Septanose carbohydrates. VII. Preparation of mono-O-isopropylidene derivatives of methyl β-D-glucoseptanoside and preparation of methyl α-L-idoseptanoside and its derivatives

Article abstract of DOI:10.1071/ch01196

Three mono-O-isopropylidene derivatives of methyl β-D-glucoseptanoside have been prepared by acid-catalysed hydrolysis of methyl 2,3:4,5-di-O-isopropylidene-β-D-glucoseptanoside or by acetonation of methyl β-D-glucoseptanoside. Two of these derivatives have been used for the preparation of methyl 2,3-O-isopropylidene-α-L-idoseptanoside (8a) and methyl 3,4-O-isopropylidene-α-L-idoseptanoside (10a). Hydrolysis of (10a) yielded methyl α-L-idoseptanoside (12a) and acetonation of (8a) and (12a) yielded methyl 2,3:4,5-di-O-isopropylidene-α-L-idoseptanoside. Possible conformations of these compounds are discussed.

Full text of DOI:10.1071/ch01196

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Aust. J. Chem. 2002, 55, 171–178
Septanose Carbohydrates. VII.* Preparation of Mono-O-isopropylidene
Derivatives of Methyl β-D-glucoseptanoside and Preparation of
Methyl α-L-idoseptanoside and its Derivatives
Trung Q. TranA and John D. StevensA,B
A School of Chemistry, University of New South Wales, Sydney, N.S.W. 2052, Australia.
B Author to whom correspondence should be addressed (e-mail johndstevens@yahoo.com).
Three mono-O-isopropylidene derivatives of methyl β-D-glucoseptanoside have been prepared by acid-catalysed
hydrolysis of methyl 2,3:4,5-di-O-isopropylidene-β-D-glucoseptanoside or by acetonation of methyl
β-D-glucoseptanoside. Two of these derivatives have been used for the preparation of methyl
2,3-O-isopropylidene-α-L-idoseptanoside (8a) and methyl 3,4-O-isopropylidene-α-L-idoseptanoside (10a).
Hydrolysis of (10a) yielded methyl α-L-idoseptanoside (12a) and acetonation of (8a) and (12a) yielded methyl
2,3:4,5-di-O-isopropylidene-α-L-idoseptanoside. Possible conformations of these compounds are discussed.
Manuscript received: 7 December 2001.
Final version: 19 April 2001.
C
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01196
S
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a
n
C
a
r
o
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y
d
a
e
s
.
I
O
O
O
Introduction
OMe
OMe
6
4
1
5
Methyl 2,3:4,5-di-O-isopropylidene-β-D-glucoseptanoside
(1) may be prepared by the reaction of D-glucose with an
acidified mixture of acetone and methanol[2,3] or by
methylation of 2,3:4,5-di-O-isopropylidene-D-glucosep-
tanose, a minor product from the reaction of D-glucose with
acidified acetone[4] or prepared from D-glucose diethyl
dithioacetal.[5] In this paper, we describe the preparation of
three mono-O-isopropylidene derivatives from (1) or from
methyl β-D-glucoseptanoside (2)[4] and the conversion of
two of these into methyl α-L-idoseptanoside and its
derivatives.
O
O
2
R2O
R1O
3
O
O
O
Me2C
CMe2
CMe2
(1)
R1 R2
O
OMe
(3a)
H
H
OH
Ac Ac
Bz Bz
(3b)
(3c)
(3d)
HO
OH
OH
Ac
H
(2)
O
O
OMe
OMe
Results and Discussion
OR2
O
R2O
O
Treatment of (1) with a mixture of dioxan and dilute
hydrochloric acid gave a mixture of five products. These
were identified as the starting material (1), methyl 2,3-
O-isopropylidene-β-D-glucoseptanoside (3a), methyl 3,4-O-
isopropylidene-β-D-glucoseptanoside (4a), methyl 4,5-O-
isopropylidene-β-D-glucoseptanoside (5a), and (2). GLC
(gas–liquid chromatography) analysis of the acetylated
products showed a ratio of (3a)/(4a)/(5a) of 7:1:4 when
approximately 50% of (1) remained. Prolonged hydrolysis
resulted in the formation of increasing amounts of (2) but
only small changes in the ratios of the three monoacetals.
As initial attempts at the separation of the monoacetals
using column chromatography over silicic acid were only
partially successful, the possibility of achieving a separation
using ion-exchange resins was examined. Two procedures
were considered. The first one involved the use of
cation-exchange resin in the calcium form. Columns
OR1
OR1
O
O
Me2C
CMe2
R1 R2
R1 R2
H
(5a)
(5b)
(5c)
H
H
(4a)
(4b)
H
Ac
Ac
Ac
Ac
Bz Bz
Bz Bz
(4c)
(4d)
(4e)
Bz
Bz
H
Ts
containing such resin have been used successfully for the
separation of polyhydroxy compounds and the method relies
upon the coordination of suitably disposed diols or triols
with the cation. The procedure has been reviewed recently.[6]
We expected both (3a) and (5a) to undergo complexation
with Ca2+ and hence to be retained in the resin, whereas (4a)
should be readily eluted. By using a water and methanol
*Part VI, Carbohydr. Res. 2001, 334, 81.[1]
© CSIRO 2002
10.1071/CH01196
0004-9425/02/010171

172
T. Q. Tran and J. D. Stevens
mixture as eluent, (4a) was well separated from (3a) and (5a).
Although intermediate fractions contained both (3a) and
(5a), later fractions contained only (3a). A more satisfactory
method for the separation of (3a) and (5a) involves use of the
second ion-exchange procedure, employing a strongly basic
anion-exchange resin in the hydroxide form. This procedure
that has been used for the separation of base-stable
glycosides.[7]
The formation of the three monoacetal derivatives (3a),
(4a), and (5a) is similar to the results[2] obtained for the
hydrolysis of methyl 2,3:4,5-di-O-isopropylidene-α-D-
glucoseptanoside (6). However, whereas (3a) was the major
monoacetal obtained from (1), the major product from (6)
was methyl 4,5-O-isopropylidene-α-D-glucoseptanoside.
These differences in the results of selective hydrolysis of (1)
and (6) may have their origins in the different solution-state
conformations adopted by (1) and (6).
ratio of (3a)/(4a)/(5a) as 1.2:2.8:1.0. Separation of the
products was achieved using the two ion-exchange
procedures. It is of some interest that the major monoacetal
isomer involves acetonation of a trans diol grouping in (2)
which is in contrast to the results for six-membered ring
glycosides such as methyl α-D-galactopyranoside.[9]
Acetonation of (2) using acidified acetone gave (1)
together with the three monoacetals (3a), (4a), and (5a) in the
ratio 3.2:1.7:1.0, making this a useful procedure for the
preparation of (3a).
