Stereoselective synthesis of β-D-GlcNAc-(1→4)-D-Glc disaccharide starting from lactose

Article abstract of DOI:10.1016/j.carres.2014.01.020

The stereoselective preparation of the β-D-GlcNAc-(1→4)-D-Glc disaccharide starting from known 4-O-[6-O-(1-methoxy-1-methylethyl)-3,4-O- isopropylidene-β-D-talopyranosyl]-2,3:5,6-di-O-isopropylidene-aldehydo-D- glucose dimethyl acetal (2), in turn easily obtained from lactose, is reported. Key steps of this new procedure, that avoids the glycosylation reaction, are (a) a first epimerization at C-4' through an unusual procedure involving a completely stereospecific hydroboration-oxidation of the enol ether group of the hex-4-enopyranoside 4, obtained from 3 by base promoted acetone elimination, (b) an amination with inversion by S reaction on an imidazylate intermediate, and, finally, (c) N-acetylation followed by complete deprotection.

Full text of DOI:10.1016/j.carres.2014.01.020

Carbohydrate Research 388 (2014) 44–49
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Stereoselective synthesis of b-D-GlcNAc-(1 ? 4)-D-Glc disaccharide
starting from lactose q
⇑
Lorenzo Guazzelli , Giorgio Catelani, Felicia D’Andrea , Tiziana Gragnani
Dipartimento di Farmacia, Università di Pisa, via Bonanno 33, I-56126 Pisa, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
The stereoselective preparation of the b-
D
-GlcNAc-(1 ? 4)-
D
-Glc disaccharide starting from known
-talopyranosyl]-2,3:5,6-di-O-isopropyli-
-glucose dimethyl acetal (2), in turn easily obtained from lactose, is reported. Key steps
Received 16 December 2013
Accepted 24 January 2014
Available online 19 February 2014
4-O-[6-O-(1-methoxy-1-methylethyl)-3,4-O-isopropylidene-b-
dene-aldehydo-
D
D
of this new procedure, that avoids the glycosylation reaction, are (a) a first epimerization at C-40 through
an unusual procedure involving a completely stereospecific hydroboration–oxidation of the enol ether
group of the hex-4-enopyranoside 4, obtained from 3 by base promoted acetone elimination, (b) an
amination with inversion by SN2 reaction on an imidazylate intermediate, and, finally, (c) N-acetylation
followed by complete deprotection.
Keywords:
b-D-GlcNAc-(1 ? 4)-D-Glc disaccharide
Lactose
Epimerization
Ó 2014 Elsevier Ltd. All rights reserved.
Amination with inversion
1. Introduction
OH-4.9b–d Interestingly, some derivatives of this disaccharide have
been considered recently for their aphicidal activity.9a
N-Acetylhexosamines are an important class of monosaccha-
rides found in many types of natural bioactive compounds.1 They
are present in different types of glycoconjugates (glycolipids, lipo-
polysaccharides, and proteins),2 glycosaminoglycans (heparin,
dermatan, chondroitin, and hyaluronic acid),3 blood group deter-
minants,4 and in the antigenic determinant of various pathogens.5
Owing to the difficulties in the stereoselective chemical formation
The synthesis of the target disaccharide started from the mixed
tetra-acetonide b-D-talopyranosyl disaccharide 2, easily obtained
in high yield by C-20 epimerization of corresponding lactose
derivative 1 (Fig. 1).10
The planned approach utilizes two stereocontrolled procedures:
epimerization of C-40 and amination with inversion of configura-
tion at C-20, as outlined in Chart 1.
of 1,2-cis-hexosaminyl bonds (b-
have directed our attention to an approach involving regio- and
stereoselective manipulations of b-
-galactopyranosides.7 Lactose
is a cheap and naturally abundant disaccharide which can be
transformed into a number of useful analogues such as b- -Man-
NAc-(1 ? 4)- -Glc, and b- -TalNAc-(1 ? 4)-
-Glc.7a Recently, the
synthesis of b- -GalNAc-(1 ? 4)- -Glc disaccharide from lactose
has also been performed.8 The preparation of a further hexosami-
nyl analogue of the series, that contains the b- -GlcNAc unit, is
D-manno and b-D
-talo series),6 we
2. Results and discussion
D
The first transformation involves as key step the regio- and ster-
eoselective hydroboration–oxidation of the intermediate vinyl
ether 4 (Scheme 1). Compound 2 was transformed into the com-
pletely protected derivative 3 by Williamson p-methoxybenzyla-
tion of 20-OH followed by selective and mild acidic hydrolysis (5%
aq HCl) of the 60-O-methoxyisopropyl acetal and finally 60-O-ben-
zylation. Compound 3 was obtained in good overall yield (83%)
with only one purification step.
The acetone elimination reaction was carried out according to
the conditions previously optimised for the talo series.11 Treatment
of compound 3 with t-BuOK in THF at reflux gave the correspond-
ing vinyl ether in high yield which was directly subjected to a stan-
dard benzylation reaction to afford 4 in 77% yield over two steps.
The elimination reaction required milder conditions with respect
D
D
D
D
D
D
D
reported here, starting from an intermediate obtained in our previ-
ous work.7,8 This approach avoids the glycosylation step, while
previous syntheses of the b-D-GalNAc-(1 ? 4)-D-Glc disaccharide
all involved the coupling of a suitably protected glucosamine
donor with a glucopyranoside acceptor selectively deprotected on
q
Part 30 of the series ‘Chemical Valorisation of Milk-derived Carbohydrates’. For
part 28, see Ref. 11. Ref. 17 could be considered as the part 29.
⇑
to those used for 3,4-O-isopropylidene-D-galactopyranoside
Corresponding author. Tel.: +39 0502219700; fax: +39 050700.
analogues.12 The enhanced reactivity of the talo series is probably
related to the unfavourable syn interaction between the axial
E-mail address: felicia.dandrea@farm.unipi.it (F. D’Andrea).
Present address: Centre for Synthesis and Chemical Biology, University College
Dublin, Belfield, Dublin 4, Ireland.
http://dx.doi.org/10.1016/j.carres.2014.01.020
0008-6215/Ó 2014 Elsevier Ltd. All rights reserved.

L. Guazzelli et al. / Carbohydrate Research 388 (2014) 44–49
45
O
O
O
OC(OMe)Me2
CMe2
OC(OMe)Me2
CMe2
O
O
O
OH
O
O
O
Ref 10
(92%)
Me2C
Me2C
O
Lactose
O
O
O
OH
O
CMe2
O
CMe2
(MeO)2CH
2
(MeO)2CH
1
O
Figure 1. Transformation of lactose into talopyranosyl derivative 2.
OH
OP
OP
OP
PO
OH
OH
O
O
O
HO
HO
OR
NHAc
β-D-GlcNAcp
PO
PO
OR
OR
β-D-Manp
β-D-Talp
Chart 1. Retrosynthetic approach to a b-D-N-acetylglucosamine glycosyl unit starting from a b-D-talopyranoside.
