The role of sugar configuration in the acetolysis of 6-deoxyhexose methyl glycosides

Article abstract of DOI:10.1016/j.carres.2009.08.037

The acetolysis of several perbenzylated 6-deoxyhexose methyl glycosides under two mild conditions (10 equiv ZnCl₂ in 2:1 v/v Ac₂O-AcOH at 5 °C; 10:10:1 v/v/v Ac₂O-AcOH-TFA at 70 °C) was studied. We focused on the effect of

Full text of DOI:10.1016/j.carres.2009.08.037

Carbohydrate Research 344 (2009) 2406–2411
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
The role of sugar configuration in the acetolysis of 6-deoxyhexose
methyl glycosides
*
Luigi Cirillo, Annalida Di Nola, Emiliano Bedini , Michelangelo Parrilli
Dipartimento di Chimica Organica e Biochimica, Università di Napoli ‘Federico II’, Complesso Universitario Monte S.Angelo, Via Cintia 4, 80126 Napoli, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 July 2009
Received in revised form 24 August 2009
Accepted 28 August 2009
Available online 2 September 2009
The acetolysis of several perbenzylated 6-deoxyhexose methyl glycosides under two mild conditions
(10 equiv ZnCl2 in 2:1 v/v Ac2O–AcOH at 5 °C; 10:10:1 v/v/v Ac2O–AcOH–TFA at 70 °C) was studied.
We focused on the effect of sugar configuration on the competition between mechanisms with activation
at exocyclic or endocyclic oxygen site. No effect was detected in acetolysis using the TFA protocol
promoting an exo-activation mechanism, which affords 1-O-Ac-pyranosides regardless of sugar config-
uration. On the contrary, it has a primary role in determining the endo- versus exo-product distribution
on ZnCl2-promoted acetolysis.
Keywords:
Acetolysis
6-Deoxyhexose
Zinc chloride
Methyl glycoside
Furanoside
Ó 2009 Elsevier Ltd. All rights reserved.
Acyclic acetal
Acetolysis is a widely used reaction in both synthetic and ana-
lytical carbohydrate chemistry, consisting in the cleavage of the
glycosidic bond and the contemporary acetylation of the hydroxyl
groups thus formed and/or present before the solvolysis. Acetolysis
finds extensive application to the selective depolymerization of
polysaccharides and provides useful information for their struc-
tural elucidation.1 In synthetic carbohydrate chemistry, its main
application is to convert alkyl or aryl glycosides of mono- and oli-
gosaccharides into 1-O-acetylated derivatives, which are useful
building blocks easily transformable into other derivatives.
Owing to the importance of acetolysis reaction in glycochemist-
ry, several studies on the mechanism of this reaction exist in the
literature.2 The first step is the activation of endocyclic or exocyclic
anomeric oxygen toward glycoside cleavage promoted by acetyli-
um ion, which is formed from Ac2O in acidic conditions. It has been
shown that endo-activation proceeds more rapidly, nonetheless the
distribution of acetolysis products is usually governed not by
kinetic but by thermodynamic conditions, providing 1-O-Ac-
pyranoside product A after acetic acid attack on the oxocarbenium
ion (Scheme 1). On the contrary, the activation at the endo-site first
affords acyclic acetyl methyl acetal B, which can be activated in
turn by a second acetylium ion to give acyclic diacetyl acetal D
and/or 1-O-Ac-furanoside derivative E. In acidic conditions, both
B and D derivatives are in equilibrium with the aldehyde form, C.
In the literature there are only a few scattered examples of acetol-
ysis of common hexose glycosides affording predominantly endo-
activation mechanism products.2d,e,3 In the case of 6-deoxyhexos-
es, acetolysis with activation at endo-site should be more easily
achieved because the lack of the electron-withdrawing oxygen
atom at the 6-position enhances the nucleophilicity of the endocy-
clic oxygen. Indeed, some examples were reported on the acetoly-
sis of 6-deoxyhexose glycosides affording B-, C-, D-, or E-like
derivatives as the main products.4
We very recently developed two different protocols for the mild
and selective acetolysis of 6-deoxyhexose methyl glycosides deriv-
atized with armed protecting groups. The first protocol (10:10:1 v/
v/v Ac2O–AcOH–TFA at 70 °C)5 allowed the conversion of disaccha-
ride methyl glycosides composed of rhamnose and fucose into
1-O-acetyl pyranosides (A-like products) in good to excellent yield,
without any significant competition of endo-activation mecha-
nism.6 On the contrary, the second protocol (10 equiv ZnCl2 in
2:1 v/v Ac2O–AcOH at 5 °C)7 afforded in good yields 1-O-acetyl fur-
anosides (E-like products) from rhamnose disaccharide methyl
glycosides, as products of endo-activation mechanism.8 In the pres-
ent work we study the role of sugar configuration in driving the
acetolysis of 6-deoxyhexose methyl glycosides preferentially to
an endo- or exo-activated mechanism. For this reason, we first syn-
thesized fully benzylated methyl glycosides of the most common
natural deoxysugars (compounds 1, 3, 5, 6, 8, 10 and 12) through
standard procedures. Then, these compounds were subjected to
both protocols described above. Ac2O–AcOH–TFA protocol
furnished 1-O-Ac pyranosides in all studied cases in good to excel-
lent yield (Table 1), confirming previously reported results on
* Corresponding author. Tel.: +39 81 674153; fax: +39 81 674393.
