Synthesis of glycosylated-β(1-4)-amino(methoxy) and -oxyamino carbohydrate analogues

Article abstract of DOI:10.1016/S0040-4020(02)00079-0

The synthesis of new oligosaccharides containing nitrogen or oxygen-nitrogen in interglycosidic linkage is described. Several modified β-N- and β-O-N linked disaccharides with glucose or galactose as reducing unit such as lactose or cellobiose analogues have been prepared stereoselectively using two different methods. All these compounds were fully characterised by one and two dimensional NMR studies, mass spectroscopy and the crystallographic structure of Gal-β-N-(1,4)-Gal derivative 10 was obtained. These type of structural modifications of oligosaccharides could be useful for study of various biochemical processes.

Full text of DOI:10.1016/S0040-4020(02)00079-0

TETRAHEDRON
Pergamon
Tetrahedron 58 /2002) 2127±2135
Synthesis of glycosylated-bꢀ1-4)-aminoꢀmethoxy) and -oxyamino
carbohydrate analogues
Olivier Renaudet and Pascal Dumyp
Â
LEDSS, UMR-CNRS 5616, Universite Joseph Fourier, BP 53, 38041 Grenoble Cedex 9, France
Received 9 October 2001; revised 28 November 2001; accepted 10 January 2002
AbstractÐThe synthesis of new oligosaccharides containing nitrogen or oxygen±nitrogen in interglycosidic linkage is described. Several
modi®ed b-N- and b-O-N linked disaccharides with glucose or galactose as reducing unit such as lactose or cellobiose analogues have been
prepared stereoselectively using two different methods. All these compounds were fully characterised by one and two dimensional NMR
studies, mass spectroscopy and the crystallographic structure of Gal-b-N-/1,4)-Gal derivative 10 was obtained. These type of structural
modi®cations of oligosaccharides could be useful for study of various biochemical processes. q 2002 Elsevier Science Ltd. All rights
reserved.
1. Introduction
this domain have provided elegant synthetic solutions for
the construction of this crucial linkage. Consequently, these
observations emphasise the need of synthetic oligosacchari-
dic models incorporating unnatural interglycosidic linkage
for better understanding the structural and conformational
features involved in various biochemical processes and
protein or DNA recognition.
Carbohydrates have subjected to an increasing interest
during the last few years because of their role in various
biological activities starting from fertilisation to pathologi-
cal processes suchas tumour growth. 1 As a result, consider-
able efforts have been expanded in design, synthesis and
testing enzyme inhibitors or mimic of carbohydrate±protein
interactions. As the conformation of an oligosaccharide
depends largely on the glycosidic linkage, many structural
modi®cations affect the interglycosidic atom. Particularly
some analogues containing carbon2 or sulphur3 have been
synthesised as useful tool for study of enzymatic process
and have an attracted interest as hydrolytically stable analo-
gues of O-saccharides. Only few examples of so called
pseudo-sugar containing nitrogen4 are described in literature
which appear as very promising compounds yet. Generally,
some carbohydrate mimics containing exocyclic nitrogen
atom namely aza- or iminosugars5 are known to be proto-
nated in the enzyme active site and act as ef®cient glycosi-
dase inhibitors because of their ability to mimic the shape or
charge of the presumed transition state for enzymatic glyco-
side hydrolysis. Some other sugar analogue like acarbose6
carrying nitrogen atom between sugar and pseudosugar is
the highest known carbohydrate af®nity for a binding
protein and is currently used for the oral treatment of
diabete.7 Furthermore, unusual N±O interglycosidic linkage
is rarely found in oligosaccharidic moiety of antitumour
For this purpose, we report here the synthesis and structural
characterisation of new modi®ed oligosaccharides contain-
ing bothN/OMe)- or N±O- in the glycosidic bond. Glyco-
sylation is still a major problem in organic synthesis as no
universal method has been devised for construction of
glycosidic linkage. Among all the different coupling reac-
tions strategies,10 we report two different synthetic
approaches to obtain stereoselectively b-N/OMe)- and
b-O-N- linked disaccharides and present preliminary
evaluation of these compounds in glycosidases inhibition
tests.
2. Results and discussion
We have prepared 4-deoxy-4-methoxyaminoglycosyl
sugars 5 or 6 /Scheme 1) following the method described
by Tronchet et al.11 related to the synthesis of hydroxyami-
nopyranosides. Methyl-a-d-glucopyranoside 1 was regiose-
lectively stannylated12 and then treated with benzoyl
chloride to provide compound 2 withfree OH-4. Oxidation
of 2 withruthenium tetroxide 13 afforded pure and crystalline
product 314 which was then transformed in oxime 4 by reac-
8
I9
antibiotics esperamycin A1 and calicheamicin g1 and
has been suggested to play a critical conformational role
for minor groove DNA binding. Recent investigations in
tion with methoxyamine hydrochloride in ethanol/pyridine.
Final reduction withsodium cyanoborohydride
15
at pH 3
gave 36% of galacto-5 and 44% of gluco-6 epimers
/deˆ8%). In contrast, the use of triethylamine±borane
Keywords: carbohydrates; glycosidic linkage; oligosaccharides.
Corresponding author. Tel.: 133-4-76-63-5545; fax: 133-4-76-51-4382;
e-mail: pascal.dumy@ujf-grenoble.fr.
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020/02)00079-0

2128
O. Renaudet, P. Dumy / Tetrahedron 5832002) 2127±2135
new building-blocks to synthesise modi®ed disaccharides
containing b-N/OMe) linkage /Scheme 2) by Koenigs±
Knorr like coupling reaction.
Furthermore, we found that this coupling reaction involving
bromoglycosyl donors 7 or 8 and 4-deoxy-4-methoxy-
aminoglycosyl 5 or 6 as acceptors required a very careful
choice of catalyst /Table 1). Typically, glycosyl bromide
donors are activated by treatment withsilver or ehavy
metal salt. According to Lubineau et al. results,21 we have
found that disaccharides 9 and 10 were obtained the most
effectively using stannous tri¯ate as promotor in presence of
collidine at room temperature /18 and 29% of yield; 46 and
70% of conversion rate, respectively).
In sharp contrast with Sn/OTf)2 as catalyst, no reaction
involving the 4-deoxy-4-methoxyaminoglucosyl acceptor
6 occurred. For the latter compound, the combination of
silver tri¯ate±silver carbonate22 in nitromethane at room
temperature was useful to obtain disaccharides 13 and 14
after several attempts withother catalyst. Only b-anomers
were obtained as well as unreacted starting material.23 This
stereoselectivity for b glycosidic linkage results presumably
from the well known anchimeric assistance of acetate group
at C-2 within the glycosyl donors.
Scheme 1. Reagents and conditions: /a) /i) /Bu3Sn)2O, toluene, re¯ux; /ii)
BzCl, toluene, 508C, 85%; /b) RuO4, CH2Cl2, 80%; /c) MeONH2´HCl,
EtOH/pyridine, 98%; /d) NaBH3CN, MeOH/HCl 6 M.
complex16 as reducing agent was muchmore diastereoselec-
tive providing 90% of galacto- form 5 /deˆ80%).
The structure and stereochemistry of disaccharides 9, 10, 13
and 14 were assigned by one and two dimensional NMR
techniques /coupling constant between H-1 and H-2 of non-
reducing sugar of 9.2 and 9.4 Hz for 9 and 10, 8.4 and
8.9 Hz for 13 and 14 respectively are typical for the trans
diaxial arrangement and corroborate the b stereochemistry),
mass spectroscopy /ESI). Single crystal X-ray structure
determination provided further con®rmation of the structure
of compound 10 /Fig. 2).17
The separation of those two diastereoisomers 5 and 6 was
readily achieved by recrystallisation from CH2Cl2/petro-
leum ether and diethyl ether/petroleum ether respectively.
The stereochemistry of compound 5 /Fig. 1)17 and 618 was
unambiguously con®rmed by X-ray studies. For compound
4
6, the ring adopts a quasi-perfect C1 chair conformation,
as de®ned by the Cremer and Pople19 parameters
Ê
Qˆ0.593/3) A, Qˆ2.6/2)8 and q2ˆ195/4)8. This confor-
mation is also adopted in solution, as outlined by the large
values of the NMR coupling constants /,10 Hz). The
exocyclic hydroxymethyl group adopts a staggered gg
conformation [vˆO5±C5±C6±O6ˆ270.1/2)8 and C4±
C5±C6±O6ˆ252.5/2)8], which is the conformation
usually observed in other structures containing gluco
residues.20
24
Final Zemplen de-o-acylation gave pure compounds
Â
containing amino/methoxy) interglycosidic linkage 11, 12,
15 and 16 withquantitative yields.