2-OR group and the 3,4-O-isopropylidene ring. The high strain re-
lease is presumably the reason for the observed complete regiose-
lective elimination of acetone. It is also interesting to pinpoint that
starting from the talo series, the regioselective preparation of hexe-
nopyranosides can now be achieved by two complementary routes.
We recently reported the high yielding NaH/Im2SO2 mediated
then subjected to a SN2 displacement with NaN3 in DMF at
100 °C, and afforded the azido derivative in 92% yield
9
0
0
0
0
(J1 ,2 7.8 Hz, J2 ,3 9.1 Hz). This result confirms the usefulness of
the imidazylate leaving group in comparison with other aryl and
alkyl sulfonates14 for performing efficient substitution in position
2 of a pyranoside. The first step of the deprotection strategy con-
sisted of a hydrogenolysis (H2, Pd/C) in the presence of Ac2O. These
conditions allowed for benzyl group removal, reduction of the
azido function, and direct N-acetylation.
preparation of 4-deoxy-D
-threo-hex-3-enopyranosides,10,13 while
here an approach to the 4-deoxy-D-erythro-hex-4-enopyranoside
is described.
The C-40 epimerization was accomplished with the hydrobora-
tion–oxidation reaction ((a) BH.3SMe2 in THF; (b) H2O2/NaOH/
H2O; 80% yield). The subsequent benzylation reaction of 5 afforded
6 in 93% yield and the coupling constant pattern confirmed the
The target compound 11 was finally obtained by complete
deprotection of 10 via acidic hydrolysis of all acetals using 80%
aq AcOH at 80 °C: this exposes the C-1 aldehyde group and thus
a concomitant six-membered ring closure occurs. The structure
0
0
0
0
manno configuration (J3 ,4 9.4 Hz, J4 ,5 9.6 Hz). The regioselectivity
of the hydroboration step is not surprising in light of the polarity
of the vinyl ether double bond. The complete stereoselectivity ob-
tained is attributed to the orientation of the substituents, and in
particular the axial 20-OR group, which all shield the beta face from
the borane coordination.
of 11 as well as its anomeric composition (a/b ratio about 2:3)
was established on the basis of its NMR spectra. The 13C NMR
signals (see Table 1) were assigned by comparison with those of
a
-, b-cellobiose15 and with those of methyl 2-acetamido-2-
deoxy-b-
In conclusion, we reported an easy access to the b-
(1 ? 4)- -Glc disaccharide starting from lactose. This approach is
D
-glucopyranoside.16
D-GlcNAc-
The orthogonal p-methoxybenzyl group was removed using
DDQ in a mixture of CH2Cl2–H2O (76% yield) and the leaving group
was then introduced by treating 7 with imidazyl sulfate (Im2SO2)
and NaH in DMF at ꢀ30 °C (Scheme 2). The corresponding imidazy-
late 8, isolated pure by flash chromatography in 83% yield, was
D
based on high yielding and stereoselective manipulations of the
natural disaccharide skeleton and avoids the time consuming clas-
sical preparation of protected monosaccharide donor and acceptor.
In addition, it bypasses the difficulties previously encountered in
O
OBn
OPMB
OMIP
O
O
O
CMe2
O
OBn
OPMB
CMe2
CMe2
O
O
O
OH
O
O
a
O
Me2C
O
Me2C
b
O
O
O
O
O
BnO
O
CMe2
O
CMe2
O
CMe2
(MeO)2CH
(MeO)2CH
(MeO)2CH
4
O
O
3
2
c
O
O
OBn
OBn
CMe2
CMe2
O
OPMB
O
OPMB
O
O
d
HO
BnO
BnO
O
O
BnO
O
CMe2
O
CMe2
(MeO)2CH
(MeO)2CH
6
O
O
5
Scheme 1. Stereoselective synthesis of 4’-O-(3,4,6-tri-O-benzyl-2-O-p-methoxybenzyl-b-D-mannopyranosyl)-2,3:5,6-di-O-isopropylidenealdehydo-D-glucose dimethyl acetal
(6). Reagents and conditions: (a) (1) PMBCl, NaH, DMF, room temp, 2 h; (2) CH2Cl2 and 5% aq HCl; (3) BnBr, NaH, DMF, room temp, 12 h, (83%); (b) (1) t-BuOK, THF, reflux,
20 min; (2) BnBr, NaH, DMF, room temp, 12 h (77%); (c) BH3 Me2S (5 M, Et2O), THF, room temp, 5 h, then H2O, 10% NaOH, 35% aq H2O2, room temp, 2 h (80%); (d) BnBr, NaH,
DMF, room temp, 12 h (93%).

46
L. Guazzelli et al. / Carbohydrate Research 388 (2014) 44–49
O
O
O
O
O
OBn
OR
CMe2
OBn
OSO2Im
CMe2
O
CMe2
OBn
O
O
O
O
O
b
c
BnO
BnO
BnO
BnO
BnO
BnO
O
O
O
O
CMe2
N3
O
CMe2
O
CMe2
(MeO)2CH
(MeO)2CH
(MeO)2CH
O
9
6: R=PMB
7: R=H
8
a
d
O
CMe2
O
OH
OH
O
OH
e
O
HO
HO
HO
O
OH
O
HO
HO
O
NHAc
O
CMe2
NHAc
11
OH
(MeO)2CH
O
10
Scheme 2. Synthesis of b-D-GlcNAcp-(1 ? 4)-D-Glcp disaccharide from derivative 6. Reagents and conditions: (a) DDQ, 18:1 CH2Cl2–H2O, room temp, 1 h (76%); (b) Im2SO2,
NaH, DMF, ꢀ30 °C, 1 h (83%); (c) NaN3, DMF, 100 °C, 45 min (92%); (d) H2, 10% Pd/C, 1:3 EtOAc–EtOH, Ac2O, room temp, 48 h (53%); (e) 80% aq AcOH, 80 °C, 3 h (87%).
Table 1
13C NMR chemical shifts of
a- and b-11 and related compounds
Compound
C-10
C-20
C-30
C-40
C-50
C-60
C-1
C-2
C-3
C-4
C-5
C-6
a
-Cellobiosea
b-Cellobiosea
Me b-
-GlcNAcpb
-11c
b-11c
103.3
103.3
102.8
102.3
102.3
74.1
74.1
57.9
56.4
56.4
76.5
76.5
74.8
74.3
74.3
70.4
70.4
70.8
70.6
70.6
76.8
76.8
76.8
76.7
76.7
61.6
61.6
61.6
61.4
61.4
92.7
96.6
72.3
74.9
72.3
75.3
79.6
79.5
71.0
75.6
61.1
61.1
D
a
92.5
96.5
72.3
74.5
72.3
80.7
80.3
71.5
60.9
61.0
75.3d
75.2d
a
b
c
Spectra taken in D2O with 1,4-dioxane (d 67.40) as internal reference (Ref. 15).
