 1H, 1-H), 4.39 (m, 1H, 5-H), 4.42 (d, 1H, 1-H),
ꢀ
4.80 (d, 1H, 3-H), 5.32 (dd, 1H, 4-H). 2 J
= 10.6 Hz, 3 J
= 10.3
H1,H1
H3,H4

1882
K. Polchow-Stein and J. Voss
Hz, 3 J
= 4.6 Hz, 3 J
= 1.6 Hz, 3 J
= 2.3 Hz, 2 J
= 12.5
ꢀ
ꢀ
H6,H6
H4,H5
H5,H6
H5,H6
Hz. 13C NMR (CDCl3): δ 30.8 (CH3CO), 37.9 (SO2CH3), 39.1 (SO2CH3),
39.2 (SO2CH3), 46.6 (C-5), 49.6 (OCH3), 63.6 (C-6), 66.4 (C-1), 74.1 (C-4),
74.5 (C-3), 98.9 (C-2), 193.5 (C O).
Methyl 1,5-Anhydro-3,4-di-O-mesyl-1-thio-β-D-
fructopyranoside (4)
(a) The tetramesylate 2 (1.00 g, 1.97 mmol) and CH3COSH (0.70 mL,
9.88 mmol) were dissolved in 2-methoxyethanol (90 mL). N2 was bub-
bled through the solution and KOH (0.55 g, 9.80 mmol) was added. The
mixture was heated to reflux (125◦C) for 20 h, the solvent was removed
and the residue was purified by CC (EtOAc/PE/EtOH 10:6:0.5) to yield
4 (40.4 mg, 6%) as crystals.
(b) The thioacetate 3 (0.45 g, 0.92 mmol) and Na2S · 9H2O (0.74 g,
3.07 mmol) were heated to 100◦C in DMSO (6 mL) for 20 h. Ice-water
(10 mL) was added, and the solution was extracted first with CH2Cl2
and then with PE. After drying with MgSO4, the solvent was removed
and the residue was purified by CC (EtOAc/PE 2:1) to give 4 (18.3 mg,
5%).
IR: ν 1171 (SO2), 1180 (SO2), 1350 (SO2), 1360 (SO2) cm–1. 1H NMR
(500 MHz, CDCl3): δ 2.71 (d, 1H, 1-H), 3.08 (m, 1H, 5-H), 3.14 (s, 3H,
SO2CH3), 3.19 (s, 3H, SO2CH3), 3.42 (s, 3H, OCH3), 3.48 (d, 1H, 1’-H),
4.47 (dd, 1H, 6-H), 4.50 (dd, 1H, 6-H), 4.93 (d, 1H, 3-H), 5.17 (vt, 1H,
ꢀ
4-H). 2 J
1.6 Hz, J
= 11.4 Hz, 3 J
= 3.6 Hz, 3 J
ꢀ
= 3.4 Hz, 3 J
=
H1,H1
H3,H4
H4,H5
H5,H6
3
2
= 10.2 Hz. 13C NMR (CDCl3): δ 29.6
ꢀ
= 3.0 Hz, J
H5,H6
H6,H6
(C-1) 37.5 (C-5), 38.87 (SO2CH3), 38.91 (SO2CH3), 50.2 (OCH3), 70.9
(C-6), 83.3 (C-3), 83.6 (C-4), 96.1 (C-2).
Methyl 1,3-O-Benzylidene-α-L-sorbopyranoside (5)
Compound 19 (4.85 g, 25.0 mmol) was dissolved in dry DMF (20 mL).
Benzaldehyde dimethylacetal (3.75 mL, 25.0 mmol) and camphorsul-
fonic acid (0.02 g, 0.2 mmol) were added and the reaction mixture was
kept at 50◦C under a slight vacuum (11 Torr) for 15 h. The solvent was
removed. The resulting syrup was stirred with PE to yield a slightly
syrupy solid. Recrystallization from 2-propanol gave pure 5 (3.81 g,
57%) as colorless crystals. M.p. 165–166◦C, Lit.10: 183–184◦C. [α]2D0
–
63.1 (1.01, 2-propanol), Lit.10: –54.6. IR: ν 3496 (OH) cm–1. H NMR
(500 MHz, DMSO-d6, assignment of OH by addition of D2O): δ 3.21 (s,
3H, OCH3), 3.29 (vt, 1H, 6-H), 3.33 (d, 1H, 5-OH), 3.40 (m, 1H, 5-H),
3.44 (d, 1H, 3-H), 3.52 (d, 1H, 1-H), 3.59 (dd, 1H, 6-H), 3.63 (m, 1H, 4-H),
1

Anhydro-Thiohexopyranosides and -Thiohexofuranosides
1883
4.26 (d, 1H, 1ꢀ-H), 5.13 (d, 1H, 4-OH), 5.62 (s, 1H, PhCH), 7.34–7.40 (m,
2
3
ꢀ
3H, Har), 7.45–7.47 (m, 2H, Har). J
= 11.8 Hz, J
= 9.9 Hz,
H1,H1
H3,H4
3
3
3
3 J
= 8.8 Hz, J
= 32.3 Hz, J
= 10.8 Hz, J
= 6.0
ꢀ
H4,H5
Hz, 3 J
H4,OH4
H5,H6
H5,H6
= 9.6 Hz, 2 J
= 10.9 Hz. 13C NMR (DMSO-d6): δ 47.4
ꢀ
H6,H6
H5,OH5
(OCH3), 63.3 (C-6), 66.3 (C-1), 69.8 (C-5), 70.5 (C-4), 81.6 (C-3), 92.5
(C-2), 101.1 (PhCH), 126.4 (2 Car), 127.9 (2 Car), 128.7 (1 Car), 137.9 (1
Car).