Identification and Conformations of the Monoacetals
1
Analysis of the H nuclear magnetic resonance (NMR)
spectra of the derived diacetates (see Tables 1 and 2)
identified the three monoacetals. Possible solution-state
conformations for the three monoacetal diacetates were
deduced from the spin coupling constants together with
dihedral-angle data given by Hendrickson[10] and by Bocian
and Strauss.[11]
O
For both (3b) and (5b), the large magnitudes of J2,3 and
J3,4 indicate that H2/H3 and H3/H4 are antiperiplanar and the
values of J5,6a and J5,6b are consistent with a synclinal
orientation of H5 to both hydrogen atoms on C6. Of the 28
conformations in the chair–twist-chair pseudorotational
continuum of the septanose ring, only those in the region
3,4TC1,2 to 4,5TC6,O satisfy these requirements, and of those
only the conformation 5,6TC3,4 accounts for the values of J1,2
and J4,5. The small value of J5,6a, particularly for (3b), is
consistent with an assignment of H6a as the axial hydrogen
on C6 (the pro-R hydrogen). The dihedral angle between H5
and H6a is therefore[11] ca. 73°, and with the acetoxy group
on C5 antiperiplanar to H6a, results[12] in the small value for
J5,6a. The axial orientation of the acetoxy roup on C5 also
accounts[13–16] for the large magnitude of J6a,6b and together
O
O
OMe
O
O
Me2C
CMe2
(6)
In our study on the acetonation of methyl α-D-
glucoseptanoside, it was found that the use of
2,2-dimethoxypropane (DMP) in dimethylformamide
(DMF) containing p-toluenesulfonic acid[8] resulted in the
formation of the 3,4-O-isopropylidene derivative as the
major product. As (4a) is only a minor product from the
selective hydrolysis of (1), we examined the reaction of (2)
with DMP in DMF. After thin-layer chromatography (TLC)
of the reaction mixture showed (2) was no longer present,
GLC analysis of the acetylated reaction products gave the
Table 1. 1H chemical shifts in ppm
Cpd
Solvent
H1
H2
H3
H4 H5 H6a H6b OMe
Acetate
methyls
O-isopropylidene
Other
methyls
(3b)A
(3c)B
(3d)B
(4b)A
(4c)A
(4d)B
(4e)A
(5b)B
(5c)A
(7)D
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
(CD3)2CO
CDCl3
CDCl3
(CD3)2CO
CDCl3
C6D6
CDCl3
CDCl3
+ Euroshift F
4.677 3.852 4.379 5.008 5.273 3.945 3.726 3.450 2.173
4.766 4.020 4.569 5.405 5.583 4.110 3.953 3.479
4.624 3.818 4.244 4.884 3.967 3.911 3.733 3.446 2.177
4.544 4.938 4.373 3.993 5.335 4.055 3.677 3.387 2.150
2.068
—
—
2.141
—
—
—
2.038
—
1.447
1.457
1.410
1.400
1.404
1.410
1.311
1.482
1.463
1.490
1.391
1.360
1.460
1.295
1.412
—
1.415
1.428
1.400
1.382
1.301
1.402
1.188
1.338
1.322
1.490
1.389
1.345
1.444
1.264
1.386
—
—
—
—
—
—
—
4.750 5.276 4.694 4.194 5.635 4.233 3.868 3.420
4.643 5.223 4.453 3.960 4.177 4.091 3.704 3.385
4.667 5.156 4.457 3.993 4.965 4.108 3.867 3.379
—
—
—
—
2.452C
—
4.550 4.872 5.310 4.136 4.182 4.100 3.856 3.360 2.046
4.849 5.340 5.694 4.503 4.426 4.346 3.955 3.397
4.700 4.160 4.310 5.310 4.500 3.890 3.510 2.250
—
—
—
—
—
—
—
—
—
—
—
(8b)B,E
(8b)A
(9)B
4.566 3.985 3.984 5.229 4.984 3.771 3.521 3.414 2.071
4.552 4.180 3.993 5.287 4.890 3.870 3.469 3.371 1.999
2.003
1.964
—
1.592
—
2.203
2.199
1.921
1.917
—
4.411 5.591 4.095 5.113
4.147 5.491 3.847 4.187 5.116 3.706 3.368 3.082 1.734
4.513 5.388 4.139 4.369 5.289 4.091 3.938 3.407
—
4.648 4.125 3.445
—
(10b)A
(10c)B
(12b)A
—
4.786 5.825 5.748 5.919 5.516 4.076 3.864 3.448 2.256
2.229
4.487 5.138 5.236 5.187 4.955 3.792 3.572 3.290 1.962
1.933
(12b)B,E CDCl3/
—
—
—
—
(CD3)2COF
(CD3)2CO
(13)G
4.630 3.820 3.910 3.700 3.570 3.830 3.730 3.360
—
1.390
1.370
1.370
1.370
A 300 MHz. B 500 MHz. C ArMe. D 100 MHz. E By iterative analysis of H1 to H5. F In a ratio of 2:1. G 270 MHz

Septanose Carbohydrates. VII
173
Table 2. 1H coupling constants in Hz
H
H
H
Cpd
Solvent
J1,2
J2,3
J3,4 J4,5
J5,6a J5.6b J6a,6b
3.81 14.52 0.65G
Other
MeO
H
H
H
(3b)A
(3c)B
(3d)B
(4b)A
(4c)A
(4d)B
(4e)A
(5b)B
(5c)A
(7)C
CDCl3
6.52 9.26
6.54 9.24
6.63 9.30
3.41 9.33
3.49 9.42
4.21 9.69
3.51 9.23
7.17 10.35 9.06 6.05 1.80
7.06 10.35 9.08 6.08 1.90
6.2 9.2
6.69 9.53
6.56 9.34
8.02 9.65
10.25 4.38 0.60
10.21 4.46 0.00
10.29 3.98 0.00
9.31 2.74 2.71
9.36 2.73 2.74
9.23 2.83 3.19
9.33 2.51 2.81
—
—
—
—
—
—
O
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
(CD3)2CO
CDCl3
3.77 14.54
4.04 13.96
—
—
OAc
O
2.50 14.11 0.41H 0.49G 0.48I
Me2C
OAc
2.53 14.16
3.22 13.66
2.38 14.33
2.77 14.60
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
O
H
(3b), 5,6TC3,4
2.73 14.55 0.55G
15.5
9.0
—
—
—
—
H
(8b)B,D CDCl3
9.76 8.88 11.01 4.42 12.99 0.56G
9.87 8.98 10.98 4.31 12.90 0.65G
(8b)A
(9)B
(CD3)2CO
CDCl3
O
OMe
H
H
18.75 0.72J 0.67K
Me2C
9.92
—
—
—
H
(10b)A C6D6
6.39 10.04 9.31 8.51 5.01
6.13 9.96
6.46 9.88
4.87 13.69
4.91 13.81
—
—
—
—
—
—
H
O
(10c)B
(12b)A CDCl3
+ Euroshift F
(12b)B,D CDCl3/
CDCl3
9.26 8.46 4.99
9.29 8.63 10.21 5.75 12.90
OAc
H
OAc
H
6.59 9.48
9.56 9.90 10.05 4.68 12.92
—
—
—
—
—
—
O
(CD3)2COE
(CD3)2CO
(4b), 4,5TC6,O
(13)F
6.2 9.1
9.1
8.4 10.0
2.5 12.1
A
B
C
D
E
300 MHz.
500 MHz.
100 MHz.
I J3,5
By iterative analysis of H1 to H5.
