Selective deprotection of 2',6'-di-O-benzyl-2,3:5,6:3',4'-tri-O-isopropylidenelactose dimethyl acetal

Article abstract of DOI:10.1016/S0008-6215(99)00295-5

The reactivity order of O-deisopropylidenation of the three isopropylidene protecting groups of 2',6'-di-O-benzyl-2,3:5,6:3',4'-tri-O-isopropylidenelactose dimethyl acetal (2) with various reagents was established. The 5,6-acetal group was, although to a limited extent, more reactive as compared with the 3',4' group, while the 2,3-O-isopropylidene group was definitely less reactive. Conditions were determined for the direct preparation of the 5,6,3',4'-tetraol 5 (60% aqueous acetic acid, room temperature, 48 h, 73% yield) and the 5,6-diol 4 (propylene glycol and p-toluenesulphonic acid in dichloromethane, 46% yield). The diacetonated derivative 3, formally arising from a selective 3',4'-O-deisopropylidenation, was obtained in high yield (90%) through a selective acetonation with 2-methoxypropene of the tetraol 5. Copyright (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0008-6215(99)00295-5

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Carbohydrate Research 324 (2000) 204–209
Note
Selective deprotection of
2%,6%-di-O-benzyl-2,3:5,6:3%,4%-tri-O-isopropylidenelactose
dimethyl acetalꢀ
Giorgio Catelani *, Felicia D’Andrea, Leonardo Puccioni
Dipartimento di Chimica Bioorganica e Biofarmacia, Uni6ersita` di Pisa, 6ia Bonanno 33, I-56126 Pisa, Italy
Received 13 July 1999; accepted 4 November 1999
Abstract
The reactivity order of O-deisopropylidenation of the three isopropylidene protecting groups of 2%,6%-di-O-benzyl-
2,3:5,6:3%,4%-tri-O-isopropylidenelactose dimethyl acetal (2) with various reagents was established. The 5,6-acetal
group was, although to a limited extent, more reactive as compared with the 3%,4% group, while the 2,3-O-isopropy-
lidene group was definitely less reactive. Conditions were determined for the direct preparation of the 5,6,3%,4%-tetraol
5 (60% aqueous acetic acid, room temperature, 48 h, 73% yield) and the 5,6-diol 4 (propylene glycol and
p-toluenesulphonic acid in dichloromethane, 46% yield). The diacetonated derivative 3, formally arising from a
selective 3%,4%-O-deisopropylidenation, was obtained in high yield (90%) through a selective acetonation with
2-methoxypropene of the tetraol 5. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: 2%,6%-Di-O-benzyl-2,3:5,6:3%,4%-tri-O-isopropylidenelactose dimethyl acetal; Selective O-deisopropylidenation; 2-
Methoxypropene; Selective isopropylidenation
elongations leading to biologically relevant tri-
1. Introduction
and oligosaccharides. A prerequisite for the
success of these transformations is the
availability of simple methods for the selective
protection of the eight hydroxyl groups of
lactose.
A well-established procedure for an exten-
sive protection of disaccharides, such as lac-
tose [2–4], maltose [5] and cellobiose [6], is
their reaction with 2,2-dimethoxypropane un-
der acidic catalysis, leading, in the case of
lactose, in excellent yield to the tetraacetal 1,
(‘triacetonlactose dimethyl acetal’), in which
the OH groups 2,3:5,6 and 3%,4% are protected
by isopropylidene groups and the aldehydic
Lactose, an abundant side product from the
dairy industry, is one of the cheapest natural
sugars and can therefore be of great interest as
the starting point for an approach to more
complex saccharidic structures of high added
value. Since this disaccharide is both a b-
galactopyranoside and a 4-O-protected -glu-
D
-
D
cose, it can be used for selective operations on
both its monosaccharidic moieties, and for
ꢀ A preliminary account of this work has been presented;
see Ref. [1].