Methyl 1,3-O-Benzylidene-4,5-di-O-mesyl-α-L-
sorbopyranoside (6)
The mesylate 6 was prepared by mesylation of 5 according to ref.10 IR: ν
1176 (SO2), 1360 (SO2) cm–1. 1H NMR (CDCl3): δ 2.95 (s, 3H, SO2CH3),
3.17 (s, 3H, SO2CH3), 3.38 (s, 3H, OCH3), 3.62 (d, 1H, 1-H), 3.78 (vt,
1H, 6-H), 3.79 (d, 1H, 3-H), 4.08 (dd, 1H, 6-H), 4.39 (d, 1H, 1-H), 4.69
(ddd, 1H, 5-H), 5.16 (dd, 1H, 4-H), 5.61 (s, 1H, PhCH), 7.34–7.38 (m,
ꢀ
3H, Har), 7.46–7.49 (m, 2H, Har). 2 J
= 12.3 Hz, 3 J
= 10.0 Hz,
H1,H1
H3,H4
3 J
= 8.9 Hz, 3 J
= 6.6 Hz, 3 J
= 10.4 Hz, 2 J
= 10.8
ꢀ
ꢀ
H4,H5
H5,H6
H5,H6
H6,H6
Hz. 13C NMR (CDCl3): δ 38.8 (SO2CH3), 38.9 (SO2CH3), 48.6 (OCH3),
61.6 (C-6), 66.8 (C-1), 75.2 (C-5), 77.5 (C-4), 79.4 (C-3), 92.7 (C-
2), 102.6 (PhCH), 126.2 (2 C, Car), 128.5 (2 C, Car), 129.6 (Car-4ꢀ),
136.3 (Car-1ꢀ).
Methyl 3-O-Benzoyl-1-bromo-1-deoxy-4,5-di-O-mesyl-α-L-
sorbopyranoside (7)
Compound 6 (1.50 g, 3.42 mmol) was dissolved in CCl4 (33 mL) un-
der N2. NBS (0.77 g, 4.33 mmol) and BaCO3 (2.85 g, 14.4 mmol) were
added, and the reaction mixture was heated to reflux for 4 h. After cool-
ing, the solution was filtered and the residue was washed with EtOAc.
The combined solutions were evaporated and the product was purified
by CC (EtOAc/PE 3:1) to yield 7 (1.42 g, 80%) as colorless crystals. Mp.
126–127◦C. [α]D20 –57.8 (1.00, CHCl3). IR: ν 1178 (SO2), 1363 (SO2). 1H
NMR (CDCl3): δ 2.81 (s, 3H, SO2CH3), 3.15 (s, 3H, SO2CH3), 3.35 (d, 1H,
1-H), 3.39 (s, 3H, OCH3), 3.61 (d, 1H, 1-H), 3.70 (vt, 6-H), 4.20 (dd, 1H,
6-H), 4.79 (ddd, 1H, 5-H), 5.25 (vt, 1H, 4-H), 5.66 (d, 1H, 3-H), 7.44–7.50
ꢀ
(m, 2H, Har), 7.60–7.64 (m, 1H, Har), 8.11–8.13 (m, 2H, Har). 2 J
=
H1,H1
11.7 Hz, 3 J
= 10.1 Hz, 3 J
= 9.4 Hz, 3 J
= 10.6 Hz,
H3,H4
H4,H5
H5,H6
3 J
= 6.2 Hz, 2 J
= 11.0 Hz. 13C NMR (CDCl3): δ 29.3 (C-1),
ꢀ
ꢀ
H6,H6
H5,H6
38.5 (SO2CH3), 38.9 (SO2CH3), 48.8 (OCH3), 61.1 (C-6), 70.9 (C-3), 74.0
(C-5), 77.4 (C-4), 98.8 (C-2), 128.5 (1 Car), 128.8 (2 Car), 130.2 (2 Car),
133.9 (1 Car), 165.1 (C O).

1884
K. Polchow-Stein and J. Voss
Methyl 1,5-Anhydro-3-O-benzoyl-4-O-mesyl-1-thio-β-D-
fructopyranoside (8)
The bromo compound 7 (0.64 g, 1.24 mmol) was dissolved in dry DMF
(10 mL). N2 was bubbled through the solution. Then AcSK (0.42 g, 3.68
mmol) was added and the solution was heated to reflux for 12 h. The
reaction mixture was directly submitted to CC (EtOAc/PE) to yield 8
(120 mg, 26%) as crystals. M.p. 92–93◦C (dec.). IR: ν 1176 (SO2), 1361
(SO2), 1728 (C O) cm–1. H NMR (500 MHz, CDCl3): δ 2.82 (d, 1H,
1
H-1), 3.09 (s, 3H, SO2CH3), 3.11 (m, 1H, 5-H), 3.33 (s, 3H, OCH3), 3.45
(d, 1H, 1-H), 4.52 (dd, 1H, 6-H), 4.56 (dd, 1H, 6-H), 5.26 (vt, 1H, 4-H),
5.53 (d, 1H, 3-H), 7.45–7.48 (m, 2H, Har), 7.58–7.61 (m, 1H, Har), 8.09–
ꢀ
8.11 (m, 2H, Har). 2 J
= 11.3 Hz, 3 J
= 3.4 Hz, 3 J
= 3.4
H1,H1
H3,H4
ꢀ
H6,H6
H4,H5
Hz, 3 J
= 1.7 Hz, 3 J
= 3.0 Hz, 2 J
= 10.1 Hz. 13C NMR
ꢀ
H5,H6
H5,H6
(CDCl3): δ 29.7 (C-1), 37.3 (C-5), 38.8 (SO2CH3), 50.4 (OCH3), 70.8 (C-
6), 76.7 (C-3), 82.8 (C-4), 96.4 (C-2), 128.5 (2 Car), 129.2 (Car), 130.1 (2
Car), 133.5 (Car), 165.6 (C O).