Spectra taken in D2O with acetone (d 30.89) as internal reference (Ref. 16).
Spectra taken in D2O with TMSP as internal reference.
d
Assignments may be reversed.
the optimization of the glycosylation reaction with glucosamine
donors.9a–d
An undeniable role, in the reaction pathway here reported, is
played by the axial 20-OR group which is involved both in the
regioselective hex-4-enopyranoside formation as well as in the
stereoselective C-40 epimerization.
uct (Rf 0.32). The two phases were separated, the aqueous phase
was further extracted with CH2Cl2 (20 mL) and the collected organ-
ic extracts were neutralized with satd aq NaHCO3 (30 mL). The or-
ganic phases were dried, filtered and concentrated under
diminished pressure. The crude residue was dissolved in dry
DMF (25 mL) and added to a suspension of pre-washed (hexane)
NaH (60% in mineral oil, 318 mg, 7.95 mmol) in dry DMF (10 mL)
cooled to 0 °C. The mixture was warmed to room temperature
and stirred for 20 min, cooled again to 0 °C and then treated with
BnBr (0.57 mL, 4.7 mmol). The mixture was allowed to reach room
temperature and further stirred until the starting material (Rf 0.32)
was consumed (12 h, TLC, 3:7 hexane–EtOAc). MeOH (1 mL) and
water (20 mL) were slowly added at 0 °C, and the mixture was ex-
tracted with CH2Cl2 (4 ꢁ 20 mL). The collected organic layers were
dried, filtered, and concentrated under diminished pressure. The
residue was purified by flash chromatography over silica gel, elut-
ing with 7:3 hexane–EtOAc, to give 3 (2.37 g, 83% yield) as a clear
3. Experimental
3.1. General methods
General methods are those reported in Ref. 7b. Compound 2
was prepared according to the reported procedures.10
3.2. 4-O-(6-O-Benzyl-3,4-O-isopropylidene-2-O-p-
methoxybenzyl-b-
D-talopyranosyl)-2,3:5,6-di-O-isopropylidene-
aldehydo- -glucose dimethyl acetal (3)
D
syrup; Rf 0.18 (7:3 hexane–EtOAc); [
a]
ꢀ7.41 (c 1.08; CHCl3); 1H
D
NMR (CD3CN): d 7.36–7.30 (m, 7H, Ar-H), 6.88–6.82 (m, 2H, Ar-
A suspension of pre-washed (hexane) NaH (60% in mineral oil,
345 mg, 8.61 mmol) in dry DMF (10 mL) was cooled to 0 °C and
treated under argon atmosphere with a solution of 210 (2.50 g,
4.31 mmol) in dry DMF (25 mL). The mixture was warmed to room
temperature and stirred for 30 min, cooled again to 0 °C and then
treated with PMBCl (0.70 mL, 5.17 mmol). The mixture was al-
lowed to reach room temperature and further stirred until the
starting material was consumed (2 h, TLC, 3:7 hexane–EtOAc). Ex-
cess of NaH was destroyed by dropwise addition of MeOH (1 mL)
followed by 10 min stirring at 0 °C. After removal of the solvents
under diminished pressure, the crude residue was dissolved in
CH2Cl2 (50 mL) and treated with 5% aq HCl (50 mL) until TLC anal-
ysis (3:7 hexane–EtOAc) revealed the complete disappearance of
the product at Rf 0.57 and the formation of a slower moving prod-
H), 4.65 (d, 1H, J1 ,2 1.3 Hz, H-10), 4.63 (s, 2H, CH2PMB), 4.56, 4.51
(AB system, 2H, JA,B 12.0 Hz, CH2Ph), 4.43 (dd, 1H, J1,2 6.0 Hz, J2,3
0
0
0
0
0
0
7.5 Hz, H-2), 4.34 (d, 1H, H-1), 4.25 (dd, 1H, J2 ,3 5.6 Hz, J3 ,4
6.3 Hz, H-30), 4.21 (dt, 1H, J5,6a=J5,6b 6.5 Hz, J4,5 2.0 Hz, H-5), 4.05
(dd, 1H, J3,4 1.6 Hz, H-3), 4.03 (dd, 1H, J4 ,5 2.6 Hz, H-40), 3.96 (dd,
1H, J6a,6b 8.5 Hz, H-6b), 3.91 (dd, 1H, H-6a), 3.88 (dd, 1H, H-4),
0
0
3.86 (ddd, 1H, J5 ,6 a 6.7 Hz, J5 ,6 b 5.7 Hz, H-50), 3.76 (s, 3H, OMe-
0
0
0
0
PMB), 3.67 (dd, 1H, J6 a,6 b 10.0 Hz, H-60b), 3.61 (dd, 1H, H-60a),
3.63 (dd, 1H, H-20), 3.32, 3.31 (2s, each 3H, 2 ꢁ OMe-1), 1.39,
1.35, 1.31, 1.30, 1.27, 1.26 (6s, each 3H, 3 ꢁ CMe2); 13C NMR (CD3-
CN): d 160.0, 131.7 (2 ꢁ Ar-C PMB), 139.6 (Ar-C, Bn), 131.0, 114.3
(Ar-CH PMB), 129.3-128.5 (Ar-CH, Bn), 110.5, 110.4, 108.9
(3 ꢁ CMe2), 106.2 (C-1), 102.5 (C-10), 78.4 (C-3), 78.2 (C-5), 77.4
0
0

L. Guazzelli et al. / Carbohydrate Research 388 (2014) 44–49
47
(C-4), 76.4 (C-2), 74.9 (CH2Ph), 74.7 (C-30), 74.1 (C-20), 73.8 (CH2-
PMB), 72.9 (C-50), 72.2 (C-40), 70.0 (C-60), 66.2 (C-6), 56.1, 54.5
(OMe-1), 55.8 (OMe-PMB), 27.4, 27.2, 26.9, 26.1, 26.0, 25.3 (3 ꢁ
CMe2). Anal. Calcd for C38H54O13: C, 63.49; H, 7.57. Found: C,
63.59; H, 7.67.
