Base catalysed isomerisation of aldoses of the arabino and lyxo series in the presence of aluminate

Article abstract of DOI:10.1016/S0008-6215(02)00065-4

Base-catalysed isomerisation of aldoses of the arabino and lyxo series in aluminate solution has been investigated. L-Arabinose and D-galactose give L-erythro-2-pentulose (L-ribulose) and D-lyxo-2-hexulose (D-tagatose), respectively, in good yields, whereas lower reactivity is observed for 6-deoxy-D-galactose (D-fucose). From D-lyxose, D-mannose and 6-deoxy-L-mannose (L-rhamnose) are obtained mixtures of ketoses and C-2 epimeric aldoses. Small amounts of the 3-epimers of the ketoses were also formed. 6-Deoxy-L-arabino-2-hexulose (6-deoxy-L-fructose) and 6-deoxy-L-glucose (L-quinovose) were formed in low yields from 6-deoxy-L-mannose and isolated as their O-isopropylidene derivatives. Explanations of the differences in reactivity and course of the reaction have been suggested on the basis of steric effects.

Full text of DOI:10.1016/S0008-6215(02)00065-4

Carbohydrate Research 337 (2002) 779–786
www.elsevier.com/locate/carres
Base catalysed isomerisation of aldoses of the arabino and lyxo
series in the presence of aluminate
Dag Ekeberg, Svein Morgenlie,* Yngve Stenstrøm
,
Department of Chemistry and Biotechnology, Section Chemistry, Agricultural Uni6ersity of Norway, PO Box 5040, N-1432 As, Norway
Received 3 December 2001; accepted 1 March 2002
Abstract
Base-catalysed isomerisation of aldoses of the arabino and lyxo series in aluminate solution has been investigated.
and -galactose give -erythro-2-pentulose ( -ribulose) and -lyxo-2-hexulose ( -tagatose), respectively, in good yields, whereas
lower reactivity is observed for 6-deoxy- -galactose ( -fucose). From -lyxose, -mannose and 6-deoxy- -mannose ( -rhamnose)
are obtained mixtures of ketoses and C-2 epimeric aldoses. Small amounts of the 3-epimers of the ketoses were also formed.
6-Deoxy- -arabino-2-hexulose (6-deoxy- -fructose) and 6-deoxy- -glucose ( -quinovose) were formed in low yields from 6-deoxy-
-mannose and isolated as their O-isopropylidene derivatives. Explanations of the differences in reactivity and course of the
reaction have been suggested on the basis of steric effects. © 2002 Elsevier Science Ltd. All rights reserved.
L-Arabinose
D
L
L
D
D
D
D
D
D
L
L
L
L
L
L
L
Keywords: L-erythro-2-Pentulose; 6-Deoxy-D-lyxo-2-hexulose; D-Xylulose; D-Fructose; 6-Deoxy-L-fructose; D-Xylose; D-Glucose; L-Quinovose
Through the last few years, much attention has been
focused on -lyxo-2-hexulose (tagatose), the ‘‘novel
1. Introduction
D
hexose’’, as a potential therapeutic adjunct in the man-
agement of type 2 diabetes mellitus8,9 and as a non-
calorific sweetener in food. It has been found recently
Base-catalysed isomerisation of
D-glucose to D-fruc-
tose in aluminate solution was reported in a patent in
1964.1 Since then, this method has been applied in
isomerisation, also of reducing disaccharides, lactulose
has been prepared from lactose2 and maltose has been
converted to maltulose in aluminate solution3 and on
aluminate resin.4 A possible mechanism of the isomeri-
sation of glucose to fructose has been suggested5 on the
basis of the known capability of aluminate to form
complexes with monosaccharides.6 A 9% conversion of
that
tose by the action of the same enzyme,
isomerase, that isomerises the aldopentose to
2-pentulose.10–13 The growing interest in
-lyxo-2-hex-
ulose and the similarity in the effect of -arabinose
isomerase on -arabinose and its higher homologue
-galactose, gave us the idea to compare also the effect
of aluminate on the same two sugars as well as on
6-deoxy- -galactose ( -fucose) as a third member of
the -arabino series.
