Short synthesis of hydroxylated thiolane and selenolane rings from mono-benzylated pentitols and aldoses dithioacetals bis-thionocarbonates as bis-electrophilic substrates

Article abstract of DOI:10.1016/j.tet.2005.05.008

1-O-Benzylpentitols (with d-arabino, d-lyxo, d,l-xylo and d,l-ribo configurations) and aldoses dibenzyldithioacetals (with l-arabino, d-lyxo, d-xylo, d-ribo, d-galacto, d-gluco and d-manno configurations) were directly and efficiently transformed into the

Full text of DOI:10.1016/j.tet.2005.05.008

Tetrahedron 61 (2005) 6772–6781
Short synthesis of hydroxylated thiolane and selenolane rings
from mono-benzylated pentitols and aldoses dithioacetals
bis-thionocarbonates as bis-electrophilic substrates
*
¨
Alain Danquigny, Mohamed Aıt Amer Meziane, Gilles Demailly and Mohammed Benazza
´
Laboratoire des Glucides, FRE 2779, Universite de Picardie Jules Verne, 10 rue Baudelocque, F-80039 Amiens, France
Received 4 February 2005; revised 26 April 2005; accepted 2 May 2005
Abstract—1-O-Benzylpentitols (with D-arabino, D-lyxo, D,L-xylo and D,L-ribo configurations) and aldoses dibenzyldithioacetals (with
L-arabino, D-lyxo, D-xylo, D-ribo, D-galacto, D-gluco and D-manno configurations) were directly and efficiently transformed into their cyclic
bis-thionocarbonate derivatives (61–73%) by reaction with diimidazolyl thione (Im2CS) in 1,4-dioxane. These bis-electrophilic adducts react
regioselectively with Na2S$9H2O or Se/NaBH4 to lead regioselectively to the corresponding thiolane and selenolane rings in good yields for
a short synthesis (47–65%).
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
It is currently well known that the thiaheterocycles
analogues of sugars are weak or not at all inhibitors of
glycosidases1 in contrast with aza-sugars analogues. In the
later field, considerable development was realised since the
first discovery of glycosidase inhibition effect of deoxy-
nojirimicine.2 However, since the first structural elucidation
of salacinol (A) (Fig. 1),3 potent a-glycosidases inhibitor
used in treatment of type-II non-insulinodependant
diabetes,4 a renewal of interest has demonstrated for
thioanhydro sugars. Indeed, this zwitterionic compound
involves a thiolane subunit with D-arabino configuration
where the trivalent sulfide cation mimics the oxonium ion in
transition state of the enzymatic hydrolysis process.5 We
and other groups had developed some synthetic strategy to
obtain a wide library of thiaheterosugars during the last
years.6 For instance, we had published the first short
Figure 1.
synthesis of the racemic mixture of arabinothiolane subunit
Some of them were recently used by Pinto and co-workers
of salacinol (B) from S-heterocyclisation of bis-cyclic
sulfate of monobenzyl-D,L-xylitol.6a The latter was obtained
in the synthesis of tetrathiopyrane and selenopyrane
analogues of salacinol E and F.9
from regioselective benzylation of xylitol stannylether
complex7 and subsequent two steps bis-cyclic sulfates
synthesis. Using a,u-dibromoalditol intermediates syn-
thesised regioselectively from bidirectional transformation
of free alditols we have provided one of the most versatile
synthesis of thia and selenaanhydroalditols (Scheme 1).8
Keywords: Alditols; Aldoses; Cyclic-thionocarbonate; Thiolane;
Selenolane.
*
Scheme 1. (i) AcBr, 1,4-dioxane, rt, 16 h; (ii) Ac2O, pyridine; (iii) Na2S,
DMSO; (iv) Se, NaBH4, H2O, DMSO, rt, !10 min.
Corresponding author. Tel.: C33 322827527; fax: C33 322827561;
e-mail: mohammed.benazza@u-picardie.fr
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.05.008

A. Danquigny et al. / Tetrahedron 61 (2005) 6772–6781
6773
This bis-electrophilic heterocyclisation strategy was also
developed with other intermediate such as bis-epoxides,10
bis-sulfonates,11 and more recently by us with bis-cyclic
thionocarbonates12 in the presence of sodium sulfide
nonahydrate. Some six- and seven-membered rings obtained
following this approach could subsequently be converted to
tetrahydrothiophenes by transannular processes by reaction
with trimethylsilyl halides,13 with PPh3/CBr4 and when
undergoing the Mitsunobu reaction1 or by intramolecular
SN2 substitution with appropriately mesylated thiepane.14
was carried out with a mixture of 1-O-benzyl-D-arabinitol
(1) and 1-O-benzyl-D-lyxitol (5) (Table 1, entry 1) obtained
regioselectively from the D-arabinitol stannylether complex
and BnBr in a 52% overall yield (in a 1:1 ratio).7
This inseparable mixture was transformed to the corre-
sponding bis-cyclic thionocarbonate derivatives
2
(D-arabino) and 6 (D-lyxo) separated by chromatography
on silica gel in 32 and 40% yields, respectively (yields
evaluated from the starting mixture of 1 and 5). The
identification of these two regioisomers was achieved by
NMR spectroscopy of their anhydro derivatives D-arabino
2c (from 2,3-deprotection, path 1, Scheme 3a) or L-ribo 2f
(from 4,5-deprotection, path 2) and D-lyxo 6c (from
2,3-deprotection, path 1, Scheme 3b) or L-xylo 6f (from
4,5-deprotection, path 2) obtained in 31 and 47%
yields, respectively, by reaction of 2 and 6 with a catalytic
amount of MeONa in MeOH. Compounds 2c (or 2f) and 6c
(or 6f) were characterised by coupling constants for the
H-3,4 syn-methine configuration J3,4Z5.01 Hz and for the
trans-methine configuration of H-2,3, J2,3Z3.01 Hz
respectively. Consequently, by TLC performed on
silica gel, the most polar is the bis-thionocarbonate
derivative of D-lyxose 6 (RfZ0.08, 7/3 hexane–EtOAc)
and the less polar is the D-arabino derivative 2 (RfZ0.17).
The possible regioselective deprotection of cyclic thiono-
carbonates in compounds 2 and 5 had not been elucidated
until now.
The lack of general strategies to thiolane ring with differing
configurations led us to explore the heterocyclisation of
bis-cyclicsulfates of linear polyols. If the use of this kind of
bis-electrophilic intermediate obtained by oxidation of the
corresponding cyclic sulfite gave good results in the
partially protected alditols series,6a substrates like pentose
dithioacetals met a serious limitation because of the
oxidation induced a,b-unsaturated monosulfoxide for-
mation.15 Owing to this undesirable dithioacetal oxidation,
the use of cyclic-thionocarbonates as electrophilic inter-
mediates appears to be an alternative because of their easy
formation from diols and polyols. For instance, the 1,2:4,5-
and 1,2:5,6-bis-thionocarbonates were formed regio-
selectively by reaction of the corresponding alditols
stannylene acetal complexes and PhOCSCl (Scheme 2).
We carried out, on this bis-electrophilic system, for the first
time, the thiaheterocyclisation using a S] bi-anion as a soft
binucleophilic reagent. Unfortunately this original hetero-
cyclisation often led to inseparable mixtures of endo-tet and
exo-tet thiaheterocycles.12
With the rest of the pentitol and pentose derivatives the
vicinal bis-cyclic thionocarbonates were formed similarly in
good isolated yields (from pentitols: 10 (D,L-xylo) (61%), 14
(D,L-ribo) (72%) (entries 2 and 3); from pentoses: 18
(D-xylo) (73%), 22 (D-ribo) (76%), 26 (L-arabino) (68%)
and 30 (D-lyxo) (73%) (entries 4 to 7). With hexoses bearing
five free hydroxyl groups, the configurations of the hexoses
studied appeared to control the regioselectivity of the bis-
cyclic thionocarbonate formation. Thus the D-galacto and
the D-gluco isomers 33 and 37 showed 2,3:5,6-bis-cyclic
thionocarbonate formation with the hydroxyl in the
4-position left free (entries 8 and 9). In contrast, the
manno configuration 41 led to the bis-cyclic thionocarbo-
nate derivative 42 with the free 2-OH in 23% yield and 43
with the imidazolyl thionocarbonate group in the 2-position
in 34% yield.
Scheme 2. nZ0 (Tetritols) or 1 (pentitols): n0Z2, 3 or 4; n00Z2 or 3.
