Stereoselective synthesis of a ketohexofuranose from an aldohexopyranose by a [6+1-1] strategy

Article abstract of DOI:10.1016/j.carres.2005.01.008

Ozonolysis of 2-acetoxymethyl-1,5-anhydro-3,4,6-tri-O-benzyl-2-deoxy-D- arabino-hex-1-enitol gave 1-O-acetyl-3,4,6-tri-O-benzyl-4-O-formyl-D-arabino- hex-2-ulose (5). Subsequent hydrolysis and acetylation of 5 provided 1,2-di-O-acetyl-3,4,6-tri-O-benzyl-D

Full text of DOI:10.1016/j.carres.2005.01.008

Carbohydrate
RESEARCH
Carbohydrate Research 340 (2005) 753–758
Note
Stereoselective synthesis of a ketohexofuranose from an
aldohexopyranose by a [6+1ꢀ1] strategy
Boga Sobhana Babu and Kalpattu Kuppuswamy Balasubramanian*
Department of Chemistry, Indian Institute of Technology, Madras, Chennai 600 036, India
Received 25 May 2004; received in revised form 28 December 2004; accepted 5 January 2005
´
This paper is dedicated to Professor G. Descotes, Universite Claude Bernard, Lyon I, France
Abstract—Ozonolysis of 2-acetoxymethyl-1,5-anhydro-3,4,6-tri-O-benzyl-2-deoxy-D-arabino-hex-1-enitol gave 1-O-acetyl-3,4,6-tri-
O-benzyl-4-O-formyl-D-arabino-hex-2-ulose (5). Subsequent hydrolysis and acetylation of 5 provided 1,2-di-O-acetyl-3,4,6-tri-O-
benzyl-D-fructofuranose 6 in excellent yield. This methodology allows specific deuteration at C-1 of a protected D-fructofuranose
derivative. This approach therefore could serve as [6+1ꢀ1] formulation for hexose series inter-conversion, that is, aldohexopyranose
to ketohexofuranose.
ꢀ 2005 Elsevier Ltd. All rights reserved.
Keywords: Glycal; Fructofuranose; Deuterated fructofuranose; Ozonolysis; Isotopic labelling; Ketohexofuranose; Aldohexopyranose
D-Fructofuranose is seldom available as a distinct iso-
meric entity because D-fructose rapidly mutarotates
through acyclic keto forms and can exist in as many as
five tautomers.3 In aqueous solution D-fructose exists
predominantly in the pyranose form with a very small
amount of the furanose form.4
tri-O-benzyl-2-deoxy-D-arabino-hex-1-enitol (4). Con-
ceptually, we introduced a one carbon unit at the C-2
position of the aldopyranose glucal, which in turn will
form the C-1 of the fructofuranose compound at the ex-
pense of one carbon loss from the ring during the course
of the reaction.
Synthesis of furanose oligosaccharides and their re-
lated analogues is important because they form the core
structure of bacterial cell walls and can act as either gly-
cosyl transferase substrates or inhibitors.5 Generally,
furanose oligosaccharides are synthesized using unpro-
tected reducing sugars in a controlled Fischer glycosyl-
ation reaction or via sugar dithioacetals.6 DÕSouza et al.,
have reported the synthesis of furanose oligosaccharides
by ozonolysis of protected pyranose glycals.7
As part of our ongoing research in glycal chemistry,8
we envisaged a synthetic route for the synthesis of highly
functionalized D-fructofuranose and its C-1 deuterated
counterpart from 2-acetoxymethyl-1,5-anhydro-3,4,6-
The synthesis of 4 was reported previously by our lab-
oratory1,2, starting from 1,5-anhydro-3,4,6-tri-O-benz-
yl-2-deoxy-D-arabino-hex-1-enitol (1) as outlined in
Scheme 1.
Glycal 4 was subjected to ozonolysis to give the keto-
formate 5 in excellent yield. Hydrolysis of 5 afforded the
diol 11, (Scheme 2) which was directly acetylated to give
1,2-di-O-acetyl-3,4,6-tri-O-benzyl-D-fructofuranose (6)
in good yield. The 1H NMR and 13C NMR spectra indi-
cate that this product is not a mixture of anomers but a
single anomer. Efforts were not undertaken to establish
the stereochemistry at the anomeric center. An impor-
tant point to note is that the furanose derivative 6 can-
not re-open and recyclize to give the pyranose form
*
Corresponding author. Tel.: +91 44 2451106; fax: +91 44 2452462;
e-mail: kkb@shasun.com
For preliminary communications, see in parts Refs. 1,2.
