Towards the synthesis of new dideoxy δ-dicarbonyl heptoses

Article abstract of DOI:10.1016/j.carres.2010.03.013

The preparation of a δ-dicarbonyl sugar thorough ring-opening, by a methoxymercuration-demercuration procedure, of a 5-spirocyclopropanated D-galactose derivative, is reported. This method constitutes a new route for the transformation of a hexose into new and interesting δ-dicarbonyl sugars, synthetic precursors of cyclitols, carba-and azasugars. Moreover this is, to our best knowledge, the first reported example of an elongation to a higher sugar starting from a spirocyclopropanated saccharide.

Full text of DOI:10.1016/j.carres.2010.03.013

Carbohydrate Research 345 (2010) 1482–1485
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
Towards the synthesis of new dideoxy d-dicarbonyl heptoses
*
Venerando Pistarà , Maria Assunta Chiacchio, Antonino Corsaro
Università di Catania, Dipartimento di Scienze Chimiche, I-95125 Catania, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
The preparation of a d-dicarbonyl sugar thorough ring-opening, by a methoxymercuration–demercura-
tion procedure, of a 5-spirocyclopropanated D-galactose derivative, is reported. This method constitutes
a new route for the transformation of a hexose into new and interesting d-dicarbonyl sugars, synthetic
precursors of cyclitols, carba- and azasugars. Moreover this is, to our best knowledge, the first reported
example of an elongation to a higher sugar starting from a spirocyclopropanated saccharide.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 22 January 2010
Received in revised form 11 March 2010
Accepted 15 March 2010
Available online 20 March 2010
Keywords:
Spirocyclopropyl sugars
d-Dicarbonyl heptoses
Electrophilic ring-opening
Among monosaccharide derivatives containing two carbonyl
groups (dialdoses, diuloses and aldosuloses), aldosuloses, although
yet poorly investigated, are an important class of natural dicarbonyl
monosaccharides.1 These compounds have been postulated as
intermediates in the biosynthesis of cyclitols,2 and are also useful
synthetic intermediates for the preparation of high value-added
compounds such as iminosugars3 (1-deoxynojirimycin and its
stereoisomeric analogues), carbasugars (gabosine derivatives),4
anation reaction aimed at transforming a hexose into a heptose
thorough the spirocyclopropyl pyranoside ring-opening sequence.
The spirocyclopropyl galactopyranoside 1, obtained in a nearly
quantitative yield starting from the 5-methylene derivative with
the Simmons–Smith modified cyclopropanation, following our pre-
viously reported method,10 was treated with mercuric trifluoroace-
tate in dry methanol to give, after exchange with NaCl saturated
solution, a crude material containing the two organomercuric chlo-
rides 2a,b. The mixture was purified by flash chromatography,
affording the pure organomercuric derivatives 2a and 2b in a good
total yield (78%) in a 1:1.8 ratio (Scheme 1).
cyclitols (epi- and D
-chiro-inositol),5 or polyhydroxycyclopentanes.6
A general approach to aldohexos-5-uloses was developed using
as a key reaction the epoxidation–methanolysis of 4-deoxy-hex-4-
eno-7 or 6-deoxy-hex-5-enopyranosides,8 two classes of unsaturated
sugars. Recently, the chemistry of 5,6-unsaturated pyranosides has
had some interesting developments in the reduction and function-
alization of their double bond, such as the oxidation to an epox-
ide.8b However, the chain extension by the cyclopropanation of
the exo-double bond has not been thoroughly explored, although
the resulting spirocyclopropyl-functionalized sugars are very
important as synthetic building blocks, glycosidase inhibitors or
useful scaffolds for carbohydrates mimics.9
The structure and the stereochemistry of these compounds
were deduced from their 1H and 13C NMR, COSY and NOE spectra.