D
-lyxo-2-hexulose may be produced from
-arabinose
-erythro-
D-galac-
L
L
D
L
L
D
L
-arabinose in aluminate solution to
lose ( -ribulose), determined by an enzymatic assay, has
also been reported.7 During previous, unpublished
work on aldol reactions, we needed - or -erythro-2-
pentulose as starting material and decided to prepare
the enantiomer from -arabinose on the basis of the
L-erythro-2-pentu-
D
D
L
L
Mannose, unlike glucose, is known to undergo C-2
epimerisation in aluminate solution in addition to al-
dose–ketose isomerisation.5 Mannose belongs to the
lyxo series with erythro configuration at C-2ꢀC-3,
whereas the aldoses of the arabino series, as well as
glucose have threo configuration at these carbon atoms.
In order to get further information on the importance
of configuration in the reaction of aldoses in aluminate
solution, we decided to include three aldoses of the lyxo
D
L
L
L
reported isomerisation in aluminate solution. We found
that considerably more than the reported 9% of the
pentulose could be obtained in this reaction.
* Corresponding author. Tel.: +47-64-947714; fax: +47-
64-947720.
series,
D-lyxose, D-mannose and 6-deoxy-L-mannose (L-
E-mail address: svein.morgenlie@ikb.nlh.no (S. Morgenlie).
rhamnose) in our investigation.
0008-6215/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(02)00065-4

780
D. Ekeberg et al. / Carbohydrate Research 337 (2002) 779–786
but in addition to the formation of 6-deoxy-
2-hexulose (6-deoxy- -fructose) (18), relatively more C-
2 epimerisation occurred than with 9 and 13, leading to
substantial amounts of 6-deoxy- -glucose ( -quinovose)
(19). C-3 epimerisation of 18 was also observed, giving
the ribo-isomer (20) (Scheme 3). Table 1 shows the
relative proportions of epimerisation and isomerisation
products from the aldoses after different reaction times.
On a preparative scale, and after prolonged reaction
time, the ketoses 2, 4 and 6 were obtained in 64, 78 and
42% yield, respectively, after oxidation of remaining
aldoses by bromine and removal of the resulting al-
donic acids by ion-exchange resin. The product of
L-arabino-
2. Results and discussion
L
When a sodium aluminate solution of -arabinose (1)
L
was kept at 35 °C for 20 h, GC–MS analysis of the
L
L
isopropylidene derivatives of the sugars14,15 revealed a
reaction mixture containing
and 1 in a ratio of about 2:3, whereas similar treatment
of -galactose (3) resulted in about 70% conversion to
-lyxo-2-hexulose (4). From 6-deoxy- -galactose (5)
only about 20% had isomerised to 6-deoxy- -lyxo-2-
L
-erythro-2-pentulose (2)
D
D
D
D
hexulose (6) after 20 h under the same conditions,
determined by GC–MS as its 1,2:3,4-di-O-isopropyli-
dene derivative (7). Whereas isomerisation of
binose (1) gave almost exclusively 2, small amounts of
-xylo-2-hexulose (8) ( -sorbose), and the 3-epimer of
L-ara-
aldose–ketose isomerisation of 17, 6-deoxy-L-arabino-
D
D
2-hexulose (18) was isolated as its O-isopropylidene
derivative. The isomerisation mixture was treated with
acetone–sulfuric acid and the products partitioned be-
tween hexane and water. The compounds in the water
phase were subjected to mild-acid hydrolysis, and only
4 was formed during isomerisation of
(Scheme 1).
GC–MS analysis after acetonation of the products
from the aldoses of the lyxo series showed more com-
D
-galactose (3)
plex mixtures.
