Glucuronic acid-based ulosyl donors for introducing α-d-GlcA and β-d-ManA units

Article abstract of DOI:10.1016/j.carres.2007.05.008

Practical protocols are described for a five-step conversion of d-glucuronolactone into α-d-arabino-2-ketoglucuronyl bromides, which due to their α-selective or β-specific glycosidation, and gluco- or manno-specific carbonyl reductions of the glucurono-2-ulosides formed, are expedient indirect donor substrates for the efficient introduction of α-d-GlcA or β-d-ManA residues.

Full text of DOI:10.1016/j.carres.2007.05.008

Carbohydrate Research 342 (2007) 2132–2137
Note
Glucuronic acid-based ulosyl donors for introducing
a-D-GlcA and b-D-ManA unitsq
Matthias Lergenmuller and Frieder W. Lichtenthaler*
¨
Clemens-Scho¨pf-Institut fu¨r Organische Chemie und Biochemie, Technische Universita¨t Darmstadt, D-64287 Darmstadt, Germany
Received 2 April 2007; received in revised form 3 May 2007; accepted 7 May 2007
Available online 18 May 2007
Abstract—Practical protocols are described for a five-step conversion of D-glucuronolactone into a-D-arabino-2-ketoglucuronyl bro-
mides, which due to their a-selective or b-specific glycosidation, and gluco- or manno-specific carbonyl reductions of the glucurono-
2-ulosides formed, are expedient indirect donor substrates for the efficient introduction of a-D-GlcA or b-D-ManA residues.
ꢀ 2007 Elsevier Ltd. All rights reserved.
Keywords: Glycosylation; b-D-Mannuronyl donor; Ulosyl bromides; Glucurono-2-ulosides
The 2-ulosyl donor approach for the expedient synthesis
of b-D-mannosides has successfully been employed for
the construction of various b-D-mannose-containing oli-
gosaccharides up to the hexasaccharide level.2 Central to
this procedure are the ready preparations of variously
blocked a-D-arabino-2-ketohexosyl bromides of type A
from D-glucose,2,3 their essentially b-specific glycosida-
tion (!B)—the electron-withdrawing 2-carbonyl group
suppresses oxocarbenium ion formation at the anomeric
center implementing direct SN2 displacement of the
bromine—and manno-specific (B!C) or gluco-selective
(B!D) reduction4 of the resulting b-D-glycosiduloses
(Scheme 1). Aside from its preparative simplicity, the
methodology has the advantage of providing b-D-glyco-
sides with a free 2-OH group, that is, acceptors ready for
further glycosylations toward (1!2)-oligosaccharides.
Whilst the 6-deoxy-L-ulosyl bromides of type E have
already been prepared and utilized for the straightfor-
ward synthesis of b-L-rhamnose-containing oligosaccha-
rides,5 we here report on a simple, five-step conversion
of D-glucuronolactone into ulosyl bromides F with a
6-carboxyl functionality, which are practical donor sub-
strates for the generation of a-D-GlcA and b-D-ManA
linkages:
OR
OR
O
O
R'OH
RO
RO
RO
RO
OR'
Ag silicate
O
O
Br
A
B
(sBu)3 BH
BH3
OH
O
RO
RO
RO
O
RO
RO
OR'
OR'
RO
HO
C
D
β-D-gluco
R = Ac, Bz, Bn; R' = alkyl, glycosyl
-D-manno
β
Br
COOMe
O
Scheme 1. The ‘ulosyl donor approach’ to b-D-mannosides or b-D-
glucosides with a free 2-OH.
Me
RO
O
RO
RO
O
OR
O
Br
q Sugar-Derived Building Blocks, Part 41; for Part 40, see Ref. 1.
