New and general synthesis of β-C-glycosylformaldehydes from easily available β-C-glycosylpropanones

Article abstract of DOI:10.1016/j.carres.2007.09.002

A highly effective method for the introduction of a formyl group at the anomeric position of pyranosides was developed via enolisation of β-C-d-glycopyranosylpropan-2-one using thermodynamic conditions then oxidative cleavage of the more substituted doubl

Full text of DOI:10.1016/j.carres.2007.09.002

Available online at www.sciencedirect.com
Carbohydrate Research 342 (2007) 2716–2728
New and general synthesis of b-C-glycosylformaldehydes
from easily available b-C-glycosylpropanones
*
´
´
Stephanie Norsikian, Jennifer Zeitouni, Stephanie Rat,
´
´
Sylvie Gerard and Andre Lubineau
ˆ
Laboratoire de Chimie Organique Multifonctionnelle, UMR CNRS-UPS 8614 ‘Glycochimie Mole´culaire’, Bat. 420,
Universite´ Paris Sud, F-91405 Orsay, France
Received 24 May 2007; received in revised form 2 September 2007; accepted 4 September 2007
Available online 11 September 2007
Abstract—A highly effective method for the introduction of a formyl group at the anomeric position of pyranosides was developed
via enolisation of b-C-D-glycopyranosylpropan-2-one using thermodynamic conditions then oxidative cleavage of the more substi-
tuted double bond. This sequence affords the desired aldehydes that are conveniently protected as aminals for purification and stor-
age and easily regenerated using Dowex resin H+. In this paper, the syntheses of nine differently protected aldehydes derived from
D-glucose, D-galactose, lactose and N-acetyl-D-glucosamine are presented. Our strategy proved to be very efficient in most cases
excepted in the D-mannose series.
ꢀ 2007 Elsevier Ltd. All rights reserved.
Keywords: C-Glycosyl compounds; Sugar aldehydes; Enoxysilanes; a-Hydroxyketones; Aminals
1. Introduction
glycosyl compounds are retained and sometimes even
greater.3a,d–g,k,n–r Consequently, a number of reliable
methods have been developed for the synthesis of these
compounds. One way for achieving the preparation of
complex C-glycosyl compounds is the coupling between
C-glycosylformaldehydes and another sugar moiety or
an aglycone residue. This method was already proved
to be very useful for the preparation of C-linked glyco-
peptides, C-linked glycolipids and C-linked disaccha-
rides.3d,5 Peracetylated glycopyranosylformaldehydes
can be synthesised by reductive hydrolysis of pyranosyl-
cyanide or by ozonolyzis of nitro sugar-derived silyl
nitronates.6 Perbenzylated glycopyranosylformaldehy-
des can be synthesised by ozonolyzis of C-glycosyl-
allenes7 or, in most cases, from 2,3,4,6-tetra-O-benzyl-
D-glycono-1,5-lactone after anomeric introduction of
phenylacetylene,8 dithiane,8,9 thiazole or benzothiazole
ring10 from which the formyl group can be generated.
However, several drawbacks appear to be associated
with some of these methodologies such as moderate
overall yields or the presence of an a/b anomeric
mixture thus limiting their use. We describe here an
efficient alternative protocol for incorporating a formyl
C-Glycosyl compounds, in which the anomeric oxygen
atom is replaced by a methylene group, have been the
subject of considerable interest in carbohydrate chemis-
try.1,2 These carbohydrate mimetics possess an im-
proved stability towards acid-, base and enzymatic
hydrolysis and may display interesting biological activi-
ties.1c,d,2g,3 They may serve as regulators of enzymes
such as glycosidases and glycosyltransferases that are
potential anti-cancer, antiviral or antidiabetic agents.
They may also be used as artificial ligands that can be
useful in probing cellular interactions. Moreover, de-
spite structural investigations that revealed, most of
the time, notable conformational differences between
the natural and unnatural glycosides,4 a number of
studies have shown that the biological properties of C-
*
Corresponding author at present address: Institut de Chimie des
Substances Naturelles, UPR CNRS 2301, Avenue de la Terrasse,
Baˆtiment 27, F-91198 Gif-sur-Yvette, France. Tel.: +33 (0)1 69 82 30
23; fax: +33 (0)1 69 07 72 47; e-mail: stephanie.norsikian@icsn.
cnrs-gif.fr
0008-6215/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2007.09.002

S. Norsikian et al. / Carbohydrate Research 342 (2007) 2716–2728
2717
R5
OR1
R3
R5
R5
OR1
R3
OR1
R3
R4
O
R4
R4
a
O
O
R1O
R1O
+
R1O
R2
R2
R2
OSiMe3
O
OSiMe3
1a-g
2a-e, 2g
3a-e, 2g
b
R5
OR1
R5
OR1
R3
R3
O
R4
R1
R2
R3
R4
OAc
OBn
H
R5
H
H
OAc
H
H
OH
O
R4
+
O
R1O
O
R1O
R2
1-4a, 6-7a
1-7b
1-4c, 6-7c
1-4d, 6-7d
1-4e, 6-7e
1f , 6-7f
R2
Ac OAc
Bn OBn
Ac OAc
Ac OAc
H
H
H
H
HO
4a-e, 4g
5b, 5e
c
OGal
Ph
N
R5
OR1
Ac
H
OAc OAc
H
H
R5 OR1
R3
7a-e
7g
R3
e
d
Ac NHAc
Ac NAc2
OAc
OAc
H
H
O
R4
R4
R1O
O
O
R1O
g
1-4g, 6-7g
R2
R2
N
H
7f
Ph
6a-d, 6f-g
Scheme 1. Reagents and conditions: (a) see conditions of Table 1; (b) dimethyldioxirane; (c) NaIO4, THF–water; (d) N,N-dibenzylethylenediamine,
toluene; (e) Dowex H+ resin, water–THF; (f) isopropenylacetate, TsOH (1g, 99%); (g) NH2–NH2, water, CH2Cl2 (7f, 88%).
group at the anomeric position of a sugar derivative,
which may serve as a general tool towards the
synthesis of more complex C-glycosyl compounds or
C-disaccharides of biological relevance.
Our approach towards the synthesis of sugar alde-
hydes is described in Scheme 1. It is based on the use
of peracetylated b-C-glycosylketones 1 for which a very
easy two-step synthesis was recently described.11,12 In
this strategy, we postulated that enolisation of ketones
1 in thermodynamic conditions followed by oxidative
cleavage of the more substituted double bond would
furnish the desired aldehydes 6.
The enolisation of 1a12 was performed under various
conditions and the results are presented in Table 1.
We first carried out the reaction using the Me3SiCl–
NaI–NEt3 reagent in MeCN as described by Cazeau
et al. (entry 1).14 The reaction proceeds well at rt but
the major product obtained was the less substituted
enoxysilane 3a. The reaction was also performed at
52 ꢁC without improvement of the ratio 2a:3a. To in-
crease the proportion of the thermodynamic compound,
other bases such as pyridine, lutidine and hexamethyldi-
silazane were tested using the same conditions (entries
2–5). Amongst the bases used, the best results were
obtained when triethylamine was replaced by pyridine.
In this case, the reaction, which led only to the thermo-
dynamic compound 2a as a mixture of E/Z diastereo-
mers, was slower and required 36 h in MeCN at 52 ꢁC
for complete conversion (entry 2). When carried out in
MeCN–pentane, the reaction was faster and gave more
2. Results and discussion
We started our study with the preparation of 2,3,4,6-
tetra-O-acetyl-b-D-glucopyranosylformaldehyde 6a.13
Table 1. Conditions for enolisation of ketone 1a–e, 1g
Entry
Ketone
Solvent
T (ꢁC)
Time (h)
Reagents
2:3a
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1b
1c
1c
1d
1e
1g
MeCN
MeCN
MeCN–pentaneb
MeCN
MeCN
DMF
MeCN–pentaneb
MeCN–pentaneb
MeCN–cyclohexaneb
MeCN–cyclohexaneb
MeCN–cyclohexaneb
MeCN–cyclohexaneb
rt
3
36
12
24
24
36
12
12
12
12
12
12
TMSCl, Et3N, NaI
3:7
1:0
1:0
4:1
7:3
1:0
9:1
9:1
1:0
1:0
23:2
1:0
52
52
52
52
100
rt
52
70
52
70
70
TMSCl, pyridine, NaI
TMSCl, pyridine, NaI
TMSCl, lutidine, NaI
TMSCl, HMDS, NaI
TMSCl, NEt3
TMSCl, pyridine, NaI
TMSCl, pyridine, NaI
TMSCl, pyridine, NaI
TMSCl, pyridine, NaI
TMSCl, pyridine, NaI
TMSCl, pyridine, NaI
10
11
12
a Determined by 1H NMR on the crude mixture.
b In a 6:5 ratio.

