De novo synthesis of 1-deoxythiosugars

Article abstract of DOI:10.1016/j.carres.2013.09.009

A short and efficient chemical synthesis of biologically potent and novel 1-deoxythiosugars is accomplished. Introduction of sulfur mediated by benzyltriethylammonium tetrathiomolybdate, as a sulfur transfer reagent through nucleophilic double displacemen

Full text of DOI:10.1016/j.carres.2013.09.009

Carbohydrate Research 382 (2013) 30–35
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
De novo synthesis of 1-deoxythiosugars
⇑
Thanikachalam Gunasundari, Srinivasan Chandrasekaran
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A short and efficient chemical synthesis of biologically potent and novel 1-deoxythiosugars is accom-
plished. Introduction of sulfur mediated by benzyltriethylammonium tetrathiomolybdate, as a sulfur
transfer reagent through nucleophilic double displacement of tosylate in a,x-di-O-tosyl aldonolactones
in an intramolecular fashion is the key feature. The subsequent reduction of thiosugar lactones with boro-
hydride exchange resin (BER) offers a number of deoxythiosugars in good overall yield.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 12 June 2013
Received in revised form 12 September
2013
Accepted 26 September 2013
Available online 3 October 2013
Keywords:
Tetrathiomolybdate
1-Deoxythiosugars
Aldonoditosylate
Thiosugar lactone
Borohydride exchange resin
The uniqueness of thio-analogs of carbohydrates (thiosugars1)
is preponderant as they play an important part in sulfur organics
especially, as saccharide bioisoteres with ‘biological relevance as
potentially new therapeutics’.2 In particular, the fundamental
physico-chemical properties of sulfur in thiosugars enable them
to serve as good mechanism based glycosidase inhibitors.3,4 They
provide mechanistic scope for probing enzyme mechanism by
mimicking the conventional sugars through their conformational
flexibility.3,5,6 Furthermore, the glycosidase inhibitors also serve
as potential agents against virus,7 metastasis, and diabetes8 etc.
Similarly, deoxythiosugars, the deoxy analog of thiosugars, have
become increasingly important molecules due to their enhanced
hydrophobicity pivotal in many physiological processes effecting
the rate of glycosidic hydrolysis.9 However, despite the importance
of sulfur-based glycomimetics,10 their unambiguous chemical syn-
diverse deoxythiosugars from all the available carbohydrates.
Hence, the design and development of a more general and comple-
menting methodology is vital.
Consequently, we envisioned the synthesis of appropriate sub-
strate/s for the sulfur transfer reaction with tetrathiomolybdate
through selective ditosylation of aldonolactones. The present
methodology will not require the presence of cis-hydroxy groups
at C-2 and C-3 and will widen the scope of tetrathiomolybdate
mediated synthesis of deoxythiosugars from most of the readily
available carbohydrates. Not only will this complement our earlier
report, (Scheme 1, right hand side)14b but, this strategy will also
demonstrate the efficiency of tetrathiomolybdate mediated sulfur
transfer reaction in the protection/deprotection-free synthesis of
1-deoxythiofuranoses and pyranoses from aldonolactones.
The thiosugar, 1,4-anhydro-4-thio-D-arabinitol 5, the core
thesis remains
complexity.
a
major challenge owing to their intriguing
structure present in many of the natural products such as salapri-
nol, salacinol, ponkoranol, kotalanol, and de-O-sulfonated kotala-
In this context, recently we employed benzyltriethylammonium
tetrathiomolybdate11 [BnEt3N]2MoS4 1 as an efficient sulfur trans-
fer reagent for the synthesis of biologically relevant deoxythiosu-
gars and derivatives12 starting from aldonolactones.13 Earlier
strategy12a adopted by us had the prerequisite of having the C-2
and C-3 hydroxy groups cis in the aldonolactones for an efficient
synthesis of dibromolactones. This precursor for the sulfur transfer
reaction, should have C-2-bromide and C-4-side chain in trans ori-
entation (Scheme 1, left hand side).14a This limits the synthesis of
nol (highly potent a
-glucosidase inhibitors15) known especially
for the treatment of diabetes mellitus, was of contemporary inter-
est in sulfur-based glycomimetics. Accordingly, the synthesis of
xylonoditosylate 3 was investigated through selective tosylation
employing the procedure reported by Lundt and Madsen.16 Treat-
ment of xylonolactone 2 with TsCl/ pyridine in acetone at 0 °C
afforded xylonoditosylate 3 in 28% yield.17 The reaction of xylon-
oditosylate 3 with benzyltriethylammonium tetrathiomolybdate
1 in DMSO at room temperature provided the expected bicyclic
thiosugar lactone, 1-deoxy-4-thio-D-lyxono-2,5-lactone 4 in 53%
yield (Scheme 2). Further reduction of lactone 4 with borohydride
⇑
exchange resin (BER)18 in methanol furnished the desired 1-deoxy-
Corresponding author. Tel.: +91 80 2293 2404x2360 2423; fax: +91 80 2360
0529.
thiosugar, 1,4-dideoxy-1,4-epithio-D-arabinitol 5 in good yield.