(200 mL) was added and the aq soln was extracted with CH2Cl2
(4 ꢁ 20 mL). The collected organic phase was dried, filtered, and
concentrated under diminished pressure. The crude residue was
subjected to a flash chromatographic purification on silica gel
(65:35 hexane–EtOAc) to give pure 5 (1.57 g, 80% yield) as a clear
syrup; Rf 0.22 (6:4 hexane–EtOAc); [
a
]
D
ꢀ61.6 (c 1.27, CHCl3); 1H
3.3. 4-O-(3,6-Di-O-benzyl-4-deoxy-2-O-p-methoxybenzyl-b-
erhytro-hex-4-enopyranosyl)- 2,3:5,6-di-O-isopropylidene-
D-
NMR (CD3CN): d 7.36–7.26 (m, 12H, Ar-H), 6.84-6.78 (m, 2H, Ar-
0
0
H), 4.82, 4.61 (AB system, 2H, JA,B 11.2 Hz), 4.72 (d, 1H, J1 ,2
aldehydo-
D
-glucose dimethyl acetal (4)
0.6 Hz, H-10), 4.60, 4.50 (AB system, 2H, JA,B 12.2 Hz), 4.55, 4.47
(AB system, 2H, JA,B 11.9 Hz), (2 ꢁ CH2Ph, CH2PMB), 4.45 (dd, 1H,
J1,2 6.1 Hz, J2,3 7.6 Hz, H-2), 4.35 (d, 1H, H-1), 4.26 (dt, 1H, J4,5
3.7 Hz, J5,6a = J5,6b 6.9 Hz, H-5), 4.09 (dd, 1H, J3,4 1.5 Hz, H-3),
A soln of 3 (2.37 g, 3.29 mmol) in dry THF (56 mL) was warmed
to reflux and treated with solid t-BuOK (3.70 g, 33.0 mmol). After
20 min, TLC analysis (1:1 hexane–EtOAc) showed the complete dis-
appearance of the starting material, and satd aq NaHCO3 (50 mL)
was then added. The aq phase was extracted with CH2Cl2
(3 ꢁ 75 mL) and the organic extracts were dried, filtered, and con-
centrated under diminished pressure. The crude enol ether was
dissolved in dry DMF (25 mL) and added to a suspension of pre-
washed (hexane) NaH (60% in mineral oil, 264 mg, 6.59 mmol) in
dry DMF (10 mL) cooled to 0 °C. The mixture was warmed to room
temperature and stirred for 20 min, cooled again to 0 °C and then
treated with BnBr (0.50 mL, 3.95 mmol). The mixture was allowed
to reach room temperature and further stirred until the starting
material was consumed (12 h, TLC, 6:4 hexane–EtOAc). MeOH
(1 mL) and water (30 mL) were slowly added at 0 °C, and the mix-
ture was extracted with CH2Cl2 (4 ꢁ 20 mL). The collected organic
layers were dried, filtered and concentrated under diminished
pressure. The residue (2.21 g) was subjected to flash chromatogra-
phy (7:3 hexane–EtOAc + 0.1% Et3N) to give 4 (1.91 g, 77% yield) as
4.04 (m, 2H, H-6a, H-6b), 4.01 (dd, 1H J2 ,3 3.4 Hz, H-20), 3.96
(dd, 1H, H-4), 3.75 (s, 3H, OMe-PMB), 3.74 (m, 1H, H-40), 3.71
(m, 2H, H-60a, H-60b), 3.31 (m, 2H, H-30, H-50), 3.34, 3.32 (2s, each
3H, 2 ꢁ OMe-1), 1.34, 1.33, 1.32, 1.31 (4s, each 3H, 2 ꢁ CMe2); 13C
0
0
NMR (CD3CN):
d
160.0, 132.1 (2 ꢁ Ar-C, PMB), 139.9, 139.7
(2 ꢁ Ar-C, Bn), 130.5, 114.4 (Ar-CH, PMB), 129.2-128.3 (Ar-CH,
Bn), 110.6, 108.7 (2 ꢁ CMe2), 106.2 (C-1), 103.1 (C-10), 82.6
(C-30), 78.6 (C-5), 78.5 (C-3), 77.1 (C-4), 77.0 (C-50), 76.5 (C-2),
75.6 (C-20), 74.9, 74.6, 74.1 (2 ꢁ CH2Ph, CH2PMB), 70.6 (C-60),
67.5 (C-40), 65.9 (C-6), 56.0, 54.3 (2 ꢁ OMe-1), 55.8 (OMe-PMB),
27.4, 27.3, 26.9, 25.2 (2 ꢁ CMe2). Anal. Calcd for C42H56O13
:
C, 65.61; H, 7.34. Found: C, 65.63; H, 7.38.
3.5. 4-O-(3,4,6-tri-O-Benzyl-2-O-p-methoxybenzyl-b-D-
mannopyranosyl)-2,3:5,6-di-O-isopropylidene-aldehydo-D-
glucose dimethyl acetal (6)
a clear syrup; Rf 0.46 (6:4 hexane–EtOAc); [
a
]
ꢀ38.9 (c 1.04,
To a suspension of pre-washed (hexane, 3 ꢁ 30 mL) NaH (60% in
mineral oil , 164 mg, 4.09 mmol) in dry DMF (10 mL), a soln of 5
(1.57 g, 2.05 mmol) in dry DMF (20 mL) was added at 0 °C. The
mixture was stirred for 30 min at 0 °C, then BnBr (0.30 mL,
2.45 mmol) was added and the reaction mixture was further stir-
red at room temperature until the starting compound was com-
pletely reacted (12 h, TLC, 7:3 hexane–EtOAc). Excess of NaH was
destroyed by dropwise addition of MeOH (1 mL, 30 min) at 0 °C,
and then the solvents were evaporated under diminished pressure.
The residue was partitioned between H2O (50 mL) and CH2Cl2
(50 mL). The organic phase was separated, and the aq layer ex-
tracted with CH2Cl2 (3 ꢁ 20 mL). The combined organic phases
were dried, filtered, and concentrated under diminished pressure.