In particular, in the 1H NMR spectrum, diagnostic signals were
those of the methylene protons of the CH2HgCl group (H-7a and
ClHg
OCH3
O
OCH3
OBn
OCH3
OBn
O
O
O
R
O
a
R
O
b
O
OBn
O
As part of a project on the elaboration of these 5-methylene
pyranosides, in the last few years, we have studied the reactivity
of the double bond towards the methylene–zinc iodide complex,
dichlorocarbene and rhodium ethoxycarbonyl complex addition.
These studies were carried out to clarify the stereochemical as-
pects of these reactions,10 and to obtain 1,5-dicarbonyl intermedi-
O
2a
b
3a
,
b
1
,
2a, 3a: R =
2b, 3a: R =
OCH3
OCH3
c
O
O
ates analogues to L
-arabino-heptos-5-ulose, previously reported.7a
As an extension of these studies, in this paper we describe, for
the first time, a simple sequence of reactions that use a cycloprop-
O
O
OH
OBn
HO
OBn
HO
OH
4
* Corresponding author. Tel.: +39 095 7385017; fax: +39 095 580138.
E-mail address: vpistara@unict.it (V. Pistarà).
Scheme 1. Reagents: (a) (i) Hg(CF3COO)2, MeOH; (ii) NaCl satd sol; (b) LiAlH4, THF;
(c) CF3COOH, CH3CN–H2O.
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.03.013

V. Pistarà et al. / Carbohydrate Research 345 (2010) 1482–1485
1483
H-7b), which resonate as multiplets centred at 1.82 and 2.20 ppm
for 2a, and at 2.10 and 2.19 ppm in the case of 2b. NOE experi-
ments easily allowed the stereochemical assignation of these ad-
ducts. For example, in the case of derivative 2a, a positive
enhancement (about 1.4%) was apparent on the signal of the C-5
methoxy group protons (3.31 ppm) by irradiating the protons of
the C-1 methoxy group (3.57 ppm) and vice versa, whereas the
same methoxy groups of the opposite stereoisomer 2b did not
show any appreciable NOE effect.
new prospects for its utilization. The results of these studies will
be contained in a future publication.
1. Experimental
1.1. General methods
Melting points were determined with a Kofler hot-stage appara-
tus and are uncorrected. 1H NMR spectra were recorded with a
Varian Unity INOVA instrument at 200 and 500 MHz in CDCl3 as
a solvent, unless otherwise stated (Me4Si was used as the internal
standard). 13C NMR spectra were recorded at 50 and 125 MHz.
Assignments were made, when possible, with the aid of APT, COSY
and HETCOR experiments and applying additivity rules.11 All reac-
tions were followed by TLC on Kieselgel 60 F254 with detection by
UV light and/or with ethanolic 5% sulfuric acid, and heating. Kiesel-
gel 60 (E. Merck, 230–400 mesh) was used for flash chromatogra-
phy. Solvents were dried by distillation according to standard
procedure,12 and stored over 4 Å molecular sieves activated for at
least 24 h at 400 °C. MgSO4 was used as the drying agent for solu-
tions. Spirocyclopropane galactopyranosides 1 and 5 were synthe-
sized following our previously reported method.10
Reductive demercuration with lithium aluminium hydride of
the diastereomers 2a and 2b produced, after flash chromatography,
the corresponding 6,7-dideoxy-1,5-bis-glycosides 3a (75% yield)
and 3b (77% yield) (Scheme 1). The latter compounds were finally
hydrolyzed (CF3COOH–H2O–CH3CN 0.1:0.5:1, rt, 12 h) affording
the 6,7-dideoxy-1,5-dicarbonyl heptose 4, which exists in CD3CN
as an 1:2.7
a
- and b-furanose mixture. In the 1H NMR spectrum
the H-1 proton signal appeared at 5.33 ppm (J = 0.5 Hz) for the
a-
anomer and at 5.42 ppm (J = 4.0 Hz) for the b-anomer.