epimerisaton at C-2 in addition to isomerisation to
-threo-2-pentulose (11) which further partly iso-
merised to its 3-epimeric 2-pentulose (12). From
mannose (13) was formed -glucose (14) in addition to
the main product
-fructose (15) as expected.5 Minute
amounts of the 3-epimer of 15, -ribo-2-hexulose (psi-
cose) (16) were also observed after prolonged reaction
time (Scheme 2). Traces of the arabino- and ribo-3-hex-
uloses were also formed. The major products from the
aldoses 9 and 13 were the ketoses 11 and 15. 6-Deoxy-
D
-Lyxose (9) gave
D
-xylose (10) by
the relatively stable 2,3-O-isopropylidene-6-deoxy-b-L-
arabino-2-hexulofuranose (21) was resistant and could
be extracted as a single compound in CHCl3. Its mass
spectrum revealed a M-CHÇ3 + peak at m/z 189, a
high-intensity peak at m/z 173 due to C-1ꢀC-2 cleavage
and the characteristic fragment ion pair at m/z 130 and
115 for a 2,3-O-isopropylidene derivative of a 2-ke-
tose,16,17 which is only formed from ketoses with threo
configuration at C-3ꢀC-4.17 The 1H and 13C NMR
spectra are in agreement with the structure. It is ex-
pected from the dihedral angles that no coupling is
observed between H-3 and H-4, and between H-4 and
D
D
-
D
D
D
L
-mannose (17) also gave mainly ketose as a product,
Scheme 1.

D. Ekeberg et al. / Carbohydrate Research 337 (2002) 779–786
781
Scheme 2.
1
spectrum only differed from that of the lyxo isomer 7 in
the relative abundance of some of the fragments, a fact
that excludes other possibilities (Scheme 4).
H-5 in the H NMR spectrum, which by MM2 calcula-
tions are found to be 84° and 89°, respectively. From
the hexane phase, the derivative of the aldose 19 could
be isolated as the 1,2:3,5-di-O-isopropylidene derivative
22. Advantage was taken of the great lability of the
3,5-O-isopropylidene group even with very mild-acid
hydrolysis, which allowed selective hydrolysis to the
monoisopropylidene derivative, separation from the di-
O-isopropylidene derivative 23 of compound 20 by
partitioning between hexane and water and re-acetona-
tion of the monoisopropylidene derivative from the
water phase. Compound 22 was characterised by MS
and NMR spectrometry. The M-CHÇ3 + ion at m/z 229
in its electron impact mass spectrum shows that 22 is a
di-O-isopropylidene derivative. The lack of the m/z
130–115 and 117–72 fragment ion pairs excludes the
possibility of a 6-deoxy-2-hexulose.16,17 Among the four
From our own and other investigations of the effect
of aluminate on aldoses, it appears that C-2 epimerisa-
tion requires an erythro configuration at C-2ꢀC-3 and
that the reactivity in aldose–ketose isomerisation also
depends on the configuration of the aldoses, as well as
that of the products. The ability of the ketoses to form
stable aluminate complexes is important. Rendleman
and Hodge6 have shown that fructose, which dominates
in the mannose–glucose–fructose isomerisation mix-
ture, is much more retarded on an aluminate resin
column than the aldohexoses; this is obviously due to
the formation of a more stable complex. Sorbose is also
retarded relatively to the aldoses, but much less than
fructose. The suggested reason for the high yield of
fructose obtained from glucose is the ability of the
ketose to form a 1,3,6-tridentate aluminate complex in
the a-furanose form.5 Tagatose, unlike sorbose and
psicose, also has a configuration allowing the formation
of such a complex (Fig. 1). This may explain the high
6-deoxy-L-aldohexoses known or expected to give only
or mainly di-O-isopropylidene derivatives, those with
galacto and altro configuration will give derivatives in
pyranose form, and since the mass spectrum of 22 is
very different from that of 1,2:3,4-di-O-isopropylidene-
6-deoxy-a-
L
-galactopyranose, only gluco and the very
yield of
work and its limited further isomerisation to the 3-
epimer -sorbose (8). The similar C-3 epimerisation of
fructose observed under isomerisation of mannose is
also reported to occur when glucose is isomerised to
fructose.5 The theory of favourable complex formation
D-tagatose obtained from D-galactose in our
unlikely ido configurations are possible for the com-
pound. The 13C NMR spectrum of 22 confirmed its
identity. From its mass spectrum, compound 23 was
identified as one of the anomers of 1,2:3,4-di-O-iso-
propylidene-6-deoxy-ribo-2-hexulofuranose, since the
D

782
D. Ekeberg et al. / Carbohydrate Research 337 (2002) 779–786
1
tion.5 In the case of
is then expected to be preferred (Fig. 2(a)). In the same
conformation of -fucose, the methyl group will be
L-arabinose, the C4 conformation
for fructose and tagatose is supported by our observa-
tion that
-psicose (16) in aluminate under the conditions used
in this investigation. On the basis of the 1,3,6-tridentate
theory, the much lower reactivity of -fucose than
-galactose is expected because of the lack of a hy-
D-allose was isomerised only very slowly to
D
D
axially oriented and experience syn–axial interactions
with O-1 and O-3 (Fig. 2(b)). This may explain that the
D
6-deoxyaldose reacts also more slowly than
L
-ara-
binose. C-6 will be in the axial position in C4 confor-
mation also for -glucose and -galactose. However,
the hydroxyl group at this carbon atom, with its capa-
D
1
droxyl group at C-6. The formation of a 1,3-aluminate
complex of the reacting aldose in the pyranose form has
been proposed as an important early step in the reac-
D
D
Scheme 3.