Flash chromatographic purification over silica gel of the crude
product (7:3 hexane–EtOAc) gave pure 6 (1.64 g, 93% yield) as a
D
CHCl3); 1H NMR (CD3CN): d 7.38–7.25 (m, 12H, Ar-H), 6.86–6.80
(m, 2H, Ar-H), 5.29 (t, 1H, J1 ,2 = J1 ,3 1.1 Hz, H-10), 4.90 (dd, 1H,
0
0
0
0
J3 ,4 2.8 Hz, J4 ,6 a = J4 ,6 b 0.9 Hz, H-40), 4.78, 4.66 (AB system, 2H,
JA,B 11.1 Hz, CH2Ph), 4.53, 4.45 (AB system, 2H, JA,B 11.8 Hz, CH2Ph),
4.51 (s, 2H, CH2PMB), 4.42 (dd, 1H, J2,3 7.1 Hz, J1,2 6.2 Hz, H-2), 4.33
(d, 1H, H-1), 4.26 (dt, 1H, J4,5 6.7 Hz, J5,6a = J5,6b 3.7 Hz, H-5), 4.22
0
0
0
0
0
0
0
0
(ddd, 1H, J2 ,3 6.0 Hz, H-3’), 4.10 (dd, 1H, J3,4 1.5 Hz, H-4), 4.05
(dd, 1H, H-3), 4.03 (dd, 1H, J6a,6b 10.1 Hz, H-6b), 3.98 (dd, 1H,
H-6a), 3.94 (dd, 1H, H-20), 3.89 (m, 2H, H-60a, H-60b), 3.75 (s, 3H,
OMe-PMB), 3.35, 3.33 (2s, each 3H, 2 ꢁ OMe-1), 1.33, 1.29 (2s, each
3H, CMe2), 1.31 (s, 6H, CMe2); 13C NMR (CD3CN): d 160.2, 131.8
(2 ꢁ Ar-C, PMB), 150.5 (C-50), 139.9, 139.6 (2 ꢁ Ar-C, Bn), 130.6,
114.5 (Ar-CH, PMB), 129.2–128.4 (Ar-CH, Bn), 110.6, 108.7
(2 ꢁ CMe2), 106.3 (C-1),101.2 (C-10), 100.5 (C-40), 78.7 (C-4), 78.5
(C-5), 77.0 (C-3), 76.1 (C-2), 73.6, 73.2 (2 ꢁ CH2Ph), 73.2 (C-20),
71.5 (CH2PMB), 71.4 (C-30), 69.9 (C-60), 65.9 (C-6), 55.8 (OMe-
PMB), 56.2, 53.9 (2 ꢁ OMe-1), 27.4, 27.2, 26.9, 25.6 (2 ꢁ CMe2).
Anal. Calcd for C42H54O12: C, 67.18; H, 7.25. Found: C, 67.20; H,
7.26.
clear syrup; Rf 0.52 (6:4 hexane–EtOAc), [
a]
D ꢀ36.3 (c 1.15, CHCl3);
1H NMR (CD3CN): d 7.36–7.20 (m, 17H, Ar-H), 6.86–6.80 (m, 2H,
Ar-H), 4.85, 4.65 (AB system, 2H, JA,B 11.3 Hz), 4.81, 4.52 (AB sys-
tem, 2H, JA,B 10.3 Hz), 4.74 (d, 1H, J1 ,2 0.4 Hz, H-10), 4.63, 4.48
(AB system, 2H, JA,B 11.9 Hz), 4.56, 4.48 (AB system, 2H, JA,B
11.7 Hz), (3 ꢁ CH2Ph, CH2PMB), 4.49 (dd, 1H, J1,2 6.0 Hz, J2,3
7.4 Hz, H-2), 4.36 (d, 1H, H-1), 4.27 (dt, 1H, J4,5 3.6 Hz, J5,6a = J5,6b
6.7 Hz, H-5), 4.05 (dd, 1H, J3,4 1.5 Hz, H-3), 4.03 (m, 2H, H-6a,
0
0
3.4. 4-O-(3,6-di-O-Benzyl-2-O-p-methoxybenzyl-b-D-
mannopyranosyl)-2,3:5,6-di-O-isopropylidene-aldehydo-D-
glucose dimethyl acetal (5)
H-6b), 4.02 (dd, 1H, J2 ,3 3.0 Hz, H-20), 3.96 (dd, 1H, H-4), 3.80
0
0
(dd, 1H, J3 ,4 9.4 Hz, J4 ,5 9.6 Hz, H-40), 3.76 (s, 3H, OMe-PMB),
0
0
0
0
3.75 (dd, 1H, J5 ,6 b 4.0 Hz, J6 a,6 b 11.0 Hz, H-60b), 3.68 (dd, 1H,
0
0
0
0
A soln of 4 (1.91 g, 2.54 mmol) in dry THF (101 mL) was trea-
ted at 0 °C and under argon atmosphere with a 1:10 (v/v) soln of
BH3ꢂMe2S in Et2O (5 M) in dry THF (2.28 mL, 11.4 mmol) (5 M).
The reaction mixture was allowed to reach to room temperature
and was stirred until the disappearance of the starting material
(TLC, 6:4 hexane–EtOAc, 5 h). The mixture was cooled to 0 °C,
and H2O (2.4 mL), 10% aq NaOH (7.4 mL) and 35% aq H2O2
(20 mL) were sequentially added. The biphasic mixture was stir-
red at room temperature until the TLC analysis (6:4 hexane–
EtOAc) revealed the disappearance of the borane intermediate
J5 ,6 a 1.9 Hz, H-60a), 3.53 (dd, 1H, H-30), 3.37, 3.35 (2s, each 3H,
2 ꢁ OMe-1), 3.32 (ddd, 1H, H-50), 1.35, 1.34, 1.32, 1.31 (4s, each
3H, 2 ꢁ CMe2); 13C NMR (CD3CN): d 160.2, 132.2 (2 ꢁ Ar-C, PMB),
139.9, 139.7, 139.6 (2 ꢁ Ar-C, Bn), 130.6, 114.4 (Ar-CH, PMB),
129.2–128.4 (Ar-CH, Bn), 110.6, 108.8 (2 ꢁ CMe2), 106.3 (C-1),
103.2 (C-10), 83.0 (C-30), 78.6 (C-5), 77.3 (C-4), 76.6 (C-2), 76.5
(C-50), 75.8 (C-20), 75.4 (C-40), 75.5, 74.7, 74.1, 72.0 (3 ꢁ CH2Ph, CH2-
PMB), 70.2 (C-60), 65.9 (C-6), 55.8 (OMe-PMB), 56.1, 54.4 (2 ꢁ OMe-
0
0
1), 27.4, 27.3, 27.0, 25.3 (2 ꢁ CMe2). Anal. Calcd for C49H62O13
:
(2 h) and the formation of
a
single spot (Rf 0.22). Water
C, 68.51; H, 7.27. Found: C, 68.49; H, 7.25.

48
L. Guazzelli et al. / Carbohydrate Research 388 (2014) 44–49
3.6. 4-O-(3,4,6-tri-O-Benzyl-b-
isopropylidene-aldehydo-D-glucose dimethyl acetal (7)
D
-mannopyranosyl)-2,3:5,6-di-O-
(C-3), 77.4 (C-5), 76.2 (C-2), 76.0 (C-50), 75.6, 74.1, 73.2 (3 ꢁ CH2-
Ph), 74.8 (C-40), 72.2 (C-30), 69.4 (C-60), 66.1 (C-6), 56.3, 54.4
(2 ꢁ OMe-1), 27.3, 27.2, 27.1, 25.3 (2 ꢁ CMe2). Anal. Calcd for C44-
H56N2O14S: C, 60.81; H, 6.50; N, 3.22; S, 3.69. Found: C, 60.79; H,
6.48; N, 3.20; S, 3.66.
