Preparation of α- And β-D-glucoseptanose pentaacetates

Article abstract of DOI:10.1016/j.carres.2012.03.011

The α- and β-d-glucoseptanose pentaacetates have been prepared by treatment of ethyl 1-thio-β-d-glucoseptanoside tetraacetate with mercury(II) acetate in acetic acid. The solid state structure of the β-isomer has been determined by X-ray diffraction.

Full text of DOI:10.1016/j.carres.2012.03.011

Carbohydrate Research 353 (2012) 86–91
Contents lists available at SciVerse ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
Preparation of
a
- and b-D-glucoseptanose pentaacetates q
z
⇑
Mohan Bhadbhade, Donald C. Craig , Clarence J. Ng, Leon Odier, John D. Stevens
School of Chemistry, University of New South Wales, Sydney 2052, Australia
a r t i c l e i n f o
a b s t r a c t
Article history:
The a- and b-D-glucoseptanose pentaacetates have been prepared by treatment of ethyl 1-thio-b-D-gluco-
septanoside tetraacetate with mercury(II) acetate in acetic acid. The solid state structure of the b-isomer
has been determined by X-ray diffraction.
Received 31 January 2012
Received in revised form 9 March 2012
Accepted 10 March 2012
Available online 23 March 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Septanose compounds
D-Glucoseptanose
NMR
X-ray crystallography
We have prepared several methyl aldohexoseptanosides2–6 as
part of a study of seven membered ring sugars. Although these
studies provided information on the chemical properties and con-
formations of such glycosides, access to other derivatives, such as
nucleosides, from the methyl glycosides is not feasible. It appeared
that 1-thio glycosides would be suitable for the preparation of 1-O-
acetyl septanose derivatives. These would be appropriate precur-
sors for a variety of septanosyl compounds. In this note we describe
ZnCl2 gave a mixture of the two thio glycosides, 4 and 5, in satisfac-
tory yield (see Scheme 2).
Acid catalysed hydrolysis of 4 gave a mixture of thio glycosides
identified as ethyl 1-thio-
-glucopyranoside, isolated as the tetraacetate (8), and ethyl 1-
thio- -glucoseptanoside (9), characterised as the tetraacetate
a-D-glucofuranoside (7), ethyl 1-thio-a-
D
a-D
(10), and isolated in low yield (see Scheme 3). Rearrangement of
ring forms of thio glycosides under acidic conditions is a well
known phenomenon.8
the first preparation of the two
We have shown3 that demercaptalation of 6-O-benzoyl-2,3:4,5-
di-O-isopropylidene- -glucose diethyl dithioacetal (1) followed by
debenzoylation gives the septanose compound 2,3:4,5-di-O-iso-
propylidene- -glucoseptanose (2).
If debenzoylation of 1, to give 2,3:4,5-di-O-isopropylidene-
D-glucoseptanose pentaacetates.
Acid catalysed hydrolysis of 5 was much less troublesome, giv-
D
ing the tetrol ethyl 1-thio-b-
converted into the tetraacetate, ethyl 1-thio-2,3,4,5-tetra-O-acet-
yl-b- -glucoseptanoside (12). Treatment of 12 with mercury(II)
acetate9 yielded two products: a liquid identified as
-glucosep-
-glucosepta-
D-glucoseptanoside (11) which was
D
D
D
-glu-
a-D
cose diethyl dithioacetal (3), is carried out before demercaptalation,
tanose pentaacetate (13) and a crystalline solid, b-
D
three products are formed (see Scheme 1): ethyl 1-thio-2,3:4,5-di-
nose pentaacetate (14) (see Scheme 4).
O-isopropylidene-
di-O-isopropylidene-b-
a
-
D
-glucoseptanoside (4), ethyl 1-thio-2,3:4,5-
-glucoseptanoside (5) and 2. The formation
1H NMR spectral data are given in Section 1, with 13C NMR data
for 13 and 14. J values for 13 and 14 are in reasonable agreement
with those reported2 for the corresponding methyl glycosides.
Acetolysis of 13 gave a mixture of 13 and 14 in the ratio 1:7.4.
No other products were detected (Figure 1).
D
of 2 in this reaction is suggestive of demercaptalation of 4 and 5
which limits the usefulness of this procedure for the preparation
of 4 and 5. We have resorted to another sequence for the preparation
of 4 and 5.
