Lactose as an inexpensive starting material for the preparation of aldohexos-5-uloses: synthesis of l-ribo and d-lyxo derivatives

Article abstract of DOI:10.1016/j.carres.2009.11.027

Partially protected derivatives of l-ribo- and d-lyxo-aldohexos-5-ulose have been prepared starting from triacetonlactose dimethyl acetal derivatives. Key steps of the synthetic sequences are (a) the synthesis of 4′-deoxy-4′-eno- and 6′-deoxy-5′-eno lactose derivatives, and (b) the epoxidation-methanolysis of the above-mentioned enol ethers to give 1,5-bis-glycopyranosides, masked form of the target 1,5-dicarbonyl hexoses.

Full text of DOI:10.1016/j.carres.2009.11.027

Carbohydrate Research 345 (2010) 369–376
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Lactose as an inexpensive starting material for the preparation
of aldohexos-5-uloses: synthesis of L-ribo and D-lyxo derivatives q
*
Lorenzo Guazzelli, Giorgio Catelani , Felicia D’Andrea
Dipartimento di Scienze Farmaceutiche, 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:
Received 27 October 2009
Received in revised form 18 November 2009
Accepted 23 November 2009
Available online 26 November 2009
Partially protected derivatives of L-ribo- and D-lyxo-aldohexos-5-ulose have been prepared starting from
triacetonlactose dimethyl acetal derivatives. Key steps of the synthetic sequences are (a) the synthesis of
40-deoxy-40-eno- and 60-deoxy-50-eno lactose derivatives, and (b) the epoxidation–methanolysis of the
above-mentioned enol ethers to give 1,5-bis-glycopyranosides, masked form of the target 1,5-dicarbonyl
hexoses.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Lactose
L
-ribo-Aldohexos-5-ulose
-lyxo-Aldohexos-5-ulose
D
1,5-Bis-glycopyranosides
Epimerisation
1. Introduction
investigate a different strategy with respect to that reported start-
ing from monosaccharide precursors.8 We thus considered to per-
Aldohexos-5-uloses (3) represent an interesting, although yet
poorly investigated class of dicarbonyl hexoses2 that are useful
synthetic intermediates for the preparation of high value-added
compounds such as imino sugars3 and cyclitols, as well as inosi-
tols4 and polyhydroxycyclopentanes.5
A useful approach (Chart 1) to aldohexos-5-uloses (3) is based
on a selective C-5 oxidation by epoxidation of 4-deoxy-hex-4-
eno6 (1) or 6-deoxy-hex-5-enopyranosides7 (2). In the frame of a
general research project aimed at the chemical valorisation of lac-
tose as cheap and renewable starting material, we planned the
preparation of a representative of each diastereomeric series of
form the epimerisation of the C-20 position on the
D-
galactopyranoside moiety in an earlier stage of the synthetic se-
quence (Scheme 1). Compound 47c,d was subjected to an oxidation
with the tetra-n-propyl ammonium perruthenate–N-methylmor-
pholine-N-oxide (TPAP–NMO) system in CH2Cl2, obtaining a crude
mixture of the uloside 5 and its hydrate 6 (about 3:1). The reduc-
tion (NaBH4/MeOH) of the crude mixture gave in an overall 90%
yield the corresponding
D-talo-derivative 7 as the sole isolated dia-
stereoisomer. The C-20 epimerisation was firmly confirmed by the
0
0
0
0
changes in the J1 ,2 and J2 ,3 coupling constant values from 8.1
and 6.9 Hz in compound 47c,d to 2.5 and 4.1 Hz, respectively.
The tosylate 7 was then transformed into 6-deoxy-hex-5-enol
ether by treatment with NaH in DMF under the conditions repor-
ted7c,d for the transformation of the galacto epimer 4, but only
the 2,5-anhydro derivative 8 was obtained in almost quantitative
yield (96%) as a result of an intramolecular SN2 displacement.
