Preparation of 1,2-O-isopropylidene derivatives of α-D-galactoseptanose, β-L-altroseptanose, and 3-O-methyl-α-D-guloseptanose

Article abstract of DOI:10.1016/S0008-6215(01)00179-3

Displacement of the tosyloxy group in 5-O-benzyl-1,2-O-isopropylidene-4-O-(p-toluenesulfonyl)-α-D- glucoseptanose has yielded derivatives of 1,2-O-isopropylidene-α-D-galactoseptanose. Acid catalysed acetonation then gave 1,2:3,4-di-O-isopropylidene-α-D-galactoseptanose or 1,2;4,5-di-O-isopropylidene-α-D-galactoseptanose using lower acid concentrations. Reduction of the ketone derived from 1,2:3,4-O-isopropylidene-α-D-septanose gave 1,2;3,4-di-O-isopropylidene-β-L-altroseptanose. Reaction of 3,4-anhydro-5-O-benzyl-1,2-O-isopropylidene-α-D-galactoseptanose with sodium methoxide gave 5-O-benzyl-1,2-O-isopropylidene-4-O-methyl-α-D-glucoseptanose and 5-O-benzyl-1,2-O-isopropylidene-3-O-methyl-α-D-guloseptanose. Solution-state conformations of these compounds have been deduced from their ¹H NMR spectra.

Full text of DOI:10.1016/S0008-6215(01)00179-3

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Carbohydrate Research 334 (2001) 81–89
Preparation of 1,2-O-isopropylidene derivatives of
a-
D
-galactoseptanose, b-
L
-altroseptanose, and
3-O-methyl-a-
D
-guloseptanoseꢀ
Graham E. Driver,1 John D. Stevens*
School of Chemistry, Uni6ersity of New South Wales, Sydney, NSW 2052, Australia
Received 10 April 2001; accepted 26 June 2001
Abstract
Displacement of the tosyloxy group in 5-O-benzyl-1,2-O-isopropylidene-4-O-(p-toluenesulfonyl)-a-
tanose has yielded derivatives of 1,2-O-isopropylidene-a- -galactoseptanose. Acid catalysed acetonation then gave
1,2:3,4-di-O-isopropylidene-a- -galactoseptanose or 1,2;4,5-di-O-isopropylidene-a- -galactoseptanose using lower
acid concentrations. Reduction of the ketone derived from 1,2:3,4-O-isopropylidene-a- -septanose gave 1,2;3,4-di-O-
isopropylidene-b- -altroseptanose. Reaction of 3,4-anhydro-5-O-benzyl-1,2-O-isopropylidene-a- -galactoseptanose
with sodium methoxide gave 5-O-benzyl-1,2-O-isopropylidene-4-O-methyl-a- -glucoseptanose and 5-O-benzyl-1,2-
-guloseptanose. Solution-state conformations of these compounds have been de-
D-glucosep-
D
D
D
D
L
D
D
O-isopropylidene-3-O-methyl-a-
D
1
duced from their H NMR spectra. © 2001 Published by Elsevier Science Ltd.
Keywords: Septanose compounds; Acetals; Conformations
2. Results and discussion
The benzyl ether (1b) of 1,2:3,4-di-O-iso-
1. Introduction
Inversion of configuration at C-4 of
D
-glu-
propylidene-a- -glucoseptanose (1a) was cho-
sen as the starting material for the preparation
of -galactoseptanose compounds. Crystalline
D
cose gives rise to
D
-galactose. We describe
here the conversion of a derivative of 1,2-O-
D
isopropylidene-a-
D
-glucoseptanose into
a
1b was obtained in 90% yield by benzylation
of 1a using sodium hydride in DMF, followed
by benzyl chloride. Hydrolysis of 1b using an
aqueous hydrochloric acid–dioxane mixture
derivative of 1,2-O-isopropylidene-a-
D
-galac-
toseptanose and the preparation of other
D
-
galactoseptanose compounds from this
product. Inversion of configuration at C-4 and
gave
5-O-benzyl-1,2-O-isopropylidene-a- -
D
C-5 gave
L
-altro derivatives, and inversion at
-gulo derivatives.
glucoseptanose (2a) in 47% yield, based on a
41% recovery of starting material. As this
procedure involved recycling of recovered
starting material several times in order to
C-3 and C-4 gave
D
avoid hydrolysis of 2a to 5-O-benzyl- -glu-
D
ꢀ Septanose carbohydrates, Part 6. For Part 5, see Ref. 1.
* Corresponding author. Fax: +61-2-93856141.
E-mail address: johndstevens@yahoo.com (J.D. Stevens).