To date, no route to amino-glycosylated carbohydrate have
been described. Having in hands the b-N/OMe) disacchar-
ides, we were interested to reduce the N±OMe bond to
obtain the corresponding aminoglycosidic linkage and
thus assess their stability. According to literature, reductive
cleavage of N±O bond can be accomplished under a variety
of conditions,25 including hydrogenolysis /H2/Pd, 1 atm, H2,
Many procedures have been reported for the construction of
glycosidic linkage but none of them involves 4-deoxy-4-
methoxyaminoglycosyl derivatives as glycosidic acceptor.
Here, we demonstrated that these nucleophiles represent
Raney nickel, 1 atm), reduction withZn/AcOH, withTiCl ,
3
withSmI or withMo/CO) .
2
6
Unfortunately, all tried methods failed in our hands /Table
2) and no evidence for the corresponding reduced
compounds was obtained.
In most cases, the starting material were recovered. In
comparison, reduction of N±OMe bond of compounds 5
or 6 was achieved easily with quantitative yields. A possible
explanation of this failure could be hence attributed to steric
hindrance exhibited in disaccharide which prevents it to
react under the numerous conditions investigated in this
study.
Unusual N±O linkage is found in some few compounds
Figure 1. ORTEP drawing of compound 5.

O. Renaudet, P. Dumy / Tetrahedron 5832002) 2127±2135
2129
Ê
Scheme 2. Reagents and conditions: /a) 5, Sn/OTf)2, collidine, CH2Cl2, 4 A MS, 18% /46% of conversion rate) for 9, 29% /70% of conversion rate) for 10;
0
Ê
/a ) 6, AgOTf, Ag2CO3, nitromethane, 4 A MS, 10% for 13 and 14; /b) NaOMe/MeOH, quant. yield.
suchas calicheamicin gI 9 which is an extremely potent
antitumour antibiotic that cleaves DNA sequence speci®-
cally. Only a few general methods of preparation of this
type of linkage are described in literature.26 For this
purpose, we have adapted an ef®cient approach for stereo-
selective incorporation of this interglycosidic linkage in
oligosaccharide following oxime bond formation as
described by Nicolaou et al.27 in 1990.
The key step of the synthesis involved the selective conden-
sation between carbonyl compound 3 and compounds 17 or
18 /Scheme 3). This reaction occurred at room temperature
during 24 hin ethanol/pyridine to afford mixture of oxime
bond disaccharides 19 and 20 in 52 and 35% of yield; 48%
and 88% conversion rate, respectively as determined by
NMR /ratio E/Z about 1/2 for 19 and 1/10 for 20). Indeed,
3
the coupling constant between H-30 and H-20 / J2 ,3 ) is more
important for isomer Z /8.7 and 8.4 Hz for 19 and 20) than
for isomer E /4.8 and 5.2 Hz for 19 and 20) due to the
presence allylic A1,3 strain involving H-30 or H-50 within
the pyranose cycle.29 Moreover, these coupling constant
values measured are in very good agreement withprevious
E/Z attribution.11 Subsequent reduction using borane±
triethylamine complex16 in dry diethyl ether saturated with
HCl provided the diastereoisomer mixture of glucose and
0
0
This method required the preparation of aminooxy glycosyl
intermediate 17 and 18 that we have obtained by stereo-
selective phase transfer catalysed glycosylation between
glycosylbromide and N-hydroxysuccinimide as described
by Roy et al.28 in 1995. Acetate deprotection and cleavage
of the succinimide group were ®nally performed with hydra-
zine to give unprotected aminooxy derivatives 17 and 18.
Table 1. Yields and conditions for coupling reaction between aminooxy glycosyl acceptors and glycosyl donors
Glycosyl acceptor
Glycosyl donor
Promotor
Disaccharide
Yield /after puri®cation) /%)
5
5
5
5
5
5
6
6
6
6
7
7
7
8
8
8
7
7
8
8
Sn/OTf)2, collidine
AgOTf, collidine
BF3/Et2O, triethylamine
Sn/OTf)2, collidine
AgOTf/Ag2CO3
AgOTf, collidine
AgOTf/Ag2CO3
Sn/OTf)2, collidine
AgOTf, collidine
AgOTf/Ag2CO3
9
18
21
±
29
17
±
10
±
±
10
9
No reaction
10
10
No reaction
13
No reaction
No reaction
14

2130
O. Renaudet, P. Dumy / Tetrahedron 5832002) 2127±2135
galactose derivatives 23 and 24 in very good yield /91±97%)
while no reaction were performed using classical sodium
cyanoborohydride method.15 This reduction reaction
favoured the galacto stereochemistry at C-40 /de<33%).
Indeed according to NMR data, the major H-30 signal
3
provided coupling constant values, J3 Gal,4 Gal, of 4.3 Hz
0
0
3
0
0
for 23 as well as J3 Gal,4 Galˆ4.7 Hz for 24 while the
minor
0
signal
exhibited
much
0
larger
values
/3J3 Glc,4 Glcˆ10.0 Hz for 23; J3 Glc,4 Glcˆ10.0 Hz for 24).
3
0
0
4
These values are typically encountered in C1 pyranoside
system withaxial±equatorial or axial±axial between H-4
and H-3 proton arrangements thus inferring that here the
galacto-form was obtained as the major isomer.
Â
Further Zemplen de-o-acylation of oxime-linked disacchar-
ides 19 and 20 as well as diastereoisomer mixtures 23 and
24 leads to pure and stable compounds 21, 22, 25 and 26
withquantitative yields.
Finally, the six unprotected compounds 11, 12, 21, 22, 25
and 26 have been tested for their inhibitory activities toward
the following enzymes under pH and standard conditions:30
a-l-fucosidase from bovine epididymis, a-galactosidase
from coffee beans, from Aspergillus niger and from
Escherichia coli, b-galactosidase from E. coli, from bovine
liver, from A. niger, from Aspergilus orizae and from jack
beans, a-glucosidase /maltase) from yeast and from rice,
a-glucosidase /isomaltase) from baker yeasts, amylogluco-
sidase from A. niger and from Rhizopus mold, b-glucosi-
dase from almonds and from Caldocellum saccharolyticum,
a-mannosidase from jack beans and from almonds,
b-mannosidase from Helix pomentia, b-xylosidase from
A. niger, a-N-acetylgalactosaminidase from chiken liver
and b-N-acetylglucosaminidase from jack bean, from
bovine epididymis A and from bovine epididymis B. At
1 mM concentration /solution buffered just before use) of
11, 12 and 25, b-galactosidase from bovine liver was selec-
tively inhibited by 42, 52 and 29%, respectively. 21
inhibited a-l-fucosidase from bovine epididymis by 25%.
22 and 26 were not found to have any inhibiton activity.
Figure 2. ORTEP drawing of compound 10
Table 2. Reaction condition for N±O reductive cleavage
Compound
Method
Result
9
9
9
9
H2 1 atm, Pd/C or PdH2O2, MeOH
H2 1 atm, PtO2, MeOH
Zn/AcOH or AcOH/H2O, 608C
SmI2, THF
No reaction
No reaction
No reaction
No reaction
No reaction
No reaction
Degradation
No reaction
No reaction
No reaction
No reaction
No reaction
No reaction
No reaction
No reaction
No reaction
9
9
9
Mo/CO)6, CH3CN, H2O
Al/Ni, KOH, MeOH
TiCl3, HCl
11
11
11
10
10
13
13
14
14
H2 1 atm, Pd/C, MeOH
Zn/AcOH
Al/Ni, KOH, MeOH
H2 1 atm, Pd/C, MeOH
Zn/AcOH
H2 1 atm, Pd/C, MeOH
Zn/AcOH
H2 1 atm, Pd/C, MeOH
Zn/AcOH
Scheme 3. Reagents and conditions: /a) EtOH/pyridine, 52% /48% of conversion rate) for 19, 35% /88% of conversion rate) for 20; /b) BH3/triethylamine,
Et2O/HCl, 97±91%; /c) NaOMe/MeOH, quant. yield.

O. Renaudet, P. Dumy / Tetrahedron 5832002) 2127±2135
2131
3. Conclusion
mixture was concentrated and taken up in ethyl acetate.