The presence of this concurrent pathway was not unexpected in
view of the favourable axial orientation of the C-20 alkoxide. Fur-
thermore, the conformational flattening caused by the 30,40-cis-
dioxolane ring, and the high stability of the 2,5-dioxabicy-
clo[2,2,2]octane system could explain the exclusive formation of 8.
In order to suppress this unwanted reaction, we considered the
preparation of a 60-O-sulfonate analog of 4, protected as benzyl
ether at HO-20. The alcohol 10 was first prepared, which was easily
aldohexos-5-uloses and attained the goal by preparing the
no,7c,d the -xylo7e and the -lyxo7e examples.
In this communication, we present the preparation of partially
protected -ribo and -lyxo derivatives following either the hex-4-
L-arabi-
D
L
L
D
or hex-5-enopyranoside approach. Some unexpected results ob-
served during the planned synthetic routes are also described
and discussed.
2. Results and discussion
To prepare a representative of the remaining aldohexos-5-ulose
stereoseries, that is the ribo example, from lactose, we decided to
q
Part 28 of the series ‘Chemical Valorisation of Milk-derived Carbohydrates’. For
part 27 see Ref. 1.
* Corresponding author. Tel.: +39 0502219700; fax: +39 0502219660.
E-mail address: giocate@farm.unipi.it (G. Catelani).
The high stability of this kind of bicyclooctane system originates the unexpected
high preference for the ring-closed hemiacetal form of 6-OH-3,4-O-isopropylidene-b-
D-lyxo-2-ulopyranosides (Ref. 9).
0008-6215/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2009.11.027

370
L. Guazzelli et al. / Carbohydrate Research 345 (2010) 369–376
OP
OP
PO
O
O
O
PO
PO
OR
OR
CHO
PO
OP
OP
PO
OP
1
3
2
P = H or protecting group
Chart 1. General approach to aldohexos-5-uloses from hex-4- and hex-5-enopyranosides.
OTs
OTs
OTs
OTs
O
O
O
O
OH
O
OH
O
b
a
O
O
Me2C
Me2C
Me2C
Me2C
OGlc
OGlc
OGlc
OGlc
O
O
O
O
OH
O
OH
4
7
5
6
c
OC(OMe)Me2
OH
O
O
O
OBn
O
OH
O
O
Me2C
O
e
d
Me2C
Me2C
OGlc
OGlc
OGlc
O
O
O
10
8
9
Scheme 1. Attempts to prepare a b-
D-talo-6-deoxy-hex-5-enopyranoside. Reagent and conditions: (a) TPAP, NMO, CH2Cl2, 4 Å, rt, 1 h (91%); (b) NaBH4, MeOH, rt, 1 h, (90%
from 4); (c) NaH, DMF, rt, 1.5 h (96%); (d) BnBr, NaH, DMF, rt, 40 min, then 5% aq HCl, CH2Cl2 (90%); (e) NaHꢁDMF, Im2SO2, ꢀ30 °C, 3 h (96%).
obtained in 90% yield by treatment (Scheme 1) of the known alco-
hol 910 with NaH and BnBr in dry DMF, followed by selective re-
moval of the mixed acetal 60-O-protecting group by mild acid
treatment of the crude benzylation product in a biphasic system
(CH2Cl2–5% aq HCl). However, the subsequent introduction of a
leaving group in the primary position failed using Ts2O in pyridine,
leaving alcohol 10 completely unchanged, probably because of the
steric hindrance of either the 30,40-O-isopropylidene or the 20-O-
benzyl ether protecting group. An effective activation of the alco-
hol 10 was obtained using the conditions (NaH–DMF followed by
Im2SO2) usually employed for the preparation of imidazylates,11
but, surprisingly, derivative 8 was again obtained in excellent yield
(96%) as the sole reaction product. Although intramolecular substi-
tution involving a benzyl ether group as a nucleophile is known,12
the observed behaviour corroborates the above-mentioned
hypothesis of a high conformational strain due to the talo-configu-
ration and the 30,40-O-isopropylidene ring fusion which facilitates
this reaction.
treating a crude sample of 12–13 with NaBH4 in MeOH at ꢀ40 °C.