J J4,6a K J4,6b
In a ratio of
H
2:1. F 270 MHz. G J1,6a
.
H J1,5
.
.
.
.
H
H
MeO
H
H
with the close proximity of H3 to the ring oxygen atom,
accounts for H3 coming into resonance 0.45 ppm to lower
field than H2.
O
O
AcO
H
O
C
Me2
It is of interest to attempt an explanation for the selective
hydrolysis of (1) which results in the formation of (3a) in
high yield. An X-ray study[17] on (1) yielded the (average)
values of 29 and –32° for the torsional angles
O2–C2–C3–O3 and O4–C4–C5–O5 respectively. As the
calculated[11] values for these torsional angles for the
twist-chair C conformation of oxepane are 29 and –51°,
respectively, we conclude that the greater reactivity of the
4,5-O-isopropylidene group in (1) towards acid hydrolysis
reflects the greater amount of strain that is relieved when that
grouping is converted into the diol. This is in contrast to the
2,3-O-isopropylidene group the hydrolysis of which gives
(5a). From an X-ray study[17] on the 3-O-benzoyl derivative
of (5a), the O2–C2–C3–O3 torsional angle is 32°, almost the
same as in (1).
AcO
H
(5b), 5,6TC3,4
acetyl-2,3-O-isopropylidene-β-D-xylo-hexoseptanosid-5-ul-
ose (7). Reduction of (7) using sodium borohydride gave two
products in approximately equal amounts. Separation of the
reduction products after deacetylation was achieved by
chromatography using a cation ion-exchange resin. The
acetylated products were identified by 1H NMR spectra as the
gluco isomer (3b), and methyl 4,5-di-O-acetyl-2,3-
O-isopropylidene-α-L-idoseptanoside (8b). The values of
J4,5, J5,6a, and J6a,6b for (8b) are considerably different from
those of (3b) in keeping with the change of configuration at
C5.
Treatment of (4a) with an equimolar amount of benzoyl
chloride in pyridine gave two products that were readily
separated by silica gel chromatography. The first eluted
compound showed no absorption due to OH groups in the
infrared spectum. An examination of the 1H NMR spectrum
identified this product as the dibenzoate (4c). The major
product, 72% yield, was identified from its 1H NMR
spectrum as the 2-O-benzoyl derivative (4d). The high yield
of (4d) may be attributed to the low reactivity of the axially
oriented hydroxyl group on C5 compared with that of the
more reactive iso-clinal[10] hydroxyl group on C2.
For (4b), the magnitudes of J2,3 and J3,4 indicate H2/H3
and H3/H4 are antiperiplanar, and from the values of J5,6a
and J5,6b, that H5 is synclinal to both H6a and H6b. A
4,5TC6,O conformation accounts well for these NMR values,
as well as for J1,2 as the calculated[11] H1/H2 dihedral angle
for the twist-chair B of oxepane is 73°. This conformation
also accounts for the chemical shift of H3, which comes into
resonance 0.38 ppm to low field of H4/ H3, it being opposed
by the axial acetoxy group on C5 and being affected by the
ring oxygen atom.
Methyl α-L-Idoseptanoside and its Derivatives
Oxidation of (4d) with ruthenium tetroxide gave the
ketone methyl 2-O-benzoyl-3,4-O-isopropylidene-β-D-xylo-
hexoseptanosid-5-ulose (9), in high yield. Sodium
borohydride reduction of (9) was carried out using two
procedures. In the first, a solution of (9) was added slowly to
the hydride solution. Two products, separated by silica gel
chromatography, were identified as (4d) and methyl 2-
O-benzoyl-3,4-O-isopropylidene-α-L-idoseptanoside (10d),
Compounds (3a) and (4a) are both possible precursors of
methyl α-L-idoseptanoside derivatives produced by inversion
of configuration at C5. Treatment of (3a) with an equimolar
quantity of acetic anhydride in pyridine resulted in the
formation of only one monoacetate, isolated in 40% yield by
crystallization and identified as methyl 4-O-acetyl-2,3-O-
isopropylidene-β-D-glucoseptanoside (3d) from its 1H NMR
spectrum (Tables 1 and 2). Oxidation of (3d) using ruthenium
tetroxide gave the crystalline ketone, methyl 4-O-
1
by examination of the H NMR spectra of the diacetate
derivatives formed from the products of debenzoylation (4a)

174
T. Q. Tran and J. D. Stevens
gave an acetylation product with the same GLC retention
time as (8b). After separation of the reaction products using
a cation ion-exchange resin, the identification of the new
product as (8a), obtained in 60% yield, was verified by mixed
melting point and infrared and NMR spectra of the derived
diacetate. A similar result has been reported for the
corresponding β-L-idoseptanoside derivative.[19]
O
O
O
O
R2O
OMe
OMe
O
O
O
R1O
AcO
CMe2
CMe2
1
2
(7)
R
R
H
(8a)
H
O
(8b)
(8c)
O
O
Ac
H
Ac
Ac
HO
OMe RO
O
OMe
OMe
O
OR
O
Me2C
OBz
OR
O
O
OR
O
CMe2
O
R2O
O
O
OMe
OMe
CMe2
(12a)
R = H
HO
OMe
O
O
(13)
O
(12b) R = Ac
O
OR1
OBz
O
O
CMe2
CMe2
OBz
O
CMe2
1
2
R
R
H
(9)
(11)
(10a)
(10b)
(10c)
(10d)
H
Ac
Ac
Methyl α-L-Idoseptanoside (12a)
Bz Bz
Bz
Treatment of (10a) with dilute hydrochloric acid gave
crystalline (12a) in high yield. Acetylation of (12a) gave the
crystalline tetraacetate (12b). Simple analysis of the H
H
1
NMR spectra of (12b) was precluded by the small chemical
shift differences between H2 and H3 and also H4 and H5.
Addition of a shift reagent to a CDCl3 solution of (12b)
resulted in these hydrogen pairs being sufficiently dispersed
to allow the full analysis of the spectrum. Earlier X-ray
studies verified the structure of (12a)[20] and (12b).[21]
Treatment of (8a) with an acidified mixture of acetone
and DMP gave crystalline methyl 2,3:4,5-di-O-iso-
propylidene-α-L-idoseptanoside (13), in 21% yield.
Compound (13) together with (10a) was also obtained by
similar treatment of (12a).
and (10a) respectively. In the second procedure, a sodium
borohydride solution was added slowly to a solution of (9).
This gave rise to (4d), (10d), and a third product (A). The 1H
NMR spectrum of (A) showed the presence of two methoxy
groups, two O-isopropylidene groups and two 1H doublets
of doublets at δ 5.40 and 5.29. The remainder of the
non-aromatic portion of the spectrum integrated for 10H. A
sharp singlet at δ 1.74 disappeared when the solution was
shaken with D2O, indicating a tertiary hydroxyl group.