E-mail address: ebedini@unina.it (E. Bedini).
0008-6215/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2009.08.037

L. Cirillo et al. / Carbohydrate Research 344 (2009) 2406–2411
2407
POH2C
PO
POH2C
PO
POH2C
PO
O+
O
O
AcOH
O+Me
Ac
OAc
Ac+
-MeOAc
AcOH
POH2C
PO
PO
OP
PO
OP
O
PO
OP
path "exo"
OMe
A
P
POH2C
PO
Ac
POH2C
PO
POH2C
path "endo"
O+
OAc
OP
OAc
OAc
PO
O+
OP
OAc
OAc
Ac+
-MeOAc
AcOH
OMe
PO
OAc
Ac+
POH2C
OMe
O+Me
Ac
PO
OP
PO
PO
OP
PO
AcOH
OP
-POAc
B
AcOH
AcOH
AcOH
-Ac2O, -MeOH
-MeOAc
-Ac2O, -MeOH
POH2C
PO
POH2C
OAc
O
OAc
OAc
Ac2O
P=protecting group
OAc
OAc
PO
PO
POH2C
CHO
OAc
-Ac2O
PO
OP
PO
OP
OP
C
D
E
Scheme 1. Endo- versus exo-activation acetolysis mechanism.
rhamnose and fucose disaccharides.6 Therefore, it seems that, in
such conditions, acetolysis with activation at exocyclic oxygen is
rather independent of sugar as well as anomeric configuration.
On the contrary, acetolysis using the ZnCl2 protocol afforded differ-
ent compounds on the basis of the starting 6-deoxyhexose (Table
2). 6-Deoxy-mannose (rhamnose) methyl glycoside 1 gave 1-O-
Ac furanoside E-like derivative 11 as the main product (62%) (entry
1). 6-Deoxy-talose (epifucose) glycoside 12 was acetolyzed using
the ZnCl2 protocol through an endo-activation mechanism, giving
open-chain B- and C-like derivatives 13 and 14, respectively (entry
2). Open-chain C- and D-like derivatives 15 and 16 were obtained
from b-methyl 6-deoxy-glucoside (quinovoside) 3, together with
fucoside 12 afford products derived by an endo-activation,
whereas -methyl glycosides having an equatorial O-2 (quinovo-
a
side 5 and fucoside 8) gave 1-O-Ac-pyranosides in high yields
through an exo-activation mechanism. This could be ascribed to
the antiperiplanar relationship of the C2–O2 and C1–O1 bonds,
which enhances the electron-withdrawing effect of the axial O-2
on the exo-oxygen atom,11 thus favoring an activation at the
endo-site. With methyl 6-deoxy-a-altroside 6, other stereoelec-
tronic factors could countervail the O-2 axial effect, giving the
simultaneous formation of products from both exo- and endo-
mechanism. Interestingly, these results were very well replicated
on disaccharide cases,6,8 suggesting that a potential Zn(II)-sugar
complexation12 has a minor effect on the competition between
exo- and endo-mechanism, because the geometry of such coordi-
nation should be highly dependent on saccharide structure.
Regardless, a precise and detailed understanding of the role of
6-deoxysugar configuration on acetolysis reactions under kinetic
control will surely need kinetics studies.
E-like furanoside 17, whereas a-counterpart 5 afforded exclusively
1-O-Ac pyranoside 49 (73%), as the product of an exo-activation
mechanism (entries 3 and 4). A balanced competition between
exo- and endo-mechanism can be hypothesized for 6-deoxy-altrose
(altromethylose) glycoside 6, which afforded an ꢀ1:1 mixture be-
tween 1-O-Ac pyranoside 7 (50%) and C-like open-chain derivative
18 (42%) (entry 5). Finally, both
a
- and b-methyl fucoside gave
To summarize, this work demonstrated that the 6-deoxyhexose
configuration has no effect in acetolysis under Ac2O–AcOH–TFA
reaction conditions, which promote an exo-activation mechanism
affording 1-O-Ac-pyranosides. On the contrary, 6-deoxyhexose
configuration has a primary role in determining the endo- versus
exo-activation product distribution on ZnCl2-promoted acetolysis.
exclusively 1-O-Ac pyranoside 910 through the exo-activation
mechanism (entries 6 and 7).