* Corresponding author. Tel.: +39-050-44-074; fax: +39-
050-43-321.
group of the acyclic
D-glucose moiety as a
E-mail address: giocate@farm.unipi.it (G. Catelani)
dimethyl acetal. This compound is useful for
0008-6215/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(99)00295-5

G. Catelani et al. / Carbohydrate Research 324 (2000) 204–209
205
operations on the free 2%- and 6%-OH of the
galactosyl moiety, such as the preparation of
the fully protected di-O-benzyl derivative 2,
which can thus be obtained from lactose on a
large scale and in high yield [4].
Compound 2 can be used as the starting
material for further transformations if efficient
methods for the selective removal of each of
the three cyclic acetal functions are available.
Rules for the prediction of the relative hydrol-
ysis rates of isopropylidene groups located an
structurally different diol functions have been
formulated [7] and the purpose of the present
work was to extend these rules to the specific
case of 2.
tests at various times within 48 h revealed that
mixtures of three product were always formed.
Pure samples of the three O-deisopropylidena-
tion products were easily obtained by flash
chromatography of the above mixtures. The
spectra of the two products having higher Rf
values than silica were both characterized by
the presence of two isopropylidene acetal
groups, whereas in the spectra of the third
hydrolysis product only one dioxolane ring
1
remained. The H NMR spectra of the perac-
etates of these products showed, in all cases,
well separated and diagnostic signals for the
protons geminal to the acetoxy groups (Sec-
tion 3), which thus allowed their structures to
be established, which were, in order of de-
creasing Rf, the 3%,4%-diol 3, the 5,6-diol 4 and
the 3%,4%,5,6-tetraol 5.
2. Results and discussion
This first phase of the hydrolysis reaction
was characterized by a practically constant
ratio between the two mono-deacetonated
products 3 and 4, ranging from 1:2 to 1:3.5,
while the ratio 5:3+4 constantly increased
with time. From a practical point of view,
these hydrolytic conditions are useful for the
preparation of tetraol 5, obtained by simple
crystallization of the crude product of a 48 h
reaction in an acceptable 73% yield. In no
case, however, was an acceptable yield of the
major mono deacetonation product 4 ob-
tained, the best result being lower than 15%.
The above results indicate that the 5,6-O-
isopropylidene group of 2 involving a primary
hydroxyl group, although to a limited extent,
is more sensitive to acidic hydrolysis than the
3%,4% one. Conversely, the third isopropylidene
group of 2, located on the secondary threo-
disposed hydroxyl groups 2 and 3 of the
acyclic portion, is much less reactive, in accor-
dance with previous results on 2%-acetamido
polyacetonated disaccharide analogues [9,10].
When the reaction time was further pro-
longed, a more polar product was formed,
obtained practically pure under more forcing
conditions, i.e., by treatment with 80% (v/v)
aqueous acetic acid for 24 h at 50 °C. Flash
chromatography of the crude product left an
analytically pure sample of this compound
(75% yield) that was characterized as the pre-
viously unreported 2%,6%-di-O-benzyllactose
(6).
The hydrolysis of 2 with aqueous acetic acid
was studied first, the reagent previously re-
ported for the complete O-deisopropylidena-
tion of several derivatives of triacetonlactose
dimethyl acetal substituted in positions 2% [3,8]
and 2%,6% [3]. The deacetonation was per-
formed in these cases by prolonged heating
with 60–80% (v/v) aqueous acetic acid and led
to the simultaneous liberation of the aldehyde
function with the spontaneous hemiacetaliza-
tion with re-pyranylization of the reducing
unit.
A preliminary estimation of the evolution of
the hydrolysis reaction with 60% (v/v)
aqueous acetic acid at room temperature with

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G. Catelani et al. / Carbohydrate Research 324 (2000) 204–209
Method A (with 60% (6/6) aq AcOH). A
Some other O-deisopropylidenation meth-
solution of 2 (5.70 g, 8.27 mmol) in AcOH (37
mL) was treated with water (25 mL) and
stirred at rt. After 48 h, TLC analysis (3:7
hexane–EtOAc) revealed almost complete
transformation of 2 (Rf 0.71) with the preva-
lent formation of 5 (Rf 0.12) and small
amounts of products 4 (Rf 0.31) and 3 (Rf
0.42). The aq soln was extracted with toluene
(4×50 mL) in order to remove the more
lipophilic compounds 3 and 4. The aq phase
was carefully neutralized at 0 °C by addition
of aq 50% NaOH and extracted with CH2Cl2
(5×50 mL). The combined organic extracts
were washed with H2O (30 mL), dried,
filtered, and concentrated. The residue (3.98 g)
was crystallized from EtOAc to give pure 5
(3.68 g, 73% yield).
ods were further tried in order to improve the
selectivity of the mono-deacetonation of 2.
