Carbohydrate Research 347 (2012) 9–15
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Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Preparation and properties of the aldohexofuranose pentaacetates
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
Article history:
Received 9 August 2011
Received in revised form 9 September 2011
Accepted 13 September 2011
Available online 21 September 2011
a b s t r a c t
The preparation of one isomer of each of the 16 enantiomeric pairs of the aldohexofuranose pentaacetates
is described together with 1H and 13C NMR data. Eight of the isomers have been obtained crystalline.
Equilibrium values for the anomeric pairs have been determined.
Ó 2011 Elsevier Ltd. All rights reserved.
Dedicated to Professor Stephen J. Angyal on
the occasion of his 97th birthday
Keywords:
Aldohexofuranose acetates
NMR spectroscopy
Anomer equilibria
1. Introduction
2. Results and discussion
In contrast to hexopyranose pentaacetates, for which there is
a voluminous literature, acetates of the furanose forms of aldohexoses have been little studied. The earliest preparations1 involved high-temperature acetylation of D-galactose that yielded
b-D-galactofuranose pentaacetate as well as the two pyranose
isomers. Furanose acetates may also be prepared by acetolysis
of acetylated glycofuranosides, a procedure used by Guthrie
and Smith in their preparation2 of b-D-ribofuranose tetraacetate
and used later for the preparation of eight aldopentofuranose
tetraacetates3 and more recently for the preparation of furanose
pentaacetates of D-galactose, D-glucose and D-mannose.4
In earlier work aimed at the preparation of the all-important
b-D-ribofuranose esters, selectively protected derivatives in the
furanose form were employed.5,6 High temperature acetylation7,8
of D-ribose also provided a satisfactory large-scale preparation of
the required furanose tetraacetate. In other procedures for the
preparation of furanose 1-acetates, esterified 1-thioglycofuranosides have been converted directly into 1-acetates using mercury(II) acetate.9 We have made use of all of the methods
described above for this work. In this paper we describe the
preparation and properties of furanose pentaacetates of eight
aldohexoses, in the D-series except for L-idose (Fig. 1).
2.1. Preparation of compounds
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0008-6215/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2011.09.009
The a- and b-D-allofuranose pentaacetates 1a and 1b were prepared by hydrolysis10 of 3,5,6-tri-O-acetyl-1,2-O-isopropylidenea-D-allofuranose (9)11 followed by acetylation (Scheme 1). Column
chromatography over silica gel separated the two liquid acetates.
High-temperature acetylation of D-galactose was used to prepare1 b-D-galactofuranose pentaacetate (3b) and acetolysis of 3b
gave a mixture of anomers from which a-D-galactofuranose pentaacetate (3a) was isolated by crystallization.12 Improved methods
for the preparation of 3b include the acetolysis of acetylated alkyl
4,13
D-galactofuranosides,
bis-3-methyl-2-butyl-borane reduction of
14
D-galactono-1,4-lactone tetraacetate followed by acetylation
and
acetolysis of D-galactose diethyl dithioacetal.15
Whereas b-D-galactopyranose has only one axial hydroxy
group, b-D-altropyranose has two destabilizing axial hydroxyl
groups, and it was reasonable to expect that high-temperature
acetylation of D-altrose would give rise to a mixture of acetates
containing a significant proportion of furanoses. This view is
supported by an NMR analysis of pyridine solutions of the
reducing sugars that showed a much higher proportion of furanose forms for D-altrose than for D-galactose.16 This proved to
be correct, and the crystalline a- and b-D-altrofuranose pentaacetates 2a and 2b were isolated by chromatography over silica gel.
The L-isomer of 2a has been prepared by the acetolysis of 3,5,6tri-O-acetyl-1,2-O-isopropylidene-b-L-altrofuranose.17
10
J. D. Stevens / Carbohydrate Research 347 (2012) 9–15
Figure 1. The 16 hexofuranose pentaacetates.
AcO
CH2 OAc
AcO
O
H
CF3 CO 2H
O
OAc
CH 2OAc
OH
Ac 2 O, Pyr
1α + 1β
H 2O
CMe 2
O
O
H
OAc
OH
9
Scheme 1.
AcO
H
CH2 OAc
AcO
O
CF3 CO 2 H
OAc
O
O
OH
OAc
CMe 2
Ac 2 O, Pyr
4α + 4β
OH
AcO
+
O
H
H 2O
10
4α
CH 2 OAc
CH2 OAc
O
CF3 CO 2H, H 2O
H
OH
OAc
OAc
Scheme 2.