E
F
*
Corresponding author. Tel.: +49 6151 162376; fax: +49 6151
166674; e-mail: lichtenthaler@chemie.tu-darmstadt.de
R = Ac, Bz, Bn
R = Ac, Bz
0008-6215/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2007.05.008

M. Lergenmu¨ller, F. W. Lichtenthaler / Carbohydrate Research 342 (2007) 2132–2137
2133
O
COOMe
COOMe
1. MeOH
2. RCl
HO
O
O
OAc
O
Me2NH
DMF
OH
RO
RO
O
3. HBr/HOAc
~ 70%
OR
RO
2 R = Ac
3 R = Bz
Br
AcO
OH
4 R = Ac
5 R = Bz
1
NBS/MeOH
COOMe
O
COOMe
COOMe
O
O
BzO
BzO
CxOH
iPrOH
RO
RO
BzO
BzO
OiPr
Ag alumosilicate
Ag triflate
- 78 ˚C
O
O
O
OCx
Br
6 R = Ac
7 R = Bz
8
9
BH3 Pyr
NH2OH
LiB(iBu)3H
COOMe
COOMe
O
OH
O
MeOOC
BzO
BzO
O
BzO
BzO
BzO
BzO
OiPr
OiPr
HO
11
HON
10
OCx
12
Cx = cyclohexyl
Scheme 2.
Commercially available glucuronolactone 1 was con-
verted into its methyl ester,6 then acylated with either
acetic anhydride6 or benzoyl chloride,7 followed by expo-
sure to HBr/HOAc6,7 to give glucuronyl bromides 2 and
3, overall yields for the three steps being in the 75%
range. The subsequent HBr elimination was effected by
dimethylamine/tetrabutylammonium bromide in DMF,
affording 2-acyloxyglucuronals 48 and 5 in nicely crystal-
line form each. Interestingly, yet not entirely unex-
respective ulosyl bromides 6 and 7 in 66–70% yield.
Particularly compound 7, isolable in crystalline form
and storable for weeks, appeared to lend itself as a
suitable donor substrate, as glycosidations can simply
be effected in either an a- or b-specific manner: When
exposed to cyclohexanol in dichloromethane in the
presence of silver triflate at ꢀ78 ꢁC, a-D-uloside 8 is
formed exclusively (isolated yield: 85%)ꢁ as the reaction
obviously proceeds through a b-triflate intermediate,
which then undergoes SN2-type alcoholysis. When using
an insoluble silver catalyst, such as silver aluminosili-
cate,5,10 however, and 2-propanol as the acceptor, the
well-crystallizing b-D-glucuronosidulose 9 is generated
in essentially quantitative yield.
Reductions of the carbonyl group in b-D-2-ketoglucu-
ronide 9 follow the stereoselectivity patterns observed
previously with b-D-glucosiduloses:3,4 exposure to
BH3Æpyridine in THF at ꢀ78 ꢁC generates an approxi-
mate 10:1 mixture of glucuronide 11 and its manno-iso-
mer 12, from which 11 is isolable in useful yield (76%),
whereas the selectride reduction of 9 provides mannuro-
nide 12 in an essentially stereospecific manner (84% iso-
lated yield).
5
pected,ꢀ 4 and 5 adopt the uncommon H4 half-chair
conformation in solution as well as in the solid state: in
CDCl3, the H-4/H-5 couplings are small (2.2 and
2.3 Hz, respectively) and the occurrence of a 1.4-Hz
long-range coupling between H-3 and H-5 indicates these
hydrogens to be in a W arrangement as depicted in the
formulae (Scheme 2); this steric disposition, ‘inverse’ to
that in the parent glucal esters, is even more lucidly
exposed in the solid-state structure of 4 (Fig. 1), revealing
an essentially antiparallel arrangement (dihedral angle
O4–C4–C5–C6: 175.8ꢁ) of the 4-acetoxy and 5-carbo-
methoxy groups perpendicular to the ring plane.
Exposure of either 2-acetoxyglucuronals 4 or 5 to
methoxybromination conditions (NBS/methanol in
dichloromethane, 15 min, 25 ꢁC) smoothly afforded the
ꢀ The parent 3,4,6-tri-O-acetyl-D-glucuronal, in acetone solution,
predominantly adopts the 5H4 half-chair conformation as evidenced
by a small J4,5 value (3.9 Hz) and the appearance of a long range
coupling (1.2 Hz) between H-3 and H-5.9
ꢁ On performing the silver triflate-induced glycosidation of 9 with
cyclohexanol at 0 ꢁC or at ambient temperature a/b-mixtures are
obtained with the latter anomer preponderating, conceivably due to
extensive direct SN2-type displacement of the bromine.