6-S-Acetyl-2,3-O-isopropylidene-6-thio-α-L-sorbofuranose (10)
and 1,6-Di-S-acetyl-2,3-O-isopropylidene-1,6-dithio-α-L-
sorbofuranose (11)
PPh3 (6.39 g, 24.4 mmol) was dissolved in dry THF (50 mL) under
N2. After cooling to 0◦C, diisopropyl azodicarboxylate (DIAD, 4.70 mL,
24.4 mmol) was dropped in and the solution (1) was stirred at 0◦C for
30 min. AcSH (2.00 mL, 28.1 mmol) was dropped into a solution of 2,3-O-
isopropylidene-α-L-sorbofuranose 913,14 (4.27 g, 19.4 mmol) in dry THF
(40 mL) under N2 at 0◦C. After 30 min stirring at 0◦C, this solution (2)
was dropped into solution (1). The reaction mixture was stirred at 20◦C
for 3 days. The solvent was removed and the residue was separated by
CC (EtOAc/PE 3:2) to yield F1, R = 0.76 (0.71 g, contaminated with
f
DIHD: 11% of 11), and F2, R = 0.51 (4.20 g, contaminated with DIHD:
f
62% of 10) as syrups.
10: IR: ν 1689 (C O), 3464 (OH) cm–1. 1H NMR (acetone-d6): δ 1.30
(s, 3H, CH3), 1.39 (s, 3H, CH3), 2.32 (s, 3H, COCH3), 3.08 (dd, 1H, 6-
H), 3.13 (dd, 1H, 6-H), 3.83–3.86 (m, 2H, 1-H, 1-H), 4.01 (dd, 1H, 4-H),
4.22 (m, 1H, 5-H), 4.34 (d, 1H, 4-OH), 4.43 (s, 1H, 3-H), 4.56 (dd, 1H,
1-OH). 2 J
= 10.3 Hz, 3 J
= 1.8 Hz, 3 J
= 5.8 Hz, 3 J
=
ꢀ
ꢀ
H1,H1
H4,H5
H6,H6ꢀ
2.3 Hz, 3 J
= 8.1 Hz, 3 JH1,OH= 1.7 Hz, 3 JH1 ,OH= 7.0 Hz, 2 J
=
H4,OH
H5,H6
H5,H6ꢀ
13.4 Hz. 13C NMR (acetone-d6): δ 26.6 (CH3), 27.6 (CH3), 27.7 (C-6),
30.4 (COCH3), 63.7 (C-1), 75.1 (C-4), 81.4 (C-5), 86.6 (C-3), 112.4 (C-2),
115.0 (CMe2), 195.4 (C O).
11: IR: ν 1709 (C O), 1718 (C O), 3315 (OH) cm–1. 1H NMR (acetone-
d6): δ 1.34 (s, 3H, CH3), 1.37 (s, 3H, CH3), 2.325 (s, 3H, COCH3), 2.328

Anhydro-Thiohexopyranosides and -Thiohexofuranosides
1885
(s, 3H, COCH3), 3.09–3.18 (m, 2H, 6-H, 6-H), 3.39 (d, 1H, 1-H), 3.43
(d, 1H, 1-H), 4.11 (ddd, 1H, 4-H), 4.22 (vtd, 1H, 5-H), 4.29 (bs, 1H, 3-
H), 4.50 (dd, 1H, 4-OH). 2 J
= 13.9 Hz, 3 J
= 0.5 Hz, 3 J
=
ꢀ
H1,H1
H4,H5
H6,H6ꢀ
2.1 Hz, 3 J
= 4.6 Hz, 3 J
= 7.1 Hz, 3 J H3,H4 = 7.1 Hz, 2 J
=
H4,OH
H5,H6
H5,H6ꢀ
13.4 Hz. 13C NMR (acetone-d6): δ 26.8 (CH3), 27.6 (CH3), 27.7 (C-1), 30.8
(COCH3), 30.9 (COCH3), 35.2 (C-6), 75.3 (C-4), 81.6 (C-5), 87.6 (C-3),
112.3 (C-2), 114.3 (CMe2), 194.6 (C O), 195.6 (C O).