0008-6215/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2005.01.008

754
B. S. Babu, K. K. Balasubramanian / Carbohydrate Research 340 (2005) 753–758
1H NMR spectrum of 8 did not throwany light on this
OBn
O
OBn
O
OBn
O
point and it was not possible to determine whether it
was a single diastereomer. As a result, no useful infor-
mation about the diastereoselectivity could be obtained
BnO
BnO
b
a
c
BnO
BnO
BnO
BnO
H
R
CHO
HO
1
from the H NMR spectrum of 8. Fortunately, an an-
swer to this question was provided by careful analysis
R = H; 3
R = D; 7
1
2
1
of the H NMR spectra of 9 and 5 derived from the
ozonolysis of monodeuteroacetate glycal 8 and undeu-
terated acetate glycal 4, respectively.
OBn
O
OBn
OBn
O
O
OAc
BnO
BnO
BnO
BnO
e
O
d
CHO
OAc
H
1
The H NMR spectrum of 5 displayed a distinct AB
H
H
R
quartet pattern for the diastereotopic methylene protons
of –COCHaHb–OAc, with a doublet at d 4.78 ppm (J
18.1 Hz) and the other doublet at d 5.04 ppm (J
R
R
OBn
BnO
AcO
AcO
R = H; 4
R = D; 8
R = H; 5
R = D; 9
R = H; 6
R = D; 10
1
18.1 Hz). This AB quartet was clearly absent in the H
NMR spectrum of 9. The doublet seen at d 5.04 ppm
due to one of the diastereotopic proton of –CO-
CHaHb–OAc of 5 disappeared almost completely in
the case of 9. Also the doublet at d 4.78 ppm due to
the other geminal diastereotopic proton of 5 had col-
lapsed into a singlet, integrating nearly for one proton
Scheme 1. Reagents and conditions: (a) DMF, POCl3, 0 ꢁC to rt,
60%;1 (b) (R = H) NaBH4, MeOH, 90% or (R = D) LiAlD4, THF,
86%; (c) Ac2O, Et3N, cat DMAP, CH2Cl2, 92%;2 (d) O3, PPh3,
CH2Cl2, ꢀ78 ꢁC, 90%; (e) Na2CO3/MeOH, Ac2O, Et3N, cat DMAP,
CH2Cl2, 92%.
1
in the case of the monodeuteroacetate 9. From the H
NMR spectral data, it is evident that the lithium alumi-
num deuteride reduction of 2 exhibited high diastereo-
selectivity to the tune of 95:5, although the
configuration of the newchiral center could not be
determined from the available data.
Deuteroglycal 8 was successfully subjected to ozo-
nolysis to provide the deutero-keto-formate 9, which
was subsequently hydrolyzed, cyclized and acetylated to
give the C-1 deuterated furanose sugar viz., 1,2-di-O-
acetyl-3,4,6-tri-O-benzyl-10-deutero-D-fructofuranose 10
in 90% yield.
OBn
O
OBn
O
OBn
O
OAc
OAc
OH
a
b
O
OH
OBn
OBn
OBn
BnO
BnO
BnO
12
6
11
e
OBn
O
OBn
OBn
O
O
OH
BnO
BnO
CHO
BnO
BnO
O
H
OBn
BnO
The presence of the intact furanose ring in 6 was also
established by chemical means. Hydrolysis of 6 with
Na2CO3/MeOH gave the diol 11 (Scheme 2) which,
upon subsequent periodate oxidation, afforded 2,3,5-
tri-O-benzyl-D-arabinono-1,4-lactone 12 in 78% yield
with a rotation in agreement with the reported literature
value.9 Lactone 12 was also compared with an authentic
sample, prepared by an unambiguous route starting
with the ozonolysis of 1 to yield the formate aldehyde
13 in 86% yield (Scheme 2). Hydrolysis of 13 followed
by oxidation of the acetal 14 with PDC afforded 12 in
84% yield, which was identical in all respects with the
product obtained from degradation of the fructofuran-
ose compound 6.