2134
M. Lergenmu¨ller, F. W. Lichtenthaler / Carbohydrate Research 342 (2007) 2132–2137
8 (!10), they may also be utilized for the generation
of b-D-ManNAcA oligosaccharides.
1. Experimental
1.1. General
Melting points were determined with a Bock hot-stage
microscope, and are uncorrected. Optical rotations were
measured on a Perkin–Elmer 241 polarimeter at 20 ꢁC
using a cell of 1 dm path length; concentration (c) in
1
g/100 mL and solvent are given in parantheses. H and
13C NMR spectra were recorded on a Bruker ARX-
300 spectrometer in the solvents given. Mass spectra
were acquired on Varian MAT 311 and MAT 212 spec-
trometers. Microanalyses were determined on a Perkin–
Elmer 240 elemental analyzer. Analytical thin-layer
chromatography (TLC) was performed on precoated
E. Merck plastic sheets (0.2 mm Silica Gel 60 F254) with
detection by UV (254 nm) and/or spraying with H2SO4
(50%) and heating. Column and flash chromatography
was carried out on Fluka Silica Gel 60 (70–230 mesh)
using the specified eluents.
1.2. Methyl 2-acetoxy-3,4-di-O-acetyl-D-arabino-hex-1-
enopyranuronate (4)
The product was prepared by HBr elimination from
methyl (2,3,4-tri-O-acetyl-a-D-glucopyranosyl)uronate
bromide (2) according to Kaji et al.8 Crystals suitable
for X-ray structure determination were obtained by
recrystallization from diisopropyl ether: well-formed
20
rodlets of mp 92–93 ꢁC and ½aꢁD ꢀ51.5 (c 1.1,
20
CHCl3); lit.:8 mp 101–101.5 ꢁC and ½aꢁD ꢀ51 (c 1.0,
20
CHCl3);8 mp 76 ꢁC and ½aꢁ ꢀ54 (c 0.5, CHCl3).11
D
X-ray diffraction analysis was carried out on an Euraf–
Nonius CAD diffractometer with graphite monochro-
˚
mated MoKa radiation (k = 0.71073 A). Details for
crystal data, data collection, and refinement parameters
are given in Table 1. Programs used for structure solu-
tion, refinement, and analysis include SHELXS97,12 and
SHELXL97.13 The ball-and-stick model representation of
Figure 1 was generated by the MolArchTM program.14
Hydrogen atoms were positioned geometrically; the car-
bonyl oxygens of the acetyl groups are disordered.
Figure 1. X-ray structure of methyl 2-acetoxy-3,4-di-O-acetyl-D-ara-
bino-hex-1-enopyranuronate (4) with a view accentuating the antipar-
allel arrangement of 3-OAc, 4-OAc, and 5-COOMe. Selected torsional
angles: H3–C3–C4–H-4 +78, H4–C4–C5–H5 ꢀ63, O51–C1–C2–C3
+1.5, O51–C5–C4–C3 +56.9, O31–C3–C4–O41 ꢀ162.0, O4–C4–C5–
C6 +175.8. The deviations of C4 (ꢀ0.30) and C5 (+0.38) from the
˚
plane formed by the ring oxygen, C1, C2, and C3 are given in A.
Although only verified with a single secondary alcohol
(2-propanol), the experiments described suffice to extend
the ulosyl donor approach2–5 to 2-ketoglucuronyl bro-
mides for the straightforward assembly of oligosaccha-
rides with a-D-GlcA or, preparatively more important,
with b-D-ManA units, thereby complementing the use
of 2-oximinoglucuronyl bromides8 as effective indirect
b-D-ManNAcA donors. As the 2-ketoglucuronides are
readily converted into their oximes, as shown here for
1.3. Methyl 3,4-di-O-benzoyl-2-benzoyloxy-D-arabino-
hex-1-enopyranuronate (5)
A solution of methyl (2,3,4-tri-O-benzoyl-a-D-gluco-
pyranosyl)uronate bromide (3)7 (15.8 g, 27.1 mmol) in
150 mL of dry DMF was cooled to ꢀ20 ꢁC, followed
by the addition of tetrabutylammonium bromide
˚
(9.20 g, 28.5 mmol) and 3 A molecular sieves (4 g) with
stirring. Then, a solution of Me2NH (4.36 mL, 42 mmol)

1.4. Methyl (3,4-di-O-acetyl-a-D-arabino-hexos-2-ulo-
pyranosyl)uronate bromide (6)
M. Lergenmu¨ller, F. W. Lichtenthaler / Carbohydrate Research 342 (2007) 2132–2137
2135
Table 1. Crystal data and structure refinement for 4
Empirical formula
Formula weight
Temperature (K)
C13H16O9
316.29
299
0.71069
˚
MeOH (260 lL, 0.63 mmol) and 3 A molecular sieves
were added to a CH2Cl2 solution of D-gluronal 4
(2.00 g, 6.3 mmol, in 50 mL), followed, after stirring
for 15 min, by N-bromosuccinimide (1.13 g, 6.3 mmol).