2718
S. Norsikian et al. / Carbohydrate Research 342 (2007) 2716–2728
reproducible results (entry 3). The reaction was also per-
formed using the conditions described by House with
trimethylsilyl chloride in the presence of triethylamine
in DMF at 100 ꢁC for 36 h (entry 6).15 A complete con-
version as well as a complete regioselectivity in favour of
the thermodynamic compound was obtained but these
conditions gave less reproducible results, which led us
to prefer the conditions described in entry 3.
column chromatography at the end of the synthesis.
This four-step sequence could be performed on multi-
gram scale (7 g of ketone 1a). The deprotection of the
aminal function with Dowex H+ resin led quantitatively
to 6a, which can be used directly without further purifi-
cation. It is also worth to note that, under these depro-
tection conditions, the anomeric integrity of the
aldehyde is maintained and only the b-form is obtained.
The synthesis of 2,3,4,6-tetra-O-benzyl-b-D-gluco-
pyranosylformaldehyde 6b was more challenging since
obtaining O-benzylated ketone 1b directly from 8
proved to be non-trivial (Scheme 2). With the classical
benzylation method (NaH, DMF and BnBr), a complex
mixture was obtained whereas no reaction was observed
under milder conditions. Only the use of Ag2O in DMF
allowed us to obtained the desired compound 1b. This
reaction required 8 equiv of the expensive Ag2O and
only poor yields (30–45%) were observed. We decided
then to synthesise ketone 1b in a four-step sequence
from 1a: this latter was first protected with ethylene
glycol in toluene, then deacetylation (MeONa in
MeOH), followed by benzylation with NaH in DMF
and removal of intermediate cyclic ketal gave 1b in
83% overall yield from 1a. Only a final purification
was necessary to obtain multigrams of ketone 1b. A
shorter synthesis of 1b can also be performed from 8,
which can be directly protected with ethylene glycol in
a mixture of benzene–MeCN. Benzylation and deprotec-
tion of the cyclic ketal furnished the desired compound
in 69% yield over three steps.
The enolisation reaction was carried out as described
above, albeit at rt since degradation was observed with
heating at 52 ꢁC (Table 1, entry 7). In these conditions,
the formation of the thermodynamic product 2b was
observed along with a minor quantity of the kinetic
compound 3b (in a 9:1 ratio). The crude mixture of
enoxysilanes was then oxidised with dimethyldioxirane
affording a mixture of hydroxyketones 4b and 5b in
72% yield after purification. After treatment with
sodium periodate, aldehyde 6b was isolated by column
chromatography in 90% yield. In this case, the aldehyde
is stable enough to be stored without protection for few
months in the freezer.
Once obtained, the resulting enoxysilane 2a was di-
rectly engaged (without purification) in an oxidation
reaction with ozone at ꢀ78 ꢁC in CH2Cl2. Under these
conditions, moderate yields of the aldehyde were
obtained (40–50%). To improve these results, we decided
to perform the oxidation in a two-step sequence. The
enoxysilane was then transformed into the a-hydroxy-
ketone 4a by a freshly prepared solution of dimethyl-
dioxirane (DMDO).16 Since the enoxysilane is quite
sensitive to acidic conditions, the reaction was carried
out in the presence of potassium carbonate (0.5 equiv)
and led to 4a along with its O-silylated form (5%) that
gave after acidic treatment pure 4a in a good 85% yield
as a 9:1 mixture of diastereomer. The major diastereomer
could be isolated by recrystallisation in EtOAc and the
absolute configuration at C-1 (R) of the newly formed
stereocentre was determined by X-ray diffraction (Fig. 1).
This major configuration could be explained by the pref-
erential formation of the epoxide on the alpha face (Si
face) of the enoxysilane that is less sterically hindered.
It also worth to be noticed that other oxidants such as
m-CPBA or oxone were less efficient or led to degrada-
tion of the acidic labile enoxysilane.
Further treatment of a-hydroxyketone 4a with so-
dium metaperiodate in THF–water provided the desired
aldehyde 6a. Due to its instability and to achieve better
purification by column chromatography, the product
was protected and stored as aminal 7a in 77% yield from
4a. Aminal 7a could also be obtained in 68% overall
yield from ketone 1a after a single purification by
Alternatively and in a simpler manner, 2,3,4,6-tetra-
O-benzyl-b-D-glucopyranosylformaldehyde 6b could be
prepared in a three-step procedure from aminal 7a
(Scheme 3). After deacetylation (NaOMe in MeOH)
and benzylation with NaH in DMF, 7b was obtained
in 90% yield over two steps. The deprotection of the
aminal with Dowex H+ resin led to 6b, which was
isolated in 94% yield after purification.
The synthesis of aminal 7a also allowed us to prepare
the free hydrated aldehyde 1017 (Scheme 3). This was
achieved by simple acetate deprotection (NaOMe in
MeOH) followed by removal of the aminal function
(Dowex H+). For proof of structure of aldehyde 10,
Figure 1. ORTEP drawing of 4a. Ellipsoids are drawn at the 50%
probability level.

S. Norsikian et al. / Carbohydrate Research 342 (2007) 2716–2728
2719
f
OBn
OH
OH
OAc
c
b
d
O
O
O
O
HO
HO
BnO
BnO
HO
HO
AcO
AcO
O
O
O O
OBn
OH
OH
O
O
OAc
9a
O
9c
8
9b
OBn
a
e
O
BnO
BnO
OBn
O
1b
Scheme 2. Reagents and conditions: (a) BnBr, Ag2O, DMF (1b, 30–45%); (b) (i) Ac2O, pyridine (1a, 91%); (ii) ethylene glycol, toluene, PPTS (9a); (c)
MeONa, MeOH (9b); (d) BnBr, NaH, DMF (9c); (e) TFA–water (1b); (f) ethylene glycol, benzene–MeCN, PPTS (9b).
Ph
OBn
OBn
b
O
O
a
c
N
O
BnO
BnO
BnO
BnO
H
N
OBn
6b
Ph
N
OBn
OAc
7b
Ph
O
AcO
AcO
N
OAc
7a
OH
OAc
Ph
OH
e
OAc
O
O
HO
HO
AcO
AcO
OH
OH
OAc
10
11
Scheme 3. Reagents and conditions: (a) (i) NaOMe, MeOH; (ii) NaH, BnBr, DMF (7b, 90%); (b) Dowex H+ resin, water–THF (6b, 94%); (c) (i)
NaOMe, MeOH; (ii) Dowex H+ resin, water–THF (10); (e) (i) allyl bromide, In, water–THF; (ii) Ac2O, pyridine (11, 85% over 4 steps).
it was allowed to react in a 1:1 mixture of THF–water in
the presence of allyl bromide and indium. After acetyl-
ation of the reaction mixture, 11 was obtained as a 7:3
mixture of diastereomers and in 85% yield over four
steps.
a-hydroxyketone 4d is obtained as a 4:1 mixture of
diastereomers. Then, the cleavage with sodium perio-
date and protection of the resulting aldehyde 6d with
N,N-dibenzylethylenediamine allowed the obtention of
aminal 7d in 70% yield.
We then extended the methodology to other pyranose
derivatives such as D-galactose and lactose. In the case
of ketone 1c18 derived from D-galactose (Scheme 1),
we reproduced first the conditions of enolisation descri-
bed for the D-glucose series. However, a mixture of
thermodynamic enol 2c and kinetic one 3c was obtained
in a 9:1 ratio (Table 1, entry 8). To diminish the forma-
tion of the latter, the reaction was carried out at higher
temperature (70 ꢁC) by replacing pentane by cyclo-
hexane. Using the biphasic MeCN–cyclohexane solvent,
the thermodynamic compound was the sole product
obtained in a quantitative way (Table 1, entry 9). The
oxidation of the trimethylsilyl enol ether with DMDO
provided the resulting a-hydroxyketone 4c, which was
obtained as a 9:1 mixture of two diastereomers. After
treatment with sodium periodate in THF–water, alde-
hyde 6c was protected as an aminal that was obtained
in 65% overall yield from ketone 1c.
It is worth to be noticed that a limitation to our strat-
egy was found for the synthesis of aldehyde derived
from D-mannose. In this case, the enolisation of ketone
1e at 52 ꢁC in MeCN–pentane led to an incomplete reac-
tion. The reaction was then carried out at 70 ꢁC and the
desired product was obtained along with some kinetic
product (Table 1, entry 11). Then, the oxidation reaction
with DMDO led to a mixture of diatereomeric
a-hydroxyketones 4e along with 5e (Scheme 1). How-
ever, 4e could be isolated after flash chromatography
in 69% yield and in a 14:11 diastereomeric ratio. The dif-
ficulty was found after treatment of 4e with NaIO4 then
protection of the resulting aldehyde as an aminal. This
latter was found to be very sensitive to elimination
and after flash chromatography, we obtained a mixture
of the desired aminal 7e and adduct 12 that are difficult
to separate (Scheme 4).
This methodology could be extended to the prepara-
tion of the highly-coveted GlcNAc 1-formyl deriva-
tives10b,19 from 20-acetamido-20-deoxy-30,40,60-tri-O-
For ketone 1d, derived from lactose, the enolisation
step was carried out at 52 ꢁC with the TMSCl–NaI–
pyridine system in MeCN–pentane and led only to the
thermodynamic compound 2d in a quantitative manner
(Table 1, entry 10). After treatment with DMDO, the
acetyl-b-D-glucopyranosylpropane-2-one
1f.20
The
synthesis of C-glycosyl compounds of GlcNAc is of
particular interest since amino sugars are widely