Hydrogen chloride in methanol failed to bring
about selective hydrolysis of the tetra-acetal.
2,3-Dichloro-5,6-dicyano-1,4-benzoquinone
(DDQ) in CD3CN–H2O [11] showed a similar
selectivity to 60% aqueous acetic acid, yielding
5 in 72% yield.
Interestingly, the selectivity of mono-deacet-
onation sensibly increased when 2 was O-
deisopropylidenated through the ‘sacrificial
glycol’ method proposed by Andrews and
Gould [12]. The treatment of 2 with 1,2-
propanediol and p-toluenesulfonic acid in
dichloromethane at room temperature for 1 h
led to a mixture of compounds 3–5, the major
component of which was the 5,6-diol 4, iso-
lated after flash chromatography in 46% yield,
together with 3 and 5 isolated in 10 and 25%
yield, respectively.
Owing to the virtual impossibility of obtain-
ing the diol 3 in an acceptable yield through
direct hydrolysis of 2, an alternative method
for its preparation was devised, involving a
selective acetonation of the 5,6-diol function
of 5. Treatment of 5 with 2-methoxypropene
and pyridinium tosylate as catalyst led to the
formation of 3 as the sole product, obtained
after usual work-up in analytically pure form
either by flash chromatographic purification
(90% yield) or by crystallization from Et2O–
hexane (87% yield).
Method B [with 2,3-dichloro-5,6-dicyano-
1,4-benzoquinone (DDQ)]. To a solution of 2
(2.00 g, 2.90 mmol) in 9:1 CH3CN–H2O (30
mL) was added DDQ (70 mg, 0.30 mmol) and
the dark-red reaction mixture was stirred at rt.
After 24 h, TLC analysis (3:7 hexane–EtOAc)
revealed the complete disappearance of 2. The
solution was decolourized by addition of char-
coal (500 mg), followed by stirring at 80 °C
for 2–3 min. The suspension was allowed to
reach rt, filtered, and extensively washed with
MeCN (30 mL) and hot MeOH (100 mL).
The solution and washings were combined,
evaporated in vacuo, and the residue (1.86 g)
was subjected to crystallization from EtOAc
(40 mL) to give pure 5 (1.28 g, 72%): Rf 0.12
(3:7
hexane–EtOAc);
mp
171–173 °C
1
(EtOAc); [h]D −11.4° (c 1.0, CHCl3). H
NMR (CD3CN–D2O): l 7.35–7.28 (m, 10 H,
aromatic H), 4.77, and 4.64 (AB system, 2 H,
JA,B 11.0 Hz, benzylic CH2), 4.48 (s, 2 H,
benzylic CH2), 4.52–4.36 (m, 3 H, H-1, H-2,
and H-1%), 4.29 (dd, 1 H, J2,3 6.0, J3,4 1.2 Hz,
H-3), 3.77–3.51 (m, 9 H, H-4, H-5, H-6a,
H-6b, H-3%, H-4%, H-5%, H-6%a, and H-6%b), 3.38
(dd, 1 H, J1%,2% 7.5, J2%,3% 9.8 Hz, H-2%), 3.26, and
3.25 (2 s, each 3 H, 2×OMe), 1.40, and 1.34
(2 s, each 3 H, CMe2). 13C NMR (CD3CN–
D2O): l 139.00, and 138.67 (aromatic C),
129.38–128.78 (aromatic CH), 111.61 (CMe2),
105.42 (C-1), 102.90 (C-1%), 80.57 (C-2%), 78.16
(C-3), 76.69 (C-2), 76.46 (C-4), 75.88 (benzylic
CH2), 74.10 (C-3%), 73.96 (benzylic CH2), 73.57
3. Experimental
General methods.—Compound 2 was pre-
pared according to the published procedure
[4]. The following standard procedure was
used for acetylation: a solution of the com-
pound in a 2:1 (v/v) mixture (15 mL/mmol) of
pyridine and Ac2O was left at room tempera-
ture (rt) for 24 h, then repeatedly co-evapo-
rated under diminished pressure with toluene
and the residue was purified by chromatogra-
phy on silica.