E-mail address: scn@orgchem.iisc.ernet.in (S. Chandrasekaran).
0008-6215/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.carres.2013.09.009

T. Gunasundari, S. Chandrasekaran / Carbohydrate Research 382 (2013) 30–35
31
n
n
n
n
OH
OH
OH
OH
O
O
O
O
O
HBr/AcOH
O
O
O
TsCl
Br
OH
HO
n = 0, 1
OH
HO
n = 0, 1
TsO
HO
S2−
Br
OH
OH
This Work!
HO
S2−
OTs
Known
Ref. 12a
O
O
S
S
Synthesis of diverse thiosugars and its
O
O
application in glycobiology and pharmacokinetics
as glycosidase inhibitors
HO
HO
n
n
HO
HO
Scheme 1. Effect of bromide and tosylate as leaving groups on aldono-c-lactone on the course of reaction with tetrathiomolybdate 1.
This result demonstrates a short synthesis of 1,4-dideoxy-1,4-
1,4-lactone 10 was achieved using tosyl chloride/pyridine.17 Reac-
tion of 2,6-di-O-tosyl-allono lactone 11 with tetrathiomolybdate 1
epithio-
nine19a,b or six19c linear steps from
from -glucose.
To further demonstrate the usefulness of this methodology, we
decided to synthesize 1,4-anhydro-4-thio- -lyxitol 9, a pentose su-
D
-arabinitol 5 from
D
-xylose which otherwise requires
D
-xylose and 12 linear steps19d
smoothly furnished the expected 1-deoxy-5-thio-
3,6-lactone 12 in 49% yield (Scheme 5, Fig. 2). Subsequently, BER
reduction of 1-deoxy-5-thio- -talopyrano-3,6-lactone 12 resulted
D-talopyrano-
D
D
D
in the formation of 1-deoxythiotalonojirimycin 13 in 58% yield.
Interestingly, the synthesis of 1-deoxythioidonojirimycin 17
was also achieved from gulono-1,4-lactone 14. The ditosylate,
2,6-di-O-tosyl-gulono lactone 15 was obtained in 69% yield, by
adding a neat solution of tosyl chloride in acetone to a solution
gar, ubiquitous and fundamental in many biological processes.
Tosylation of ribonolactone 6 with tosyl chloride/pyridine gener-
ated the ribono ditosylate 716 in 63% yield. Treatment of ribono
ditosylate 7, with benzyltriethylammonium tetrathiomolybdate 1
furnished the 1-deoxy-4-thio-
(68%) (Scheme 3). The structure of the bicyclic lactone 8 was fur-
ther confirmed by X-ray analysis (Fig. 1). Reduction of 1-deoxy-
D
-arabino-2,5-lactone 8 in good yield
of
L
-(+)-gulono-1,4-lactone 14 in pyridine at 0 °C for 3 h, as
reported.16 However, a slight change in the work-up procedure
was essential to improve the isolated yield of aldonoditosylate 15
when compared to the literature report (reported yield 44%). Fur-
ther, treatment of 2,6-di-O-tosyl-gulono lactone 15 with benzyltri-
ethylammonium tetrathiomolybdate 1, in DMSO at room
temperature gave the bicyclic lactone ring system 16, 1-deoxy-5-
4-thio-D-arabino-2,5-lactone 8 with borohydride exchange resin
in methanol produced the thiosugar, 1,4-anhydro-4-thio-
D
-lyxitol
9 in 67% yield. Remarkably, the synthesis of 9 is achieved in three
steps with an overall yield of 29%. This route is superior to the only
known report20 that utilizes eleven linear steps for the synthesis of
thio-D-glucopyrano-2,6-lactone in 56% yield as a white crystalline
1,4-anhydro-4-thio-
D
-lyxitol 9 starting from
D
-lyxose.
solid (Scheme 6). The structure of the bicylic lactone 16 was
further confirmed by X-ray analysis (Fig. 3). The formation of the
bicyclic lactone is anticipated through the rearrangement of
2,6-di-O-tosyl-gulono lactone 15 or its corresponding C-2-sulfide
to the reactive d-lactone 15a, since the aldonoditosylate 15
cannot undergo double displacement due to the syn-orientation
of C-2-tosyl and C-4-side chain. Lactone 15a then undergoes subse-
A plausible mechanism is proposed to rationalize the formation
of thiosugar lactone 8 from ditosylaldono lactone 7 (Scheme 4).