1 Present address: Defence Nutrition Research Centre,
DSTO, 76 George Street, Scottsdale, TAS 7620, Australia.
cose, the use of an acidified solution of 1b in
ethanol was examined. Although no advan-
tage was found using this procedure, it is of
some interest that two additional byproducts,
0008-6215/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0008-6215(01)00179-3

82
G.E. Dri6er, J.D. Ste6ens / Carbohydrate Research 334 (2001) 81–89
proximity of the C-4 hydroxyl group to the
oxygen function on C-5. In an earlier study, it
was noted that the more reactive hydroxyl
group towards tosylation of a diol was
strongly intramolecularly hydrogen bonded.3
From later studies,4 it was concluded that
polar interactions provide a more satisfactory
explanation of the enhanced reactivity. The
phenomenon has been reviewed.5
1,2-O-Isopropylidene-h- -galactoseptanose
D
(4d).—Treatment of 2b with sodium benzoate
in DMF at 100 °C gave a mixture of products.
Chromatography of these products over silicic
acid gave as the first eluted compound, crys-
talline epoxide 3, which showed no carbonyl
or hydroxyl group absorptions in the infrared
1
spectrum. The H NMR spectrum of 3 confi-
rmed the epoxide structure, the low frequen-
cies of H-3 and H-4 being typical of hydrogen
atoms attached to oxirane rings,6 and this
product is formulated as 3,4-anhydro-5-O-
benzyl-1,2-O-isopropylidene-a- -galactosep-
D
tanose (3) with the configuration at C-3 and
C-4 following from the mode of formation
and from the structures of ring opening prod-
ucts (see below). A syrupy material eluted
after 3 showed carbonyl absorption in the
1
infrared spectrum, and the H NMR spectrum
indicated a mixture of the 3-O-benzoyl and
4-O-benzoyl derivatives of 5-O-benzyl-1,2-O-
the a and b isomers of ethyl 5-O-benzyl- -glu-
D
cofuranoside steadily increased in concentra-
isopropylidene-a- -galactoseptanose (4a). Sa-
D
tion,
notwithstanding
the
significant
ponification of this mixture gave the
crystalline diol 4a which yielded 4b on hy-
drogenolysis. Acetylation of 4b yielded a liq-
uid triacetate 4c. Proton coupling constants
percentage of water in the hydrolysis mixture.
Tosylation of 2a gave a mixture of products
that afforded the 4-O-tosyl derivative (2b) in
49% yield. A small amount of the isomeric
monotosylate (2c) as well as the ditosylate (2d)
(15%) was also isolated. The identity of the
major monotosylate as 2b followed from the
1
chemical shifts of H-3 and H-4. In the H
NMR spectrum of 1,2-O-isopropylidene-a- -
D
glucoseptanose, H-3 comes into resonance at
higher frequency than H-4.2 For 2b, H-4 ap-
pears at higher frequency than H-3, and for
the benzoate derivative of 2b, compound 2e,
H-3 comes into resonance at significantly
higher frequency than H-4 (see Table 1).
Confirmation of the structure of 2b is pro-
vided by the structures of products formed by
ring opening of an epoxide (see below) derived
from 2b. The relatively high yield of monoto-
sylate 2b may be accounted for by the close

G.E. Dri6er, J.D. Ste6ens / Carbohydrate Research 334 (2001) 81–89
83
for 1,2-O-isopropylidene-a-
D
-glucoseptanose
triacetate (2f), except for those involving H-4,
are similar to those of 4c, indicating similar
conformations for these two compounds,
probably the twist-chair conformation,
4,5TC6,0.2 Four-bond spin coupling between
H-4 and H-6a (a W configuration) is consistent
with this conformation.
1,2:3.4-Di-O-isopropylidene-h- -galactosep-
D
tanose (4d).—Treatment of 4a with acidified
acetone and 2,2-dimethoxypropane yielded a
liquid compound, which on hydrogenolysis
gave the crystalline alcohol 4d. In order to
eliminate the possibility of a change of
configuration at C-1 during the acetonation of
4a, 4d was hydrolysed to give a 1,2-O-iso-
propylidene compound whose triacetate was
identified as 4c, thereby confirming the alpha
configuration of 4d. Proton spin-coupling con-
stants obtained for the acetate 4e derived from
4d are markedly different from those of the
gluco analog,2 indicating a different confor-
mation. Earlier calculations by Hendrickson7
showed that it is not possible to fuse two
five-membered rings cis–anti–cis to a seven-
membered ring in a chair or twist-confor-
mation without considerable distortion. If the
seven-membered ring is in a boat or twist-boat
conformation, such a fusion of five-membered
rings can take place without undue strain.