The X-ray structure determination on 14 confirms the struc-
ture proposed on the basis of the method of preparation and the
1H NMR data. The ring conformation may be described as a
Treatment of the b-anomer of 21 with trichloroacetonitrile pro-
duces the trichloroactimidate, (6). Reaction7 of 6 with EtSH and
10
twist-chair,5,6 TC3,4 with the ring torsional angles in excellent
agreement with the values computed11,12 for the twist-chair C
form of oxepane. This conformation was also found for four
methyl aldohexoseptanoside compounds for which the pseudo
axis-of-symmetry passes through C-1. The relevant angles are gi-
ven in Table 1.
q
Septanose carbohydrates, Part 9. For part 8, see Ref. 1.
⇑
Corresponding author. Tel.: +61 296633175.
E-mail address: johndstevens@yahoo.com (J.D. Stevens).
Deceased 12th May, 2009.
z
0008-6215/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.carres.2012.03.011

M. Bhadbhade et al. / Carbohydrate Research 353 (2012) 86–91
87
O
O
R1
R2
CH(SEt)2
O
OH
O
O
O
O
+
3 +
HgCl2
Me2C
Me2C
O
CMe2
CMe2
O
O
O
O
CMe2
CMe2
O
O
R1
H
R2
2
4
5
SEt
H
CH2OR
SEt
1
3
R = COC6H5
R = H
Scheme 1.
NH
CCl3
O
O
OH
O
CCl3CN
K2CO3
EtSH
+
4
5
O
O
O
O
ZnCl2
Me2C
Me2C
O
O
O
O
CMe2
CMe2
6
2
β
Scheme 2.
at 125 MHz and assignments were made using one-bond 13C/1H
2D NMR spectroscopy using standard Bruker programs. JC-1,H-1 spin
coupling constants were determined17 directly from 1H NMR
spectra.
1. Experimental
1.1. General methods
Column chromatography was performed using Merck silica gel
7736, generally using a height of packed column ca. 15 times its
diameter. Thin layer chromatography used silica gel supported
on glass slides (Analtech). Ether refers to diethyl ether and light
petroleum refers to the fraction boiling 60–80 °C. Gas chromatog-
raphy was carried out on a custom built instrument fitted with a
Optical rotations were determined using a Bendix automatic
polarimeter or a Perkin–Elmer 141 automatic polarimeter. Melting
points were determined on a Reichert hot-stage microscope and
are uncorrected. Infrared spectra were obtained using a Perkin El-
mer Infracord 137 spectrometer. NMR spectra were recorded using
a Bruker DMX-500 spectrometer. 13C NMR spectra were recorded
CH2OH
CH2OH
O
HO
O
O
O
+
H3O
H
O
+
+
O
SEt
OH
OH
OH
Me2C
SEt
OH
HO
HO
SEt
OH
O
O
CMe2
SEt
HO
OH
9
4
7
Ac2O/Pyr
Ac2O/Pyr
CH2OAc
O
O
OAc
OAc
SEt
OAc
AcO
AcO
SEt
OAc
AcO
8
10
Scheme 3.

88
M. Bhadbhade et al. / Carbohydrate Research 353 (2012) 86–91
O
O
SEt
SEt
O
R1
R2
1. H3O+
2. Ac2O/Pyr AcO
Hg(OAc)2
O
OAc
OAc
O
AcO
AcO
Me2C
O
O
AcO
OAc
OAc
CMe2
R1
H
OAc
R2
OAc
H
5
12
13
14
Scheme 4.
Figure 1. ORTEP plot of 14 showing atomic notation and thermal ellipsoids.
flame ionisation detector and a quartz tube lined injection block.
The column used was a coiled 240 cm glass column packed with
3% DEGA (stabilised, Analabs) on Chromosorb W (AW-DMCS).
Oven temperature was 200 °C using N2 carrier gas. Retention times
are in minutes and recorded as rt. High resolution mass spectra
were recorded using a Bruker Apex II 7T FT/ICR spectrometer
equipped with an Analytica ESI source operating in positive ion
mode. The digital was 0.00252 m/z.
a lightly coloured liquid (15.3 g, 41.74 mmol, 98%); IR (thin film)
3400 cmꢁ1, no C@O absorption.