When the reduction was run at higher temperatures, a substantial
drop of the yield was observed, pointing out again the low stability
of 12–13. Furthermore, the presence of some fragmentation path-
ways was evidenced by the formation of appreciable amounts of
the known14 2,3:5,6-di-O-isopropylidene-aldehydo dimethyl acetal
(not shown). The L
-ribo configuration of the 60-deoxy-hex-50-eno-
0
0
pyranoside 14 was well confirmed by the J1 ,2 coupling constant
value (3.3 Hz), which highlighted the new H-10, H-20 axial–equato-
rial disposition.
Compound 14 was then subjected to the epoxidation–methan-
olysis reaction (MCPBA–MeOH) in order to oxidise the C-50 enol
ether group. This reaction gave some unexpected results, showing
the formation of 15 (13%) and of only one of the two possible C-50
anomers (16, 47%). The C-50 configuration of 15 and 16 was as-
signed on the basis of 1D NOE experiments. Thus, the irradiation
of the H-10 resonance for 16 gave enhancements for the H-30 and
50-OMe resonances, whereas 15 gave enhancements for the H-30,
H-60a and H-60b resonances. On the basis of the epoxidation–meth-
anolysis results of analogous exo-glycals,7 one could suppose the
formation of two non-isolable epoxide intermediates, which were
opened in an anti fashion, in the case of the b-epoxide by means
This problem was obviated by following a different strategy,
which first involved the elimination reaction and then the C-20
inversion (Scheme 2). Compound 4 was treated with NaH in
DMF, and the hex-5-enopyranoside 11 was obtained in 85% yield.
However, the oxidation of 11 with the TPAP–NMO system was
much less evident than expected.
of an intermolecular
a
a-attack of methanol, and in the case of the
one by means of an intramolecular 20-OH b-attack. Derivative
A complete conversion of the alcohol 4 into a 1:4 mixture of the
uloside 12 and its hydrate 13 was obtained by operating at low
temperature (0 °C) and by employing 9:1 CH2Cl2–CH3CN as the sol-
vent, which is reported in some cases to enhance the catalytic turn-
over.13 A reduced stability of the hex-5-eno-2-ulopyranoside 12–
13 was evidenced by the loss of material observed during the silica
gel chromatographic purification, lowering the yield to a rather
modest 55%. The following reduction step was accomplished with
high stereoselectivity, but in a rather modest overall yield (50%) by
16 was then benzylated by treatment with powdered KOH and
BnBr in wet THF, which led to the formation of 17 in excellent yield
(94%).
Although with this sequence the targeted 1,5-bis-L-ribo-hexo-
pyranosides were obtained, the rather modest yields of the overall
process (about 20% from the tosylate 4), as well as the chemical
fragility of some intermediates, pushed us to explore the comple-
mentary hex-4-enopyranoside approach as illustrated in the
Scheme 3. Known compound 1810 was subjected to an acetone

L. Guazzelli et al. / Carbohydrate Research 345 (2010) 369–376
371
OTs
O
HO
Me2C
O
Me2C O
Me2C
O
O
Me2C
a
b
O
O
O
OGlc
O
O
O
O
OGlc
OGlc
OGlc
OH
HO
O
HO
4
11
12
13
c
OBn
OBn
OH
O
O
O
O
OH
O
HO
e
Me2C
O
O
O
d
Me2C
Me2C
Me2C
O
+
OGlc
OGlc
OGlc
O
O
O
O
OGlc
OMe
OMe
OH
17
16
15
14
Scheme 2. Synthesis of L-ribo-hexos-5-ulose-1,5-bis-glycopyranosides through the hex-5-enopyranosides approach. Reagent and conditions: (a) NaH, DMF, rt, 3.2 h (85%);
(b) TPAP, NMO, 9:1 CH2Cl2–CH3CN, 4 Å, rt, 2.5 h; (c) NaBH4, MeOH, ꢀ40 °C, 2.5 h, (50% from 11); (d) MCPBA, MeOH, rt, 4.5 h (15: 13% + 16: 47%); (e) KOH, BnBr, 18-crown-6, rt,
4.5 h (94%).