The organic layer was washed with aqueous NaHCO3 solu-
tion, dried over sodium sulfate and evaporated. Separation
of each epimers was accomplished by column chromato-
graphy /CH2Cl2/ethyl acetate, 20/1) then recrystallisation
to give 5 /0.42 g, 36% yield) from CH2Cl2/petroleum
ether and 6 /0.51 g, 44% yield) from diethyl ether/petroleum
ether. 5: mp: 1338C; 1H NMR /300 MHz, CDCl3): dˆ8.09±
7.34 /m, 15H, Har.), 6.05 /d, 1H, 3J4,NHˆ4.6 Hz, NH), 5.80
We have described here the stereoselective preparation of
new type of interglycosidic linkage. For this purpose, we
have prepared several original modi®ed disaccharides 11,
12, 15, 16, 21, 22, 25 and 26 containing either b-1!4-N- or
b-1!4-O-N linkage using methoxyaminoglycosyl deriva-
tives 5 and 6 as glycosidic acceptor in Koenigs±Knorr
like coupling reaction on the one hand. The stereochemistry
of the b-1!4-N- interglycosidic linkage was con®rmed by
one and two dimensional NMR studies as well as by the
X-ray analysis of compound 10. On the other hand, we have
developed a method of condensation between aminoxy-
glycosyl derivatives 17 or 18 and ketone-glycosyl 3
followed by reduction of oxime-linked disaccharides.
Preliminary glycosidases inhibition assays were also
initiated to evaluate enzymatic activity of suchcompounds.
Further biological screening with these compounds are
currently under investigated.
3
3
/dd, 1H, J3,4ˆ4.6 Hz, J2,3ˆ11.0 Hz, H-3), 5.50 /dd, 1H,
3J1,2ˆ3.8 Hz, H-2), 5.19 /d, 1H, H-1), 4.67±4.61 /m, 2H,
H-6a, H-6b), 4.45 /m, 1H, H-5), 3.83 /td, 1H, 3J4,5ˆ1.5 Hz,
H-4), 3.52 /s, 3H, HNOCH3), 3.42 /s, 3H, OCH3); 13C NMR
/75 MHz, CDCl3): dˆ166.4 /CvO), 166.1 /CvO), 165.8
/CvO), 133.5 /Car.), 133.4 /Car.), 133.2 /Car.), 130.0
/Car.), 129.9 /Car.), 129.8 /Car.), 128.6 /Car.), 128.5
/Car.), 97.5 /C-1), 69.6 /C-3), 69.4 /C-2), 67.9 /C-5), 65.1
/C-6), 62.0 /HNOCH3), 60.2 /C-4), 55.7 /OCH3); MS /ESI):
1
m/zˆ536.1 /M1H)1. 6: mp: 1238C; H NMR /300 MHz,
CDCl3): dˆ8.12±7.34 /m, 15H, Har.), 6.17 /t, 1H,
3
3J2,3ˆ3J3,4ˆ10.0 Hz, H-3), 5.91 /d, 1H, J4,NHˆ2.1 Hz,
3
NH), 5.20 /dd, 1H, J1,2ˆ3.6 Hz, H-2), 5.16 /d, 1H, H-1),
4. Experimental
4.1. Generality
4.76±4.72 /m, 2H, H-6a, H-6b), 4.42 /td, 1H, 3J5,6ˆ3.6 Hz,
3J4,5ˆ10.3 Hz, H-5), 3.51 /s, 3H, OCH3), 3.44 /s, 3H,
HNOCH3) 3.19 /bt, 1H, H-4); 13C NMR /75 MHz,
CDCl3): dˆ166.7 /CvO), 166.2 /CvO), 166.0 /CvO),
133.4 /Car.), 133.3 /Car.), 130.1 /Car.), 129.9 /Car.),
129.7 /Car.), 129.3 /Car.), 128.6 /Car.), 128.5 /Car.), 97.2
/C-1), 73.3 /C-2), 67.8 /C-3), 67.3 /C-5), 64.3 /C-6), 62.9
/HNOCH3), 61.4 /C-4), 55.6 /OCH3); MS /ESI): m/zˆ536.1
/M1H)1.
All chemical reagents were purchased from Sigma Alrdich,
Flucka or Acros and were used without further puri®cation.
Analytical TLC were performed on 0.2 mm silica 60 coated
aluminium foils withF-254 indicator /Merck). Prep. column
chromatographies were done using silica gel /Merck 60,
200±63 mm). Melting points were measured on an Electro-
thermal Serie IA9100 apparatus. NMR spectra were
recorded on Bruker Avance spectrometers. Spectra were
referenced to the residual proton solvent peaks. The exact
mass spectra were recorded on a Finnigan MAT95XL
spectrometer /LSIMS) using a glycerol matrix in positive
mode. ES-MS analyses were performed on a VG Platform II
/Micromass) in the positive ion mode.
4.1.3. Methyl 2,3,6-tri-O-benzoyl-4-deoxy-4-methoxy-
amino-4-N-ꢀ2,3,4,6-tetra-O-acetyl-b-d-glucopyranosyl)-
a-d-galactopyranoside ꢀ9). Under inert gas, a solution of 5
/0.73 g, 1.4 mmol) and collidine /0.36 mL, 2.8 mmol) in
anhydrous CH2Cl2 /5 mL) was added to a stirring solution
of 7 /1.12 g, 2.8 mmol), stannous tri¯ate /0.85 g, 2.1 mmol)
Ê
and 4 A molecular sieves in anhydrous CH2Cl2 /5 mL).
After one night at room temperature, the solution was
®ltrated, concentrated in vacuo and taken up in ethyl
acetate. The organic layer was washed with aqueous
NaHCO3 solution and water, dried over sodium sulfate
and evaporated. Column chromatography /CH2Cl2/ethyl
acetate, 15/1) of the resulting oil gave starting material 5
/0.36 g) and coupling product 9 /0.28 g, 18% yield, 46%
conversion rate) after precipitation from CH2Cl2/pentane.
4.1.1. Methyl 2,3,6-tri-O-benzoyl-4-deoxy-4-methoxy-
imino-a-d-xylo-hexopyranoside ꢀ4). To a stirring solution
of 3 /2.01 g, 4.0 mmol) in ethanol /40 mL) and pyridine
/5 mL) was added methoxylamine hydrochloride salt
/1.33 g, 16 mmol). After 4 hat 20 8C, the solvent was
removed in vacuo and the residue diluted with ethyl acetate,
then wasched with 5% solution of NaHCO3 and ®nally with
water. The organic layer was dried with sodium sulfate and
evaporated to afford pure product 4 /1/4 Z/E mixture) as a
1
Mp: 112±1148C; H NMR /300 MHz, CDCl3): dˆ8.11±
3
7.39 /m, 15H, H0ar.), 5.80 /dd, 1H, J3 ,4 ˆ4.6 Hz,
1
0
0
colourless oil /98% yield). H NMR /200 MHz, CDCl3):
3
3
0
0
3
0
0
0
0
J2 ,3 ˆ10.9 Hz, H-3 ), 5.08 /dd, 1H, J1 ,2 ˆ3.9 Hz, H-2 ),
dˆ8.16±7.30 /m, Har.Z,E), 6.53 /d, J2Z,3Zˆ7.5 Hz, H-3Z),
5.37 /t, 1H, J1,2ˆ3J2,3ˆ9.2 Hz, H-2), 5.24 /d, 1H, H-10),
5.22±5.18 /m, 2H, H-3, H-4), 4.76 /d, 1H, H-1), 4.67±
4.48 /m, 4H, H-50, H-6a0, H-6b0, H-6a), 4.33 /dd, 1H,
3
6.12 /d, 3J2E,3Eˆ4.8 Hz, H-3E), 5.56 /dd, 3J1Z,2Zˆ3.1 Hz, H-
3
2Z), 5.49 /dd, J1E,2Eˆ3.6 Hz, H-2E), 5.27±5.23 /m, H-1E,
H-5Z,E), 5.19 /d, H-1Z), 4.95±4.61 /m, H-6Z,E), 3.92
/s, CvNOCH3E), 3.73 /s, CvNOCH3Z), 3.46 /s, OCH3Z),
3.44 /s, OCH3E).