These results suggest that the role of configuration is crucial
for driving the acetolysis using the ZnCl2 protocol toward an
exo- or endo-activation mechanism. The preference for a mecha-
nism with activation at the endocyclic or exocyclic oxygen atom
is strongly dictated by the anomeric configuration. The exocyclic
oxygen is involved in the exo-anomeric effect in both anomers,
whereas the endocyclic oxygen is involved in n?r* donation to
1. Experimental
the C1–O bond only in the a
-anomer.2e The overall effect is a gen-
1.1. General methods
eral increased nucleophilicity of the endocyclic oxygen in the b-
anomers, which explains the preference of b-quinovoside 3 to
1H and 13C NMR spectra were recorded on a Bruker DRX-400
(1H: 400 MHz, 13C: 100 MHz) instrument in CDCl3 (CHCl3 as an
internal standard, 1H: CHCl3 at d 7.26; 13C: CDCl3 at d 77.0). Assign-
ment of proton chemical shifts was based on 1D HOHAHA experi-
ments. Positive MALDI-MS spectra were recorded on an Applied
Biosystem Voyager DE-PRO MALDI-TOF mass spectrometer in the
positive mode: compounds were dissolved in CH3CN at a concen-
give endo-derived products with respect to
a-counterpart 5. In
the b-fucoside case the main stereoelectronic effect is the strong
through-space electron donation of the axially oriented O-4 sub-
stituent into the oxocarbenium ion formation, which highly en-
hances the first-order rate constant for the exo-activation
involving galacto-configured alkyl glycosides with respect to glu-
co-configured counterparts;2g the result is that both fucoside ano-
mers afford exclusively 1-O-Ac-pyranosides through an exo-
tration of 1 mg/mL, and 1
lL of these solutions was mixed with
1
lL of a 20 mg/mL solution of 2,5-dihydroxybenzoic acid in 7:3
CH3CN–0.1 M trifluoroacetic acid. Optical rotations were measured
on a JASCO P-1010 polarimeter. Elemental analyses were per-
formed on a Carlo Erba 1108 instrument. Analytical thin layer
activation mechanism. With the
configuration at O-2 seems to be very important too. Indeed,
compounds having an axial O-2 such as rhamnoside 1 and epi-
a-methyl glycosides, the role of

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L. Cirillo et al. / Carbohydrate Research 344 (2009) 2406–2411
Table 1
Acetolysis on 6-deoxyhexose methyl glycosides with 10:10:1 v/v/v Ac2O–AcOH–TFA at 70 °C (see Section 2 for details)
Entrya
Methyl glycoside
Time (h)
Productsb
OAc
OMe
O
O
16b
21
BnO
BnO
BnO
BnO
OBn
OBn
c
1
2
(61%;62 )
O
O
BnO
BnO
BnO
BnO
OM
2
3
4
46
19
21
OBn
OBn
OAc
49 (59%, α/β = 3.5:1)d
3
O
BnO
BnO
49 (72%, /b = 3:1)d
a
OBn
OMe
5
OMe
OAc
OBn
O
OBn
O
BnO
BnO
7 (66%, β/αO=Bn1.5:1)e
OBn
6
OMe
OAc
O
O
OBn
OBn
5
6
24
24
OBn
B9nO
OBn
BnO
d
10 (99%, α/β = 4:1)
8
OMe
OBn
O
910 (83%, /b = 3:1)d
a
OBn
BnO
10
a
b
c
Reaction conducted on 0.1 mmol scale, unless otherwise specified.
Isolated yield.
Yield on 1 mmol scale.
d
e
Anomeric ratio measured by 1H NMR.
Anomeric ratio measured by isolation of the two anomers.
chromatography (TLC) was performed on aluminum plates pre-
coated with Merck Silica Gel 60 F254 as the adsorbent. The plates
were developed with 10% H2SO4 ethanolic solution and then
heated to 130 °C. Column chromatography was performed on
Merck Kieselgel 60 (63–200 mesh).
(ꢁ10%) of unreacted starting material could be still detected in
some cases; nonetheless, longer reaction times were detrimental
for the yield, as the products could react further by debenzylation.