The electrophilic ring-opening reaction, by methoxymercura-
tion–demercuration sequence, leading to 3a,b from 1, was also car-
ried out without the purification of the organomercuric derivatives
2a,b. In this case 1,5-bis-glycosides 3a,b were obtained in 71% glo-
bal yield over two steps from 1. Keeping in mind our simple proce-
dure10 for the synthesis of spirocyclopropane carboxylates 5 (a
mixture of four stereoisomers, global yield 89%) from the addition
of ethoxycarbonyl carbene (generated from the metal (Rh2+) cata-
lyzed decomposition of ethyldiazoacetate) to 5-methylene galacto-
pyranosides, and the high yield of 3 from the ring-opening
procedure conducted without purification on adducts 2, we
decided to apply the same reactions to the syntheses of hydroxy-
methyl derivatives of heptoses 6, after the mixture of stereoiso-
mers 5 was reduced with lithium aluminium hydride (Scheme 2).
The methoxymercuration–demercuration sequence of the ob-
tained hydroxymethyl derivatives produced the corresponding
1,5-bis-glycosides, analogues to 3, which upon hydrolysis afforded
1.2. General method for the electrophilic ring-opening of 1
1.2.1. Methoxymercuration
To a stirred solutionof 1 (1 g, 1.74 mmol) in dry MeOH (10.75 mL)
mercury(II) trifluoroacetate (1.14 g, 2.47 mmol) was added at room
temperature under a nitrogen atmosphere. The reaction was moni-
tored by TLC (cyclohexane–EtOAc 4:1) until 1 disappeared. After
about 2 h, the reaction was quenched by the addition of brine
(5 mL), and the solution was stirred vigorously for 30 min and then
extracted with dichloromethane (3 Â 20 mL). The combined organic
extracts were washed with water and dried (Na2SO4). After filtra-
tion, the solvent was removed under reduced pressure to give a
residual syrup, which afforded 2a and 2b as pure samples (global
yield 78%) by flash chromatography (cyclohexane–EtOAc 9:1).
a mixture of diastereomeric 6-deoxy-6-methyl-D,L-arabino-heptos-
5-uloses 6 (Scheme 2). The 1H NMR spectrum in CD3CN–D2O solu-
tion of the unseparated diastereomeric mixture of 6 is further com-
plicated because of the interconverting anomers showing doublets
(in the range 1.08 and 1.14 ppm, J = 7.0–7.5 Hz) for the protons of
the methyl groups. This indicates that heptos-5-uloses 6 exist, al-
1.2.1.1. Methyl 2-O-benzyl-7-chloromercurio-6,7-dideoxy-3,4-
O-isopropilidene-5-C-methoxy-b-
2a. Amorphous solid, yield 35%; [a D
D
-galacto-heptopyranoside,
]
À3.5 (c 0.8, CHCl3); 1H NMR
(CDCl3, 500 MHz): d 7.27–7.40 (m, 5H, aromatics H), 4.83–4.78
(AB system, 2H, J = 11.5 Hz, CH2Ph), 4.46 (d, 1H, J = 8.0 Hz, H-1),
4.26 (dd, 1H, J = 5.0, 8.0 Hz, H-3), 4.06 (d, 1H, J = 5.0 Hz, H-4),
3.75 (m, 2H, H-6a, H-6b), 3.57 (s, 3H, C1–OCH3), 3.73 (t, 1H,
J = 8.0 Hz, H-2), 3.31 (s, 3H, C5–OCH3), 2.19 (m, 1H, H-7b), 2.10
(m, 1H, H-7a), 1.33 (s, 3H, CH3), 1.25 (s, 3H, CH3); 13C NMR (CDCl3,
50 MHz): d 138.56 (aromatic C), 127.48, 127.36, 127.26 (aromatics
CH), 111.05 (C(CH3)2), 101.11 (C-1), 100.75 (C-5), 80.29, 78.30,
75.08 (C-2, C-3, C-4), 73.05 (CH2Ph), 55.97 (C1–OCH3), 48.50 (C5–
OCH3), 32.34 (CH2), 26.67, 24.04 (2 Â CH3), 21.98 (CH2Hg). Anal.