2720
S. Norsikian et al. / Carbohydrate Research 342 (2007) 2716–2728
Ph
Ph
OAc
OAc
OAc
OAc
O
OAc
O
1°) NaIO4, THF-water
N
OH
N
O
AcO
AcO
AcO
AcO
+
AcO
AcO
O
N
N
2°) N,N-dibenzylethylenediamine
Ph
toluene
4e
Ph
7e, 51%
12, 27%
Scheme 4. Oxidative cleavage of a-hydroxyketone 4e.
distributed in biological systems and are fundamental
constituents of glycoproteins, a class of natural prod-
ucts with crucial roles in biological recognition
phenomena.21
afford the desired compound in 68% yield after puri-
fication. The synthesis of aldehyde 6f could also be
achieved by treatment of aminal 7g with hydrazine
monohydrate in a mixture of MeOH–THF as described
by Burk and Allen.22 However, using these conditions,
some decomposition occurred and aminal 7f was
obtained in only 54% yield. In contrast, performing
the reaction in pure CH2Cl2 allowed us to obtain aminal
7f in 88% yield (Scheme 1). The deprotection of the ami-
nal function with Dowex H+ resin led quantitatively to
6f, which can be used without purification.
Aminal 7g can also serve as a precursor of other alde-
hydes such as the benzylated aldehyde 14 and the free
hydrated aldehyde 16 (Scheme 6). Indeed, after deacety-
lation of 7g (NaOMe in MeOH), a benzylation step
carried out with NaH in DMF produced 14 in 75% yield
over two steps. Further treatment of 14 with Dowex H+
resin gave the desired aldehyde 15 quantitatively. Final-
ly, the synthesis of 16 was achieved after deprotection of
the alcohols directly followed by removal of the aminal
function. Compound 16 was found to be rather unstable
and was not isolated but for proof of efficiency it was
allowed to react with allylbromide in the presence of
indium in a 1:1 mixture of THF–water. After acetylation
of the reaction mixture, the allylated compound 17 was
obtained as a 3:1 mixture of diastereomers in 87% yield
over four steps.
In summary, we reported an efficient synthesis of syn-
thetically useful b-C-glycosylformaldehydes from easily
available C-glycosyl-propanones. Our strategy allows
the direct access to peracetylated glycosylformaldehydes
such as 2,3,4,6-tetra-O-acetyl-b-D-glucopyranosylform-
aldehyde (five steps, 57% overall yield from D-glucose),
2,3,4,6-tetra-O-acetyl-b-D-galactopyranosylformaldehyde
(five steps, 58% overall yield from D-galactose) or
peracetylated lactopyranosyl formaldehyde (five steps,
57% overall yield from lactose). An alternative to the
preparation of perbenzylated derivatives from the
peracetylated compounds can be achieved by simple
protection–deprotection sequences. This methodology,
In the first instance, the enolisation of ketone 1f18 was
studied. However, under various conditions, no reaction
was observed. A second acetate group was then intro-
duced onto the nitrogen centre by treating 1f with iso-
propenyl acetate in the presence of APTS to afford the
N,N-diacetate derivative 1g in a quantitative yield
(Scheme 1). Using the conditions described for the
D-glucose series, the enolisation of ketone 1g with the
Me3SiCl–NaI–pyridine system at 52 ꢁC in a mixture of
MeCN–pentane was not complete. However, when pen-
tane was replaced by cyclohexane to perform the reac-
tion at 70 ꢁC, a complete conversion was observed
(Table 1, entry 12). Moreover, the thermodynamic enox-
ysilane 2g was the sole compound obtained as a mixture
of E/Z stereoisomers that was directly engaged in the
oxidation reaction using dimethyldioxirane. The reac-
tion was first carried out in the presence of potassium
carbonate (0.5 equiv) as described for other sugar deriv-
atives. In this case, we obtained a mixture of a-hydroxy-
ketones 4g and 13 in a 3:2 ratio (Scheme 5). The
formation of 13 may be explained by the internal migra-
tion of one acetate group from the nitrogen atom to the
free alcohol at the C-1 position probably through a six-
membered transition state. This problem was solved
when the reaction was performed in the absence of
potassium carbonate and after flash chromatography
the desired a-hydroxyketone 4g was obtained in 70%
yield as a single diastereomer.
Further treatment with sodium metaperiodate in
THF–water provided aldehyde 6g, which was converted
for storage into aminal 7g in 65% overall yield from
1g.20 Aldehyde 6g can be regenerated by simple treat-
ment with Dowex H+ resin and can be used directly
without further purification. Aldehyde 6f can be syn-
`
thesised in a two-step sequence from 6g by Zemplen
deacetylation then reacetylation (Ac2O, pyridine) to
OAc O
OAc
OH
OAc
O
OAc
O
AcO
AcO
K2CO3
O
AcO
AcO
AcO
AcO
H
O
N
NAc2
NHAc
O
O
O
O
4g
13
Scheme 5. Formation of 13 by acetate migration.

S. Norsikian et al. / Carbohydrate Research 342 (2007) 2716–2728
2721
Ph
OBn
OBn
N
a, b
a, c
c
O
O
O
BnO
BnO
BnO
BnO
Ph
N
H
OAc
NHAc
14
NHAc
N
15
Ph
O
AcO
AcO
N
NAc2
OH
OAc
7g
Ph
d
OAc
OH
O
O
HO
HO
AcO
AcO
OH
NHAc
16
NHAc
17
Scheme 6. Reagents and conditions: (a) NaOMe, MeOH; (b) NaH, BnBr, DMF (14, 75%); (c) Dowex H+ resin, water–THF; (d) (i) allyl bromide, In,
water–THF; (ii) Ac2O, pyridine (17, 87% over 4 steps).
which does not require the use of the hardly available
perbenzyl glyconolactone, allowed us to prepare
2,3,4,6-tetra-O-benzyl-b-D-glucopyranosylformaldehyde
in nine steps (50% overall yield from D-glucose). The
methodology was then efficiently applied to the prepara-
tion and synthetically useful protected or unprotected
2-acetamido-2-deoxy-b-D-glucopyranosylformaldehydes
in good yields. Further applications of the above
method for the synthesis of more complex C-glycosyl
compounds or C-disaccharides of biological relevance
will be presented in due course.
with graphite-monochromated MoKa radiation (k =
0.71073 A). The temperature of the crystal was main-
˚
tained at the selected value (180 K) by means of a 700
series Cryostream cooling device to within an accuracy
of 1 K. The data were corrected for Lorentz, polarisa-
tion and absorption effects. The structures were solved
by direct methods using SHELXS-97 and refined against
F2 by full-matrix least-squares techniques using SHEL-
XL-97 with anisotropic displacement parameters for all
non-hydrogen atoms. Hydrogen atoms were located on
a difference Fourier map and introduced into the calcu-
lations as a riding model with isotropic thermal para-
meters. All calculations were performed by using the
Crystal Structure crystallographic software package
WINGX. The absolute configuration was determined
by refining the Flack’s parameter using a large of
Friedel’s pairs. The drawing of the molecule was realised
with the help of ORTEP32.
3. Experimental
3.1. General methods and materials
All moisture sensitive reactions were performed under
argon using oven-dried glassware. If necessary, solvents
were dried and distilled prior to use. Reactions were
monitored on Silica Gel plates 60 F254 (E. Merck).
Detection was performed using UV light and/or 5%
H2SO4 in EtOH, followed by heating. Flash chromato-
3.2. General procedure A: enolisation of ketone (1a–e) and
(1g)
1
graphy was performed on silica gel 6–35 lm. H and 13C
To a soln of ketone in 6:5 MeCN–solvent were added
pyridine, TMSCl and then sodium iodide. The soln
was stirred under argon for 12 h at T ꢁC. The reaction
was poured into satd aq NaHCO3 (15 mL) and ex-
tracted with EtOAc (3 · 15 mL). The combined organics
layers were washed with brine (15 mL), dried (Na2SO4),
filtered and concentrated to afford the crude enoxy-
silane, which was used without further purification.
NMR spectra were recorded at rt with Bruker AC
200, 250 or AM 400 spectrometers. Chemical shifts are
1
reported in d versus Me4Si for H NMR spectra (exter-
nal reference for D2O) and relative to the CDCl3 reso-
nance at 77.00 ppm for 13C NMR spectra in CDCl3
and relative to Me4Si for 13C NMR spectra in D2O.
Melting points were measured on a Buchi Melting Point
¨
B-545 apparatus. Optical rotations were measured on an
Electronic Digital Jasco DIP-370 Polarimeter. Mass
spectra were recorded in positive mode on a Finnigan
MAT 95 S spectrometer using electrospray ionisation.
Elemental analyses were performed at the Service Cen-
tral de Microanalyses du CNRS (Gif-sur-Yvette,
France). It is worth to note that the percent oxygen val-
ues are measured with Elementar apparatus using pyro-
lysis and catharometric detection.
3.3. General procedure B: synthesis of a-hydroxyketone
(4a–e), (5b) and (5e)
To a mixture of the crude enol ether (2 mmol) and
potassium carbonate (0.5 equiv) was added a soln of
dimethyldioxirane (0.1 M in acetone, 3 equiv). The soln
was stirred for 3 h at rt, filtered and concentrated. The
residue was dissolved in 3:1 THF–water (4 mL) and aq
HCl (1.5 N, 1 mL) was added. After stirring for 1 h,
the soln was neutralised with satd aq NaHCO3. Brine
X-ray diffraction data for 4a were collected by
using a Kappa X8 APPEX II Bruker diffractometer