Compound (A) is therefore a ‘dimer’, probably formed by
the reaction of an enediolate ion from (9) with the keto group
of another molecule of (9), followed by reduction of the
remaining keto group. A detailed analysis of the spectrum
(see Experimental) has led to a structure of the type
displayed in (11), although the configuration at C5 in ring A
and at C5 and C6 in ring B have not been defined. There is
precedent for the formation of a ‘dimeric’ product from an
aldosulose derivative. Treatment of 1,6-anhydro-2,3-O-iso-
propylidene-β-D-lyxo-hexopyranos-4-ulose with triethyl-
amine and acetic anhydride gave a crystalline dimeric
product.[18]
Conformational Analysis
Spin coupling constants J1,2, J2,3, and J3,4 for the ketone (7)
are essentially the same as those for the parent alcohol (3d),
which suggests that (7) adopts a conformation, probably
5,6TC3,4, similar to that of (3b). In this conformation, one of
the C6 hydrogen atoms has a dihedral angle of approximately
60° with respect to one of the adjacent p-orbitals of the keto
carbon atom, resulting in an increase in the magnitude of
J6a,6b of ca. 1 Hz over that of (3b).[22]
A notable feature of the spin coupling constants of ketone
(9) is the large magnitude of J6a,6b. This could be accounted
for by a conformation in which the plane of the keto group
Another procedure for the obtention of an L-ido
compound involves displacement of a sulfonyloxy group
from C5 of the D-gluco compound. p-Toluenesulfonylation
of (4d) gave (4e) in near quantitative yield. Treatment of (4e)
with lithium benzoate in DMF gave methyl
2,5-di-O-benzoyl-α-L-idoseptanoside (10c), in 78% yield,
identified by comparison with the dibenzoate obtained from
(10d). The high yield of (10c) makes this the procedure of
choice, rather than the oxidation/reduction route, which
requires a chromatographic separation.
2
bisects the H6a–C6–H6b angle.[22] Conformation C5,6
satisfies this requirement and accounts for the magnitudes of
H
Me2C
H
O
O
BzO
H
O
MeO
O
H
Isomerization of (10a)
H
H
Treatment of (10a) with acetone containing sulfuric acid
gave rise to another mono-O-isopropylidene derivative that
2
(9), C5,6

Septanose Carbohydrates. VII
175
J1,2, J2,3, and J3,4. It also accounts for the chemical shift of
H4, 1 ppm to low field of H3, as one of the sp3-hybridized
lone-pair orbitals of the ring oxygen atom is directed
towards H4.
five-membered ring in (8b) are not extant in (12b). In the
solid state (12b) exists in the 5,6TC3,4 conformation.[21]
Although the spin coupling constants for the
di-O-isopropylidene derivative (13) are similar to those of
(8b) and (12b), the geometric constraints imposed by the
presence of two fused five-membered rings appear to
exclude the conformation 5,6TC3,4 for this compound.
The large magnitudes of J2,3, J3,4, J4,5, and J5,6a for (8b)
require these hydrogen pairs to be antiperiplanar.
2
Conformations C5,6 to 1,2C5 in the pseudorotational
chair–twist-chair continuum were examined as possible
conformations. Of these, conformation 5,6TC3,4 accounts for
the coupling constants reasonably well. It is also favoured by
the anomeric effect and by the 29° torsional angle[11]
O2–C2–C3–O3, a favourable angle for fusion of the
five-membered ring. An alternative conformation, 3,4TC1,2,
which is also a twist-chair C conformation,[11] also accounts
reasonably well for the observed coupling constants.
However, formation of the five-membered ring at O2/O3
would involve flattening of the seven-membered ring at
C2/C3 in order to reduce the O2–C2–C3–O3 torsional angle
from 69°.
Conformation
2,3TC4,5,
for
which
the
pseudo
axis-of-symmetry of the seven-membered ring passes
through the ring oxygen atom, accounts for the NMR
parameters and, with some ring distortion, allows for the
fusion of the two five-membered rings.
H
Me2C
O
O
H
O
H
MeO
O
H
H
H
CMe2
O
H
The coupling constants for (10b) are not readily
accounted for by one chair or twist-chair conformation.
However, a conformational equilibrium
(13), 2,3TC4,5
We would like to stress that the energy differences
between the different conformations of the oxepan ring are
not large and consequently, the deduction of solution-state
conformations of septanose compounds is associated with a
high degree of speculation.
3,4
2
0,1TC2,3 → C5,6 →
←
← TC 1,2
could account for all of the J values, including J5,6a and J5,6b
It is of some interest that inversion of configuration at C5 of
(4b) has resulted in a change of conformation, from 4,5TC6,0
for (4b) to the equilibrium above for (10b). A similar
conformational change was noted for the corresponding
α-D-gluco, β-L-ido pair of compounds.[19]
.
Experimental
Optical rotations were determined using 2 cm cells in a Bendix NPL
Automatic Polarimeter 143C equipped with a JANUS digital voltmeter.
Melting points (m.p.) were determined on a Reichert hot-stage
microscope and are uncorrected. Mixed melting points were
determined in capillaries using a Mel-Temp apparatus. Infrared spectra
were recorded using a Pye Unicam SP1000 Infrared Spectrophotometer
and solids were examined as mulls with liquid paraffin and, unless
otherwise stated, only very strong and sharp absorptions are reported.
NMR spectra were obtained using Jeol JNM-FX-100, Bruker HX-270,
Bruker CXP-300, or Bruker AM-500 spectrometers. Tetramethylsilane
was used as an internal reference and chemical shifts are reported as
ppm using the δ scale. For the data presented in Tables 1 and 2, the
program GNMR (Cherwell Scientific) was used for analysis of H5,
H6a, and H6b as three-spin systems and for the iterative analyses.
Chemical ionization (CI) mass spectra were recorded using an A.E.I.
MS 902 mass spectrometer. Silica gel supported on microscope slides
was used for TLC, visualization being achieved by charring on a hot
plate after spraying the slide with 10% sulfuric acid in ethanol. Column
chromatography with silica gel was performed using Merck silica gel H
(type 60), generally using a height of packed column ca. 15 times its
diameter and a ratio of silica gel to products of 10:1.
Calcium ion-exchange resin columns were prepared using Bio-Rad
AG 50W-X4 resin (200–400 mesh, hydrogen form) which was
converted into the calcium form by stirring the resin (454 g) with 1 M
calcium acetate solution (1 L) followed by pouring the mixture into a
glass column (3.5 cm diameter). The resin was washed with 1M
calcium acetate solution (500 mL) followed by water, or a mixture of
water and methanol, until the eluate was neutral. Hydroxide
ion-exchange resin columns were prepared using Bio-Rad AG1-X2
resin (200–400 mesh, chloride form) which was stirred with CO2 free
water (200 mL), poured into a glass column (3 cm diameter), washed
with 1 M NaOH solution until the eluate, after acidification with nitric
acid, gave no precipitation upon addition of silver nitrate solution. The
resin was washed with CO2 free water until the eluate was neutral. GLC
was carried out on a custom-built instrument fitted with glass-lined
O
OMe
OAc
H
H
H
H
O
H
H
CMe2
AcO
H
O
(10b), 0, 1TC2,3
2C5,6
Me2
C
H
O
O
H
H
H
OAc
O
H
H
OAc
H
MeO
(10b), 3,4TC1,2
As the spin-coupling constants of the glycoside
tetraacetate (12b) are very similar to those of (8b), the
conformational arguments in favour of one or more
conformations of (12b) are similar to those given above for
(8b), with the exception that the geometric restraints of the

176
T. Q. Tran and J. D. Stevens
insert and flame-ionization detector. Columns used were No. 1, 3%
SP2401 on Chromosorb W (AW-DMCS) in a 2.13 m glass column and
No. 2, 2% DEGA (stabilized, Analabs) on Chromosorb W (AW-DMCS)
in a 2.13 m glass column. Ether refers to diethyl ether, light petroleum
refers to the fraction boiling at 60–80°C unless otherwise stated.