Calcd for C19H27ClHgO6: C, 38.85; H, 4.63. Found: C, 38.87; H, 4.59.
most exclusively, as a mixture of 1:2 a- and b-furanosic forms with
the H-1 proton resonating as doublets centred at 5.50 ppm
(J = 0.5 Hz) and 5.48 ppm (J = 3.5 Hz), respectively.
In conclusion this paper describes a new route for the prepara-
tion of a d-dicarbonyl heptoses thorough the ring-opening by a
methoxymercuration–demercuration procedure of a 5-spirocyclo-
propanated D-galactose derivative, which represents, to our best
knowledge, the first reported example of the elongation of 5-spiro-
cyclopropanated sugars to a higher carbon sugar. The same reac-
tion sequence should be of considerable importance as it can be
applied to spirocyclopropanated lactose (analogous to the spiro-
galactopyranoside derivative investigated here). This will expand
the applications of this natural disaccharide, a by-product of the
cheese-industry obtained in great amounts from whey, opening
1.2.1.2. Methyl 2-O-benzyl-7-chloromercurio-6,7-dideoxy-3,4-
O-isopropilidene-5-C-methoxy-b-
2b. Amorphous solid, yield 43%; [
L-galacto-heptopyranoside,
]
a
D À19.1 (c 0.6, CHCl3); 1H NMR
(CDCl3, 500 MHz): d 7.28–7.39 (m, 5H, aromatics H), 4.83–4.75 (AB
system, 2H, J = 11.5 Hz, CH2Ph), 4.52 (d, 1H, J = 7.5 Hz, H-1), 4.30 (dd,
1H, J = 7.0, 8.5 Hz, H-3), 4.19 (d, 1H, J = 8.5 Hz, H-4), 4.12 (dd, 1H,
J = 7.0, 7.5 Hz, H-2), 3.74 (m, 1H, H-6b), 3.48 (s, 3H, C1–OCH3), 3.28
(s, 3H, C5–OCH3), 3.18 (dd, 1H, J = 6.0, 8.0 Hz, H-6a), 2.20 (dq, 1H,
J = 3.5, 6.0, 15.0 Hz, H-7b), 1.82 (dq, 1H, J = 4.0, 8.0, 15.0 Hz, H-7a),
1.50 (s, 3H, CH3), 1.35 (s, 3H, CH3); 13C NMR (CDCl3, 125 MHz): d
138.16 (aromatic C), 128.05, 127.99, 127.53 (aromatics CH),
109.64 (C(CH3)2), 100.60 (C-1), 98.86 (C-5), 78.42, 76.86, 77.72 (C-
2, C-3, C-4), 73.40 (CH2Ph), 56.84 (C1–OCH3), 47.32 (C5–OCH3),
CO2Et
CH2OH
O
OCH3
OBn
O
O
O
O
a
OH
OBn
HO
O
HO
OBn
HO
O
OH
6
5
Scheme 2. Reagents: (a) (i) LiAlH4, THF; (ii) Hg(CF3COO)2, MeOH; (iii) NaCl satd sol;
(iv) LiAlH4, THF; (v) CF3COOH, CH3CN–H2O.

1484
V. Pistarà et al. / Carbohydrate Research 345 (2010) 1482–1485
29.55 (CH2), 27.72, 26.54 (2 Â CH3), 22.56 (CH2Hg). Anal. Calcd for
19H27ClHgO6: C, 38.85; H, 4.63. Found: C, 38.91; H, 4.65.