Table 1
Composition in percent in the reaction mixtures of unreacted aldose (A); ketose (K); 2-epimeric aldose (EA); and 3-epimeric
ketose (EK) after different reaction times a
3 h
A
20 h
A
40 h
A
K
EA
EK
K
EA
EK
1
K
EA
EK
5
L
-Arabinose
-Galactose
6-Deoxy- -galactose
93
83
97
85
85
95
7
17
3
12
11
3
60
30
80
52
45
75
40
69
20
38
44
16
31
10
62
44
35
56
69
85
38
40
53
22
D
D
D
-Lyxose
-Mannose b
-mannose
3
3
2
6
9
8
4
2
1
8
9
17
8
3
5
D
1
6-Deoxy-
L
a Other products, which sometimes were formed in minor amounts, are not included.
b From mannose were formed small amounts of arabino- and ribo-3-hexulose.

D. Ekeberg et al. / Carbohydrate Research 337 (2002) 779–786
783
Scheme 4.
bility to participate in 1,3,6-tridentate aluminate com-
plex formation, may be a driving force in the aldose–
ketose isomerisation instead of representing steric
hindrance. That the order of reactivity in aldose–ketose
isomerisation in the lyxo series is hexose\pentose\6-
deoxyhexose, just as observed for the sugars of the
arabino series, supports the suggested explanations.
lows attack of OH-5 at C-1 from the side leading to the
aldose with erythro configuration at these carbon
atoms.
Other complexing agents such as borate19,20 and
21–23
Ca2+
,
alone or in combination with amines, as
well as pentasilicate24 have been applied in base
catalysed aldose–ketose isomerisation. Ca2+ also ef-
fects C-2 epimerisation22,23,25–27 with a mechanism in-
volving C-1ꢀC-2 interconversion as in the B´ılik reaction
with molybdate.28 That aluminate gives some C-2
epimerisation for mannose, lyxose and rhamnose raises
the question about the possibility of a similar C-1ꢀC-2
interconversion mechanism operating also with this
complexing agent. Mannose and lyxose are, however,
reported to show considerable resistance to both C-2
epimerisation and aldose–ketose isomerisation with
The observation that
L
-erythro-2-pentulose (2) un-
dergoes negligible C-3 epimerisation to the threo isomer
in aluminate solution under the conditions applied in
this investigation, whereas substantial amounts of the
erythro isomer are formed from the latter, shows that
the configuration of the 2-pentuloses is important for
the stability of their aluminate complexes. This could
indicate that OH-4 participates directly in a 1,3,4-alu-
minate complex of 2, but despite the fact that the
closely related borate ion is known to form complexes
with vicinal hydroxyl groups,18 such complexations
with aluminate in carbohydrates have been considered
as unlikely.5
The necessity of having an erythro configuration at
C-2ꢀC-3 in aldoses to give C-2 epimerisation in alumi-
nate solution is in accordance with the model proposed
by Shaw and Tsao5 for the mannose–glucose isomerisa-
tion. The suggested common acyclic intermediate from
two aldoses differing only in configuration at C-2,
shown in Fig. 3, can only reform the aldose with threo
configuration at C-2ꢀC-3, no rotational orientation al-
Fig. 1. 1,3,6-Tridentate aluminate complex of a-D-tagatofura-
nose.