Conformation of 4e.—Of the 28 boat, twist-
boat conformations that are involved in the
boat–twist-boat pseudorotational continuum
for the septanose ring,8 three conformations,
1,2,5B, 1,2TB3,4, and 3,4,0B, appear to be most
likely for 4e. Of these, conformation 1,2,5B
corresponds to the lowest-energy boat confor-
mation of oxepan, boat-2, deduced by Bocian
and Strauss.9 However, none of the mentioned
conformations account well for the observed
proton coupling constants listed in Table 2; in
particular, the value of J3,4, is far too large for
a dihedral angle of 34° in conformation 1,2,5B.9
It may be that the molecule is undergoing
pseudolibration over the three mentioned
conformations in solution. In the solid state,
the septanose ring of 4e has been described10 as
a boat, 1,2,5B, flattened in the region of C-3 and
C-4. If the solution-state conformation is
similar to that observed in the solid state, this
flattening in the C-3–C-4 region would
account for the large magnitude of J3,4.

84
G.E. Dri6er, J.D. Ste6ens / Carbohydrate Research 334 (2001) 81–89
3-O-Acetyl-1,2:4,5-di-O-isopropylidene-h- -
D
galactoseptanose (4g).—Treatment of 4b with
acetone containing 0.02% sulfuric acid by vol-
ume gave a mixture of two products, one of
which was identified as 4d by gas chroma-
tography. The major product was identified
1
by acetylation and analysis of the H NMR
spectrum as 1,2:4,5-di-O-isopropylidene-a- -
D
galactoseptanose (4f) derived acetate 4g. In-
creasing the reaction time resulted in an
increase in the ratio of 4d to 4f. Isomer 4f is
therefore the kinetically controlled product,
and 4d the product of thermodynamic control.
Similar results were reported for the gluco and
ido analogs.2,11
A probable conformation of 4g in solution
has been deduced by examination of the pro-
ton-spin coupling constants. Various boat and
twist-boat conformations are excluded by the
values of J2,3 and J3,4. Of the two twist-chair
conformations, 6,0TC4,5 and 3,4TC5,6 formed by
twisting around C-1–C-2 of the chair confor-
5
mation, C1,2, conformation, 3,4TC5,6, with an
expected dihedral angle of 32° for H-2–H-3
does not account for the value of 3.0 Hz for
J2,3. Conformation 6,0TC4,5 appears to account
for the observed coupling constants.
1,2:3,4-Di-O-isopropylidene-i- -altrosep-
L
tanose (6a).—Oxidation of 4d with ruthe-
nium tetroxide gave a ketone that was
reduced with sodium borohydride to give a
Table 2
1H NMR coupling constants (J, Hz)
Compound
Solvent
J1,2
J2,3
J3,4
9.60
J4,5
J5,6a
1.65
J5,6b
1.60
J6a,6b
JCH2
Other
1b
2b
2c
2d
2e
2h
3
4c
4e
4g
5b
5b
5c
5c
6b
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
C6D6
CDCl3
CDCl3
CDCl3
CDCl3
C6D6
3.94
3.93
4.00
4.14
4.00
3.95
3.65
3.75
4.93
3.8
5.13
5.10
5.11
5.07
4.7
7.16
6.71
7.56
6.72
7.46
7.72
1.94
7.45
8.20
3.0
1.33
1.23
1.33
1.25
6.3
2.17
1.92
2.23
2.03
1.90
1.75
5.60
6.01
9.97
ND
9.01
9.03
9.44
9.36
2.2
13.79
13.83
13.93
13.50
13.65
13.40
12.04
14.17
11.35
11.6
12.60
12.74
12.65
12.56
13.5
11.59
11.98
11.78
12.01
12.21
12.35
12.10
9.61
9.26
8.86
9.63
9.30
4.37
0.88
7.61
1.5
10.18
10.28
10.16
10.24
8.0
3.08
2.99
4.29
3.48
3.28
8.82
2.22
6.28
5.6
10.86
11.00
10.86
10.97
4.3
1.87
1.85
1.93
1.87
1.96
5.21
2.28
10.66
8.8
4.09
4.25
4.42
4.49
1.8
J2,4 0.56
J4,6a 1.15
11.80
11.97
CDCl3
C6D6
C6D6

G.E. Dri6er, J.D. Ste6ens / Carbohydrate Research 334 (2001) 81–89
85
C-1–C-2. Either of these twist-chair confor-
mations would account for the observed
NMR parameters, including the unusually
high frequency of absorption of H-4, the re-
sult of close proximity of H-4 and O-1 or
O-2.14 The former conformation is expected to
be favoured by the anomeric effect.
mixture of two products, separable by silicic
acid column chromatography, giving 4d and a
new, crystalline product, 6a. Identification of
the new product as the altro isomer was con-
firmed by treatment with aqueous acid, fol-
lowed by sodium borohydride. Acetylation
gave a hexitol hexaacetate that had the same
GLC retention time as hexa-O-acetylaltritol.