(5 Â 10 mL) under reduced pressure. The crude residue was parti-
tioned between brine (10 mL) and EtOAc (20 mL) and the aqueous
phase was extracted with EtOAc (3 Â 20 mL). The organic phases
collected and dried were concentrated under reduced pressure to
give a residue (385 mg), which was directly purified by flash chro-
matography (cyclohexane–EtOAc, 7:3), to give 4 (184 mg, 55%
yield) as colourless syrup. The d-dicarbonyl heptose 4 exists almost
C
1.2.2. Demercuration
To stirred suspension of lithium aluminium hydride
a
(6.75 mmol, 5 equiv) in dry THF (8.5 mL) at the temperature of
an ice bath, a solution of 2a or 2b (1 equiv) in anhydrous THF
(8.5 mL) was slowly added under a nitrogen atmosphere, monitor-
ing the reaction by TLC (cyclohexane–EtOAc 4:1). After about 2 h,
the starting material disappeared and the solution was diluted
with Et2O (10 mL) and a minimal amount of H2O (0.25 mL) and
then 0.25 mL of a NaOH 15% aqueous solution was added. The
resulting mixture was stirred for an additional 30 min and then fil-
tered over Celite; the solvent was removed at reduced pressure and
the obtained crude was purified by flash chromatography (cyclo-
hexane–EtOAc 75:25), affording 3a (74% yield) or 3b (75% yield).
exclusively as 1:2.7 mixture of a- and b-furanosic forms.
1.4.1. 6,7-Dideoxy-2-O-benzyl-
Syrup, yield 55%; [
+9.1 (c 0.7, CHCl3); 1H NMR (CD3CN,
500 MHz) -furanosic anomer: d 7.21–7.38 (m, 5H, aromatics H),
L-arabino-heptos-5-ulose, 4.
a
]
D
a
5.38 (d, 1H, J = 0.5 Hz, H-1), 4.50 (s, 2H, CH2Ph), 4.40 (d, 1H,
J = 5.0 Hz, H-4), 4.22 (m, 1H, H-3), 3.71 (dd, 1H, J = 0.5, 4.5 Hz, H-
2), 2.55 (q, 2H, J = 7.2 Hz, CH2), 0.87 (t, 3H, J = 7.2 Hz, CH3); b-fur-
anosic anomer: d 7.21–7.38 (m, 5H, aromatics H), 5.42 (d, 1H,
J = 5.0 Hz, H-1), 4.55 (s, 2H, CH2Ph), 4.42 (d, 1H, J = 5.0 Hz, H-4),
4.32 (t, 1H, J = 5.0 Hz, H-3), 3.76 (dd, 1H, J = 4.0, 5.0 Hz, H-2), 2.56
(q, 2H, J = 7.2 Hz, CH2), 0.91 (t, 3H, J = 7.5 Hz, CH3); 13C NMR (CDCl3,
1.2.2.1. Methyl (5S)-2-O-benzyl-6,7-dideoxy-3,4-O-isopropyli-
dene-5-C-methoxy-
phous solid, yield 74%; [
a-L-arabino-heptopyranoside, 3a. Amor-
a]
D
À12.5 (c 1.2, CHCl3); 1H NMR (CDCl3,
50 MHz) a-furanosic anomer: d 211.39 (C@O), 138.57 (aromatic C),
500 MHz): d 7.40–7.23 (m, 5H, aromatics H), 4.84–4.78 (AB system,
2H, J = 12.0 Hz, CH2Ph), 4.46 (d, 1H, J = 8.0 Hz, H-1), 4.22 (ddd, 1H,
J = 5.5, 7.5, 8.0 Hz, H-3), 4.00 (d, 1H, J = 5.5 Hz, H-4), 3.71 (dd, 1H,
J = 8.0, 7.5 Hz, H-2), 3.57 (s, 1H, C1–OCH3), 3.25 (s, 3H, C5–OCH3),
1.84 (dd, 2H, J = 5.5, 7.5 Hz, CH2CH3), 1.33 (s, 3H, CH3), 1.32 (s,
3H, CH3), 0.89 (t, 3H, J = 7.5 Hz, CH3CH2); 13C NMR (CDCl3,
50 MHz): d 139.42 (aromatic C), 128.85, 128.40, 128.13 (aromatics
CH), 109.90 (C(CH3)2), 101.85 (C-5), 99.53 (C-1), 79.60, 78.53, 75.66
(C-2, C-3, C-4), 74.24 (CH2Ph), 57.57 (C1–OCH3), 47.75 (C5–OCH3),
28.54, 26.96 (2 Â CH3), 25.04 (CH2CH3), 7.87 (CH3CH2). Anal. Calcd
for C19H28O6: C, 64.75; H, 8.01. Found: C, 64.81; H, 7.98.