Ethanol is 95% and mixed solvents were prepared on a v/v ratio.
N,N-Dimethylformamide (DMF) was dried over phosphorus pentoxide
as reported by Evans.[23] Pyridine refers to reagent pyridine kept over
sodium hydroxide pellets.
[α]2D3 –113.7° (c, 1.00 in CHCl3), [α]2D3 –134.2° (c, 1.00 in H2O)
(Found: C, 51.1; H, 8.0%. C10H18O6 requires C, 51.3; H, 7.8%). νmax
3500, 3495, 1095, 1075, 1065, 1050 cm–1. The residue (3.47 g) left on
evaporation of fractions 31–37 was dissolved in water freed from
carbon dioxide (6 mL) and added to a column of AG1-X2 ion-exchange
resin (hydroxide form). Carbon dioxide free water was used as eluent
and 10 mL fractions were collected. Fractions 20–32 yielded (3a)
(2.24 g) and fractions 41–48 gave (5a) (1.20 g). Total yields based on
unrecovered (1): (3a), 46%; (4a), 12%; (5a), 24%.
The standard procedure for acetylations involved treatment of the
hydroxylic compound with a 1:1 mixture of acetic anhydride and
pyridine. After removing volatiles on a Buchi evaporator, the residue
was dissolved in absolute ethanol and this solution was kept at room
temperature for ca. 20 min in order to destroy any remaining acetic
anhydride. After evaporation of the of the ethanol solution, a
chloroform solution of the residue was shaken with 1 M sulfuric acid
followed by saturated sodium bicarbonate solution, it was then filtered
through a short bed of silicic acid and evaporated.
The standard procedure for benzoylations involved addition of an
excess of benzoyl chloride to an ice-cold solution of the hydroxylic
compound in anhydrous pyridine. After the reaction mixture had stood
for 3 h at room temperature, a few drops of water were added to destroy
excess reagent. A chloroform solution of the reaction products was
washed successively with 1 M sulfuric acid and saturated sodium
bicarbonate solution and then passed through a short column of silicic
acid and evaporated.
Using Silica Gel. A solution of the mixture of three monoacetals
(2 g) in ethyl acetate/light petroleum (1:1) was added to a column of
silica gel (140 g) and the column developed with the same solvent
mixture, fractions of 75 mL being collected. Fractions 12–14 contained
(1) (0.10 g), and fractions 52–54 gave (4a) (0.02 g). Fractions 55–72
contained (3a), (4a), and (5a) and fractions 73–80 (eluted with a 2:1
mixture) gave (3a) (0.40 g).
Preparation of Monoacetal Derivatives
Acetylation of (3a) gave liquid methyl 4,5-di-O-acetyl-2,3-O-isopro-
pylidene-β-D-glucoseptanoside (3b), short path distilled, [α]2D2 –110.0°
(c, 1.36 in CHCl3) (Found: C, 52.6; H, 7.3%. C14H22O8 requires C, 52.8;
H, 7.0%). νmax (thin film) 1753, 1253, 1226, 1065 cm–1. Benzoylation
of (3a) gave liquid methyl 4,5-di-O-benzoyl- 2,3-O-isopro-
pylidene-β-D-glucoseptanoside (3c), short path distilled, [α]2D2 –140.3°
(c, 1.66 in CHCl3) (Found: C, 65.5; H, 5.7%. C24H26O8 requires C, 65.2;
H, 5.9%). νmax (thin film) 1730, 1285, 1090, 1065 cm–1.
Acetylation of (4a) gave methyl 2,5-di-O-acetyl-3,4-O-isopro-
pylidene-β-D-glucoseptanoside (4b), which crystallized from
benzene/light petroleum as needles, m.p. 93–94°C, [α]2D3 –95.6° (c,
1.00 in CHCl3) (Found : C, 53.0; H, 7.1%. C14H22O8 requires C, 52.8;
H, 7.0%). νmax 1732, 1230 cm–1.
Selective Hydrolysis of Methyl
2,3:4,5-Di-O-isopropylidene-β-D-glucoseptanoside (1)
To a solution of (1)[2–5] (17.00 g) in dioxan (340 mL) was added
hydrochloric acid (0.05 M, 340 mL). After the reaction mixture had
–
been kept at ca. 22°C for 24 h, Amberlite IRA-400 (HCO3 ) resin (20
Acetylation of (5a) gave liquid methyl 2,3-di-O-acetyl-4,5-O-iso-
propylidene-β-D-glucoseptanoside (5b), short path distilled,
[α]2D2 –140.3° (c, 1.64 in CHCl3) (Found: C, 52.6; H, 7.1%. C14H22O8
requires C, 52.8; H, 7.0%). νmax (thin film) 1760, 1245, 1220 cm–1.
Benzoylation of (5a) yielded crystalline methyl 2,3-di-O-
benzoyl-4,5-O-isopropylidene-β-D-glucoseptanoside (5c), as needles
from ethanol, m.p. 135–136°C, [α]2D2 –74.9° (c, 1.03 in CHCl3)
(Found: C, 65.4; H, 5.9%. C24H26O8 requires C, 65.2; H, 5.9%). νmax
1735, 1600, 1263, 1085, 1063, 700 cm–1.
mL) was added and the mixture stirred until pH-test paper indicated
neutrality. Evaporation of the filtered solution gave a light brown
residue (16.8 g), which was shaken with water (200 mL) and carbon
tetrachloride (100 mL). Evaporation of the organic extract, after
washing with water (20 mL), gave (1) (8.34 g) which was identified by
TLC and infrared spectroscopy. Evaporation of the aqueous solutions
gave 8.37 g of a mixture which showed three spots on TLC, at RF 0.62,
0.56, and 0.48, identified below as corresponding to (4a), (5a), and (3a),
respectively, using 11:1 ethyl acetate/ethanol. GLC of an acetylated
sample showed three peaks (column 1), retention times 15.0, 13.4, and
9.3 min in the ratio 1:4:7, identified below as due to (4b), (5b), and
(3b), respectively.
Methyl β-D-Glucoseptanoside (2)
A suspension of finely ground (1) (10.00 g) in hydrochloric acid
(0.05 M, 200 mL) was stirred at room temperature for 24 h. After
Separation of the Monoacetals
–
neutralization using Amberlite IRA-400 (HCO3 ) resin (10 mL), the
Using Ion-Exchange Resins. A solution of the three monoacetals
(9.00 g) in water (20 mL) was added to a column of cation ion-exchange
resin in the Ca2+ form and water was used as eluent. Fractions of 10 mL
were collected. Evaporation of fractions 26–31 gave (4a) (0.30 g) as a
liquid and fractions 32–44 contained (1), (3a), and (5a).
filtered mixture was evaporated and the residue was freed of water by
evaporating
a solution in a mixture of ethanol and benzene.