The reaction of ditosylaldono lactone 7 with benzyltriethylammo-
nium tetrathiomolybdate 1 involves SN2 displacement of the tosyl-
oxy group at carbon alpha (a-) to the carbonyl (the most reactive
position of the available reactive sites) to form the intermediate
A.21 An internal redox process takes place in the intermediate A
where the oxidation of the ligand and concomitant reduction of
the metal center gives the disulfide B.22 Based on our earlier
work11c–e and that of Stiefel and co-workers,23 disulfide B can then
undergo reductive cleavage of the disulfide bond mediated by ben-
zyltriethylammonium tetrathiomolybdate 1 to afford the thiolate
intermediate C.24 Finally the displacement of the primary tosylate
by the resultant sulfide anion in intermediate C in an intramolecu-
lar fashion is hypothesized to result in the formation of the bicyclic
thiosugar lactone 8 in a stereospecific manner.11f
quent reaction to provide the 1-deoxy-5-thio-D-glucopyrano-2,6-
lactone 16. The reduction of bicyclic lactone 16 with BER in
methanol provided the 1-deoxythioidonojirimycin 17 in 67% yield.
In conclusion, synthesis of biologically relevant thiofuranoses,
1,4-dideoxy-1,4-epithio-D-arabinitol and 1,4-anhydro-4-thio-D-
lyxitol and the synthesis of rare thiopyranoses such as 1-deoxythi-
otalonojirimycin and 1-deoxythioidonojirimycin were achieved.
The present methodology involves the synthesis of ditosylates, sul-
fur transfer reaction with [BnEt3N]2MoS4 1 followed by BER reduc-
tion reactions. The examples developed through this approach
demonstrate the generality of this methodology and wider applica-
bility of the synthesis of 1-deoxythiosugars through a protection/
deprotection-free sequence.
The generality of the approach was further demonstrated in the
synthesis of thiopyrano sugar, 1-deoxythiotalonojirimycin 13
which was envisaged from the rare sugar derivative,
D
-allono-
-allono-
1,4-lactone 10.25 Thus, the tosylation of the resulting
D
HO
OH
O
O
O
O
O
HO
TsO
a
b
c
OH
OH
S
O
HO
OH
HO
OTs
S
2
D-(+)-Xylono-1,4-lactone
3
4
1,4-Dideoxy-1,4-epithio-D-arabinitol 5
Scheme 2. Synthesis of 1,4-dideoxy-1,4-epithio-
(c) BER, MeOH, 0 °C–rt, 7.5 h, 65%.
D-arabinitol 5. Reagents and conditions: (a) TsCl/pyridine:acetone, 0 °C, 5 h, 28%; (b) [BnEt3N]2MoS4 1, DMSO, rt, 16 h, 53%;

32
T. Gunasundari, S. Chandrasekaran / Carbohydrate Research 382 (2013) 30–35
O
O
HO
OH
O
O
O
HO
TsO
a
b
c
OH
O
OH
S
HO
OH
HO
OTs
S
D-(+)-Ribono-1,4-lactone 6
7
8
1,4-Anhydro-4-thio-D-lyxitol 9
Scheme 3. Synthesis of 1,4-anhydro-4-thio-
MeOH, 0 °C–rt, 10 h, 67%.
D-lyxitol 9. Reagents and conditions: (a) TsCl/pyridine:acetone, 0 °C, 5 h, 63%; (b) [BnEt3N]2MoS4 1, DMSO, rt, 12 h, 68%; (c) BER,
1. Experimental
1.1. General methods
Melting points were recorded on a BUCHI B540 melting point
apparatus and are uncorrected. 1H and 13C NMR spectra were re-
corded on a BRUKER-400 and 100 MHz spectrometer, respectively.