6-S-Acetyl-2,3-O-isopropylidene-1,4-di-O-mesyl-6-thio-α-L-
sorbofuranose (12)
Compound 10 (5.81 g = 16.8 mmol of 10) was mesylated with methane-
sulfonyl chloride (9.80 mL, 126 mmol) in pyridine (65 mL) as described
for 2. Purification by CC (EtOAc) gave 12 as a syrup (7.56 g, contami-
nated with 14% DIHD: 90% of 12). IR: ν 1176 (SO2), 1360 (SO2), 1697
1
(C O) cm–1. H NMR (CDCl3): δ 1.39 (d, 3H, CH3), 1.52 (s, 3H, CH3),
2.37 (s, 3H, COCH3), 3.08 (s, 3H, SO2CH3), 3.158 (dd, 1H, 6-H), 3.159
(s, 3H, SO2CH3), 3.23 (dd, 1H, 6-H), 4.33 (d, 1H, 1-H), 4.37 (d, 1H, 1-
H), 4.48 (vtd, 1H, 5-H), 4.82 (s, 1H, 3-H), 5.05 (d, 1H, 4-H). 2 J
=
ꢀ
H1,H1
11.4 Hz, 3 J
= 2.8 Hz, 3 J
= 7.2 Hz, 3 J
= 6.9 Hz, 2 J
=
ꢀ
ꢀ
H4,H5
H5,H6
H5,H6
H6,H6
13.8 Hz. 13C NMR (CDCl3): δ 26.3 (CH3), 26.4 (C-6), 27.2 (CH3), 30.5
(COCH3), 37.7 (SO2CH3), 38.7 (SO2CH3), 67.5 (C-1), 79.2 (C-5), 80.7
(C-4), 83.5 (C-3), 111.5 (C-2), 113.8 (C-Me2), 194.4 (C O).
1,6-Anhydro-2,3-O-isopropylidene-4-O-mesyl-1-thio-α-L-
sorbofuranose (13)
Irrespective of its contamination, 12 (2.56 g, 5.05 mmol 12) and
NaHCO3 (1.00 g, 11.9 mmol) were refluxed under N2 in 2-
methoxyethanol/H2O (19:1) for 14 h. The solvents were removed and
the residue chromatographed (EtOAc/PE 1:1) to yield 13 (0.40 g, con-
taminated with DIHD, 18% 13) as a syrup. IR: ν 1180 (SO2), 1360 (SO2)
cm–1. 1H NMR (CDCl3): δ 1.42 (s, 3H, CH3), 1.57 (s, 3H, CH3), 2.36 (dd,
3H, 6-H), 2.42 (d, 1H, 1-H), 3.03 (dd, 1H, 6-H), 3.15 (s, 3H, SO2CH3),
3.31 (d, 1H, 1ꢀ-H), 5.05 (d, 1H, 3-H), 5.07–5.10 (m, 1H, 5-H), 5.15 (dd, 1H,
ꢀ
4-H). 2 J
0.7 Hz, J
= 12.5 Hz, 3 J
= 1.8 Hz, 3 J
ꢀ
= 6.9 Hz, 3 J
=
H1,H1
H3,H4
H4,H5
H5,H6
3
2
= 13.8 Hz. 13C NMR (CDCl3): δ 24.1
ꢀ
= 3.2 Hz, J
H5,H6
H6,H6
(C-6), 27.6 (CH3), 28.3 (CH3), 30.6 (C-1), 38.1 (SO2CH3), 81.0 (C-5), 82.2
(C-4), 86.4 (C-3), 110.4 (C-2), 117.7 (CMe2).
1,6-Anhydro-4-O-mesyl-1-thio-α-L-sorbofuranose (14)
Without further purification, 13 (0.30 g = 0.68 mmol 13) was refluxed
in aqueous HOAc (10 mL, 20%) for 4 h. NaHCO3 (1.85 g) was added for

1886
K. Polchow-Stein and J. Voss
neutralization. The solution was saturated with NaCl and extracted
with CH2Cl2. After drying, the organic phase was evaporated and the
residue was chromatographed (EtOAc/PE 3:1) to yield pure 14 as a
syrup (31 mg, 18%). 1H NMR (acetone-d6): δ 2.28 (dd, 1H, 6-H), 2.36 (d,
1H, 1-H), 2.87 (dd, 1H, 6-H), 3.02 (m, 3H, 1ꢀ-H, 2-OH, 3-OH), 3.25 (s,
3H, SO2CH3), 4.65 (d, 1H, 3-H), 4.69–4.72 (m, 1H, 5-H), 4.94 (dd, 1H,
ꢀ
4-H). 2 J
= 12.5 Hz, 3 J
= 3.1 Hz, 3 J
= 7.3 Hz, 3 J
=
H1,H1
H3,H4
ꢀ
H6,H6
H4,H5
H5,H6
1.0 Hz, 3 J
= 3.2 Hz, 2 J
= 13.7 Hz. 13C NMR (acetone-d6): δ
ꢀ
H5,H6
23.9 (C-6), 33.4 (C-1), 38.0 (SO2CH3), 75.76 (C-3 or C-5), 75.82 (C-5 or
C-3), 87.1 (C-4), 99.7 (C-2).
Methyl 1,6-Anhydro-4-O-mesyl-1-thio-α-L-sorbofuranoside
(15) and Methyl 1,6-Anhydro-1-thio-α-L-sorbofuranoside (16)
Acetyl chloride (3.40 mL) was dissolved in MeOH (23 mL) to form a
solution of HCl in MeOH. Purified 13 (0.42 g, 1.42 mmol) was added
and the mixture was stirred at 20◦C for 4 d. After neutralization with
NEt3, the solvents were removed and the residue was extracted with
EtOAc. The solvent was removed from the extract. Chromatography
(EtOAc/PE 3:1) gave 15 (0.233 g, 61%) as a syrup.