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D. Ekeberg et al. / Carbohydrate Research 337 (2002) 779–786
1
Fig. 2. 1,3-Bidentate aluminate complex of a-
L
-arabinopyranose (a) and b-D-fucopyranose (b) in C4 conformation.
Ca2+ –amine combinations, whereas glucose undergoes
extensive C-2 epimerisation to mannose.23 This is the
opposite order of reactivity to that observed in C-2
epimerisation in the presence of aluminate, which does
not effect C-2 epimerisation of glucose. This fact argues
against the possibility of similarities in the two epimeri-
sation mechanisms. A suggested explanation for the
resistance of mannose and lyxose to isomerisation and
epimerisation in Ca2+ solution is the protection of
these aldoses by a stable 1,2,3 axial–equatorial–axial
complex,23 very different from the proposed 1,3-biden-
tate aluminate complexes. It seems likely to us that
aldose–ketose isomerisation in aluminate solution also
occurs via the acyclic intermediate shown in Fig. 3 by
OH-5 attack on C-2 instead of on C-1.
Aluminate is useful as a complexing agent in the
preparation of ketoses from aldoses of the arabino
series. In addition to galactose, the aldohexoses glucose
and mannose also give good yields of ketose, pre-
sumably since fructose, like tagatose, may form a stable
tridentate complex with aluminate. The complexity of
the product mixtures from lyxose and 6-deoxymannose
reduces the synthetic utility of base catalysed isomerisa-
tion in aluminate solution of these aldoses.
chemical ionisation (EI–CI) ion source, operated in EI
mode at 70 eV and an ion source temperature at
180 °C.
A Carlo–Erba high-resolution gas chro-
matograph (HRGC) was applied for the GC–MS com-
1
bination. H and 13C NMR spectra were recorded on a
Varian Mercury instrument at 300 and 75 MHz, respec-
tively. The assignments were based on COSY, HET-
COR, NOESY and ROESY techniques. The spectra of
the isopropylidene derivatives were recorded in CDCl3
with CHCl3 as the internal standard, while those of the
free carbohydrates were recorded in D2O with Me2SO
as internal standard (13C NMR lref 40.40 ppm).
Preparation of aluminate solution.—Aluminum pow-
der or foil (3.40 g) was added to a solution of NaOH
(5.00 g) in water (400 mL). When no more H2 gas was
evolved, small amounts of remaining solid were re-
moved by filtration.
Isomerisation of aldoses, analysis of product mix-
tures.—Aluminate solution (3 mL) containing aldose
(50 mg) was flushed with N2 gas, corked and kept at
35 °C. Aliquots (0.5 mL) were withdrawn after 3, 20
and 40 h, diluted with water (5 mL) and deionized with
Dowex 50 W (H+) ion-exchange resin. After filtration
of the solution and evaporation of the water under
reduced pressure, the residue was stirred with 2%
H2SO4 in acetone (3 mL) for 2 h. The solution was
neutralised with solid NaHCO3 and subjected to GC
and GC–MS for identification and quantification of
the aldoses,14 2-ketoses15 and 3-hexuloses30 in the
product mixtures. The results are shown in Table 1.
3. Experimental
General methods.—Optical rotations were measured
with a Carl Zeiss Kreispolarimeter 0.01°. Pre-coated
Silica Gel G plates were used for TLC with (A) 7:2:1
acetone–1-butanol–water and (B) 30:1 CHCl3–
CH3OH as eluents. Spots were detected by spraying
with diphenylamine–aniline–phosphoric acid29 fol-
lowed by H2SO4 in EtOAc and heating at 110 °C for 5
min. GC was performed with a Shimadzu GC-14B gas
chromatograph, equipped with an open tubular fused
silica column, 25 m×0.32 mm ID, wall coated with
CP-SIL 43 CB, programmed at 6°/min from 90 to
225 °C. For mass spectrometry, a JEOL JMX-DX 303
double focusing-mass spectrometer with EB geometry
was used, equipped with a 10 kV post acceleration
conversion dynode detector and an electron ionisation–
Fig. 3. Suggested intermediate in C-2 epimerisation of aldoses
and in aldose–ketose isomerisation.

D. Ekeberg et al. / Carbohydrate Research 337 (2002) 779–786
785
L
-erythro-2-Pentulose (2).—
L
-Arabinose (1, 2.0 g) in
solution was kept overnight at rt to allow selective
aluminate solution (120 mL) was kept at 35 °C under
N2 for 48 h. After deionisation and filtration of the
solution as describe above, was added CaCO3 (1 g) and
then Br2 in small portions from a water solution under
stirring in the dark until a faint brown colour remained
for 1 h (total reaction time less than 2 h). The solution
was then treated with Dowex 1 (HCO−3 ) ion exchange
resin, filtered, treated with Dowex 50 W (H+) and
finally once more with Dowex 1 (HCO−3 ) resin. Filtra-
hydrolysis of the 2,3-O-isopropylidene derivative of
unreacted 6-deoxy-L-mannose. The solution was con-
centrated to a small volume (1 mL), diluted with water
(5 mL) and evaporated to dryness. The residue was
partitioned between water, made alkaline with
NaHCO3 (4 mL) and CHCl3 (5 mL). The water solu-
tion was extracted with CHCl3 (4×5 mL) and the
combined CHCl3 solutions were dried with Na2SO4.
Filtration of the solution and evaporation of the sol-
tion and evaporation of the solvent gave syrupy
L
-ery-
vent gave 2,3-O-isopropylidene-6-deoxy-b-L-arabino-2-
thro-2-pentulose (2, 1.28 g, 64%), [h]2D0 +14° (c 2,
water); lit.31 +17°. The product was chromatographi-
cally homogeneous and indistinguishable from authen-
tic 2 by TLC, Rf 0.45 (solvent A) and by GC after
hexulofuranose (21) as a syrup that crystallised on
addition of Et2O (128 mg, 21%); mp 110–112 °C; lit.
114–115 °C for the
EtOH); lit. +8° for the
D
enantiomer;38 [h]2D0 −7° (c 2,
D
enantiomer.38 GC: Rt 14.6
1
acetonation as described above, Rt 4.8 min. The H and
min; TLC: Rf 0.25 (solvent B). EIMS: 189 (26), 173
13C NMR spectra were in accordance with those re-
(83), 171 (11), 130 (8), 129 (48), 115 (22), 111 (35), 71
1
ported for the
D
enantiomer.32
(100), 59 (98), 43 (63). H NMR: 1.21 (s, 3 H, exo-
D
-lyxo-2-Hexulose (4).—
D
-Galactose (3, 2.0 g) in
CH3), 1.30 (d, J 6.9 Hz, 3 H, H-6), 1.43 (s, 3 H,
endo-CH3), 3.44 (bs, 2 H, OH), 3.56 (d, J 11.7 Hz, 1 H,
H-1), 3.73 (d, J 11.7 Hz, 1 H, H-1), 3.91 (s, 1 H, H-4),
4.15 (q, 6.9 Hz, 1 H, H-5), 4.33 (s, 1 H, H-3); 13C
NMR: 20.49 (C-6), 26.11(exo-CH3), 26.98 (endo-CH3),
64.21 (C-1), 78.66 (C-4), 86.71 (C-5), 87.99 (C-3),
112.90 (CMe2), 114.70 (C-2).
The combined hexane solutions from above were
seen by GC to contain, in addition to compound 22,
minor amounts of 23 with Rt 5.0 min; EIMS: 229 (61),
142 (21), 129 (16), 128 (29), 117 (100), 113 (30), 111
(58), 85 (15), 84 (33), 72 (30), 70 (21), 59 (70), 43 (64).