OBn
BnO
MeO
HO
RO
OBn
O
BnO
OR
R'O
OBn
OBn
OBn
OBn
O
O
O
a
b
+
O
Me2C
OGlc
OGlc
RO
c
OGlc
O
OGlc
OMe
18
20: R = R' = H
23: R = H, R' = Bn
21: R = H
24: R = Bn
19: R = H
22: R = Bn
Scheme 3. Synthesis of
L-ribo-hexos-5-ulose 1,5-bis-glycopyranosides and D-lyxo-hexos-5-ulose 1,5-bis-glycopyranosides through the hex-4-enopyranoside approach.
Reagents and conditions: (a) t-BuOK, THF, reflux, 15 min, (81%); (b) MCPBA, MeOH, rt, 24 h (20: 58%, 21: 15%, 23: 17%, 24: 48%); (c) BnBr, NaH, DMF, rt, 30 min, (88%).
elimination employing t-BuOK in THF (reflux, 15 min), and 19 was
obtained in good yield (81%).
and L-ribo-1,5-bis-pyranosides 24 and 23 in an about 3:1 ratio and
in an overall 65% yield. The C-50 configuration of 23 is suggested
considering the close analogy between its NMR data and those of
20.
It is noteworthy to emphasise that the acetone elimination on 18
required milder conditions with respect to those used for 3,4-O-iso-
propylidene-
D
-galactopyranosides7c,d analogues, giving rise to com-
The final transformation of the 1,5-bis-glycopyranosides into
hexos-5-uloses, thereby exposing both the dicarbonyl groups,
was performed by acid hydrolysis (90% aq CF3COOH in 4:1
plex mixtures of inseparable products using t-BuOK in DMF at 80 °C
or lower temperatures. Probably the enhanced reactivity of the talo
series is due to the unfavourable syn interaction between the axial
20-OR group and the 30,40-O-isopropylidene group, giving rise to a
higher strain release with the acetone elimination. Derivative 19
was subjected to the epoxidation–methanolysis reaction (MCPBA–
MeOH) that gave the two 1,5-bis-glycosides 20 and 21, easily iso-
lated in 58% and 15% yield, respectively, through chromatography.
CH3CN–water at 50 °C) of the two L-ribo derivatives 17 and 20
(Scheme 4). After separation from D-glucose, the known dicarbonyl
hexose 258 was obtained in satisfactory isolated yield (66–73%). In
an identical way bis-glycoside 21 gave 26, which is the enantio-
form of the previously reported 2,6-di-Obenzyl-
5-ulose, in 72% yield, as an anomeric mixture of 1,4-furanose
tautomers (26
:26b 66:34).16
L-lyxo-aldohexos-
0
0
The structure of 20 was confirmed by NMR spectroscopy (J3 ,4
a
3.0 Hz), and its C-50 configuration was established by its transforma-
tion into 17 through an acid-promoted transacetalation reaction
with TsOH in 2,2-dimethoxypropane (DMP, 93% yield). In the case
In conclusion, with this work the usefulness of lactose as the
starting material for accessing all the diastereoisomeric series of
aldohexos-5-uloses has been demonstrated, opening the way to a
new synthetic channel for the valorisation of whey, a waste prod-
uct of the cheese industry, into sophisticated chemical synthons for
the preparation of biologically active compounds. Some examples
of synthetic use of hexos-5-uloses belonging to the lyxo-series
of 21, the
D
-lyxo configuration was easily assigned by NMR spectros-
0
0
0
copy (J3 ,4 10.0 Hz), but the anomeric C-5 configuration could not be
inferred by routine NMR analysis.