The mixture was then diluted with CH2Cl2 (25 mL) and washed
successively with water (25 mL) and 1 M NaHCO3 (25 mL). The
organic layer was dried over anhydrous Na2SO4, filtered, and
1.2. General procedure for acetolysis using TFA6b
concentrated to give
chromatography.
a residue that was subjected to flash
Methyl glycoside (100
lmol) was dissolved in Ac2O (1.5 mL)
and treated with AcOH (1.5 mL) and TFA (150
lL). The solution
1.3. General procedure for acetolysis using ZnCl2
was stirred at 70 °C in a round-bottomed flask closed with a glass
stopper. The reaction was stopped by cooling to rt when TLC (3:1
petroleum ether–EtOAc or 7:1 pentane–EtOAc or 9:1 toluene–
EtOAc) showed full or almost complete disappearance of the start-
ing material (see Table 1). It is worth noting that a small amount
Methyl glycoside (100 mol) was dissolved in a 2:1 v/v Ac2O/
l
AcOH mixture (1.5 mL), cooled to 5 °C, and then treated with
freshly fused ZnCl2 (1.0 mmol). The reaction was worked up as
indicated for TFA protocol.

L. Cirillo et al. / Carbohydrate Research 344 (2009) 2406–2411
2409
Table 2
Acetolysis on 6-deoxyhexose methyl glycosides with 10 equiv ZnCl2 in 2:1 v/v Ac2O–AcOH at 5 °C (see Section 2 for details)
Entrya
Methyl glycoside
Time (h)
Productsb
OAc
OMe
OBn
OBn
O
AcO
O
O
1
21
BnO
BnO
BnO
BnO
OAc
OBn
OBn
13 (22%; 25%c)
1
11 (63%; 62%c)
2
MeO
OAc
CHO
OBn
OMe
OBn
OBn
OAc
OBn
O
OBn
OAc
2
48
AcO
AcO
BnO
BnO
OBn
12
CH3
CH3
13 (48%, dr = 1.5:1)d
14 (16%)
CHO
OBn
CH(OAc)2
OBn
OBn
O
O
AcO
BnO
BnO
OMe
OAc
BnO
OAc
OAc
OAc
OAc
3
46
OBn
3
OBn
CH3
CH3
15 (25%)
16 (23%)
17 (24%; α/β = 2.5:1)e
O
O
BnO
BnO
BnO
BnO
4
5
19
21
OBn OAc
OBn
OMe
49 (73%, α/β = 4.5:1)e
5
MeO
OAc
OBn
OMe
OAc
OBn
OBn
O
BnO
AcO
AcO
O
BnO
BnO
OBn
f
OBn
6
CH3
7
18 (42%, dr = 1.2:1)d
(50%, β/α = 1.7:1)
OMe
OAc
O
O
OBn
OBn
6
7
24
24
OBn
BnO
OBn
OBn
BnO
BnO
9
10 (98%, α/β = 4:1)e
8
OMe
OBn
O
910 (72%, /b = 5:1)e
a
a
b
c
d
e
f
Reaction conducted on 0.1 mmol scale, unless otherwise specified.
Isolated yield.
Yield on 1 mmol scale.
Diastereoisomeric ratio measured by 1H NMR.
Anomeric ratio measured by 1H NMR.
Anomeric ratio measured by isolation of the two anomers.

2410
L. Cirillo et al. / Carbohydrate Research 344 (2009) 2406–2411
1.4. 1-O-Acetyl-2,3,4-tri-O-benzyl-6-deoxy-
a
-
L
-altropyranose (7
a
)
2OCH2Ph0), 78.3, 76.6, 74.3, 73.4, 72.6, 69.2 (C-200, C-300, C-400, C-500,
2OCH2Ph00), 57.9 (OCH030), 57.3 (OCH30 ), 21.1–21.0 (2COCH0 ,
3
[a
]
D
+4 (c 0.9; CH2Cl2); 1H NMR (400 MHz, CDCl3): d 7.36–7.25
2COCH300), 20.9 (COCH03), 20.8 (COCH300), 17.0 (C-600), 16.8 (C-60); MAL-
DI TOF-MS:calcd for C27H34O9 (m/z), 502.22; found, 525.02 [M+Na]+;
Anal. Calcd for C27H34O9: C, 64.53; H, 6.82. Found: C, 64.49; H, 6.85.