15: IR: ν 1178 (SO2), 1354 (SO2), 3454 (OH) cm–1. 1H NMR (CDCl3):
δ 2.25 (d, 1H, 1-H), 2.35 (dd, 1H, 6-H), 2.79 (bs, 1H, OH), 2.94 (dd,
1H, 6-H), 3.19 (s, 3H, SO2CH3), 3.35 (d, 1H, 1ꢀ-H), 3.54 (s, 3H, OCH3),
ꢀ
4.76 (d, 1H, 3-H), 4.84 (m, 1H, 5-H), 4.99 (dd, 1H, 4-H). 2 J
= 12.3
H1,H1
3
3
3
3
ꢀ
Hz, J
= 3.2 Hz, J
= 7.2 Hz, J
= 1.0 Hz, J
= 3.1
H3,H4
H4,H5
H5,H6
H5,H6
Hz, 2 J
= 13.8 Hz. 13C NMR (CDCl3): δ 23.8 (C-6), 30.4 (C-1), 38.0
ꢀ
H6,H6
(SO2CH3), 51.9 (OCH3), 76.6 (C-3 or C-5), 76.9 (C-3 or C-5), 86.0 (C-4),
102.4 (C-2).
When unpurified 13 (containing its hydrolysis product 1,6-anhydro-
2,3-O-isopropylidene-1-thio-α-L-sorbofuranose) was used as starting
material, a 4% yield of 16 was isolated after CC (EtOAc/PE 3:1) in
addition to 15.
1
16: H NMR (CDCl3): δ 2.25 (ddd, 1H, 1-H), 2.34 (ddd, 1H, 6-H),
2.58 (s, 2H, 3-OH, 4-OH), 2.91 (dd, 1H, 6-H), 3.36 (d, 1H, 1-H), 3.52 (s,
3H, OCH3), 4.28 (d, 1H, 3-H), 4.41 (dd, 1H, 4-H), 4.70 (dvt, 1H, 5-H).
2 J
H4,H5
= 12.3 Hz, 4 J
= 0.4 Hz, 5 J
= 0.8 Hz, 3 J
= 2.3 Hz,
ꢀ
H1,H1
H1,H5
H5,H6ꢀ
H3,H4
3 J
= 7.4 Hz, 3 J H1,H=6 2.2 Hz, 3 J
= 2.8 Hz, 2 J
= 13.6 Hz.
ꢀ
H6,H6
H5,H6
13C NMR (CDCl3): δ 24.2 (C-6), 30.0 (C-1), 51.8 (OCH3), 78.0 (C-5), 80.8
(C-3 or C-4), 81.0 (C-3 or C-4), 100.7 (C-2).
Methyl 1,6:3,4-Dianhydro-1-thio-α-L-psicofuranoside (17)
The mesylate 15 (0.144 g, 0.53 mmol) and LiN3 (0.080 g, 1.63 mmol)
were refluxed in DMF (10 mL) for 18 h. The solvent was removed

Anhydro-Thiohexopyranosides and -Thiohexofuranosides
1887
and the residue was purified by CC (EtOAc/PE 3:1) to yield 17 as a
1
syrup (0.085 g, 92%). H NMR (CDCl3): δ 2.30 (dd, 1H, 6-H), 2.48 (d,
1H, 1-H), 3.05 (d, 1H, 1-H), 3.15 (dd, 1H, 6-H), 3.54 (s, 3H, OCH3),
3.63 (d, 1H, 3-H or 4-H), 3.71 (d, 1H, 3-H or 4-H), 4.51 (ddd, 1H, 5-H).
2 J
H5,H6
= 12.9 Hz, 3 J
= 3.2 Hz, 3 J
ꢀ
= 3.2 Hz, 3 J
= 1.8 Hz,
ꢀ
H1,H1
H3,H4
H4,H5
H5,H6
3 J
= 3.2 Hz, 2 J
= 13.4 Hz. 13C NMR (CDCl3): δ 25.7 (C-6),
ꢀ
H6,H6
30.1 (C-1), 52.5 (CH3), 52.8 (C-3 or C-4), 53.0 (C-3 or C-4), 74.3 (C-5),
101.6 (C-2).
1-O-Acetyl-2,3-O-isopropylidene-α-L-sorbofuranose (18)18
Reaction of 912−14 with Ac2O gave 1-O-acetyl-2,3:4,6-di-O-
isopropylidene-α-L-sorbofuranose18 (purified by CC with EtOAc
instead of distillation,18 99% yield). The di-O-isopropylidene derivative
(5.70 g, 18.85 mmol) was dissolved in 60% aqueous HOAc (67 mL) and
heated to 80–85◦C for 1 h. The solvent was removed. After repeated
codistillation with toluene and CC (EtOAc), 18 (R = 0.47, 4.51 g, 91%)
f
was obtained as a syrup. [α]2D0 –51.0 (1.0, acetone). IR: ν 1747 (C O),
3423 (OH) cm–1. 1H NMR (acetone-d6): δ 1.30 (s. 3H, CH3), 1.40 (s, 3H,
CH3), 2.02 (s, 3H, COCH3), 3.71 (dd, 1H, 6-H), 3.78 (dd, 1H, 6-H), 4.02
(d, 1H, 1-H), 4.19 (d, 1H, 4-H), 4.23 (dvt, 2H, 5-H, OH), 4.35–4.38 (m,
ꢀ
2H, 1-H, 3-H), 4.58 (d, 1H, OH). 2 J
= 11.8 Hz, 3 J
= 2.8 Hz,
= 2.8 Hz.