3
3
J4 ,5 ˆ2.5 Hz, H-40), 4.08 /dd, 1H, J5,6bˆ2.1 Hz,
0
0
2J6a,6bˆ12.5 Hz, H-6b), 3.80 /bs, 1H, H-5), 3.42 /s, 3H,
OCH3), 3.34 /s, 3H, NOCH3), 2.17, 2.01, 2.00, 1.96 /4 s,
12H, 4OCOCH3); 13C NMR /75 MHz, CDCl3): dˆ171.1
/CvO), 170.7 /CvO), 170.3 /CvO), 169.8 /CvO),
167.1 /CvO), 166.7 /CvO), 166.6 /CvO), 133.4 /Car0.),
133.2 /Car0.), 133.1 /Car0.), 129.9 /Car0.), 129.8 /Car0.),
129.7 /Car0.), 129.5 /Car0.), 129.3 /Car0.), 128.6 /Car0.),
128.5 /Car0.), 128.3 /Car0.), 124.6 /Car0.), 97.2 /C-10),
90.1 /C-1), 74.6 /C-3), 73.6 /C-4), 69.4 /C-30), 69.3 /C-20),
4.1.2. Methyl 2,3,6-tri-O-benzoyl-4-deoxy-4-methoxy-
amino-a-d-galactopyranoside ꢀ5) and methyl 2,3,6-tri-
O-benzoyl-4-deoxy-4-methoxyamino-a-d-glucopyrano-
side ꢀ6). To a stirring solution of 4 /1.16 g, 2.2 mmol) in
methanol /20 mL) was added sodium cyanoborohydride
/2.74 g, 44 mmol) followed by a mixture of 6 M HCl/metha-
nol dropwise to keep the reaction at pH 3. After 3 h the

2132
O. Renaudet, P. Dumy / Tetrahedron 5832002) 2127±2135
68.9 /C-2), 67.8 /C-5, C-50), 65.3 /C-60), 62.2 /C-6), 61.3
/NOCH3), 58.5 /C-40), 55.4 /OCH3), 20.9 /OCOCH3), 20.8
/OCOCH3), 20.7 /OCOCH3), 20.6 /OCOCH3); MS /ESI):
m/zˆ866.4 /M1H)1, 888.4 /M1Na)1; MS /FAB /1),
NBA1NaCl): m/zˆ806 /M2OAc)1, 866 /M1H)1, 888
/M1Na)1.
129.5 /Car0.), 129.4 /Car0.), 129.0 /Car0.), 128.5 /Car0.),
128.4 /Car0.), 96.7 /C-10), 86.6 /C-1), 74.5, 73.4, 73.3
/C-2, C-3, C-5), 68.6 /C-50), 68.2 /C-4), 67.9 /C-20), 66.9
/C-30), 65.5 /C-60), 62.5 /C-6), 61.6 /C-40), 60.7 /NOCH3),
55.6 /OCH3), 20.6 /OCOCH3), 20.5 /OCOCH3), 19.7
/OCOCH3); MS /ESI): m/zˆ866.1 /M1H)1, 867.1
/M12H)1, 883.1 /M1H2O)1.
4.1.4. Methyl 2,3,6-tri-O-benzoyl-4-deoxy-4-methoxy
amino-4-N-ꢀ2,3,4,6-tetra-O-acetyl-b-d-galactopyranosyl)-
a-d-galactopyranoside ꢀ10). Compound 10 was prepared
following the procedure described for 9. 29% yield /70%
conversion rate); mp: 96±988C; 1H NMR /300 MHz,
CDCl3): dˆ8.06±7.34 /m, 15H, H0ar.), 5.78 /dd, 1H,
4.1.6. Methyl 2,3,6-tri-O-benzoyl-4-deoxy-4-methoxy-
amino-4-N-ꢀ2,3,4,6-tetra-O-acetyl-b-d-galactopyranosyl)-
a-d-glucopyranoside ꢀ14). Compound 14 was prepared
following the procedure described for 13. 10% yield; mp:
1
106±1088C; H NMR /300 MHz, CDCl3): dˆ8.26±7.32
3
3
3
3
J3 ,4 ˆ3.5 Hz, J2 ,3 ˆ10.9 Hz, H-30), 5.73 /dd, 1H,
/m, 15H, Har.), 0 5.86 /dd, 1H,
J2 ,3 ˆ9.5 Hz,
0
0
0
0
0
00
3
3
3
0
0
0
0
J1 ,2 ˆ3.2 Hz, H-2 ), 5.48 /t, 1H, J1,2ˆ9.4 Hz, H-2), 5.39
J3 ,4 ˆ11.0 Hz, H-3 ), 5.37 /t, 1H, J1,2ˆ8.9 Hz, H-2),
3
3
/bd, 1H, J3,4ˆ3.5 Hz, H-4), 5.23 /d, 1H, H-10), 5.04 /dd,
5.33 /bd, 1H, J3,4ˆ3.6 Hz, H-4), 5.16 /dd, 1H,
3
3
1H, J2,3ˆ10.1 Hz, H-3), 5.06±4.54 /m, 4H, H-1, H-50,
J1 ,2 ˆ3.8 Hz, H-2 ), 5.09 /d, 1H, H-1 ), 4.96 /dd, 1H, H-
0
0
0
0
3
2
H-60), 4.32 /bt, 1H, H-40), 4.26±4.15 /m, 2H, H-6), 3.96
3), 4.81 /dd, 1H, J5 ,6a ˆ1.8 Hz, J6a ,6b ˆ11.8 Hz, H-6a ),
0
0
0
0
0
3
3
0
0
0
/bt, 1H, J5,6ˆ6.4 Hz, H-5), 3.45 /s, 3H, NOCH3), 3.43 /s,
4.66 /dd, 1H, J5 ,6b ˆ5.1 Hz, H-6b ), 4.52 /d, 1H, H-1),
3H, OCH3), 2.18, 2.17, 1.99, 1.94 /4 s, 12H, 4OCOCH3);
13C NMR /75 MHz, CDCl3): dˆ170.8 /CvO), 170.7
/CvO), 170.5 /CvO), 170.2 /CvO), 166.7 /CvO),
166.6 /CvO), 166.5 /CvO), 133.7 /Car0.), 133.6 /Car0.),
130.6 /Car0.), 130.3 /Car0.), 129.9 /Car0.), 129.7 /Car0.),
128.9 /Car0.), 128.8 /Car0.), 128.7 /Car0.), 97.7 /C-10),
91.4 /C-1), 72.9 /C-3), 72.7 /C-5), 70.1 /C-30), 69.6 /C-20),
68.6 /C-50), 67.5 /C-4), 66.9 /C-2), 66.0 /C-60), 62.0
/NOCH3), 61.4 /C-6), 59.4 /C-40), 55.7 /OCH3), 21.3
/OCOCH3), 21.2 /OCOCH3), 20.9 /OCOCH3); MS /ESI):
m/zˆ806.3 /M2OAc)1, 865.9 /M)1, 866.2 /M1H)1, 867.5
/M12H)1, 887.8 /M1Na)1, 889.4 /M1H1Na)1.
4.41±4.34 /m, 1H, H-50), 4.12±3.98 /m, 2H, H-6), 3.91
3
/t, 1H, J5,6ˆ6.1 Hz, H-5), 3.79 /t, 1H, H-40), 3.38 /s, 3H,
OCH3), 3.29 /s, 3H, NOCH3), 2.10, 1.93, 1.85, 1.22 /4 s,
12H, 4OCOCH3); NMR /75 MHz, CDCl3): dˆ170.5
/CvO), 170.2 /CvO), 169.9 /CvO), 169.6 /CvO),
166.2 /CvO), 165.8 /CvO), 165.3 /CvO), 133.4 /Car0.),
133.3 /Car0.), 132.9 /Car0.), 130.3 /Car0.), 129.9 /Car0.),
129.6 /Car0.), 129.5 /Car0.), 129.4 /Car0.), 129.1 /Car0.),
128.4 /Car0.), 128.3 /Car0.), 96.7 /C-10), 86.9 /C-1), 73.3
/C-20), 72.6 /C-3), 72.4 /C-5), 68.6 /C-50), 67.3 /C-4),
66.9 /C-30), 65.5 /C-60), 65.2 /C-2), 62.1 /C-6), 61.7 /C-40),
60.6 /NOCH3), 55.6 /OCH3), 20.8 /OCOCH3), 20.6
/OCOCH3), 20.5 /OCOCH3), 19.8 /OCOCH3); MS /ESI):
m/zˆ866.1 /M1H)1, 867.1 /M12H)1, 867.9 /M13H)1.
4.1.5. Methyl 2,3,6-tri-O-benzoyl-4-deoxy-4-methoxy-
amino-4-N-ꢀ2,3,4,6-tetra-O-acetyl-b-d-glucopyranosyl)-
a-d-glucopyranoside ꢀ13). In the dark at room temperature,
a suspension of silver carbonate /0.18 g, 0.66 mmol), silver
4.1.7. Methyl 2,3,6-tri-O-benzoyl-4-deoxy-ꢀO-b-d-gluco-
pyranosylhydroxyimino)-a-d-xylo-hexopyranoside ꢀ19).