(m, 15H, H-Ar), 5.99 (br s, 1H, H-1), 4.66 (d, 1H, Jgem = 12.1 Hz,
OCHHPh), 4.52–4.45 (m, 5H, 5 OCHHPh), 4.35–4.31 (dq, 1H,
J5,4 = 9.2 Hz, J5,6 = 6.5 Hz, H-5), 3.78–3.75 (m, 2H, H-2, H-3), 3.50
(dd, 1H, J4,5 = 9.2 Hz, J4,3 = 2.8 Hz, H-4), 2.02 (s, 3H, CH3CO), 1.29
(d, 3H, J6,5 = 6.3 Hz, H-6); 13C NMR (100 MHz, CDCl3) d 169.9
(CO), 138.1, 138.0, 137.6 (3Cipso–Bn), 128.6–127.7 (C-Ar), 92.3 (C-
1), 73.7, 72.7, 72.6, 72.1, 71.5, 66.1, 65.9 (C-2, C-3, C-4, C-5,
3OCH2Ph), 21.1 (CH3CO), 17.8 (C-6). MALDI TOF-MS: calcd for
C29H32O6 (m/z), 476.22; found, 499.05 [M+Na]+; Anal. Calcd for
C29H32O6: C, 73.09; H, 6.77. Found: C, 73.30; H, 6.62.
1.8. 4,5-Di-O-acetyl-2,3-di-O-benzyl-6-deoxy-L-talose (14)
1H NMR (400 MHz, CDCl3): d 9.57 (s, 1H, H-1), 7.34–7.26 (m,
10H, H-Ar), 5.33–5.29 (m, 2H, H-5, H-4), 4.73 (d, 1H, Jgem = 10.0 Hz,
OCHHPh), 4.70 (d, 1H, Jgem = 10.0 Hz, OCHHPh), 4.51 (d, 1H,
Jgem = 11.1 Hz, OCHHPh), 4.42 (d, 1H, Jgem = 11.1 Hz, OCHHPh),
4.05 (d, 1H, J2,3 = 2.2 Hz, H-2), 3.97 (dd, 1H, J3,4 = 8.2 Hz,
J3,2 = 2.2 Hz, H-3), 2.05 (s, 3H, CH3CO), 1.99 (s, 3H, CH3CO), 1.17
(d, 3H, J6,5 = 6.4 Hz, H-6); 13C NMR (100 MHz, CDCl3): d 200.7 (C-
1), 170.9, 169.4 (2CO), 137.9, 137.3 (2Cipso–Bn), 128.4–127.6 (C-
Ar), 81.3, 78.5, 73.2, 72.6, 72.1, 68.4 (C-2, C-3, C-4, C-5, 2OCH2Ph),
20.9, 20.7 (2COCH3), 16.7 (C-6); MALDI TOF-MS: calcd for C24H28O7
(m/z), 428.18; found, 451.00 [M+Na]+; Anal. Calcd for C24H28O7: C,
67.28; H, 6.59. Found: C, 67.46; H, 6.48.
1.5. 1-O-Acetyl-2,3,4-tri-O-benzyl-6-deoxy-b-L-altropyranose (7b)
[a
]
D ꢂ4.2 (c 1.6; CH2Cl2); 1H NMR (400 MHz, CDCl3): d 7.34–7.22
(m, 15H, H-Ar), 6.02 (d, 1H, J1,2 = 1.5 Hz, H-1), 4.63 (d, 1H,
Jgem = 12.4 Hz, OCHHPh), 4.56 (d, 1H, Jgem = 12.1 Hz, OCHHPh), 4.50
(d, 1H, Jgem = 12.4 Hz, OCHHPh), 4.49 (d, 1H, Jgem = 12.1 Hz, OCHHPh),
4.45 (d, 1H, Jgem = 11.8 Hz, OCHHPh), 4.42 (d, 1H, Jgem = 11.8 Hz,
OCHHPh), 4.09 (dq, 1H, J5,4 = 9.0 Hz, J5,6 = 6.3 Hz, H-5), 3.74 (dd, 1H,
J3,2 = 4.3 Hz, J3,4 = 2.9 Hz, H-3), 3.65 (dd, 1H, J2,3 = 4.4 Hz,
J2,1 = 1,5 Hz, H-2), 3.49 (dd, 1H, J4,5 = 9.0 Hz, J4,3 = 2.9 Hz, H-4), 2.10
(s, 3H, CH3CO), 1.31 (d, 3H, J6,5 = 6.3 Hz, H-6); 13C NMR (100 MHz,
CDCl3) d 169.1 (CO), 138.0–137.9 (3Cipso–Bn), 128.5–127.8 (C-Ar),
91.8 (C-1), 77.7, 74.6, 73.5, 72.9, 72.8, 72.0, 70.4 (C-2, C-3, C-4, C-5,
3OCH2Ph), 21.1 (CH3CO), 18.1 (C-6); MALDI TOF-MS: calcd for
C29H32O6 (m/z), 476.22; found, 499.06 [M+Na]+; Anal. Calcd for
C29H32O6: C, 73.09; H, 6.77. Found: C, 72.95; H, 6.56.