2722
S. Norsikian et al. / Carbohydrate Research 342 (2007) 2716–2728
(15 mL) was added and the aq phase was extracted with
EtOAc (3 · 15 mL), dried (MgSO4), concentrated and
purified by flash chromatography.
alytic amount of sodium methoxide (30 mg) was added.
The suspension was stirred for 8 h at rt and concen-
trated to afford 9b. 1H NMR (250 MHz, D2O): d
(ppm) 1.35 (s, 3H, CH3–CO), 1.75 (dd, 1H, J3a,4 10
and J3a,3b 12 Hz, H-3a), 2.20 (d, 1H, J3b,3a 16 Hz, H-
3b), 3.10 (t, 1H, J5,4 = J5,6 10 Hz, H-5), 3.25–3.45 (m,
4H, H-4, H-5, H-6 and H-7), 3.65 (dd, 1H, J9a,8 5,
J9a,9b 12 Hz, H-9a), 3.83 (d, 1H, J9b,9a 12 Hz, H-9b),
3.98 (s, 4H, OCH2CH2O); 13C NMR (62.5 MHz,
D2O): d (ppm) 24.0 (C-1), 39.8 (C-3), 61.3 (C-9), 64.5,
64.8 (OCH2CH2O), 70.2, 73.6, 76.4, 77.8, 79.9 (C-4,
C-5, C-6, C-7, C-8), 109.8 (C-2). The crude residue
was dissolved in anhyd DMF (13 mL) and sodium hy-
dride (60% dispersion in mineral oil, 262 mg, 7.8 mmol)
was added portionwise. The soln was stirred for 20 min
at rt and benzyl bromide (0.8 mL, 7.8 mmol) was intro-
duced over a period of 10 min. After 2 h, MeOH
(0.5 mL) was added. Water (20 mL) was introduced
and the aq phase was extracted with EtOAc
(3 · 20 mL). The combined organic layers were washed
with water (2 · 20 mL) then brine (20 mL) and dried
(MgSO4). After concentration, crude 9c was obtained.
3.4. General procedure C: synthesis of aminals (7a–e),
(7g)
To a soln of a-hydroxyketone (0.5 mmol) in 3:4 THF–
water (3.5 mL) was added sodium metaperiodate. The
mixture was stirred at rt and neutralised with satd aq
NaHCO3. After addition of brine (10 mL) the aq phase
was extracted with EtOAc (3 · 10 mL). The combined
organic phases were washed with brine (2 · 15 mL),
dried (Na2SO4), filtrated and concentrated. After
work-up, toluene (10 mL) and N,N-dibenzylethylene-
diamine (1.05 equiv) were added to the crude aldehyde.
The soln was concentrated under diminished pressure
and toluene (2 · 10 mL) was added and evaporated.
Pure aminal was obtained after flash chromatography.
3.5. General procedure D: synthesis of aldehydes (6a–d)
and (6g)
25
Mp 91–92 ꢁC; ½aꢁD ꢀ9.3 (c 1, CHCl3); mmax (thin film):
1
To a soln of the aminal (0.3 mmol) in 1:1 THF–water
(2 mL) was added Dowex H+ resin and the suspension
was stirred for 4 h at rt. After filtration and concentra-
tion, the residue was used directly (6a, 6c,d and 6f,g)
or purified by flash chromatography (6b).
2871, 1496, 1454, 1360, 1099, 1028, 735, 697 cmꢀ1; H
NMR (250 MHz, CDCl3): d (ppm) 1.45 (s, 3H,
CH3CO), 1.75 (dd, 1H, J3,4 9, J3a,3b 14 Hz, H-3a), 2.10
(d, 1H, J3b,3a 14 Hz, H-3b), 3.28 (t, 1H, J5,4 = J5,6
9 Hz, H-5), 3.40–3.55 (m, 2H, H-4 and H-8), 3.60–3.77
(m, 4H, H-6, H-7, H-9a and H-9b), 3.84–3.94 (m, 4H,
OCH2CH2O), 4.57–4.69 (m, 4H, CH2-Ph), 4.82–4.99
(m, 4H, CH2-Ph), 7.15–7.35 (m, 20H, Ph); 13C NMR
(62.5 MHz, CDCl3): d (ppm) 24.9 (C-1), 39.7 (C-3),
64.4 (OCH2CH2O), 69.0 (C-9), 73.4, 74.9, 75.1, 75.5
(CH2-Ph), 76.3 (C-4), 78.5 (C-7), 78.6 (C-8), 81.9 (C-
5), 87.3 (C-6), 109.2 (C-1), 127.5, 127.6, 127.7, 127.8,
127.9, 128.3, 128.4 (Ph); ESIMS: m/z = 647 (M+Na)+;
Anal. Calcd for C39H44O7: C, 74.98; H, 7.10; O, 18.92.
Found: C, 74.91; H, 7.09. Finally, the residue was dis-
solved in TFA (3 mL), water (200 lL) was added and
the mixture was stirred at rt for 30 min. The soln was
poured into cold satd aq NaHCO3 (10 mL). The organic
phase was extracted with EtOAc (3 · 15 mL), the com-
bined organic layers were washed with brine (15 mL)
and dried (MgSO4). After concentration, the product
was purified by flash chromatography (9:1!4:2 petro-
leum ether–EtOAc) to afford the desired compound 1b
as a white solid (625 mg, 83% over 4 steps). Mp 70–
3.6. 4,8-Anhydro-5,6,7,9-tetra-O-benzyl-1,3-dideoxy-D-
glycero-D-gulo-non-2-ulose (1b)
3.6.1. Procedure 1. A soln of 1a (500 mg, 1.3 mmol)
and ethylene glycol (145 lL, 2.6 mmol) in toluene
(10 mL) containing
a catalytic amount of PPTS
(50 mg, 0.2 mmol) was refluxed while water was contin-
uously removed by means of a Dean Stark trap. After
8 h, toluene was removed under diminished pressure
and replaced by CH2Cl2 (15 mL). Satd aq NaHCO3
(15 mL) was added and the product was extracted with
CH2Cl2 (3 · 15 mL). The combined organic phases were
washed with brine (30 mL), dried (MgSO4) and concen-
1
trated to afford crude 9a. H NMR (250 MHz, CDCl3):
d (ppm) 1.30 (s, 3H, H-1), 1.65 (dd, 1H, J3a,3b 12, J3a,4
1 Hz, H-3a), 1.75 (dd, 1H, J3a,3b 12, J3b,4 7 Hz, H-3b),
1.86–2.05 (m, 12H, CO2CH3), 3.52–3.64 (m, 2H, H-8
and H-4), 3.75–3.90 (m, 4H, OCH2CH2O), 4.01 (dd,
1H, J9a,8 2.5 and J9a,9b 12.5 Hz, H-9a), 4.11 (dd, 1H,
25
72 ꢁC; ½aꢁD ꢀ2.2 (c 1, CHCl3); mmax (thin film): 2871,
1
J9b,8
6
and J9b,9a 12.5 Hz, H-9b), 4.76 (t, 1H,
1716, 1496, 1454, 1359, 1090, 1028, 736, 698 cmꢀ1; H
J5,6 = J5,4 9 Hz, H-5), 4.92 (t, 1H, J7,6 = J7,8 9 Hz,
H-7), 5.08 (t, 1H, J6,5 = J6,7 9 Hz, H-6); 13C NMR
(62.5 MHz, CDCl3): d (ppm) 20.2, 20.3 (4 · CO2CH3),
24.2 (C-3), 39.5 (C-1), 62.2 (C-9), 64.1 (OCH2CH2O),
68.4, 73.9, 74.4, 75.1 (C-4, C-5, C-6, C-7, C-8), 108.3
(C-2), 169.1, 169.3, 169.8, 170.1 (4 · CO2CH3). The
crude residue was dissolved in MeOH (10 mL) and a cat-
NMR (250 MHz, CDCl3): d (ppm) 2.16 (s, 3H, C-1),
2.60 (dd, 1H, J3a,4 8, J3a,3b 16 Hz, H-3a), 2.70 (dd, 1H,
J3b,4 4, J3b,3a 16 Hz, H-3b), 3.38 (m, 1H, H-8), 3.45–
3.55 (m, 1H, H-4), 3.64–3.89 (m, 4H, H-9a, H-9b and
CH2-Ph), 4.5–5.1 (m, 9H, H-5, H-6, H-7 and 3 · CH2-
Ph), 7.2–7.5 (m, 20H, 4 · Ph); 13C NMR (62.5 MHz,
CDCl3): d (ppm) 31.3 (C-1), 45.8 (C-3), 68.6 (C-9),