However the heterocyclisation involving primary–second-
ary electrophilic sites in an exo-tet process is of interest and
could be exploited in the synthesis of a wide range of
thiolane rings. Herein, we describe a short and versatile
synthesis of hydroxylated thiolane derivatives from mono-
benzylpentitols with D-arabino, D-lyxo, D,L-xylo and D,L-
ribo configurations, and from the dibenzyldithioacetal of
aldoses with L-arabino, D-lyxo, D-xylo, D-ribo, D-galacto,
D-gluco and D-manno configurations. Both pentitols and
aldose dibenzyldithioacetal substrates react smoothly with
diimidazolyle thione in dry 1,4-dioxane to give the
corresponding bis-thionocarbonates in good yields. The
subsequent thiaheterocyclisation and on other hand selena-
heterocyclisation gave thiolane and selenolane rings with
various configurations.
The 2,3:5,6 positions in 34 (galacto) and 38 (gluco) and
3,4:5,6 position of the cyclic thionocarbonate groups in 42
(manno) were easily confirmed by 13C NMR spectroscopy.
In fact, while 34 and 38 showed 2-C and 4-C chemical shifts
at approximately 84.8 and 69.6 ppm, respectively, the
manno compound 42 showed 2-C at 72.5 and 4-C at
82.6 ppm. The 2-C signals in 34 and 38, and 4-C signal in 42
were shifted upfield due to the cyclic thionocarbonate
group. The unexpected formation of the trans 2,3:5,6-bis-
thionocarbonate 38 is probably due to the bent conformation
involved by the stereoelectronic 1,3-parallel interaction
between 2-OH and 4-OH in zig-zag form of the gluco
configuration.
The first thiaheterocyclisation attempted with 2 by reaction
with Na2S$9H2O in DMSO at room temperature led to a
complex mixture with no formation of the expected
thioanhydro derivative. When the temperature was
2. Results and discussion
The first synthesis of the bis-thionocarbonate derivatives

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A. Danquigny et al. / Tetrahedron 61 (2005) 6772–6781
Table 1. Isolated yields of bis-thionocarbonates and thiaa and selenaheterocyclesb obtained from monobenzyl pentitols and aldose dithioacetal derivativesc as
substrates
Entry
1
Substrate
Bis-thionocarbonate
(yield (%))
Solated thiolane yield (%)
Isolated selenolane yield (%)
3 (47) (2,5-thioanhydro-D-ribo
or 1,4-L-ribo)
8 (50)
1 (1-O-Bn-D-arabino)
2 (32d)
C
7 (65) (1,4-Thioanhydro-L-
xylo or 2,5-D-xylo)
5 (5-O-Bn-D-arabino or 1-O-
Bn-D-lyxo)
12 (50)
6 (40d)
2
9 (D,L-xylo)
13 (D,L-ribo)
17 (D-xylo)
21 (D-ribo)
11 (55) (1,4-Thioanhydro-D,L-
arabino )
16 (50)
20 (45)
10 (61)
3
4
15 (45) (2,5-Thioanhydro-D,L-
arabino)
14 (72)
20 (45)
19 (60) (2,5-Thioanhydro-D-
lyxose)
18 (73)
5
23 (0) (2,5-Thioanhydro-D-
arabino)
24 (0)
22 (76)
26 (68)
6
7
27 (50) (2,5-Thioanhydro-L-
ribose)
28 (50)
25 (L-arabino)
29 (D-lyxo)
31 (60) (2,5-Thioanhydro-D-
xylose)
32 (55)
30 (73)
8
33 (D-galacto)
36 (55)
35 (3,6-Thioanhydro-D-
gulose)
34 (65)
9
37 (D-gluco)
39 (3,6-Thioanhydro-D-allose)
40 (53)
38 (60)

A. Danquigny et al. / Tetrahedron 61 (2005) 6772–6781
6775
Table 1 (continued)
Entry
Substrate
Bis-thionocarbonate
(yield (%))
Solated thiolane yield (%)
Isolated selenolane yield (%)
10
41 (D-manno)
44 (36e) (16f)
42 RZH (23) 43 R0ZCSIm
(34)
45 (50)
a 1.5 equiv of Na2S$9H2O, 80 8C, 1 h, DMSO.
b Se, NaBH4, H2O, DMSO, 80 8C, 45 mn.
c HCl (12 N), BnSH (2.2 equiv).
d From starting mixture of 2 and 5.
e From isolated 42.
f
From isolated 43. RZCH(SBn).
increased to 80 8C for 1 h, 2,3-di-O-acetyl-5-O-benzyl-1,4-
thioanhydro-L-ribitol (3) was isolated after acetylation in
47% yield (entry 1). The same conditions, when applied to 6
with the D-lyxo configuration, led to the L-xylo thioanhydro
derivative 7 in a better yield (65%) (entry 1). This is
probably due to the steric hindrance caused by the cis-
configuration of the 3-OH/4-OH groups in the transition
state which limits the thiaheterocyclisation of 2. Steric
hindrance could also be invoked in the cases of 15 (entry 3,
45%) and in a large part with 23 (entry 5) for which the
formation was excluded due to the interaction between
3-OH, 4-OH and the bulky dibenzyldithioacetal group in the
syn-position.
On other hand, it is well recognised that some diseases such
cancer,16 aids and the neurodegenerative diseases (e.g.,
Parkinson and Alzheimer)17 emerging from abnormally
high production of free radicals (oxidative stress).18 This is
attributed to antioxidants deficiency like vitamins19 or
enzymes such selenodependent glutathione peroxidase.20
This enzymatic antioxidant catalysed the hydroperoxyde
reduction (reduced metabolite precursor of deleterious HO%
free radical) with concomitant oxidation of a biologically
important thiol, the glutathione.21
It was reported that small organic molecules like Ebselen
G22 or the diphenyldiselenide H23 play an important part as
glutathione peroxidase mimics (Fig. 2). Schiesser and
co-workers reported the ten steps synthesis of D (described
in its perbenzylated xylo, ribo and D-arabino configurations)
(Fig. 1) which is an hydrosoluble possible antioxidant.24
More recently we had described the expedious synthesis of
the later and other configurations in two steps including
direct alditols bromination and subsequent selenahetero-
cyclisation at room temperature in DMSO by reaction
A very interesting result was obtained with hexose
dithioacetals where the 1,4-thiolane rings were formed
regioselectively from both 2,3:5,6 and 3,4:5,6-bis-cyclic
thionocarbonate derivatives. Thus the 2,4,5-tri-O-acetyl-
3,6-thioanhydro-D-gulose (35), D-allose (39) and D-altrose
(44) (Entries 8 to 10) were obtained in 60, 51 and 36%
yields, respectively. With the D-manno configuration, the
2-imidazolylthionocarbonate 43 was also submitted to the
thiaheterocyclisation reaction. Only a 16% yield was
extracted from a complex mixture.
The 3,6-thiaheterocyclisation leading to 35, 39 and 44 is
justified by 13C NMR spectroscopy which shows 3-C
signals at 50.6, 49.2 and 49.6 ppm, and 6-C signals at 36.1,
31.0 and 31.1 ppm, respectively.
Figure 2.
Scheme 3. (i) MeONa in MeOH, rt, 16 h; (ii) Ac2O, pyridine.

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A. Danquigny et al. / Tetrahedron 61 (2005) 6772–6781
with Se] prepared from Se/NaBH4 mixture in water
(Scheme 1).8
5.6 Hz, H2), 5.00 (t, 1H, J3,4Z5.6 Hz, H3), 5.15 (m, 1H,
J4,5bZJ5a,5bZ9.5 Hz, J4,5aZ6.2 Hz, H4), 4.55 (m, 1H, H5a),
4.80 (t, 1H, H5b), 7.20–7.30 (m, 5H, Ph), 4.60 (m, 2H, CH2);
13C NMR: d 68.4 (C1), 82.2 (C2), 80.7 (C3), 79.2 (C4), 71.0
(C5), 74.2 (CH2), 128.3–137.7 (Ph), 190.1–190.3 (CS).
Anal. Calcd for C14H14O5S2: C, 51.52; H, 4.32; O, 24.51; S,
19.65. Found: C, 51.86; H, 4.34. ESMS m/z calcd (MCC
Na) 349.01. Found 349.10.