To a soln of 6 (1.64 g, 1.91 mmol) in 18:1 CH2Cl2–H2O (50 mL),
DDQ (650 mg, 2.86 mmol) was added and the resulting mixture
was stirred until TLC analysis (6:4 hexane–EtOAc, 1 h) revealed
the complete disappearance of the starting material. The reaction
mixture was washed with satd aq NaHCO3 (50 mL) and the organic
phase was separated. The aqueous layer was repeatedly extracted
with CH2Cl2 (4 ꢁ 50 mL), and the collected organic phases were
dried, filtered, and concentrated under diminished pressure. Flash
chromatographic purification over silica gel (6:4 hexane–EtOAc)
afforded pure 7 (1.05 g, 76% yield) as a clear syrup; Rf 0.29 (6:4
3.8. 4-O-(2-Azido-3,4,6-tri-O-benzyl-2-deoxy-b-D-
glucopyranosyl)-2,3:5,6-di-O-isopropylidene-aldehydo-D-
glucose dimethyl acetal (9)
A soln of 8 (954 mg, 1.09 mmol) and NaN3 (142 mg, 2.18 mmol)
in dry DMF (32 mL) was stirred at 100 °C under argon atmosphere.
After 45 min, TLC analysis (1:1 hexane–EtOAc) revealed the com-
plete disappearance of the starting material; the mixture was then
cooled to room temperature and partitioned between satd aq
NaHCO3 (50 mL) and Et2O (50 mL). The organic phase was sepa-
rated and the aq layer extracted with Et2O (4 ꢁ 50 mL). The organic
extracts were dried, filtered, and concentrated under diminished
pressure. Purification of the crude by flash chromatography over
silica gel (7:3 hexane–EtOAc) afforded pure 9 (762 mg, 92% yield)
hexane–EtOAc), [
7.42–7.20 (m, 15H, Ar-H), 4.82, 4.47 (AB system, 2H, JA,B 11.2 Hz,
a
]
ꢀ2.57 (c 1.13, CHCl3); 1H NMR (CD3CN): d
D
CH2Ph), 4.73, 4.57 (AB system, 2H, JA,B 10.9 Hz, CH2Ph), 4.71 (d,
1H, J1 ,2 0.9 Hz, H-10), 4.55, 4.46 (AB system, 2H, JA,B 11.8 Hz, CH2-
Ph), 4.45 (dd, 1H, J1,2 6.2 Hz, J2,3 7.0 Hz, H-2), 4.34 (d, 1H, H-1),
0
0
0
0
4.22 (dt, 1H, J4,5 4.3 Hz, J5,6a = J5,6b 6.2 Hz, H- 5), 4.14 (dd, 1H, J2 ,3
3.0 Hz, H-20), 4.05 (dd, 1H, J3,4 1.5 Hz, H-3), 3.98 (m, 2H, H-6a, H-
6b), 3.91 (dd, 1H, H-4), 3.74 (t, 1H, J4 ,5 = J3 ,4 9.4 Hz, H-40), 3.70
as a clear syrup; Rf 0.68 (1:1 hexane–EtOAc), [
a
]
ꢀ53.5 (c 1.02,
0
0
0
0
D
(m, 2H, H-60a, H-60b), 3.55 (dd, 1H, H-30), 3.35, 3.34 (2s, each 3H,
CHCl3); 1H NMR (CD3CN): d 7.40–7.20 (m, 15H, Ar-H), 4.83, 4.78
(AB system, 2H, JA,B 11.1 Hz, CH2Ph), 4.75, 4.57 (AB system, 2H,
2 ꢁ OMe-1), 3.32 (m, 1H, H-50), 2.86 (d, J2 ,OH 3.7 Hz, OH-20), 1.38,
0
1.34, 1.33, 1.29 (4s, each 3H, 2 ꢁ CMe2); 13C NMR (63 MHz, CD3-
CN): d 139.8, 139.6, 139.5 (3 ꢁ Ar-C), 129.2–128.4 (Ar-CH), 110.9,
108.8 (2 ꢁ CMe2), 106.1 (C-1), 101.5 (C-10), 82.6 (C-30), 78.7 (C-3),
78.1 (C-5), 76.7 (C-4), 76.5 (C-2), 76.0 (C-50), 75.5, 73.9, 71.4
(3 ꢁ CH2Ph), 74.0 (C-40), 70.2 (C-60), 68.7 (C-20), 66.0 (C-6), 56.0,
54.2 (2 ꢁ OMe-1), 27.7, 27.1, 26.9, 25.4 (2 ꢁ CMe2). Anal. Calcd
for C41H54O12: C, 66.65; H, 7.37. Found: C, 66.61; H, 7.34.
JA,B 10.9 Hz, CH2Ph), 4.70 (d, 1H, J1 ,2 7.8 Hz, H-10), 4.56, 4.47 (AB
system, 2H, JA,B 11.8 Hz, CH2Ph), 4.43 (dd, 1H, J1,2 6.2 Hz, J2,3
7.0 Hz, H-2), 4.34 (d, 1H, H-1), 4.29 (dt, 1H, J4,5 4.7 Hz, J5,6a = J5,6b
6.4 Hz, H- 5), 4.12 (dd, 1H, J6a,6b 8.4 Hz, H6b), 4.10 (dd, 1H, J3,4
1.4 Hz, H-3), 4.03 (dd, 1H, H-6a), 3.97 (dd, 1H, H-4), 3.74 (dd, 1H,
0
0
J5 ,6 b 3.6 Hz, J6 a,6 b 11.1 Hz, H60b), 3.67 (dd, 1H, J5 ,6 a 3.1 Hz, H-
0
0
0
0
0
0
60a), 3.62 (dd, 1H, J2 ,3 9.1 Hz, J3 ,4 8.6 Hz, H-30), 3.48-3.35 (m, 3H,
H-20, H-40, H-50), 3.37, 3.35 (2s, each 3H, 2 ꢁ OMe-1), 1.46, 1.36,
1.34, 1.30 (4s, each 3H, 2 ꢁ CMe2); 13C NMR (CD3CN): d 139.5,
139.4, 139.3 (3 ꢁ Ar-C), 129.2–128.5 (Ar-CH), 110.9, 108.9
(2 ꢁ CMe2), 106.4 (C-1), 102.2 (C-10), 83.6 (C-40), 78.6 (C-30), 78.5
(C-3), 78.0 (C-5), 76.6 (C-2), 76.1 (C-4), 75.6 (C-50), 75.8, 75.6,
74.1 (3 ꢁ CH2Bn), 69.7 (C-60), 68.1 (C-20), 66.0 (C-6), 56.1, 54.4
(2 ꢁ OMe-1), 27.7, 27.2, 26.8, 25.3 (2 ꢁ CMe2). Anal. Calcd for
0
0
0
0
3.7. 4-O-(3,4,6-tri-O-Benzyl-2-O-imidazoylsulfonyl-b-D-
mannopyranosyl)-2,3:5,6-di-O-isopropylidene-aldehydo-D-
glucose dimethyl acetal (8)
To a pre-washed (hexane) suspension of NaH (60% in mineral
oil, 284 mg, 7.11 mmol) in dry DMF (10 mL), a soln of 7 (1.06 g,
1.42 mmol) in dry DMF (15 mL) was slowly added under argon
atmosphere at 0 °C. The mixture was stirred at 0 °C for 30 min,
cooled to ꢀ30 °C, treated with Im2SO2 (411.5 mg, 2.08 mmol) and
further stirred at ꢀ30 °C. After 1 h, TLC analysis (4:6 hexane–
EtOAc) revealed the complete disappearance of the starting mate-
rial. The reaction mixture was then cooled to ꢀ40 °C, the excess of
NaH was destroyed by addition of MeOH (0.5 mL). After 10 min,
Et2O (20 mL) and crushed iced-water were added. The organic
phase was separated and the aqueous layer was extracted with
Et2O (3 ꢁ 50 mL). The collected organic phases were dried, filtered,
and concentrated under diminished pressure. Flash chromato-
graphic purification over silica gel of the reaction product (6:4 hex-
ane–EtOAc) gave pure 8 (1.02 g, 83% yield) as a clear syrup; Rf 0.37
C41H53N3O11: C, 64.47; H, 6.99; N, 5.50. Found: C, 64.45; H, 6.97;
N, 5.48.