Chemical shifts are reported in parts per million downfield from
the internal reference, tetramethylsilane. Coupling constants are
reported wherever necessary in Hertz (Hz). Column chromatogra-
phy was performed on silica gel (230–400 mesh). IR spectra were
recorded on a Jasco FTIR 410 spectrophotometer. Mass spectra
were recorded on a Q-TOF electrospray instrument. Micro analysis
was recorded on Thermo Finnigan FLASH EA 1112 CHNS analyser.
Optical rotation was recorded on polarimeter model P-1020
(A077860638). X-ray data collection was recorded on a BRUKER-
SMART APEX CCD-single crystal diffractometer.
1.2. Typical procedure for the synthesis of 2,5-ditosyloxy-2,5-
Figure 1. ORTEP diagram of 1-deoxy-4-thio-
D-arabino-2,5-lactone 8.
dideoxy- and 2,6-ditosyloxy-2,6-dideoxy-D-glycono-1,4-
lactones16
R2 R1
R2 R1
HO
O
O
O
O
O
O
X
X
TsO
O
2
HO
OH
OTs
O
MoS4
S
S
HO
HO
S
S
TsO
Mo
O
R1 = R2 = H; X = OH
R1 = H; R2 = OH; X = CH2OH
R1 = R2 = H; X = OTs
R1 = H; R2 = OH; X = CH2OTs
HO
OTs
2 OTs
TsO
7
O
A
To a solution of aldono-1,4-lactone (3.0 g, 0.02 mol) in dry pyr-
idine (15 mL) at 0 °C was added TsCl (8.88 g, 0.047 mol) dissolved
in acetone (15 mL) over a period of 10 min. The reaction mixture
was then stirred at 0 °C for a given period of time after which it
was neutralized with 6 M HCl until pH 1. The compound was ex-
tracted using EtOAc (3 Â 15 mL), dried (Na2SO4), and concentrated
and subjected to column chromatography (elution with
EtOAc:hexanes) to give the pure ditosylaldono lactone.
O
O
TsO
TsO
OTs
O
2
O
HO
HO
S
MoS4
O
OH
O
S
S
HO
S
8
O
O
B
C
1.2.1. 2,5-Di-O-tosyl-xylono-1,4-lactone (3)
IR (neat): 3430, 1777, 1420, 1211, 1180, 1070, 1027, 996 cmÀ1
;
Scheme 4. Proposed mechanism for the nucleophilic double displacement of
ditosylaldono lactone 7 in an intramolecular fashion mediated by [BnEt3N]2MoS4 1.
1H NMR (400 MHz, CD3COCD3) d 2.53 (s, 6H), 3.98–4.08 (m, 2H),
4.7 (t, J = 3.1 Hz, 1H), 5.22 (d, J = 4.9 Hz, 1H), 5.49 (t, J = 4.3 Hz,
1H), 7.56–7.58 (m, 4H), 7.83–7.89 (m, 4H) ppm; 13C NMR
OH
OH
O
OH
O
O
O
a
HO
S
c
HO
OH
OH
1-Deoxythiotalonojirimycin 13
O
b
O
HO
OH
OTs
HO
11
HO
OH
S
OTs
D-Allono-1,4-lactone 10
12
Scheme 5. Synthesis of 1-deoxythiotalonojirimycin 13. Reagents and conditions: (a) TsCl/pyridine:acetone, 0 °C, 3 h, 29%; (b) [BnEt3N]2MoS4 1, DMSO, rt, 48 h, 49%; (c) BER,
MeOH, 0 °C–rt, 4 h, 58%.

T. Gunasundari, S. Chandrasekaran / Carbohydrate Research 382 (2013) 30–35
33
Figure 2. ORTEP structure of 1-deoxy-5-thio-D-talopyrano-3,6-lactone 12.
(100 MHz, CD3COCD3) d 20.5, 20.6, 70.0, 71.0, 75.2, 81.0, 128.0,
Figure 3. ORTEP diagram of 1-deoxy-5-thio-D-glucopyrano-2,6-lactone 16.
128.1, 129.9, 130.0, 130.2, 130.3, 137.0, 138.1, 165.6 ppm.