The rather low diastereoselection (L-ribo/D-lyxo ratio of about
4:1) observed in the epoxidation–methanolysis was somewhat
unexpected, owing to the influence of a complete syn-directing ef-
fect, which is generally observed for a free allylic hydroxyl group in
the epoxidation reaction.15 The presence of an appreciable amount
of the bis-glycoside 21 arising from a peroxide attack anti to the
allylic 30-OH group, followed by epoxide opening by MeOH, could
reasonably be attributed to the steric hindrance of the axial 20-
OBn, which shields the b face of 19. Reasoning on this point, we
tried to reverse the stereoselectivity of the formation of 1,5-bis-
glycosides by performing the epoxidation–methanolysis on the
30-O-benzyl derivative 22, which is easily obtained in good yield
by routine benzylation of 19. This objective was achieved, although
are reported,4b,17 while synthetic elaboration of
L-ribo-hexos-5-
ulose derivatives are currently under investigation in our group
and will be reported in a forthcoming paper.à
3. Experimental
3.1. General methods
General methods are those reported in Ref. 19. Compounds 4,7c
9
10 and 1810 were prepared according to the described procedures.
à
The stereoselective synthesis of cis- and epi-inositol derivatives have been
in a not complete manner, as we obtained a mixture of the
D-lyxo-
recently achieved starting from L-ribo-hexos-5-ulose precursors (Ref. 18).

372
L. Guazzelli et al. / Carbohydrate Research 345 (2010) 369–376
OBn
OBn
OBn
OH
OBn
O
OH
HO
OBn
O
OBn
O
O
Me2C
a
a
OGlc
OGlc
OGlc
HO
CHO
O
OMe
17
OMe
20
25
BnO
MeO
HO
HO
OBn
OBn
O
OBn
O
a
HO
HO
CHO
21
26
Scheme 4. Synthesis of 2,6-di-O-benzyl-L-ribo- and 2,6-di-O-benzyl-D-lyxo-hexos-5-uloses. Reagent and conditions: (a) 90% aq CF3COOH, 4:1 CH3CN–H2O, 50 °C, 4–5 h (25:
66% from 17 and 73% from 20, 26: 72%).
3.2. 3,4-O-Isopropylidene-6-O-p-toluenesulfonyl-
2-ulopyranosyl-(1?4)-2,3:5,6-di-O-isopropylidene-aldehydo-D-
glucose dimethyl acetal (5) and its hydrate (6)
a
-
D
-lyxo-hex-
Rf 0.40 (9:1 CH2Cl2–Me2CO); 1H NMR (200 MHz, CDCl3): d 7.80,
7.36 (AA0XX0 system, 4H, Ar–H), 4.93 (d, 1H, J1 ,2 2.5 Hz, H-10),
4.47 (dd, 1H, J2,3 7.1 Hz, H-2), 4.38 (d, 1H, J1,2 6.2 Hz, H-1), 4.32
0
0
(dd, 1H, J3 ,4 6.7 Hz, H-30), 4.28–4.00 (m, 7H, H-40, H-60a, H-60b,
0
0
A suspension of 47c (2.02 g, 3.00 mmol) in dry CH2Cl2 (20 mL)
and pre-dried 4-methylmorpholine-N-oxide (NMO) (618 mg,
5.30 mmol) containing 4 Å powdered molecular sieves (240 mg)
was stirred under an argon atmosphere for 30 min at room tem-
perature. Tetrapropylammonium perruthenate (TPAP) (106 mg,
10%) was added, and the resulting green mixture was stirred at
room temperature (1 h). The reaction mixture was filtered through
alternate pads of Celite and silica gel and was extensively washed
with CH2Cl2 and then EtOAc. The combined organic phases were
concentrated under diminished pressure to give a syrup (2.00 g)
consisting of a mixture of 5 and 6 in a ratio of about 3:2, as esti-