1.3. Ethyl 1-thio-2,3:4,5-di-O-isopropylidene-a-D-glucoseptano
side (4) and ethyl 1-thio-2,3:4,5-di-O-isopropylidene-b-D-gluco
septanoside (5)
After a mixture of CdCO3 (54 g), HgCl2 (36 g) and acetone
(200 mL) had been stirred for 0.5 h, 3 (15.3 g, 41.74 mmol) was
added and the mixture stirred for 2 h after which time TLC
(EtOAc/light petroleum = 1:3) showed the absence of 3 (Rf 0.22).
A solution of the residue left on concentration of the filtered reac-
tion mixture in CHCl3 (200 mL) was extracted with satd KI solution
(2 ꢀ 150 mL), washed with H2O, dried over MgSO4 and concen-
trated. Chromatography of the syrupy products over silica gel
(200 g), using Et2O/light petroleum = 1:1), collecting fractions of
25 mL, gave the first product (0.68 g) in fractions 28–41. Crystalli-
sation from light petroleum gave colourless prisms of 4 (Rf 0.49)
1.2. 2,3:4,5-Di-O-isopropylidene-D-glucose diethyl dithioacetal
(3)
To a solution of 1 (20 g, 42.50 mmol) in EtOH (200 mL) was
added a solution of NaOH (10 g) in water (50 mL). After the mix-
ture had been kept at 60 °C for 1 h, TLC (EtOac/light petro-
leum = 1:3) showed the absence of 1 (Rf 0.55). A solution of the
residue (left on concentration of the reaction mixture) in CHCl3
(200 mL) was shaken with H2O (2 ꢀ 200 mL), filtered through a
short column of silica gel and concentrated to give 3 (Rf 0.22) as
(0.52 g, 1.71 mmol, 4.1%), mp 102–103 °C, ½a D23
ꢂ
+212.1 (c 1.17,

M. Bhadbhade et al. / Carbohydrate Research 353 (2012) 86–91
89
Table 1
Selected torsional angles (°)
14
40.5
45.0
ꢁ88.4
63.9
Oxepane twist-chair C
513
53.5
35.7
ꢁ91.2
60.4
16a
46.0
37.2
ꢁ78.2
61.0
17b
55.3
30.8
ꢁ83.9
68.2
18c
54.9
35.4
ꢁ88.7
68.1
C-6–O-6–C-1–C-2
O-6–C-1–C-2–C-3
C-1–C-2–C-3–C-4
C-2–C-3–C-4–C-5
C-3–C-4–C-5–C-6
C-4–C-5–C-6–O-6
C-5–C-6–O-6–C-1
43.0
44.4
ꢁ90.9
67.7
ꢁ44.6
ꢁ50.8
72.9
ꢁ96.4
ꢁ33.6
ꢁ48.8
ꢁ46.1
ꢁ43.9
69.0
57.7
73.2
67.5
64.9
ꢁ95.9
ꢁ97.9
ꢁ99.1
ꢁ101.5
ꢁ102.2
a
Methyl 2,3,4,5-tetra-O-acetyl-b-
D
-alloseptanoside.14
Methyl a-L
-idoseptanoside.15
b
c
Methyl 2,3,4,5-tetra-O-acetyl-a-L
-idoseptanoside.16
CHCl3). Anal: Calcd for C14H24O5S: C, 55.25; H, 7.95. Found: C.
55.24; H, 8.03. 1H NMR (C6D6, 500 MHz) d 5.518 (d, 1H, J1,2
4.13 Hz, H-1), 4.694 (dd, 1H, J2,3 9.84 Hz, J3,4 7.25 Hz, H-3), 4.378
(dd, 1H, J5,6a 10.81 Hz, J6a,6b 12.87 Hz, H-6a), 4.311 (ddd, 1H, J4,5
6.98 Hz, J4.6b 0.92 Hz, H-4), 4.211 (ddd, 1H, J5,6b 3.40 Hz, H-5),
3.829 (dd, 1H, H-2), 3.581 (ddd, 1H, H-6b), 2.405 (m. 2H, CH2),
1.515 (s, 3H, CH3), 1.466 (s, 3H, CH3), 1.455 (s, 3H, CH3), 1.260 (s,
3H, CH3), 1.127 (t, 3H, JCH2CH3 7.42 Hz, CH3). Fractions 42–78 gave
the second product which crystallised from toluene/light petro-
leum as prisms of 5 (Rf 0.39) (2.95 g, 9.69 mmol, 23.2%), mp 66–
after which ZnCl2 (4.0 g) was added. After the mixture had been
stirred for 15 h, TLC (Et2O/light petroleum = 1:1) showed 6 (Rf
0.35) was still present. More EtSH (3 mL) was added and stirring
continued for 10 h at which time TLC showed the absence of 6.