The hexane solution was evaporated, and 80% formic
acid (1 mL) was added to the residue. After 15 min,
water (10 mL) was added, and the water solution
extracted with hexane (2×5 mL) and pH adjusted to 7
with NaHCO3. After saturation with Na2SO4, the solu-
tion was extracted with CHCl3 (5×6 mL). The CHCl3
was evaporated, and the residue stirred for 20 min with
0.4% H2SO4 in acetone (10 mL). Neutralisation, filtra-
tion and evaporation followed by partitioning of the
residue between water (5 mL) and hexane (10 mL)
gave, after evaporation of the solvent from the hexane
aluminate solution (120 mL) was treated as described
for compound 1. The syrupy product crystallised slowly
on addition of 96% EtOH to give 4 (1.56 g, 78%), mp
132–134 °C; lit. 131–132 °C.33 [h]D20 −3° (c 5, water);
lit. −2°.33 The product was chromatographically ho-
mogeneous and indistinguishable from authentic 4 by
TLC, Rf 0.39 (solvent A) and by GC after acetonation,
Rt 12.0 min. The 1H and 13C NMR spectra were
identical with those of an authentic sample and in
accordance with reported spectra.34,35
6-Deoxy-
D
-lyxo-2-hexulose (6).—Isomerisation of 6-
deoxy- -galactose (5, 0.50 g) and treatment of the
D
product mixture with bromine as described for 1 and 3
gave syrupy 6 (0.21 g, 42%). [h]2D0 −3° (c 2, water); lit.
−2°.36 TLC (solvent A) showed a single spot, Rf 0.56.
The H and 13C NMR data were in accordance with
1
those reported for the
L
enantiomer.37 After treatment
of a small sample of 6 with acetone–H2SO4 as de-
scribed above, GC showed the presence of almost ex-
clusively one compound, 1,2:3,4-di-O-isopropylidene-6-
deoxy-a- -lyxo-2-hexulofuranose (7), with Rt 4.6 min;
D
EIMS m/z (% rel. int.): 229 (100), 142 (80), 129 (19),
128 (27), 117 (97), 113 (86), 111 (53), 85 (25), 84 (71), 72
(36), 70 (28), 59 (89), 57 (24), 43 (82).
phase, 1,2:3,5-di-O-isopropylidene-6-deoxy-a-
furanose (22) as a syrup (66 mg, 9%). [h]2D0 −35° (c 0.5,
CHCl3); lit. +38° for the
enantiomer.39 GC: Rt 6.1
L-gluco-
Isomerisation of 6-deoxy-
L
-mannose (17).—Com-
D
pound 17 (0.50 g) in aluminate solution (30 mL) was
kept at 35 °C for 48 h. The solution was then treated
with Dowex 50 W (H+) ion-exchange resin, filtered and
the water removed under reduced pressure. The residue
was stirred with 2% H2SO4 in acetone (25 mL) for 2 h,
then the solution was neutralised, filtered and concen-
trated. The residue was partitioned between water (15
mL) and hexane (20 mL) and the water phase was
extracted with hexane (2×5 mL).
min; TLC: Rf 0.80 (solvent B). EIMS: 229 (7), 171 (6),
142 (16), 129 (18), 113 (100), 100 (12), 85 (15), 84 (11),
71 (10), 59 (43), 43 (71). The 13C NMR spectrum was in
accordance with data reported for the
D
enantiomer.40
References
1. Haack, E.; Braun, F.; Kohler, K. Ger. Offen. 1,163,307
(February 20, 1964); Chem. Abstr. 1964, 60, 14598.
2. Guth, J. H.; Tumerman, L. US Patent 3,546,206 (Decem-
ber 8, 1970); Chem. Abstr. 1971, 74, 100810.
From the water phase the solvent was removed by
evaporation. The residue was dissolved in 80% formic
acid (2 mL) and then water (4 mL) was added and the

786
D. Ekeberg et al. / Carbohydrate Research 337 (2002) 779–786
3. Machida, I.; Kaneda, J.; Miki, H.; Kubomura, S.; Toda,
Patent 5,002,612 (March 26, 1991); Chem. Abstr. 1991,
115, 52172.
H.; Shiroishi, T. Japan Kokai 73 49,938 (July 14, 1973);
Chem. Abstr. 1973, 79, 126744.
4. Rendleman, J. A.; Hodge, J. E. Carbohydr. Res. 1979, 75,
83–99.
5. Shaw, A. J., III; Tsao, G. T. Carbohydr. Res. 1978, 60,
327–335.
6. Rendleman, J. A.; Hodge, J. E. Carbohydr. Res. 1975, 44,
155–167.
7. Raushel, F. M.; Cleland, W. W. Biochemistry 1977, 16,
2169–2175.
8. Zehner, L. R. Levin, G. V.; Saunders, J. P.; Beadle, J. R.
U.S. Patent 5,356,879 (October 18, 1994); Chem. Abstr.