J = 10.1, 3.9 Hz, 1H), 4.46 (d, J = 3.7 Hz, 1H), 4.71 (t, J = 4.3 Hz,
1H), 4.95 (d, J = 3.1 Hz, 1H), 5.53 (d, J = 4.8 Hz, 1H), 7.34 (d,
J = 8.0 Hz, 1H), 7.50 (d, J = 8.0 Hz, 1H), 7.74 (d, J = 8.2 Hz, 1H),
7.885 (d, J = 8.2 Hz, 1H) ppm; 13C NMR (100 MHz, CD3COCD3) d
21.3, 21.5, 74.6, 75.4, 76.0, 77.4, 86.3, 127.1, 128.7, 128.9, 129.0,
130.0, 130.9, 133.9, 140.2, 143.1, 146.5 169.9 ppm; HRMS for C20-
H22O10S2Na [M+Na]+ calcd 509.0552; found 509.0556.
1.2.2. 2,5-Di-O-tosyl-ribono lactone (7)
IR (neat): 3438, 1777, 1424, 1219, 1181, 1073, 1028, 993 cmÀ1
;
1H NMR (400 MHz, CD3COCD3) d 2.44 (s, 6H), 4.34–4.49 (m, 2H),
4.66 (t, J = 3.4 Hz, 1H), 5.23 (d, J = 5.2 Hz, 1H), 5.38 (t, J = 4.4 Hz,
1H), 7.48 (d, J = 7.9 Hz, 4H), 7.77 (d, J = 8.3 Hz, 2H), 7.84 (d,
J = 8.3 Hz, 2H) ppm; 13C NMR (100 MHz, CD3COCD3) d 20.6, 20.7,
68.17, 68.3, 73.8, 82.7, 127.8, 128.1, 130.0, 130.2, 132.3, 132.7,
145.6, 145.7, 168.7 ppm; HRMS for C19H20O9S2Na [M+Na]+ calcd
479.0446; found 479.0443.
1.3. Typical procedure for the synthesis of thiosugar lactones
A solution of aldonoditosylate (1.0 mmol) in DMSO (2 mL) was
added to a solution of [BnEt3N]2MoS4 1 (2.19 mmol) in DMSO
(15 mL) over a period of 5 min. The reaction mixture was stirred
at room temperature for the given period of time. The work-up
procedure was performed by two different methods which are as
follows:
Method A: DMSO from the reaction mixture was removed under
reduced pressure and the residue was repeatedly extracted with
THF (4 Â 5 mL) and filtered over a Celite pad. The solvent was con-
centrated to give the crude product which was subjected to col-
umn chromatography on silica gel (elution with hexanes:ethyl
acetate 1:1) furnishing the thiosugar lactone.
1.2.3. 2,6-Di-O-tosyl-allono lactone (11)
IR (neat): 3509, 1803, 1598, 1362, 1192, 1177, 1096, 814,
670 cmÀ1 1H NMR (400 MHz, CD3COCD3) d 2.53 (s, 6H), 4.18 (dd,
;
J = 7.2, 9.9 Hz, 2H), 4.31–4.24 (m, 3H), 4.48 (d, J = 1.8 Hz, 2H),
5.11 (t, J = 5.5 Hz, 2H), 5.28 (d, J = 4.5 Hz, 1H), 7.56 (d, J = 8.1 Hz,
4H), 7.90 (d, J = 8.2 Hz, 2H) ppm; 13C NMR (100 MHz, CD3COCD3)
d 20.6, 29.8, 68.1, 70.3, 72.7, 74.5, 79.2, 127.8, 130.0, 133.0,
145.1, 173.4 ppm; HRMS for
509.0552; found 509.0553.
C
20H22O10S2Na [M+Na]+ calcd
1.2.4. 2,6-Di-O-tosyl gulonolactone (15)
Method B: The reaction mixture was diluted with H2O (20 mL)
and the compound was extracted using EtOAc (3 Â 8 mL). The ex-
tracted organic layer was dried (Na2SO4), and concentrated to give
the crude product which was subjected to column chromatography
on silica gel (elution with hexanes:ethyl acetate 1:1) furnishing the
thiosugar lactone.
A slight change from the typical procedure was necessary in or-
der to improve the yield of aldonoditosylate 15. Thus, the work-up
involved removal of the solvent under vacuum followed by short
column chromatography to yield the ditosylgulono lactone 15 in
69% (6.36 g).