To a stirring solution of 3 /0.24 g, 0.5 mmol) in ethanol
/10 mL) and pyridine /1 mL) was added compound 17
/0.09 g, 0.5 mmol). The solution was ajusted to pH 3
with few drops of hydrochloric acid. After 12 h at 208C,
the solvent was removed in vacuo and the residue diluted
withetyhl acetate, tehn wacehd with5% solution of
Ê
tri¯ate /0.02 g, 0.07 mmol) and 4 A molecular sieve in
nitromethane /5 mL) was stirred for 1 h. Bromide
compound 7 /0.41 g, 0.99 mmol) was then added to the
catalyst suspension at room temperature. After 15 min,
solid compound 6 /0.19 g, 0.37 mmol) was added and stir-
red at room temperature for 3 h. The reaction mixture was
then ®ltered through celite, the ®ltrate evaporated in vacuo,
taken up in ethyl acetate and washed with water and dried
over sodium sulfate. The yellow oil residue remaining after
evaporation was chromatographed on silica gel with
CH2Cl2/ethyl acetate /10/1) to give 13 as a white powder
/0.02 g, 10% yield) after precipitation from ether/pentane.
NaHCO3 and ®nally withwater. The organic layer was
dried withanyhdrous sodium sulfate and evaporated.
Column chromatography /ethyl acetate) afford product
19 /Z/E, 1/2 mixture) after precipitation from CH2Cl2/
pentane /52% yield, 48% conversion rate). 1H NMR
/300 MHz, CDCl3): dˆ8.19±7.21 /m, Har.Z,E), 6.61 /d,
1
3
3
J2 Z,3 Zˆ8.7 Hz, H-30Z), 6.11 /d, J2 E,3 Eˆ4.8 Hz, H-30E),
0
0
0
0
Mp: 104±1068C; H NMR /300 MHz, CDCl3): dˆ8.09±
3
3
3
7.33 /m, 15H, Har.), 5.87 /dd, 1H, J2 ,3 ˆ9.6 Hz,
5.56 /dd, J1 Z,2 Zˆ3.0 Hz, H-20Z), 5.52 /t, J1 E,2 Eˆ4.4 Hz,
0
0
0
0
0
0
3
3
0
0
J3 ,4 ˆ10.9 Hz, H-3 ), 5.30 /t, 1H, H-2 ), 5.29±5.21
H-20E), 5.21 /d, H-10Z), 5.16 /dd, J5 E,6a Eˆ2.3 Hz,
0
0
0
0
3
3
0
/m, 2H, H-2, H-3), 5.17 /d, 1H, J1 ,2 ˆ3.8 Hz, H-1 ),
J5 E,6b Eˆ5.6 Hz, H-50E), 5.27 /d, H-10E), 5.03 /d,
0
0
0
0
5.01 /t, 1H, J3,4ˆ3J4,5ˆ10.0 Hz, H-4), 4.86 /dd, 1H,
3J1E,2Eˆ7.5 Hz, H-1E), 4.97±4.85 /m, H-60E, H-50Z, H-6a0Z),
3
3
2
3
3
0
0
0
0
0
0
0
J5 ,6a ˆ1.8 Hz, J6a ,6b ˆ12.1 Hz, H-6a ), 4.68 /dd, 1H,
4.78 /d, J1Z,2Zˆ8.3 Hz, H-1Z), 4.69 /dd, J5 Z,6b Zˆ2.6 Hz,
3
3
2
3
0
0
0
J5 ,6b ˆ5.4 Hz, H-6b ), 4.65 /d, 1H, J1,2ˆ8.4 Hz, H-1),
J6a Z,6b Zˆ11.3 Hz, H-6b0Z), 3.92 /dd, J5E,6aEˆ3.4 Hz,
0
0
3
4.49±4.42 /m, 1H, H-50), 4.20 /dd, 1H, J5,6aˆ2.3 Hz,
2J6aE,6bEˆ12.0 Hz, H-6aE), 3.80 /dd, 3J5E,6bEˆ3.4 Hz, H-6bE),
2J6a,6bˆ12.6 Hz, H-6a), 4.09 /dd, 1H, J5,6bˆ5.4 Hz, H-6b),
3.72 /dd, J5Z,6aZˆ3.0 Hz, J6aZ,6bZˆ12.0 Hz, H-6aZ), 3.66±
3.61 /m, H-2E, H-4E, H-4Z), 3.54±3.41 /m, H-3E,Z, H-5E,Z, H-
6bZ), 3.50 /s, OCH3Z), 3.44 /s, OCH3E), 2.93 /t, 3J2Z,3Zˆ8.3 Hz,
H-2Z); 13C NMR /75 MHz, CDCl3): dˆ168.1 /CvO), 167.3
/CvO), 166.7 /CvO), 166.5 /CvO), 166.2 /CvO), 165.9
3
3
2
3.84 /t, 1H, H-40), 3.80±3.73 /m, 1H, H-5), 3.38 /s, 3H,
OCH3), 3.29 /s, 3H, NOCH3), 2.10, 1.93, 1.85, 1.22 /4 s,
12H, 4OCOCH3); NMR /75 MHz, CDCl3): dˆ170.4
/CvO), 170.2 /CvO), 169.6 /CvO), 169.4 /CvO),
166.1 /CvO), 165.8 /CvO), 165.3 /CvO), 133.3 /Car0.),
132.9 /Car0.), 130.2 /Car0.), 129.9 /Car0.), 129.6 /Car0.),
/CvO), 165.4 /CvO), 154.0 /C-40Z), 153.8 /C-40 ), 133.9
/Car0.), 133.8 /Car0.), 132.7 /Car0.), 131.3 /Car0.), 130.4
E

O. Renaudet, P. Dumy / Tetrahedron 5832002) 2127±2135
2133
/Car0.), 130.3 /Car0.), 130.2 /Car0.), 130.0 /Car0.), 129.7
/Car0.), 129.4 /Car0.), 129.3 /Car0.), 129.2 /Car0.), 129.0
/Car0.), 128.9 /Car0.), 128.8 /Car0.), 128.7 /Car0.), 104.8
/C-1E), 103.4 /C-1Z), 96.9 /C-10Z), 96.0 /C-10E), 75.6, 75.5
/C-3E, C-5E), 72.2 /C-2Z), 72.1 /C-2E), 71.9 /C-20E), 69.9 /C-
4E), 69.0 /C-30E), 68.0 /C-50 ), 65.8 /C-30 ), 64.1 /C-60 ),
62.1 /C-6E), 56.7 /OCH3E), 56.4 /OCH3Z); MS /ESI): m/
zˆ682.6 /M1H)1, 704.5 /M1Na)1.
pyranoside ꢀ24). Compound 24 was prepared following
the procedure described for 23. 91% yield, Glc 1/4, Gal 3/
4); 1H NMR /300 MHz, CDCl3): dˆ8.09±7.28 /m,
3
3
0
0
0
0
Har.Gal,Glc), 6.33 /t, J2 Glc,3 Glcˆ J3 Glc,4 Glcˆ10.0 Hz, H-
3
3
0
0
0
0
0
3 Glc), 5.77 /dd, J3 Gal,4 Galˆ4.7 Hz, J2 Gal,3 Galˆ11.0 Hz,
3
0
0
0
0
H-3 Gal), 5.49 /dd, J1 Gal,2 Galˆ3.6 Hz, H-2 Gal), 5.18 /dd,
E
Z
E
3
J1 Glc,2 Glcˆ3.6 Hz, H-2 Glc), 5.15 /d, H-10Gal), 5.12 /d, H-
0
0
0
10Glc), 4.84±4.61 /m, H-60
,
H-50Glc), 4.58 /d,
Gal,Glc
3J1Gal,2Galˆ7.9 Hz, H-1Gal), 4.50 /d, J1Glc,2Glcˆ7.9 Hz,
3
3
0
0
0
4.1.8. Methyl 2,3,6-tri-O-benzoyl-4-deoxy-ꢀO-b-d-galacto-
pyranosylhydroxyimino)-a-d-xylo-hexopyranoside ꢀ20).