Crystallization of the product from ethanol gave the title compound
(6.02 g, 85%) with m.p. and optical rotation identical to those reported
earlier.[4,5]
A solution of the three monoacetals (8.4 g) in methanol (15 mL) and
water (3 mL) was added to a column of cation ion-exchange resin (Ca2+
form) packed in methanol/water (4:1). Fractions of 10 mL were eluted
with methanol/water (4:1). Fractions 18–20 contained (1) and (4a)
which were separated using a small column of silica gel in ethyl
acetate/light petroleum (1:1) to give (1) (0.80 g) and methyl
3,4-O-isopropylidene-β-D-glucoseptanoside (4a) (0.33 g), distilled at
0.3 mm Hg (100°C bath), [α]2D2 –78.7° (c, 1.08 in CHCl3), [α]2D2 –97.0°
(c, 1.03 in H2O) (Found: C, 51.2; H, 8.0%. C10H18O6 requires C, 51.3;
H, 7.8%). νmax (thin film) 3450, 1080, 1035 cm–1. A further 0.15 g of
(4a) was obtained from fractions 21 and 22. Fractions 29 and 30
contained methyl 4,5-O-isopropylidene-β-D-gluco-septanoside (5a)
(0.43 g), which crystallized from ethyl acetate as plates, m.p. 94–95°C,
[α]2D3 –136.5° (c, 1.00 in CHCl3), [α]2D3 –170.0° (c, 1.00 in H2O)
(Found: C, 51.5; H, 7.7%. C10H18O6 requires C, 51.3; H, 7.8%). νmax
3440, 3400, 1070, 1035, 1015 cm–1. Fractions 38–43 gave methyl
2,3-O-isopropylidene-β-D-glucoseptanoside (3a) (0.83 g), which
crystallized from benzene/light petroleum as needles, m.p. 87–89°C,
Acetonation of Methyl β-D-Glucoseptanoside (2)
Using DMP. To a well stirred solution of (2) (4.00 g) in anhydrous
DMF (40 mL) were added DMP (2.58 g) and p-toluenesulfonic acid
(0.25 g). After the solution had stood for 14 h at ca. 23°C, TLC (ethyl
acetate/ethanol 11:1) showed no starting material and the formation of
the three monoacetals and (1). After neutralization of the reaction
–
mixture by stirring with Amberlite IRA-400 (HCO3 ) resin, the filtered
solution was evaporated and the residue freed of DMF by the addition
of xylene and evaporation. Separation of the products was carried out
using the two ion-exchange columns as described above to give (1)
(1.10 g, 20%), (3a) (0.90 g, 19%), (4a) (2.00 g, 42%), and (5a) (0.70 g,
15%).
Using Acetone. To a solution of sulfuric acid (10 µL) in acetone
(50 mL) was added (2) (1.00 g). After 3 h at 23°C, the stirred solution
showed no starting glycoside by TLC. After addition of a few drops of
aqueous ammonia solution, the filtered solution was evaporated and the

Septanose Carbohydrates. VII
177
residue was chromatographed using the two ion-exchange columns as
above, yielding (1) (0.25 g, 18%), (3a) (0.41 g, 34%), (4a) (0.25 g,
21%), and (5a) (0.15 g, 12%).
were chromatographed using silica gel (15 g) and benzene/ether (15:1)
as eluent. The first compound eluted (0.72 g, 27%) was methyl
2,5-di-O-benzoyl-3,4-O-isopropylidene-β-D-glucoseptanoside
(4c)
which crystallized from benzene/light petroleum as plates, m.p.
125–126°C, [α]2D4 –71.2° (c, 1.0 in CHCl3) (Found: C, 65.4; H, 5.8%.
C24H26O8 requires C, 65.2; H, 5.9%). νmax 1741, 1280, 1115, 1050, 712
cm–1. The next compound eluted (1.46 g, 72%) was methyl
2-O-benzoyl-3,4-O-isopropylidene-β-D-glucoseptanoside (4d) which
crystallized from benzene/light petroleum as needles, m.p. 103–105°C,
[α]2D3 –35.4° (c, 1.73 in CHCl3) (Found: C, 60.6; H, 6.8%. C17H22O7
requires C, 60.4; H, 6.6%). νmax 3500, 3400, 1722, 1700, 1285, 1120,
1078, 713 cm–1.
Methyl 4-O-Acetyl-2,3-O-isopropylidene-β-D-glucoseptanoside (3d)
To a solution of (3a) (2.57 g) in pyridine (25 mL) was added acetic
anhydride (1.04 mL) (1.0 mole equiv.) at room temperature. The
reaction was monitored by TLC using benzene/ethyl acetate (1:2)
which showed (3a) (RF 0.10), (3d) (RF 0.31), and (3b) (RF 0.62), and by
GLC (Col 1 at 180°C) which showed three peaks with retention times
9.8 (3b), 8.2 (3d), and 5.3 min (3a). After the reaction mixture had been
kept at room temperature for 7 h, absolute ethanol (2 mL) was added
and the mixture was processed using the standard procedure. A solution
of the products in a mixture of benzene and light petroleum gave needle
crystals (1.20 g, 40%). Recrystallization from ethanol gave the title
compound as needles, m.p. 132–133°C, [α]2D4 –108.7° (c, 0.6 in
CHCl3) (Found: C, 52.3; H, 7.3%. C12H20O7 requires C, 52.2; H, 7.3%).
Methyl 2-O-Benzoyl-3,4-O-isopropylidene-β-D-xylo-
hexoseptanosid-5-ulose (9)
Ruthenium tetroxide oxidation of (4d) (1.46 g) was carried out as for
(3d). The title product (1.12 g, 77%) crystallized from benzene as
prisms, m.p. 180–182°C, [α]2D3 +27.0° (c, 1.03 in CHCl3) (Found: C,
60.7; H, 6.1%. C17H20O7 requires C, 60.7; H, 6.0%). νmax 1750, 1725,
1280, 1120, 1085, 710 cm–1.
ν
max 3500, 1732, 1252, 1240, 1079, 1058 cm–1.
Methyl 4-O-Acetyl-2,3-O-isopropylidene-β-D-xylo-
hexoseptanosid-5-ulose (7)
A mixture containing sodium metaperiodate (5 g), ruthenium dioxide
(hydrated, Engelhard, New Jersey, 1 g) and water (40 mL) was shaken
until no dioxide was present. Ethanol-free chloroform was added and
the mixture shaken vigorously. The chloroform extract was added to a
solution of (3d)/1.00 g) in chloroform and the mixture was kept at room
temperature. The reaction was monitored by TLC using light
petroleum/ethyl acetate (1:1) (two developments) which showed (3d)
(RF 0.36) and (7) (RF 0.61), and by GLC (Col. 1, 180°C) which showed
two peaks with retention times 8.0 (3d) and 7.1 min (7). After the
starting material could not be detected (3 h), excess ruthenium
tetraoxide was destroyed by the addition of propan-2-ol (15 mL).