In summary, we have developed a stereoselective syn-
thetic route to 1,2-di-O-acetyl-3,4,5-tri-O-benzyl-D-fruc-
tofuranose (6), which is useful for the introduction of
specific labelling at C-1 position as in 10. This approach
therefore could serve as [6 + 1 ꢀ 1] strategy for hexose
series interconversion, that is, aldohexopyranose to
ketohexofuranose. This methodology can be extended
to other glycals also, enabling the synthesis of other
ketohexofuranose sugars viz., D-tagatofuranose, D-sorbo-
furanose and D-psicofuranose.
14
1
13
Scheme 2. Reagents and conditions: (a) Na2CO3, MeOH, 90%; (b)
NaIO4, CH2Cl2, 78%; (c) O3, PPh3, ꢀ78 ꢁC, 86%; (d) Na2CO3, MeOH,
90%; (e) PDC, EtOAc, 84%.
because the C-6 hydroxyl group is protected as benzyl
ether in the furanose form (Scheme 1).
This synthetic route offers scope for specific deuterium
labelling in the furanose product at the C-1 position.
Reduction of 1,5-anhydro-3,4,6-tri-O-benzyl-2-deoxy-
2-formyl-D-arabino-hex-1-enitol (2) with LiAlD4 fur-
nished the alcohol 7, which was acetylated to give the
2-acetoxymonodeuteromethyl-1,5-anhydro-3,4,6-tri-O-
benzyl-2-deoxy-D-arabino-hex-1-enitol (8, Scheme 1). By
virtue of introduction of a deuterium atom, one could
expect the formation of diastereomers in the reduction
of aldehyde 2 by lithium aluminum deuteride. In the
1H NMR spectrum of 8, the signal due to the proton at-
tached to the newly generated chiral center bearing the
deuterium and acetoxy group overlapped with the sig-
nals of the benzylic protons in the region of d 4.43–
4.72 ppm and could not be identified distinctly. The

B. S. Babu, K. K. Balasubramanian / Carbohydrate Research 340 (2005) 753–758
755
1. Experimental
for 4 h followed by the addition of satd NaHCO3
(10 mL). The reaction mixture was then extracted with
ether (3 · 25 mL). The combined organic washings were
evaporated under diminished pressure and the product
was purified by column chromatography over silica gel
using 9:1 hexane–EtOAc as eluent to give 2 (0.32 g,
1.1. General
1.1.1. Procedure for the reduction of glycal 2 with NaBH4
or LiAlD4. To a soln of aldehyde 2 (1 mmol) in MeOH
(5 mL) [THF 5 mL in the case of LiAlD4] was added
NaBH4 or LiAlD4 (2 mmol) and the reaction mixture
was stirred at room temperature for 16 h (0 ꢁC to room
temperature for 6 h in the case of LiAlD4). The reaction
mixture was quenched with satd NH4Cl and extracted
with ether (3 · 25 mL). The combined organic washings
were evaporated under diminished pressure and the
products, 3 and 7 were subjected to acetylation without
purification.
60%) as a viscous liquid; Rf 0.4 (4:1 hexane–EtOAc);