S. Norsikian et al. / Carbohydrate Research 342 (2007) 2716–2728
2723
73.3, 74.82, 74.85, 75.4 (4 · CH2-Ph), 75.4, 78.2, 78.8,
81.1 (C-5, C-6, C-7, C-8), 87.0 (C-4), 127.5, 127.6,
127.7, 127.8, 128.2, 128.3, 128.32 (C@H Ph), 137.84,
137.91, 137.98, 138.3 (Cq Ph), 206.4 (C-2); ESIMS:
m/z = 603 (M+Na)+; Anal. Calcd for C37H40O6: C,
76.53; H, 6.94; O, 16.53. Found: C, 76.74; H, 7.03; O,
16.45.
1H NMR (400 MHz, CDCl3): d (ppm) 2.25 (s, 3H,
C-1), 3.46 (m, 1H, H-8), 3.58 (t, 1H, J7,6 = J7,8 9.5 Hz,
H-7), 3.59–3.65 (m, 1H, H-9a), 3.64 (dd, 1H, J9b,8 1.7
and J9b,9a 11 Hz, H-9a), 3.72 (dd, 1H, J4,3 2.5 and J4,5
9.5 Hz, H-4), 3.77 (t, 1H, J6,5 = J6,7 9.5 Hz, H-6), 3.89
(t, 1H, J5,6 = J5,4 9.5 Hz, H-5), 4.42–4.46 (br s, 1H,
H-3), 4.47–4.58 (m, 2H, CH2-Ph), 4.62 (d, 1H, J
11 Hz, CH2-Ph), 4.82–4.89 (m, 2H, CH2-Ph), 4.93–5.02
(m, 3H, CH2-Ph), 7.15–7.45 (m, 20H, Ph); 13C NMR
(100 MHz, CDCl3): d (ppm) 25.4 (C-1), 69.0 (C-9),
73.4, 75.2, 75.3, 75.7 (CH2-Ph), 76.9 (C-3), 78.2 (C-5),
78.3 (C-7), 79.2 (C-4), 79.9 (C-8), 87.0 (C-6), 127.6,
127.7, 127.8, 127.9, 128.0, 128.1, 128.4, 128.5, 128.6
(Ph), 138.1, 138.3, 138.4, 138.7 (Cq Ph), 207.1 (C-2);
ESIMS: m/z = 619 (M+Na)+; Anal. Calcd for
C37H40O7: C, 74.47; H, 6.76; O, 18.77. Found: C,
74.56; H, 6.91; O, 18.76.
Aldehyde 6b was obtained according to general proce-
dure C. The reaction was performed on 0.3 g of the mix-
ture of 4b and 5b using NaIO4 (1 g, 4.5 mmol, 9 equiv)
for 18 h. After work-up, the residue was purified by flash
chromatography (4:1 petroleum ether–EtOAc + 0.1%
Et3N) to afford the pure aldehyde 6b (248 mg, 90%).
The NMR data were consistent with those reported in
the literature.9
3.6.2. Procedure 2. A soln of 811 (220 mg, 1 mmol) and
ethylene glycol (130 lL, 2.2 mmol) in 1:1 benzene–
MeCN (6 mL) containing a catalytic amount of PPTS
(50 mg, 0.2 mmol) was refluxed while water was contin-
uously removed by means of a Dean Stark trap. After
20 min, benzene was eliminated, aq NaOH (0.03 M,
10 mL, 0.3 mmol) was introduced and the soln was con-
centrated under diminished pressure. The crude residue
was purified by flash chromatography (5:3:1 EtOAc–i-
PrOH–water) to afford 9b. Compound 9b was dissolved
in anhyd DMF (3 mL) and sodium hydride (60% disper-
sion in mineral oil, 400 mg, 10 mmol) was added
portionwise. The soln was stirred for 20 min at rt before
benzyl bromide (1.2 mL, 10 mmol) was added over a
period of 10 min. The reaction was completed in 2 h
and MeOH (1 mL) was added. After addition of water
(10 mL), the aq phase was extracted with EtOAc
(3 · 20 mL). The combined organics phases were
washed with water (2 · 20 mL) then brine (20 mL), dried
(Na2SO4), filtered and concentrated. Flash chromato-
graphy (4:1 petroleum ether–EtOAc) gave the desired
product 9c (437 mg, 70%). Finally, the product was dis-
solved in TFA (3 mL), water (200 lL) was added and
the mixture was stirred at rt for 30 min. The soln was
poured into satd aq NaHCO3 (10 mL). The aq phase
was extracted with EtOAc (3 · 15 mL), the combined
organic layers were washed with brine (15 mL) and dried
(MgSO4). After concentration, the product was purified
by flash chromatography (9:1!4:1 petroleum ether–
EtOAc) to afford the desired compound 1b as a white
solid (400 mg, 69% over 3 steps). The NMR data were
identical to those previously obtained with procedure 1.
3.8. 3,4,5,7-Tetra-O-acetyl-2,6-anhydro-D-glycero-L-
manno-heptose (6c)
The enolisation reaction was performed on ketone 1c
(94 mg, 0.5 mmol) according to general procedure A
using pyridine (160 lL), TMSCl (260 lL) and then
NaI (300 mg) in 6:5 MeCN–cyclohexane (1.37 mL) at
70 ꢁC. After work-up, general procedure B was applied
to the crude enol ether 2c (0.5 mmol) using DMDO
(15 mL, 3 equiv) and K2CO3 (34.5 mg). Flash chroma-
tography (7:3 petroleum ether–EtOAc) gave 4c as a col-
25
ourless oil (133 mg, 66% from 1c). ½aꢁD +5 (c 1, CHCl3);
1
mmax (thin film): 1758, 1371, 1230, 1053 cmꢀ1; H NMR
(360 MHz, CDCl3): d (ppm) 2.00 (s, 3H, CO2CH3), 2.02
(s, 3H, CO2CH3), 2.05 (s, 3H, CO2CH3), 2.17 (s, 3H,
CO2CH3), 2.29 (s, 3H, C-1), 3.87–3.92 (m, 2H, H-4
and H-8), 4.01–4.15 (m, 3H, H-9a, H-9b and H-3),
5.12 (dd, 1H, J6,7 3 and J6,5 10 Hz, H-6), 5.38–5.50 (m,
2H, H-5 and H-7); 13C NMR (90 MHz, CDCl3): d
(ppm) 20.6, 20.7, 20.8 (4 · CO2CH3), 26.2 (C-1), 61.4
(C-9), 65.9, 67.4 (C-5, C-7), 71.9 (C-6), 73.8 (C-3), 74.7
(C-8), 75.1 (C-4), 170.1, 170.3 (CO2CH3), 207.4 (C-2);
ESIMS: m/z = 427 [(M+Na)+, 100%], ESIHRMS: m/z
427.1202. C17H24O11Na1 requires 427.1211.
Aminal 7c was then synthesised according to general
procedure C. The reaction was performed with crude
4c (0.5 mmol) using NaIO4 (341 mg) for 3 h. After
work-up then treatment with N,N-dibenzylethylene-
diamine, 7c (colourless oil, 213 mg, 70% from 1c) was
obtained after flash chromatography (4:1 petroleum
3.7. Synthesis of 3,4,5,7-tetra-O-benzyl-2,6-anhydro-D-
glycero-D-gulo-heptose (6b) from 1b
The enolisation reaction was performed on ketone 1b
(780 mg, 2 mmol) according to general procedure A
using pyridine (480 lL), TMSCl (760 lL) and then
NaI (900 mg) in 6:5 MeCN–pentane (5.5 mL) at rt.
After treatment, the oxidation reaction was performed
with DMDO (30 mL, 1.5 equiv) according to general
procedure B. Flash chromatography (17:3!7:3 petro-
leum ether–EtOAc) led first to the major diastereoiso-
mer of 4b then a mixture of the minor isomer of 4b with
5b (0.858 g, 72%). For the major isomer: white solid,
mp 108–109 ꢁC; ½aꢁD25 +46.6 (c 1, CHCl3); mmax (thin film):
3425, 2870, 1716, 1454, 1360, 1103, 736, 698 cmꢀ1
;

2724
S. Norsikian et al. / Carbohydrate Research 342 (2007) 2716–2728
25
ether–EtOAc + 0.1% Et3N). ½aꢁD +9.2 (c 1, CHCl3);
afford the desired compound 1b as a white solid (0.78 g,
25
mmax (thin film): 3054, 2986, 1748, 1265, 739, 705 cmꢀ1
;
81% over 2 steps). Mp 79–81 ꢁC; ½aꢁD ꢀ15.0 (c 1,
1H NMR (360 MHz, CDCl3): d (ppm) 1.86 (s, 3H,
CO2CH3), 1.90 (s, 3H, CO2 CH3), 1.96 (s, 3H, CO2
CH3), 1.97 (m, 3H, CO2 CH3), 2.33–2.44 (m, 1H, N–
CH2–), 2.45–2.53 (m, 1H, N–CH2–), 2.75–2.83 (m,
1H, N–CH2–), 2.93 (dt, 1H, J 5.5 Hz, J 7.5 Hz, N–
CH2–), 3.51 (d, 1H, J 13 Hz, CH2-Ph), 3.56 (d, 1H, J
1 Hz, H-1), 3.58 (d, 1H, J 13 Hz, CH2-Ph), 3.71 (dd,
1H, J2,3 9.5 Hz, J2,1 1.5 Hz, H-2), 3.88 (td, 1H, J5,6 1,
J6,7a = J6,7b 6 Hz, H-6), 4.01–4.07 (m, 2H, H-7a and
CH2-Ph), 4.11 (dd, 1H, J7a,6 6, J7a,7b 11 Hz, H-7b),
4.22 (d, 1H, J 13 Hz, CH2-Ph), 5.12 (dd, 1H, J4,5 3.5
and J4,3 10 Hz, H-4), 5.41 (dd, 1H, J5,6 1, J5,4 3.5 Hz,
H-5), 5.90 (t, 1H, J3,4 = J3,2 10 Hz, H-3), 7.20–7.50 (m,
10H, Ph); 13C NMR (90 MHz, CDCl3): d (ppm) 20.5,
20.7, 20.7, 20.8, 21.1 (CH3CO2), 50.7 (CH2–N), 50.9
(CH2–N), 59.5 (CH2-Ph), 59.8 (CH2-Ph), 61.9 (C-7),
66.4 (C-3), 67.8 (C-5), 73.0 (C-4), 73.7 (C-6), 78.4 (C-
2), 85.8 (C-1), 126.7, 127.1, 128.1, 128.2, 128.3, 128.4,
128.8 (Ph), 139.3, 140.0 (Cq Ph), 169.5, 170.3, 170.4
(CO); ESIMS: m/z = 605 [(M+Na)+, 30%]; Anal. Calcd
for C31H38N2O9: C, 63.90; H, 6.57; N, 4.81; O, 24.71.
Found: C, 63.95; H, 6.87; N, 4.78; O, 24.59.
CHCl3); mmax (thin film): 1739, 1369, 1218, 1041 cmꢀ1
;
1H NMR (400 MHz, CDCl3): d (ppm) 1.93 (s, 3H,
CH3), 1.99 (s, 3H, CH3), 2.00 (s, 3H, CH3), 2.01 (s,
3H, CH3), 2.04 (s, 3H, CH3), 2.06 (s, 3H, CH3), 2.12
(s, 3H, CH3), 2.13 (s, 3H, CH3), 2.42 (dd, 1H, J3a,4 3,
J3a,3b 16 Hz, H-3a), 2.61 (dd, 1H, J3b,4 9, J3b,3a 16 Hz,
H-3b), 3.57 (ddd, 1H, J8,9a 2, J8,9b 5, J8,7 10 Hz, H-8),
3.72 (t, 1H, J7,8 = J7,6 10 Hz, H-7), 3.84 (t, 1H,
J50;60a ¼ J5 ;6 b 7 Hz, H-50), 3.89 (td, 1H, J4,3a 2,
J4,3b = J4,5 9 Hz, H-4), 4.01–4.14 (m, 4H, H-9b, H60a
and H-60b), 4.37 (dd, 1H, J9a,8 2, J9b,9a 12 Hz, H-9b),
0
0
4.44 (d, 1H, J1 ;2 8 Hz, H-10), 4.77 (t, 1H, J5,6 = J5,4
0
0
0
0
0
0
9.5 Hz, H-5), 4.92 (dd, 1H, J3 ;4 3; J3 ;2 10:5 Hz, H-
30), 5.07 (dd, 1H, J2 ;1 8; J2 ;3 10:5 Hz, H-20), 5.15 (t,
0
0
0
0
0
0
1H, J6,5 = J6,7 10 Hz, H-6), 5.31 (d, 1H, J4 ;3 3 Hz, H-
40); 13C NMR (90 MHz, CDCl3): d (ppm) 20.4, 20.5,
20.6, 20.7 (7 · CO2CH3), 30.9 (C-1), 45.1 (C-3), 60.8
(C-60), 62.1 (C-9), 66.6 (C-40), 69.0 (C-20), 70.6 (C-30),
70.9 (C-50), 71.8 (C-5), 73.6 (C-6), 73.8 (C-4), 76.3 (C-
7), 77.6 (C-8), 100.9 (C-10), 169.0, 169.9, 170.0, 170.1,
170.2, 170.3 (CO2CH3), 206.4 (C-2); ESIMS:
m/z = 699.3 [(M+Na)+, 100%]; Anal. Calcd for
C29H40O18: C, 51.48; H, 5.96; O, 42.56. Found: C,
51.11; H, 6.04; O, 42.65.
Using general procedure D, aldehyde 6c was ob-
tained: H NMR (500 MHz, CDCl3): d (ppm) 2.00 (s,
1
3H, CO2CH3), 2.07 (s, 6H, 2 · CO2CH3), 2.17 (s, 3H,
CO2CH3), 3.80 (dd, 1H, J2,1 2.0 Hz and J2,3 10.0 Hz,
H-2), 4.01 (t, 1H, J6,7a = J6,7b 7.0 Hz, H-6), 4.15–4.20
(m, 2H, H-7a and H-7b), 5.11 (dd, 1H, J4,5 3, J4,3
10.0 Hz, H-4), 5.36 (t, 1H, J3,4 = J3,2 10.0 Hz, H-3),
5.48 (d, 1H, J5,4 3.0 Hz, H-5), 9.58 (d, 1H, J1,2 2.0 Hz,
H-1); 13C NMR (75 MHz, CDCl3) d (ppm): 20.5, 20.6
(CH3CO2), 61.7 (C-7), 62.6 (C-5), 67.3 (C-3), 71.3 (C-
4), 74.5 (C-6), 80.5 (C-2), 169.8, 169.9, 170.1, 170.4
(CH3CO2), 196.0 (C-1).
3.10. 5-O-(b-D-20,30,40,60-Tetra-O-acetylgalactopyran-
osyl)-3,4,7-tri-O-acetyl-2,6-anhydro-D-glycero-D-gulo-
heptose (6d)
The enolisation reaction was performed on ketone 1d11
(304 mg, 0.45 mmol) according to general procedure A
using pyridine (110 lL), TMSCl (172 lL) and then
NaI (202 mg) in 6:5 MeCN–pentane (1.62 mL) at
52 ꢁC. After work-up, general procedure B was applied
to the crude enol ether 2d (0.45 mmol) using DMDO
(13.5 mL, 3 equiv) and K2CO3 (69 mg). Flash chroma-
tography of the residue (1:1 petroleum ether–EtOAc)
gave 4d (white solid, 4:1 mixture of two diastereoiso-
mers, 210 mg, 68% from 1d). Mp 99–100 ꢁC; mmax (thin
3.9. 7-O-(b-D-20,30,40,60-Tetra-O-acetylgalactopyranosyl)-
5,6,9-tri-O-acetyl-4,8-anhydro-1,3-dideoxy-D-glycero-
D-gulo-non-2-ulose (1d)
To a soln of lactose monohydrate (0.5 g, 1.39 mmol) in
2:1 water–THF (9 mL) was added pentane-2,4-dione
(0.28 mL, 2.77 mmol, 2 equiv) and NaHCO3 (0.47 g,
5.56 mmol, 4 equiv). After heating at 90 ꢁC for 36 h,
the reaction mixture was neutralised with Dowex H+
resin and filtrated. The aq phase was washed with
CH2Cl2 (3 · 10 mL) and was concentrated under dimin-
ished pressure. After co-evaporation with toluene
(3 · 10 mL), the residue was dissolved in 2:1 pyridine–
Ac2O (6 mL) and was stirred for 6 h at rt. After co-evap-
oration with toluene (3 · 10 mL), the residue was taken
up in CH2Cl2 (15 mL) and was washed successively with
satd aq NaHCO3 (10 mL) and brine (10 mL) and dried
(MgSO4). After concentration, the product was purified
by flash chromatography (11:9!2:3 heptane–EtOAc) to
film): 1738, 1386, 1217, 1042 cmꢀ1
;
1H NMR
(400 MHz, CDCl3) for the major diastereoisomer: d
(ppm) 1.95 (s, 3H, CH3), 2.01 (s, 3H, CH3), 2.05–2.08
(m, 12H, 4 · CH3), 2.15 (s, 3H, CH3), 2.25 (s, 3H,
CH3), 3.50 (d, 1H, OH), 3.57 (ddd, 1H, J8,9a 6, J8,9b 2,
J8,7 10 Hz, H-8), 3.72 (t, 1H, J7,8 = J7,6 10 Hz, H-7),
3.84–3.91 (m, 2H, H-4 and H-50), 4.01–4.14 (m, 4H,
H-3, H60a, H-60b and H-9a, ), 4.36 (dd, 1H, J9b,8 2,
J9b,9a 12 Hz, H-9b), 4.47 (d, 1H, J1 ;2 8 Hz, H-10), 4.95
0
0
(dd, 1H, J3 ;4 3; J3 ;2 10:5 Hz, H-30), 5.10 (dd, 1H,
0
0
0
0
J2 ;1 8; J2 ;3 10:5 Hz, H-20), 5.19 (t, 1H, J5,6 = J5,4
10 Hz, H-5), 5.26 (t, 1H, J6,5 = J6,7 10 Hz, H-6), 5.34
0
0
0
0
(dd, 1H, J4 ;5 1; J4 ;3 3 Hz, H-40); 13C NMR (90 MHz,
CDCl3): d (ppm) 20.5, 20.6, 20.7, 20.8 (7 · CO2CH3),
25.7 (C-1), 60.9 (C-60), 62.2 (C-9), 66.6 (C-40), 68.6
0
0
0
0