Acetylation of 6a gave the liquid acetate, 6b
whose 1H NMR spectrum was readily
analysed (data in Tables 1 and 2).
3. Experimental
The solution-state conformation of 6b is
probably similar to that of 4e as the spin
coupling constants, except for those involving
H-5, are similar to those of 4e. We note that
the value of J6a,6b, 13.5 Hz, is consistent with
O-5 being antiperiplanar to one of the geminal
hydrogen atoms,12 as expected for the 1,2TB3,4
conformation.
General methods.—See Ref. 11. For the
data presented in Tables 1 and 2 the methyl-
ene hydrogens of benzyl ether groups were
analysed as AB systems, H-5, H-6a, and H-6b
were analysed as ABX systems,15 except for 5b
for which the program GNMR (Cherwell Scien-
tific) was used iteratively for H-4, H-5, H-6a,
and H-6b as a four-spin system. Data for
aromatic hydrogens are not reported.
4,5-Di-O-acetyl-1,2-O-isopropylidene-3-O-
methyl-h- -guloseptanose (5c).—Refluxing a
D
5-O-Benzyl-1,2:3,4-di-O-isopropylidene-h- -
D
solution of epoxide 3 with sodium methoxide
in methanol gave two products in approxi-
mately equal amounts. Separation of these
products was effected by column chromatog-
raphy. The second product that eluted, 2g,
glucoseptanose (1b).—Sodium hydride (5 g.
1:1 emulsion with mineral oil, washed with
anhyd ether) was added to a solution of 1a
(8.02 g, 30.8 mmol) in DMF (40 mL), and the
suspension was stirred for 1.5 h. Benzyl chlo-
ride (4 mL, 34.8 mmol) was added whilst
cooling, and the solution was stirred for a
further 2 h. Water was added in small por-
tions in order to destroy excess sodium hy-
dride. After adding water (400 mL), the
mixture was kept at rt until crystallisation was
complete. Crude 1b (10.6 g) was collected by
filtration and recrystallised from an EtOH–
water mixture to give 1b (9.8 g, 91%) as white
needles: mp 130–131 °C; [h]2D3 −47.1° (c 1.3,
CHCl3). Anal. Calcd for C19H26O6: C, 65.13;
H, 7.48. Found: C, 65.30; H, 7.65.
1
was identified by analysis of the H NMR
spectrum of the derived acetate and by com-
parison of the coupling constants and chemi-
cal shifts with those of 2e as 3-O-acetyl-5-O-
benzyl-1,2-O-isopropylidene-4-O-methyl-a- -
D
glucoseptanose (2h). This confirmed the
galacto configuration of 3. The first eluted
product was identified as 5-O-benzyl-1,2-O-
isopropylidene-3-O-methyl-a- -guloseptanose
D
1
(5a) by analysis of the H NMR spectrum of
the derived acetate 5b. Hydrogenolysis of 5a,
followed by acetylation, gave the crystalline
diacetate 5c whose structure has been confi-
rmed by X-ray diffraction.13 A one-step con-
version of 2b into 2g and 5a involves
treatment of 2b with sodium methoxide in
methanol.