4-O-(2,6-Di-O-benzyl-i- -galactopyran-
osyl)-2,3-O-isopropylidene-aldehydo-
dimethyl acetal (5)
D
D-glucose

G. Catelani et al. / Carbohydrate Research 324 (2000) 204–209
207
mL) to eliminate the excess propylene glycol,
dried, filtered, evaporated under reduced pres-
sure, and the crude products (7.25 g) subjected
to flash chromatography on silica gel (9:1
CH2Cl2–Me2CO). The following products
were obtained in the order: unreacted 2 (1.10
g), 3 (776 mg, 10.5% yield), 4 (3.40 g, 46%
yield), and 5 (1.73 g, 25% yield).
(C-5%), 72.36 (C-5), 70.01 (C-6%), 69.96 (C-4%),
62.80 (C-6), 56.10, and 53.72 (2×OMe),
27.91, and 27.28 (CMe2). Anal. Calcd for
C31H44O12: C, 61.17; H, 7.29. Found: C, 61.31;
H, 7.45.
The acetylation of 5 (500 mg, 0.82 mmol)
gave, after flash chromatography on silica gel
(EtOAc), its 3%,4%,5,6-tetra-O-acetyl derivative
(595 mg, 93%) as a syrup; Rf 0.71 (EtOAc);
[h]D +0.3° (c 1.2, CHCl3). 1H NMR
(CD3CN): l 7.38–7.29 (m, 10 H, aromatic H),
5.36 (dd, 1 H, J4%,5% 1.0 Hz, H-4%), 5.27 (ddd, 1
H, J4,5 5.6 Hz, H-5), 5.04 (dd, 1 H, J3%,4% 3.6
Hz, H-3%), 4.78 (d, 1 H, H-1%), 4.67 (dd, 1 H,
J5,6a 2.5 Hz, H-6a), 4.87, and 4.63 (AB system,
2 H, JA,B 11.5 Hz, benzylic CH2), 4.53, and
4.42 (AB system, 2 H, JA,B 11.9 Hz, benzylic
CH2), 4.41 (m, 2 H, H-1, and H-2), 4.33 (dd,
1 H, J6a,6b 12.3, J5,6b 7.0 Hz, H-6b), 4.13 (m, 1
H, H-3), 4.10 (m, 1 H, H-4), 3.96 (ddd, 1 H,
H-5%), 3.61 (dd, 1 H, J1%,2% 7.8, J2%,3% 10.1 Hz,
H-2%), 3.55 (dd, 1 H, J5%,6%a 5.8 Hz, H-6%a), 3.45
(dd, 1 H, J6%a,6%b 9.6, J5%,6%b 7.3 Hz, H-6%b), 3.35,
and 3.34 (2 s, each 3 H, 2×OMe), 2.03, 2.02,
2.00, and 1.91 (4 s, each 3 H, 4×MeCO),
1.46, and 1.40 (2 s, each 3 H, CMe2). 13C
NMR (CD3CN): l 171.28, 171.04, 170.77, and
170.77 (4×MeCO), 139.24, and 139.08 (aro-
matic C), 129.25–128.61 (aromatic CH),
110.94 (CMe2), 106.19 (C-1), 103.07 (C-1%),
78.16 (C-2%), 78.04 (C-3), 76.52 (C-2), 75.80
(C-4), 75.72, and 73.85 (2×benzylic CH2),
73.52 (C-5), 73.36 (C-3%), 72.44 (C-5%), 68.70
(C-4%), 68.18 (C-6%), 61.91 (C-6), 56.27, and
54.00 (2×OMe), 27.67, and 27.30 (CMe2),
21.20, 20.96, 20.96 and 20.78 (4×MeCO).
Anal. Calcd for C39H52O16: C, 60.30; H, 6.75.
Found: C, 60.10; H, 6.83.