S. Norsikian et al. / Carbohydrate Research 342 (2007) 2716–2728
2725
(C-5), 69.1 (C-20), 70.7 (C-50), 70.9 (C-30), 74.0 (C-6),
74.8 (C-3), 76.4 (C-7), 77.2 (C-8), 77.5 (C-4), 101.1 (C-
10), 169.0, 169.9, 170.0, 170.1, 170.2, 170.3 (CO2CH3),
206.4 (C-2); ESIMS: m/z = 715 [(M+Na)+, 100%]; ESI-
HRMS: m/z 715.2047. C29H40O19Na1 requires 715.2056.
Aminal 7d was then synthesised according to general
procedure C. The reaction was performed with crude
4d (0.45 mmol) using NaIO4 (289 mg) for 2 h. After
work-up then treatment with N,N-dibenzylethylene-
diamine, 7d (amorphous solid, 213 mg, 70% from 1d)
was obtained after flash chromatography (13:7 petro-
NMR (62.5 MHz, CDCl3): d (ppm) 20.5, 20.6, 20.7,
21.3 (CH3CO2), 60.8 (C-60), 62.0 (C-7), 66.6 (C-40),
67.7 (C-4), 69.0 (C-20), 70.7, 70.8 (C-30, C-50), 72.9 (C-
3), 75.8 (C-5), 76.4 (C-6), 79.7 (C-2), 101.0 (C-10),
169.0, 169.6, 169.7, 169.9, 170.0, 170.2 (CH3CO2),
195.9 (C-1).
3.11. 5,6,7,9-Tetra-O-acetyl-4,8-anhydro-1,3-dideoxy-
D-glycero-D-galacto-non-2-ulose (1e)
A
mixture of 4,8-anhydro-1,3-dideoxy-D-glycero-D-
25
leum ether–EtOAc + 0.05% Et3N). ½aꢁD ꢀ8.2 (c 1,
galacto-non-2-ulose11 (0.31 g, 0.127 mmol) in 2:1 pyri-
dine–Ac2O (4.5 mL) was stirred for 5 h at rt. After
co-evaporation with toluene (3 · 10 mL), the residue
was purified by flash chromatography (13:7!1:1
heptane–EtOAc) to afford the desired compound 1e as
CHCl3); mmax (thin film): 2944, 1739, 1597, 1436, 1368,
1
1218, 1041, 908, 742, 704 cmꢀ1; H NMR (400 MHz,
CDCl3): d (ppm) 1.86 (s, 6H, CO2CH3), 1.92 (s, 3H,
CO2 CH3), 1.99 (s, 3H, CO2 CH3), 2.01 (s, 6H, CO2
CH3), 2.11 (s, 3H, CO2 CH3), 2.39 (td, 1H, J 7, J
9 Hz, N–CH2–), 2.51 (ddd, 1H, J 5, 7, 12 Hz, N–
CH2–), 2.70–2.80 (m, 1H, N–CH2–), 2.87 (td, 1H, J 7,
9.5 Hz, N–CH2–), 3.44 (d, 1H, J 14 Hz, CH2-Ph),
3.47–3.52 (m, 1H, H-6), 3.51 (d, 1H, J 1.5 Hz, H-1),
3.58 (d, 1H, J 14 Hz, CH2-Ph), 3.68 (dd, 1H, J2,3 9 Hz,
J2,1 1.5 Hz, H-2), 3.70 (t, 1H, J5,6 = J5,4 9 Hz, H-5),
25
a white solid (0.50 g, 91%). Mp 137–138 ꢁC; ½aꢁD
ꢀ30.5 (c 1, CHCl3); mmax (thin film): 1740, 1369, 1219,
1042, 907 cmꢀ1; H NMR (250 MHz, CDCl3): d (ppm)
1
1.99 (s, 3H, CH3), 2.05 (s, 3H, CH3), 2.08 (s, 3H,
CH3), 2.17 (s, 3H, CH3), 2.20 (s, 3H, CH3), 2.47 (dd,
1H, J3a,4 4, J3a,3b 17 Hz, H-3a), 2.61 (dd, 1H, J3b,4 9.5,
J3b,3a 17 Hz, H-3b), 3.64–3.75 (m, 1H, H-8), 4.05 (d,
1H, J9a,9b 12 Hz, H-9a), 4.16–4.24 (m, 1H, H-4), 4.27
(dd, 1H, J9a,8 5, J9b,9a 12 Hz, H-9b), 5.11 (dd, 1H, J6,5
1, J6,7 10 Hz, H-6), 5.22 (t, 1H, J7,6 = J7,8 10 Hz, H-7),
5.32 (d, 1H, J5,6 1 Hz, H-5); 13C NMR (62.5 MHz,
CDCl3): d (ppm) 20.3, 20.5 (4 · CO2CH3), 30.4 (C-1),
43.9 (C-3), 62.4 (C-9), 65.8 (C-7), 69.8 (C-5), 71.8 (C-
6), 72.6 (C-4), 76.0 (C-8), 169.5, 169.7, 170.2, 170.4
(CO2CH3), 204.3 (C-2); ESIMS: m/z = 411.1
[(M+Na)+, 100%]; ESIHRMS: m/z 411.1287. C17H24-
O10Na1 requires 411.1267; Anal. Calcd. for C17H24O10:
C, 52.57; H, 6.23; O, 41.20. Found: C, 52.72; H, 6.13;
O, 41.13.
3.83 (t, 1H, J5 ;6 a ¼ J5 ;6 b 7 Hz, H-50), 3.88 (d, 1H, J
13 Hz, CH2-Ph), 3.96 (dd, 1H, J7a,6 4 Hz, J7a,7b 12 Hz,
H-7a), 3.98 (d, 1H, J 13 Hz, CH2-Ph), 4.04 (dd,
0
0
0
0
1H, J6 a;5 7:5 Hz, J6 a;6 b 11 Hz, H-60a), 4.11 (dd, 1H,
0
0
0
0
J6 bꢀ5 6:5 Hz, J6 a;6 b 11 Hz, H-60b), 4.45 (d, 1H,
0
0
0
0
J1 ;2 8 Hz, H-10), 4.52 (dd, 1H, J7b,6 2, J7b,7a 12 Hz, H-
0
0
7b), 4.91 (dd, 1H, J3 ;4 3; J3 ;2 10:5 Hz, H-30), 5.07
0
0
0
0
(dd, 1H, J2 ;1 8; J2 ;3 10:5 Hz, H-20), 5.19 (t, 1H,
0
0
0
0
J3,2 = J3,4 9 Hz, H-3), 5.29 (d, 1H, J4 ;3 3 Hz, H-40),
5.45 (t, 1H, J4,3 = J4,5 9 Hz, H-4), 7.10–7.40 (m, 10H,
Ph); 13C NMR (100 MHz, CDCl3): d (ppm) 20.5, 20.6,
20.9, 21.0 (7 · CO2CH3), 50.7, 50.8 (2 · CH2–N), 59.2,
60.0 (2 · CH2Ph), 60.7 (C-60), 61.9 (C-7), 66.6 (C-40),
69.1 (C-20), 69.5 (C-4), 70.5 (C-50), 71.0 (C-30), 75.0
(C-3), 76.3 (C-5, C-6), 78.1 (C-2), 85.1 (C-1), 101.1 (C-
10), 126.8, 127.1, 128.2, 128.3, 128.9 (CH Ph), 139.1,
139.8 (Cq Ph), 169.0, 169.7, 170.1, 170.2, 170.3
(CO2CH3); ESIMS: m/z = 893.3 [(M+Na)+, 30%]; ESI-
HRMS: m/z 893.3309; C43H54O17N2Na1 requires
893.3315. Anal. Calcd for C43H54N2O17: C, 59.30; H,
6.25; N, 3.22; O, 31.23. Found: C, 59.25; H, 6.44; N,
3.21; O, 30.97.
0
0
3.12. 5,6,7,9-Tetra-O-acetyl-4,8-anhydro-1-deoxy-D-
erythro-L-gluco-non-2-ulose and 5,6,7,9-tetra-O-acetyl-
4,8-anhydro-1-deoxy-D-erythro-L-manno-non-2-ulose
as a mixture (4e) and 5,6,7,9-tetra-O-acetyl-4,8-anhydro-
3-deoxy-D-glycero-D-galacto-non-2-ulose (5e)
The enolisation reaction was performed on ketone 1e
(400 mg, 1.03 mmol) according to general procedure A
using pyridine (250 lL), TMSCl (390 lL) and then
NaI (460 mg) in 6:5 MeCN–cyclohexane (3.8 mL) at
70 ꢁC. After work-up, general procedure B was applied
to the crude enol ether 2e using DMDO (31 mL,
3 equiv) and K2CO3 (71 mg). Flash chromatography
(7:3!1:1 petroleum ether–EtOAc) gave first 4e (3:2 mix-
ture of diastereoisomers, 289 mg, 69% from 1e) followed
with 5e (59 mg, 14%). The major isomer of 4e can be
recrystallised in EtOAc: white solid, mp 163–164 ꢁC;
Using general procedure D, aldehyde 6d was ob-
tained: 1H NMR (400 MHz): d (ppm) 2.05 (s, 3H,
CO2CH3), 2.11–2.18 (m, 9H, 3 · CO2CH3), 2.21–2.27
(m, 6H, CO2CH3), 2.44 (s, 3H, CO2CH3), 3.75–3.82
(m, 1H, H-6), 3.88 (d, 1H, J2,3 9 Hz, H-2), 3.90 (t, 1H,
J5,4 = J5,6 10 Hz, H-5), 3.95–4.01 (m, 1H, H-50),
4.14–4.28 (m, 3H, H-7a, H60a and H-60b), 4.56–4.64
(m, 2H, H-2 and H-7b), 5.06 (dd, 1H,
25
J3 ;4 3; J3 ;2 10:5 Hz, H-30), 5.14–5.24 (m, 2H, H-4,
and H-20), 5.36 (t, 1H, J3,4 = J3,2 8.0 Hz, H-3), 5.25 (d,
½aꢁD +49.3 (c 1, CHCl3); mmax (thin film): 3409, 1722,
0
0
0
0
1371, 1230, 1102, 1045, 962, 909, 747, 709 cmꢀ1 1H
;
1H, J4 ;3 3 Hz, H-40), 9.59–9.63 (m, 1H, H-7); 13C
NMR (400 MHz, CDCl3): d (ppm) 1.95 (s, 3H,
0
0