mated on the basis of the relative C-10 NMR signal intensities (d
99.5 and 103.7, respectively). Flash chromatographic purification
of a crude sample, eluting with 9:1 CH2Cl2–Me2CO, afforded a
3:1 mixture of 5 and 6 (1.81 g, combined yield about 91%) as a col-
H-4, H-5, H-6a, H-6b), 3.93 (m, 1H, H-50), 3.92 (dd, 1H, J3,4 1.4 Hz,
H-3), 3.79 (dd, 1H, J2 ,3 4.1 Hz, H-20), 3.42, 3.41 (2s, each 3H,
2 ꢂ OMe), 2.46 (s, 3H, MePh), 2.45 (br s, 1H, OH), 1.49, 1.42, 1.37,
1.36, 1.35, 1.28 (6s, each 3H, 3 ꢂ CMe2); 13C NMR (50 MHz, CDCl3):
d 144.8, 132.4 (2 ꢂ Ar–C), 129.8, 127.8 (Ar–CH), 110.1, 110.1, 107.8
(3 ꢂ CMe2), 104.7 (C-1), 100.5 (C-10), 77.9, 77.7, 76.0, 74.7 (C-2, C-4,
C-3, C-5), 73.7, 71.0, 70.0 (C-30, C-40, C-50), 68.3 (C-60), 66.5 (C-20),
64.8 (C-6), 55.6, 53.0 (2 ꢂ OMe), 27.1, 26.2, 26.1, 25.4, 25.1, 24.8
(3 ꢂ CMe2), 21.5 (MePh). Anal. Calcd for C30H46O14S: C, 54.37; H,
7.00. Found: C, 54.41; H, 7.08.
0
0
3.4. 2-O-Benzyl-3,4-O-isopropylidene-b-
D-talopyranosyl-(1?4)-
2,3:5,6-di-O-isopropylidene-aldehydo-
D-glucose dimethyl acetal
(10)
ourless syrup; [
a
]
ꢀ9.9 (c 1.17, CHCl3); Rf 0.45 (9:1 CH2Cl2–
A suspension of pre-washed (hexane) 60% NaH in mineral oil
(417 mg, 10.4 mmol) in dry DMF (20 mL) was cooled to 0 °C and
treated under argon atmosphere with a solution of 910 (2.02 g,
3.48 mmol) in dry DMF (30 mL). The mixture was warmed to room
temperature and stirred for 10 min, cooled again to 0 °C and then
treated with BnBr (0.66 mL, 5.57 mmol). The mixture was warmed
to room temperature and further stirred until the starting material
was consumed (40 min, TLC, 3:7 hexane–EtOAc). MeOH (5 mL) and
water (20 mL) were slowly added, and the mixture was extracted
with CH2Cl2 (4 ꢂ 20 mL). The collected organic layers were treated
with 5% aq HCl until TLC analysis (3:7 hexane–EtOAc) revealed the
complete disappearance of the product with Rf 0.58 and the forma-
tion of a slower moving product (Rf 0.39). The aqueous phase was
further extracted with CH2Cl2 (20 mL), and the organic extracts
were dried, filtered and concentrated under diminished pressure.
The residue was subjected to flash chromatography, eluting with
1:1 hexane–EtOAc, to give 10 (1.87 g, 90% yield) as a colourless syr-
D
Me2CO); selected 13C NMR (50 MHz, CDCl3) signals: major compo-
nent 5: d 196.4 (C-20), 144.9, 132.0 (2 ꢂ Ar–C), 111.1, 110.2, 107.7
(3 ꢂ Me2C), 104.7 (C-1), 99.5 (C-10), 77.4, 77.3, 77.0, 76.9 (C-4, C-
2, C-3, C-5), 75.7, 74.7 (C-30, C-40), 70.2 (C-50), 67.5 (C-60), 64.8 (C-
6), 55.4, 53.1 (2 ꢂ OMe-1), 27.0, 26.6, 25.9, 25.8, 25.7, 25.3
(3 ꢂ CMe2), minor component 6: d 144.6, 132.1 (2 ꢂ Ar–C), 110.1,
109.7, 107.9 (3 ꢂ Me2C), 104.3 (C-1), 103.7 (C-10), 90.0 (C-20),
77.6, 77.5, 77.2, 76.3 (C-4, C-2, C-3, C-5), 74.4, 72.2 (C-30, C-40),
70.0 (C-50), 68.1 (C-60), 64.2 (C-6), 55.8, 52.6 (2 ꢂ OMe-1), 26.8,
26.1, 25.6, 25.5, 24.4, 24.0 (3 ꢂ CMe2). Cluster of signals for both
components: d 129.7, 127.6 (Ar–CH), 21.2 (MePh). The mixture
was directly used for the preparation of 7, which follows in
Section 3.3.