Evaporation of the filtered mixture gave a crystalline ketone (7) (0.85
g, 86%) which crystallized from benzene as plates, m.p. 143–144.5°C,
[α]2D3 –164.0° (c, 1.0 in CHCl3) (Found: C, 52.7; H, 6.7%. C12H18O7
requires C, 52.6; H, 6.6%). νmax 1760, 1742, 1240, 1080, 1070 cm–1.
Methyl 2-O-Benzoyl-3,4-O-isopropylidene-α-L-idoseptanoside (10d)
Reduction of (9), using sodium borohydride, was carried out using two
procedures.
(a) A solution of the ketone (9) (0.43 g) in chloroform (4 mL) was
added dropwise to a stirred solution of sodium borohydride (0.40 g) in
ethanol (4 mL). The reaction was monitored by TLC using
benzene/methanol (25:1) (threefold development) which showed (9)
(RF 0.72), (4d) (RF 0.46), and (10d) (RF 0.34). After 20 min the starting
ketone could not be detected. Excess borohydride was destroyed by the
addition of acetone. Sodium ions were removed by stirring the mixture
with Amberlite IRC-50, H+ resin until pH indicator paper showed
neutrality. Evaporation of the filtered solution gave a colourless residue
(0.50 g) which was chromatographed using silica gel (25 g) and
chloroform/benzene (1:1) as eluent. The first compound eluted was
identified as (4d) (0.24 g, 55%), m.p. 103–105°C, GLC of a sample
after debenzoylation followed by acetylation showed the same retention
time as (4b). The second compound eluted (0.15 g, 35%) was methyl
2-O-benzoyl-3,4-O-isopropylidene-α-L-idoseptanoside (10d) which
crystallized from benzene/light petroleum as plates, m.p. 188–190°C,
[α]2D3 –19.7° (c, 0.87 in CHCl3) (Found: C, 60.5; H, 6.4%. C17H22O7
requires C, 60.4; H, 6.6%). νmax 3460, 1730, 1285, 1270, 1060, 705
cm–1.
Reduction of (7)
To a solution of (7) (0.50 g) in ethanol (15 mL), sodium borohydride
(0.3 g) in ethanol (6 mL) was added dropwise with stirring. After no (7)
could be detected by TLC, acetone (2 mL) was added to the stirred
mixture, followed by Amberlite IRC-50 (H+) ion-exchange resin, and
stirring was continued until pH indicator paper showed neutrality.
Evaporation of the filtered solution gave a liquid (0.48 g), which was
treated with a catalytic amount of sodium methoxide in methanol
followed by the addition of Amberlite IRC-50 (H+) resin. Evaporation
of the filtered mixture gave a liquid (0.39 g). GLC analysis of an
acetylated sample (Column 2, 180°C) showed two products with
retention times 10.35 (3b) and 7.6 min (8b) in the ratio 3:2. Separation
of (3a) and (8a) was effected by chromatography on a column of cation
exchange resin (Ca2+) using methanol/water (4:1) as eluent. Fractions
(10 mL) 24–26 gave crystalline methyl 2,3-O-isopro-
pylidene-α-L-idoseptanoside (8a) (0.16 g, 38%), which crystallized
from ethyl acetate as prisms, m.p. 132–133.5°C, [α]2D3 –99.0° (c, 1.67
in CHCl3) (Found: C, 51.1; H, 7.9%. C10H18O6 requires C, 51.3; H,
7.8%). νmax 3502, 1245, 1083, 1070, 1040 cm–1.
Debenzoylation of (10d) was effected by dissolving the ester in
methanol containing catalytic amount of sodium methoxide followed
by stirring with Amberlite IRC-50, H+ to remove sodium ions.
Evaporation of the filtered solution gave a colourless liquid which was
chromatographed on silica gel using chloroform/light petroleum (1:1)
in order to remove methyl benzoate. Appropriate fractions gave methyl
3,4-O-isopropylidene-α-L-idoseptanoside (10a), which crystallized
from ethyl acetate as prisms, m.p. 165–167°C, [α]2D3 –66.2° (c, 1.10 in
CHCl3) (Found: C, 51.5; H, 7.9%. C10H18O6 requires C, 51.3; H, 7.8%).
ν
max 3480, 1060, 1050, 995 cm–1.
Acetylation of (10a) gave methyl 2,5-di-O-acetyl-3,4-O-isopro-
pylidene-α-L-idoseptanoside (10b) which crystallized from
benzene/light petroleum as plates, m.p. 138–139°C, [α]2D3 –17.0° (c,
1.06 in CHCl3) (Found: C, 53.2; H, 7.0%. C14H22O8 requires C, 52.8;
H, 7.0%). νmax 1750, 1240, 1040 cm–1.
Benzoylation of (10d) gave methyl 2,5-di-O-benzoyl-3,4-O-isopro-
pylidene-α-L-idoseptanoside (10c) which crystallized from benzene as
plates, m.p. 222–224°C, [α]2D3 +45.0° (c, 1.45 in CHCl3) (Found: C,
64.9; H, 5.8%. C24H26O8 requires C, 65.2; H, 5.9%). νmax 1728, 1283,
1269, 1110, 1100, 1073, 705 cm–1.
Acetylation of (8a) gave methyl 4,5-di-O-acetyl-2,3-O-isopro-
pylidene-α-L-idoseptanoside
(8b)
which
crystallized
from
benzene/light petroleum as needles, m.p. 123–125°C, [α]2D5 –75.0° (c,
1.7 in CHCl3) (Found: C, 53.0; H, 7.2%. C14H22O8 requires C, 52.8; H,
7.0%). νmax 1760, 1238, 1085, 1060, 1035 cm–1.