In the present work, we increased the library of selenasugars
using the selenaheterocyclisation of bis-thionocarbonates of
pentitols and aldoses. The selenolane ring was obtained by
addition of the bis-cyclic thionocarbonates 2 to 42 solutions
in DMSO as solvent, respectively (entries 1 to 10) to the
mixture of Se and NaBH4 in water and heating for 1 h. The
selenolane compounds 4, 8, 12, 16, 20, 28, 32, 36, 40 and 45
obtained after acetylation were isolated in 45 to 55% yields
(Table 1). Despite the higher nucleophilicity of Se] as
binucleophile, similar results were obtained as in the case of
sulfur.
3.2.2. 1-O-Benzyl-2,3:4,5-di-O-thiocarbonyl-D-lyxitol (6).
40% Yield; colorless syrup; [a]D K18.7 (c 2, CH2Cl2); Rf
0.19 (5:5, hexane–EtOAc); H NMR (CDCl3): d 3.90 (m,
1
2H, H1a,1b), 5.10 (m, 1H, J2,3ZJ3,4Z3.1 Hz, H2), 5.19 (t,
1H, H3), 5.30 (ddd, 1H, J4,5bZJ5a,5bZ9.1 Hz, J4,5a
Z
6.5 Hz, H4), 4.60 (dd, 1H, H5a), 4.70 (t, 1H, H5b), 7.30–
7.45 (m, 5H, Ph), 4.55 (m, 2H, CH2); 13C NMR: d 66.2 (C1),
81.7 (C2), 80.6 (C3), d 78.4 (C4), 71.2 (C5), 74.6 (CH2),
128.7–136.9 (Ph), 189.8–190.6 (CS). Anal. Calcd for
C14H14O5S2: C, 51.52; H, 4.32; O, 24.51; S, 19.65.
Found: C, 51.81; H, 4.54. ESMS m/z calcd (MCCNa)
349.01. Found 349.10.
In conclusion, herein we report a short and versatile use of
bis-cyclic thionocarbonates as intermediates for a wide
range of polyhydroxylated 1,4-, 2,5- and 3,6-thio and
selenolanes from both pentitols and linear aldose substrates.
It is of interest to point out that the major part of thia and
selenaheterosugar analogues described are enantiopure.
3.2.3. 1-O-Benzyl-2,3:4,5-di-O-thiocarbonyl-D,L-xylitol
(10). 61% Yield; white solid: mp 115–117 8C; Rf 0.60
(EtOAc); H NMR (CDCl3): 3.75 (q, 1H, J1a,1bZ11.8 Hz,
3. Experimental
1
3.1. General methods
H1a), 3.75 (dd, 1H, J1a,2ZJ1b,2Z2.4 Hz, H1b), 5.30 (t, 1H,
J2,3Z4.6 Hz, H2), 5.35 (dd, 1H, J3,4Z1.7 Hz, H3), d 5.50
(dq, 1H, J4,5aZJ5a,5bZ9.1 Hz, J4,5bZ5.9 Hz, H4), 4.80 (t,
1H, H5a), 4.90 (q, 1H, H5b), 7.25–7.40 (m, 5H, Ph), d 4.60
(m, 2H, CH2); 13C NMR: d 69.1 (C1), 83.3 (C2), 82.0 (C3),
81.3 (C4), 71.8 (C5), 73.4 (CH2), 128.3–138.5 (Ph), 191.4–
191.8 (CS). Anal. Calcd for C14H14O5S2: C, 51.52; H, 4.32;
O, 24.51; S, 19.65. Found: C, 51.91; H, 4.17. ESMS m/z
calcd (MCCNa) 349.01. Found 349.30.
Melting points were determined with a Buchi 535 apparatus
and are uncorrected. 1H and 13C NMR spectra were
recorded in CDCl3 on Bruker 300 WB spectrometer;
chemical shifts are reported in d (ppm) relative to Me4Si.
Coupling constants, assigned by double irradiation, are in
Hz. All 13C NMR signals were assigned through C,H-
correlated spectra with hsqc.grad experiment. TLC was
performed on silica Gel 60 F254 230 mesh (E. Merck) with
hexane–EtOAc as eluant, and zones were detected by
vanillin–H2SO4 reagent. The silica gel used in column
chromatography was 35–70 m (Amicon). Optical rotations
were determined with Perkin–Elmer instruments, model
343 polarimeter (1 mL cell). Elemental analyses were
performed by the ‘Service de Microanalyse du CNRS
3.2.4. 1-O-Benzyl-2,3:4,5-di-O-thiocarbonyl-D,L-ribitol
(14). 72% Yield; white solid: mp 118–120 8C; Rf 0.51
(5:5, hexane–EtOAc); H NMR (CDCl3): d 3.85 (s, 2H,
1
H1a,1b), 5.20 (m, 2H, H2,3), 5.40 (m, 1H, H4), 4.70 (m, 2H,
H5a,5b), 7.20–7.30 (m, 5H, Ph), 4.60 (m, 2H, CH2); 13C
NMR: d 66.2 (C1), d 81.9 (C2), 80.5 (C3), 78.4 (C4), 71.6
(C5), 74.8 (CH2), 128.5–136.4 (Ph), 189.8–190.6 (CS).
Anal. Calcd for C14H14O5S2: C, 51.52; H, 4.32; O, 24.51; S,
19.65. Found: C, 51.86; H, 4.42. ESMS m/z calcd (MCC
Na) 349.01. Found 349.13.
´
(Laboratoire de Bioorganique, Universite de Reims
Champagne Ardenne’). Low resolution electrospray mass
spectra (ESI-MS) in the positive ion mode were obtained on
Waters-Micromass ZQ quadripole instrument, equiped with
an electrospray (Z-spray) ion source (Waters-Micromass,
Manchester, UK).
3.2.5. 2,3:4,5-Di-O-thiocarbonyl-D-xylose dibenzyl
dithioacetal (18). 73% Yield; white solid: mp 85–87 8C;
[a]D K100.1 (c 0.3; CH2Cl2); Rf 0.31 (7:3, hexane–EtOAc);
1H NMR (CDCl3): 3.80 (d, 1H, J1,2Z4.8 Hz, H1), 5.04 (q,
1H, J2,3Z5.7 Hz, H2), 4.70 (dd, 1H, J3,4Z1.5 Hz, H3), 4.88
(dq, 1H, H4), 4.60–4.75 (m, 2H, H5a,b), 7.10–7.30 (m, 10H,
Ph), 3.73–3.92 (m, 4H, CH2); 13C NMR: d 49.8 (C1), 84.2
(C2), 81.7 (C3), 79.9 (C4), 70.3 (C5), 36.7–37.0 (CH2),
128.3–136.9 (Ph), 188.9–190.0 (CS). Anal. Calcd for
C21H20O4S4: C, 54.28; H, 4.34; O, 13.77; S, 27.60.
Found: C, 54.61; H, 4.34. ESMS m/z calcd (MCCNa)
487.01. Found 487.24.
3.2. Synthesis of bis-cyclicthionocarbonate derivatives 2,
6, 10, 14, 18, 22, 26, 30, 34, 38, 42 and 43
General procedure. To a suspension monobenzyl alditols or
aldosedibenzyldithioacetals (1 mmol) in 1,4-dioxane
(0.05 g mlK1), was added Im2CS (2.2 mmol) and the mixture
was stirred at room temperature overnight. The crude product
obtained after concentration was purified by chromatography
on silica gel and mixture of hexane–EtOAc as eluant.
3.2.1. 1-O-Benzyl-2,3:4,5-di-O-thiocarbonyl-D-arabinitol
(2). 32% Yield; colorless syrup; [a]D C24.1 (c 1.4,
CH2Cl2); Rf 0.36 (5:5, hexane–EtOAc); 1H NMR
(CDCl3): d 3.70 (dd, 1H, J1a,1bZ11.3 Hz, J1a,2Z2.4 Hz,
3.2.6. 2,3:4,5-Di-O-thiocarbonyl-D-ribose dibenzyl dithio
acetal (22). 76% Yield; white solid: mp 71–73 8C; [a]D 1C
22.5 (c 1.0; CH2Cl2); Rf 0.42 (8:2, hexane–EtOAc); H
NMR (CDCl3): d 3.48 (d, 1H, J1,2Z5.0 Hz, H1), 5.25 (dd,
H1a), 3.85 (dd, 1H, J1b,2Z3.5 Hz, H1b), 4.90 (m, 1H, J2,3
Z

A. Danquigny et al. / Tetrahedron 61 (2005) 6772–6781
6777
1H, J2,3Z8.2 Hz, H2), 4.87 (dd, 1H, J3,4ZJ4,5aZ6.8 Hz,
H3), 4.88 (dq, 1H, J4,5bZ14.8 Hz, H4), 3.99 (m, 1H, J5a,5b
3.2.11. 3,4:5,6-Di-O-thiocarbonyl-D-mannose dibenzyl
dithioacetal (42). 23% Yield; colorless syrup; [a]D C6.5
(c 1.1; CH2Cl2); Rf 0.45 (5:5, hexane–EtOAc); H NMR
(DMSO-d6): d 3.82 (d, 1H, J1,2Z10.0 Hz, H1), 4.18 (q, 1H,
J2,3ZJ3,4Z5.3 Hz, H2), 5.01 (t, 1H, H3), 5.36 (dd, 1H,
Z
1
9.3 Hz, H5a), 4.25 (dd, 1H, H5b), 6.95–7.40 (m, 10H, Ph),
3.82 (m, 4H, CH2); 13C NMR: 46.2 (C1), 85.6 (C2), 80.9
(C3), 75.7 (C4), 70.4 (C5), 36.6–36.7 (CH2), 128.4–137.4
(Ph), 188.5–189.5 (CS). Anal. Calcd for C21H20O4S4: C,
54.28; H, 4.34; O, 13.77; S, 27.60. Found: C, 55.26; H, 4.42.
ESMS m/z calcd (MCCNa) 487.01. Found 487.54.
J4,5Z2.7 Hz, H4), 5.13 (ddd, 1H, J5,6aZ6.1 Hz, J5,6b
Z
J6a,6bZ9.0 Hz, H5), 4.25 (dd, 1H, H6a), 4.60 (t, 1H, H6b),
7.18–7.36 (m, 10H, Ph), 3.75–3.90 (m, 4H, CH2); 13C NMR:
d 53.5 (C1), 72.8 (C2), 82.6 (C3,C4), 75.6 (C5), 65.5 (C6),
35.6–35.8 (CH2), 127.9–138.6 (Ph), 191.0–191.8 (CS).
ESMS m/z calcd (MCCNa) 517.02, found 517.05.
3.2.7. 2,3:4,5-Di-O-thiocarbonyl-L-arabinose dibenzyl
dithioacetal (26). 68% Yield; white solid: mp 118–
120 8C; [a]D K123.1 (c 1.2; CH2Cl2); Rf 0.57 (6:4,
1
hexane–EtOAc); H NMR (CDCl3): d 3.70 (d, 1H, J1,2
J2,3Z4.5 Hz, H1), 4.80 (t, 1H, H2), 4.60 (dd, 1H, J3,4
Z
Z
3.2.12. 2-O-Imidazolylthiocarbonyl-3,4:5,6-di-O-thio
carbonyl-D-mannose dibenzyl dithioacetal (43). 34%
Yield; green solid: mp 85–87 8C; Rf 0.24 (5:5, hexane–
J,5aZ6.0 Hz, H3), 5.00 (dt, 1H, J4,5bZ8.3 Hz, H4), 4.50 (dd,
1H, J5a,5bZ9.6 Hz, H5a), 4.70 (dd, 1H, H5b), 7.10–7.60 (m,
10H, Ph), 3.70–3.90 (m, 4H, CH2); 13C NMR: d 49.9 (C1), d
84.3 (C2), 81.5 (C3), 78.9 (C4), 70.6 (C5), 36.8–37.0 (CH2),
128.3–137.0 (Ph), 189.0–189.7 (CS). Anal. calcd for
C21H20O4S4: C, 54.28; H, 4.34; O, 13.77; S, 27.60.
Found: C, 54.41; H, 4.33. ESMS m/z calcd (MCCNa)
487.01, found 487.12.
EtOAc); 1H NMR (CDCl3): d 3.98 (d, 1H, J1,2ZJ2,3ZJ3,4
Z
4.5 Hz, H1), 6.00 (t, 1H, H2), 5.32 (t, 1H, H3), 5.22 (dt, 1H,
J4,5ZJ5,6aZ2.7 Hz, H4), 5.13 (q, 1H, J5,6bZJ6a,6b
Z
10.0 Hz, H5), 4.25 (dd, 1H, H6a), 4.60 (t, 1H, H6b), 7.00–
8.25 (m, 12H, Ph), 4.60–4.90 (m, 4H, CH2); 13C NMR: d
48.4 (C1), 80.2 (C2), 81.1 (C3), 80.1 (C4), 78.6 (C5), 70.6
(C6), 36.8–37.1 (CH2), 118.6–137.6 (Ph), 182.5–189.4 (CS).
Anal. Calcd for C26H24N2O5S5: C, 51.63; H, 4.00; N, 4.63;
O, 13.23; S, 26.51. Found: C, 53.18; H, 4.25; N, 4.13.
3.2.8. 2,3:4,5-Di-O-thiocarbonyl-D-lyxose dibenzyl
dithioacetal (30). 73% Yield; white solid: mp 158–
160 8C; [a]D C32.6 (c 0.9; CH2Cl2); Rf 0.21 (7:3,
hexane–EtOAc); 1H NMR (DMSO-d6): d 3.75 (d, 1H,
J1,2Z10.7 Hz, H1), 5.48 (q, 1H, J2,3Z7.8 Hz, H2), 5.40 (m,
1H, J3,4Z11.7 Hz, H3), 4.50 (m, 3H, H4,5a,5b), 6.75–7.50
(m, 10H, Ph), 3.53–4.10 (m, 4H, CH2); 13C NMR: d 45.4
(C1), 85.8 (C2), 82.1 (C3), 78.1 (C4), 71.8 (C5), 34.9–37.3
(CH2), 128.1–138.5 (Ph), 190.0–190.9 (CS). Anal. Calcd for
C21H20O4S4: C, 54.28; H, 4.34; O, 13.77; S, 27.60. Found:
C, 54.40; H, 4.04. ESMS m/z calcd (MCCNa) 487.01.
Found 487.09.
3.3. Synthesis of anhydroalditols 2c (or 2f) and 6c (or 6f)
To a solution of bis-cyclic thionocarbonate 2 (D-arabino) or
6 (D-lyxo) was added Na (10 mg). The mixture was stirred
overnight and neutralised with Amberlite IRN-120 (HC).
The filtrate was concentrated and acetylated following the
standard procedure (Ac2O, pyridine). The crude product
obtained after concentration was separated by chromato-
graphy on silica gel and mixture of hexane–EtOAc as an
eluant.
3.2.9. 2,3:5,6-Di-O-thiocarbonyl-D-galactose dibenzyl
dithioacetal (34). 65% Yield; white solid: mp 148–
150 8C; Rf 0.28 (7:3, hexane–EtOAc); H NMR (DMSO-
3.3.1. 3,4-Di-O-acetyl-1-O-benzyl-2,5-anhydro-D-arabi-
nitol (2c) (or 3,4-di-O-acetyl-1-O-benzyl-2,5-anhydro-L-
ribitol (2f)). 31% Yield; syrup; Rf 0.17 (7:3, hexane–
EtOAc); 1H NMR (CDCl3): d 3.65 (d, 2H, H1a,1b), 5.39 (m,
1H, H2), 5.50 (t, 1H, J2,3ZJ3,4Z5.0 Hz, H3), 4.25 (m, 1H,
H4), 3.87 (dd, 2H, J4,5aZJ4,5bZ6.0 Hz, J5a,5bZ9.60 Hz,
H5a), 4.08 (dd, 2H, H5b), 4.50 (d, 1H, Ja,bZ12.1, Ha
1
d6): d 4.05 (d, 1H, J1,2ZJ2,3ZJ3,4Z3.9 Hz, H1), 5.35 (t, 1H,
H2), 4.87 (t, 1H, H3), 4.10 (m, 1H, H4), 5.18 (dq, 1H, J5,6a
Z
J6a,6bZ8.6 Hz, J5,6bZ5.6 Hz, H5), 4.51 (t, 1H, H6a), 4.82 (q,
1H, H6b), 7.25–7.40 (m, 10H, Ph), 3.80–4.00 (m, 4H, CH2);
13C NMR: d 52.2 (C1), 84.9 (C2), 85.2 (C3), d 69.5 (C4), d
82.4 (C5), 72.4 (C6), d 36.0–36.3 (CH2), 128.1–137.9 (Ph),
191.2–192.6 (CS). Anal. Calcd for C22H22O5S4: C, 53.42;
H, 4.48; O, 16.17; S, 25.93. Found: C, 53.48; H, 4.42. ESMS
m/z calcd (MCCNa) 517.02. Found 517.22.
(CH2Ph)), 4.50 (d, 1H, Hb (CH2Ph)), 2.05 (s, 3H, CH3); 13
C
NMR: d 69.8 (C1), 78.5 (C2), 71.9 (C3), 72.3 (C4), 68.6 (C5),
73.9 (CH2Ph), 20.9, 21.0 (2!CH3), 128.2–138.2 (Ph),
170.2 (CO). Anal Calcd for C16H20O6: C, 62.33; H, 6.54; O,
31.13. Found C, 62.45; H, 6.73.
3.2.10. 2,3:5,6-Di-O-thiocarbonyl-D-glucose dibenzyl
dithioacetal (38). 60% Yield; white solid: mp 129–
131 8C; [a]D K115.3 (c 0.5; CH2Cl2); Rf 0.24 (5:5,
3.3.2. 2,3-Di-O-acetyl-5-O-benzyl-1,4-anhydro-D-arabi-
nitol (6c) (or 2,3-di-O-acetyl-5-O-benzyl-1,4-anhydro-D-
xylitol 6f). 47% Yield; syrup; Rf 0.08 (7:3, hexane–EtOAc);
1H NMR (CDCl3): d 4.00 (m, 2H, H1a,1b,4), 5.20 (d, 2H,
J2,3Z3.0 Hz, J3,4Z0 Hz, H2,3), 3.68 (dd, 1H, J4,5aZ4.1 Hz,
J5a,5bZ10.3 Hz, H5a), 3.69 (dd, 1H, J4,5bZ6 Hz, H5b), 4.61
(s, 2H, CH2Ph)), 4.50 (d, 1H, Hb (CH2Ph)), 2.05 (s, 3H,
CH3); 13C NMR: d 72.4 (C1), 78.5 (C2), 78.8 (C3), 83.4 (C4),
70.2 (C5), 73.9 (CH2Ph), 21.2 (2!CH3), 128.1–138.4 (Ph),
170.3, 170.6 (CO). Anal calcd for C16H20O6: C, 62.33; H,
6.54; O, 31.13. Found C, 62.63; H, 6. 58.
hexane–EtOAc); 1H NMR (CDCl3): 3.75 (d, 1H, J1,2
J2,3Z5.3 Hz, H1), 5.03 (t, 1H, H2), 4.68 (dd, 1H, J3,4
Z
Z
1.5 Hz, H3), 4.00 (m, 1H, J4,5Z3.8 Hz, H4), 4.90 (ddd, 1H,
J5,6aZ1.1 Hz, J5,6bZ7.4 Hz, H5), 4.75 (m, 2H, J6a,6b
Z
9.1 Hz, H6a,6b), 7.12–7.37 (m, 10H, Ph), 3.70–3.90 (m, 4H,
CH2); 13C NMR: d 50.0 (C1), 84.7 (C2),83.7 (C3), 69.7 (C4),
81.7 (C5), 70.7 (C6), 36.6–36.7 (CH2), 128.2–137.1 (Ph),
190.3–191.8 (CS). Anal. Calcd for C22H22O5S4: C, 53.42;
H, 4.48; O, 16.17; S, 25.93. Found: C, 54.79; H, 4.50. ESMS
m/z calcd (MCCNa) 517.02. Found 517.30.

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A. Danquigny et al. / Tetrahedron 61 (2005) 6772–6781
3.4. Synthesis of thiaheterocycles 3, 7, 11, 15, 19, 27, 31,
35, 39 and 44
0.4; CH2Cl2); Rf 0.17 (7:1, hexane–EtOAc); 1H NMR
(CDCl3): d 3.76 (d, 1H, J1,2Z7.5 Hz, H1), 3.62 (dd, 1H,
J2,3ZJ3,4Z5.1 Hz, H2), 5.60 (t, 1H, H3), 5,22 (q, 1H, J4,5a
Z
General procedure. To a solution of bis-cyclicthionocarbo-
nates (1 mmol) in DMSO (5 mL), was added Na2S, 9H2O
(1.5 mmol) and the mixture was stirred at 80 8C during 1 h.
After concentration and acetylation of crude product with
Ac2O in pyridine, the desired compounds were extracted by
chromatography on silica gel and mixture of hexane–EtOAc
as eluant.
J4,5bZ11.4 Hz, H4), 2.90 (dd, 1H, J5a,5bZ5.8 Hz, H5a), 3.15
(dd, 1H, H5b), 7.20–7.30 (m, 10H, Ph), 3.83 (m,4H, CH2),
1.88–1.99 (2s, CH3); 13C NMR: d 54.5 (C1), 54.3 (C2), 78.9
(C3), d 77.8 (C4), d 32.6 (C5), 35.5–35.7 (CH2), 127.5–138.0
(Ph), 21.3–21.5 (CH3), 169.8–170.3 (CO). ESMS m/z calcd
for C23H26O4S3 (MCCNa) 485.09. Found 485.20.
3.4.6. 3,4-Di-O-acetyl-2,5-thioanhydro-L-ribose dibenzyl
dithioacetal (27). 50% Yield; yellow syrup; [a]D C108.3 (c
0.3; CH2Cl2) Rf 0.48 (7:3, hexane–EtOAc); 1H NMR
(CDCl3): d 3.61 (d, 1H, J1,2Z4.2 Hz, H1), 3.95 (dd, 1H,
J2,3Z7.7 Hz, H2), 5.12 (dd, 1H, J3,4Z3.6 Hz, H3), 5.53 (q,
3.4.1. 2,3-Di-O-acetyl-5-O-benzyl-1,4-thioanhydro-L-
ribitol (3). 47% Yield; yellow syrup; [a]D K59.4 (c 0.4;
CH2Cl2); Rf 0.33 (8:2, hexane–EtOAc); 1H NMR (CDCl3):
d 2.96 (dd, 1H, J1a,1bZ11.3 Hz, H1a), 3.17 (dd, 1H, J1a,2
J1b,2Z5.6 Hz, H1b), 5.47 (m, 1H, J2,3Z3.6 Hz, H2), 5.32
(dd, 1H, J3,4ZJ4,5aZ4.8 Hz, H3), 3.65 (m, 1H, J5a,5b
Z
1H, J4,5aZ3.6 Hz, J4,5bZ7.9 Hz, H4), 2.86 (dd, 1H, J5a,5b
Z
Z
12.0 Hz, H5a), 3.16 (dd, 1H, H5b), 7.00–7.40 (m, 10H, Ph),
3.80 (s, 4H, CH2), 1.87–2.13 (2s, CH3); 13C NMR: d 51.6
(C1), 52.9 (C2), 76.6 (C3), 74.1 (C4), d 31.9 (C5), 35.6–36.5
(2CH2), 21.0–21.4 (2 CH3), 127.4–138.1 (Ph), 169.8-170.4
(CO). ESMS m/z calcd for C23H26O4S3 (MCCNa) 485.09.
Found 485.20.
J4,5bZ7.9 Hz, H4), 3.55–3.62 (m, 2H, H5a,5b), 7.25–7.40 (m,
5H, Ph), 4.56 (m, 2H, CH2), 2.05–2.10 (2s, 2CH3); 13C
NMR: d 31.2 (C1), 74.1 (C2), 76.0 (C3), 47.3 (C4), 71.8 (C5),
d 73.7 (CH2), 21.3 (2 CH3), 128.1–138.2 (Ph), 170.4–170.5
(CO). ESMS m/z calcd for C16H20O5S (MCCNa) 347.09.
Found 347.29.
3.4.7. 3,4-Di-O-acetyl-2,5-thioanhydro-D-xylose-dibenzyl
dithioacetal (31). 60% Yield; yellow syrup; Rf 0.18 (7:1,
3.4.2. 2,3-Di-O-acetyl-5-O-benzyl-1,4-thioanhydro-L-
xylitol (7). 65% Yield; yellow syrup; [a]D K65.1 (c 0.7;
CH2Cl2); Rf 0.13 (9:1, hexane–EtOAc); 1H NMR (CDCl3):
d 2.85 (dd, 1H, J1a,1bZ12.0 Hz, J1a,2Z2.8 Hz, H1a), 3.25
1
hexane–EtOAc); H NMR (CDCl3): d 3.80 (d, 1H, J1,2
Z
4.8 Hz, H1), 3.90 (m, 1H, J2,3Z3.7 Hz, H2), 5.18 (dd, 1H,
J3,4Z2.6 Hz, H3), 5.30 (m, 1H, J4,5aZ4.6 Hz, J4,5b
Z
(dd, 1H, J1b,2Z5.1 Hz, H1b), 5.36 (m, 1H, J2,3ZJ3,4
Z
1.8 Hz, H4), 2.80 (dd, 1H, J5a,5bZ12.5 Hz, H5a), 3.20 (dd,
1H, H5b), 7.20–7.45 (m, 10H, Ph), 3.75–3.90 (m, 4H, CH2),
1.70–2.10 (2s, CH3); 13C NMR: d 51.4 (C1), 54.7 (C2), 76.8
(C3), 78.9 (C4), 34.9 (C5), 34.4–34.9 (2CH2), 20.9–21.5 (2
CH3), 127.3–138.1 (Ph), 169.8–169.9 (CO). ESMS m/z
calcd for C23H26O4S3 (MCCNa) 485.09. Found 485.24.
4.3 Hz, H2), 5.42 (t, 1H, H3), 3.92 (q, 1H, J4,5aZ7.4 Hz,
J4,5bZ6.1 Hz, H4), 3.52 (dd, 1H, J5a,5bZ9.3 Hz, H5a), 3.70
(dd, 1H, H5b), 7.25–7.40 (m, 5H, Ph), 4.51 (m, 2H, CH2),
2.00–2.10 (2s, 2CH3); 13C NMR: 33.3 (C1), 77.7 (C2), 77.0
(C3), 46.8 (C4), 69.2 (C5), d 73.7 (CH2), 21.1–21.4 (2CH3),
128.2–138.2 (Ph), 170.1–170.2 (CO). ESMS m/z calcd for
C16H20O5S (MCCNa) 347.09. Found 347.29.
3.4.8.
2,4,5-Tri-O-acetyl-3,6-thioanhydro-D-gulose
dibenzyl dithioacetal (35). 60% Yield; yellow syrup;
[a]D K140.4 (c 0.5; CH2Cl2); Rf 0.32 (8:2, hexane–
EtOAc); H NMR (CDCl3): d 3.60 (d, 1H, J1,2Z2.1 Hz,
3.4.3. 2,3-Di-O-acetyl 5-O-benzyl-1,4-thioanhydro-D,L-
arabinitol (11). 50% Yield; yellow syrup; Rf 0.14 (9:1,
1
hexane–EtOAc); 1H NMR (CDCl3): d 2.91 (dd, 1H, J1a,1b
Z
H1), 5.55 (dd, 1H, J2,3Z10.4 Hz, H2), 4.15 (dd, 1H, J3,4
3.9 Hz, H3), 5.40 (dd, 1H, J4,5Z1.4 Hz, H4), 5.20 (m, 1H,
J5,6aZ0 Hz, J5,6bZ4.2 Hz, H5), 2.80 (d, 1H, J6a,6b
Z
11.9 Hz, J1a,2ZJ1b,2Z4.8 Hz, H1a), 3.23 (dd, 1H, H1b), 5.31
(q, 1H, J2,3ZJ3,4Z4.8 Hz, H2), 5.39 (t, 1H, H3), 3.50 (m,
1H, H4), 3.52 (m, 1H, H5a), 3.73 (m, 1H, H5b), 7.25–7.40 (m,
5H, Ph), 4.60 (m, 2H, CH2), 1.90–2.10 (2s, 2CH3); 13C
NMR: d 33.4 (C1), 78.5 (C2), 79.2 (C3), 49.4 (C4), d 72.3
(C5), 73.6 (CH2), 21.3–21.4 (2CH3), 128.2–138.3 (Ph),
170.1–170.2 (CO). ESMS m/z calcd for C16H20O5S (MCC
Na) 347.09. Found 347.29.
Z
12.4 Hz, H6a), 3.25 (dd, 1H, H6b), 7.10–7.30 (m, 10H, Ph),
3.70–3.80 (m, 4H, CH2), 2.05–2.15 (3s, CH3); 13C NMR: d
53.6 (C1), 72.2 (C2), 50.6 (C3), 76.3 (C4), 78.0 (C5), 36.1
(C6), 36.0–36.8 (2CH2), 21.1–21.5 (3CH3), 127.6–137.8
(Ph), 170.0–170.2 (CO). ESMS m/z calcd for C26H30O6S3
(MCCNa) 557.11. Found 557.28.
3.4.4. 3,4-Di-O-acetyl-1-O-benzyl-2,5-thioanhydro-D,L-
arabinitol (15). 40% Yield; yellow syrup; Rf 0.27 (8:2,
hexane–EtOAc); 1H NMR (CDCl3): d 3.47–3.77 (2 dd, 2H,
J1a,1bZ7.9 Hz, J1a,2Z8.9 Hz, J1b,2Z6.4 Hz, H1a,1b), 3.85
(m, 1H, J2,3Z4.3 Hz, H2), 5.70 (dd, 1H, J3,4Z3.3 Hz, H3),
5.30 (m, 1H, J4,5aZ6.9 Hz, J4,5bZ9.4 Hz, H4), 3.00 (m, 2H,
J5a,5bZ10.0 Hz), 7.25–7.40 (m, 5H, Ph), 4.52 (m, 2H, CH2),
2.02–2.04 (2s, 2CH3); 13C NMR: d 69.7 (C1), 45.0 (C2), 72.9
(C3), 75.4 (C4), 30.4 (C5), 73.2 (CH2), 21.1 (CH3), 128.2–
138.2 (Ph), 170.2–170.4 (CO). ESMS m/z calcd for
C16H20O5S (MCCNa) 347.09 Found 347.20.
3.4.9. 2,4,5-Tri-O-acetyl-3,6-thioanhydro-D-allose di-
benzyl dithioacetal (39). 60% Yield; yellow syrup; [a]D
K57.6 (c 0.4; CH2Cl2); Rf 0.16 (8:2, hexane–EtOAc); H
1
NMR (CDCl3): 3.90 (d, 1H, J1,2Z3.2 Hz, H1), 5.25 (dd, 1H,
J2,3Z9.1 Hz, H2), 3.70 (dd, 1H, J3,4ZJ4,5Z3.9 Hz, H3),
5.21 (t, 1H, H4), 5.30 (m, 1H, J5,6aZ5.6 Hz, J5,6bZ6.5 Hz,
H5), 2.80 (dd, 1H, J6a,6bZ10.9 Hz, H6a), 3.20 (dd, 1H, H6b),
7.10–7.45 (m, 10H, Ph), 3.75–3.85 (m, 4H, CH2), 1.90–2.10
(m, CH3); 13C NMR: d 52.8 (C1), 72.2, 76.3 (C2, C4),, 49.2
(C3), 74.0 (C5), 31.0 (C6), 35.5–36.2 (2CH2), 20.3 (3CH3),
127.5–138.2 (Ph), 169.5–170.0 (CO). ESMS m/z calcd for
C26H30O6S3 (MCCNa) 557.11. Found 557.19.
3.4.5. 3,4-Di-O-acetyl-2,5-thioanhydro-D-lyxose dibenzyl
dithioacetal (19). 60% Yield; yellow syrup; [a]D C36 (c
3.4.10. 2,4,5-Tri-O-acetyl-3,6-thioanhydro-D-altrose

A. Danquigny et al. / Tetrahedron 61 (2005) 6772–6781
6779
dibenzyl dithioacetal (44). 52% Yield; yellow syrup; [a]D
K36.2 (c 0.5; CH2Cl2); Rf 0.15 (8:2, hexane–EtOAc); H
170.4, 170.5 (CO), ESMS calcd for C23H26O4S2Se (MCC
Na) 395.04. Found 395.12.
1
NMR (CDCl3): d 3.68 (d, 1H, J1,2Z7.7 Hz, H1), 5.35 (dd,
1H, J2,3Z4.1 Hz, H2), 4.00 (dd, 1H, J3,4Z6.1 Hz, H3), 5.00
3.5.4. 3,4-Di-O-acetyl-1-O-benzyl-2,5-selenoanhydro-D,L-
arabinitol (16). 50% Yield; colorless syrup; Rf 0.27 (8:2,
(t, 1H, J4,5Z3.6 Hz, H4), d 5.40 (q, 1H, J5,6aZJ5,6b
Z
hexane–EtOAc); 1H NMR (CDCl3):d 3.07 (dd, 2H, J5a,5b
Z
5.4 Hz, H5), 2.83 (dd, 1H, J6a,6bZ11.3 Hz, H6a), 3.02
(dd, 1H, H6b), 7.20–7.40 (m, 10H, Ph), 3.75–3.95 (m,
4H, CH2), 2.00–2.20 (m, CH3); 13C NMR: 54.0 (C1), 71.9,
73.5, 75.5 (C2,C4,C5), 49.6 (C3), 31.1 (C6), 35.4–35.7
(2CH2), 21.2, 21.3 (3CH3), 127.6–137.6 (Ph), 170.5 (CO).