The filtered reaction mixture was shaken successively with HCl
solution (0.2 M, 200 mL, 50 mL) and satd NaHCO3 solution, dried
over MgSO4 and concentrated. To a solution of the products in
Et2O (15 mL) was added light petroleum (21 mL) and this solution
was added to a column of silica gel (200 g) which was developed
using Et2O/light petroleum = 1:9, 50 mL fractions, until fraction
34 when the eluent was changed to Et2O/light petroleum = 1:4.
Using TLC to monitor elution, fractions 28–46 showed a single spot,
Rf 0.50. Concentration of these fractions gave a residue which crys-
tallised from light petroleum as prisms of 4 (2 crops, 2.88 g,
67 °C, ½a 2D3
ꢁ156.0 (c 1.19, CHCl3). Anal. Calcd for C14H24O5S: C,
ꢂ
55.25; H, 7.95. Found: C, 55.37; H, 8.06. 1H NMR (C6D6, 500 MHz)
d 4.842 (d, 1H, J1,2 8.91 Hz, H-1), 4.363 (dd, 1H, J2,3 9.05 Hz, J3,4
8.54 Hz, H-3), 4.002 (dd, 1H, J4,5 6.86 Hz, H-4), 3.976 (dd, 1H, J5,6a
2.56 Hz, J6a,6b 14.00 Hz, H-6a), 3.876 (ddd, 1H, J5,6b 5.30 Hz, H-5),
3.595 (dd, 1H, H-6b), 3.571 (dd, 1H, H-2), 2.619 (dq, 1H, JCHaCHb
12.82 Hz, JCH2CH3 7.42 Hz, Ha), 2.519 (dq, 1H, Hb), 1.573 (s, 3H,
CH3), 1.418 (s, 3H, CH3), 1.394 (s, 3H, CH3), 1.290 (s, 3H, CH3),
1.940 (t, 3H, CH3). Later fractions yielded 2 (3.20 g, 12.31 mmol,
29.4%), identified by acetylation to give the two acetates,2 1-O-
9.46 mmol, 31.4%), mp 101–102 °C, ½a D23
ꢂ
+209.2 (c 2.05, CHCl3),
the 1H NMR spectrum agreed with that given in 1.3. Fractions
50–64 showed a single spot, Rf 0.42. Concentration of these frac-
tions gave a syrupy product (2.94 g) which yielded prisms from
light petroleum of 5 (3 crops, 2.73 g, 8.97 mmol, 29.8%), mp 67–
68 °C, ½a 2D3
ꢂ
ꢁ152.9 (c 1.10, CHCl3), the 1H NMR spectrum agreed
acetyl-2,3:4,5-di-O-isopropylidene-
acetyl-2,3:4,5-di-O-isopropylidene-b-
CDCl3 NMR spectrum of 2 was consistent with published values.1
a
-
D
D
-glucoseptanose and 1-O-
with that given in 1.3.