1995, 122, 1093.
9. Donner, T. W.; Wilber, J. F.; Ostrowski, D. Diabetes
Obes. Metab. 1999, 1, 285–291.
10. Cheetham, P. S. J.; Wootton, A. N. Enzyme Microb.
Technol. 1993, 15, 105–108.
11. Roh, H. J.; Kim, P.; Park, Y. C.; Choi, J. H. Biotechnol.
Appl. Biochem. 2000, 31, 1–4.
12. Kim, P.; Yoon, S. M.; Roh, H. J.; Choi, J. H. Biotechnol.
Prog. 2001, 17, 208–210.
13. Ibrahim, O. O.; Spradlin, J. E. U.S. Patent 6,057,135
(May 2, 2000); Chem. Abstr. 2000, 132, 307346.
14. Morgenlie, S. Carbohydr. Res. 1975, 41, 285–289.
15. Morgenlie, S. Carbohydr. Res. 1980, 80, 215–222.
16. DeJongh, D. C.; Biemann, K. J. Am. Chem. Soc. 1964,
86, 67–74.
17. Brady, R. F., Jr. Ad6. Carbohydr. Chem. Biochem. 1971,
26, 197–278.
18. Chapelle, S.; Verchere, J.-F. Carbohydr. Res. 1989, 191,
63–70.
22. Yamauchi, T.; Fukushima, K.; Yanagihara, R.; Osanai,
S.; Yoshikawa, S. Carbohydr. Res. 1990, 204, 233–239.
23. Tanase, T.; Takei, T.; Hidai, M.; Yano, S. Carbohydr.
Res. 2001, 333, 303–312.
24. Asaoka, H. Carbohydr. Res. 1985, 137, 99–109.
25. Kusin, A. Ber. Dtsch. Chem. Ges. 1936, 69, 1041–1049.
26. Yanagihara, R.; Soeda, K.; Shiina, S.; Osanai, S.;
Yoshikava, S. Bull. Chem. Soc. Jpn. 1993, 66, 2268–2272.
27. Angyal, S. J. Carbohydr. Res. 1997, 300, 279–281.
28. B´ılik, V. Chem. Z6esti. 1972, 26, 372–375.
29. Schwimmer, S.; Bevenue, A. Science 1956, 123, 543–544.
30. Ekeberg, D.; Morgenlie, S.; Stenstrøm, Y. Carbohydr.
Res. 2001, 335, 141–146.
31. Levene, P. A.; Tipson, R. S. J. Biol. Chem. 1936, 115,
731–747.
32. de Wit, D.; van Rantwijk, F.; Maat, L.; Kieboom, A. P.
G. Recl. Tra6. Chim. Pays-Bas 1991, 110, 271–274.
33. Reichstein, T.; Bosshard, W. Hel6. Chim. Acta 1934, 17,
753–761.
34. Freimund, S.; Huwig, A.; Giffhorn, F.; Ko¨pper, S. J.
Carbohydr. Chem. 1996, 15, 115–120.
35. Angyal, S. J.; Bethell, G. S. Aust. J. Chem. 1976, 29,
1249–1265.
36. Barnett, J.; Reichstein, T. Hel6. Chim. Acta 1937, 20,
1529–1536.
37. Liu, K. K.-C.; Kajimoto, T.; Chen, L.; Zhong, Z.;
Ichikawa, Y.; Wong, C.-H. J. Org. Chem. 1991, 56,
6280–6289.
38. Morgan, W. T. J.; Reichstein, T. Hel6. Chim. Acta 1938,
21, 1023–1031.
19. Mendicino, J. F. J. Am. Chem. Soc. 1960, 82, 4975–4979.
20. Hicks, K. B.; Symanski, E. V.; Pfeffer, P. E. Carbohydr.
Res. 1983, 112, 37–50.
39. Meyer, A. S.; Reichstein, T. Hel6. Chim. Acta 1946, 29,
139–152.
40. Lipta´k, A.; Na´na´si, P.; Neszme´lyi, A.; Wagner, H. Car-
bohydr. Res. 1980, 86, 133–136.
21. Beadle, J. R.; Saunders, J. P.; Wajda, T. J., Jr. U.S.