Following the procedure used for the preparation of 1a and 1b,
a mixture of a- and b-D-glucofuranose pentaacetates 4a and 4b
was prepared from 3,5,6-tri-O-acetyl-1,2-O-isopropylidene-a-Dglucofuranose (10) (Scheme 2). This procedure had been used earlier18 for the preparation of the mixed anomers, whose 13C NMR
spectra are consistent with Table 4 values. No detectable separation of these isomers was achieved by thin-layer chromatography
(TLC) using a variety of developing solvents. It is well known that
sugar acetates in which the acetoxy groups at C-1 and C-2 are trans
are significantly more reactive than the cis isomers, due to the
greater possibility of anchimeric assistance, towards a variety of
reagents. The enhanced reactivity is typified by the greater rate
of reaction of b-D-glucopyranose pentaacetate compared with the
a-isomer towards ethanethiol.19 In a fusion synthesis of a nucleoside analogue in which the 1,2-trans isomer of a furanose derivative reacted, the corresponding 1,2-cis isomer was recovered in
high yield.20 Likewise, treatment of the 1,2-trans isomer, b-D-glucopyranose pentaacetate, with aqueous trifluoroacetic acid resulted in the solvolysis of the C-1 acetoxy group, whereas the
corresponding 1,2-cis isomer was recovered.21 We have made
11
J. D. Stevens / Carbohydrate Research 347 (2012) 9–15
use of this differential reactivity to convert 1,2-trans isomer 4b in
the mixture of anomers mentioned above into a product readily
separated from 4a by chromatography. Initially, this was done
by treating the mixture with ethanethiol and zinc chloride. This
procedure resulted in the isolation of 4a as a crystalline product.22
A less odorous procedure used the trifluoroacetolysis reaction21
that produced the readily separated 4a and 2,3,5,6-tetra-O-acetyl-D-glucofuranose. Attempts to crystallize 4a from solutions of
the mixed anomers were unsuccessful. In an earlier preparation,23
4a was obtained as an oil whose 1H NMR spectrum was in good
agreement with values reported here.
Preparation of 1,2-trans isomer 4b contaminated with a trace
of 4a was effected by the treatment of ethyl 1-thio-a-D-glucofuranoside tetraacetate (11) with mercury(II) acetate in acetic acid.9
NMR analysis of the liquid product gave the percentage of 4a
present from which the optical rotation of the liquid 4b was
calculated.
Acetolysis of methyl b-D-gulofuranoside tetraacetate (12) gave a
mixture of the D-gulofuranose esters 5a and 5b, which were separated by column chromatography to give crystalline 5a and, initially, 5b as a liquid. It is a common observation that attempts to
induce crystallization from a solution of a compound by addition
of a crystal fragment of a different compound is generally unsuccessful although the use of a structurally related compound may
be effective.24 In view of the excellent crystallizing properties of
12 and the close structural similarity of 12 and 5b, we added a minute fragment of a crystal of 12 to the liquid pentaacetate, which resulted in rapid crystallization.
Hydrolysis of 3,5,6-tri-O-acetyl-1,2-O-isopropylidene-b-L-idofuranose (13)25,26 using aqueous trifluoroacetic acid,10 followed
by acetylation, gave a mixture of L-idofuranose pentaacetates
which yielded the two isomers 6a and 6b as liquid compounds
by column chromatography.
Acetolysis of methyl a-D-mannofuranoside tetracetate (14)27
yielded a mixture of the two D-mannofuranose pentaacetates that
was resolved to give the known crystalline a-isomer, 7a,28 and bisomer 7b as a liquid. The structure of 7a has been placed beyond
any doubt by an X-ray diffraction study.4
In view of the fact that D-talose and L-ribose have the same relative configurations at C-2, C-3 and C-4 and that high temperature
acetylation of D-ribose gives a high yield of b-furanose tetraacetate,7,8 we treated a hot solution of D-talose in pyridine with acetic
anhydride. Chromatography of the products gave 8a as a liquid
product, which on acetolysis yielded a mixture of two anomers
8a and 8b that were readily separated by chromatography. Preparation of 8a by the low-temperature acetylation of D-talose has
been reported.29
2.2. NMR spectra
Of the 16 pentaacetates reported here, only 8a gave a 1H CDCl3
solution NMR spectrum that showed strong coupling between H-2
and H-3. For that compound we used a C6D6 solution to give the 1H
NMR values. 1H NMR chemical shifts and spin-coupling constants
are reported in Tables 1 and 2. As noted for aldopentofuranose acetates,3 H-1 of cis-1,2 compounds occurs at higher frequency than
H-1 of trans-1,2 compounds. This difference is replicated for pentaacetates reported here. We have noted earlier30 the clear-cut difference for the J1,2 values for the anomeric pairs of furanose
esters. We see from Table 2 that for ring hydrogen atoms, any vicinal couplings (including J1,2) less than 3.9 Hz requires the hydrogen atoms to be trans. Vicinal J’s for cis-hydrogen atoms vary
from 4.19 to 8.0 Hz and for trans hydrogen atoms from 0.8 to
8.31 Hz. It is notable that for these furanose compounds, 4- and
5-bond couplings are common.
Furanose ring conformations of methyl hexofuranosides have
been studied in detail.31 A comparison of the spin coupling constants for methyl furanosides in D2O with those given in Table 2
shows a remarkable similarly in most cases. Exceptions to this
are the values for the two L-ido anomers which show significant
differences for the coupling constants for methyl glycosides compared with furanose acetates. The conclusions drawn31 on the ring
and side chain conformations are therefore equally applicable to
furanose acetates presented here. We note that for pairs of furanose acetates epimeric at C-5, ring and side chain coupling constants for the pairs D-allo, L-talo; D-altro, L-galacto and D-manno,
L-gulo are in good agreement for both 1,2-cis and 1,2-trans isomers.
This indicates that for these six C-5 epimeric pairs, the ring conformations are little changed by the change of configuration at C-5.