3.9. 4-O-(2-Acetamido-2-deoxy-b-D-glucopyranosyl)-2,3:5,6-di-
O-isopropylidene-aldehydo-D-glucose dimethyl acetal (10)
A soln of 9 (123 mg, 0.16 mmol) in 1:3 EtOAc–EtOH (18 mL)
containing 10% Pd on charcoal (63 mg) and Ac2O (0.08 mL,
0.42 mmol) was stirred at room temperature under an H2 atmo-
sphere until TLC analysis (8:2 CHCl3–MeOH, 48 h) revealed the dis-
appearance of the starting material. The mixture was diluted with
EtOH (30 mL), filtered over Celite, concentrated under diminished
pressure. Purification of the residue by flash chromatography over
silica gel (95:5 CHCl3–MeOH + 0.01% Et3N) gave 10 (44 mg, 53%) as
(6:4 hexane–EtOAc), [
8.01 (dd, 1H, J2,4 1.3 Hz, Im-H2), 7.46 (dd, 1H, J2,5 0.9 Hz, J4,5 1.6 Hz,
a
]
D ꢀ13.6 (c 1.16, CHCl3); 1H NMR (CD3CN): d
a white foam; Rf 0.52 (8:2 CHCl3–MeOH); [
a]
D ꢀ48.0 (c 1.0, CHCl3);
1H NMR (CD3CN): d 6.79 (d, 1H, J2 ,NH 7.4 Hz, NH), 4.56 (d, 1H, J1 ,2
0
0 0
Im-H4), 7.40–7.24 (m, 15H, Ar-H), 7.01 (dd, 1H, Im-H5), 5.25 (dd,
1H, J1 ,2 0.6 Hz, J2 ,3 2.3 Hz, H-20), 4.94 (d, 1H, H-10), 4.68, 4.48
(AB system, 2H, JA,B 10.8 Hz, CH2Ph), 4.64, 4.49 (AB system, 2H,
JA,B 11.8 Hz, CH2Ph), 4.56, 4.47 (AB system, 2H, JA,B 11.9 Hz, CH2Ph),
4.35 (m, 2H, H-1, H-2), 4.20 (dt, 1H, J4,5 4.9 Hz, J5,6a = J5,6b 6.4 Hz,
H-5), 4.03 (dd, 1H, J2,3 7.3 Hz, J3,4 1.9 Hz, H-3), 3.94 (m, 2H, H-6a,
8.1 Hz, H-10), 4.43 (dd, 1H, J1,2 6.8 Hz, J2,3 7.4 Hz, H-2), 4.35 (d, 1H,
H-1), 4.21 (m, 1H, H-5), 4.05-3.85 (m, 4H, H-30, H-3, H-6a, H-6b),
3.81 (m, 1H, H-60b), 3.73 (m, 1H, H-4), 3.59-3.45 (m, 5H, H-20,
H-60a, 3 ꢁ OH), 3.40, 3.39 (2s, each 3H, 2 ꢁ OMe-1), 3.22 (m, 2H,
H-40, H-50), 1.92 (s, 3H, MeCO), 1.42, 1.31, 1.30, 1.29 (4s, each 3H,
0
0
0
0
H-6b), 3.89 (dd, 1H, H-4), 3.70 (dd, 1H, J3 ,4 10.5 Hz, H-30), 3.68
(m, 3H, H-40, H-60a, H60b), 3.39 (m, 1H, H-50), 3.38, 3.35 (2s, each
3H, 2 ꢁ OMe-1), 1.35, 1.34, 1.32, 1.29 (4s, each 3H, 2 ꢁ CMe2);
13C NMR (CD3CN): d 139.3, 139.1, 138.4 (3 ꢁ Ar-C), 138.1 (Im-C2),
131.2 (Im-C4), 129.3-128.6 (Ar-CH), 119.7 (Im-C5), 110.5, 109.0
(2 ꢁ CMe2), 106.3 (C-1), 99.0 (C-10), 84.6 (C-20), 78.7 (C-4), 78.0
2 ꢁ CMe2); 13C NMR (CD3CN):
d
172.2 (CO), 110.4, 108.9
0
0
(2 ꢁ CMe2), 107.5 (C-1), 102.3 (C-10), 78.9 (C-3), 77.7 (C-5), 77.2
(C-50), 76.5 (C-4), 76.0 (C-2), 75.9 (C-30), 72.5 (C-40), 65.9 (C-6),
63.2 (C-60), 57.4 (C-20), 57.3, 54.5 (2 ꢁ OMe-1), 27.3, 26.7, 26.6,
24.6 (2 ꢁ CMe2), 23.3 (MeCO). Anal. Calcd for C22H39NO12
:
C, 51.86; H, 7.71; N, 2.75. Found: C, 52.03; H, 7.68; N, 2.84.

L. Guazzelli et al. / Carbohydrate Research 388 (2014) 44–49
49
2. (a) Dwek, R. A. Chem. Rev. 1996, 96, 683–720; (b) Mooran, A. P.; Holst, O.;
Brennan, P. J. Microbial Glycobiology: Structures, relevance and Applications;
Elsevier, 2009. pp 957–979.
3.10. 4-O-(2-Acetamido-2-deoxy-b-D-glucopyranosyl)-a,b-D-
glucopyranose (11)
3. Casu, B. Adv. Carbohydr. Chem. Biochem. 1985, 43, 51–134.
4. (a) Sharon, N. Complex Carbohydrates. Their Chemistry, Biosynthesis, and
Functions; Addison-Wesley, 1975; (b) Varki, A. Glycobiology 1993, 3, 97–130.