Upon another 15 min of stirring the mixture was diluted
with CH2Cl2 (50 mL), washed with 10% aq Na2S2O3
(50 mL) and water (2 · 50 mL), dried (Na2SO4), and
evaporated to dryness in vacuo, to give 1.46 g (66%) of
ulosyl bromide 6 as a chromatographically uniform
˚
Wavelength (A)
Crystal system, space group
Unit cell dimensions
Orthorombic, P212121
˚
A (A)
8.4500(10)
9.0720(10)
˚
B (A)
˚
C (A)
20.410(2)
a (ꢁ)
b (ꢁ)
c (ꢁ)
90
90
90
3
˚
Volume (A )
1.564.6(3)
4, 1.343
0.075
664
20
Z, Calculated density (mg/m3)
(Rf 0.05 in 5:1 toluene–EtOAc), colorless syrup: ½aꢁD
Absorption coefficient (mmꢀ1
F(000)
)
1
+192.4 (c 0.7, CHCl3). H NMR (300 MHz, CDCl3): d
2.04, 2.12 (two 3H-s, AcCH3), 3.73 (s, 3H, OCH3),
4.73 (d, 1H, H-5), 5.45 (dd, 1H, H-4), 6.02 (d, 1H, H-
3), 6.34 (s, 1H, H-1), J3,4 = J4,5 10.4 Hz; 13C NMR
(75.5 MHz, CDCl3): d 20.4, 20.6 (2CH3CO), 53.5
(CH3O), 69.0 (C-4), 71.6 (C-3), 72.2 (C-5), 81.6 (C-1),
165.9, 169.1, 169.5 (2CH3CO, C-6), 188.0 (C-2). FDMS
(5 mA): m/z 352, 354 [M+]. Anal. Calcd for C11H13BrO8
(353.13): C, 37.41; H, 3.71. Found: C, 37.53; H, 3.80.
The compound is liable to decomposition, stable in a
refrigerator no longer than 24 h.
Crystal size (mm)
h Range for data collection (ꢁ)
0.55 · 0.20 · 1.00
2.00–22.96
Index ranges
ꢀ9 6 h 6 9,
0 6 k9,
0 6 l 6 22
Reflections collected
2386 [R(int) = 0.0281]
2170/0/253
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > r(I)]
R indices (all data)
1.094
R1 = 0.0525, wR2 = 0.1269
R1 = 0.0585, wR2 = 0.1337
0.166 and ꢀ0.276
Largestꢀd3ifference in peak and
˚
hole (A
)
1.5. Methyl (3,4-di-O-benzoyl-a-D-arabino-hexos-2-ulo-
pyranosyl)uronate bromide (7)
in DMF (50 mL) was added dropwise during the course
of 1 h, and the mixture was stirred for 1 d at ꢀ20 ꢁC
and another at ꢀ10 ꢁC. The dark-red solution was
then diluted with CH2Cl2 (200 mL), filtered through
kieselgur, and successively washed with 2 N HCl
(3 · 100 mL), satd aq NaHCO3 (3 · 50 mL) and water
(50 mL). Drying (Na2SO4), removal of the solvent in
vacuo and coevaporation of the residue with toluene left
a syrup that was eluted from a silica gel column
(5.5 · 12 cm) with 50:1 toluene–EtOAc. Evaporation of
the eluate to dryness left crude glucuronal 5 as a yellow-
ish foam (9.2 g, 67%, Rf 0.46 in 3:2 cyclohexane–
EtOAc), containing about 3% of methyl 2,3,4-tri-O-
benzoyl-D-glucopyranuronate (Rf 0.42). This product
was used for the methoxybromination of 5!7.