This however, is not the case for D-gluco, L-ido pairs. For the b-Lido isomer, the large value of J2,3 points to the 2T3(L) conformation
of the furanose ring. The small value of J4,5 is consistent with a zigzag conformation of the side chain. The very large value for J3,4,
involving cis-hydrogen atoms on the five-membered ring, is noteworthy. For the a-L-ido isomer, the smaller value of J2,3 is consistent with the 3T2(L) conformation with the J4,5 value pointing to a
sickle conformation of the side chain as noted earlier.31
We propose that the significantly different conformations of
the two L-ido compounds may account for the fact that in an
equilibrium solution, 1,2-cis isomer preponderates in stark contrast to the seven other anomeric pairs. Table 3 gives the ratios
of 1,2-cis to 1,2-trans isomers as determined in acetolysis
solutions.
13
C NMR chemical shifts are given in Table 4, together with JC3,32–34
carbon atoms
1,H-1 spin coupling constants. As noted earlier,
Table 1
1
H NMR chemical shifts (ppm)
Hexofuranose pentaacetates
H-1
H-2
H-3
H-4
H-5
H-6a
H-6b
OAc
OAc
OAc
OAc
OAc
a-D-allo
6.392
6.177
6.198
6.395
6.325
6.186
6.455
6.123
6.306
6.240
6.087
6.431
6.237
6.349
6.362
6.427
5.184
5.327
5.139
5.307
5.321
5.185
5.210
5.114
5.298
5.393
5.278
5.362
5.379
5.268
5.502
5.239
5.500
5.511
5.227
5.536
5.550
5.091
5.546
5.422
5.634
5.616
5.364
5.539
5.615
6.651
5.577
5.175
4.403
4.321
4.312
4.151
4.194
4.367
4.505
4.551
4.371
4.532
4.585
4.643
4.487
4.424
4.425
4.470
5.205
5.199
5.253
5.247
5.272
5.359
5.231
5.288
5.470
5.341
5.335
5.094
5.300
5.324
5.412
5.313
4.398
4.431
4.459
4.484
4.301
4.337
4.570
4.617
4.351
4.369
4.301
4.256
4.590
4.616
4.289
4.313
4.138
4.062
4.120
4.052
4.149
4.218
4.104
4.084
3.946
4.049
4.045
4.139
4.099
4.110
4.191
4.184
2.137
2.129
2.145
2.132
2.127
2.135
2.110
2.135
2.175
2.118
2.131
2.146
2.111
2.119
1.726
2.140
2.119
2.113
2.132
2.109
2.120
2.132
2.089
2.122
2.114
2.108
2.130
2.100
2.085
2.091
1.678
2.124
2.107
2.081
2.122
2.079
2.093
2.122
2.086
2.090
2.106
2.101
2.119
2.080
2.080
2.071
1.661
2.121
2.062
2.075
2.101
2.078
2.086
2.115
2.065
2.073
2.056
2.097
2.118
2.069
2.065
2.045
1.640
2.065
2.058
2.068
2.066
2.067
2.056
2.055
2.018
2.009
2.040
2.053
2.050
2.035
2.014
2.005
1.616
2.064
b-D-allo
a-D-altro
b-D-altro
a-D-galacto
b-D-galacto
a-D-gluco
b-D-gluco
a-D-gulo
b-D-gulo
a-L-ido
b-L-ido
a-D-manno
b-D-manno
a-D-talo (C6D6)
b-D-talo
12
J. D. Stevens / Carbohydrate Research 347 (2012) 9–15
Table 2
1
H NMR coupling constants (Hz)
Hexofuranose pentaacetates
J1,2
J2,3
J3,4
J4,5
J5,6a
J5,6b
J6a,6b
a-D-allo
4.56
1.23
0.52
4.66
4.67
0.79
4.58
0.46
4.83
2.43
1.45
4.56
6.75
4.97
1.23
6.24
7.29
2.04
2.93
0.89
5.43
5.44
3.91
8.31
2.77
6.42
3.82
4.87
6.31
5.43
5.00
4.82
5.00
5.40
6.21
8.00
4.23
6.12
6.80
8.43
6.32
4.07
8.51
9.38
8.55
6.21
6.20
1.97
4.31
3.62
3.29
2.98
4.13
4.10
2.68
2.49
3.23
3.67
3.92
5.02
5.20
5.81
5.83
5.59
6.03
6.91
5.72
5.12
5.75
6.28
6.63
7.65
12.18
12.16
12.23
12.23
12.12
12.00
12.26
12.34
12.27
12.13
11.96
11.54
3.35
4.82
0.87
4.58
5.02
5.38
4.75
6.57
4.19
4.72
7.59
3.02
8.68
9.45
5.19
3.13
2.50
2.40
4.30
4.86
5.66
4.82
6.27
6.72
12.34
12.41
12.03
11.77
b-D-allo
a-D-altro
b-D-altro
a-D-galacto
b-D-galacto
a-D-gluco
b-D-gluco
a-D-gulo
b-D-gulo
a-L-ido
b-L-ido
a-D-manno
b-D-manno
a-D-talo (C6D6)
b-D-talo
1,2-cis:1,2-trans
1.00:3.33
D-Altrofuranose
1.00:3.51
D-Galactofuranose
1.00:3.87
D-Glucofuranose
1.00:2.27
D-Gulofuranose
1.00:4.15
L-Idofuranose
1.00:0.58
D-Mannofuranose
1.00:3.38
D-Talofuranose
1.00:3.16
0.49
0.67
0.54
0.59
0.69
0.61
0.58
0.52
0.54
0.52
0.84
J1,4
J2,4
0.42
0.35
0.44
0.44
0.48
Other
J1,5, 0.38
J1,5, 0.42
0.50
0.51
0.50
0.50
0.52
0.52
0.53
0.55
0.49
0.43
0.56
0.40
0.42
0.46
0.42
0.52
0.59
J1,5, 0.32
J3,5, 0.36
J1,5, 0.42
Similarly, 1b gave rise to only 1a and 1b. Thus no epimerisation occurred. These results, which are in direct contrast to those reported,41 are similar to the report of the treatment of 7a plus
boric acid with an acetolysis solution: no epimerisation was observed.44 Clearly the mechanism for epimerisation given earlier39
is inconsistent with the present results, and more detailed studies
on the acetolysis reaction that leads to inversion of configuration at
C-2 are required to elucidate the scope and mechanism of this
reaction.