129.90, 129.11, 128.55 (aromatics CH), 102.45 (C-1), 90.39 (C-4),
87.99 (C-2), 78.02 (C-3), 72.07 (CH2Ph), 32.27 (CH2), 7.21 (CH3);
b-furanosic anomer: d 212.60 (C@O), 138.63 (aromatic C), 129.34,
128.81, 128.73 (aromatics CH), 98.35 (C-1), 88.15 (C-4), 83.68 (C-
2), 76.78 (C-3), 72.75 (CH2Ph), 32.34 (CH2), 7.34 (CH3). Anal. Calcd
for C14H18O5: C, 63.15; H, 6.81. Found: C, 63.21; H, 6.86.
1.5. General method for the electrophilic ring-opening of 5
1.5.1. Reduction
A mixture of the four stereoisomers of spirocyclopropane car-
boxylates 5 (1 mmol) and LiAlH4 (1.5 mmol) in dry THF (20 mL)
was stirred at 0 °C for 1.5 h. The reaction mixture was then diluted
with Et2O (10 mL) and then quenched by the addition of H2O
(0.25 mL) and 15% aqueous solution of NaOH (0.25 mL). After the
stirring for another 30 min, the reaction mixture was filtered over
Celite, and the solvent was removed under reduced pressure to
give a crude mixture that was purified by flash chromatography
(cyclohexane–EtOAc 4:1). The corresponding hydroxymethyl
derivatives were afforded as a mixture of four stereoisomers (85%
yield), which were not separated. Their structures were confirmed
form the 1H NMR spectrum (CDCl3, 500 MHz), which showed the
cyclopropane methyl group protons (dd, J = 6.5, 10.5 Hz) in the
range 0.60–1.09 ppm, four multiplets at about 1.70–1.90 ppm for
the H-6 protons, and other multiplets in the range 3.24–3.52 and
3.72–3.93 ppm for the hydroxymethyl groups protons.
1.2.2.2. Methyl (5R)-2-O-benzyl-6,7-dideoxy-3,4-O-isopropyli-
dene-5-C-methoxy-
phous solid, yield 75%; [
a-L-arabino-heptopyranoside, 3b. Amor-
a]
À38.2 (c 0.8, CHCl3); 1H NMR (CDCl3,
D
500 MHz): d 7.40–7.24 (m, 5H, aromatics H), 4.84–4.76 (AB system,
2H, J = 12.0 Hz, CH2Ph), 4.49 (d, 1H, J = 7.0 Hz, H-1), 4.23 (d, 1H,
J = 7.0 Hz, H-4), 4.08 (dd, 1H, J = 7.0, 8.0 Hz, H-3), 3.48 (s, 1H, C1–
OCH3), 3.28 (s, 1H, C5–OCH3), 3.24 (dd, 1H, J = 6.0, 7.0 Hz, H-2),
1.85 (q, 1H, J = 7.5, 8.0 Hz, CH2CH3), 1.69 (q, 1H, J = 7.5 Hz, CH2CH3),
1.20 (dd, 3H, J = 7.5, 8.0 Hz, CH3CH2); 13C NMR (CDCl3, 125 MHz): d
138.44 (aromatic C), 128.09, 127.66, 127.40 (aromatics CH), 110.44
(C(CH3)2), 101.42 (C-1), 101.15 (C-5), 78.93, 76.92, 77.10 (C-2, C-3,
C-4), 73.10 (CH2Ph), 55.74 (C1–OCH3), 48.69 (C5–OCH3), 27.50,
26.67 (2 Â CH3), 25.15 (CH2CH3), 7.57 (CH3CH2). Anal. Calcd for
C19H28O6: C, 64.75; H, 8.01. Found: C, 64.69; H, 8.03.