˚
MeOH (0.45 mL, 11 mmol) and 3 A molecular sieves
were added to a solution of 5.00 g (10 mmol) of crude
glucuronal 5, as obtained above, in 50 mL of CH2Cl2.
After stirring for 15 min, N-bromosuccinimide (2.0 g,
11 mmol) was added, and stirring at ambient tempera-
ture was continued for 3 h. Subsequent washing with
10% aq Na2S2O3 (10 mL) and water (2 · 10 mL), fol-
lowed by drying (Na2SO4) and evaporation to dryness,
left a syrup that crystallized on trituration with
CH2Cl2–diisopropyl ether: 3.34 g (70%) of ulosyl bro-
20
mide 7 as colorless needles: mp 171–173 ꢁC; ½aꢁD
1
+151.6 (c 1, CHCl3). H NMR (300 MHz, CDCl3): d
3.71 (s, 3H, CH3O), 5.04 (d, 1H, H-5), 5.96 (dd, 1H,
H-4), 6.52 (s, 1H, H-1), 6.57 (d, 1H, H-3), 7.40–8.05
(m, 10H, 2C6H5). J3,4 = J4,5 10.4 Hz; 13C NMR
(75.5 MHz, CDCl3): d 53.5 (CH3O), 69.6 (C-5), 72.1
(C-3), 72.5 (C-4), 81.8 (C-1), 128.3–134.1 (2C6H5),
164.8, 165.2, 166.0 (2C6H5CO, C-6), 188.0 (C-2); FDMS
(15 mA): m/z 479, 477 [M++H], 478, 476 [M+], 397
[M+ꢀBr]. Anal. Calcd for C21H17BrO8 (477.27): C,
52.85; H, 3.59. Found: C, 52.93; H, 3.51.
A 500 mg portion of crude 5 was subjected to purifica-
tion on a silica gel column (2 · 20 cm, elution with 50:1
toluene–EtOAc) to give upon evaporation of the eluate
containing 5 in vacuo and trituration of the residual
foam with 2-propanol 295 mg (59%) of 5 as wad-like
20
crystals: mp 123 ꢁC; ½aꢁD ꢀ167.4 (c 1, CHCl3). 1H
NMR (500 MHz, CDCl3): d 3.56 (s, 3H, CH3O), 5.10
(dd, 1H, H-5), 5.82 (d, 1H, H-3), 5.89 (dd, 1H, H-4),
7.07 (s, 1H, H-1), 7.35–8.11 (m, 15H, 3C6H5); J3,4 2.4;
J4,5 2.3; J3,5 1.4 Hz; 13C NMR (125.7 MHz, CDCl3): d
51.8 (CH3O), 63.9 (C-3), 67.5 (C-4), 71.5 (C-5), 126.6
(C-2), 127.5–133.9 (3C6H5), 139.3 (C-1), 165.0, 165.1,
165.2, 166.8 (3C6H5CO, C-6). Anal. Calcd for
C28H22O9 (502.48): C, 66.93; H, 4.41. Found C, 66.83;
H, 4.39.
1.6. Methyl (cyclohexyl 3,4-di-O-benzoyl-a-D-arabino-
hexos-2-ulopyranosid)uronate (8)
A solution of cyclohexanol (105 mg, 1.05 mmol) in
˚
CH2Cl2 (10 mL) containing 3 A molecular sieves
(500 mg) was cooled to ꢀ78 ꢁC. Then ulosyl bromide 7

2136
M. Lergenmu¨ller, F. W. Lichtenthaler / Carbohydrate Research 342 (2007) 2132–2137
(500 mg, 1.05 mmol) and silver triflate were added with
vigorous stirring, followed by letting the temperature
rise to ꢀ35 ꢁC. After 5 h, the mixture was filtered
through kieselgur, the filtrate was diluted with CH2Cl2
(40 mL) and washed consecutively with satd aq
NaHCO3, 10% aq Na2S2O3 and water (20 mL each).