Table 3
Equilibrium values for aldohexofuranose pentaacetates
D-Allofuranose
J1,3
3. Experimental
3.1. General methods
bearing cis-vicinal groups occur at lower frequency (i.e., upfield)
than those bearing trans-vicinal groups. This holds for the four-ring
carbon atoms for all furanose acetates reported here. In contrast to
pyranose compounds for which the JC-1,H-1 values may be used to
determine axial or equatorial orientation of C-1 substituents,35,36
these values cannot be used to assign anomeric configurations
for furanose compounds, as noted earlier.37
With the various aldohexofuranose acetates in hand, we examined the products from the treatment of 8a under the acetolysis
conditions that lead to inversion of configuration at C-2 for a variety of furanose compounds.38–43 Analysis of the products from 8a
by 1H NMR spectroscopy showed only two compounds 8a and 8b.
Optical rotations were determined using a Perkin–Elmer 141
automatic polarimeter. Melting points were determined on a Reichert hot-stage microscope and are uncorrected. NMR spectra were
recorded using a Bruker AM-500 or Bruker DMX-500 spectrometer.
1
H NMR spectra were recorded for 0.1 M solutions using TMS as
the internal reference. Spectra were resolution enhanced by application of an exponential multiplier to the FID followed by a shifted
sine-bell multiplier and three-fold zero fill prior to Fourier transformation. 13C NMR spectra were recorded at 125 MHz and assignments were made using one-bond 13C/1H 2D NMR spectroscopy
using standard Bruker programmes. As a result of H-2 and H-3
being strongly coupled in the CHCl3 solution spectrum of 7a, an
Table 4
13
C NMR chemical shifts (ppm)
Hexofuranose
pentaacetates
C-1
C-2
C-3
C-4
C-5
C-6
a-D-allo
93.58
98.38
99.34
94.03
93.14
99.17
93.90
98.97
92.58
98.20
98.23
92.19
98.37
93.10
97.75
93.92
69.91
74.41
80.37
75.78
75.37
80.65
76.44
79.68
70.62
75.08
79.69
74.02
75.45
70.52
73.98
69.74
68.92
71.06
76.15
75.18
73.49
76.36
74.02
72.99
68.61
70.54
74.30
73.16
70.33
68.10
70.02
69.84
82.69
80.15
83.26
79.75
79.15
82.18
76.67
79.64
77.77
77.58
79.34
75.21
77.39
77.28
79.33
81.95
70.28
71.10
69.98
71.09
70.39
69.30
67.88
68.33
69.94
69.01
69.16
68.10
68.00
68.55
69.74
69.75
62.00
62.16
62.27
62.30
62.14
62.59
62.74
63.03
62.53
62.63
62.57
62.29
62.64
62.57
62.37
62.03
b-D-allo
a-D-altro
b-D-altro
a-D-galacto
b-D-galacto
a-D-gluco
b-D-gluco
a-D-gulo
b-D-gulo
a-L-ido
b-L-ido
a-D-manno
b-D-manno
a-D-talo
b-D-talo
Acetyl methyl carbons
Acetyl carbonyl carbons
JC-1,H1
20.98
20.97
20.99
20.98
21.03
20.99
20.81
20.99
21.09
21.01
21.01
21.08
21.01
21.08
20.99
21.01
20.84
20.79
20.84
20.82
20.78
20.81
20.75
20.73
20.92
20.97
20.97
20.93
20.74
20.73
20.74
20.79
20.60
20.68
20.74
20.79
20.67
20.69
20.72
20.71
20.62
20.66
20.64
20.66
20.73
20.72
20.67
20.69
20.60
20.46
20.70
20.69
20.63
20.66
20.63
20.59
20.53
20.42
20.64
20.52
20.35
20.43
20.49
20.56
20.25
20.43
20.65
20.41
20.46
20.63
20.35
20.58
20.23
20.41
20.63
20.44
20.33
20.25
20.37
20.27
170.37
170.47
170.49
170.49
170.39
170.55
170.56
170.55
170.37
170.46
170.43
170.59
170.57
170.57
170.46
170.48
169.80
169.77
170.08
170.04
169.91
170.03
169.62
169.66
170.06
169.93
169.90
170.41
169.55
169.68
169.93
169.93
169.76
169.38
169.41
169.73
169.86
169.79
169.58
169.29
169.75
169.73
169.78
169.82
169.55
169.61
169.52
169.88
169.56
169.36
169.34
169.59
169.84
169.43
169.28
169.11
169.73
169.27
169.41
169.80
169.42
169.60
169.40
169.54
169.22
168.93
169.08
169.12
169.30
169.06
168.94
168.99
169.16
169.26
169.27
169.29
169.31
169.25
168.88
169.31
182.3
182.6
181.5
183.6
183.8
181.3
181.5
180.9
182.9
181.5
180.6
184.5
180.9
183.2
182.8
182.1
J. D. Stevens / Carbohydrate Research 347 (2012) 9–15
HSQC spectrum, with no decoupling in the 1H direction, was used