Selective Benzoylation of (4a)
To a solution of (4a) (1.40 g) in pyridine (7 mL), a solution of benzoyl
chloride (1 mL, 1.44 equiv.) in pyridine (2 mL) was added dropwise
with stirring. The reaction was monitored by TLC using benzene/ether
(1:1) which showed spots for (4a), (4d), and (4c) with RF 0.08, 0.38,
and 0.77, respectively. After the reaction mixture had been kept at room
temperature for 2 h, the usual work-up gave 2.22 g of products which
(b) A solution of sodium borohydride (0.10 g) in ethanol (3 mL) was
added dropwise to a stirred solution of (9) (0.40 g) in chloroform (4
mL). TLC of the reaction mixture as in (a) showed an extra spot at RF
0.24. Work up and chromatography of the products as in (a) gave (4d)
(0.17 g, 42%), (10d) (0.11 g, 27%), and (tentatively) methyl
2-O-benzoyl-6-C-(methyl 2-O-benzoyl-3,4-O-isopropylidene-α-L-ido-

178
T. Q. Tran and J. D. Stevens
septanoside-5-yl)-3,4-O-isopropylidene-α-L-idoseptanoside (11) (0.10
g, 12%), which crystallized from benzene/light petroleum as needles,
m.p. 138–140°C, [α]2D3 –3.0° (c, 0.99 in CHCl3) (Found: C, 59.5; H,
6.4%. C34H42O14 requires C, 60.5; H, 6.3%). νmax 3460, 1738, 1720,
1600, 1270, 1070, 705 cm–1. 1H NMR (500 MHz) δ 1.395, 3H, s,
C–Me; 1.434, 3H, s, C–Me; 1.439, 3H, s, C–Me; 1.445, 3H, s, C–Me;
1.591, s, OH; 3.748, d, J 13.72 Hz, H6b,B; 3.931, d, J 4.28 Hz, H6,A;
4.041, dd, J 10.02, 9.37 Hz, H3,A; 4.188, d, J 9.00 Hz, H4,B; 4.266, m,
J 9.37, 7.39 Hz, H4,A; 4.274, m, J 4.28, 7.39 Hz, H5,A; 4.430, d, J 7.70
Hz, H1,A; 4.455, dd, J 9.00, 9.83 Hz, H3,B; 4.483, d, J 6.60 Hz, H1,B;
4.590, d, J 13.72 Hz, H6a,B; 5.284, dd, J 6.60, 9.83 Hz, H2,B; 5.392,
dd, J 7.70, 10.02 Hz, H2,A. Analysis of H3,A; H4,A; H5,A; and H6,A
was achieved by iterative analysis as a four-spin system using the
program GNMR (Cherwell Scientific). Correlations were obtained
using the correlation spectroscopy (COSY) program. CI mass spectrum
(isobutane): m/z 675 ([M+H]+, 26%), 643 (20), 337 (54), 273 (98), 123
(100).
C, 43.0; H, 7.4%. C7H14O6 requires C, 43.3; H, 7.3%). νmax 3550, 3440,
3405, 3300, 1230, 1055, 1030 cm–1.
Acetylation of (12a) gave methyl 2,3,4,5-tetra-O-acetyl-α-L-
idoseptanoside (12b), which crystallized from benzene/light petroleum
as prisms, m.p. 133–134°C, [α]2D2 –85.1° (c, 1.03 in CHCl3) (Found: C,
50.0; H, 6.2%. C15H22O10 requires C, 49.7; H, 6.1%). νmax 1771, 1765,
1745, 1235, 1220, 1040, 1025 cm–1.
Methyl 2,3:4,5-Di-O-isopropylidene-α-L-idoseptanoside (13)
To a stirred solution of sulfuric acid (10 µL) in acetone (1 mL) at room
temperature was added (12a) (0.10 g) and 2,2-dimethoxypropoane (10
mL). The reaction was monitored by TLC using ethyl acetate/light
petroleum (1:1) which showed (13) and (12a) with RF 0.48 and 0.05,
respectively. No (12a) could be detected after 7 h. The reaction mixture
–
was neutralized using Amberlite IRA-400 (HCO3 ) resin and the
products obtained by evaporation of the filtered mixture were
chromatographed on silica gel using ether/light petroleum (1:5). The
title compound, eluted first, crystallized from light petroleum as
needles (30 mg, 21%), m.p. 97–100°C, [α]2D2 –72.4° (c, 0.85 in CHCl3)
(Found: C, 57.2; H, 8.1%. C13H22O6 requires C, 56.9; H, 8.1%). νmax
1232, 1083, 1064 cm–1.
Methyl 2-O-Benzoyl-3,4-O-isopropylidene-5-O-
p-toluenesulfonyl-β-D-glucoseptanoside (4e)
To a solution of (4d) (1.97 g) in pyridine (20 mL) was added
p-toluenesulfonyl chloride (4.43 g, 4 equiv.). The reaction mixture was
kept at 50°C and the reaction was monitored by TLC using ethyl
acetate/light petroleum (1:1), which showed (4d) and (4e) with RF 0.37
and 0.69, respectively. After 48 h (4d) could not be detected and the
mixture was worked-up using the same procedure as for benzoylations
to give the title compound (2.82 g, 98%) which crystallized from
benzene as prisms, m.p. 174–175°C, [α]2D2 –12.4° (c, 1.00 in CHCl3)
(Found: C, 58.5; H, 5.7%. C24H28O9S requires: C, 58.5; H, 5.7%). νmax
1731, 1610, 1275, 1180, 1115, 1100, 995, 710 cm–1.
Similar treatment of (8a) gave crystals of (13) with the same m.p.
and optical rotation as the product obtained above.
Acknowledgments
Microanalyses were performed by Mr J. Sussman of this
School. We are grateful to Mrs H. Stender of the University
of New South Wales High-Field NMR Facility for the 500
MHz spectra and to Mr D. Nelson for the CI mass spectra.
Reaction of (4e) with Lithium Benzoate in DMF
A suspension containing (4e) (1.00 g) and lithium benzoate (2 g) in
DMF (10 mL) was heated under reflux. The course of the reaction was
monitored by TLC using benzene/ether (5:1) which showed (4e) and
(10c) with RF 0.68 and 0.50, respectively. After 3.5 h (4e) could not be
detected and water (20 mL) was added to the reaction mixture followed
by extraction with chloroform (2 × 8 mL). The residue left upon
evaporation of the extracts was freed of DMF by threefold evaporation
with xylene to give a crystalline product (0.70 g, 78%), which
crystallized from benzene as plates which had the same m.p., optical
rotation, infrared and NMR spectra as (10c) prepared as above.
References
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[17] S. J. Foster, V. J. James, J. D. Stevens, Acta Crystallogr., Sect. C:
Cryst. Struct. Commun. 1989, 45, 1329.
[18] D. Horton, E. K. Just, Carbohydr. Res. 1969, 9, 129.
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Equilibration of Methyl 3,4-O-Isopropylidene-α-L-idoseptanoside
(10a)
To a well-stirred solution of sulfuric acid (4.4 µL) in acetone (22 mL)
at room temperature was added (10a) (0.43 g). The course of the
reaction was followed by TLC using ethyl acetate/light petroleum (2:1)
(3 developments) which showed (8a) and (10a) with RF 0.45 and 0.37,
respectively. GLC (Column 2 at 155°C) of the diacetate derivatives
showed peaks at 12.3 and 15.5 min for (8b) and (10b), respectively.
After 2.5 h, the neutralized (ammonia solution) and filtered solution
was evaporated, and the residue chromatographed on an ion-exchange
resin (Ca2+ form) using water/methanol (3:2). Fractions (10 mL) 28
and 29 gave (10a) (0.17 g, 40%), and fractions 33 and 34 gave (8a)
(0.26 g, 60%).
Methyl α-L-Idoseptanoside (12a)
A suspension of (10a) (0.37 g) in hydrochloric acid (0.05 M, 8 mL) was
stirred at room temperature. The reaction was monitored by TLC using
ethyl acetate/ethanol (11:1) which showed (10a) and (12a) with RF 0.66
and 0.25, respectively. After 55 h, the mixture was neutralized using
–
Amberlite IRA-400 (HCO3 ) resin. Evaporation of the filtered solution
gave the title compound (0.27 g, 88%) which crystallized from ethanol
as needles, m.p. 160–163°C, [α]2D2 –103.2° (c, 1.59 in MeOH) (Found: