Prearranged glycosides, 9. - Chemical synthesis of a tetrasaccharide fragment related to the exopolysaccharide of Arthrobacter sp. CE-17

Article abstract of DOI:10.1002/(SICI)1099-0690(200001)2000:1<181::AID-EJOC181>3.0.CO;2-7

The tetrasaccharide 5-aminopentyl glycoside β-D-Manp-(1→4)-β-D-Glcp- (1→4)-α-L-Rhap-(1→3)-β-D-Glcp-1-O-(CH₂)₅NH₂(22) related to the exopolysaccharide of Arthrobacter sp. CE-17 was synthesized by coupling of the properly protected disaccharide blocks β-D-Manp-(1→4)-β-D-Glcp-1-S-Ph (11) and α-L-Rhap-(1→3)-β-D-Glcp-1-O-(CH₂)₅NHZ (20). Building block 11 was obtained by intramolecular β-mannosylation of a malonyl-tethered disaccharide glycoside which was prepared from phenyl 4,6-O-benzylidene-1- thio-β-D-glucopyranoside (1) and ethyl 2,3,4-tri-O-benzyl-1-thio-α-D- mannopyranoside (5) in 5 steps. Building block 20 was obtained by coupling N- Z-protected 5-aminopentyl 2-O-benzyl-4,6-O-benzylidene-β-D-glucopyranoside (14) obtained from the non-benzylated counterpart 12 with ethyl 2,3-di-O- benzoyl-4-O-chloroacetyl-1-thio-α-L-rhamnopyrano- side (18) obtained in 3 steps from ethyl 2,3-O-isopropylidene- 1-thio-α-L-rhamnopyranoside (15).

Full text of DOI:10.1002/(SICI)1099-0690(200001)2000:1<181::AID-EJOC181>3.0.CO;2-7

FULL PAPER
Prearranged Glycosides, 9[°]
Chemical Synthesis of a Tetrasaccharide Fragment Related to the
Exopolysaccharide of Arthrobacter sp. CE-17
Gregor Lemanski[a] and Thomas Ziegler*[a]
Keywords: Carbohydrates / Oligosaccharides / Glycosylation / Organic synthesis
The tetrasaccharide 5-aminopentyl glycoside β-
D
-Manp-
O-benzylidene-1-thio-β-
2,3,4-tri-O-benzyl-1-thio-α -D
D
-glucopyranoside (1) and ethyl
-mannopyranoside (5) in 5
(1Ǟ4)-β- -Glcp-(1Ǟ4)-α - -Rhap-(1Ǟ3)-β- -Glcp-1-O-
D
L
D
(CH2 )5 NH2 (22) related to the exopolysaccharide of
Arthrobacter sp. CE-17 was synthesized by coupling of the
steps. Building block 20 was obtained by coupling N-Z-
protected 5-aminopentyl 2-O-benzyl-4,6-O-benzylidene-β-
properly protected disaccharide blocks β-
-Glcp-1-S-Ph (11) and α - -Rhap-(1Ǟ3)-β-
(CH2)5NHZ (20). Building block 11 was obtained by 1-thio-α-
intramolecular β-mannosylation of a malonyl-tethered ethyl 2,3-O-isopropylidene-1-thio-α-
D
-Manp-(1Ǟ4)-β-
D
-glucopyranoside (14) obtained from the non-benzylated
counterpart 12 with ethyl 2,3-di-O-benzoyl-4-O-chloroacetyl-
-rhamnopyrano- side (18) obtained in 3 steps from
-rhamnopyranoside
D
L
D
-Glcp-1-O-
L
L
disaccharide glycoside which was prepared from phenyl 4,6- (15).
In 1996, the first reports appeared that soil bacteria of
the genus Arthrobacter can cause hitherto unknown severe
infections in men. In this initial case, a patient who went
through eye surgery developed a severe endophthalmitis
caused by Arthrobacter.[1][2] Several other cases of Arthrob-
acter-associated infections have previously been reported in-
cluding chronic uveitis, different forms of kryptogenic poly-
arthritis, seronegative spondilarthropathy, meningitis and
lymphadenopathy (WhippleЈs syndrome).[3] Thus, synthetic
fragments related to the exopolysaccharides of Arthobacter
species are likely to be interesting targets because such oli-
gosaccharide fragments could be used for diagnostic pur-
poses or as artificial vaccines. Furthermore, exopolysacch-
arides of Arthrobacter are of significant importance as
thickeners for the food industry or as stabilizers for foams
and emulsions and as a flocculant.
Of the various Arthrobacter exopolysaccharides[4Ϫ9] stud-
ied so far only a few structures have been determined in
detail.[7Ϫ9] As part of a project toward the synthesis of py-
ruvated oligosaccharides[10] we were especially interested in
Simusan,[9] an acidic exopolysaccharide of Arthrobacter sp.,
strain CE-17 which exhibits an octasaccharide repeating
unit that contains a 4,6-pyruvated β--mannopyranosyl
residue (Figure 1). In particular, the synthesis of a 5-amino-
pentyl glycoside tetrasaccharide related to the sequence
ABCD of Simusan (Figure 1) that contains a β--mannopy-
ranosyl residue is described here.
Figure 1. Repeating unit of the exopolysaccharide of Arthrobacter
sp. CE-17
For the synthesis of the tetrasaccharide related to the se-
quence ABCD of Simusan we chose a blockwise approach.
Thus, two disaccharide building blocks Ϫ β--Manp-
(1Ǟ4)--Glcp as the disaccharide donor and α--Rhap-
(1Ǟ3)--Glcp as the disaccharide acceptor Ϫ were needed.
The donor block contains a β--mannosyl residue which
was planned to be introduced by intramolecular glycosyl-
ation of a suitable prearranged glycoside. Recently, we de-
veloped a highly selective β-mannosylation procedure[11]
which was applied to the preparation of the latter as fol-
lows. Starting from known[12] phenyl 4,6-O-benzylidene-1-
thio-β--glucopyranose (1), phase-transfer catalyzed ben-
zoylation[13] afforded dibenzoate 2 (11%), 3-O-benzoate 3
(16%), and the desired 2-O-benzoate 4 (54%). Alternative
selective benzoylations of 1 gave lower yields of compound
4 (see Experimental Section for details). Next, readily avail-
able[14] ethyl 2,3,4-tri-O-benzyl-1-thio-α--mannopyrano-
side (5) was esterified with tert-butyl malonate[15] (6) to give
mannoside 7 (64%), the tert-butyl group of which was fi-
nally cleaved with trifluoroacetic acid to afford mannosyl
malonate 8 in quantitative yield. The malonic acid tether in
compound 8 was chosen for linking the mannose unit with
glucoside 4 because previously, similarly tethered glycosides
[°] Part 8: T. Ziegler, R. Dettmann, Ariffadhillah, U. Zettl, J. Car-
bohydr. Chem., in press.
[a]
Institute of Organic Chemistry, University of Cologne,
Greinstraße 4, D-50939 Cologne, Germany
Fax: (internat.) ϩ 49-221/470-5057
E-mail: thomas.ziegler@uni-koeln.de
Eur. J. Org. Chem. 2000, 181Ϫ186
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
1434Ϫ193X/00/0101Ϫ181 $ 17.50ϩ.50/0
181

G. Lemanski, T. Ziegler
FULL PAPER
Scheme 1
gave high β-selectivities for intramolecular mannosyla- Thus, the disaccharide 19 was obtained in 79% yield and
tions.[11] Furthermore, combining the phenylthio group in the α-linkage of the rhamnosyl group was once again pro-
the glucose moiety 4 with the ethylthio group in 8 allows ven by measuring the C,H coupling constant at the anom-
us to make use of the principle of armed-disarmed glyco- eric center of 174.4 Hz. Finally, the chloroacetyl group of
sides[16] since mannosylation (i.e. activation of the ethylthio compound 19 was removed with thiourea to afford the di-
group) is possible without affecting the phenylthio group. saccharide acceptor 20 (87%).
Thus, according to previous procedures,[17][18] compounds
4 and 8 were condensed to give first saccharide 9 (81%),
the benzylidene acetal of the glucose moiety of which was
[17Ϫ19]
subsequently opened with NaCNBH3
to afford the
prearranged glycoside 10 in 71% yield. As was expected
from previous experiments,[11] intramolecular mannosyl-
ation of the latter with methyl trifluoromethanesulfonate
(MeOTf) as the promotor proceeded smoothly to give ex-
clusively the desired β--Manp-(1Ǟ4)--Glcp disaccharide
donor block 11 in 69% yield. The β-linkage of the mannosyl
moiety in 11 was evident from the NMR spectra of that
compound which showed a typical[20Ϫ22] C,H-coupling con-
stant at the anomeric center of 153.7 Hz.
The required α--Rhap-(1Ǟ3)--Glcp disaccharide ac-
ceptor was prepared conventionally from 5-benzyloxy-
carbonylpentyl 4,6-O-benzylidene-β--glucopyranoside[23]
(12). First, regioselective benzylation of the latter under
phase-transfer conditions[24] afforded 13 (21%) and 14
(53%). Next, a properly protected rhamnose derivative was
Scheme 2
The coupling of disaccharide blocks 11 and 20 was
prepared from ethyl 2,3-O-isopropylidene-1-thio-α--rham- somehow crucial. Several methods for the activation of
nopyranoside[25] (15) by chloroacetylation at the 4-position thioglycosides including NIS/trifluoromethanesulfonic
to give rhamnoside 16 (81%) followed by acidic hydrolysis acid (TfOH),[26] bromine/silver trifluoromethanesulfonate
of the isopropylidene group via 17 (88%) and reben- (AgOTf),[27] and dimethyl (methylthio)sulfonium triflate
zoylation of the free OH-groups to give monosaccharide 18 (DMTST)[28] failed completely and resulted in products of
(83%). Coupling of the latter to the 3-position of compound decomposition. Only NIS/trimethylsilyl trifluoromethanes-
14 was best performed with N-iodosuccinimide (NIS) in the ulfonate (TMSOTf)[29] gave the desired tetrasaccharide 21.
presence of 0.5 equiv. of TMSOTf in dichloromethane. However, the reaction showed an unusual temperature de-
182
Eur. J. Org. Chem. 2000, 181Ϫ186

Prearranged Glycosides, 9
FULL PAPER
reflux in a Dean-Stark apparatus, cooled to room temperature and
concentrated. The residue was dissolved in benzene (50 mL), a
solution of benzoyl chloride (0.18 mL, 1.53 mmol) in benzene
(25 mL) was added dropwise at room temperature and the solution
was stirred for 24 h. The mixture was diluted with CH2Cl2, filtered
through a layer of Celite and concentrated. Chromatography as
pendence. At 0°C, compound 21 was obtained in poor 9%
yield, whereas at Ϫ30°C or Ϫ70°C the yield of tetrasac-
charide 21 could be enhanced to 32% and 64%, respectively.
Final deblocking of the latter afforded the tetrasaccharide
5-aminopentyl glycoside (22) in 87% yield.
In summary, the efficient construction of the β-manno-
syl-containing disaccharide block 11 using intramolecular
glycosylation techniques in combination with the principle
of armed and disarmed glycosyl donors demonstrated the
described above afforded first 3 (0.38 g, 59%). Eluted next was 4
20
(0.15 g, 23%), which was obtained as a colorless foam. Ϫ [α]D
ϭ
1
Ϫ27.1 (c ϭ 0.7, CHCl3). Ϫ H NMR (CDCl3): δ ϭ 5.54 (s, 1 H,
PhCH), 5.15 (dd, J2,3 ϭ 8.8 Hz, 1 H, 2-H), 4.88 (d, J1,2 ϭ 10.0 Hz,
usefulness of this appraoch for the construction of higher 1 H, 1-H), 4.40 (dd, J5,6a ϭ 4.6 Hz, J6a,6b ϭ Ϫ10.5 Hz, 1 H, 6a-H),
4.03 (t, J3,4 ϭ 8.9 Hz, 1 H 3-H), 3.81 (t, J5,6b ϭ 10.0 Hz, 1 H, 6b-
H), 3.64Ϫ3.58 (m, J4,5 ϭ 9.3 Hz, 2 H, 4-H, 5-H), 2.85 (br. s, 1 H,
OH). Ϫ 13C NMR (CDCl3): δ ϭ 165.8 (PhCO), 101.9 (PhCH),
86.6 (C-1), 80.6 (C-4), 73.6 (C-3), 73.2 (C-2), 70.4 (C-5), 68.5 (C-
6). Ϫ C26H24O6S (464.5): calcd. C 67.23, H 5.21, S 6.90; found C
67.17, H 5.08, S 7.04.
oligosaccharides. Furthermore, compound 11 can be used
for the synthesis of other oligosaccharides containing this
disaccharide fragment.
Experimental Section
C) An aqueous NaOH solution (5%, 32 mL) was added with vigur-
General: Thin-layer chromatography (TLC) was performed on pre-
coated plastic sheets, Polygram SIL G/UV254, 40 ϫ 80 mm (Mach-
ereyϪNagel) using appropriately adjusted mixtures of toluene/ace-
tone for the developing. Spots were detected by UV light and by
charring with 5% sulfuric acid in ethanol. Ϫ Column chromatogra-
phy (CC) was performed by elution from columns of silica gel S
(MachereyϪNagel, 0.032Ϫ0.063 mm). Ϫ Solutions in organic sol-
vents were dried with anhydrous sodium sulfate, and concentrated
at 40°C, <200 Pa. Ϫ NMR spectra were recorded for solutions in
CDCl3 (with TMS as an internal standard) at 25°C on a Bruker
AC 250 F spectrometer. Proton signal assignments were made by
first order analysis of the spectra and by H,H-cosy techniques. Of
two magnetically nonequivalent geminal protons, the one resonat-
ing at lower field was designated as Ha and the one resonating at
higher field was designated as Hb. Carbon signal assignments were
made by C,H-correlation and by comparison of the peaks with
those of related compounds. Ϫ Optical rotations were measured at
20°C with a PerkinϪElmer automatic polarimeter, Model 241. Ϫ
Melting points were determined with a Büchi apparatus, Model
SMP-20.
ous stirring Ϫ5°C to
a solution of 1 (4.54 g, 12.6 mmol),
Bu4NHSO4 (0.83 g, 2.58 mmol) and benzoyl chloride (1.97 mL,
17.02 mmol) in CH2Cl2 (230 mL). The mixture was stirred for
10 min, the organic layer was separated, washed with water, dried
and concentrated. Chromatography as described above afforded
first 2 (0.77 g, 11%), then 3 (0.96 g, 16%), and finally 4 (3.14 g,
54%).
Ethyl 2,3,4-Tri-O-benzyl-6-O-(tert-butyloxycarbonylethanoyl)-1-thio-
α-D-mannopyranoside (7): DCC (0.96 g, 4.65 mmol) was added at
0°C to a solution of 5[14] (2.09 g, 4.23 mmol), 6[15] (0.75 g,
4.65 mmol) and 1-hydroxy-1H-benzotriazole (0.69 g, 5.08 mmol) in
CH2Cl2 (30 mL). The mixture was stirred at room temperature for
24 h, diluted with CH2Cl2 and filtered through a layer of Celite .
The filtrate was subsequently washed with aqueous HCl and
NaHCO3 solution, dried and concentrated. Chromatography (n-
hexane/ethyl acetate 6:1 v/v) of the residue afforded 7 (1.73 g, 64%)
20
as a colorless foam. Ϫ [α]D ϭ ϩ58.0 (c ϭ 1.1, CHCl3). Ϫ 1H
NMR (CDCl3): δ ϭ 5.33 (d, J1,2 ϭ 1.0 Hz, 1 H, 1-H), 4.92 (d, J ϭ
Ϫ10.7 Hz, 1 H, PhCH2), 4.71 (d, J ϭ Ϫ12.5 Hz, 1 H, PhCH2), 4.65
(d, J ϭ Ϫ12.5 Hz, 1 H, PhCH2), 4.60Ϫ4.56 (m, 3 H, PhCH2), 4.44
(dd, J5,6a ϭ 5.1 Hz, J6a,6b ϭ Ϫ11.8 Hz, 1 H, 6a-H), 4.36 (dd, J5,6b ϭ
2.2 Hz, 1 H, 6b-H), 4.18 (ddd, 1 H, 5-H), 3.93 (t, J4,5 ϭ 9.4 Hz, 1
H, 4-H), 3.83 (2 dd, J2,3 ϭ 3.2 Hz, J3,4 ϭ 10.1 Hz, 2 H, 2-H, 3-H),
3.29 (s, 2 H, COCH2), 2.66Ϫ2.47 (m, 2 H, SCH2CH3), 1.44 [s, 9
H, C(CH3)3], 1.23 (t, J ϭ 7.4 Hz, 3 H, SCH2CH3). Ϫ 13C NMR
(CDCl3): δ ϭ 166.9 (CO), 165.4 (CO), 82.0 (C(CH3)3), 81.9 (C-1),
80.2 (C-3), 76.2 (C-2), 75.2 (PhCH2), 74.6 (C-4), 72.0 (2 C, PhCH2),
70.1 (C-5), 64.3 (C-6), 42.6 (COCH2), 27.9 (C(CH3)3), 25.4
(SCH2CH3), 14.9 (SCH2CH3). Ϫ C36H44O8S (636.8): calcd. C
67.90, H 6.96, S 5.04; found C 67.94, H 7.08, S 5.11.
Phenyl 2,3-di-O-Benzoyl-4,6-O-benzylidene-1-thio-β-
side (2), Phenyl 3-O-Benzoyl-4,6-O-benzylidene-1-thio-β-
anoside (3), and Phenyl 2-O-Benzoyl-4,6-O-benzylidene-1-thio-β-
D
-glucopyrano-
D-glucopyr-
D-
glucopyranoside (4): A) Benzoyl chloride (165 µL, 1.39 mmol) was
added at Ϫ50°C to a solution of 1[12] (0.50 g, 1.39 mmol) in pyri-
dine (15 mL), the mixture was stirred for 48 h, poured into ice-cold
water and extracted with CH2Cl2. The combined organic phases
were subsequently washed with aqueous HCl and NaHCO3 solu-
tion, dried and concentrated. Chromatography (gradient elution
with toluene/acetone 55:1Ǟ35:1 v/v) afforded first 2 (116 mg, 15%),
20
m.p. 203°C [ref.[30] 203Ϫ205°C (EtOH/ethyl acetate)]. Ϫ [α]D
ϭ
ϩ42.6 (c ϭ 1.1, CHCl3) {ref.[30] [α]D ϭ ϩ40 (c ϭ 1.0, CHCl3)}.
Eluted next was 3 (295 mg, 46%), m.p. 154Ϫ156°C (EtOH). Ϫ
[α]D ϭ Ϫ98.4 (c ϭ 1.3, CHCl3). Ϫ 1H NMR (CDCl3): δ ϭ 5.51 (s,
Ethyl 2,3,4-Tri-O-benzyl-6-O-(hydroxycarbonylethanoyl)-1-thio-α-D-
mannopyranoside (8): Trifluoroacetic acid (5.3 mL, 51.8 mmol) was
added at room temperature to a solution of 7 (1.65 g, 2.59 mmol) in
CH2Cl2 (80 mL), the mixture was stirred for 3 h and concentrated.
Coevaporation of toluene (3 times) afforded crude 8 (2.58 g, 100%)
which was used without further purification in the next step.
1 H, PhCH), 5.50 (dd, J3,4 ϭ 9.5 Hz, 1 H, 3-H), 4.76 (d, J1,2
ϭ
9.7 Hz, 1 H, 1-H), 4.39 (dd, J5,6a ϭ 4.9 Hz, J6a,6b ϭ Ϫ10.4 Hz, 1
H, 6a-H), 3.81 (t, J5,6b ϭ 9.6 Hz, 1 H, 6b-H), 3.77 (t, J4,5 ϭ 9.6 Hz,
1 H, 4-H), 3.70 (bd, J2,3 ϭ 8.9 Hz, 1 H, 2-H), 3.62 (dt, 1 H, 5-H),
3.04 (br. s, 1 H, OH). Ϫ 13C NMR (CDCl3): δ ϭ 166.6 (PhCO),
101.4 (PhCH), 89.2 (C-1), 78.2 (C-4), 75.6 (C-3), 70.7 (C-5), 68.5
(2 C, C-2, C-6). Ϫ C26H24O6S (464.5): calcd. C 67.23, H 5.21, S
6.90; found C 67.19, H 5.26, S 6.95.
Ethyl 2,3,4-tri-O-benzyl-6-O-[(2-O-benzoyl-4,6-O-benzylidene-1-phen-
ylthio-β-D-glucopyranos-3-yloxy)carbonylethanoyl]-1-thio-α-D-
mannopyranoside (9): DCC (0.47 g, 2.28 mmol) was added at room
temperature to a solution of 4 (1.04 g, 2.24 mmol), crude 8 (1.19 g,
2.05 mmol) and a catalytic amount of DMAP (ca. 20 mg) in
CH2Cl2 (30 mL), and the mixture was stirred for 24 h. Workup as
described for the preparation of 7 and chromatography (toluene/
ethyl acetate 22:1 v/v) afforded 9 (1.86 g, 81%) as a colorless foam.
Eluted next was unchanged 1 (69 mg, 14%).
B) A mixture of 1 (0.50 g, 1.39 mmol) and di-n-butyltin oxide
(0.36 g, 1.45 mmol) in benzene (100 mL) was heated for 24 h under
Eur. J. Org. Chem. 2000, 181Ϫ186
183

G. Lemanski, T. Ziegler
FULL PAPER
20
Ϫ [α]D ϭ ϩ36.8 (c ϭ 1.1, CHCl3). Ϫ 1H NMR (CDCl3): δ ϭ
8.8 Hz, 3Ј-H), 3.17 (bd, 2 H, COCH2). Ϫ 13C NMR (CDCl3): δ ϭ
165.6, 165.2, 164.5 (CO), 103.5 (C-1Ј, JC-1Ј,1Ј-H ϭ 153.7 Hz), 85.5
5.54 (t, J3,4 ϭ 9.3 Hz, 1 H, 3-H), 5.49 (s, 1 H, PhCH), 5.28 (dd,
J2,3 ϭ 9.1 Hz, 1 H, 2-H), 5.27 (s, 1 H, 1Ј-H), 4.93 (d, J1,2 ϭ 10.0 Hz, (C-1, JC-1,1-H ϭ 157.0 Hz), 82.2 (C-3Ј), 78.9 (C-5), 78.6 (C-4), 76.7
1 H, 1-H), 4.85 (d, J ϭ Ϫ10.9 Hz, 1 H, PhCH2), 4.68 (d, J ϭ (2 C, C-3, C-4Ј), 74.8 (PhCH2), 74.4 (C-2Ј), 73.7, 73.5, 72.0
Ϫ12.1 Hz, 1 H, PhCH2), 4.62 (d,, J ϭ Ϫ12.3 Hz 1 H, PhCH2), 4.54 (PhCH2), 71.2 (C-2), 70.4 (C-5Ј), 68.4 (C-6), 64.2 (C-6Ј), 42.7
(s, 2 H, PhCH2), 4.49 (d, J ϭ Ϫ10.9 Hz, 1 H, PhCH2), 4.41 (dd, (COCH2). Ϫ C56H54O13S (967.1): calcd. C 69.55, H 5.63, S 3.32;
J5,6a ϭ 4.7 Hz, J6a,6b ϭ Ϫ10.4 Hz, 1 H, 6a-H), 4.25Ϫ4.20 (m, 2 H,
6aЈ-H, 6bЈ-H), 4.10Ϫ4.04 (m, 1 H, 5Ј-H), 3.83Ϫ3.76 (m, J5,6b
found C 69.26, H 5.41, S 3.26.
ϭ
5-Benzyloxycarbonylaminopentyl 3-O-Benzyl-4,6-O-benzylidene-β-
9.6 Hz, 4 H, 2Ј-H, 3Ј-H, 4Ј-H, 6b-H), 3.75 (t, J4,5 ϭ 9.6 Hz, 1 H,
4-H), 3.63 (dt, 1 H, 5-H), 3.27 (s, 2 H, COCH2), 2.60Ϫ2.43 (m, 2
H, SCH2CH3), 1.19 (t, J ϭ 7.4 Hz, 3 H, SCH2CH3). Ϫ 13C NMR
(CDCl3): δ ϭ 165.4 (CO), 165.3 (CO), 165.2 (CO), 101.4 (PhCH),
87.0 (C-1), 81.8 (C-1Ј), 80.2 (C-3Ј), 78.0 (C-4), 76.1, 74.6 (C-2Ј,4Ј),
75.0 (PhCH2), 73.6 (C-3), 72.0 (2 C, PhCH2), 70.8 (2 C, C-2, C-5),
70.0 (C-5Ј), 68.4 (C-6), 64.4 (C-6Ј), 40.8 (COCH2), 25.3
(SCH2CH3), 14.9 (SCH2CH3). Ϫ C58H58O13S2 (1027.2): calcd. C
67.82, H 5.69, S 6.24; found C 67.77, H 5.73, S 6.22.
D-glucopyranoside (13) and 5-Benzyloxycarbonylaminopentyl 2-O-
Benzyl-4,6-O-benzylidene-β- -glucopyranoside (14): Aqueous 5%
D
NaOH solution (7.95 mL) was added with vigurous stirring at
room temperature to a solution of 12[23] (2.79 g, 5.72 mmol), BnBr
(1.19 mL, 10.02 mmol) and Bu4NHSO4 (0.38 g, 1.13 mmol) in
CH2Cl2 (50 mL) and the mixture was refluxed for 72 h. The mix-
ture was diluted with CH2Cl2, washed with water, dried and con-
centrated. Chromatography (gradient elution with toluene/acetone
15:1Ǟ10:1 v/v) of the residue afforded first 14 (1.82 g, 53%), m.p.
20
112Ϫ113°C (EtOH). Ϫ [α]D ϭ Ϫ19.3 (c ϭ 1.6, CHCl3). Ϫ 1H
Ethyl
thio-β-
2,3,4-tri-O-benzyl-6-O-[(2-O-benzoyl-6-O-benzyl-1-phenyl-
-glucopyranos-3-yloxy)carbonylethanoyl]-1-thio-α- -manno-
D
D
NMR (CDCl3): δ ϭ 5.49 (s, 1 H, PhCH), 5.07 (s, 2 H,
PhCH2OCO), 4.92 (d, J ϭ Ϫ11.5 Hz, 1 H, PhCH2), 4.73 (bd, J ϭ
Ϫ11.5 Hz, 2 H, PhCH2, NH), 4.48 (d, J1,2 ϭ 7.7 Hz, 1 H, 1-H),
4.32 (dd, J5,6a ϭ 4.9 Hz, J6a,6b ϭ Ϫ10.4 Hz, 1 H, 6a-H), 3.93Ϫ3.87
(m, 1 H, OCH2), 3.85Ϫ3.79 (m, J3,4 ϭ 9.1 Hz, J3,OH ϭ 2.1 Hz, 1
H, 3-H), 3.75 (t, J5,6b ϭ 10.2 Hz, 1 H, 6b-H), 3.58Ϫ3.53 (m, 1 H,
pyranoside (10): A solution of HCl in THF was added portionwise
at room temperature to a suspension of 9 (1.60 g, 1.51 mmol),
˚
NaCNBH3 (1.19 g, 18.9 mmol) and 3 A molecular sieves (ca. 1.0 g)
in THF (50 mL) until the evolution of gas ceased. The mixture was
diluted with CH2Cl2 and filtered through a layer of Celite . The
filtrate was washed with an aqueous NaHCO3 solution, dried and
concentrated. Chromatography (toluene/ethyl acetate 8:1 v/v) af-
forded 10 (1.10 g, 71%) as a colorless foam. Ϫ [α]D20 ϭ ϩ42.5 (c ϭ
1.6, CHCl3). Ϫ 1H NMR (CDCl3): δ ϭ 5.30 (s, 1 H, 1Ј-H),
5.30Ϫ5.25 (m, J3,4 ϭ 8.9 Hz, 1 H, 3-H), 5.13 (t, J2,3 ϭ 9.7 Hz, 1
OCH2), 3.52 (t, J4,5 ϭ 9.3 Hz, 1 H, 4-H), 3.43Ϫ3.37 (m, J5,6a
ϭ
4.9 Hz, 1 H, 5-H), 3.33 (dd, J2,3 ϭ 8.8 Hz, 1 H, 2-H), 3.17Ϫ3.11
(m, 2 H, CH2), 2.59 (d, 1 H, OH), 1.66Ϫ1.33 (m, 6 H, CH2). Ϫ
13C NMR (CDCl3): δ ϭ 156.3 (OCONH), 103.7 (C-1), 101.7
(PhCH), 81.8 (C-2), 80.4 (C-4), 74.7 (PhCH2), 73.1 (C-3), 70.1
(OCH2), 68.7 (C-6), 66.5 (PhCH2OCO), 66.0 (C-5), 40.8 (CH2NH),
29.6, 29.3, 23.2 (CH2). Ϫ C33H39NO8 (577.7): calcd. C 68.61, H
6.81, N 2.43; found C 68.58, H 6.79, N 2.37.
H, 2-H), 4.89 (d, J ϭ Ϫ11.0 Hz, 1 H, PhCH2), 4.81 (d, J1,2
ϭ
9.9 Hz, 1 H, 1-H), 4.68 (d, J ϭ Ϫ12.3 Hz, 1 H, PhCH2), 4.55 (br.
s, 5 H, PhCH2), 4.53 (d, J ϭ Ϫ11.3 Hz, 1 H, PhCH2), 4.37Ϫ4.27
(m, 2 H, 6aЈ-H, 6bЈ-H), 4.15Ϫ4.10 (m, 1 H, 5Ј-H), 3.92 (t, J4Ј,5Ј
ϭ
Eluted next was 13 (0.68 g, 21%), m.p. 119Ϫ120°C (EtOH). Ϫ
9.2 Hz, 1 H, 4Ј-H), 3.84 (m, 3 H, 2Ј-H, 3Ј-H, 6a-H), 3.73Ϫ3.66 (m,
2 H, 6b-H, OH), 3.61 (bm, 2 H, 4-H, 5-H), 3.35 (d, J ϭ Ϫ16.1 Hz,
1 H, COCH2), 3.20 (d, J ϭ Ϫ16.1 Hz, 1 H, COCH2), 2.59Ϫ2.46
(m, 2 H, SCH2CH3), 1.20 (t, J ϭ 7.4 Hz, 3 H, SCH2CH3). Ϫ 13C
20
1
[α]D ϭ Ϫ26.0 (c ϭ 1.8, CHCl3). Ϫ H NMR (CDCl3): δ ϭ 5.54
(s, 1 H, PhCH), 5.09 (s, 2 H, PhCH2OCO), 4.95 (d, J ϭ Ϫ11.7 Hz,
1 H, PhCH2), 4.85 (br. s, 1 H, NH), 4.80 (d, J ϭ Ϫ11.8 Hz, 1 H,
PhCH2), 4.37 (d, J1,2 ϭ 7.7 Hz, 1 H, 1-H), 4.33 (dd, J5,6a ϭ 5.0 Hz,
J6a,6b ϭ Ϫ10.4 Hz, 1 H, 6a-H), 3.92Ϫ3.84 (m, 1 H, OCH2), 3.78
(t, J5,6b ϭ 10.3 Hz, 1 H, 6b-H), 3.72Ϫ3.66 (m, 1 H, 4-H), 3.65 (t,
J3,4 ϭ 8.7 Hz, 1 H, 3-H), 3.58Ϫ3.48 (m, 2 H, 2-H, OCH2),
3.46Ϫ3.88 (m, 1 H, 5-H), 3.19Ϫ3.15 (m, 2 H, CH2), 2.70 (br. s, 1
H, OH), 1.69Ϫ1.36 (m, 6 H, CH2). Ϫ 13C NMR (CDCl3): δ ϭ
156.4 (OCONH), 103.3 (C-1), 101.2 (PhCH), 81.3 (C-3), 80.3 (C-
4), 74.5 (PhCH2), 74.3 (C-2), 68.7 (C-6), 66.6 (PhCH2OCO), 66.4
(C-5), 40.8 (CH2NH), 29.5, 20.9, 23.0 (CH2). Ϫ C33H39NO8
(577.7): calcd. C 68.61, H 6.81, N 2.43; found C 68.52, H 6.84,
N 2.36.
NMR (CDCl3):
δ ϭ 166.9 (PhCO), 165.6 (COCH2), 165.2
(COCH2), 85.9 (C-1), 81.9 (C-1Ј), 80.0 (C-3Ј), 79.4 (C-5), 78.2 (C-
3), 76.2 (C-2Ј), 75.1 (PhCH2), 74.0 (C-4Ј), 73.5 (PhCH2), 72.0
(PhCH2), 71.9 (PhCH2), 70.2 (C-2), 69.8 (C-5Ј), 69.4 (C-6), 68.9
(C-4), 64.6 (C-6Ј), 41.3 (COCH2), 25.5 (SCH2CH3), 14.9
(SCH2CH3). Ϫ C58H60O13S2 (1029.2): calcd. C 67.69, H 5.88, S
6.23; found C 67.57, H 5.88, S 6.21.
Phenyl
O-(2,3,4-Tri-O-benzyl-β-D-mannopyranosyl)-(1Ǟ4)-2-O-
benzoyl-6-O-benzyl-1-thio-β-
D-glucopyranoside 3,6Ј-Malonate (11):
MeOTf (0.37 mL, 3.40 mmol) was added at room temperature un-
˚
der argon to a mixture of 10 (0.70 g, 0.68 mmol) and 4 A molecular
sieves (1.76 g) in acetonitrile (30 mL). The mixture was stirred for
6 h, diluted with CH2Cl2 and filtered. The filtrate was washed with
water, dried and concentrated. Chromatography (toluene/acetone
Ethyl 4-O-Chloroacetyl-2,3-O-isopropylidene-1-thio-α-L-rhamnopyr-
anoside (16): Chloroacetyl chloride (4.7 mL, 59.3 mmol) was added
dropwise at 0°C to a solution of 15[25] (9.2 g, 37.1 mmol) and pyri-
dine (4.0 mL, 49.6 mmol) in CH2Cl2 (180 mL). The mixture was
40:1 v/v) of the residue afforded 11 (0.45 g, 69%) as a colorless
20
foam. Ϫ [α]D ϭ Ϫ4.2 (c ϭ 1.0, CHCl3). Ϫ 1H NMR (CDCl3): stirred for 16 h at room temperature and poured into water. The
δ ϭ 5.31 (t, J3,4 ϭ 9.1 Hz, 1 H, 3-H), 5.15 (t, J2,3 ϭ 9.6 Hz, 1 H, organic layer was separated, washed with aqueous HCl and
2-H), 4.86 (d, J ϭ Ϫ11.3 Hz, 1 H, PhCH2), 4.82 (d, J1,2 ϭ 10.1 Hz,
NaHCO3 solution, dried and concentrated. Crystallisation of the
1 H, 1-H), 4.74 (d, J ϭ Ϫ11.8 Hz, 1 H, PhCH2), 4.70 (d, J ϭ residue from acetone afforded 16 (9.74 g, 81%), m.p. 122°C. Ϫ
20
1
Ϫ12.5 Hz, 1 H, PhCH2), 4.56Ϫ4.50 (m, J6aЈ,6bЈ ϭ Ϫ11.1 Hz, 1 H, [α]D ϭ Ϫ43.1 (c ϭ 1.0, CHCl3). Ϫ H NMR (CDCl3): δ ϭ 5.56
6aЈ-H), 4.50 (s, 3 H, PhCH2), 4.47 (d, J ϭ Ϫ11.8 Hz, 1 H, PhCH2), (s, 1 H, 1-H), 4.96 (dd, J4,5 ϭ 10.1 Hz, 1 H, 4-H), 4.22Ϫ4.19 (m, 1
4.36 (d, J ϭ Ϫ12.1 Hz, 1 H, PhCH2), 4.29 (s, 1 H, 1Ј-H), 4.03 (dd,
J5Ј,6bЈ ϭ 8.4 Hz, 1 H, 6bЈ-H), 3.97 (t, J4,5 ϭ 9.3 Hz, 1 H, 4-H), 3.74 H), 4.11 (2 s, 2 H, ClCH2CO), 2.74Ϫ2.49 (m, 2 H, SCH2CH3), 1.57
(t, J4Ј,5Ј ϭ 9.2 Hz, 1 H, 4Ј-H), 3.60 (bd, J2Ј,3Ј ϭ 2.9 Hz, J5,6a [s, 3 H, C(CH3)2], 1.34 [s, 3 H, C(CH3)2], 1.31 (t, J ϭ 7.5 Hz, 3 H,
10.0 Hz, J6a,6b ϭ Ϫ11.0 Hz, 3 H, 2Ј-H, 5Ј-H, 6a-H), 3.53 (bt, SCH2CH3), 1.19 (d, 1 H, 6-H). Ϫ 13C NMR (CDCl3): δ ϭ 166.6
H, 2-H), 4.18Ϫ4.12 (m, J3,4 ϭ 7.5 Hz, J5,6 ϭ 6.3 Hz, 2 H, 3-H, 5-
ϭ
J5,6b ϭ 3.7 Hz, 1 H, 5-H), 3.44 (dd, 1 H, 6b-H), 3.38 (dd, J3Ј,4Ј
ϭ
(ClCH2CO), 110.0 [C(CH3)2], 79.4 (C-1), 76.9, 76.8 (C-2,4), 75.2
184
Eur. J. Org. Chem. 2000, 181Ϫ186

Prearranged Glycosides, 9
FULL PAPER
(C-3), 64.2 (C-5), 27.7 [C(CH3)2], 26.4 [C(CH3)2], 24.5 (SCH2CH3), OCH2, 2-H), 3.48Ϫ3.40 (m, 1 H, 5-H), 3.19Ϫ3.12 (m, 2 H, CH2),
16.9 (C-6), 14.6 (SCH2CH3). Ϫ C13H21ClO5S (324.8): calcd C 1.68Ϫ1.64 (m, 2 H, CH2), 1.54Ϫ1.37 (m, 4 H, CH2), 0.86 (d, 1 H,
48.07, H 6.52, Cl 10.92, S 9.87; found C 48.05, H 6.56, Cl 10.94, 6Ј-H). Ϫ 13C NMR (CDCl3): δ ϭ 166.6, 165.6, 165.2 (CO), 156.4
S 9.79.
(OCONH), 104.2 (C-1), 101.9 (PhCH), 97.9 (C-1Ј, JC-1Ј,1Ј-H ϭ
174.4 Hz), 82.7 (C-2), 79.1 (C-4), 76.4 (C-3), 75.2 (PhCH2), 73.3
(C-4Ј), 70.4 (C-2Ј), 70.2 (OCH2), 70.0 (C-3Ј), 68.8 (C-6), 66.6
(PhCH2OCO), 66.4 (C-5), 65.8 (C-5Ј), 40.9 (CH2NH), 40.4
(ClCH2CO), 29.7 (CH2), 29.4 (CH2), 23.3 (CH2), 16.8 (C-6Ј). Ϫ
C55H58ClNO15 (1008.5): calcd C 65.50, H 5.80, N 1.39; found C
65.41, H 5.93, N 1.30.
Ethyl 4-O-Chloroacetyl-1-thio-α-L-rhamnopyranoside (17): Acetic
acid (150 mL) was added to a solution of 16 (8.39 g, 25.82 mmol)
in a small amount of CH2Cl2. The mixture was stirred for 7 h at
60°C, cooled to room temperature and concentrated. Crystallis-
ation of the residue from n-hexane/acetone afforded 17 (6.47 g,
88%), m.p. 137Ϫ139°C. Ϫ [α]D20 ϭ Ϫ89.5 (c ϭ 0.7, CHCl3). Ϫ 1H
NMR ([D6]acetone): δ ϭ 5.25 (d, J1,2 ϭ 1.0 Hz, 1 H, 1-H), 4.99 (t,
J4,5 ϭ 9.7 Hz, 1 H, 4-H), 4.49 (d, J2,OH ϭ 4.1 Hz, 1 H, OH), 4.34
(d, J ϭ Ϫ15.0 Hz, 1 H, ClCH2CO), 4.26 (d, J ϭ Ϫ15.0 Hz, 1 H,
ClCH2CO), 4.16 (d, J3,OH ϭ 7.0 Hz, 1 H, OH), 4.13Ϫ4.03 (m,
J5,6 ϭ 6.3 Hz, 1 H, 5-H), 3.97 (dt, J2,3 ϭ 3.4 Hz, 1 H, 2-H), 3.78
(ddd, J3,4 ϭ 9.6 Hz, 1 H, 3-H), 2.70Ϫ2.52 (m, 2 H, SCH2CH3),
1.25 (t, J ϭ 7.4 Hz, 3 H, SCH2CH3), 1.14 (d, 1 H, 6-H). Ϫ 13C
NMR ([D6]acetone): δ ϭ 167.8 (ClCH2CO), 85.4 (C-1), 77.3 (C-4),
73.4 (C-2), 70.5 (C-3), 67.0 (C-5), 41.7 (SCH2CH3), 17.6 (C-6), 15.3
(SCH2CH3). Ϫ C10H17ClO5S (284.8): calcd C 42.18, H 6.02, Cl
12.45, S 11.26; found C 42.33, H 5.99, Cl 12.97, S 11.16.
5-Benzyloxycarbonylaminopentyl O-(2,3-Di-O-benzoyl-α-
L-rhamno-
pyranosyl)-(1Ǟ3)-2-O-benzyl-4,6-O-benzylidene-β- -glucopyr-
D
anoside (20): A solution of 19 (0.60 g, 0.6 mmol) and thiourea
(0.2 g, 2.63 mmol) in a mixture of MeOH (17 mL) and CH2Cl2
(6 mL) was stirred at room temperature for 3 d and concentrated.
The residue was dissolved in CH2Cl2, washed with water, dried and
concentrated. Chromatography (toluene/acetone 12:1 v/v) of the
20
residue afforded 20 (0.48 g, 87%) as a colorless foam. Ϫ [α]D
ϭ
ϩ17.4 (c ϭ 1.0, CHCl3). Ϫ 1H NMR (CDCl3): δ ϭ 5.67 (dd,
J2Ј,3Ј ϭ 3.4 Hz 1 H, 2Ј-H), 5.56 (s, 1 H, PhCH), 5.50 (dd, J3Ј,4Ј
ϭ
9.9 Hz, 1 H, 3Ј-H), 5.33 (d, J1Ј,2Ј ϭ 1.4 Hz, 1 H, 1Ј-H), 5.07 (s, 2
H, PhCH2OCO), 4.89 (d, J ϭ Ϫ10.7 Hz, 1 H, PhCH2), 4.73 (bd, 2
H, PhCH2, NH), 4.49 (d, J1,2 ϭ 7.7 Hz, 1 H, 1-H), 4.36 (dd, J5,6a ϭ
Ethyl 2,3-Di-O-benzoyl-4-O-chloroacetyl-1-thio-α-L-rhamnopyrano-
side (18): A mixture of BzCl (11.7 mL, 100.6 mmol) and pyridine
(8.0 mL, 98.59 mmol) was slowly dropped at 0°C into a solution
of 17 (5.73 g, 20.12 mmol) in acetonitrile (80 mL). The mixture was
stirred for 2 h at room temperature, poured into water and ex-
tracted with CH2Cl2. The combined extracts were washed with
aqueous HCl and NaHCO3 solution, dried and concentrated.
Chromatography (n-hexane/ethyl acetate 12:1 v/v) of the residue
and crystallisation from n-hexane/diethyl ether afforded 18 (8.23 g,
83%), m.p. 73Ϫ75°C. Ϫ [α]D ϭ ϩ31.9 (c ϭ 1.5, CHCl3). Ϫ H
NMR (CDCl3): δ ϭ 5.73 (dd, J2,3 ϭ 3.3 Hz, 1 H, 2-H), 5.61 (dd,
J3,4 ϭ 10.1 Hz, 1 H, 3-H), 5.49 (t, J4,5 ϭ 9.8 Hz, 1 H, 4-H), 5.45
(d, J1,2 ϭ 1.4 Hz, 1 H, 1-H), 4.48Ϫ4.41 (m, J5,6 ϭ 6.2 Hz, 1 H, 5-
H), 4.01 (d, J ϭ Ϫ14.5 Hz, 1 H, ClCH2CO), 3.94 (d, J ϭ Ϫ14.5 Hz,
1 H, ClCH2CO), 2.78Ϫ2.64 (m, 2 H, SCH2CH3), 1.35 (t, J ϭ
7.4 Hz, 3 H, SCH2CH3), 1.35 (d, 1 H, 6-H). Ϫ 13C NMR (CDCl3):
δ ϭ 166.7 (ClCH2CO), 165.4 (PhCO), 165.3 (PhCO), 82.0 (C-1),
73.4 (C-4), 72.5 (C-2), 70.2 (C-3), 66.7 (C-5), 40.5 (ClCH2CO), 25.6
(SCH2CH3), 17.4 (C-6), 14.9 (SCH2CH3). Ϫ C24H25ClO7S (493.0):
calcd C 58.47, H 5.11, S 6.50; found C 58.49, H 5.03, S 6.56.
4.9 Hz, J6a,6b ϭ Ϫ10.3 Hz, 1 H, 6a-H), 4.21Ϫ4.16 (m, J5Ј,6Ј
6.1 Hz, 1 H, 5Ј-H), 3.97 (t, J3,4 ϭ 9.2 Hz, 1 H, 3-H), 3.95Ϫ3.88 (m,
1 H, OCH2), 3.80 (t, J5,6b ϭ 9.6 Hz, 1 H, 6b-H), 3.75 (dt, J4Ј,5Ј
9.7 Hz, J4Ј,OH ϭ 5.5 Hz, 1 H, 4Ј-H), 3.63 (t, J4,5 ϭ 9.4 Hz, 1 H, 4-
H), 3.57Ϫ3.50 (m, 2 H, OCH2, 2-H), 3.44 (dt, 1 H, 5-H), 3.16Ϫ3.11
(m, 2 H, CH2), 2.13 (d, 1 H, OH), 1.68Ϫ1.62 (m, 2 H, CH2),
1.53Ϫ1.36 (m, 4 H, CH2), 1.02 (d, 1 H, 6Ј-H). Ϫ 13C NMR
(CDCl3): δ ϭ 167.0, 165.2 (CO), 156.3 (OCONH), 104.1 (C-1,
ϭ
ϭ
20
1
JC-1ϪH-1 ϭ 158.1 Hz), 101.6 (PhCH), 98.1 (C-1Ј, JC-1ЈϪH-1Ј
ϭ
175.0 Hz), 82.8 (C-2), 79.1 (C-4), 76.6 (C-3), 75.1 (PhCH2), 73.3
(C-3Ј), 71.9 (C-4Ј), 70.1 (OCH2), 70.7 (C-2Ј), 68.7 (C-6), 68.5 (C-
5Ј), 66.6 (PhCH2OCO), 66.4 (C-5), 40.9 (CH2NH), 29.6 (CH2),
29.3 (CH2), 23.2 (CH2), 17.0 (C-6Ј). Ϫ C53H57NO14 (932.0): calcd
C 68.30, H 6.16, N 1.50; found C 68.12, H 6.31, N 1.39.
5-Benzyloxycarbonylaminopentyl O-(2,3,4-Tri-O-benzyl-β-
pyranosyl)-(1Ǟ4)-2-O-benzoyl-6-O-benzyl-β- -glucopyranosyl)-
(1Ǟ4)-(2,3-di-O-benzoyl-α- -rhamnopyranosyl)-(1Ǟ3)-2-O-benzyl-
4,6-O-benzylidene-β- -glucopyranoside 3ЈЈ,6ЈЈЈ-Malonate (21):
D-manno-
D
L
D
Treatment of a mixture of 11 (120 mg, 0.12 mmol), 20 (116 mg,
˚
5-Benzyloxycarbonylaminopentyl
roacetyl-α- -rhamnopyranosyl)-(1Ǟ3)-2-O-benzyl-4,6-O-benzy-
lidene-β- -glucopyranoside (19):
O-(2,3-Di-O-benzoyl-4-O-chlo-
0.12 mmol) and 3 A molecular sieves (ca. 0.2 g) in CH2Cl2 (5 mL)
L
under argon at Ϫ70°C with NIS (28.0 mg, 0.12 mmol) and
TMSOTf (11 µL, 62 µmol) for 6 h and workup as described for
D
A
mixture of 14 (0.98 g,
˚
1.70 mmol), 18 (1.01 g, 2.04 mmol) and 4 A molecular sieves (ca. the preparation of 19 followed by chromatography (toluene/acetone
1.0 g) in CH2Cl2 (25 mL) was cooled under argon to 0°C and 20:1 v/v) afforded 21 (141 mg, 64%) as a colorless foam. Ϫ [α]D20 ϭ
stirred for 10 min. NIS (0.46 g, 2.04 mmol) and TMSOTf (184 µL,
1.02 mmol) were successively added, the mixture was stirred for
20 min, neutralized by the addition of triethylamine and filtered
ϩ36.1 (c ϭ 0.8, CHCl3). Ϫ 1H NMR (CDCl3): δ ϭ 5.65 (dd,
J2Ј,3Ј ϭ 3.5 Hz, 1 H, 2Ј-H), 5.52 (s, 1 H, PhCH), 5.45 (dd, J3Ј,4Ј
ϭ
9.8 Hz, 1 H, 3Ј-H), 5.22 (d, J1Ј,2Ј ϭ 1.3 Hz, 1 H, 1Ј-H), 5.14 (dd,
through a layer of Celite . The filtrate was washed with aqueous J2Љ,3Љ ϭ 9.5 Hz, 1 H, 2Љ-H), 5.06 (t, s, J3Љ,4Љ ϭ 9.3 Hz, 1 H, 2 H, 3Љ-
Na2S2O3 solution, dried and concentrated. Chromatography (tolu- H, PhCH2OCO), 4.72 (s, 1 H, NH), 4.71 (d, J1Љ,2Љ ϭ 7.8 Hz, 1 H,
ene/acetone 17:1 v/v) of the residue afforded 19 (1.35 g, 79%) as a 1Љ-H), 4.86 (d, J ϭ Ϫ11.4 Hz, 1 H, PhCH2), 4.83 (d, J ϭ Ϫ10.7 Hz,
20
1
colorless foam. Ϫ [α]D ϭ ϩ38.4 (c ϭ 1.2, CHCl3). Ϫ H NMR
(CDCl3): δ ϭ 5.71 (dd, J2Ј,3Ј ϭ 3.5 Hz, 1 H, 2Ј-H), 5.64 (dd, J3Ј,4Ј
10.0 Hz, 1 H, 3Ј-H), 5.55 (s, 1 H, PhCH), 5.35 (d, J1Ј,2Ј ϭ 1.3 Hz,
1 H, PhCH2), 4.79 (d, J ϭ Ϫ12.5 Hz, 1 H, PhCH2), 4.70 (d, J ϭ
Ϫ12.6 Hz, 1 H, PhCH2), 4.62 (d, J ϭ Ϫ10.6 Hz, 1 H, PhCH2), 4.56
(d, J ϭ Ϫ10.9 Hz, 1 H, PhCH2), 4.54 (d, J ϭ Ϫ10.9 Hz, 1 H,
ϭ
1 H, 1Ј-H), 5.27 (t, J4Ј,5Ј ϭ 10.0 Hz, 1 H, 4Ј-H), 5.08 (br. s, 2 H, PhCH2), 4.52 (s, 1 H, PhCH2), 4.50 (dd, J6aЈЈЈ,6bЈЈЈ ϭ Ϫ11.4 Hz, 1
PhCH2OCO), 4.89 (d, J ϭ Ϫ10.7 Hz, 1 H, PhCH2), 4.73 (bd, 2 H, H, 6aЈЈЈ-H), 4.48 (d, J ϭ Ϫ12.4 Hz, 1 H, PhCH2), 4.44 (d, J1,2
PhCH2, NH), 4.49 (d, J1,2 ϭ 7.7 Hz, 1 H, 1-H), 4.42Ϫ4.32 (m, 7.7 Hz, 1 H, 1-H), 4.39 (d, J ϭ Ϫ12.3 Hz, 1 H, PhCH2), 4.37Ϫ4.32
J5Ј,6Ј ϭ 6.2 Hz, 2 H, 5Ј-H, 6a-H), 3.96 (t, J3,4 ϭ 9.2 Hz, 1 H, 3-H), (m, J6a,6b ϭ Ϫ10.5 Hz, 2 H, 6a-H, 1ЈЈЈ-H), 4.27Ϫ4.22 (m, J5Ј,6Ј
3.90Ϫ3.88 (m, 1 H, OCH2), 3.84Ϫ3.77 (m, 2 H, 6b-H), 3.83 (d, 6.2 Hz, 1 H, 5Ј-H), 4.05 (dd, 1 H, 6bЈЈЈ-H), 4.01 (t, J4Љ,5Љ ϭ 9.3 Hz,
J ϭ Ϫ14.5 Hz, 1 H, ClCH2CO), 3.78 (d, J ϭ Ϫ14.5 Hz, 1 H, 1 H, 4Љ-H), 3.91Ϫ3.87 (m, 1 H, OCH2), 3.87 (t, J3,4 ϭ 9.2 Hz, 1 H,
ClCH2CO), 3.64 (t, J4,5 ϭ 9.5 Hz, 1 H, 4-H), 3.60Ϫ3.50 (m, 2 H, 3-H), 3.82 (t, J4Ј,5Ј ϭ 9.8 Hz, 1 H, 4Ј-H), 3.78 (t, J5,6b ϭ 10.5 Hz,
ϭ
ϭ
Eur. J. Org. Chem. 2000, 181Ϫ186
185

G. Lemanski, T. Ziegler
FULL PAPER
[1]
[2]
[3]
´
L. Lesprit, M. Lafaurie, F. Liote, J.-M. Dcazes, J. Moda¨ı, Clin.
1 H, 6b-H), 3.74 (t, J4ЈЈЈ,5ЈЈЈ ϭ 9.4 Hz, 1 H, 4ЈЈЈ-H), 3.67 (bd,
J2ЈЈЈ,3ЈЈЈ ϭ 3.2 Hz, 1 H, 2ЈЈЈ-H), 3.62 (t, J4,5 ϭ 9.2 Hz, 1 H, 4-H),
3.61Ϫ3.57 (m, J5ЈЈЈ,6aЈЈЈ ϭ 7.5 Hz, J5ЈЈЈ,6bЈЈЈ ϭ 8.1 Hz, 1 H, 5ЈЈЈ-H),
3.55Ϫ3.49 (m, 3 H, 6aЉ-H, 6bЉ-H, OCH2), 3.47Ϫ3.35 (m, 4 H, 2-
H, 3ЈЈЈ-H, 5-H, 5Љ-H), 3.14Ϫ3.11 (m, 2 H, CONHCH2), 3.12 (d,
J ϭ Ϫ12.2 Hz, 1 H, COCH2), 3.07 (d, J ϭ Ϫ12.2 Hz, 1 H,
COCH2), 1.66Ϫ1.35 (m, 6 H, CH2), 0.90 (d, 1 H, 6Ј-H). Ϫ 13C
NMR (CDCl3): δ ϭ 165.6 (COCH2), 165.1, 165.0 (1 C, 2 C,
Infect. Dis. 1996, 23, 1180Ϫ1181.
G. Funke, R. A. Hutson, K. A. Bernard, G. E. Pfyffer, G. Waut-
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C. Forni, A. Haegi, M. del Gallo, M. G. Caiola, FEMS Micro-
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PhCO), 164.4 (COCH2), 156.3 (OCONH), 104.1 (C-1, JC-1ϪH-1
160.2 Hz), 103.5 (C-1ЈЈЈ, JC-1ЈЈЈ,H-1ЈЈЈ ϭ 154.1 Hz), 101.5 (PhCH),
100.5 (C-1Љ, JC-1Љ,H-1Љ 162.1 Hz), 98.3 (C-1Ј, JC-1Ј,H-1Ј
ϭ
J. H. Sloneker, D. G. Orentas, C. A. Knutson, P. R. Watson, A.
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ϭ
ϭ
174.8 Hz), 82.6 (C-2), 82.0 (C-3ЈЈЈ), 78.8 (C-4), 78.5 (C-4Љ), 77.0 (C-
3), 76.6 (2 C, C-4Ј, C-4ЈЈЈ), 75.6 (C-3Љ), 75.1 (PhCH2), 74.9
(PhCH2), 74.6 (C-2ЈЈЈ), 74.5 (C-5Љ), 73.6, 73.5 (PhCH2), 72.6 (C-
3Ј), 72.4 (C-2Љ), 72.0 (PhCH2), 70.5 (C-5ЈЈЈ), 70.4 (C-2Ј), 70.1
(OCH2), 68.6 (C-6), 68.4 (C-6Љ), 66.7 (C-5Ј), 66.5 (2 C, C-5,
PhCH2OCO), 64.1 (C-6ЈЈЈ), 42.8 (COCH2), 40.8 (CH2NH), 30.0,
29.3, 23.2 (CH2), 17.2 (C-6Ј). Ϫ C103H105NO27 (1789.0): calcd C
69.15, H 5.92, N 0.78; found C 69.09, H 6.07, N 0.69.
E. V. Vinogradov, A. S. Shashkov, Y. A. Knirel, N. A. GrigorЈ-
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5-Aminopentyl O-(β-
D-Mannopyranosyl)-(1Ǟ4)-(β-
D-glucopyrano-
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syl)-(1Ǟ4)-(α- -rhamnopyranosyl)-(1Ǟ3)-β-
L
D-glucopyranoside (22):
A solution of 21 (60 mg, 33 µmol) and a catalytic amount of
NaOMe in methanol (4 mL) was stirred at room temperature for
30 h, neutralized with ion exchange resin (Dowex 1X8, Hϩ form)
and concentrated. The residue was dissolved in methanol/acetic
acid (1:1 v/v, 10 mL), a catalytic amount of Pd(OH)2 on charcoal
was added, the suspension was hydrogenized (1013 hPa H2) at
room temperature for 6 d, filtered and concentrated. Chromatogra-
phy of the residue with water on Biogel P2 and lyophilisation of
the carbohydrate-containing fractions afforded 22 (21 mg, 87%) as
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
20
a colorless foam. Ϫ [α]D ϭ ϩ73.4 (c ϭ 1.1, H2O). Ϫ 13C NMR
(D2O): δ ϭ 104.2 (C-1ЈЈ), 102.5 (C-1), 102.1 (C-1Ј), 101.3 (C-1ЈЈЈ),
83.3 (C-3), 82.3 (C-4Ј), 79.2 (C-4ЈЈ), 77.2 (C-5), 75.1 (C-2), 75.0 (C-
5ЈЈ), 74.8 (C-3ЈЈ), 73.9 (C-2ЈЈ), 72.5 (C-3ЈЈЈ), 72.2 (C-5ЈЈЈ), 71.6,
71.4, 71.3 (C-2Ј,3Ј,2ЈЈЈ), 71.2 (OCH2), 70.7 (C-4ЈЈЈ), 69.7 (C-4), 69.1
(C-5Ј), 62.0 (C-6), 61.3, 61.1 (C-6ЈЈ,6ЈЈЈ), 39.8 (NCH2), 28.4, 26.6,
22.2 (CH2), 17.9 (C-6Ј). Ϫ C29H53NO20 (735.7): FAB MS (pos.);
m/z: 737 (M ϩ Hϩ).
[23]
[24]
[25]
[26]
[27]
[28]
Acknowledgments
[29]
[30]
We thank the Deutsche Forschungsgemeinschaft and the Fonds der
Chemischen Industrie for financial support. We also thank Dr. H.
Schmickler for measuring the NMR spectra and C. Schmitz for
determining the elemental analyses.
Received July 29, 1999
[O99469]
186
Eur. J. Org. Chem. 2000, 181Ϫ186