H1,H1
H4,H5
3 J
= 5.6 Hz, 3 J
= 5.5 Hz, 2 J
= 11.6 Hz, 3 J
ꢀ
ꢀ
H5,H6
H5,H6
H6,H6
H,OH
13C NMR (acetone-d6): δ 20.7 (COCH3), 26.6 (CH3), 27.7 (CH3), 60.7
(C-6), 63.9 (C-1), 75.8 (C-4), 82.4 (C-5), 86.4 (C-3), 112.3 (C-2), 113.4
(CMe2), 170.4 (C O).
1-O-Acetyl-2,3-O-isopropylidene-4,6-di-O-mesyl-α-L-
sorbofuranose(19)
Compound 1818 (4.39 g, 16.7 mmol) was mesylated as described for 2.
CC (EtOAc) gave 19 (6.64 g, 95%) as a colorless syrup. IR: ν 1174 (SO2),
1361 (SO2), 1745 (C O) cm–1. 1H NMR (acetone-d6): δ 1.38 (s, 3H, CH3),
1.49 (s, 3H, CH3), 2.07 (s, 3H, COCH3), 3.17 (s, 3H, SO2CH3), 3.30 (s,
3H, SO2CH3), 4.23 (s, 1H, 1-H), 4.37 (d, 1H, 1-H), 4.40 (dd, 1H, 6-H),
4.50 (dd, 1H, 6-H), 4.71 (ddd, 1H, 5-H), 4.83 (s, 1H, 3-H), 5.18 (dd, 1H,
ꢀ
4-H). 2 J
= 12.0 Hz, 3 J
= 0.5 Hz, 3 J
= 3.0 Hz, 3 J
=
H1,H1
H3,H4
ꢀ
H6,H6
H4,H5
H5,H6
7.4 Hz, 3 J
= 4.4 Hz, 2 J
= 10.9 Hz. 13C NMR (acetone-d6): δ
ꢀ
H5,H6
20.7 (COCH3), 26.6 (CH3), 27.4 (CH3), 37.3 (SO2CH3), 38.2 (SO2CH3),
63.5 (C-1), 67.7 (C-6), 78.3 (C-5), 82.4 (C-4), 86.8 (C-3), 113.7 (C-2), 113.8
(CMe2), 170.5 (C O).

1888
K. Polchow-Stein and J. Voss
Methyl 4,6-Di-O-mesyl-β-L-sorbofuranoside(20) and Methyl
4,6-Di-O-mesyl-α-L-sorbofuranoside (21)
Compound 19 (4.18 g, 11.5 mmol) was dissolved in methanolic HCl
(96 mL), prepared from acetyl chloride (14.4 mL). The solution was
stirred at 20◦C for 42 h, then neutralized with NEt3 (21 mL), and the
solvent was removed. The residue was extracted with EtOAc, the sol-
vent was removed from the extract, and the residue was repeatedly
chromatographed (EtOAc) to yield 20 (0.420 g, 10%, R = 0.39) and 21
f
(0.674 g, 17%, R = 0.31) as syrups.
f
20: [α]2D0+15.4 (1.0, acetone). IR: ν 1174 (SO2), 1350 (SO2), 3427
(OH) cm–1. H NMR (acetone-d6): δ 3.17 (s, 3H, SO2CH3), 3.22 (s, 3H,
1
SO2CH3), 3.32 (s, 3H, OCH3), 3.70 (d, 1H, 1-H), 3.81 (d, 1H, 1-H), 4.36
(dd, 1H, 6-H), 4.43 (dd, 1H, 6-H), 4.45 (d, 1H, 3-H), 4.70–4.74 (m, 1H,
5-H), 5.16 (dd, 1H, 4-H). 2 J
= 12.0 Hz, 3 J
= 3.2 Hz, 3 J
=
ꢀ
H1,H1
H3,H4
ꢀ
H6,H6
H4,H5
6.3 Hz, 3 J
= 7.2 Hz, 3 J
= 4.1 Hz, 2 J
= 10.8 Hz. 13C NMR
ꢀ
H5,H6
H5,H6
(acetone-d6): δ 37.9 (SO2CH3), 38.2 (SO2CH3), 49.2 (OCH3), 59.8 (C-1),
69.5 (C-6), 77.5 (C-5), 79.0 (C-3), 84.4 (C-4), 109.8 (C-2).