Elution with EtOAc:hexanes (2:3); IR (neat): 3438, 1777, 1424,
1219, 1181, 1073, 1028, 993 cmÀ1 1H NMR (400 MHz, CD3COCD3)
;
Method A was adopted as work-up procedure in all cases unless
otherwise mentioned.
d 2.40 (s, 3H), 2.46 (s, 3H), 3.84 (d, J = 10.1 Hz, 2H), 3.98 (dd,
OH
OH
OH
HO
S
HO
OH
OH
O
O
TsO
O
O
a
b
O
c
HO
OH
HO
O
S
OH
OH
L-(+)-Gulono-1,4-lactone
OTs
14
15
16
1-Deoxythioidonojirimycin 17
TsO
HO
O
O
HO
X
-
15a
; X = OTs or S
Scheme 6. Synthesis of 1-deoxythioidonojirimycin 17. Reagents and conditions: (a) TsCl/pyridine:acetone, 0 °C, 3 h, 69%; (b) [BnEt3N]2MoS4 1, DMSO, rt, 2 h, 56%; (c) BER,
MeOH, 0 °C–rt, 20 h, 67%.

34
T. Gunasundari, S. Chandrasekaran / Carbohydrate Research 382 (2013) 30–35
1.3.1. Synthesis of 1-deoxy-4-thio-
D
-lyxono-2,5-lactone (4)
1H NMR
1.4.1. 1,4-Dideoxy-1,4-epithio-D-arabinitol (5)
IR (neat): 3400, 1779, 1436, 1330, 1126, 1046 cmÀ1
;
1H NMR (400 MHz, CD3OD) d 2.71 (dd, J = 6.2, 10.8 Hz, 1H, –
SCH2–), 2.99 (dd, J = 5.6, 10.8 Hz, 1H), 3.23 (dd, J = 5.5, 17.5 Hz,
1H), 3.60 (dd, J = 6.8, 11.0 Hz, 1H), 3.80 (d, J = 5.4 Hz, 1H), 3.85
(dd, J = 5.5, 11.0 Hz, 1H), 4.12 (dd, J = 5.8, 11.7 Hz, 1H) ppm; 13C
NMR (100 MHz, CD3OD) d 32.9 (–SCH2–), 52.3 (–SCH–), 64.1 (–CH2-
OH–), 77.8 [–CH(OH)–], 79.2 [–CH(OH)–] ppm; HRMS for C5H10O3-
SNa [M+Na]+ calcd 173.0248; found 173.0278.
(400 MHz, CD3COCD3)
d 3.01 (d, J = 10.9 Hz, 1H), 3.25 (d,
J = 10.9 Hz, 1H), 3.62 (s, 1H), 3.68 (d, J = 11.4 Hz, 1H), 4.48 (s, 1H),
4.88 (s, 1H) ppm; 13C NMR (100 MHz, CD3COCD3) d 33.0, 48.2,
72.5, 80.8, 171.1 ppm; HRMS for C5H6O3SNa [M+Na]+ calcd
168.9922; found 168.9933.
1.3.2. Synthesis of 1-deoxy-4-thio-
CCDC 870210; mp: 88–90 °C; IR (neat): 3402, 1781, 1436, 1332,
1131, 1018, 1054 cmÀ1 1H NMR (400 MHz, CD3COCD3) d 2.96 (d,
J = 11.0 Hz, 1H), 3.30 (d, J = 11.1 Hz, 1H), 4.41 (s, 1H), 4.87 (s, 1H),
5.33 (d, J = 2.7 Hz, 1H) ppm; 13C NMR (100 MHz, CD3COCD3) d
31.8, 44.9, 78.7, 82.4, 173.2 ppm; HRMS for C5H6O3SNa [M+Na]+
calcd 168.9935; found 168.9933; Anal. Calcd for: C, 41.09; H,
4.14; S, 21.94. Found: C, 41.1; H, 4.24; S, 21.51.
D-arabino-1,4-lactone (8)
1.4.2. Synthesis of 1,4-anhydro-4-thio-D-lyxitol (9)
1H NMR (400 MHz, CD3OD) d 2.82 (d, J = 7.4 Hz, 2H, –SCH2–),
3.45 (dd, J = 6.3, 11.0 Hz, 1H), 3.57 (dd, J = 6.4, 10.9 Hz, 1H), 3.86
(dd, J = 6.9, 10.9 Hz, 1H), 4.13–4.19 (m, 2H), 4.57 (t, J = 3.3 Hz,
1H), 4.83 (t, J = 2.0 Hz, 1H) ppm; 13C NMR (100 MHz, CD3OD) d
31.7 (–SCH2–), 48.9 (–SCH–), 61.5 (–CH2OH–), 73.6 [–CH(OH)–],
75.9 [–CH(OH)–] ppm; HRMS for C5H10O3SNa [M+Na]+ calcd
173.0248; found 173.0243.