Compound 20 was prepared following the procedure
described for 19. 35% yield, 88% conversion rate /Z/E,
H-1Glc), 4.43 /m, J5 Gal,6 Galˆ6.4 Hz, H-5 Gal), 4.03 /bd, H-
40Gal), 3.90 /bs, H-3Gal), 3.80 /bd, 3J3Gal,4Galˆ6.1 Hz, H-4Gal),
3.75±3.36 /m, H-2Gal,Glc, H-5Gal, H-6Gal, H-3Glc), 3.42 /s,
OCH3Gal), 3.41 /s, OCH3Glc), 3.27 /t, H-40Glc); 13C NMR
/75 MHz, CDCl3): d 167.3 /CvO), 166.9 /CvO), 166.4
/CvO), 166.4 /CvO), 133.9 /Car0.), 133.7 /Car0.), 133.6
/Car0.), 130.6 /Car0.), 130.3 /Car0.), 130.2 /Car0.), 130.1
/Car0.), 130.0 /Car0.), 129.6 /Car0.), 129.5 /Car0.), 129.4
/Car0.), 128.8 /Car0.), 0 128.7 /Car0.), 128.2 /Car0.), 105.7
/C-10Gal), 105.4 /C-1 Glc), 97.5 /C-1Gal), 97.4 /C-1Glc),
77.8, 77.4, 76.6, 76.0, 75.9, 73.5, 72.5, 72.2, 69.9, 69.7,
69.6, 69.4, 68.1, 67.0, 65.9 /C-60Gal), 64.6, 61.5 /C-6Gal),
60.7, 55.8 /OCH3Glc), 55.6 /OCH3Gal); MS /ESI): m/
zˆ684.4 /M1H)1, 706.4 /M1Na)1.
1/10); 1H NMR /300 MHz, CDCl3): dˆ8.09±7.26 /m,
3
15H, Har.Z,E), 6.63 /d, J2 Z,3 Zˆ8.4 Hz, H-30Z), 6.17 /d,
0
0
3
3
J2 E,3 Eˆ5.2 Hz, H-30E), 5.54 /dd, J1 E,2 Eˆ4.1 Hz, H-20E),
0
0
0
0
5.23±5.20 /m, H-50E), 5.22 /d, H-10E), 5.06 /dd,
3
2
J5 E,6a Eˆ5.9 Hz,
J6a E,6b Eˆ11.5 Hz, H-6a0E), 4.97
0
0
0
0
/d,,3J1E,2Eˆ8.2 Hz, H-1E), 4.80 /bd, H-6b0 ), 4.07±3.82
E
/m, H-4E, H-5E), 3.97 /bt, H-2E), 3.69±3.58 /m, H-3E, H-
6E), 3.48 /s, OCH3Z), 3.42 /s, OCH3E); 13C NMR /75 MHz,
CDCl3): dˆ167.4 /CvO), 165.9 /CvO), 165.3 /CvO),
153.7 /C-40), 133.9 /Car0.), 133.7 /Car0.), 130.4 /Car0.),
130.2 /Car0.), 129.6 /Car0.), 129.4 /Car0.), 128.9 /Car0.),
128.8 /Car0.), 128.7 /Car0.), 105.8 /C-1), 96.5 /C-10), 74.9
/C-6), 73.9 /C-3), 72.2 /C-20), 70.3 /C-2), 69.4 /C-4), 69.2
/C-30), 68.4 /C-50), 64.5 /C-60), 62.3 /C-5), 57.0 /OCH3);
MS /ESI): m/zˆ682.4 /M1H)1, 699.3 /M1H2O)1.
4.1.11. Methyl 4-deoxy-4-methoxyamino-4-N-ꢀb-d-gluco-
pyranosyl)-a-d-galactopyranoside ꢀ11). Compound 9
/0.11 g, 0.1 mmol) in methanol /2 mL) was treated with
few drops /pH 9±10) of sodium methanoate /30% in metha-
nol). After 2 hat room temperature, the solution was neutra-
lised withcation exchange resin Amberlite IR-120 /H 1),
®ltrated and concentrated in vacuo. The residue was then
taken up in water and extracted three times with CH2Cl2.
The aqueous phase was lyophilised to give 11 withquanti-
4.1.9. Methyl 2,3,6-tri-O-benzoyl-4-deoxy-ꢀO-b-d-gluco-
pyranosylhydroxyamino)-a-d-gluco, galactopyranoside
ꢀ23). Oxime 19 /0.11 g, 0.2 mmol) was dissolved in diethyl
ether /50 mL) saturated with dry HCl and BH3/Et3N
complex /0.23 mL, 2 mmol) was added. This solution was
stirred at room temperature for 2 hand was taken up in
diethyl ether. The organic layer was washed with aqueous
NaHCO3 solution, dried withsodium sulfate and evapo-
rated. The resulting white powder was chromatographied
on silica gel column /solvent gradient of CH2Cl2 through
pure ethyl acetate) to give gluco- and galacto- mixture 23
/87% yield, 1/3:2/3) as white solid after precipitation from
1
tative yield. H NMR /300 MHz, D2O): dˆ4.91 /d, 1H,
3
3
0
0
0
J1 ,2 ˆ4.2 Hz, H-1 ), 4.38 /d, 1H, J1,2ˆ8.7 Hz, H-1), 4.09
3
/m, 1H, H-50), 4.04 /dd, 1H, J2 ,3 ˆ10.2 Hz, H-2 ), 3.95±
0
0
0
3.81 /m, 5H, H-30, H-40, H-60, H-6a), 3.79±3.70 /m, 1H, H-
3
2
0
0
0
0
5), 3.74 /dd, 1H, J5 ,6b ˆ5.5 Hz, J6a ,6b ˆ12.2 Hz, H-6b),
3.58 /s, 3H, OCH3), 3.55±3.42 /m, 3H, H-2, H-3, H-4),
3.41 /s, 3H, NOCH3); 13C NMR /75 MHz, D2O): dˆ99.5
/C-10), 93.0 /C-1), 77.7, 77.2 /C-2, C-3 or C-4), 71.1 /C-50),
70.3, 70.0, 69.5, 69.4 /C-20, C-30, C-40, C-2, C-3 or C-4),
62.5 /C-60), 61.5 /C-30 or C-40), 61.4 /NOCH3), 61.1 /C-6),
CH2Cl2/pentane. 1H NMR /300 MHz, CDCl3): dˆ8.06±
3
7.27 /m, Har.Gal,Glc), 6.29 /t, 3J2 Glc,3 Glcˆ J3 Glc,4 Glcˆ10.0 Hz,
0
0
0
0
3
3
20
20
0
0
0
0
0
H-3 Glc), 5.75 /dd, J3 Gal,4 Galˆ4.3 Hz, J2 Gal,3 Galˆ11.1 Hz,
55.4 /OCH3); [a]589 ˆ126.98, [a]546 ˆ139.28 /cˆ0.36,
methanol); MS /ESI): m/zˆ386.2 /M1H)1, 408.1
/M1Na)1, 793.7 /2M1Na)1; HRMS /FAB): calcd for
C14H28NO11: 386.1662, found 386.1656.
3
0
0
0
00
0
H-3 Gal), 5.43 /dd, J1 Gal,2 Galˆ3.7 Hz, H-2 Gal), 5.18 /dd,
3
0
0
J1 Glc,2 Glcˆ3.4 Hz, H-2 Glc), 5.13 /m, H-1 Gal,Glc), 4.81±4.50
3
/m, H-60Gal), 4.62 /d, J1Gal,2Galˆ7.4 Hz, H-1Gal), 4.54 /d,
3J1Glc,2Glcˆ7.4 Hz, H-1Glc), 4.35 /m, H-50Gal), 4.02 /d, H-
40Gal), 3.65±3.55 /m, H-5Gal), 3.54±3.31 /m, H-2Glc, H-3Gal),
3.31±3.18 /m, H-2Gal, H-40Glc), 3.36 /s, OCH3), 3.09 /bd,
3J3Gal,4Galˆ8.7 Hz, H-4Gal); 13C NMR /75 MHz, CDCl3):
dˆ166.8 /CvO), 166.0 /CvO), 165.9 /CvO), 133.5
/Car0.), 133.2 /Car0.), 133.1 /Car0.), 129.8 /Car0.), 129.7
/Car0.), 129.6 /Car0.), 129.2 /Car0.), 129.1 /Car0.), 128.9
/Car0.), 128.5 /Car0.), 128.4 /Car0.), 128.3 /Car0.), 105.3
/C-10 Gal), 105.2 /C-10Glc), 97.1 /C-1Gal), 97.0 /C-1Glc),
77.2, 76.2, 75.6, 75.5, 73.1, 71.9, 71.8, 69.3, 69.2, 69.1,
67.8, 66.6, 65.5 /C-60 Gal), 64.2, 61.1 /C-6Gal), 60.9, 60.3,
55.4 /OCH3Glc), 55.1 /OCH3Gal); MS /ESI): m/zˆ684.6
/M1H)1, 706.5 /M1Na)1.