-glucoseptanose. The 1H
1.6. Ethyl 1-thio-a-D-glucoseptanoside (9)
1.4. O-(2,3:4,5-Di-O-isopropylidene-b-
trichloroacetimidate (6)
D
-glucoseptanosyl)
To a solution of 4 (2.00 g, 6.57 mmol) in EtOH (40 mL) at 40 °C
was added 0.1 M HCl (20 mL). After the mixture had been kept at
40 °C for 16 h, TLC (EtOH/EtOAc = 1:19 showed the presence of sig-
nificant amounts of 4 (Rf 0.92) as well as lower Rf compounds. After
the addition of 0.1 M HCl (20 mL) the mixture was kept a further
54 h at 40 °C at which time TLC showed only a trace of 4. Concen-
tration of the neutralised (Amberlite IRA-400, HCO3ꢁ) hydrolysate
gave syrupy products (1.69 g). A solution of the syrup in a mixture
of EtOH and EtOAc (ca 1:2) yielded crystals (100 mg, 0.46 mmol,
A mixture of 2b (13.00 g, 49.94 mmol), K2CO3 (oven dried at
400 °C for 6 h, 30 g), CH2Cl2 (100 mL) and CCl3CN (10 mL) was stir-
red at 22 °C. After 7 h, CCl3CN (15 mL) was added and the mixture
stirred for a further 24 h. After the reaction mixture was shaken
with water (2 ꢀ 100 mL), the organic layer was filtered through a
short bed of silica gel, concentrated, and the residue dissolved in
EtOAc to give needle crystals (3 crops, 15.06 g, 37.37 mmol,
74.8%), TLC (EtOAc/light petroleum = 1:1) Rf 0.63. Recrystallisation
7.0%) of ethyl 1-thio-a-D-glucofuranoside (7), mp 153–155 °C,
lit.8,19 153 °C, Rf (EtOH/EtOAc = 1:19) 0.23, Rf of authentic 7,8
0.23. TLC of the filtrate showed the presence of low Rf material,
of a sample from EtOAc gave needles of 6, mp 130–134 °C, ½a D22
ꢂ
ꢁ113.5 (c 1.31, CHCl3); HRESIMS: Calcd for C14H20O6NCl3Na+:
426.0248; Found: 426.0260. 1H NMR (C6D6, 500 MHz) d 6.438 (d,
1H, J1,2 7.29 Hz, H-1), 4.325 (dd, 1H, J2,3 9.63 Hz, J3,4 8.53 Hz, H-
3), 3.981 (dd, 1H, J4,5 6.62 Hz, H-4), 3.863 (dd, 1H, H-2), 3.844
(dd, 1H, J5,6a 2.36 Hz, J6a,6b 14.28 Hz, H-6a), 3.811 (dd, 1H, J5,6b
3.77 Hz, H-6b), 3.724 (ddd, 1H, H-5), (H-6a and H-6b calculated18
as the AB portion of an ABX spectrum), 1.564 (s, 3H, CH3), 1.406
(s, 3H, CH3), 1.292 (s, 3H, CH3), 1.260 (s, 3H, CH3).
same Rf as D-glucose which was removed by chromatography over
silica gel (20 g) using EtOH/EtOAc = 1:4 as eluent. Concentration of
the eluate gave a syrupy residue (1.32 g) which yielded crystals
(0.43 g, 1.87 mmol, 28.5%) of 7 from EtOH/EtOAc. Addition of light
petroleum to the filtrate gave crystals (0.23 g, 1.026 mmol, 15.6%),
Rf 0.13. Recrystallisation from EtOH gave needle crystals of 9, mp
112–113 °C, ½a 2D5
ꢁ4.0 (c 4.15, H2O) , acetylation of which gave
ꢂ
the tetraacetate (10) (see below). Concentration of the filtrate gave
a syrupy residue (0.51 g)which was acetylated and the products
chromatographed over silica gel (25 g) using EtOAc/light petro-
leum = 1:3. Early fractions contained only the tetraacetate of 7
(80 mg, 0.204 mmol, 3.1%), Rf 0.18, rt 8.27. Intermediate fractions
yielded crystals (0.31 g, 0.79 mmol, 12.0%), Rf 0.16 which gave nee-