25
D
½aꢂ +6.8 (c 0.34, CHCl3); IR (CCl4) m (cmꢀ1): 3080,
3020, 2860, 2725, 1665, 1620, 1450, 1365, 1270, 1200,
1060, 870, 700; 1H NMR (400 MHz): 9.39 (s, 1H,
CHO), 7.20–7.50 (m, 16HÕs, Ar–H, H-1), 4.40–4.70 (m,
8H, 3 · –OCH2Ph, H-6a, H-5), 3.50–3.90 (m, 3H, H-
6b, H-4, H-3); 13C NMR (100 MHz): d 190.40 (d,
CHO), 164.34 (d, C-1), 138.11 (s, Ar–C), 137.58 (s,
Ar–C), 137.17 (s, Ar–C), 128.55 (d, Ar–CH), 128.44
(d, Ar–CH), 128.35 (d, Ar–CH), 128.05 (d, Ar–CH),
127.89 (d, Ar–CH), 127.83 (d, Ar–CH), 127.76 (d, Ar–
CH), 127.71 (d, Ar–CH), 117.69 (s, C-2), 79.34 (d, C-
5), 73.36 (t), 72.43 (t), 71.63 (t), 71.29 (d), 68.39 (t),
65.22 (d). Anal. Calcd for C28H28O5: C, 75.67; H,
6.30. Found: C, 75.29, H, 6.05.
1.1.2. Procedure for the acetylation of 3, 7, 11. To com-
pound 3 or 7, 11 (1 mmol) in dry CH2Cl2 (10 mL) was
added Ac2O (2.5 mmol), Et3N (4 mmol) and DMAP
(5 mol % with respect to Et3N) and the reaction mixture
was stirred for 3 h at room temperature. The reaction
mixture was diluted with CH2Cl2 and washed succes-
sively with 2 N HCl (2 · 25 mL), satd NaHCO3 and
water. The organic layer was evaporated under dimin-
ished pressure, purified by column chromatography over
silica gel using 9:1 hexane–EtOAc as eluent to afford 1,2-
di-O-acetyl-3,4,6-tri-O-benzyl-D-fructofuranose 4, 8 and
6, respectively.
1.3. 1,5-Anhydro-3,4,6-tri-O-benzyl-2-deoxy-2-hydroxy-
methyl-D-arabino-hex-1-enitol (3)
From 2 (0.44 g); viscous liquid (0.34 g, 76%); Rf 0.2 (4:1
26
D
hexane–EtOAc); ½aꢂ +40.4 (c 0.2, CHCl3); IR (CHCl3)
m (cmꢀ1): 3410, 2916, 2881, 1651, 1590, 1486, 1454, 1397,
1362, 1321, 1261, 1220, 1202, 1163, 1089, 906, 655; H
1
1.1.3. General procedure for the ozonolysis of glycals 1, 4
and 8. Compound 1 or 4 or 8 (1 mmol) in dry CH2Cl2
(15 mL) was treated with O3 at ꢀ78 ꢁC until the soln be-
came light blue in colour (ꢁ45 min). Subsequently, PPh3
(2 mmol) was added and the reaction mixture was al-
lowed to warm up to room temperature and stirred for
3 h. The reaction mixture was diluted with CH2Cl2
(10 mL), concentrated under diminished pressure, puri-
fied by column chromatography over silica gel using
4:1 hexane–EtOAc, as eluent.
NMR (400 MHz): d 7.16–7.29 (m, 15HÕs, Ar–H), 6.44
(s, 1H, H-1), 4.47–4.70 (m, 6H, 3 · –OCH2Ph), 4.21
(m, 1H, H-5), 4.06 (dd, 1H, J6a,6b 12.2 Hz, J5,6a
4.4 Hz, H-6a), 3.92 (m, 2H, H-3, H-4), 3.66–3.78 (m,
3H, H-6b, –CH2OH), 2.30–2.40 (br s, 1H, –OH); 13C
NMR (100 MHz): d 143.12 (d, C-1), 137.79 (s, Ar–C),
137.70 (s, Ar–C), 137.61 (s, Ar–C), 128.37 (d, Ar–CH),
128.28 (d, Ar–CH), 128.23 (d, Ar–CH), 128.08 (d, Ar–
CH), 127.90 (d, Ar–CH), 127.80 (d, Ar–CH), 127.76
(d, Ar–CH), 127.70 (d, Ar–CH), 127.56 (d, Ar–CH),
127.53 (d, Ar–CH), 127.26 (d, Ar–CH), 126.73 (d, Ar–
CH), 117.76 (s, C-2), 75.95 (d, C-5), 74.80 (d, C-3),
73.65 (d, C-4), 73.72 (t), 72.80 (t), 72.46 (t), 67.79 (t),
61.38 (t). Anal. Calcd for C28H30O5: C, 75.33; H, 6.72.
Found: C, 75.12; H, 6.63.
1.1.4. General procedure for the hydrolysis of 5, 6, 9 and
13. To compound 5 or 6 or 9 or 13 (1 mmol) in MeOH
(15 mL) was added anhyd Na2CO3 (2 mmol). The reac-
tion mixture was stirred at room temperature for
30 min. The solids were removed by filtration and the fil-
trate was evaporated under diminished pressure. The
thick syrup was used further without purification.