5. (a) Jennings, H. J. Adv. Carbohydr. Chem. Biochem. 1983, 41, 155–208; (b)
Pozsgay, V. Adv. Carbohydr. Chem. Biochem. 2001, 56, 153–199.
6. (a) Gridley, J. J.; Osborn, H. M. I. J. Chem. Soc., Perkin Trans. 1 2000, 1471–1491;
(b) Bongat, A. F. G.; Demchenko, A. V. Carbohydr. Res. 2007, 342, 374–406.
7. (a) Attolino, E.; Bonaccorsi, F.; Catelani, G.; D’Andrea, F.; Krenel, K.; Bešouska,
K.; Kren, V. J. Carbohydr. Chem. 2008, 27, 156–171; (b) Attolino, E.; Bonaccorsi,
F.; Catelani, G.; D’Andrea, F. Carbohydr. Res. 2008, 343, 2545–2556; (c) Attolino,
E.; Catelani, G.; D’Andrea, F.; Nicolardi, M. J. Carbohydr. Chem. 2004, 23, 179–
190; (d) Barili, P. L.; Berti, G.; Catelani, G.; D’Andrea, F.; Puccioni, L. J. Carbohydr.
Chem. 2000, 19, 79–91; (e) Barili, P. L.; Berti, G.; Catelani, G.; D’Andrea, F.; Di
Bussolo, V. Carbohydr. Res. 1996, 290, 17–31.
A soln of 10 (73 mg, 0.14 mmol) in 80% aq. AcOH (2.7 mL) was
stirred at 80 °C until TLC analysis (7:3 CHCl3–MeOH, 3 h) revealed
the disappearance of the starting material. The reaction mixture
was concentrated under diminished pressure by coevaporation
with toluene (4 ꢁ 30 ml). The crude residue was triturated with
EtOAc to give an amorphous white solid (47.6 mg, 87% yield) com-
posed by a 2:3
basis of the integration of the H-1 signals at d 5.05 and 4.57 respec-
tively; [ D +30 (c, 0.7, water); mp
D1 +27 (c, 0.81, water); lit.9d
195–197 °C (MeOH–Et2O), lit.9d mp 190–195 °C (MeOH–Et2O); se-
lected 1H NMR (D2O) signals:
-11): d 5.05 (d, 1H, J1,2 3.8 Hz, H-1),
4.40 (d, 1H, J1 ,2 8.0 Hz, Hz, H-10); 1.97 (s, 3H, MeCO), b-11: d 4.47
a/b anomeric mixture of 11, as established on the
a
]
[a]
8. Guazzelli, L.; Catelani, G.; D’Andrea, F.; Giannarelli, G. Carbohydr. Res. 2009, 344,
298–303.
a
0
0
9. (a) Dussouy, C.; Bultel, L.; Saguez, J.; Cherqui, A.; Khelifa, M.; Grand, E.;
Giordanengo, P.; Kovensky, J. Chemistry 2012, 18, 10021–10028; (b) Koto, S.;
Asami, K.; Hirooka, M.; Nagura, N.; Takizawa, M.; Yamamoto, S.; Nami
Okamoto, N.; Sato, M.; Tajima, H.; Yoshida, T.; Nonaka, N.; Sato, T.; Zen, S.;
Kazuo Yago, K.; Tomonaga, F. Bull. Chem. Soc. Jpn. 1999, 72, 765–777; (c) Sarah,
E.; O’Connor, S. E.; Imperiali, B. Chem. Biol. 1998, 5, 427–437; (d) Shapiro, D.;
Rabinsohn, Y.; Acher, A. J.; Haber, D. J. Org. Chem. 1970, 35, 1464–1467.
10. Attolino, E.; Catelani, G.; D’Andrea, F. Eur. J. Org. Chem. 2006, 23, 5279–
5292.
11. Guazzelli, L.; Catelani, G.; D’Andrea, F. Carbohydr. Res. 2010, 345, 369–376.
12. (a) Catelani, G.; Corsaro, A.; D’Andrea, F.; Mariani, M.; Pistarà, V.; Vittorino, E.
Carbohydr. Res. 2003, 338, 2349–2358; (b) Corsaro, A.; Catelani, G.; D’Andrea,
F.; Fisichella, S.; Mariani, M.; Pistarà, V. Environ. Sci. Pollut. Res. 2003, 10, 325–
328.
(d, 1H, J1,2 8.0 Hz, H-1), 4.39 (d, 1H, J1 ,2 8.1 Hz, Hz, H-10); 3.80 (dd,
0
0
1H, J5 ,6 b 1.7 Hz, J6 a,6 b 12.1 Hz, H-60b); 3.12 (dd, 1H, J2,3 9.1 Hz,
H-2); 1.89 (s, 3H, MeCO); 13C NMR (D2O) signals:
-11: d 175.4
0
0
0
0
a
(CO), 102.3 (C-10), 92.5 (C-1), 80.7 (C-4), 76.7 (C-50), 74.3 (C-30),
72.3 (C-3), 72.2 (C-2), 71.5 (C-5), 70.6 (C-40), 61.4 (C-60), 60.9
(C-6), 56.4 (C-20), 22.9 (MeCO), b-11: d 175.4 (CO), 102.3 (C-10),
96.5 (C-1), 80.3 (C-4), 73.7 (C-50), 75.3, 75.2 (C-3, C-5), 74.5 (C-2),
74.3 (C-30), 70.6 (C-40), 61.4 (C-60), 61.0 (C-6), 56.4 (C-20), 22.9 (MeCO).
Acknowledgement
13. Attolino, E.; Catelani, G.; D’Andrea, F.; Guazzelli, L.; Scherrmann, M.-C.
Carbohydr. Chem.: Proven Synth. Methods 2012, 1, 11–26.
14. (a) David, S.; Malleron, A.; Dini, C. Carbohydr. Res. 1989, 188, 193–200; (b)
Vatele, J.-M.; Hanessian, S. In Preparative Carbohydrate Chemistry; Hanessian, S.,
Ed.; M. Dekker: New York, 1997; pp 127–149.
This research was supported by the Ministero dell’Università e
della Ricerca (MIUR, Rome, Italy) in the frame of the COFIN national
project (2010–2011).
15. Bock, K.; Thogersen, H. Annu. Rep. NMR Spectrosc. 1982, 13, 1–57.
16. Cai, Y.; Ling, C.-C.; Bundle, D. R. Org. Lett. 2005, 7, 4021–4024.
17. Pistarà, V.; Corsaro, A.; Rescifina, A.; Catelani, G.; D’Andrea, F.; Guazzelli, L. J.
Org. Chem. 2013, 78, 9444–9449.
References
1. Horton, D.; Wander, J. D. Amino Sugars In Carbohydrates. Chemistry and
Biochemistry; Pigman, W., Horton, D., Eds.; Academic Press: New York, 1980;
Vol. 1B, pp 643–760.