1.5. Ethyl 1-thio-2,3:4,5-di-O-isopropylidene-a-D-glucoseptano
side (4) and ethyl 1-thio-2,3:4,5-di-O-isopropylidene-b-D-gluco
septanoside (5) from 6
A mixture of 6 (12.15 g, 30.15 mmol), molecular sieves (Aldrich,
3 Å) (8 g), EtSH (4 mL), and CH2Cl2 (150 mL) was stirred for 1 h
dles of ethyl 1-thio-a-D-glucopyranoside tetraacetate (8) from
EtOH, mp 95–98 °C, lit.8 95 °C, ½a D23
ꢂ
+200.6 (c 1.74, CHCl3), lit.8

90
M. Bhadbhade et al. / Carbohydrate Research 353 (2012) 86–91
½
a 2D0
ꢂ
+194 (c 1.6, CHCl3), the CDCl3 1H NMR spectrum is consistent
Recrystallisation from EtOH gave needles of 14, Rf 0.30, mp 126–
with published values20,21 except for the assignments of H-3 and
H-4 (CDCl3, 500 MHz, d, 5.34, J2,3 10.25 Hz. J3,4 9.30 Hz, H-3; 5.02,
J4,5 10.07 Hz, H-4; confirmed by double irradiation), rt 7.95. The
last eluted material (160 mg, 0.408 mmol, 6.2%) (Rf 0.09) crystal-
lised from EtOH to give needles (0.11 g) of ethyl 1-thio-2,3,4,5-tet-
127 °C, ½a 2D0
ꢂ
ꢁ24.4 (c 1.55, CHCl3), rt 7.40. 1H NMR (CDCl3,
500 MHz) d 5.866 (d, 1H, J1,2 8.48 Hz, H-1), 5.476 (ddd, 1H, J2,3
6.71 Hz, J3,4 9.25 Hz, J3,5 0.39 Hz, H-3), 5.353 (dddd, 1H, J5,6a
5.02 Hz, J5,6b 4.12 Hz, H-5), 5.302 (dd, 1H, J4,5 1.96 Hz, H-4), 5.159
(dd, 1H, H-2), 4.114 (dd, 1H, J6a,6b 13.38 Hz, H-6a), 3.895 (dd, 1H,
H-6b), 2.138 (s, 3H, CH3), 2.064 (s, 3H, CH3), 2.040 (s, 3H, CH3),
2.039 (s, 3H, CH3), 2.022 (s, 3H, CH3), JC-1,H-1 168.5 Hz.
ra-O-acetyl-
a-
D
-glucoseptanoside (10), mp 109–110 °C, ½a D21
ꢁ16.4
ꢂ
(c 1.33, CHCl3), HRESIMS: Calcd for C16H24O9SNa+: 415.1033:
Found: 415.1036; rt 13.07. 1H NMR (CDCl3, 500 MHz) d 5.600
(dd, 1H, J2,3 9.70 Hz, J3,4 6.17 Hz, H-3), 5.388 (dd, 1H, J4,5 3.04 Hz,
H-4), 5.300 (dd, 1H, J1,2 3.06 Hz, H-2), 5.241 (ddd, 1H, J5,6a
3.00 Hz, J5,6b 2.56 Hz, H-5), 4.870 (d, 1H, H-1), 4.207 (dd, 1H,
J6a,6b 13.83 Hz, H-6a), 3.718 (dd, 1H, H-6b), 2.565 (m, 2H, CH2),
2.148 (s, 3H, CH3), 2.105 (s, 3H, CH3), 2.015 (s, 3H, CH3), 2.010 (s,
3H, CH3), 1.279 (t, 3H, JCH2CH3 7.44 Hz, CH3).
13C NMR (CDCl3, 125 MHz) d 169.61 (C@O), 169.51 (C@O),
169.34 (C@O), 169.19 (C@O), 168.84 (C@O), 93.36 (C-1), 72.63
(C-2), 70.53 (C-4), 70.25 C-5), 69.20 (C-3), 67.15 (C-6), 20.79
(CH3), 20.71 (CH3), 20.50 (CH3), 20.45 (CH3), 20.43 (CH3).
Fractions 48–74 yielded 1.22 g (3.125 mmol, 64.6%) of a colour-
less liquid, 13, ½a D20
ꢁ13.7 (c 1.48, CHCl3); HRESIMS: Calcd for
ꢂ
C
16H22O11Na+: 413.1054; Found: 413.1056, rt 11.10. 1H NMR
(CDCl3, 500 MHz) d 5.813 (d, 1H, J1,2 2.24 Hz, H-1), 5.536 (dd, 1H,
J2,3 5.61 Hz, J3,4 8.85 Hz, H-3), 5.309 (dd, 1H, J4,5 1.87 Hz, H-4),
5.291 (ddd, 1H, J5,6a 3.70 Hz, J5,6b 3.04 Hz, H-5), 5.283 (dd, 1H, H-
2), 4.027 (dd, 1H, J6a,6b 13.67 Hz, H-6a), 4.009 (dd, 1H, H-6b), H-
6a and H-6b analysed18 as the AB portion of an ABX spectrum,
2.135 (s, 3H, CH3), 2.120 (s, 3H, CH3), 2.080 (s, 3H, CH3), 2.037 (s,
3H, CH3), 2.021 (s, 3H, CH3), JC-1,H-1 161.9 Hz.