21: [α]2D0+74.8 (1.02, acetone). IR: ν 1174 (SO2), 1352 (SO2), 3408
(OH) cm–1. H NMR (acetone-d6): δ 3.16 (s, 3H, SO2CH3), 3.26 (s, 3H,
1
SO2CH3), 3.36 (s, 3H, OCH3), 3.66 (d, 1H, 1-H), 3.73 (d, 1H, 1-H), 3.94
(m, 1H, OH), 4.22 (d, 1H, OH), 4.32 (dd, 1H, 6-H), 4.43 (dd, 1H, 6-
H), 4.46 (dd, 1H, 3-H), 4.57 (vtd, 1H, 5-H), 5.17 (dd, 1H, 4-H). 2 J
=
ꢀ
H1,H1
12.1 Hz, 3 J
= 6.3 Hz, 3 J
= 7.7 Hz, 3 J
= 6.9 Hz, 3 J
=
H4,H5
H5,H6
6.2 Hz, 3 JH3,H4 = 3.5 Hz, 2 JH3,OH3 = 11.3 Hz. 13C NMR (acetone-d6): δ
H5,H6ꢀ
H6,H6ꢀ
36.6 (SO2CH3), 38.4 (SO2CH3), 49.7 (OCH3), 60.5 (C-1), 68.9 (C-6), 74.3
(C-5), 76.7 (C-3), 85.3 (C-4), 104.8 (C-2).
Methyl 1-S-Acetyl-4,6-di-O-mesyl-1-thio-β-L-sorbofuranoside
(22)
Thio-Mitsunobu reaction of 20 (0.29 g, 0.84 mmol) with AcSH (0.15
mL, 2.11 mmol), DIAD (0.40 mL, 2.03 mmol), and PPh3 (0.54 g (2.06
mmol) in THF as described for 10, and CC (EtOAc) gave 22 as a syrup,
which was slightly contaminated with DIHD (0.117 g, 35% of pure 22
according to its 1H NMR spectrum). IR: ν 1178 (SO2), 1369 (SO2), 1724
(C O), 3352 (OH) cm–1. 1H NMR (CDCl3): δ 2.37 (s, 3H, COCH3), 3.09
(s, 6H, 2 SO2CH3), 3.28 (s, 3H, OCH3), 3.39 (s, 2H, 1-H, 1-H), 4.28 (d,
1H, 3-H), 4.35–4.46 (m, 2H, 6-H, 6-H), 4.77 (vt, 1H, 5-H), 5.09 (dd, 1H,
ꢀ
4-H). 3 J
= 1.4 Hz, 3 J
= 5.9 Hz, 3 J
= 5.9 Hz, 3 J
= 5.9
H3,H4
H4,H5
H5,H6
H5,H6
Hz. 13C NMR (CDCl3): δ 28.2 (C-1), 30.2 (COCH3), 38.2 (SO2CH3), 38.4
(SO2CH3), 49.0 (OCH3), 66.9 (C-6), 77.5 (C-5), 78.4 (C-3), 82.3 (C-4),
109.8 (C-2), 194.4 (C O).

Anhydro-Thiohexopyranosides and -Thiohexofuranosides
1889
Methyl 1,4-Anhydro-6-O-mesyl-1-thio-β-L-psicofuranoside(23)
The thioacetate 22 (0.117 g, 0.29 mmol) and NaHCO3 (0.200 g, 2.38
mmol) were refluxed in 2-methoxyethanol/H2O (19:1, 200 mL) for 22 h
as described for 13. CC (EtOAc) gave 23 as a syrup, which was slightly
contaminated with DIHD (55 mg, 70% of pure 23). IR: ν 1176 (SO2),
1354 (SO2) cm–1. 1H NMR (CDCl3): δ 3.02 (s, 2H, 1H, 1-H), 3.06 (s, 3H,
SO2CH3), 3.26 (d, 1H, 4-H), 3.39 (s, 3H, OCH3), 4.22 (d, 1H, 6-H), 4.23
(d, 1H, 6-H), 4.44 (m, 1H, 3-H), 4.61 (vt, 1H, 5-H). 3 J
= 2.5 Hz,
H3,H4
3 J
= 5.7 Hz, 3 J
= 5.0 Hz. 13C NMR (CDCl3): δ 33.0 (C-1), 37.7
ꢀ
H5,H6
H5,H6
(SO2CH3), 48.1 (C-4), 58.9 (OCH3), 69.1 (C-6), 70.3 (C-3), 82.6 (C-5),
111.8 (C-2).
Methyl 1-S-Acetyl-4,6-di-O-mesyl-1-thio-α-L-sorbofuranoside
(24)
Thio-Mitsunobu reaction of 21 (0.584 g, 1.667 mmol) with AcSH (0.30
mL, 4.22 mmol), DIAD (0.75 mL, 3.81 mmol) and PPh3 (1.00 g, 3.81
mmol) in THF as described for 22, and CC (EtOAc) gave 24 as a syrup,
which was slightly contaminated with DIHD (0.418 g, 61% of pure 24 ac-
cording to its NMR spectrum). IR: ν 1178 (SO2), 1360 (SO2), 1729 (C O)
cm–1. H NMR (CDCl3): δ 2.39 (s, 3H, COCH3), 3.08 (s, 3H, SO2CH3),
1
3.17 (s, 3H, SO2CH3), 3.27 (d, 1H, 1-H), 3.31 (d, 1H, 1-H), 3.37 (s, 3H,
OCH3), 4.20 (d, 1H, 3-H), 4.33 (dd, 1H, 6-H), 4.39 (dd, 1H, 6-H), 4.45
2
3
ꢀ
(m, 1 H, 5-H), 5.16 (vt, 1 H, 4-H). J
= 14.6 Hz, J
= 6.3 Hz,
H1,H1
H3,H4
3 J
= 6.9 Hz, 3 J
= 4.9 Hz, 3 J
= 3.8 Hz, 2 J
= 11.0
ꢀ
ꢀ
H4,H5
H5,H6
H5,H6
H6,H6
Hz. 13C NMR (CDCl3): δ 29.7 (C-1), 30.4 (COCH3), 37.5 (SO2CH3), 38.5
(SO2CH3), 49.4 (OCH3), 67.0 (C-6), 73.5 (C-5), 77.6 (C-3), 83.6 (C-4),
103.2 (C-2), 195.1 (C O).