;
Crystal structure data: CCDC 870210: C5H6O3S1, Mwt = 146.14,
crystal dimensions 0.28 Â 0.24 Â 0.15, T = 296(2) K, tetragonal,
space group P2(1), a = 6.0800(5), b = 8.4996(8), c = 6.0825(6) Å,
1.4.3. 1-Deoxythiotalonojirimycin (13)
a
=
c
= 90.00°,
b = 111.262(2)°,
Z = 2,
V = 292.93(5) cm3,
= 4.72 mm
2h = 3.59–29.89°; of 1043 reflections collected, 681 were
[
a]
D +20.6 (c 1.0, MeOH), lit. [
a]
D +28.0 (c 1.1, MeOH); IR (neat):
;
q
calcd = 1.657 g/cm3, MoK radiation (k° = 0.71073 Å),
l
a
3369, 2916, 1420, 1073, 1018 cmÀ1
1H NMR (400 MHz, CD3OD) d
À1
,
2.57 (bd, J = 13.1 Hz, 1H, –SCH2–), 2.78 (dd, J = 13.5, 7.6 Hz, 1H),
2.87 (td, J = 6.1, 3.5 Hz, 1H), 3.59 (s, 1H), 3.85–3.74 (m, 2H), 3.89
(dt, J = 7.6, 3.2 Hz, 1H), 4.00 (t, J = 3.0 Hz, 1H) ppm; 13C NMR
(100 MHz, D2O) d 30.1 (–SCH2–), 47.5 (–SCH–), 61.3 (–CH2OH–),
69.5 [–CH(OH)–], 70.9 [–CH(OH)–], 71.4 [–CH(OH)–] ppm; HRMS
for C6H12O4SNa [M+Na]+ calcd 203.0354; found 203.0356.
independent (R(int) = 0.0468); refinement method full matrix least
squares on F2, 83 refined parameters, absorption correction
(SADABS, Bruker, 1996 software, Tmin 0.8793 and Tmax 0.9326),
GooF = 1.008, R1 = 0.0468, wR2 = 0.0965 (
r >2r(I)), absolute struc-
ture parameter 0.02(14), residual electron density 0.134/
À0.185 eÅÀ3
.
1.4.4. 1-Deoxythioidonojirimycin (17)
1.3.3. 1-Deoxy-5-thio-
CCDC 774512; mp: 145–146 °C; [
(neat): 3419, 3265, 1421, 1358, 1159, 1037 cmÀ1
D
-talopyrano-3,6-lactone (12)
[
a]
D
À34.5 (c, 1.0, MeOH); IR (neat): 3448, 3444, 3410, 1699,
a
]
D
+24.5 (c 1.0, MeOH); IR
1526, 1253, 1169, 1033 cmÀ1 1H NMR (400 MHz, D2O) d 2.45
;
;
1H NMR
(dd, J = 13.8, 4.4 Hz, 1H, –SCH2–), 2.58 (t, J = 13.7 Hz, 1H, –SCH2–),
2.89–2.84 (m, 1H, –SCH–), 3.23 (dd, J = 18.3, 9.1 Hz, 1H, –CH2OH),
3.58–3.53 (m, 1H, –CH2OH), 3.62 (t, J = 10.4 Hz, 1H, –CH(OH)–),
3.82–3.80 (m, 1H, –CH(OH)–), 3.87 (dd, J = 11.6, 4.0 Hz, 1H, –
CH(OH)–) ppm; 13C NMR (100 MHz, D2O) d 27.3 (–SCH2–), 45.9
(–SCH–), 57.1 (–CH2OH–), 72.9 [–CH(OH)–], 73.6 [–CH(OH)–],
73.7 [–CH(OH)–] ppm; HRMS for C6H12O4SNa [M+Na]+ calcd
203.0354; found 203.0356.
(400 MHz, CD3COCD3) d 2.61 (dd, J = 13.0, 10.2 Hz, 1H), 2.86 (dd,
J = 13.1, 5.8 Hz, 1H), 3.26 (s, 1H), 4.08 (td, J = 10.1, 5.9 Hz, 1H),
4.27 (d, J = 2.9 Hz, 1H), 4.59 (s, 1H), 4.78 (d, J = 6.1 Hz, 1H), 5.21
(d, J = 2.9, 1H) ppm; 13C NMR (100 MHz, CD3COCD3) d 28.8, 44.7,
70.0, 77.1, 89.2, 173.7 ppm; HRMS for C6H8O4SNa [M+Na]+ calcd
199.0041; found 199.3421; Anal. Calcd for: C, 40.85; H,5.27; S,
17.92. Found: C, 40.90; H, 4.58; S, 18.20.
The structures of compounds 8, 12, and 16 were solved and re-
fined using the programs WinGXv1.64.05, Sir92, and SHELXL-97.