5-O-Benzyl-1,2-O-isopropylidene-h- -glu-
D
coseptanose (2a).—A solution of 1b (13.9 g,
39.7 mmol) in dioxane (100 mL) and HCl (2
M, 50 mL) was left at 40 °C for 24 h. Partial
evaporation of the neutralised (2 M aq
NaOH) reaction mixture followed by dilution
with water to ca. 300 mL resulted in crystalli-
sation of 1b, which was collected and washed
with water. Chloroform (3×50 mL) extracts
of the aq filtrates were washed with water (50
mL), dried and evaporated to give crude 2a
(2.70 g). The recovered 1b was treated as
The solution-state conformation of 5c may
be deduced from the NMR data. The large
magnitudes of J3,4, J4,5, and J5,6a require these
pairs of hydrogens to be antiperiplanar. The
5
chair conformation C1,2 satisfies this require-
ment. Twisting around the C-1–C-2 bond
gives the twist-chair conformations, 3,4TC5,6
and 6,0TC4,5, thereby relieving eclipsing around

86
G.E. Dri6er, J.D. Ste6ens / Carbohydrate Research 334 (2001) 81–89
J6a,6b 12.20 Hz, H-6ab), 4.706 (d, JAB 11.25
Hz, PhCHAHBꢀOꢀ), 4.688 (JCD 11.45 Hz,
PhCHCHDꢀOꢀ), 4.609 (dd, J5,6a 2.54, J6a,6b
12.10 Hz, H-6aa), 4.461 (d, HB), 4.435 (d,
HD), 4.395 (dd, J4,5 9.12 Hz, H-4b), 4.363 (dd,
J4,5 8.12 Hz, H-4a), 4.167 (dd, J5,6b 4.90 Hz,
H-6ba), 4.150 (dd, J5,6b 4.04 Hz, H-6bb), 3.957
(ddd, H-5b), 3.854 (ddd, H-5a), 3.735 (dq, 1
above (dioxane, 80 mL, aq 2 M HCl, 40 mL)
to give crude 2a (1.54 g) and recovered 1b,
which yielded a further 1.34 g of crude 2a
after similar treatment; total yield of crude 2a,
5.58 g and recovered 1b (5.64 g). Recrystallisa-
tion of crude 2a from benzene gave 3.05 g of
2a with a further 0.44 g obtained by adding
light petroleum to the filtrate, giving a total
yield of 3.49 g of 2a (47% based on unrecov-
ered 1b). A sample was recrystallized from
benzene–light petroleum to needles, mp 120–
122 °C; [h]2D3 −19.3° (c 0.21, CHCl3). Anal.
Calcd for C16H22O6: C, 61.92; H, 7.15. Found:
C, 62.05; H, 6.96.
H, JCH 9.79, JCH ,Me 7.08 Hz, OꢀCH2ꢀMe),
2
3.731 (2dq, 1 H, JCH 9.79, JCH ,Me 7.08 Hz,
2
2
OꢀCH2ꢀMe) 3.507 (dq, 1 H, OꢀCH2ꢀMe),
3.487 (dq, 1 H, OꢀCH2ꢀMe), 2.103 (s, 3 H,
OAc), 2.100 (s, 6 H, OAc), 2.068 (s, 3 H,
OAc), 1.970 (s, 3 H, OAc), 1.964 (s, 3 H,
OAc), 1.201 (tr, 3 H, CH3), 1.170 (tr, 3 H,
ꢀCH3) (assignments by spin-decoupling). Ra-
tio of anomers, a:b=1:1.
Hydrolysis of 1b using acidified aq EtOH.—
To a solution of 1b (6.00 g, 17.1 mmol) in
EtOH (200 mL) at 30 °C was added aq HCl
(0.2 M, 100 mL). The reaction mixture was
kept at 30 °C for 70 h. Samples examined
using TLC (silica gel, EtOAc eluent) showed
four spots, 1b (Rf 0.73), 2a (Rf 0.54), ethyl
Treatment of 5-O-benzyl-1,2-O-isopropyli-
dene-h- -glucoseptanose (2a) with p-toluene-
D
sulfonyl chloride.—A solution of 2a (4.65 g,
15 mmol) and p-toluenesulfonyl chloride (4.00
g, 21 mmol) in pyridine (30 mL) was kept for
50 h at 25 °C. After the addition of water (1
mL), the reaction mixture was kept for 1 h at
25 °C then shaken with CHCl3 (30 mL) and
water (100 mL). The aqueous solution was
extracted with CHCl3 (30 mL), and the com-
bined CHCl3 solutions were washed with 1.5
M aq H2SO4, followed by satd aq NaHCO3,
filtered through a short bed of silica gel (E.
Merck 7734), and evaporated. A benzene solu-
tion of the products gave needle crystals (3.55
g) that were recrystallised from MeOH to
give 5-O-benzyl-1,2-O-isopropylidene-4-O-(p-
glycosides (Rf 0.47) and 5-O-benzyl- -glucose
D
(Rf 0.23). The intensities of spots due to 1b
and 2a were approximately equal after 70 h,
and the intensity of spot Rf 0.47 steadily in-
creased during the reaction time. After neu-
tralising the reaction mixture with Amberlite
IRA-400 (HCO−3 ), the filtered mixture was
evaporated until the residue contained a large
number of needle crystals which were col-
lected, washed with 1:4 EtOH–water and air
dried to give 1b (1.18 g), mp 128–129 °C.
Chloroform (4×30 mL) extracts of the evap-
orated filtrate (ca. 100 mL) were filtered
through a short bed of silicic acid, evaporated,
and a benzene solution of the residue evapo-
rated. Seeding a solution of the residue in a
small volume of light petroleum gave needle
crystals of 2a (1.12 g, 21%), mp 119–121 °C.