to allow assignment of C-2 and C-3 in the 13C NMR CDCl3 solution
spectrum. Assignment was unambiguous as a result of the large
difference in the values of J1,2 and J3,4. JC-1,H-1 spin coupling constants were determined directly from the 1H NMR spectra. Column
chromatography was performed using E. Merck silica gel 7736,
generally using a height of packed column ca. 15 times its diameter. Thin-layer chromatography (TLC) used silica gel supported on
glass slides (Analtech). Light petroleum refers to the fraction boiling 60–80 °C. Gas chromatography was carried out on a custom
built instrument fitted with a flame ionisation detector and a
quartz tube lined injection block. Coiled 240 cm glass columns
packed with 3% SP2401 on Chromosorb W (AW-DMCS) (column
a) and with 3% DEGA (stabilised, Analabs) on Chromosorb W
(AW-DMCS) (column b). Oven temperature was 200 °C for both
columns using N2 carrier gas. Retention times are in minutes and
recorded as rta and rtb for the two columns. High-resolution mass
spectra were recorded using a Bruker Apex II 7T FT/ICR spectrometer equipped with an Analytica ESI source operating in positiveion mode. The digital resolution was 0.00252 m/z.
3.2. 1,2,3,5,6-Penta-O-acetyl-a-D-allofuranose (1a) and 1,2,3,5,6penta-O-acetyl-b-D-allofuranose (1b)
To a mixture of trifluoroacetic acid (9 mL) and H2O (1 mL) was
added 3,5,6-tri-O-acetyl-1,2-O-isopropylidene-a-D-allofuranose (9)11
11
[mp 81–83 °C, lit.11 79–81 °C; ½a25
½a20
D +121 (c 1.38, CHCl3), lit.
D
1
+111 (c 1.8, CHCl3); for H NMR data, see Supplementary data] which
was kept at 25 °C for 1 h. To the residue left after the mixture was
concentrated was added Ac2O (6 mL) and pyridine (2 mL). This solution was kept at 25 °C for 1 h then warmed to 50 °C for 1 h, after
which time it was concentrated and the residue was dissolved in
abs EtOH. After 1 h the mixture was concentrated and a CHCl3 solution of the residue was extracted successively with H2SO4 (3 M) and
satd NaHCO3 solution, filtered through a short bed of silica gel and
concentrated, and finally heated to 60 °C at 0.1 Torr. Chromatography of the products over silica gel (40 g) in a mixture of 1:2
EtOAc–light petroleum, and collecting 20-mL fractions monitored
by TLC (silica gel, 1:2 EtOAc–light petroleum) gave products in fractions 17–21 (Rf 0.22) and 25–28 (Rf 0.15). Concentration of fractions
17–21, finally at 60 °C and 0.1 Torr gave 1b as a colourless oil (0.50 g,
+
44%): ½a25
D 16.2 (c, 1.11, CHCl3); HRESIMS: Calcd for C16H22O11Na ,
413.1054; found, 413.1018; rta11.4; rtb 13.3. Similar concentration
of fractions 25–28 gave 1a as a colourless oil (0.20 g, 18%): ½a25
D
+78.7 (c, 1.27, CHCl3); HRESIMS: Calcd for C16H22O11Na+,
413.1054; found, 413.1018; rta 13.0; rtb 15.1.
3.3. 1,2,3,5,6-Penta-O-acetyl-a-D-altrofuranose (2a) and
1,2,3,5,6-penta-O-acetyl-b-D-altrofuranose (2b)
To a solution of 1,2,3,4,6-penta-O-acetyl-a-D-altropyranose45
(2.62 g) in anhyd MeOH (40 mL) was added a solution of NaOMe
in MeOH (2 M, 0.5 mL). After the mixture had been kept at 5 °C
for 40 h, HOAc (0.3 mL) was added and the mixture was concentrated. A stirred solution of the residue in anhyd pyridine was
heated to 120 °C for 5 min before the addition of Ac2O (at 80 °C)
in portions. After the mixture had been kept for 5 min at 120 °C, it
was concentrated and a CHCl3 solution of the reaction products
was processed as for the preparation of compounds1a and 1b. Chromatography of the reaction products (2.65 g) over silica gel [90 g
after heating at 116 °C for 3 h, packed using a mixture of 1:1
Et2O–light petroleum] To a solution of the acetates in Et2O (4 mL)
was added light petroleum (1 mL). This homogeneous solution
was added to the column, and development was carried out using
a mixture of 1:2 light petroleum–Et2O collecting 10-mL fractions.