1.3. General method for the direct methoxymercuration–
demercuration of 1
1.5.2. Methoxymercuration–demercuration and hydrolysis
To a stirred mixture of the four stereoisomers of hydroxymethyl
spirocyclopropane (1 equiv, 2 mmol) in dry MeOH (10 mL), mer-
cury(II) trifluoroacetate (1.4 equiv) was added at room tempera-
ture and under a nitrogen atmosphere and the reaction progress
was monitored by TLC (cyclohexane–EtOAc, 85:15) until starting
material disappeared (about 2 h). The reaction was quenched by
the addition of brine and then extracted with dichloromethane
(3 Â 20 mL); the combined organic extracts were washed with
H2O and dried (Na2SO4). After filtration, the solvent was removed
under reduced pressure to give a residue (1 equiv) that was dis-
solved in anhydrous THF (8.5 mL). The resulting mixture was
slowly added to a stirred suspension of LiAlH4 (6.75 mmol, 5 equiv)
in dry THF (8.5 mL), under a nitrogen atmosphere at the tempera-
ture of an ice bath, and then monitored by TLC (cyclohexane–
EtOAc 85:15) until the starting material disappeared (about 2 h).
The reaction mixture was diluted with Et2O (10 mL) and then
quenched by the addition of H2O (0.25 mL) and a 15% aqueous
solution NaOH (0.25 mL). After stirring for other 30 min, the solu-
The reaction mixture obtained from the methoxymercuration
step (Section 1.2.1) was used directly without separating the two
organomercuric chlorides 2a,b, for the demercuration with LiAlH4,
following the above reported procedure (Section 1.2.2). The result-
ing reaction mixture was filtered through Celite and the solvent
was removed at reduced pressure. The obtained crude material
was then purified by flash chromatography yielding the expected
bis-glycosides 3a,b with a 71% global yield.
1.4. General method for the hydrolysis of bis-glycosides 3a,b
A solution of 3a,b (456 mg, 1.25 mmol) in a 2:1 (v/v) mixture of
CH3CN–H2O (10 mL) was added of CF3COOH (2.5 mL) and stirred at
50 °C until the TLC analysis (cyclohexane–EtOAc 1:1) showed the
complete disappearance of the starting material (5 h). The mixture
was concentrated and repeatedly co-evaporated with toluene

V. Pistarà et al. / Carbohydrate Research 345 (2010) 1482–1485
1485
tion was filtered over Celite; the solvent was removed under re-
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3. Barili, P. L.; Berti, G.; Catelani, G.; D’Andrea, F.; De Rensis, F.; Puccioni, L.
Tetrahedron 1997, 53, 3407–3416.
4. Corsaro, A.; Chiacchio, M. A.; Catelani, G.; D’Andrea, F.; Adamo, R.; Pistarà, V.
Tetrahedron Lett. 2006, 47, 6591–6594.
5. Pistarà, V.; Barili, P. L.; Catelani, G.; Corsaro, A.; D’Andrea, F.; Fisichella, S.
Tetrahedron Lett. 2000, 41, 3253–3256; Catelani, G.; Corsaro, A.; D’Andrea, F.;
Mariani, M.; Pistarà, V. Bioorg. Med. Chem. Lett. 2002, 12, 3313–3315.
6. Adinolfi, M.; Barone, G.; Iadonisi, A.; Mangoni, L. Tetrahedron Lett. 1998, 39,
2021–2024.