Chromatography of the filtrate using silica gel
and ether gave 1b (0.18 g), 2a (0.48 g, 9%), a
mixture of 2a and ethyl glycosides (0.47 g) and
ethyl glycosides (0.22 g, 4.3%). Acetylation of
the glycosides fraction using acetic anhydride
and pyridine with the usual workup gave a
toluenesulfonyl)-a- -glucoseptanose (2b) (3.40
D
g, 49%): mp 141–143 °C; [h]2D3 −48.5° (c 0.7,
CHCl3). Anal. Calcd for C23H28O8S: C, 59.47;
H, 6.08. Found: C, 59.44; H, 6.31.
Chromatography of the products in the
benzene filtrates over silica gel (E. Merck
7736, 80 g) using 1:6 Et2O–benzene as eluent
and 20 mL fractions, gave 5-O-benzyl-1,2-O-
isopropylidene-3,4-di-O-(p-toluenesulfonyl)-a-
D
-glucoseptanose (2d, 1.41 g, 15%) in frac-
tions 10–16. Recrystallisation of the ditosylate
from a mixture of MeOH and EtOAc gave
colourless needles (1.35 g): mp 149–151 °C;
[h]2D0 +30.9° (c 1.26, CHCl3). Anal. Calcd for
C30H34O10S2: C, 58.24; H, 5.54. Found: C,
58,50; H, 5.57. TLC of fractions 29–38
showed only one spot. Crystallisation of this
1
colourless liquid product: H NMR (CHCl3):
l 5.505 (ddd, J2,3 2.84, J3,4 5.01, J1,3 0.48 Hz,
H-3a), 5.314 (dd, J2,3 1.12, J3,4 4.75 Hz, H-3b),
5.221 (dt, J1,2 4.65, J1,4 0.60 Hz, H-1a), 5.227
(dd, J1,2 0.46, J2,3 1.12 Hz, H-2b). 4.950 (d,
H-1b). 4.933 (dd, H-2a), 4.779 (dd, J5,6a 2.39,

G.E. Dri6er, J.D. Ste6ens / Carbohydrate Research 334 (2001) 81–89
87
1,2-O-Isopropylidene-h-
D
-galactoseptanose
product (0.45 g) from MeOH gave needles
(0.18 g, 2.5%), recrystallised from EtOH to
give 5-O-benzyl-1,2-O-isopropylidene-3-O-(p-
(4b).—A solution of 4a (0.175 g, 0.56 mmol)
in MeOH (5 mL) was stirred with hydrogen
and 5% Pd–C at rt and pressure. After uptake
of hydrogen uptake had ceased, the solution
was filtered through Celite and evaporated to
give 0.132 g of a liquid which crystallised on
addition of a few drops of EtOAc. Recrystalli-
sation from EtOAc–acetone gave colourless
prisms of 4b (100 mg, 81%): mp 178–180 °C;
[h]2D0 −14.8° (c 0.8, water). Anal. Calcd for
C9H16O6: C, 49.09; H, 7.32. Found: C, 49.36;
H, 7.33. Acetylation of 4b (0.100 g) using
pyridine and Ac2O with the usual workup
gave a colourless liquid product, 4c (0.173 g):
[h]2D1 −8.6° (c 1.33, CHCl3).
toluenesulfonyl)-a- -glucoseptanose (2c): mp
D
120–121 °C; [h]2D0 +31.4° (c 1.55, CHCl3).
Anal. Calcd for C23H28O8S: C, 59.47; H, 6.08.
Found: C, 59.56; H, 6.27. Fractions 20–28
(0.49 g) contained 2b and 2c by TLC.
3-O-Benzoyl-5-O-benzyl-1,2-O-isopropyli-
dene-4-O-(p-toluenesulfonyl)-h- -glucosepta-
D
nose (2e).—Benzoylation of 2b (147 mg, 0.32
mmol) using BzCl in pyridine and standard
workup gave needle crystals of 2e (89 mg,
49%) from EtOH: mp 129–131 °C, [h]D20
−45.6° (c 1.12, CHCl3). Anal. Calcd for
C30H32O9S: C, 63.37; H, 5.67. Found: C,
63.24; H, 5.83.