4.1.12. Methyl 4-deoxy-4-methoxyamino-4-N-ꢀb-d-galac-
topyranosyl)-a-d-galactopyranoside ꢀ12). Compound 12
was prepared following the procedure described for 11.
1
Quantitative yield; H NMR /300 MHz, D2O): dˆ4.95 /d,
3
3
0
0
0
1H, J1 ,2 ˆ4.2 Hz, H-1 ), 4.39 /d, 1H, J1,2ˆ8.3 Hz, H-1),
3
3
0
0
0
0
4.34 /dd, 1H, J5 ,6a ˆ2.3 Hz, J5 ,6b ˆ8.3 Hz, H-5), 4.20±
3
0
0
0
4.08 /m, 1H, H-4), 4.03 /dd, 1H, J2 ,3 ˆ9.9 Hz H-2 ),
4.05±3.88 /m, 3H, H-3, H-6a, H-50), 3.82 /m, 1H, H-40),
3.78±3.69 /m, 4H, H-2, H-6b, H-60), 3.64 /s, 3H, NOCH3),
3.63 /m, 1H, H-30), 3.46 /s, 3H, OCH3); 13C NMR /75 MHz,
D2O): dˆ99.6 /C-10), 93.6 /C-1), 77.0 /C-40), 74.2 /C-2),
70.8 /C-20), 70.5, 70.0, 69.6, 69.1, /C-3, C-5, C-30, C-50),
68.0 /C-4), 63.6 /C-60), 62.4 /C-6), 61.2 /NOCH3), 55.4
20
20
4.1.10. Methyl 2,3,6-tri-O-benzoyl-4-deoxy-ꢀO-b-d-
galacto-
/OCH3); [a]589 ˆ1109.98, [a]546 ˆ1145.48 /cˆ0.24,
galactopyranosylhydroxyamino)-a-d-gluco,
methanol); MS /ESI): m/zˆ387.0 /M1H)1, 408.9

2134
O. Renaudet, P. Dumy / Tetrahedron 5832002) 2127±2135
/M1Na)1, 793.5 /2M1Na)1; HRMS /FAB): calcd for
C14H28NO11: 386.1662, found 386.1662.
Quantitative yield; 1H NMR /300 MHz, D2O): dˆ5.08
/d, 3J1 E,2 Eˆ3.0 Hz, H-10E), 5.05±5.03 /m, H-1E, H-50E,
0
0
3
H-1Z), 4.99 /d, J1 ,2 Zˆ3.0 Hz, H-10Z), 4.93 /d,
0
0
3
3
J5 Z,6 Zˆ6.4 Hz, H-50Z), 4.36 /d, J2 E,3 Eˆ5.3 Hz, H-30E),
0
0
0
0
4.1.13. Methyl 4-deoxy-4-methoxyamino-4-N-ꢀb-d-gluco-
pyranosyl)-a-d-glucopyranoside ꢀ15). Compound 15 was
prepared following the procedure described for 11. Quanti-
3
3
4.53 /dd, J5Z,6aZˆ4.1 Hz, J5Z,6bZˆ5.7 Hz, H-5Z), 4.08 /dd,
3
2
J5 E,6a Eˆ7.2 Hz, J6a E,6b Eˆ12.1 Hz, H-6a0 ), 4.01 /m,
0
0
0
0
E
1
3
0
H-20E, H-3E, H-6 Z), 3.90 /dd, J5 E,6b Eˆ7.2 Hz, H-6b0E),
3.87±3.75 /m, H-2E, H-4E, H-5E, H-4Z, H-6Z,E, H-20Z),
3.53 /s, OCH3E), 3.50 /s, OCH3Z); 13C NMR /75 MHz,
D2O): dˆ158.3 /C-4Z), 157.8 /C-4E), 105.0 /C-1Z), 104.1
0
0
tative yield; H NMR /300 MHz, D2O): dˆ4.84 /d, 1H,
3
3
0
0
0
J1 ,2 ˆ3.8 Hz, H-1 ), 4.25 /d, 1H, J1,2ˆ8.6 Hz, H-1), 4.10
3
2
0
0
0
0
0
/dd, 1H, J5 ,6a ˆ2.3 Hz, J6a ,6b ˆ12.5 Hz, H-6a ), 4.04±
3.90 /m, 3H, H-50, H-6a, H-30), 3.83 /dd, 1H,
3
0
0
J5 ,6b ˆ5.5 Hz, H-6b ), 3.76±3.62 /m, 3H, H-2 , H-6b, H-
2), 3.68 /s, 3H, NOCH3), 3.58±3.50 /m, 2H, H-3, H-5), 3.46
/s, 3H, OCH3), 3.41 /t, 1H, 3J3,4ˆ3J4,5ˆ9.3 Hz, H-4), 3.10 /t,
/C-1E), 98,2 /C-10Z), 96.9 /C-10 ), 75.8, 72.9 /C-4E, C-5E),
0
0
E
72.0 /C-5Z), 71.2 /C-20E or C-3E), 70.5 /C-50E), 70.0 /C-30E),
69.1 /C-2E), 68.6 /C-20E or C-3E), 65.2 /C-50 ), 61.0 /C-6E),
Z
1H, J3 ,4 ˆ J4 ,5 ˆ10.2 Hz, H-4 ); 13C NMR /75 MHz,
D2O): dˆ98.1 /C-10), 90.7 /C-1), 77.0, 76.1 /C-3, C-5),
71.1 /C-2 or C-20), 69.8 /C-30 or C-50), 69.1 /C-2 or C-
20), 68.6 /C-4), 66.4 /C-30 or C-50), 65.1 /C-40), 62.5
/NOCH3), 61.5 /C-60), 60.1 /C-6), 54.4 /OCH3);
60.7
/C-60E),
56.4
/OCH3);
[a]589 ˆ170.08,
3
3
20
0
0
0
0
0
20
[a]546 ˆ191.98 /cˆ0.38, methanol); MS /ESI): m/zˆ370.4
/M1H)1, 387.4 /M1H2O)1, 392.3 /M1Na)1, 756.3
/2M1H2O)1, 760.8 /2M1Na)1; HRMS /FAB): calcd for
C13H24NO11: 370.1349, found 370.1345.
20
20
[a]589 ˆ111.48, [a]546 ˆ126.38 /cˆ0.23, methanol);
HRMS /FAB): calcd for C14H28NO11: 386.1662, found
386.1664.
4.1.17. Methyl 4-deoxy-ꢀO-b-d-glucopyranosylhydroxy-
amino)-a-d-gluco, galactopyranoside ꢀ25). Compound
25 was prepared following the procedure described for 11.
1
4.1.14. Methyl 4-deoxy-4-methoxyamino-4-N-ꢀb-d-galac-
topyranosyl)-a-d-glucopyranoside ꢀ16). Compound 16
was prepared following the procedure described for 11.