Elution was monitored by GLC (3% OV210 at 205 °C). Frs 58–62
13
showed only one peak. Concentration of these fractions gave a residue (0.34 g, 13%) that crystallized at 5 °C. Recrystallization of this
product from a small volume of EtOH gave prisms of 2b (0.23 g,
9%): mp 80–81 °C; ½a25
D 50.4 (c 1.14, CHCl3); HRESIMS: Calcd for
C16H22O11Na+, 413.1054; found, 413.1029; rta 7.6; rtb 9.6. Fractions
67–70 showed only one peak (GLC). Concentration of these fractions gave a residue (0.42 g, 16%) that crystallized. Recrystallization
from EtOH gave needles of 2a (0.23 g, 9%): mp 75–76 °C, ½a25
D +57.7
(c 0.98, CHCl3); HRESIMS: Calcd for C16H22O11Na+, 413.1054; found,
413.1028; rta 9.1; rtb 9.1.
3.4. 1,2,3,5,6-Penta-O-acetyl-a-D-galactofuranose (3a) and
1,2,3,5,6-penta-O-acetyl-b-D-galactofuranose (3b)
Compound 3b,1,13 [needles from EtOH: mp 101–102 °C, lit.13 mp
13
96–97 °C, ½a25
½a25
D 43.1 (c 1.23, CHCl3), lit.
D 41.5 (CH2Cl2), rta
9.1; rtb 11.3] (23.00 g) was dissolved in a mixture of HOAc (30 mL)
and Ac2O (70 mL) containing ZnCl2 (2 g). After the reaction mixture
had been kept at 100 °C for 15 min, it was cooled and poured into
H2O (500 mL). Addition of seed crystals of 3b resulted in crystallization of 3b that was collected, washed with water, and air dried to
give 3b (11.45 g, shown by GLC to be a single compound). CHCl3 extracts (3) of the filtrates were extracted with satd NaHCO3 solution,
filtered through a short bed of silica gel and evaporated. Fractional
crystallization of the products from EtOH gave crude 3a (3.72 g), a
portion of which was recrystallised twice (EtOH) to give 3a: mp
12
87–88 °C, lit.12 87 °C, ½a25
½a25
D +61.5 (c 1.05, CHCl3), lit
D +61.2
(CHCl3), rta 8.5, rtb 11.0.
3.5. 1,2,3,5,6-Penta-O-acetyl-a-D-glucofuranose (4a)
To a mixture of trifluoroacetic acid (45 mL) and H2O (5 mL)10
was added 3,5,6-tri-O-acetyl-1,2-O-isopropylidene-a-D-glucofuranose (10)46 [mp 76–77 °C, lit.47 75 °C, ½a25
+22.1 (c 3.01,
D
1
CHCl3), lit.47 ½a20
D +24.6 (CHCl3); for H NMR data, see Supplementary data] (5.00 g). The reaction mixture was concentrated after 1 h
at 25 °C and a solution of the residue in benzene was concentrated.
After acetylation of the products using Ac2O (10 mL) and pyridine
(5 mL), the acetates were isolated as for compounds 1a and 1b,
above. GLC of the products showed the presence of only a trace
of the starting material and of the pyranose acetates. After a solution of the syrupy acetates in a mixture of TFA (45 mL) and H2O
(5 mL) had been kept at 25 °C for 2.5 h, it was concentrated, followed by the addition of benzene. Concentration then gave crude
acetates that were chromatographed over silica gel (100 g) using
a mixture of 1:1 Et2O–light petroleum, collecting 20-mL fractions.
TLC (silica gel, 1:1 Et2O–light petroleum) showed only one spot in
fractions 48–59, after which the eluting solvent was changed to 2:1
Et2O–light petroleum. The next-eluted compound appeared in
fraction 73. Concentration of fractions 73–83 gave a residue
(1.91 g), probably 2,3,5,6-tetra-O-acetyl-D-glucofuranose, as acetylation (Ac2O/py) gave a mixture of 4a and 4b (approx 1:1 by GLC).
Concentration of fractions 48–59 gave a liquid product that crystallized as prisms. Crystallization of this material from EtOH (ca.
2 mL) gave prisms (0.65 g) and a further 0.17 g by addition of
H2O to the filtrate, for a total yield of 0.82 g (14.6%). Recrystallization (EtOH) of a portion of this product gave prisms of 4a: mp 79–
23
80 °C, ½a25
[a]D +61. HRESIMS: Calcd for
D +97.8 (c 1.40, CHCl3) lit.
+
C16H22O11Na , 413.1054; found, 413.1018; rta 9.7; rtb, 12.4.
3.6. 1,2,3,5,6-Penta-O-acetyl-b-D-glucofuranose (4b)
Acetylation (Ac2O/py) of ethyl 1-thio-a-D-glucofuranoside27,48
gave the crystalline tetraacetate 11 [(1:1 EtOH–H2O), mp 67–
50
68 °C, lit.49 mp 63–64 °C, ½a25
½a25
D +150.2 (c 1.25, CHCl3), lit.