1,2:3,4-Di-O-isopropylidene-h- -galactosep-
D
Treatment of 2b with sodium benzoate.—A
stirred mixture of 2b (1.20 g, 2.58 mmol),
sodium benzoate (1.2 g, 8.3 mmol) and DMF
(30 mL) was kept at 100–105 °C for 3 h. After
the addition of water (200 mL), the cooled
reaction mixture was extracted with benzene
(3×50 mL), and each extract was shaken
with water (100 mL), dried and evaporated to
give a total of 1.13 g of liquid products that
were warmed with aq NaOH (2 M, 5 mL) and
sufficient MeOH to give a homogeneous solu-
tion. After 1 h, MeOH was removed by evap-
oration, and the mixture was extracted with
CHCl3 (3×20 mL). The extracts were washed
with water (20 mL), dried, and evaporated to
give 0.78 g of products that crystallised from
benzene–light petroleum to give needles of
tanose (4d).—A mixture of 4a (0.29 g, 0.94
mmol), anhyd CuSO4 (0.44 g), 2,2-
dimethoxypropane (5 mL), and acetone con-
taining 2% v/v H2SO4 (0.1 mL) was stirred at
22 °C for 16 h. The filtered reaction mixture
was neutralised using ammonia gas. It was
then shaken with water (20 mL) and CHCl3
(20 mL), and the CHCl3 extract was evapo-
rated to give a pale-yellow liquid (0.34 g).
Hydrogenolysis of this product as above gave
a colourless liquid (0.26 g) which crystallised
as prisms (0.145 g, 60%) from benzene–light
petroleum. Recrystallisation from benzene–
light petroleum gave prisms of 4d: mp 102–
103 °C; [h]2D0 +18.9° (c 0.5, CHCl3). Anal.
Calcd for C12H20O6: C, 55.37; H, 7.75. Found:
C, 55.52; H, 7.59.
5-O-benzyl-1,2-O-isopropylidene-a-
D
-galac-
Acetylation of 4d using Ac2O and pyridine
with usual workup gave needle crystals of 4e
from light petroleum: mp 103–104 °C; [h]D20
+27.6° (c 1.55, CHCl3). Analysis by X-ray
diffraction.7
toseptanose (4a) (0.55 g, 69%). Recrystallisa-
tion from CHCl3 –benzene gave needles of 4a:
mp 143–145 °C; [h]2D4 −57.9 ° (c 1.25, CHCl3).
Anal. Calcd for C16H22O6: C, 61.92; H, 7.15.
Found: C, 61.82; H, 7.12.
Proof of h-configuration in 4d.—A solution
of 4d (5 mg) in HCl (0.2 M, 0.06 mL) was
kept for 70 h at 30 °C. Evaporation of the
neutralised reaction mixture, followed by
acetylation and GLC analysis, revealed only
one peak with the same retention time as 4c.
Chromatography of the benzene–light
petroleum filtrates over silicic acid using 1:1
ether–light petroleum as eluent gave 3,4-anhy-
dro-5-O-benzyl-1.2-O-isopropylidene-a- -
D
galactoseptanose (3) (0.17 g) as the first-eluted
material and a further 0.03 g of 4a (total yield
of 4a, 72%). Recrystallisation of 3 from
CHCl3–benzene gave white needles: mp 75–
76 °C; [h]2D0 −43.0° (c 0.8, CHCl3). Anal.
Calcd for C16H20O5: C, 65.74; H, 6.90. Found:
C, 65.94; H, 7.21.
3-O-Acetyl-1,2:4,5-di-O-isopropylidene-h- -
D
galactoseptanose (4g).—To a solution of 4b
(200 mg, 0.91 mmol) in acetone (50 mL) was
added concd H2SO4 (10 mL). After 1 h, the
neutralised (aq NH3) mixture was evaporated,
and the residue was shaken with water and

88
G.E. Dri6er, J.D. Ste6ens / Carbohydrate Research 334 (2001) 81–89
CHCl3 (3×10 mL). Chromatography of the
liquid products (0.080 g) left on evaporation
of the CHCl3 extracts over silicic acid gave
chromatography over silicic acid, followed by
short-path distillation at 0.25 mm Hg and
105–110 °C bath, gave 6b as a colourless liq-
uid; [h]2D4 +23.9° (c 1.2, CHCl3). Anal. Calcd
for C14H22O7: C, 55.62; H, 7.34. Found: C,
55.28; H, 7.65.
1,2:4,5-di-O-isopropylidene-a- -galactosep-
D
tanose (4f, 61.1 mg, 92% based on unrecov-
ered 4b); Rf 0.2, silica, 1:1 ether–light
petroleum) eluted with 1:1 ether–light
petroleum and 4d (6.4 mg; Rf 0.1). Evapora-
tion of the aqueous solution gave 4b (0.144 g).
Acetylation of 4f using Ac2O and pyridine and
the usual workup gave crystalline 4g (65 mg),
which crystallised from light petroleum to give
white needles: mp 118–121 °C; [h]2D3 −65.3°
(c 0.45, CHCl3). Anal. Calcd for C14H22O7: C,
55.62; H, 7.34. Found: C, 55.66; H, 7.33.