1.7. Ethyl 1-thio-b-D-glucoseptanoside (11)
To a solution of 5 (2.00 g, 6.57 mmol) in EtOH (20 mL) was
added 0.1 M HCl (20 mL). The hydrolysis solution was kept at
40 °C for 28 h after which time TLC (EtOH/EtOAc = 1:19) showed
the absence of 5. The neutralised (Amberlite IRA-400 resin in the
ꢁ
HCO3 form) reaction mixture was concentrated and the residue
1H NMR (C6D6, 500 MHz) d 6.061 (dd, 1H, J2,3 6.07 Hz, J3,4
9.61 Hz, H-3), 5.772 (d, 1H, J1,2 2.48 Hz, H-1), 5.525 (dd, 1H, H-2),
5.498 (dd, 1H, J4,5 1.94 Hz, H-4), 5.407 (ddd, 1H, J5,6a 3.15 Hz, J5,6b
2.65 Hz, H-5), 3.875 (dd, 1H, J6a,6b 13.81 Hz, H-6a), 3.705 (dd, 1H,
H-6b), 1.827 (s, 3H, CH3), 1.782 (s, 3H, CH3), 1.768 (s, 3H, CH3),
1.764 (s, 3H, CH3), 1.653 (s, 3H, CH3). 13C NMR (CDCl3, 125 MHz)
d 169.82 (C@O), 169.54 (C@O), 169.37 (C@O), 169.14 (C@O),
168.82 (C@O), 93.04 (C-1), 72.81 (C-2), 70.79 (C-5), 70.47 (C-4),
70.09 (C-3), 68.44 (C-6), 20.69 (CH3), 20.52 (CH3), 20.50 (CH3),
20.47 (CH3), 20.43 (CH3).
in a mixture of EtOH and EtOAc yielded needle crystals (1.09 g,
4.86 mmol, 74%). Recrystallisation from EtOH gave needles of 11,
mp 120–121 °C,
C8H16O5S: C, 42.84; H, 7.19. Found: C, 42.73; H 7.28.
½
a 2D3
ꢂ
ꢁ221.0 (c 1.30, H2O). Anal. Calcd for
1.8. Ethyl 1-thio-2,3,4,5-tetra-O-acetyl-b-D-glucoseptanoside (12)
A solution of 11 (0.95 g, 4.24 mmol) in pyridine (3 mL) and Ac2O
(6 mL) was kept at 22 °C for 16 h. The residue left on concentration
of the reaction mixture was dissolved in CH2Cl2 (50 mL) and this
solution was extracted successively with 1 M HCl (50 mL) and satd
NaHCO3 solution (50 mL). Concentration of the organic solution
after filtration through a short bed of silica gel gave a crystalline
residue which was recrystallised from EtOH to give needle crystals
1.10. Acid catalysed isomerisation of 13
A solution of 13 (1.04 g, 2.66 mmol) in a mixture of HOAc
(6 mL), Ac2O (14 mL), and conc H2SO4 (100 mL) was kept at 22 °C
for 30 min at which time the optical rotation of the mixture was
constant. After the addition of pyridine (1 mL) and water (6 mL)
the mixture was allowed to cool to 22 °C after which it was shaken
with water (150 mL) and CHCl3 (20 mL). The aqueous layer was ex-
tracted with CHCl3 (2 ꢀ 10 mL) and the combined CHCl3 solutions
washed with satd NaHCO3 solution, filtered through a short bed of
silica gel and concentrated to give a liquid product (1.18 g). A solu-
tion of product (0.93 g) in EtOH gave crystals (0.62 g, 1.59 mmol,
60%) of 14, mp 125–126 °C. A 1H NMR analysis of the liquid prod-
uct showed the ratio of 13:14 = 1:7.4.