1.9. 4,5-Di-O-acetyl-2,3-di-O-benzyl-D-quinovose (15)
[a]
D
+10 (c 0.4; CH2Cl2); 1H NMR (400 MHz, CDCl3): d 9.73 (s,
1H, CHO), 7.36–7.23 (m, 10H, H-Ar), 5.35 (dd, 1H, J4,5 = 6.4 Hz,
J4,3 = 3.0 Hz, H-4), 5.10 (quintet, 1H, J5,4 = J5,6 6.4 Hz, H-5), 4.77 (d,
1H, Jgem = 12.0 Hz, OCHHPh), 4.57 (s, 2H, OCH2Ph), 4.52 (d, 1H,
Jgem = 12.0 Hz, OCHHPh), 3.92 (m, 2H, H-2, H-3), 2.02 (s, 3H,
CH3CO), 1.97 (s, 3H, CH3CO), 1.19 (d, 3H, J6,5 = 6.4 Hz, H-6); 13C
NMR (100 MHz, CDCl3): d 201.1 (CHO), 169.9, 169.7 (2CO), 136.9,
136.8 (2Cipso–Bn), 128.6–128.0 (C-Ar), 80.6, 77.5, 74.1, 73.2, 72.1,
68.6 (C-2, C-3, C-4, C-5, 2OCH2Ph), 21.2, 20.8 (2CH3CO), 15.8 (C-
6); MALDI TOF-MS: calcd for C24H28O7 (m/z), 428.18; found,
451.01 [M+Na]+; Anal. Calcd for C24H28O7: C, 67.28; H, 6.59. Found:
C, 67.09; H, 6.49.
1.6. 1,5-Di-O-acetyl-2,3-di-O-benzyl-a-L-rhamnofuranose (11)
[a
]D ꢂ11.8 (c 1.6; CH2Cl2); 1H NMR (400 MHz, CDCl3): d 7.35–7.30
(m, 10H, H-Ar), 6.29 (d, 1H, J1,2 = 2.3 Hz, H-1), 5.27 (quintet, 1H,
J5,6 = J5,4 = 6.0 Hz, H-5), 4.71 (d, 1H, Jgem = 1.6 Hz, OCHHPh), 4.68 (d,
1H, Jgem = 11.6 Hz, OCHHPh), 4.63 (d, 1H, Jgem = 11.6 Hz, OCHHPh),
4.50 (d, 1H, Jgem = 11.6 Hz, OCHHPh), 4.23 (m, 2H, H-3, H-4), 4.02
(dd, 1H, J2,3 = 4.4 Hz, J2,1 = 2.3 Hz, H-2), 2.07, 1.92 (2s, 6H, 2CH3CO),
1.32 (d, 3H, J6,5 = 6.4 Hz, H-6); 13C NMR (100 MHz, CDCl3) d 170.0,
169.8 (2CO), 137.7, 137.4 (2Cipso–Bn), 128.5–127.5 (C-Ar), 99.3
(C-1), 81.7, 81.6, 76.8, 73.2, 72.6, 69.2 (C-2, C-3, C-4, C-5, 2OCH2Ph),
21.2 (2CH3CO), 16.1 (C-6); MALDI TOF-MS: calcd for C24H28O7 (m/z),
428.18;found, 450.99[M+Na]+;Anal. CalcdforC24H28O7:C, 67.28;H,
6.59. Found: C, 67.46; H, 6.50.
1.10. 1,1,4,5-Tetra-O-acetyl-2,3-di-O-benzyl-D-quinovose acetal
(16)
[a]
D +19 (c 0.5; CH2Cl2); 1H NMR (400 MHz, CDCl3): d 7.34–7.28
(m, 10H, H-Ar), 6.97 (d, 1H, J1,2 = 3.2 Hz, H-1), 5.24 (d, 1H,
J4,5 = 5.9 Hz, J4,3 = 3.2 Hz, H-4), 5.16 (quintet, 1H, J5,4 = J5,6 = 6.2 Hz,
H-5), 4.78 (d, 1H, Jgem = 10.9 Hz, OCHHPh), 4.74 (d, 1H, Jgem = 11.6 Hz,
OCHHPh), 4.71 (d, 1H, Jgem = 11.6 Hz, OCHHPh, 4.52 (d, 1H,
Jgem = 10.9 Hz, OCHHPh), 3.81 (m, 2H, H-2, H-3), 2.09 (s, 3H, CH3CO),
2.08 (s, 3H, CH3CO), 2.03 (s, 3H, CH3CO), 1.97 (s, 3H, CH3CO), 1.21 (d,
3H, J6,5 = 6.2 Hz, H-6); 13C NMR (100 MHz, CDCl3): d 170.2, 170.0,
168.7, 168.5 (4 CO), 137.7, 137.5 (2Cipso–Bn), 128.6–127.8 (C-Ar),
88.1 (C-1), 78.0, 76.1, 74.7, 74.1, 73.3, 69.2 (C-2, C-3, C-4, C-5,
2OCH2Ph), 21.1, 20.9, 20.8, 20.7 (4CH3CO), 15.8 (C-6); MALDI TOF-
MS: calcd for C28H34O10 (m/z), 530.22, found, 552.89 [M+Na]+; Anal.