Drying of the organic phase (Na2SO4) and removal of
the solvent in vacuo left a syrup that was purified by
elution from a silical gel column with 5:1 toluene–
EtOAc to give 445 mg (85%) of 8 as a colorless foam:
1H NMR (300 MHz, CDCl3): d 1.05–2.20 (m, 10H,
5CH2), 3.71 (s, 3H, CH3O), 3.78 (m, 1H, CH), 4.99 (d,
1H, H-5), 5.21 (s, 1H, H-1), 5.87 (dd, 1H, H-4), 6.20
(d, 1H, H-3), 7.40–8.05 (m, 10H, 2 C6H5); J3,4 0.3;
J4,5 10.1 Hz. Anal. Calcd for C27H28O9 (496.49): C,
65.31; H, 5.68. Found: C, 65.19; H, 5.60.
(3 · 15 cm) with 8:1 cyclohexane–EtOAc and evapora-
tion to dryness of the fractions with Rf 0.45 (3:2 cyclo-
hexane–EtOAc) left 245 mg (51%) of 10 as a syrup:
20
½aꢁD +12.5 (c 0.6, CHCl3). 1H NMR (300 MHz, CDCl3):
d 1.10–1.83 (m, 10H, 5CH2), 3.66 (s, 3H, CH3O), 3.65–
3.72 (m, 1H, CH), 4.77 (d, 1H, H-5), 5.70 (dd, 1H, H-4),
6.18 (s, 1H, H-1), 6.26 (d, 1H, H-3), 7.35–8.00 (m, 10H,
2C6H5), 8.87 (s, 1H, NOH); J3,4 9.7; J4,5 9.8 Hz; 13C
NMR (75.5 MHz, CDCl3): d 24.1, 24.4, 25.9, 31.7,
33.6 (5CH2), 53.2 (CH3O), 69.5 (C-5), 69.6 (C-3), 71.6
(C-4), 77.6 (cyclohexyl-CH), 89.3 (C-1), 128.7–133.8
(2C6H5), 148.8 (C-2), 165.5, 165.6, 168.5 (2C6H5CO,
C-6); JC-1,1-H 176.6 Hz. Anal. Calcd for C27H29NO9
(511.51): C, 63.40; H, 5.71; N, 2.74. Found C: 63.32;
H, 5.57; N, 2.63.
1.9. Methyl (isopropyl 3,4-di-O-benzoyl-b-D-gluco-
pyranosid)uronate (11)
1.7. Methyl (isopropyl 3,4-di-O-benzoyl-b-D-arabino-
hexos-2-ulopyranosid)uronate (9)
A THF solution of uloside 9 (460 mg, 1 mmol, in 5 mL)
was added in portions to a cooled (ꢀ78 ꢁC) solution of
BH3Æpyridine (0.5 mL, 5 mmol) in THF (10 mL). The
mixture was stirred for 1 h, then allowed to warm to
ambient temperature, and quenched with water
(2 mL). After removal of the solvents the syrupy residue
was dissolved in CH2Cl2 (20 mL), followed by vigorous
stirring with 2 N HCl (5 mL) for 30 min, separation of
the layers and washing of the organic phase with satd
aq NaHCO3 (5 mL) and water (5 mL). Drying (Na2SO4)
and evaporation of the solvent led to a crude product,
comprising (1H NMR) an approximate 10:1 mixture of
glucuronide 11 and its manno isomer 12. Purification
by elution from a silica gel column (3 · 15 cm) with
30:1 CH2Cl2–acetone gave 320 mg (76%) of 11 as a hard
foam. 1H NMR (300 MHz, CDCl3): d 1.24, 1.27 (2d, 3H
each, CH(CH3)2), 2.55 (d, 1H, 2-OH), 3.69 (3H-s,
OCH3), 3.78 (ddd, 1H, H-2) 4.05 (m, 2H, H-5,
CH(CH3)2), 4.63 (d, 1H, H-1), 5.55 (dd, 1H, H-4),
5.63 (dd, 1H, H-3); J1,2 7.7; J2,3 9.4; J2,OH 2.5;
J3,4 = J4,5 9.5 Hz. Anal. Calcd for C21H26O9 (422.4):
C, 59.71; H, 6.20. Found C: 59.60; H, 6.11.