ESMS m/z calcd for C26H30O6S3 (MCCNa) 557.11. Found
557.40.
9.6 Hz, J5,4Z6.5 Hz, H5), 5.26 (m, 1H, H4), 5.77 (m, 1H,
H3), 3.97 (m, 1H, H2), 3.15 (dd, 1H, J1a,1bZ9.3 Hz, J1a,2
Z
7.4 Hz, H1a), 3.85 (dd, 1H, H1b, J1b,2Z7.5 Hz), 4.48 (d, H6,
2H, J6a6bZ12.01 Hz), 2.03, 2.06 (2s, 3H), 7.27–7.35 (m,
5H, Ph). 13C NMR: d 70.06 (C1), 38.31 (C2), 77.42 (C3),
77.00 (C4), 21.97 (C5), 71.47 (C6), 21.1, 21.2 (2 CH3),
128.13, 128.83 C(Ph), 138.20 (Cipso), 170.26 and 170.42
(CO). ESMS calcd for C23H26O4S2Se (MCCNa) 395.03.
Found 395.16.
3.5. Synthesis of selenaheterocycles 4, 8, 12, 16, 20, 28, 32,
36, 40 and 45
3.5.5. 3,4-Di-O-acetyl-2,5-selenoanhydro-D-lyxose di-
benzyl dithioacetal (20). 45% Yield; colorless syrup; Rf
0.28 (6:4, hexane–EtOAc); [a]D C72.1 (c 0.6; CH2Cl2); 1H
NMR (CDCl3): d 3.80 (m, 6H, H1,2CCH2Ph), 5.60 (dd, 1H,
J3,2ZJ3,4Z6.3 Hz, H3), 5.30 (dt, 1H, H4, J4,5aZ7 Hz,), 2.90
(dd, 1H, J5a,5bZ10.2 Hz, J5a,4Z7 Hz, H5a), 3.10 (dd, 1H,
J5,4Z6 Hz, H5b), 1.89 (s, 3H), 1.95 (s, 3H), 7.20–7.33 (m,
Ph). 13C NMR: d 46.70 (C1), 54.56 (C2), 78.38 (C3), 78.67
(C4), 21.57 (C5), 21.20, 21.33 (CH3), 35.35, 35.74 (CH2Ph),
127–137 (Ph), 169.68, 170.25 (CO). ESMS calcd for
C23H26O4S2Se (MCCNa) 533.034. Found 533.10.
General procedure. To a suspension freshly prepared from
Se powder (3 mmol) and NaBH4 (6 mmol) in H2O (1 mL)
was added a solution of bis-cyclicthionocarbonates of
alditols or aldoses dibenzyldithioacetal (1 mmol) in
DMSO (1 mL). The mixture was stirred at 80 8C during
1 h. After concentration and acetylation of crude product
with Ac2O in pyridine, the desired compounds were
extracted by chromatography on silica gel and mixture of
hexane–EtOAc as eluant.
3.5.1. 2,3-Di-O-acetyl-5-O-benzyl-1,4-selenoanhydro-L-
ribitol (4). 53% Yield; colorless syrup; Rf 0.29 (7:3,
hexane–EtOAc); [a]D C64.7 (c 1.4; CH2Cl2); H NMR
3.5.6. 3,4-Di-O-acetyl-2,5-selenoanhydro-L-ribose di-
benzyl dithioacetal (28). 50% Yield; colorless syrup; Rf
0.35 (8:2, hexane–EtOAc); [a]D C128 (c 0.75; CH2Cl2); 1H
NMR (CDCl3): d 3.65 (d, 1H, J1,2Z4 Hz, H1), 4.1 (dd, 1H,
J2,3Z9.81 Hz, H2), 5.2 (dd, 1H, J34Z3.5 Hz, H3), 5.63 (dt,
1
(CDCl3): d 2.92 (dd, 1H, H1, J1a1bZ11.21 Hz, J12Z5.43),
3.17 (dd, 1H, H1b, J1b1aZ10.52 Hz; J1b2 Z5.32 Hz), 5.53
(dd, 1H, H2, J23Z3.29 Hz, J21Z5.49 Hz), 5.35 (dd, 1H, H3,
J32Z3.3 Hz, J34Z5.81 Hz), 3.58 (m, 1H, H4), 3.79 (dd, 2H,
H5, J5a,5bZ11 Hz, J5b,4 Z6.6 Hz); 4.56 (s, 2H, H6), 2.05 (s,
3H), 2.09 (s, 3H), 7.35 (m, 5H, HAr). 13C NMR: d 22.08
(C1), 77.36 (C2), 75.64 (C3); 40.85 (C4), 72.50 (C5), 73.64
(C6); 21.27 (CH3), 21.33 (CH3), 128.09–128.82 (Ph);
138.19 Cipso, 170.47, 170.57 (CO). ESMS calcd for
C23H26O4S2Se (MCCNa) 395.04. Found 395.15.
1H, J4,5Z8 Hz, H4), 2.84 (dd, 1H, J5a5bZ11.13 Hz, J5a4
Z
3.73 Hz, H5a), 3.16 (dd, 1H, J5b4 Z4.56 Hz, H5b), 3.69 (s,
2H, CH2Ph), 3.81 (s, 2H, CH2Ph), 1.8 (s, 3H), 2.1 (s, 3H),
7.03–7.33 (m, Ph). 13C NMR: d 47.23 (C1), 52.11 (C2),
77.79 (C3), 75.53 (C4), 22.69 (C5), 35.53 (CH2), 36.49
(CH2), 21.01 (CH3), 21.4 (CH3), 127–138 C(Ph), 169.89
and 170.4 (CO). ESMS calcd for C23H26O4S2Se (MCCNa)
533.032. Found 533.11.
3.5.2. 2,3-Di-O-acetyl-5-O-benzyl-1,4-selenoanhydro-L-
xylitol (8). 50% Yield; colorless syrup; Rf 0.28 (8:2,
hexane–EtOAc); [a]D C76 (c 2.1; CH2Cl2); 1H NMR
(CDCl3): d 2.80 (dd, 1H, J1a,1bZ11.4 Hz, J1a,2Z3 Hz, H1a),
3.28 (dd, 1H, J1b2 Z3 Hz, H1b), 5.42 (m, 2H, H2,3), 4.08 (m,
1H, H4), 3.54 (dd, 1H, J5a,5bZ9.5 Hz, J5a,4Z5.9 Hz, H5a),
3.5.7. 3,4-Di-O-acetyl-2,5-selenoanhydro-D-xylose di-
benzyl dithioacetal (32). 55% Yield; colorless syrup; Rf
0.23 (6:4, hexane–EtOAc); [a]D K9.4 (c 2.1; CH2Cl2); H
1
NMR (CDCl3): d 3.96 (d, 1H, J12Z11.4 Hz, H1), 4.13 (dd,
1H, J23Z4 Hz, H2), 5.2 (dd, 1H, J34Z2.3 Hz, H3), 5.4 (m,
1H, H4), 2.86 (dd, 1H, J5a,5bZ11.7 Hz, J5a,4Z4.3 Hz, H5a),
3.16 (dd, 1H, J5b,4Z4.3 Hz, H5b), 3.85 (s, 2H, CH2 Ph), 3.89
(s, 2H, CH2 Ph), 1.75 (s, 3H), 2.06 (s, 3H), 7.27–7.36 (m,
Ph). 13C NMR: d 49.53 (C1), 52.21 (C2), 77.29 (C3), 79.31
(C4), 25.57 (C5), 34.31 (CH2), 35.06 (CH2), 20.88 (CH3);
21.51 (CH3); 125.5–138.64 C(Ph); 169.7 and 169.77 (CO),
ESMS calcd for C23H26O4S2Se (MCCNa) 533.03. Found
533.11.
3.82 (dd, 1H, J5b,4Z7.3 Hz, H5b), 4.53 (d, 2H, CH2, J6a,6b
Z
6.7 Hz), 2.01 (s, 3H), 2.09 (s, 3H), 7.35 (m, 5H, Ph). 13C
NMR: d 24.54 (C1), 78.28 (C2), 77.68 (C3), 40.8 (C4), 69.9
(C5), 73.7 (CH2), 21.1 (CH3), 21.4 (CH3), 128.1–128.8
C(Ph), 138.2 Cipso, 170.1 (CO), ESMS calcd for
C23H26O4S2Se (MCCNa) 395.04. Found 395.22.