Calcd for C28H34O10: C, 63.39; H, 6.46. Found: C, 63.11; H, 6.24.
1.7. 1,4,5-Tri-O-acetyl-2,3-di-O-benzyl-6-deoxy-1-O-methyl-L-
talose acetal (13)
1H NMR (400 MHz, CDCl3): d 7.39–7.26 (m, 10H0 + 10H00, H-Ar),
5.98 (d, 1H0, J1,2 = 6.8 Hz, H-10), 5.89 (d, 1H00, J1,2 = 4.2 Hz, H-100),
5.31 (dq, 1H0, J5,6 = 6.5 Hz, J5,4 = 2.8 Hz, H-50), 5.27 (m, 2H00, H-400, H-
500), 5.23 (dd, 1H0, J4,3 = 8.3 Hz, J4,5 = 2.8 Hz, H-40), 4.81 (d, 1H00,
Jgem = 11.5 Hz, OCHHPh00), 4.74 (d, 1H0, Jgem = 11.9 Hz, OCHHPh0),
4.72 (d, 1H00, Jgem = 11.5 Hz, OCHHPh00), 4.68 (d, 1H0, Jgem = 11.9 Hz,
OCHHPh0), 4.62 (d, 1H0, Jgem = 10.7 Hz, OCHHPh0), 4.55 (s, 2H00,
OCH2Ph00), 4.40 (d, 1H0, Jgem = 10.7 Hz, OCHHPh0), 3.84 (dd, 1H0,
J3,4 = 8.3 Hz, J3,2 = 2.2 Hz, H-30), 3.76 (m, 2H00, H-200, H-300), 3.73 (dd,
1H0, J2,1 = 6.8 Hz, J2,3 = 2.2 Hz, H-20), 3.43 (s, 3H0 + 3H00, 2OCH3), 2.12
(s, 3H0, CH3CO0), 2.09 (s, 3H00, CH3CO00), 2.07 (s, 3H00, CH3CO00), 2.03
(s, 3H0, CH3CO0), 1.97 (s, 3H0, CH3CO0), 1.93 (s, 3H00, CH3CO00), 1.16
(d, 3H0, J6,5 = 6.5 Hz, H-60), 1.13 (d, 3H00, J6,5 = 6.1 Hz, H-600); 13C
NMR (100 MHz, CDCl3): d 170.9 (CO0), 170.3 (CO00), 170.0 (CO0),
169.8 (2CO00), 169.7 (CO0), 137.9 (Cipso–Bn0), 137.8 (Cipso–Bn00), 137.3
(Cipso–Bn0), 137.2 (Cipso–Bn00), 128.5–127.5 (C-Ar), 98.1 (C-100), 97.8
(C-10), 78.7, 76.8, 74.0, 73.1, 72.8, 69.1 (C-20, C-30, C-40, C-50,
1.11. 1,5-Di-O-acetyl-2,3-di-O-benzyl-D-quinovofuranose (17)
1H NMR (400 MHz, CDCl3): d 7.36–7.24 (m, 10H + 10Hb, H-Ar),
a
6.35 (d, 1H , J1,2 = 4.2 Hz, H-1 ), 6.16 (br s, 1Hb, H-1b), 5.24 (dq,
a
a
1Hb, J5,6 = 7.4 Hz, J5,6 = 6.3 Hz, H-5b), 5.18 (dq, 1H , J5,6 = 6.2 Hz,
a
J5,4 = 4.5 Hz, H-5 ), 4.64 (m, 2H + 1Hb, 2OCHHPh + OCHHPhb),
a
a
a
4.58 (d, 1H , Jgem = 12.0 Hz, OCHHPh ), 4.55 (d, 1Hb, Jgem = 12.0 Hz,
a
a
OCHHPhb), 4.50 (d, 1H , Jgem = 11.5 OCHHPh ), 4.48 (d, 1Hb,
a
a
Jgem = 12.0 Hz, OCHHPhb), 4.41 (d, 1Hb, Jgem = 12.0 Hz, OCHHPhb),
4.36 (dd, 1H , J4,3 = 5.8 Hz, J4,5 = 4.5 Hz, H-4 ), 4.29 (dd, 1Hb,
a
a
J4,5 = 7.4 Hz, J4,3 = 5.0 Hz, H-4b), 4.12 (m, 2H , H-2 , H-3 ), 4.04 (br
a
a
a
s, 1Hb, H-2b), 4.03 (dd, 1Hb, J3,4 = 5.0 Hz, J3,2 = 1.3 Hz, H-3b), 2.09 (s,

L. Cirillo et al. / Carbohydrate Research 344 (2009) 2406–2411
2411
3H , CH3CO ), 2.04 (s, 3Hb, CH3COb), 1.97 (s, 3H , CH3CO ), 1.91 (s,
Acknowledgments
a
a
a
a
3Hb, CH3COb), 1.34 (d, 3Hb, J6,5 = 6.2 Hz, H-6b), 1.30 (d, 3H ,
a
J6,5 = 6.2 Hz, H-6 ); 13C NMR (100 MHz, CDCl3): d 170.1, 169.9
NMR and MS facilities of CIMCF (Centro Interdipartimentale di
Metodologie Chimiche Fisiche) are acknowledged.