To a suspension of silver aluminosilicate10 (2.0 g,
6.2 mmol) and 3 A molecular sieves (2 g) in CH2Cl2
˚
(20 mL) containing 380 lL (5.0 mmol) of 2-propanol
was added ulosyl bromide 7 (2.0 g, 2.1 mmol). The mix-
ture was stirred at ambient temperature for 10 min, then
filtered through kieselgur and evaporated to dryness in
vacuo to give 1.85 g (97%) of uloside 9 as colorless crys-
20
tals: mp 152–153 ꢁC; ½aꢁD ꢀ91.1 (c 1.6, CHCl3); Rf 0.48
1
in 5:1 CH2Cl2–EtOAc. H NMR (300 MHz, CDCl3): d
1.24, 1.24 (two 3H-d, CH(CH3)2), 3.75 (s, 3H, CH3O),
4.15 (qq, 1H, CH(CH3)2), 4.73 (d, 1H, H-5), 5.18 (s,
1H, H-1), 6.06 (d, 1H, H-3), 6.21 (dd, 1H, H-4), 7.30–
8.10 (m, 10H, 2C6H5); J3,4 = 10.5; J4,5 = 7.8 Hz; 13C
NMR (75.5 MHz, CDCl3): d 21.4, 22.8 (CH(CH3)2),
53.0 (CH3O), 69.3 (C-4), 72.9 (CH(CH3)2), 73.5 (C-5),
75.4 (C-3), 97.0 (C-1), 128.6–133.7 (2C6H5), 164.8,
165.5, 168.4 (2C6H5CO, C-6), 193.4 (C-2). Anal. Calcd
for C24H24O9 (456.45): C, 63.15; H, 5.30. Found C,
62.95; H, 5.18.
The product contained about 3% of the hydrated form
as evidenced by a second set of ring protons: d 4.74 (H-1),
5.53 (H-3), 5.78 (H-4) and 4.28 (H-5) with J3,4 = J4,5
9.9 Hz. The water of hydration could only partially be
removed by extensive drying over P2O5 at 56 ꢁC.
1.10. Methyl (isopropyl 3,4-di-O-benzoyl-b-D-manno-
pyranosid)uronate (12)
1.8. Methyl (cyclohexyl 3,4-di-O-benzoyl-a-D-arabino-
hexos-2-ulopyranosid)uronate Z-oxime (10)
A M solution of L-selectride (lithium tri-sec-butyl boro-
hydride, 1 mL) was added under Ar to a cooled
(ꢀ78 ꢁC), stirred solution of uloside 9 (460 mg, 1 mmol)
in THF (5 mL). After 1 min the reaction was quenched
by the addition of HOAc (0.2 mL). Dilution with
CH2Cl2 (20 mL), followed by washing with 2 M HCl
(10 mL) and satd aq NaHCO3 (10 mL), drying (MgSO4)
and evaporation of the solvent in vacuo left a residue
that was purified by flash elution from a silica gel
column with 50:1 CH2Cl2–EtOAc to give, after removal
of the solvents from the appropriate fraction, 360 mg
To a solution of a-glycosidulose 8 in 10 mL of 1:1 pyr-
idine–MeOH was added NH2OHÆHCl (350 mg,
5 mmol), and the mixture was stirred for 24 h at ambient
temperature, followed by dilution with CH2Cl2 (50 mL)
and washings with 2 N HCl (2 · 10 mL), satd aq
NaHCO3 (10 mL) and water (10 mL). Drying (Na2SO4),
removal of the solvent in vacuo, purification of the
yellowish syrup by elution from a silica gel column

M. Lergenmu¨ller, F. W. Lichtenthaler / Carbohydrate Research 342 (2007) 2132–2137
2137
1
2. For reviews, see: (a) Kaji, E.; Lichtenthaler, F. W.. Trends
Glycosci. Glycotechnol. 1993, 5, 121–142; (b) Gridley, J. J.;
Osborn, H. M. I. J. Chem. Soc., Perkin Trans. 1 2000,
1471–1491; (c) Pozsgay, V. In Carbohydrates in Chemistry
(84%) of 12 as a colorless foam: H NMR (300 MHz,
CDCl3): d 1.21, 1.27 (2d each, 3H, CH(CH3)2), 2.56
(d, 1H, 2-OH), 3.71 (3H-s, OCH3), 4.09 (ddd, 1H,
H-5), 4.10 (qq, 1H, OCH(CH3)2), 4.33 (m, 1H, H-2)
4.87 (d, 1H, H-1), 5.40 (dd, 1H, H-3), 5.95 (dd, 1H,
H-4); J1,2 0.9, J2,3 3.2, J3,4 9.8, J4,5 9.6 Hz. Anal. Calcd
for C21H26O9 (422.4): C, 59.71; H, 6.20. Found C:
59.66; H, 6.09.