EtOAc 60:40) gave 6-deoxy-2-O-benzyl-6-C-methyl-
D,L-arabino-
heptos-5-ulose 6 as a 1:2 - and b-furanosic anomeric mixture.
a
1.5.2.1. 6-Deoxy-2-O-benzyl-6-C-methyl-
ulose, 6. As - and b-furanosic anomeric mixture: syrup, yield
55%; [
+11.2 (c 0.4, CHCl3); 1H NMR (CD3Cl, 500 MHz): d 7.36–
7.19 (m, 20H, aromatics H), 5.51 (d, 1H, J = 0.5 Hz, H-1
1H, J = 0.5 Hz, H-1 ), 5.48 (d, 1H, J = 5.5 Hz, H-1b), 5.47 (d, 1H,
D,L-arabino-heptos-5-
a
a]
D
a), 5.50 (d,
a
J = 5.5 Hz, H-1b), 4.74–4.66 (AB system  2, each 2H, J = 11.5 Hz,
CH2Ph), 4.40–4.38 (m, 4H, H-4), 4.19 (m, 4H, H-3), 4.05–3.98 (m,
4H, H-2), 3.90–3.78 (AB system  2, each 2H, J = 11.0 Hz, CH2OH),
3.01–2.97 (dd  4, each 1H, J = 6.0, 7.5 Hz, H-6), 1.12–1.10 (d  2,
each 3H, J = 7.0 Hz, CH3); 13C NMR (CDCl3, 50 MHz): d 212.79,
211.21, 211.10, 210.85 (C@O), 138.57, 138.51, 138.43, 138.22 (aro-
matic C), 129.91, 129.57, 129.41 129.31, 128.89, 128.5 (aromatics
CH), 102.45, 102.10, 98.81, 98.44 (C-1), 91.36, 90.39, 89.66 (C-4),
85.99, 84.56, 83.10, 82.78 (C-2), 78.02, 76.22, 74.54, 74.15 (C-3),
73.65, 72.07, 71.81 (CH2Ph), 67.22, 66.15, 65.22, 65.05 (CH2OH),
45.60, 45.34 42.72, 42.17 (CH–CH3), 13.21, 12.44, 11.37 (CH3). Anal.
Calcd for C15H20O6: C, 60.80; H, 6.80. Found: C, 60.86; H, 6.82.
7.
(
L
-arabino): (a) Barili, P. L.; Berti, G.; Catelani, G.; D’Andrea, F. Gazz. Chim. Ital.
1992, 122, 135–142; Corsaro, A.; Catelani, G.; D’Andrea, F.; Fisichella, S.;
Mariani, M.; Pistarà, V. Environ. Sci. Pollut. Res. 2003, 10, 325–328; ( -xylo): (b)
Barili, P. L.; Berti, G.; Catelani, G.; D’Andrea, F.; De Rensis, F. Tetrahedron 1997,
53, 8665–8674; ( -lyxo): (c) Barili, P. L.; Catelani, G.; D’Andrea, F.; De Rensis, F.;
Goracci, G. J. Carbohydr. Chem. 1998, 17, 1167–1184; ( -ribo): (d) Barili, P. L.;
D
L
L
Bergonzi, C.; Berti, G.; Catelani, G.; D’Andrea, F.; De Rensis, F. J. Carbohydr. Chem.
1999, 18, 1037–1049.
8. (a) Catelani, G.; Corsaro, A.; D’Andrea, F.; Mariani, M.; Pistarà, V.; Vittorino, E.
Carbohydr. Res. 2003, 338, 2349–2358; (b) Enright, P. M.; Tosin, M.;
Nieuwenhuyzen, M.; Cronin, L.; Murphy, P. V. J. Org. Chem. 2002, 67, 3733–
3741.
9. Huber, R.; Molleyres, L. P.; Vasella, A. Helv. Chim. Acta 1990, 73, 1329–
1337.
10. Corsaro, A.; Chiacchio, M. A.; Pistarà, V.; Rescifina, A.; Vittorino, E. Tetrahedron
2008, 64, 8652–8658.
Acknowledgements
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Chemicals, 2nd ed.; Pergamon Press: Oxford, 1980.
Financial supports from the University of Catania, from MIUR
(Rome) and Consortia CINMPIS (Bari) and INCA (Venice) are grate-
fully acknowledged.