Treatment of epoxide 3 with sodium methox-
ide.—A solution of 3 (787 mg, 2.69 mmol) in
3 M sodium methoxide in MeOH (12 mL) in
a tightly stoppered r.b. flask was kept at 90 °C
for 48 h. After evaporation, an aqueous solu-
tion of the reaction products was extracted
with CHCl3. TLC (silica gel, ether) showed
two spots of approximately equal intensity Rf
0.35 and 0.20. Chromatography of the extract
over silicic acid (10 g) using 1:2 Et2O–light
petroleum gave 5a (Rf 0.35, 288 mg, 33%)
followed by 2g (Rf 0.20, 200 mg, 23%). Acety-
lation of 2g using Ac2O and pyridine with the
usual workup gave crystals of 2h. Recrystalli-
sation from benzene–light petroleum gave 2h
as needles: mp 87–88 °C; [h]2D2 −28.5° (c 1.75,
CHCl3). Anal. Calcd for C19H26O7: C, 62.28;
H, 7.15. Found: C, 62.43; H, 7.02. Acetylation
of 5a gave crystals of 5b that yielded needles
from benzene–light petroleum: mp 105–
106 °C; [h]2D2 −2.0° (c 1.75, CHCl3). Anal.
Calcd for C19H26O7: C, 62.28; H, 7.15. Found:
C. 62.15; H, 7.07.
A solution of 5a (0.25 g, 0.77 mmol) in
MeOH (20 mL) was stirred with 10% Pd–C
(Aldrich) under hydrogen for 1 h, after which
time no further uptake of hydrogen occurred.
Acetylation (Ac2O–pyridine) of the residue
left upon filtration and evaporation of the
reaction product with usual workup gave a
crystalline product which yielded colourless
prisms of 5c (0.17 g, 69%) from benzene–light
petroleum: mp 114–116 °C; [h]2D2 +35.0° (c
1.45, CHCl3). Analysis by X-ray diffraction.10
Treatment of 2b with sodium methoxide.—
After a solution of 2b (1.86 g, 4.0 mmol) in 3
M NaOMe (20 mL) had been kept at 22 °C
for 3.5 h, the mixture was kept at 70 °C for 60
h. TLC (silica, 1:1 EtOAc–light petroleum)
showed only 2g and 5a at Rf 0.10 and 0.23,
respectively. The residue left upon evapora-
tion of the reaction mixture was shaken with
CHCl3 and water, and the CHCl3 extracts
were chromatographed over silicic acid using
1:1 EtOAc–light petroleum and monitored by
TLC to give 5a (0.89 g, 68%) and 2g (0.34 g,
1,2:3,4-Di-O-isopropylidene-i- -altrosep-
L
tanose (6a).—To a solution of 4d (180 mg,
0.69 mmol) in EtOH-free CHCl3 (4 mL) was
added a mixture of K2CO3 (0.40 g), sodium
metaperiodate (0.50 g) and ruthenium dioxide
(Engelhard, 50 mg) in water (4 mL) and the
mixture was stirred vigorously for 1 h. After
addition of 2-propanol (0.5 mL) and stirring
for 10 min, water (16 mL) was added. Separa-
tion of the CHCl3 layer, followed by two
further extractions with CHCl3 and evapora-
tion of the combined dried extracts, gave a
colourless liquid ketone (0.175 g). A solution
of the crude ketone in EtOH (10 mL) was
added dropwise over 15 min to a stirred solu-
tion of NaBH4 (0.3 g) in EtOH (5 mL). After
stirring the reaction mixture for 0.75 h, ace-
tone (2 mL) was added to destroy excess
borohydride. After evaporating the reaction
mixture, the residue was shaken with water
and CHCl3. Evaporation of the CHCl3 ex-
tracts gave a mixture of 1:1.4 4d and 6a (0.175
g), by GLC analysis (160 °C, retention times
6.3 and 5.3 min, respectively). Chromatogra-
phy of the products over silicic acid (6 g) using
1:1 ether–light petroleum, gave fractions con-
taining mainly 6a that were combined to give
crude 6a (70 mg). Crystallisation from a ben-
zene–light petroleum mixture gave needles (49
mg, 27%) that were recrystallised from ben-
zene–light petroleum to give 6a: mp 101–
102 °C; [h]2D4 +38.7° (c 0.6, CHCl3). Anal.
Calcd for C12H20O6: C, 55.37; H, 7.75. Found:
C, 55.20; H, 7.64.
5-O-Acetyl-1,2:3,4-di-O-isopropylidene-i- -
L
altroseptanose (6b).—Acetylation of 6b using
Ac2O and pyridine with the usual workup and

G.E. Dri6er, J.D. Ste6ens / Carbohydrate Research 334 (2001) 81–89
89
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Acknowledgements
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