Quantitative yield; H NMR /300 MHz, D2O): dˆ4.86 /d,
3
3
0
0
0
0
0
J1 Glc,2 Glcˆ3.6 Hz, H-1 Glc), 4.85 /d, J1 Gal,2 Galˆ3.6 Hz,
3
H-10Gal), 4.71 /d, J1Gal,2Glalˆ8.3 Hz, H-1Gal), 4.61 /d,
1
3
3
3
0
0
0
0
Quantitative yield; H NMR /300 MHz, D2O): dˆ4.84 /d,
J1Glc,2Glcˆ8.4 Hz, H-1Glc), 4.13 /t, J2 Glc,3 Glcˆ J3 Glc,4 Glc
ˆ
3
3
3
0
1H, J1 ,2 ˆ3.7 Hz, H-1 ), 4.19 /d, 1H, J1,2ˆ9.0 Hz, H-1),
9.9 Hz,
0
H-30Glc),
4.08
/dd,
J2 Gal,3 Galˆ4.8 Hz,
0
0
0
0
3
2
3
0
0
0
0
0
0
0
4.16 /dd, 1H, J5 ,6b ˆ2.2 Hz, J6a ,6b ˆ11.9 Hz, H-6a ),
J3 Gal,4 Galˆ10.5 Hz, H-3 Gal), 4.11±4.05 /m, H-4Glc),
4.07±3.92 /m, 3H, H-30, H-50, H-4), 3.90 /t, 1H, H-2),
4.04±3.89 /m, H-5Gal, H-6Gal, H-4Glc, H-3Glc, H-60Glc),
3
3.84 /dd, 1H, J5 ,6a ˆ5.4 Hz, H-6b ), 3.80±3.66 /m, 5H,
3.88±3.72 /m, H-4Gal, H-6Glc), 3.65 /dd, 3J2 Gal,3 Galˆ8.0 Hz,
0
0
0
0
0
H-20, H-3, H-5, H-6), 3.70 /s, 3H, NOCH3), 3.47 /s, 3H,
H-20Gal), 3.62 /dd, H-20Glc), 3.57±3.46 /m, H-3Gal, H-40Gal
,
OCH3), 3.10 /t, 1H, J3 ,4 ˆ J4 ,5 ˆ10.2 Hz, H-4 ); 13C
NMR /75 MHz, D2O): dˆ97.0 /C-10), 91.2 /C-1), 75.3,
72.0, 70.1 /C-20, C-3, C-5), 68.7, 66.9, 65.7 /C-30, C-50,
H-60Gal), 3.45 /s, OCH3Gal), 3.45±3.38 /m, H-50Gal), 3.34 /t,
3
3
0
0
0
0
0
3
3
0
0
J2Glc,3Glcˆ8.3 Hz, H-2Glc), 3.31 /t, J4 Glc,5 Glcˆ9.9 Hz, H-
40Glc); 13C NMR /75 MHz, D2O): dˆ105.0 /C-1Glc), 104.3
/C-1Gal), 99.8 /C-10Glc), 99.5 /C-10Gal), 76.1 /C-3Gal or C-
40Gal), 76.0, 72.4, 72.2 /C-2Glc), 72.1 /C-2Gal), 70.7, 69.9
/C-50Gal), 69.1 /C-20Glc), 68.9 /C-20Gal), 68.2 /C-30Gal), 67.1
/C-30Glc), 62.7 /C-6Gal), 62.2 /C-40Glc), 62.1 /C-60Glc), 61.6
/C-6Gl2c0), 61.0 /C-6Gal), 55.4 /OCH3Gal), 55.3 /OCH3Glc);
C-4), 65.3 /C-2), 64.1 /C-40), 61.5 /NOCH3), 60.4 /C-60),
20
59.3
/C-6),
53.3
/OCH3);
[a]589 ˆ169.08,
20
[a]546 ˆ1112.08 /cˆ0.11, methanol); HRMS /FAB):
calcd for C14H28NO11: 386.1662, found 386.1656.
20
4.1.15. Methyl 4-deoxy-ꢀO-b-d-glucopyranosylhydroxy-
imino)-a-d-xylo-hexopyranoside ꢀ21). Compound 21 was
prepared following the procedure described for 11. Quanti-
tative yield; 1H NMR /300 MHz, D2O): dˆ5.11 /d,
[a]589 ˆ155.08, [a]546 ˆ181.58 /cˆ0.20, methanol);
MS /ESI): m/zˆ372.3 /M1H)1, 394.4 /M1Na)1, 765.3
/2M1Na)1; HRMS /FAB): calcd for C13H26NO11:
370.1505, found 370.150.
3
3
J1E,2Eˆ7.9 Hz, H-1E), 5.07 /d, J1 E,2 Eˆ3.0 Hz, H-10E, H-
0
0
3
3
1Z), 5.04 /dd, J5 E,6a Eˆ3.0 Hz, J5 E,6b Eˆ7.5 Hz, H-50E),
4.1.18. Methyl 4-deoxy-ꢀO-b-d-galactopyranosylhydroxy-
amino)-a-d-gluco, galactopyranoside ꢀ26). Compound
26 was prepared following the procedure described for 11.
0
0
0
0
3
3
5.00 /d, J1 Z,2 Zˆ2.6 Hz, H-10Z), 4.92 /d, J5 Z,6 Zˆ6.4 Hz,
0
0
0
0
3
3
H-50Z), 4.53 /dd, J5Z,6aZˆ4.1 Hz, J5Z,6bZˆ5.7 Hz, H-5Z),
3
1
4.35 /d, J2 E,3 Eˆ4.5 Hz, H-30E), 4.02-3.90 /m, H-2 Z,Z, H-
6a0E, H-60Z), 3.89±3.74 /m, H-6b0E, H-5E, H-6E, H-6Z),
3.73±3.60 /m, H-4E), 3.54±3.32, /m, H-2Z,Z, H-3E), 3.53
/s, OCH3E), 3.50 /s, OCH3Z); 13C NMR /75 MHz, D2O):
dˆ158.9 /C-40 ), 158.5 /C-40 ), 104.5 /C-1Z), 104.0 /C-
Quantitative yield; H NMR /300 MHz, D2O): dˆ4.87±
0
0
0
3
0
0
0
0
4.83 /m, J1 Gal,2 Galˆ3.8 Hz, H-1 Gal, H-1 Glc), 4.65 /d,
3J1Gal,2Galˆ8.3 Hz, H-1Gal), 4.55 /d, J1Glc,2Glcˆ8.3 Hz,
3
3
3
0
0
0
0
0
0
H-1Glc), 4.15 /t, J2 Glc,3 Glcˆ J3 Glc,4 Glcˆ9.8 Hz, H-3 Glc),
3
3
0
0
0
0
4.07 /dd, J3 Gal,4 Galˆ4.9 Hz, J2 Gal,3 Galˆ10.6 Hz, H-3 Gal),
4.12±4.07 /m, H-50Glc), 4.03±3.94 /m, H-4Gal, H-50Gal),
3.90±3.62 /m, H-3Gal, H-6Gal, H-3Glc, H-20Gal, H-60Gal),
3.55 /t, H-2Glc), 3.55±3.48 /m, H-2Gal, H-40Gal), 3.44 /s,
OCH3Gal), 2.79 /t, H-40Glc); 13C NMR /75 MHz, D2O):
dˆ105.5 /C-1Glc), 104.7 /C-1Gal), 99.7 /C-10Glc), 99.5 /C-
10Gal), 75.3, 73.0, 72.3, 70.7, 69.9, 69.7, 69.1, 68.9 /C-4Gal or
C-50Gal), 68.2, 67.0, 62.7 /C-40Glc), 62.0 /C-60Gal or C-6Gal),
61.6, 61.4, 61.3 /C-60Gal or C-6Gal), 57.8 /OCH3Glc), 55.4
Z
E
1E), 98.6 /C-10Z), 97.4 /C-10E), 77.0, 76.9, 76.4, 76.3, 72.5
/C-5Z), 72.0, 71.9, 71.7, 71.1, 70.9 /C-50E), 70.6, 69.9, 69.8,
65.6 /C-50Z), 63.3 /C-6E), 61.2 /C-60E), 61.0 /C-6Z), 56.9
20
20
/OCH3E), 56.5 /OCH3Z); [a]589 ˆ133.68, [a]546 ˆ171.88
/cˆ0.11, methanol); MS /ESI): m/zˆ370.4 /M1H)1, 387.4
/M1H2O)1, 392.3 /M1Na)1, 761.8 /2M1Na)1; HRMS
/FAB): calcd for C13H23NO11Na: 392.1168, found 392.1161.
20
4.1.16. Methyl 4-deoxy-ꢀO-b-d-galactopyranosylhydroxy-
imino)-a-d-xylo-hexopyranoside ꢀ22). Compound 22 was
prepared following the procedure described for 11.
/OCH3Gal); [a]589 ˆ187.58, [a]546201157.58 /cˆ0.28,
methanol); MS /ESI): m/zˆ372.3 /M1H)1, 394.4
/M1Na)1, 743.3 /2M)1, 765.3 /2M1Na)1.

O. Renaudet, P. Dumy / Tetrahedron 5832002) 2127±2135
2135
J. D. M.; Colstee, J. H.; Ottenheijm, H. C. J. J. Org. Chem.
1981, 46, 3346±3348.
Acknowledgements
17. Crystallographic data /excluding structure factors) for the
structures in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary
publication numbers CCDC. Deposition number for
compound 5: 167751. Deposition number for compound 10:
167750. Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ,
UK [fax: 144-/0)-1223-336033 or e-mail: deposit@ccdc.
cam.ac.uk].
This work was supported by the Association pour la
Recherche contre le Cancer /ARC), the Centre National
pour la Recherche Scienti®que /CNRS) for speci®c action
/AIP) and the Institut Universitaire de France /IUF). We
also thank the MENRT for grant No. 98-4-23548 to O. R.
P. Vogel and R. Demange are warmly acknowledged for
preliminary biological assays. We also thank C. Philouze
and M. T. Averbuch-Pouchot for performing the RX studies
presented here.
18. Renaudet, O.; Dumy, P.; Philouze, C. Acta Crystallogr. 2001,
C57, 309±310.
19. Cremer, D.; Pople, J. A. J. Am. Chem. Soc. 1975, 97, 1354±
1358.
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