3.5.3. 2,3-Di-O-acetyl-5-O-benzyl-1,4-selenoanhydro-D,L-
arabinitol (12). 50% Yield; colorless syrup; Rf 0.32 (8:3,
hexane–EtOAc); 1H NMR (CDCl3): d 2.94 (dd, 1H, J1a,1b
Z
3.5.8. 2,4,5-Tri-O-acetyl-3,6-selenoanhydro-D-gulose
dibenzyl dithioacetal (36). 55% Yield; colorless syrup; Rf
0.42 (6:4, hexane–EtOAc); [a]D K136.9 (c 2.15; CH2Cl2);
1H NMR (CDCl3): d 3.49 (d, 1H, J1,2Z2.6 Hz, H1), 5.63
(dd, 1H, J2,3Z10.7 Hz, H2), 4.24 (dd, 1H, J3,4Z3.9 Hz, H3),
11.1 Hz, J1,2Z5.4, H1), 3.30 (dd, 1H, J1b,2Z5.5 Hz, H1b),
5.60 (m, 2H, H2, H3), 3.68 (m, 1H, H4), 3.82 (dd, 2H,
J5a,5bZ10.0 Hz, J5b,4Z5.6 Hz, H5), 4.50 (s, 2H, CH2Ph),
2.07 (s, 3H), 2.1 (s, 3H), 7.4 (m, 5H, Ph). 13C NMR: d 22.0
(C1), 77.4 (C2), 75.7 (C3), 40.9 (C4), 72.7 (C5), 73.8 (CH2),
5.54 (m, 1H, H4), 5.29 (m, 1H, H5), 2.95 (dd, 1H, J6a,6b
Z
21.3 (CH3), 21.4 (CH3), 127.1–127.8 (Ph), 134.2 Cipso
,
11.7 Hz, H6a), 3.29 (dd, 1H, J6b,5Z4.13 Hz, H6b), 3.72 (s,

6780
A. Danquigny et al. / Tetrahedron 61 (2005) 6772–6781
5. Yuasa, H.; Izumi, M.; Hashimoto, H. Yuki Gosei Kagaku
Kyokaishi 2002, 60, 774–782.
`
6. (a) Glac¸on, V.; Benazza, M.; Beaupere, D.; Demailly, G.
2H, CH2Ph), 3.75 (s, 2H, CH2 Ph), 2.02 (s, 3H), 2.95 (s, 3H),
2.11 (s, 3H), 7.12–7.33 (m, Ph). 13C NMR: d 53.69 (C1),
72.59 (C2), 44.62 (C3), 77.46 (C4), 78.38 (C5), 28.82 (C6),
36.10 (CH2), 36.70 (CH2), 21.09 (CH3), 21.37 (CH3), 21.49
(CH3), 127.62–137.81 C(Ph), 169.96, 170.09 and 170.21
(CO). ESMS calcd for C26H30O6S2Se (MCCNa) 605.05.
Found 605.11.
Tetrahedron Lett. 2000, 41, 5053–5056. (b) Halila, S.;
Benazza, M.; Demailly, G. Tetrahedron Lett. 2001, 42,
3307–3310. (c) Arcelli, A.; Cere, V.; Peri, F.; Pollicino, S.;
Ricci, A. Tetrahedron: Asymmetry 2002, 13, 191–196.
7. Halila, S.; Benazza, M.; Demailly, G. J. Carbohydr. Chem.
2001, 20, 467–483.
3.5.9. 2,4,5-Tri-O-acetyl-3,6-selenoanhydro-D-allose
dibenzyl dithioacetal (40). 53% Yield; colorless syrup; Rf
0.45 (7:3, hexane–EtOAc); [a]D K124.1 (c 1; CH2Cl2); 1H
NMR (CDCl3): d 3.75 (m, 5H, H1C2 CH2Ph), 5.24–5.3 (m,
3H, H2,4,5), 3.68 (dd, 1H, J3,2Z6.8 Hz, J3,4Z6.1 Hz, H3),
2.83 (dd, 1H, J5,6aZ5.6 Hz, J6a,6bZ9.4 Hz, H6a), 3.09 (dd,
1H, J5,6bZ5.9 Hz, H6b), 2.05 (s, 3H), 2.06 (s, 3H), 2.17 (s,
3H), 7.07–7.33 (m, 10H, Ph). 13C NMR: d 52.55 (C1), 75.56,
76.27, 77.65 (C2, C4, C5), 42.72 (C3), 22.85 (C6), 21.1;
21.25; 21.29 (CH3), 35.57 (CH2), 36.69 (CH2), 127.64–
129.58 (Ph), 170.01, 170.38, 170.85 (CO). ESMS calcd for
C26H30O6S2Se (MCCNa) 605.08. Found 605.05.
8. Benazza, M.; Halila, S.; Viot, C.; Danquigny, A.; Demailly, G.
Tetrahedron Lett. 2004, 60, 2889–2895.
9. Szczepina, M. G.; Johnston, B. D.; Yuan, Y.; Svensson, B.;
Pinto, B. M. J. Am. Chem. Soc. 2004, 126, 12458–12469.
10. (a) Le Merrer, Y.; Gravier, C.; Maton, W.; Numa, M.;
Depezay, J. C. Synlett 1999, 8, 1322–1324. (b) Lohray, B. B.;
Jayamma, Y.; Chatterjee, M. J. Org. Chem. 1995, 60,
5958–5960. (c) Qian, X.; Varas, F. M.; Wong, C. H. Bioorg.
Med. Chem. Lett. 1996, 6, 1117–1122.
11. (a) Esposito, A.; Falorni, M.; Taddei, M. Tetrahedron Lett.
´
1998, 39, 6543–6546. (b) Dureault, A.; Portal, M.; Depezay,
J. C. Synlett 1991, 225–226.
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43, 815–818.
3.5.10. 2,4,5-Tri-O-acetyl-3,6-selenoanhydro-D-altrose
dibenzyl dithioacetal (45). 50% Yield; colorless syrup; Rf
0.29 (7:3, hexane–EtOAc); [a]D K90.3 (c 1.25; CH2Cl2);
1H NMR (CDCl3): d 3.61 (d, 1H, J1,2Z6.93 Hz, H1), 5.00
(dd, 1H, J2,3Z3.58 Hz, H2), 4.02 (dd, 1H, J3,4Z6.94 Hz,
13. Cere, V.; Peri, F.; Pollicino, S. J. Org. Chem. 1997, 62,
8572–8574.
´
14. Arcelli, A.; Cere, V.; Peri, F.; Pollicino, S.; Ricci, A.
Tetrahedron 2001, 57, 3439–3444.
H3), 5.38 (dd, 1H, J4,5Z3.3 Hz, H4), 5.49 (dt, H, J6a5
Z
15. Danquigny, A.; Benazza, M.; Protois, S.; Demailly, G.
Tetrahedron Lett. 2004, 45, 4365–4369.
5.42 Hz, J5,6bZ5.13 Hz, H5), 2.86 (dd, 1H, J6a,6bZ10.6 Hz,
H6a), 3.04 (dd, 1H, H6b), 3.84 (s, 4H, CH2Ph), 1.95 (s, 3H), 2
(s, 3H), 2.08 (s, 3H), 7.2–7.3 (m, 10H, Ph). 13C NMR: d
54.85 (C1), 71.83 (C2), 43.60 (C3), 77 (C4), 74.57 (C5),
22.48 (C6), 35.44 (CH2); 35.86 (CH2), 21.19, 21.20, 21.36
(CH3), 127–137 C(Ph), 170 (CO). ESMS calcd for
C26H30O6S2Se (MCCNa) 605.05. Found 605.02.
16. Sun, Y. Free Rad. Biol. Med. 1990, 8, 583–599.
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Montine, T. J. Curr. Neuropharmacol. 2003, 1, 125–134. (b)
Bouvard, S.; Faure, P.; Roucard, C.; Favier, A.; Halimi, S.
Free Rad. Res. 2002, 36, 1017–1022. (c) Warner, H. R. Free
Rad. Biol. Med. 1994, 17, 249–258. (d) Adams, J. D., Jr;
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Acknowledgements
18. Klotz, L. O.; Kroncke, K. D.; Buchczyk, D. P.; Sies, H. J. Nutr.
2003, 133, 1448S–1451S.
´
The authors thank the Conseil regional de Picardie & le
fonds social Europeen for their financial support.
´
19. (a) Lairon, D.; Bertrais, S.; Vincent, S.; Arnault, N.; Galan, P.;
Boutron, M. C.; Hercberg, S. Proc. Nutr. Soc. 2003, 62, 11–15.
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