‘Complete crystallographic data for the structural analysis have
been deposited with the Cambridge Crystallographic Data Centre,
CCDC 870210 (compound 8), CCDC 774512 (compound 12), and
CCDC 802220 (compound 16). Copies of this information may be
obtained free of charge from the Director, Cambridge Crystallo-
graphic Data Centre, 12 Union Road, Cambrige, CB2 1EZ, UK. (fax:
+44 1223 336033, email: deposit@ccdc.cam.ac.uk or via:
www.ccdc.cam.ac.uk).’
1.3.4. 1-Deoxy-5-thio-
CCDC 802220; mp: 178–179 °C; [
(neat): 3350, 3339, 1734, 1527, 1156, 1038, 672 cmÀ1
D
-glucopyrano-2,6-lactone (16)
a
]
D
À43.5 (c 1.0, MeOH); IR
;
1H NMR
(400 MHz, CD3COCD3) d 2.99 (dd, J = 11.7, 3.8 Hz, 1H, –SCH2–),
3.22 (m, J = 20.7, 11.7 Hz, 2H, –SCH2– and –SCH–), 3.96 (br s, 1H),
4.15 (d, J = 2.1 Hz, 1H), 4.87 (t, J = 4.1 Hz, 1H), 5.03 (d, J = 4.5 Hz,
1H), 5.10 (d, J = 3.4 Hz, 1H, –CHOCO–) ppm; 13C NMR (100 MHz,
CD3COCD3) d 23.2 (–SCH2–), 40.6 (–SCH–), 73.9 [–CH(OH)–], 77.7
[–CH(OH)–], 78.0 (–CHOCO–), 169.3 [–OC(O)–] ppm; HRMS for C6-
H8O4SNa [M+Na]+ calcd 199.0041; found 199.0039; Anal. Calcd for:
C, 40.9; H, 4.58; S, 18.2. Found: C, 40.8; H, 4.6; S, 18.2.
Acknowledgments
1.4. Typical procedure for reduction of the thiosugar lactone
using BER
The authors thank IISc, Bangalore for the award of senior re-
search fellowship to T.G., and the Department of Science and Tech-
nology (DST), New Delhi for the CCD X-ray facility. We also thank
DST for the award of J.C. Bose National Fellowship to S.C.N. Finally
we thank Mr. Amol Dikundwar and Mr. Sajesh P. Thomas for help
in single crystal analysis.
To a stirred solution of thiosugar lactone (1.0 mmol) in dry meth-
anol (12.5 mL) at 0 °C was added borohydride exchange resin
(7.5 mmol, 2.5 g) and the solution was stirred for a given period of
time. The reaction mixture was filtered and methanol (10 mL) was
added to the resin and was sonicated (ultrasonic cleaning bath,
20 kHz) for 5 min at room temperature. The reaction mixture was
then neutralized using glacial acetic acid. The reaction mixture
was filtered and concentrated in vacuo to afford the crude product
whichwas subjectedto column chromatography on silica gel elution
with methanol/chloroform 1.5:8.5 to furnish the 1-deoxythiosugar.
Supplementary data
Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.carres.2013.
09.009.

T. Gunasundari, S. Chandrasekaran / Carbohydrate Research 382 (2013) 30–35
35
12. (a) Gunasundari, T.; Chandrasekaran, S. J. Org. Chem. 2010, 75, 6685–6688; (b)
Gunasundari, T.; Chandrasekaran, S. Eur. J. Org. Chem. 2012, 6986–6995.
13. (a) Lundt, I. Top. Curr. Chem. 1997, 187, 117–156; (b) Xavier, N. M.; Rauter, A. P.;
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14. (a) For instance considering the prerequisite of the reactions out of eight
hexose sugars, only two (mannose and gulose) will undergo bromination
followed by tetrathiomolybdate reaction to give corresponding thiosugars.; (b)
The present methodology will convert (tosylation followed by
tetrathiomolybdate reaction) four hexose sugars (allose, glucose, idose, and
talose) to corresponding thiosugars. However, we investigated only few
substrates due to their limited availability.
15. (a) Jayakanthan, K.; Mohan, S.; Pinto, B. M. J. Am. Chem. Soc. 2009, 131, 5621–
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