1.4. 2-Acetoxymethyl-1,5-anhydro-3,4,6-tri-O-benzyl-2-
deoxy-D-arabino-hex-1-enitol (4)
1.2. 1,5-Anhydro-3,4,6-tri-O-benzyl-2-deoxy-2-C-formyl-
D-arabino-hex-1-enitol (2)
From 3 (0.25 g); viscous liquid (0.25 g, 92%); Rf 0.4 (4:1
29
D
hexane–EtOAc); ½aꢂ +48.1 (c 1, CHCl3); IR (CHCl3)
(cmꢀ1): 3038, 2912, 2880, 1738, 1593, 1491, 1452,
1392, 1363, 1324, 1257, 1222, 1206, 1161, 1088, 908,
To a soln of 1,5-anhydro-3,4,6-tri-O-benzyl-2-deoxy-D-
arabino-hex-1-enitol (1 (0.5 g, 1.2 mmol) in DMF
(2 mL) was added POCl3 (0.33 mL, 3.6 mmol) slowly
at 0 ꢁC. The reaction was stirred at room temperature
1
654; H NMR (400 MHz): d 7.24–7.33 (m, 15H, Ar–
H), 6.55 (s, 1H, H-1), 4.43–4.72 (m, 8H, 3 · –OCH2Ph,
–CH2OAc), 4.24–4.28 (m, 1H, H-5), 4.11 (d, 1H, J3,4

756
B. S. Babu, K. K. Balasubramanian / Carbohydrate Research 340 (2005) 753–758
4.88 Hz, H-3), 3.93 (dd, J4,5 6.35 Hz, J3,4 4.86 Hz, H-4),
3.79 (dd, 1H, J6a,6b 10.74 Hz, J5,6b 5.86 Hz, H-6b),
3.69 (dd, 1H, J6a,6b 10.74 Hz, J5,6a 3.9 Hz, H-6a), 1.94
(s, 3H, OCOCH3); 13C NMR (100 MHz): d 170.91 (s,
–OCOCH3), 145.45 (d, C-1), 138.03 (s, Ar–C), 137.85
(s, Ar–C), 128.42 (d, Ar–CH), 128.35 (d, Ar–CH),
128.32 (d, Ar–CH), 127.83 (d, Ar–CH), 127.78 (d, Ar–
CH), 127.71 (d, Ar–CH), 127.64 (d, Ar–CH), 107.98
(s, C-2), 76.36 (d, C-4), 73.87 (d, C-5), 73.50 (t), 73.35
(d), 72.91 (t), 72.33 (t), 67.94 (t), 62.55 (t), 20.96 (q,
–OCOCH3). Anal. Calcd for C30H32O6: C, 73.77; H,
6.55. Found: C, 73.67; H, 6.60.
73.22 (t, –OCH2Ar), 72.58 (t, –OCH2Ar), 71.89 (t,
–OCH2Ar), 69.22 (t, C-6), 62.51 (t, C-1), 21.68 (q,
–OCOCH3), 20.60 (q, –OCOCH3); MS: m/z 534 (M+),
461, 384, 313, 292, 278, 248, 235, 216, 175, 131, 105,
77, 65.
1.7. 2-Acetoxymonodeuteromethyl1,5-anhydro-3,4,6-tri-
O-benzyl-2-deoxy-D-arabino-hex-1-enitol (8)
From 7 (0.25 g); viscous liquid (0.22 g, 80%); Rf 0.4 (4:1
29
D
hexane–EtOAc); ½aꢂ +25.7 (c 1, CHCl3); IR (CHCl3)
(cmꢀ1): 2928, 2848, 1731, 1603, 1491, 1452, 1366,
1
1308, 1283, 1107, 992, 972, 908; H NMR (200 MHz):
d 7.22–7.55 (m, 15H, Ar–H), 6.46 (s, 1H, H-1), 4.38-
4.87 (m, 7H, 3 · –OCH2 Ph, –CHDOAc), 4.24–4.31
(m, 1H, H-5), 4.19 (d, 1H, J3,4 3.73 Hz, H-3), 3.93 (t,
J4,5 = J3,4 3.58 Hz, H-4), 3.80 (dd, 1H, J6a,6b 10.40 Hz,
J5,6b 7.16 Hz, H-6b), 3.69 (dd, 1H, J6a,6b 10.44 Hz,
J5,6a 4.97 Hz, H-6a), 1.94 (s, 3H, OCOCH3); 13C
NMR (50 MHz): d 170.88 (s, –OCOCH3), 144.86 (d,
C-1), 138.24 (s, Ar–C), 138.05 (s, Ar–C), 137.89 (s,
Ar–C), 128.32 (d, ArCH), 127.85 (d, ArCH), 127.81
(d, ArCH), 127.78 (d, ArCH), 127.73 (d, ArCH),
127.65 (d, ArCH), 127.62 (d, ArCH), 108.20 (s, C-2),
75.33 (d), 73.33 (t), 73.23 (t), 73.07 (t), 71.75 (d), 70.99
(d), 67.95 (t), 20.99 (q, –OCOCH3).
1.5. 1-O-Acetyl-3,4,6-tri-O-benzyl-4-O-formyl-D-
arabino-hex-2-ulose (5)
From 4 (0.25 g); viscous liquid (0.23 g, 90%); Rf 0.4 (4:1
29
hexane–EtOAc); ½aꢂ ꢀ4.2 (c 1.45, CHCl3); IR (CHCl3)
D
m (cmꢀ1): 3050, 2912, 2880, 1753, 1738, 1593, 1491, 1452,
1392, 1363, 1324, 1257, 1222, 1206, 1161, 1088, 908, 654;
1H NMR (400 MHz): d 7.83 (s, 1H, OCHO), 7.17–7.32
(m, 15HÕs, Ar–H), 5.23 (m, 1H, H-5), 5.04 (d, B of AB,
1H, J 18.06 Hz, H-1b), 4.78 (d, A of AB, 1H, J
18.06 Hz, H-1a), 4.41-4.68 (m, 6H, 3 · –OCH2Ph),
4.18 (dd, J4,5 7.81 Hz, J3,4 3.45 Hz, H-4), 4.12 (d, 1H,
J3,4 2.93 Hz, H-3), 3.80 (dd, 1H, J6a,6b 11.2 Hz, J5,6b
2.45 Hz, H-6b), 3.73 (dd, 1H, J6a,6b 11.2 Hz, J5,6a
4.4 Hz, H-6a), 2.15 (s, 3H, OCOCH3); 13C NMR
(50 MHz): d 205.17 (s, C@O), 170.20 (s, –OCOCH3),
159.79 (d, –OCHO), 136.95 (s, Ar–C), 137.44 (s, Ar–
C), 136.11 (s, Ar–C), 128.83 (d, Ar–CH), 128.38 (d,
Ar–CH), 128.24 (d, Ar–CH), 128.00 (d, Ar–CH),
127.81 (d, Ar–CH), 127.75 (d, Ar–CH), 83.10 (d, C-3),
77.99 (d, C-5), 74.83 (t, –OCH2Ar), 74.29 (t, –OCH2Ar),
73.28 (t, –OCH2Ar), 71.40 (d, C-4), 68.14 (t, C-1), 67.56
(t, C-6), 20.42 (q, –OCOCH3). MS: m/z 463
(M+ꢀCH2OAc), 277, 199, 183, 105, 91, 77, 65.
1.8. 1-O-Acetyl-1-deutero-3,4,6-tri-O-benzyl-4-O-formyl-
D-arabino-hex-2-ulose (9)
From 8 (0.2 g); viscous liquid (0.19 g, 90%); Rf 0.4 (4:1
29
hexane–EtOAc); ½aꢂ ꢀ13.2 (c 1.4, CHCl3); IR (CHCl3)
D
m (cmꢀ1): 2944, 2880, 1755, 1728, 1600, 1491, 1452, 1369,
1331, 1270, 1158, 1150, 992, 905; 1H NMR (200 MHz): d
7.83 (s, 1H, OCHO), 7.15–7.42 (m, 15H, Ar–H), 5.20–
5.27 (m, 1H, H-5), 4.76 (s, 1H, H-1a), 4.35–4.69 (m,
6H, 3 · –OCH2Ph), 4.18 (dd, J4,5 7.50 Hz, J3,4 3.01 Hz,
H-4), 4.12 (d, 1H, J3,4 3.05 Hz, H-3), 3.80 (dd, 1H,
J6a,6b 11.16 Hz, J5,6b 2.95 Hz, H-6b), 3.72 (dd, 1H,
J6a,6b 11.16 Hz, J5,6a 4.15 Hz, H-6a), 2.14 (s, 3H,
OCOCH3); 13C NMR (50 MHz): d 205.13 (s, C@O),
170.12 (s, –OCOCH3), 159.74 (d, –OCHO), 137.37 (s,
Ar–C), 136.89 (s, Ar–C), 136.05 (s, Ar–C), 128.54 (d,
Ar–CH), 128.29 (d, Ar–CH), 128.16 (d, Ar–CH),
127.91 (d, Ar–CH), 127.72 (d, Ar–CH), 127.67 (d,
Ar–CH), 126.90 (d, Ar–CH), 83.04 (d, C-3), 77.92 (d,
C-5), 74.73 (t, –OCH2Ar), 74.18 (t, –OCH2Ar), 73.18
(t, –OCH2Ar), 71.30 (d, C-4), [67.49,67.79, 68.22-C-1],
67.49 (t, C-6), 20.31 (q, –OCOCH3).
1.6. 1,2-Di-O-acetyl-3,4,6-tri-O-benzyl-D-fructofuranose
(6)
From 5 (0.2 g); viscous liquid (0.18 g, 92%); Rf 0.5 (1:1
29
hexane–EtOAc); ½aꢂ +20.6 (c 3.1, CHCl3); IR (CHCl3)
D
m (cmꢀ1): 2944, 2880. 1737, 1494, 1452, 1369, 1107, 998;
1H NMR (200 MHz): d 7.20–7.38 (m, 15H, Ar–H), 4.39-
4.74 (m, 10H, 3 · –OCH2Ph, H-5, H-3, H-1a, H-1b),
4.01 (dd, 1H, J4,5 5.42 Hz, J3,4 3.03 Hz, H-4), 3.64 (dd,
1H, J6a,6b 10.75 Hz, J5,6b 5.10 Hz, H-6b), 3.57 (dd, 1H,
J6a,6b 10.75 Hz, J5,6a 5.07 Hz, H-6a), 2.00 (s, 6H,
2 · OCOCH3); 13C NMR (50 MHz): d 170.06 (s,
–OCOCH3), 169.53 (s, –OCOCH3), 137.85 (s, Ar–C),
137.53 (s, Ar–C), 137.14 (s, Ar–C), 128.33 (d, Ar–CH),
128.20 (d, Ar–CH), 127.85 (d, Ar–CH), 127.78 (d, Ar–
CH), 127.68 (d, Ar–CH), 127.60 (d, Ar–CH), 109.38
(s, C-2), 85.79 (d, C-3), 82.77 (d, C-4), 82.68 (d, C-5),
1.9. 1,2-Di-O-acetyl-3,4,6-tri-O-benzyl-10-deutero-D-
fructofuranose (10)
From 9 (0.15 g); viscous liquid (0.14 g, 92%); Rf 0.5 (1:1
29
D
hexane–EtOAc); ½aꢂ +17.9 (c 4.9, CHCl3); IR (CHCl3)

B. S. Babu, K. K. Balasubramanian / Carbohydrate Research 340 (2005) 753–758
757
m (cmꢀ1): 2928, 2804, 1737, 1600, 1491, 1452, 1366, 1308,
1.11. (2S, 3R, 4R)-2,3,5-Tri-O-benzyl-4-O-formyl-
pentanal (13)
1276, 1107, 992, 940, 902, 807, 601; 1H NMR
(200 MHz): d 7.20–7.38 (m, 15H, Ar–H), 4.32–4.67 (m,
9H, 3 · –OCH2Ph, H-5, H-3, H-1), 4.00 (dd, 1H, J4,5
5.32 Hz, J3,4 2.97 Hz, H-4), 3.63 (dd, 1H, J6a,6b
10.95 Hz, J5,6b 5.34 Hz, H-6b), 3.57 (dd, 1H, J6a,6b
10.62 Hz, J5,6a 5.07 Hz, H-6a), 2.00 (s, 6H,
2 · OCOCH3); 13C NMR (50 MHz): d 170.11 (s,
–OCOCH3), 169.57 (s, –OCOCH3), 137.87 (s, Ar–CH),
137.55 (s, Ar–CH), 137.16 (s, Ar–C), 128.36 (d, Ar
–CH), 128.26 (d, Ar–CH), 128.23 (d, Ar–CH), 127.88
(d, Ar–CH), 127.81 (d, Ar–CH), 127.70 (d, Ar–CH),
127.62 (d, Ar–CH), 127.55 (d, Ar–CH), 109.37 (s, C-
2), 85.82 (d, C-3), 82.80 (d, C-4), 82.71 (d, C-5), 73.25
(t, –OCH2Ar), 72.60 (t, –OCH2Ar), 71.91 (t, –OCH2Ar),
69.24 (t, C-6), 21.70 (q, –OCOCH3), 20.62 (q,
–OCOCH3); MS: m/z 535 (M+), 475, 473, 384, 313,
278, 235, 221, 181, 105, 91, 77, 65.