Compound 4 was a syrup; Rf 0.31 (3:7
hexane–EtOAc); [h]D −13.5° (c 1.0, CHCl3).
1H NMR (CD3CN–D2O): l 7.36–7.27 (m, 10
H, aromatic H), 4.77, and 4.69 (AB system, 2
H, JA,B 12.0 Hz, benzylic CH2), 4.55, and 4.48
(AB system, 2 H, JA,B 12.2 Hz, benzylic CH2),
4.53 (d, 1 H, H-1%), 4.44–4.33 (m, 2 H, H-1,
and H-2), 4.26 (m, 1 H, H-3), 4.13–4.08 (m, 2
H, H-3%, and H-4%), 3.94 (m, 1 H, H-5%), 3.79–
3.57 (m, 6 H, H-4, H-5, H-6a, H-6b, H-6%a,
and H-6%b), 3.29, and 3.28 (2 s, each 3 H,
2×OMe), 3.26 (m, 1 H, H-2%), 1.36 (s, 6 H,
CMe2), 1.25, and 1.24 (2 s, each 3 H, CMe2).
13C NMR (CD3CN–D2O): l 139.02 (aromatic
C), 129.32–128.59 (aromatic CH), 110.87, and
110.44 (2×CMe2), 106.05 (C-1), 102.63 (C-
1%), 80.83 (C-2%), 79.56 (C-3%), 77.92 (C-3),
77.14 (C-2), 76.52 (C-4), 74.83 (C-4%), 74.13
(benzylic CH2), 73.83 (C-5), 72.79 (benzylic
CH2), 72.32 (C-5%), 69.63 (C-6%), 62.96 (C-6),
56.24, and 54.32 (2×OMe), 28.09, 27.69,
27.29, and 26.49 (2×CMe2). Anal. Calcd for
C34H48O12: C, 62.95; H, 7.46. Found: C, 63.00;
H, 7.71.
Acetylation of 4 (500 mg, 0.77 mmol) gave,
after flash chromatography on silica gel (4:6
hexane–EtOAc), its 5,6-di-O-acetyl derivative
(547 mg, 96%) as a syrup; Rf 0.56 (4:6 hex-
1
ane–EtOAc); [h]D +6.7° (c 1.1, CHCl3). H
NMR (CD3CN): l 7.39–7.31 (m, 10 H, aro-
matic H), 5.25 (ddd, 1 H, J4,5 5.2 Hz, H-5),
4.84, and 4.75 (AB system, 2 H, JA,B 12.00 Hz,
benzylic CH2), 4.66 (dd, 1 H, J5,6a 2.5 Hz,
H-6a), 4.61 (m, 1 H, H-1%), 4.59, and 4.52 (AB
system, 2 H, JA,B 12.1 Hz, benzylic CH2), 4.39
(m, 1 H, H-1), 4.38 (m, 1 H, H-2), 4.32 (dd, 1
H, J6a,6b 12.4, J5,6b 7.1 Hz, H-6b), 4.20 (m, 1
H, H-4%), 4.19 (m, 1 H, H-3%), 4.13 (m, 1 H,
H-3), 4.07 (m, 1 H, H-4), 3.96 (m, 1 H, H-5%),
3.70 (dd, 1 H, J5%,6%a 5.7 Hz, H-6%a), 3.64 (dd, 1
H, J6%a,6%b 10.0, J5%,6%b 6.6 Hz, H-6%b), 3.34, and
3.33 (2 s, each 3 H, 2×OMe), 3.29 (m, 1 H,
4-O-(2,6-Di-O-benzyl-3,4-O-isopropylidene-
i-
D
-galactopyranosyl)-2,3-O-isopropylidene-
-glucose dimethyl acetal (4).—A
aldehydo-
D
solution of 2 (7.84 g, 11.4 mmol) in dry
CH2Cl2 (200 mL) was treated with 1,2-
propanediol (5.90 mL, 79.7 mmol), TsOH
(400 mg, 2.30 mmol), and stirred at rt. After 1
h, TLC analysis (3:7 hexane–EtOAc) revealed
four spots corresponding to the products 3, 4,
5 and unreacted 2. The reaction mixture was
quenched by addition of satd aq NaHCO3 (10
mL), followed by stirring at rt for 10 min. The
organic phase was washed with water (3×50

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G. Catelani et al. / Carbohydrate Research 324 (2000) 204–209
1.41, 1.35, 1.33, and 1.26 (4 s, each 3 H,
2×CMe2). 13C NMR (CD3CN–D2O): l
139.72, and 139.12 (aromatic C), 129.12–
128.44 (aromatic CH), 111.30, and 109.35
(2×CMe2), 105.86 (C-1), 103.67 (C-1%), 80.89
(C-2%), 78.63 (C-3), 77.53 (C-2), 76.43 (C-4),
76.25 (C-5), 75.61 (benzylic CH2), 74.22 (C-3%),
73.87 (benzylic CH2), 73.81 (C-5%), 70.00 (C-
6%), 69.96 (C-4%), 66.41 (C-6), 56.08, and 53.94
(2×OMe), 27.85, 27.22, 26.92, and 25.52
(2×CMe2). Anal. Calcd for C34H48O12: C,
62.95; H, 7.46. Found: C, 62.82; H, 7.45.