a
(2CO ), 170.1, 169.8 (2COb), 137.6, 137.2 (2Cipso–Bn ), 137.4, 137.1
a
a
(2Cipso–Bnb), 128.5–127.5 (C-Ar), 100.2 (C-1b), 94.4 (C-1 ), 84.5,
a
84.2, 80.5, 72.1, 72.0, 68.6 (C-2b, C-3b, C-4b, C-5b, 2OCH2Phb), 83.2,
References
80.0, 77.0, 73.3, 72.6, 69.0 (C-2 , C-3 , C-4 , C-5 , 2OCH2Ph ),
a
a
a
a
a
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a
a
TOF-MS: calcd for C24H28O7 (m/z), 428.18; found, 451.39 [M+Na]+;
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1H NMR (400 MHz, CDCl3): d 7.36–7.26 (m, 10H0 + 10H00, H-Ar),
6.00 (d, 1H0, J1,2 = 6.3 Hz, H-10), 5.94 (d, 1H00, J1,2 = 4.1 Hz, H-100), 5.47
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5.25 (dq, 1H00, J6,5 = 6.5 Hz, J5,4 = 4.0 Hz, H-500), 4.74 (d, 1H0,
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4.70 (d, 1H00, Jgem = 11.2 Hz, OCHHPh00), 4.69 (d, 1H0, Jgem = 11.5 Hz,
OCHHPh0), 4.67 (d, 1H00, Jgem = 11.2 Hz, OCHHPh00), 4.66 (s, 2H0,
OCH2Ph0), 4.64 (d, 1H00, Jgem = 11.2 Hz, OCHHPh00), 3.88 (dd, 1H0,
J3,4 = 6.2 Hz, J3,2 = 3.8 Hz, H-30), 3.80 (t, 1H00, J3,2 = J3,4 = 5.3 Hz, H-
300), 3.67 (dd, 1H00, J2,3 = 5.3 Hz, J2,1 = 4.2 Hz, H-200), 3.63 (dd, 1H0,
J2,1 = 6.3 Hz, J2,3 = 3.8 Hz, H-20), 3.50 (s, 3H00, OCH030), 3.37 (s, 3H0,
OCH03), 2.06 (s, 3H0, CH3CO0), 2.05 (s, 3H00, CH3CO00), 2.03 (s, 3H00,
CH3CO00), 1.99 (s, 6H0, 2CH3CO0), 1.98 (s, 3H00, CH3CO00), 1.26 (d,
3H0 + 3H00, J6,5 = 6.5 Hz, H-60, H-600); 13C NMR (100 MHz, CDCl3): d
170.8 (CO0), 170.5 (CO00), 170.1 (CO0), 170.0 (CO0), 169.8 (2CO00),
138.1 (Cipso–Bn0), 138.0 (2Cipso–Bn00), 137.9 (Cipso–Bn0), 128.8–
127.5 (C-Ar), 97.6 (C-10, C-100), 79.5, 77.3, 74.9, 73.3, 72.4, 69.5 (C-
20, C-30, C-40, C-50, 2OCH2Ph0), 78.9, 77.7, 74.8, 73.9, 73.0, 72.2 (C-
200, C-300, C-400, C-500, 2OCH2Ph00), 57.9 (OCH300), 57.2 (OCH30 ), 21.1–
20.9 (3COCH03, 3COCH030), 15.3 (C-600), 15.2 (C-60); MALDI TOF-MS:
calcd for C27H34O9 (m/z), 502.22; found, 524.96 [M+Na]+; Anal.
Calcd for C27H34O9: C, 64.53; H, 6.82. Found: C, 64.75; H, 6.80.
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