2726
S. Norsikian et al. / Carbohydrate Research 342 (2007) 2716–2728
CO2CH3), 1.99 (s, 3H, CO2CH3), 2.05 (s, 3H, CO2CH3),
2.10 (s, 3H, CO2CH3), 2.36 (s, 3H, C-1), 3.69–3.75 (m,
2H, H-8 and OH), 4.05 (dd, 1H, J4,5 1, J4,3 6 Hz, H-
4), 4.21 (dd, 1H, J9a,8 2.5, J9a,9b 12 Hz, H-9a), 4.24–
4.30 (m, 2H, H-9b, H-3), 5.03 (dd, 1H, J6,5 3, J6,7
10 Hz, H-6), 5.23 (t, 1H, J7,8 = J7,6 10 Hz, H-7), 5.54
(dd, 1H, J5,4 1, J5,6 3 Hz, H-5); 13C NMR (100 MHz,
CDCl3): d (ppm) 20.1, 20.5, 20.6, 20.7 (4 · CO2CH3),
27.4 (C-1), 62.4 (C-9), 65.9 (C-7), 66.0 (C-5), 71.6 (C-
6), 74.4 (C-3), 76.8 (C-8), 77.5 (C-4), 169.4, 169.6,
169.9, 170.5 (CO2CH3), 207.8 (C-2); ESIMS: m/z =
427 [(M+Na)+, 100%]; ESIHRMS: m/z 427.1211.
C17H24O11Na1 requires 427.1211; Anal. Calcd for
C17H24O11: C, 50.49; H, 5.98; O, 43.52. Found: C,
128.2, 128.3, 128.4, 128.8 (Ph), 138.7 (Cq Ph), 155.0
(C-2), 169.3, 170.0, 170.2 (CO); ESIMS: m/z = 523
[(M+H)+, 30%]. Compound 7e: mmax (thin film): 2944,
1
1740, 1598, 1434, 1369, 1220, 1041, 910, 742 cmꢀ1; H
NMR (400 MHz, CDCl3): d (ppm) 1.99 (s, 3H,
CO2CH3), 2.02 (s, 3H, CO2CH3), 2.06 (s, 3H, CO2CH3),
2.14 (s, 3H, CO2CH3), 2.64–2.82 (m, 4H, N–CH2–),
3.54–3.60 (m, 3H, CH2Ph and H-1), 3.68–3.73 (m, 2H,
CH2Ph and H-2), 3.77 (ddd, 1H, J6,7a 2, J6,7b 6, J6,5
9 Hz, H-6), 4.19 (dd, 1H, J7a,6 2, J7a,7b 12 Hz, H-7a),
4.26 (dd, 1H, J7b,6 6, J7a,7b 12 Hz, H-7b), 4.34 (d, 1H,
J 13 Hz, CH2Ph), 5.13 (dd, 1H, J4,3 3, J4,5 9 Hz, H-4),
5.29 (t, 1H, J5,4 = J5,6 9 Hz, H-5), 5.91 (d, 1H, J3,4
3 Hz, H-3), 7.20–7.50 (m, 10H, Ph); 13C NMR
(90 MHz, CDCl3): d (ppm) 20.6, 20.7, 20.9 (CH3CO2),
49.5 (CH2–N), 49.7 (CH2–N), 60.4 (CH2-Ph), 60.7
(CH2-Ph), 63.3 (C-7), 66.6 (C-5), 69.2 (C-3), 72.7 (C-
4), 76.5 (C-6), 81.4 (C-2), 83.6 (C-1), 126.9, 127.2,
128.2, 128.3, 128.7, 130.0 (Ph), 138.7, 138.9 (Cq Ph),
169.8, 170.1, 170.2, 170.8 (CO); ESIMS: m/z = 605
[(M+Na)+, 100%]; ESIHRMS: m/z 605.24926.
C31H38O9N2Na1 requires 605.2470.
25
50.33; H, 5.94; O, 43.31. Compound 5e: ½aꢁD ꢀ43.8 (c
1, CHCl3); mmax (thin film): 2954, 1737, 1371, 1219,
1044, 962, 906, 734 cmꢀ1; 1H NMR (400 MHz, CDCl3):
d (ppm) 1.94 (s, 3H, CO2CH3), 2.00 (s, 3H, CO2CH3),
2.04 (s, 3H, CO2CH3), 2.14 (s, 3H, CO2CH3), 2.36–
2.43 (dd, 1H, J3a,4 4, J3a,3b 16 Hz, H-3a), 2.69–2.77
(dd, 1H, J3b,4 9, J3b,3a 16 Hz, H-3b), 3.65 (ddd, J8,9a 2,
J8,9b 6, J8,7 10 Hz, 1H, H-8), 4.03 (dd, 1H, J9a,8 2,
J9a,9b 12 Hz, H-9a), 4.17–4.24 (m, 4H, H-4, H-9b, H-
1a and H-1b), 5.07 (dd, 1H, J6,5 3, J6,7 10 Hz, H-6),
5.17 (t, 1H, J7,6 = J7,8 10 Hz, H-7), 5.31 (d, 1H, J5,6
3 Hz, H-5); 13C NMR (100 MHz, CDCl3): d (ppm)
20.4, 20.6 (4 · CO2CH3), 39.5 (C-3), 62.4 (C-9), 65.8
(C-7), 68.8 (C-1), 69.8 (C-5), 71.9 (C-6), 72.6 (C-4),
76.2 (C-8), 169.6, 169.9, 170.4, 170.6 (CO2CH3), 206.4
(C-2); ESIMS: m/z = 427 [(M+Na)+, 100%]; ESI-
HRMS: m/z 427.1211. C17H24O11Na1 requires 427.1211.
3.14. 5-N-Acetylacetamido-6,7,9-tri-O-acetyl-4,8-
anhydro-1,5-dideoxy-D-erythro-L-talo-non-2-ulose (4g)
and 5-acetamido-6,7,9-tri-O-acetyl-4,8-anhydro-1,5-di-
deoxy-D-erythro-L-talo-non-2-ulose (13)
The enolisation reaction was performed on 1g (0.429 g,
1 mmol) according to general procedure A in 6:5
MeCN–cyclohexane (2.75 mL) using pyridine (0.4 mL),
TMSCl (0.64 mL) and NaI (0.74 g) for a night at
70 ꢁC. To this crude residue was added DMDO
(30 mL, 0.1 M in acetone, 3 equiv). The soln was stirred
for 2 h at rt and concentrated. Flash chromatography
(1:1 petroleum ether–EtOAc + 0.1% NEt3) gave 4g
3.13. Bis(phenylmethyl)imidazolidine of the 3,4,5,7-tetra-
O-acetyl-2,6-anhydro-D-glycero-D-galacto-heptose (7e)
Aminal 7e was then synthesised according to general
procedure C. The reaction was performed with crude
4e (75.6 mg, 0.159 mmol) using NaIO4 (120 mg) for
3 h. After work-up, treatment with N,N-dibenzylethyl-
enediamine, then flash chromatography (17:3 toluene–
EtOAc), 12 (22.7 mg, 27%) closely followed by 7e
(47.6 mg, 51% from 1e) were obtained. Compound 12:
mmax (ATR-FT IR, diamond prism): 2923, 1741, 1367,
20
(0.311 g, 70%): ½aꢁD +2.4 (c 1, CHCl3); mmax (thin film):
3465, 1749, 1717, 1368, 1226, 1047 cmꢀ1 1H NMR
;
(250 MHz, CDCl3):
d (ppm) 1.92–2.00 (m, 9H,
3 · CH3), 2.15 (s, 3H, CH3), 2.29 (s, 3H, CH3), 2.41 (s,
3H, CH3), 3.69 (ddd, 1H, J8,9a 2.5, J8,9b 6, J8,7 9.5 Hz,
H-8), 3.74–3.82 (br s, 1H, OH), 3.91 (dd, 1H, J9a,8 2.5,
J9a,9b 13 Hz, H-9a), 3.97–4.06 (m, 2H, H-5 and H-3),
4.08 (dd, 1H, J9b,8 6, J9a,9b 13 Hz, H-9b), 4.92 (dd, 1H,
J7,8 9, J7,6 10 Hz, H-7), 5.02 (dd, 1H, J4,3 2.5, J4,5
10 Hz, H-4), 5.76 (dd, 1H, J6,5 9, J6,7 10 Hz, H-6); 13C
NMR (90 MHz, CDCl3): d (ppm) 20.3, 24.6, 24.8, 27.5
(CH3), 58.0 (C-3), 62.4 (C-9), 69.6 (C-7), 70.9 (C-6),
75.1 (C-5), 76.2 (C-4 and C-8), 169.6, 169.7, 170.4,
174.6, 175.2, (5 · CO2CH3), 205.0 (C-2); ESIMS:
m/z = 468 [(M+Na)+,100%]; Anal. Calcd. for
C19H27O11N: C, 51.23; H, 6.11; O, 39.51; N, 3.14.
Found: C, 50.97; H, 6.12; O, 39.74; N, 2.93. If the oxi-
dation of 1g is carried out in the presence of K2CO3, a
1
1218, 1048, 909, 741, 699 cmꢀ1; H NMR (400 MHz,
CDCl3): d (ppm) 2.03–2.08 (m, 9H, CO2CH3), 2.56–
2.62 (m, 2H, N–CH2–), 3.04–3.11 (m, 2H, N–CH2–),
3.51 (d, 1H, J 13 Hz, CH2-Ph), 3.53 (d, 1H, J 13 Hz,
CH2-Ph), 3.60 (s, 1H, H-1), 3.93 (d, 1H, J 13 Hz,
CH2-Ph), 3.96 (d, 1H, J 13 Hz, CH2-Ph), 4.21–4.41 (m,
3H, H-6, H-7a and H-7b), 5.10 (d, 1H, J3,4 4 Hz, H-3),
5.19 (dd, 1H, J5,4 4, J5,6 6 Hz, H-5), 5.90 (t, 1H,
J4,5 = J4,3 4 Hz, H-4), 7.20–7.50 (m, 10H, Ph); 13C
NMR (90 MHz, CDCl3): d (ppm) 20.4, 20.5, 20.8
(CH3CO2), 50.4 (CH2–N), 50.5 (CH2–N), 57.1 (CH2-
Ph), 59.8 (CH2-Ph), 61.1 (C-7), 67.0, 67.1 (C-4, C-5),
73.8 (C-6), 84.8 (C-1), 98.1 (C-3), 126.7, 127.1, 128.1,
20
substantial amount of 13 is formed. ½aꢁD ꢀ32.8 (c 1,
CHCl3); mmax (ATR-FT IR, diamond prism): 2988,

S. Norsikian et al. / Carbohydrate Research 342 (2007) 2716–2728
2727
1731, 1651, 1540, 1364, 1219, 1038 cmꢀ1
;
1H NMR
www.ccdc.cam.ac.uk). Typical procedures for the prepa-
(400 MHz, CDCl3): d (ppm) 1.86 (s, 3H, CH3), 1.99–
2.04 (m, 9H, 3 · CH3), 2.11 (s, 3H, CH3), 2.24 (s, 3H,
CH3), 3.61 (ddd, 1H, J8,9a 2.5, J8,9b 6, J8,7 9.5 Hz, H-
8), 3.87 (dd, 1H, J4,3 2.5, J4,5 10 Hz, H-4), 4.05 (dd,
1H, J9a,8 2.5, J9a,9b 13 Hz, H-9a), 4.17 (dd, 1H, J9b,8 6,
J9b,9a 13 Hz, H-9b), 4.37 (q, 1H, J5,4 = J5,6 = J5,NH
10 Hz, H-5), 4.98 (d, 1H, J4,3 2.5 Hz, H-4), 5.03 (t,
1H, J7,8 = J7,6 10 Hz, H-7), 5.08 (t, 1H, J6,5 = J6,7
10 Hz, H-6), 5.96 (d, 1H, J 10 Hz, NH); 13C NMR
(100 MHz, CDCl3): d (ppm) 20.5, 20.6, 20.7, 22.9, 26.9
(CH3), 49.2 (C-5), 62.3 (C-9), 68.6 (C-7), 74.0 (C-6),
75.8 (C-3), 76.1 (C-4), 78.7 (C-8), 169.3, 170.0, 170.4,
171.0, 171.3 (CO2CH3), 206.3 (C-2); ESIMS: m/z =
468 [(M+Na)+,100%]; ESIHRMS: m/z 468.1486.
C19H27O11N1Na1 requires 468.1476; Anal. Calcd for
C19H27O11N: C, 51.23; H, 6.11; O, 39.51; N, 3.14.
Found: C, 50.94; H, 6.11; O, 39.43; N, 3.03.
ration of 6a,b, 6f,g, 10, 11, 15 and 17 and their analysis
1
data, H and 13C NMR spectra for 7e and 12. Supple-
mentary data associated with this article can be found,
in the online version, at doi:10.1016/j.carres.
2007.09.002.
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Complete crystallographic data for the structural analy-
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