The acetylation of 3 (120 mg, 0.18 mmol)
yielded, after chromatography of the crude
product on silica gel (2:3 hexane–EtOAc), the
pure 3%,4%-di-O-acetyl derivative (124 mg, 94%)
as a syrup; Rf 0.70 (2:3 hexane–EtOAc); [h]D
H-2%), 2.03, and 2.00 (2 s, each 3 H, 2×
MeCO), 1.38, 1.37, 1.34, and 1.31 (4 s, each 3
13
H, 2×CMe2). C NMR (CD3CN): l 171.26,
and 170.75 (2×MeCO), 139.45, and 139.36
(aromatic C), 129.51–128.37 (aromatic CH),
110.95, and 110.30 (2×CMe2), 106.25 (C-1),
102.52 (C-1%), 81.19 (C-2%), 79.85 (C-3%), 78.22
(C-3), 76.85 (C-2), 75.82 (C-4), 74.79 (C-4%),
74.01, and 73.79 (2×benzylic CH2), 73.68
(C-5), 72.82 (C-5%), 69.77 (C-6%), 63.00 (C-6),
56.31, and 54.37 (2×OMe), 28.20, 27.66,
27.27, and 26.56 (2×CMe2), 21.19, and 20.96
(2×MeCO). Anal. Calcd for C38H52O14: C,
62.28; H, 7.15. Found: C, 62.40; H, 7.26.
4-O-(2,6-Di-O-benzyl-i-
D
-galactopyran-
osyl)-5,6:2,3-di-O-isopropylidene-aldehydo-
D-
glucose dimethyl acetal (3).—To a mixture of
5 (1.0 g, 1.60 mmol), pyridinium tosylate (40
1
+2.7° (c 1.0, CHCl3). H NMR (CD3CN): l
7.35–7.29 (m, 10 H, aromatic H), 5.29 (dd, 1
H, H-4%), 4.93 (dd, 1 H, J3%,4% 3.6 Hz, H-3%),
4.80 (d, 1 H, H-1%), 4.83, and 4.56 (AB system,
2 H, JA,B 11.6 Hz, benzylic CH2), 4.51, and
4.40 (AB system, 2 H, JA,B 11.4 Hz, benzylic
CH2), 4.37 (d, 1 H, H-1), 4.35 (ddd, 1 H, H-5),
4.25 (dd, 1 H, J1,2 6.5 Hz, H-2), 4.10 (dd, 1 H,
J4,5 5.5 Hz, H-3), 4.09 (dd, 1 H, J5,6a 6.4 Hz,
H-6a), 3.95 (dd, 1 H, J6a,6b 8.5, J5,6b 6.1 Hz,
H-6b), 3.92 (dd, 1 H, J2,3 6.5, J3,4 1.4 Hz, H-4),
3.89 (ddd, 1 H, J4%,5% 1.2 Hz, H-5%), 3.52 (dd, 1
H, J1%,2% 7.8, J2%,3% 10.1 Hz, H-2%), 3.51 (dd, 1 H,
J5%,6%a 5.7 Hz, H-6%a), 3.40 (dd, 1 H, J6%a,6%b 9.5,
J5%,6%b 7.4 Hz, H-6%b), 3.32, and 3.30 (2 s, each
3 H, 2×OMe), 2.18, and 2.00 (2 s, each 3 H,
2×MeCO), 1.41, 1.35, 1.34, and 1.27 (4 s,
each 3 H, 2×CMe2). 13C NMR (CD3CN): l
171.14, and 170.88 (2×MeCO), 139.52, and
139.16 (aromatic C), 129.29–128.29 (aromatic
CH), 110.78, and 109.18 (2×CMe2), 106.21
(C-1), 103.79 (C-1%), 78.52 (C-3), 78.19 (C-2%),
77.85 (C-2), 76.39 (C-4), 76.16 (C-5), 75.58,
and 73.56 (2×benzylic CH2), 73.35 (C-3%),
72.19 (C-5%), 68.72 (C-4%), 68.18 (C-6%), 66.36
(C-6), 56.06, and 53.83 (2×OMe), 27.64,
27.25, 26.87, and 25.46 (2×CMe2), 20.89, and
20.76 (2×MeCO). Anal. Calcd for