D
+150.0 (CHCl3). For NMR data, see Supplementary data Section.]
14
J. D. Stevens / Carbohydrate Research 347 (2012) 9–15
To a mixture of HOAc (10 mL), Ac2O (0.2 mL) and Hg(OAc)2 (1.5 g)
was added 11 (1.00 g). After the mixture had been heated at 85 °C
for 1.5 h, work-up followed that of the literature report9 to give a
colourless oil (0.81 g, 81%), shown by 1H NMR spectroscopy to be
a mixture of 4a and 4b (5.03:94.97). From the ½a25
D of the mixture
of 20.6 (c 1.27, CHCl3) and the rotation of 4a, ½a25
D of 4b is calculated as 26.9, lit.51 ½a23
D 21.2 (c 1.46, CHCl3), rta 9.45; rtb 11.8.
3.7. 1,2,3,5,6-Penta-O-acetyl-a-D-gulofuranose (5a) and
1,2,3,5,6-penta-O-acetyl-b-D-gulofuranose (5b)
D-Gulose, prepared by reduction of D-gulono-1,4-lactone using
NaBH4,52 was converted into methyl b-D-gulofuranoside,53 [for
1
H NMR data, see Supplementary data] followed by acetylation
(Ac2O/py) to give tetraacetate (12) as large prisms (EtOH) [mp
53
78–79 °C, lit.53 mp 75–76 °C, ½a25
D 65.0 (c 1.34, CHCl3), lit.
25
1
½aD 65.0 (CHCl3); for H NMR data, see Supplementary data].
To a mixture of Ac2O (16 mL), HOAc (8 mL) and H2SO4 (0.5 mL)
was added 12 (3.72 g). GLC of the reaction mixture after 0.5 h at
25 °C showed the absence of 12. The reaction mixture was poured
into satd NaHCO3 solution, followed by the portionwise addition of
NaHCO3 until effervescence ceased. CHCl3 extracts (3) of the neutralised solution were filtered through a short bed of silica gel,
concentrated at 0.5 torr, and 60 °C to give crude pentaacetates
(4.18 g). Chromatography of the products over silica gel (100 g)
using a mixture of 1:1 EtOAc–light petroleum, collecting 20-mL
fractions, gave a single product (TLC) in fractions 17–21. Addition
of a seed crystal of 12 to this product resulted in crystallisation.
Two-fold recrystallisation of this material from EtOH (2 mL) gave
prisms of 5b (2.14 g, 53%), mp 74–75 °C, ½a25
D 52.4 (c 2.10, CHCl3);
HRESIMS: Calcd for C16H22O11Na+, 413.1054; found, 413.1018, rta
11.0; rtb, 16.46. Fractions 23–25 contained only one product
(TLC) (0.51 g) that crystallised as prisms (EtOH, 2 mL) of 5a
(0.36 g, 9%), mp 83–84 °C, ½a25
D +57.4 (c 1.30, CHCl3); HRESIMS:
Calcd for C16H22O11Na+, 413.1054; found, 413.1018, rta 10.16;
rtb 16.1.
3.8. 1,2,3,5,6-Penta-O-acetyl-a-L-idofuranose (6a) and 1,2,3,5,6penta-O-acetyl-b-L-idofuranose (6b)
A solution of 3,5,6-tri-O-acetyl-1,2-O-isopropylidene-b-L-idofuranose (13)25,26 [mp 83–84 °C, lit.25 mp 82–84 °C, ½a25
D 20.3 (c
1
2.19, CHCl3), lit.25 ½a25
D 2 (CHCl3); for H NMR data, see Supplementary data] (2.00 g) in a mixture of TFA (45 mL) and H2O
(5 mL) was kept at 20 °C for 1 h, after which time the reaction mixture was concentrated and a benzene solution of the products was
concentrated. Acetylation (Ac2O, 20 mL, pyr 5 mL) of the cooled residue, followed by work-up as for compounds 1a and 1b, gave crude
pentaacetates (2.43 g). Chromatography of the acetates over silica
gel (55 g) using a mixture of 3:2 Et2O–light petroleum, and collecting 20-mL fractions gave the first acetate in fractions 21–25 (TLC)
and the second acetate in fractions 29–36. Concentration of fractions 21–26 gave 6b as a colourless oil (1.28 g, 57%): ½a25
D +79.2 (c
1.75, CHCl3); HRESIMS: Calcd for C16H22O11Na+, 413.1054; found,
413.1019; rta, 8.4; rtb 10.9. Concentration of fractions 29–36 gave
6a as a colourless oil (0.54 g, 24%): ½a25
D 54.2 (c 1.37, CHCl3); HRESIMS: Calcd for C16H22O11Na+, 413.1054; found, 413.1018; rta 8.5;
rtb 12.05.
3.9. 1,2,3,5,6-Penta-O-acetyl-a-D-mannofuranose (7a) and
1,2,3,5,6-penta-O-acetyl-b-D-mannofuranose (7b)
Acetylation (Ac2O/py) of methyl a-D-mannofuranoside27 gave
methyl a-D-mannofuranoside tetraaceetate (14) as prisms (EtOH)
28
[mp 65–66 °C, lit.28 mp 63 °C; ½a25
D +107.1 (c 1.79, CHCl3), lit.