Methyl 1-S-Acetyl-2,4,6-tri-O-mesyl-1-thio-α-L-
sorbofuranoside (25)
Mesylation of 24 (0.418 g, 1.022 mmol, 2 h) as described for 2, and
CC (EtOAc) gave 25 as a syrup, which was slightly contaminated with
DIHD (0.492 g, 99% of pure 25 according to its NMR spectrum). IR: ν
1178 (SO2), 1361 (SO2) cm–1. 1H NMR (CDCl3): δ 2.40 (s, 3H, COCH3),
3.10 (s, 3H, SO2CH3), 3.19 (s, 3H, SO2CH3), 3.20 (s, 3H, SO2CH3), 3.32
(d, 1H, 1-H), 3.39 (s, 3H, OCH3), 3.52 (d, 1H, 1ꢀ-H), 4.42 (m, 2H, 6-H, 6ꢀ-
ꢀ
H), 4.51 (dvt, 1H, 5-H), 5.17 (d, 1H, 3-H), 5.43 (vt, 4-H). 2 J
= 14.7
H1,H1
3
3
3
3
ꢀ
Hz, J
= 6.5 Hz, J
= 7.0 Hz, J
= 4.9 Hz, J
= 3.8
H3,H4
H4,H5
H5,H6
H5,H6
Hz. 13C NMR (CDCl3): δ 29.3 (C-1), 30.4 (COCH3), 37.7 (SO2CH3), 38.5

1890
K. Polchow-Stein and J. Voss
(SO2CH3), 38.9 (SO2CH3), 49.5 (OCH3), 66.5 (C-6), 73.7 (C-5), 79.90
(C-3), 79.94 (C-4), 103.3 (C-2), 194.1 (C O).
Methyl 1,3-Anhydro-4,6-di-O-mesyl-1-thio-α-L-
tagatofuranoside(26) and Methyl 1,6-Anhydro-3,4-di-O-mesyl-
1-thio-α-L-sorbofuranoside (27)
Irrespective of the contamination, the thioacetate 25 (1.98 g, 1.011
mmol of pure 25) and NaHCO3 (0.35 g, 4.17 mmol) were refluxed in
2-methoxyethanol/H2O (19:1, 200 mL) for 18 h as described for 13. CC
(EtOAc/PE 3:1) gave 26 (0.019 g, 6%) and 27 (0.029 g, 8%) as pure
syrups.
26: IR: ν 1178 (SO2), 1358 (SO2) cm–1. H NMR (CDCl3): δ 3.10 (d,
1
1H, 1-H), 3.13 (s, 3H, SO2CH3), 3.14 (d, 1H, 1-H), 3.15 (s, 3H, SO2CH3),
3.52 (s, 3H, OCH3), 3.53 (d, 1H, 3-H), 4.23 (dd, 1H, 6-H), 4.32 (dd, 1H,
6-H), 4.69 (dd, 1H, 5-H), 5.25 (d, 1H, 4-H). 2 J
= 12.8 Hz, 3 J
=
ꢀ
H1,H1
H3,H4
ꢀ
H6,H6
2.5 Hz, 3 J
= 6.6 Hz, 3 J
= 4.6 Hz, 3 J
= 4.2 Hz, 2 J
=
ꢀ
H4,H5
H5,H6
H5,H6
11.6 Hz. 13C NMR (CDCl3): δ 34.1 (C-1), 37.9 (SO2CH3), 39.1 (SO2CH3),
45.5 (C-3), 53.5 (OCH3), 68.2 (C-6), 74.8 (C-4), 84.0 (C-5), 110.2 (C-2).
27: IR: ν 1176 (SO2), 1354 (SO2) cm–1. H NMR (CDCl3): δ 2.25 (d,
1
1H, 1-H), 2.35 (dd, 1H, 6-H), 2.95 (dd, 1H, 6-H), 3.07 (s, 3H, SO2CH3),
3.19 (s, 3H, SO2CH3), 3.36 (d, 1H, 1-H), 3.54 (s, 3H, OCH3), 4.77 (d, 1H,
3-H), 4.84 (m, 1H, 5-H), 5.00 (dd, 1H, 4-H). 2 J
= 12.4 Hz, 3 J
=
ꢀ
H1,H1
H3,H4
ꢀ
H6,H6
3.1 Hz, 3 J
= 7.2 Hz, 3 J
= 1.0 Hz, 3 J
= 3.1 Hz, 2 J
=
ꢀ
H4,H5
H5,H6
H5,H6
13.8 Hz. 13C NMR (CDCl3): δ 23.8 (C-6), 30.4 (C-1), 37.7 (SO2CH3), 38.0
(SO2CH3), 51.9 (OCH3), 76.6 (C-3), 76.9 (C-5), 86.1 (C-4), 100.4 (C-2).
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Anhydro-Thiohexopyranosides and -Thiohexofuranosides
1891
[11] D. L. Failla, T. L. Hullar, and S. B. Siskin, Chem. Commun., 1966, 716, de-
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glucopyranoside and suggested a radical mechanism for this reaction.
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