C38H52O14: C, 62.30; H, 7.15. Found: C, 62.39;
H, 7.18.
,
mg, 0.16 mmol) and activated powdered 4 A
molecular sieves (340 mg) in dry CH2Cl2 (30
mL), was slowly added under Ar after 15 min
stirring, a 1:9 solution of 2-methoxypropene in
dry CH2Cl2 (2.0 mL, 2.0 mmol). The mixture
was stirred at rt for 40 min until the starting
material had disappeared (TLC analysis, 3:7
hexane–EtOAc). The suspension was neutral-
ized by addition of satd aq NaHCO3 (10 mL),
stirred for 15 min at rt and extracted with
CH2Cl2 (3×30 mL). The organic phase was
dried, filtered and evaporated in vacuo to give
a residue (991 mg) constituted exclusively by 3
(NMR). Flash chromatography on silica gel
(2:3 hexane–EtOAc) yielded pure 3 (935 mg,
90%). Pure samples of 3 were also obtained in
87% yield by crystallization (Et2O–hexane) of
the crude product obtained as above: Rf 0.42
(3:7 hexane–EtOAc); mp 72–75 °C (from
Et2O–hexane); [h]D +13.5° (c 1.1, CHCl3).
1H NMR (CD3CN–D2O): l 7.37–7.21 (m, 10
H, aromatic H), 4.84, and 4.68 (AB system, 2
H, JA,B 11.3 Hz, benzylic CH2), 4.57 (d, 1 H,
H-1%), 4.50 (s, 2 H, benzylic CH2), 4.43 (dd, 1
H, H-2), 4.33 (d, 1 H, J1,2 6.5 Hz, H-1), 4.20
(ddd, 1 H, H-5), 4.10 (dd, 1 H, J2,3 6.4 Hz,
H-3), 4.01 (dd, 1 H, J5,6a 6.0 Hz, H-6a), 3.87
(dd, 1 H, J5,6 6.3, J6a,6b 8.6 Hz, H-6b), 3.83
(dd, 1 H, J3,4 1.5, J4,5 6.3 Hz, H-4), 3.76 (dd, 1
H, J4%,5% 0.8 Hz, H-4%), 3.65–3.53 (m, 3 H, H-5%,
H-6%a, and H-6%b), 3.51 (dd, 1 H, J3%,4% 3.4 Hz,
H-3%), 3.34 (dd, 1 H, J1%,2% 7.6, J2%,3% 9.6 Hz,
H-2%), 3.30, and 3.28 (2 s, each 3 H, 2×OMe),
4-O-(2,6-Di-O-benzyl-i-
D
-galactopyran-
osyl)-h,i- -glucopyranose (6).—A solution of
D
2 (500 mg, 0.73 mmol) in aq 80% (v/v) AcOH
(40 mL) was stirred at 50 °C. After 24 h, TLC
analysis revealed the complete transformation

G. Catelani et al. / Carbohydrate Research 324 (2000) 204–209
209
of 2 into 6. The solution was allowed to reach
rt and co-evaporated three times with toluene
(3×50 mL). Flash chromatography of the
crude product (350 mg, quantitative) on silica
gel (93:7 CH2Cl2 –MeOH) yielded analytically
pure 6 (276 mg, 75%) as a 1:1 mixture of the
a- and b-pyranosidic forms measured on the
relative intensities of the C-1 signals (l (D2O)
93.57 and 97.79, respectively). Compound 6 is
a solid, Rf 0.14 (93:7 CHCl3–MeOH); [h]D