From 1 (0.2 g, 0.48 mmol); viscous liquid (0.18 g, 86%);
29
Rf 0.4 (4:1 hexane–EtOAc); ½aꢂ +3.8 (c 1.45, CHCl3);
D
IR (CHCl3) m (cmꢀ1): 3072, 2926, 2880, 1724, 1600,
1491, 1449, 1363, 1158, 1100, 992, 905; 1H NMR
(400 MHz): d 9.62 (s, 1H, –CHO), 7.80 (s, 1H, –OCHO),
7.14–7.32 (m, 15HÕs, Ar–H), 5.26 (m, 1H, H-4), 4.41–4.73
(m, 6H, 3 · –OCH2Ph), 4.18 (dd, J3,4 7.5 Hz, J2,3 3.3 Hz,
H-3), 3.86 (d, 1H, J2,3 2.1 Hz, H-2), 3.68–3.78 (m, 2H, H-
5a, H-5b); 13C NMR (50 MHz): d 202.48 (d, –CHO),
159.57 (d, –OCHO), 137.50 (s, Ar–C), 137.01 (s, Ar–
C), 136.46 (s, Ar–C), 128.68 (d, Ar–CH), 128.58 (d,
Ar–CH), 128.41 (d, Ar–CH), 128.38 (d, Ar
–CH), 128.33 (d, Ar–CH), 128.11 (d, Ar–CH), 128.01
(d, Ar–CH), 127.78 (d, Ar–CH), 127.73 (d, Ar–CH),
82.37 (d), 76.57 (d), 74.22 (t, –OCH2Ar), 73.38 (t,
–OCH2Ar), 73.27 (t, –OCH2Ar), 71.22 (d), 67.61 (t, C-5).
1.10. 2,3,5-Tri-O-benzyl-D-arabinono-1,4-lactone (12)
Acknowledgements
From 11: To the diol 11 (0.1 g, 0.22 mmol) in CH2Cl2
(3 mL) was added NaIO4 (0.094 g, 0.44 mmol) followed
by satd NaHCO3 (0.1 mL). The reaction mixture was
stirred at room temperature for 1.5 h. Work-up involves
filtration of the solid material by Celite and washings
with CH2Cl2 (2 · 25 mL). The combined CH2Cl2 filtrate
were evaporated under diminished pressure and the
product was purified by column chromatography over
silica gel using 4:1 hexane–EtOAc as eluent to give 12
(0.072 g, 78%).
From 14: To the acetal 14 (0.1 g, 0.23 mmol) in
EtOAc (5 mL) containing AcOH (0.05 mL) was added
finely ground PDC (0.98 g, 0.26 mmol). The reaction
mixture was stirred at room temperature for 2 h.
Work-up involves filtration of the solid material
through a sintered-glass funnel and the filtrate was evap-
orated under diminished pressure and purified by col-
umn chromatography over silica gel using 4:1 hexane–
The authors thank the Department of Science and Tech-
nology, India, for financial support, and RSIC, IIT,
Chennai, SPIC Science Foundation, Chennai and Sun
Pharmaceutical Advanced Research Center, Baroda
for spectral data. One of us (S.B.B.) also thanks Dr.
K. Vijayakumaran, Director, R&D, Chimique Labora-
tories, Chennai for useful discussions.
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D
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