25
1
½aD +106.3 (CHCl3); for H NMR data, see Supplementary data].
Acetolysis of 14 (2.80 g) as for 12 above gave a mixture of pentaacetates (2.20 g 73%). Chromatography of the products over silica
gel (60 g) using a mixture of 1:1 Et2O–light petroleum as eluent,
and collecting 20-mL fractions gave the first compound in fractions
38–46 and the second compound in fractions 48–58. Concentration
of fractions 38–46 gave a crystalline product (1.57 g, 52%) that
crystallised from EtOH (3 mL) to give prisms of 7a: mp 80–81 °C,
28
lit.28 mp 76 °C, lit.4 mp 84–85 °C, ½a25
D +89.9 (c 1.44, CHCl3), lit.
20
4
½aD +89.6 (CHCl3), lit. ½aD +88 (CHCl3); rta 9.37; rtb 12.36. Concentration of fractions 48–58 gave 7b as a colourless oil (0.45 g,
15%): ½a25
D 35.9 (c 1.04, CHCl3); rta 9.76; rtb 12.23.
3.10. 1,2,3,5,6-Penta-O-acetyl-a-D-talofuranose (8a) and
1,2,3,5,6-penta-O-acetyl-b-D-talofuranose (8b)
A mixture of finely ground D-talose54 (2.00 g) and pyridine
(20 mL) was boiled under reflux for 2 min after which Ac2O
(10 mL) was added to the boiling solution that was refluxed for
5 min. The reaction mixture was worked-up as for compounds
1a and 1b, above. Chromatography of the crude products over silica gel (80 g) using a mixture of 1:2 Et2O–light petroleum as eluent and collecting 50-mL fractions gave a single product in
fractions 13–15 (GLC). Concentration of fractions 13–15 gave a
colourless liquid (2.23 g) (identified as a-talofuranose pentaacetate by 1H NMR spectroscopy) which was dissolved in Ac2O
(10 mL) containing ZnCl2 (ca. 100 mg). After the mixture had been
heated at 100 °C for 5 min, H2O (2 mL) was added to the cooled
solution. The cooled hydrolysate was added to H2O (200 mL),
and the mixture was neutralised by portion-wise addition of
NaHCO3 (ca. 20 g). CHCl3 extracts (3) of the aqueous solution
were filtered through a short bed of silica gel and concentrated.
A solution of the residue in a mixture of 1:2 EtOAc–light petroleum was chromatographed over silica gel (60 g) using the same
solvent mixture as eluent, collecting 20-mL fractions and monitoring by GLC. Concentration of fractions 24–30 gave a single
29
compound (1.30 g, 30%): 8a, ½a25
D +37.2 (c 1.15, CHCl3), lit.
+
½a20
+38.6
(CHCl
);
HRESIMS:
Calcd
for
C
H
O
Na
,
413.1054;
3
16
22
11
D
found, 413.1034; rta 10.55; rtb 13.23. Concentration of fractions
33–43 gave a colourless liquid (0.48 g, 11%): 8b, ½a25
D 47.3 (c
1.07, CHCl3); HRESIMS: Calcd for C16H22O11Na+, 413.1054; found,
413.1030; rta 14.41; rtb 11.42.
3.11. Equilibrium values
Equilibrium values for the aldohexofuranose pentaacetates
were determined using 2:1 Ac2O-d6–HOAc-d4 containing 0.2% by
volume concd H2SO4. Solutions for the 1H NMR measurements
were kept at 25 °C for 15 h before spectra were recorded. An
approximate T1 relaxation time for H-1 of 7a was used to determine appropriate delay times for collection of the FID’s. In a separate experiment, the optical rotation of a solution of 3b in the
acetolysis medium was constant after 1 h. No epimeric products
were detected in the solutions for 1H NMR spectroscopy.
3.12. Attempted epimerisation reaction after Jerkman38
To a mixture of HOAc (20 mL), Ac2O (2 mL) and H2SO4 (1 mL),
2 mL, was added 8a (54 mg). The reaction mixture was kept at
18 °C for 40 h, after which time it was poured into water
(50 mL). CHCl3 extracts (2) of the aqueous mixture were washed
with satd NaHCO3 solution, filtered through silicic acid and evaporated. A 1H NMR spectrum of the products showed the presence of
only two compounds, 8a and 8b. Similar treatment of 1b gave only
1a and 1b. In a comparison experiment, 9 (100 mg) was treated as
for 8a. A 1H NMR spectrum of the products showed the presence of
1a, 1b, 2a and 2b.
J. D. Stevens / Carbohydrate Research 347 (2012) 9–15
Acknowledgements
We are grateful to the late Dr J. A. Mills for a generous supply of
methyl
4,6-O-benzylidene-2,3-anhydro-4,6-O-benzylidene-a-Dallopyranoside used in the preparation of a-D-altropyranose pentaacetate, to Mrs. H. Stender of the University of New South Wales
High-Field NMR Facility for NMR spectra and to Mr. Ahmad
Mokhtari Fard for the high-resolution mass spectra.
Supplementary data
Supplementary data (1H NMR spectra for reagent compounds
9–14 and related compounds) associated with this article can be
found, in the online version, at doi:10.1016/j.carres.2011.09.009.
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