+27.2° (c 1.0, CHCl3); mp 92–94 °C. 13C
NMR (D2O): l for b-6 139.77–139.28 (aro-
matic C), 129.30–128.50 (aromatic CH),
104.31 (C-1%), 97.79 (C-1), 80.85 (C-2%), 80.57
(C-4), 75.86 (C-5%), 74.92 (C-3), 74.54 (C-5),
76.19, and 74.33 (2×benzylic CH2), 73.47
(C-2), 72.98 (C-3%), 70.53 (C-4%), 70.25 (C-6%),
61.45 (C-6); for a-6 139.77–139.28 (aromatic
C), 129.30–128.50 (aromatic CH), 104.31 (C-
1%), 93.57 (C-1), 80.85 (C-2%), 80.23 (C-4),
76.38 (C-5), 75.86 (C-5%), 76.19, and 74.33
(2×benzylic CH2), 72.98 (C-3%), 71.33 (C-3),
70.53 (C-4%), 70.53 (C-2), 70.25 (C-6%), 61.45
(C-6). Anal. Calcd for C26H34O10: C, 61.65; H,
6.77. Found: C, 61.53; H, 6.81.
ica (Rome), in the frame of the research pro-
gramme of national relevance ‘Chimica dei
Prodotti Organici di Interesse Biologico’.
References
[1] G. Catelani, F. D’Andrea, L. Puccioni, European Lac-
tose Symposium, March 25–26 1999, The Hague (NL),
Abs., p. 34.
[2] H.H. Baer, S.A. Abbas, Carbohydr. Res., 84 (1980) 53–
60.
[3] T. Yoshino, G. Reuter, S. Kelm, K. Schauer, Glycocon-
jugate J., 3 (1986) 7–14.
[4] P.L. Barili, G. Catelani, F. D’Andrea, F. De Rensis, P.
Falcini, Carbohydr. Res., 298 (1997) 75–84.
[5] Y. Ueno, K. Hori, R. Yamauchi, M. Kiso, A. Hasegawa,
K. Kato, Carbohydr. Res., 89 (1981) 271–278.
[6] Y. Ueno, K. Hori, R. Yamauchi, M. Kiso, A. Hasegawa,
K. Kato, Carbohydr. Res., 96 (1981) 65–72.
[7] (a) S.A. Barker, E.J. Bourne, Ad6. Carbohydr. Chem., 7
(1952) 137–207. (b) A.N. De Belder, Ad6. Carbohydr.
Chem. Biochem., 20 (1965) 220–302. (c) A.N. De Belder,
Ad6. Carbohydr. Chem. Biochem., 34 (1977) 179–241. (d)
A.H. Haines, Ad6. Carbohydr. Chem. Biochem., 39 (1981)
11–109.
[8] S.A. Abbas, J.J. Barlow, K.L. Matta, Carbohydr. Res.,
88 (1981) 51–60.
[9] P.L. Barili, G. Catelani, F. D’Andrea, L. Puccioni, J.
Carbohydr. Chem., in press.
[10] J.N. Glushka, A.S. Perlin, Carbohydr. Res., 205 (1990)
305–321.
[11] (a) K. Tanemura, T. Suzuki, T. Horaguchi, J. Chem.
Soc., Chem. Commun., (1992) 979–980. (b) J.M. Garcia
Fernandez, C. Ortiz Mellet, A.M. Marin, J. Fuentes,
Carbohydr. Res., 274 (1995) 263–268.
[12] M.A. Andrews, G.L. Gould, Carbohydr. Res., 229 (1992)
141–147.
Acknowledgements
This work was supported by a grant from
Ministero della Ricerca Scientifica e Tecnolog-
.