and Biology, Part I; Ernst, B., Hart, G. W., Sinay, P., Eds.;
¨
Wiley-VCH: Weinheim, 2000; pp 332–336; For recent
applications toward b-D-mannosides, see: (d) Nitz, M.;
Bundles, D. R. J. Org. Chem. 2001, 66, 8411–8423; (e)
Lichtenthaler, F. W.; Lergenmuller, M.; Schwidetzky, S.
¨
Eur. J. Org. Chem. 2003, 3094–3103.
3. (a) Lichtenthaler, F. W.; Kla¨res, U.; Lergenmuller, M.;
¨
Schwidetzky, S. Synthesis 1992, 179–184; (b) Lichtent-
haler, F. W.; Schneider-Adams, T. J. Org. Chem. 1994, 59,
6728–6734; (c) Lichtenthaler, F. W.; Kla¨res, U.; Szurmai,
Z.; Werner, B. Carbohydr. Res. 1998, 305, 293–303.
2. Supplementary data
Crystallographic data, excluding structure factors, have
been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication with CCDC
No. 630545. Copies of the data can be obtained free
of charge on application with the Director, CCDC, 12
Union Road, Cambridge CB2 1EZ, UK (fax: +44
1223 336 033; e-mail: deposit@ccdc.cam.ac.uk).
4. Lichtenthaler, F. W.; Lergenmuller, M.; Peters, S.; Varga,
¨
Z. Tetrahedron: Asymmetry 2003, 14, 727–736.
5. Lichtenthaler, F. W.; Metz, T. Eur. J. Org. Chem. 2003,
3081–3092.
6. Bollenback, G. N.; Long, J. W.; Benjamin, D. G.;
Lindquist, J. A. J. Am. Chem. Soc. 1955, 77, 3110–
3115.
7. Zorbach, W. W.; Valiaveedan, G. D. J. Org. Chem. 1964,
29, 2462–2463.
8. Kaji, E.; Osa, Y.; Takahashi, K.; Hirooka, M.; Zen, S.;
Lichtenthaler, F. W. Bull. Chem. Soc. Jpn. 1994, 67, 1130–
1140.
Acknowledgements
9. Thiem, J.; Ossowski, J. Carbohydr. Chem. 1984, 3, 287–
313.
10. Van Boeckel, C. A. A.; Beetz, T.; Kock-van-Dalen, A. C.;
van Bekkum, H. Recl. Trav. Chim. Pays-Bas 1987, 106,
596–598.
Our thanks are due to Mrs. Sabine Foro for collecting
the X-ray data and Priv. Doz. Dr. Stefan Immel for
the color graphic in Figure 1, generated with his
MolArchTM program.
11. Anderson, F. B.; Leaback, D. H. Chem. Ind. London 1960,
967–968.
12. Sheldrick, G. M. SHELXS-97. Program for the solution of
crystal structures, University of Go¨ttingen, Germany,
1997.
References
13. Sheldrick, G. M. SHELXL-97. Program for the refinement
of crystal structures, University of Go¨ttingen, Germany,
1997.
14. Immel, S. MolArchTM program, version 7.05; Darmstadt
University of Technology, 2002.
1. Cuny, E.; Mondel, S.; Lichtenthaler, F. W. Novel poly-
amides from disaccharide dicarboxylic acids, XXIII. Int.
Carbohydr. Symp., Whistler, Canada, 2006, Abstr. TUE.
PS
12;
http://csi.chemie.tu-darmstadt.de/ak/fwlicht/
paper292.pdf.