(1.59 g, 4.05 mmol, 95.5%) of 12, mp 88–90 °C, ½a D20
ꢁ98.7 (c 1.35,
ꢂ
CHCl3), TLC: Rf 0.17 (Et2O/light petroleum = 1:1), HRESIMS: Calcd
for C16H24O9SNa+: 415.1033; Found: 415.1039; rt 8.66. 1H NMR
(CDCl3, 500 MHz) d 5.577 (dd, 1H, J2,3 7.42 Hz, J3,4 9.41 Hz, H-3),
5.351 (ddd, 1H, J4,5 2.55 Hz, J5,6a 3.69 Hz, J5,6b 3.91 Hz, H-5), 5.258
(dd, 1H, H-4),5.007 (dd, 1H, J1,2 8.50 Hz, H-2), 4.983 (d, 1H, H-1),
4.254 (dd, 1H, J6a,6b 13.68 Hz, H-6a), 3.708 (dd, 1H, H-6b), 2.672
(dq, 1H, JCHaHb 12.41 Hz, Ha), 2.597 (dq, 1H, Hb), 2.160 (s, 3H,
CH3), 2.062 (s, 3H, CH3), 2.033 (s, 3H, CH3), 2.028 (s, 3H, CH3),
1.266 (t, 3H, JCH2CH3 7.44 Hz, CH3); H-1 and H-2 analysed18 as the
AB portion of an ABX spectrum.
1.11. Crystallography
1.9. 1,2,3,4,5-Penta-O-acetyl-
a-D-glucoseptanose (13) and
1,2,3,4,5-penta-O-acetyl-b- -glucoseptanose (14)
D
1.11.1. Crystal data for 14
C16H22O11, M 390.34, orthorhombic, space group P212121, a
7.77509(16), b 9.895(2), c 24.758(5) Å, V 1890.9(7) Å3, measured
at 20 °C, Z 4. Crystal size, 0.11 ꢀ 0.04 ꢀ 0.02 mm. The number of
reflexions, measured at ꢁ153 °C, was 3212 considered observed
with I >2s(I) out of 3290 unique data. Final residuals, R[F2 >2s(F2),
wR(F2), S were 0.028, 0.077, 1.07.
To a solution of Hg(OAc)2 (2.5 g) in HOAc (30 mL) and Ac2O
(0.3 mL) at 85 °C was added 12 (1.90 g, 4.84 mmol). TLC (EtOAc/
light petroleum = 1:1) showed the presence of a trace of 12 (Rf
0.17) after 60 min when Hg(OAc)2 (0.5 g) was added and the mix-
ture kept at 85 °C for 30 min. The residue left on concentration of
the reaction mixture was shaken with CHCl3 (25 mL), water
(25 mL) and pyridine (2 mL). The CHCl3 solution was extracted suc-
cessively with H2SO4 (1 M), NaHCO3 (satd solution), filtered
through a short bed of silica gel and concentrated to give a liquid
residue (2.00 g). TLC (EtOAc/light petroleum = 1:1) showed the
presence of two components, Rf 0.30 and 0.26. Chromatography
of the products over silica gel (Merck 9387, 90 g) using Et2O/light
petroleum = 1:1 as eluent, collecting 20 mL fractions. Fractions
40–46 yielded 0.24 g (0.615 mmol, 12.7%) which crystallised.
1.11.2. Structure determination
Reflexion data were measured with the 3-BM1 Australian Syn-
chrotron diffractometer. Data collection followed ‘BLU-ICE’ 22 with
cell refinement and data reduction after ‘XDS’ 23 and the structure
solution and refinement used SHELXS-97.24 ORTEP-325 was used
for the structural diagram. The structure and atom numbering
scheme are shown in Figure 1.

M. Bhadbhade et al. / Carbohydrate Research 353 (2012) 86–91
4. Ng, C. J.; Stevens, J. D. Carbohydr. Res. 1996, 284, 241–248.
91
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The authors are grateful to Mrs. H. Stender of the University of
New South Wales High Field NMR Facility for the NMR spectra, to
Mr. Ahmad Mokhtari Fard for the high resolution mass spectra and
to the Australian Synchrotron facility for the X-ray data.
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Supplementary data
Complete crystallographic data for the structural analysis have
been deposited with the Cambridge Crystallographic Data Centre,
CCDC No. 862633. Copies of this information may be obtained free
of charge from the Director, Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge, CB2 1EZ, UK. (fax: +44-1223-
336033, e-mail: deposit@ccdc.cam.ac.uk or via: www.ccdc.cam.
ac.uk).
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.carres.2012.03.
011.
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