3.3. 3,4-O-Isopropylidene-6-O-p-toluenesulfonyl-b-
osyl-(1?4)-2,3:5,6-di-O-isopropylidene-aldehydo-
dimethyl acetal (7)
D
-talopyran-
D-glucose
up; [a]
D +19.3 (c 1.23, CHCl3); Rf 0.17 (4:6 hexane–EtOAc); 1H NMR
(200 MHz, CDCl3): d 7.45–7.22 (m, 5H, Ar–H), 4.89, 4.83 (AB sys-
tem, 2H, JA,B 12.8 Hz, CH2Ph), 4.71 (dd, 1H, J2,3 7.9 Hz, H-2), 4.57
(s, 1H, H-10), 4.38 (d, 1H, J1,2 6.7 Hz, H-1), 4.30–4.15 (m, 2H, H-30,
H-40), 4.15–4.05 (m, 3H, H-5, H-6a, H-6b), 3.95 (m, 2H, H-6a’, H-
6b’), 3.90 (dd, 1H, J3,4 1.4 Hz, H-3), 3.81 (m, 1H, H-50), 3.71 (d, 1H,
A crude mixture of 5 and 6 (800 mg) was dissolved in dry MeOH
(14 mL). The solution was cooled to 0 °C, treated with NaBH4
(228 mg, 6.03 mmol) and gently warmed to room temperature.
The reaction mixture was stirred until the TLC analysis (9:1
CH2Cl2–Me2CO) showed the complete disappearance of the start-
ing material (1 h). The mixture was treated with satd aq NH4Cl
(10.0 mL), stirred for 15 min and extracted with CH2Cl2
(4 ꢂ 30 mL). The collected organic extracts were dried, filtered
and concentrated under diminished pressure to give a residue
(740 mg), which was directly subjected to flash chromatographic
purification (3:2 hexane–EtOAc) affording 7 (728 mg, 90% yield
J2 ,3 5.5 Hz, H-20), 3.69 (m, 1H, H-4), 3.48 (s, 6H, 2 ꢂ OMe), 1.50,
1.35, 1.34, 1.31, 1.26, 1.25 (6s, each 3H, 3 ꢂ CMe2); 13C NMR
(50 MHz, CDCl3): d 138.1 (Ar–C), 127.7–126.9 (Ar–CH), 110.2,
109.5, 107.4 (3 ꢂ CMe2), 106.4 (C-1), 102.1 (C-10), 78.2, 77.5, 74.9,
74.8, 74.7, 74.6 (C-2, C-3, C-4, C-5, C-30, C-40), 74.0 (CH2Ph), 72.0
(C-20), 70.8 (C-50), 64.6 (C-6), 62.0 (C-60), 57.0, 53.1 (2 ꢂ OMe-1),
26.5, 26.3, 26.1, 25.5, 25.4, 25.2 (3 ꢂ CMe2). Anal. Calcd for
C30H46O12: C, 60.19; H, 7.74. Found: C, 60.25; H, 7.81.
0
0
calculated from 4) as a colourless syrup; [
a
]D ꢀ2.2 (c 1.16, CHCl3);

L. Guazzelli et al. / Carbohydrate Research 345 (2010) 369–376
373
3.5. 2,6-Anhydro-3,4-O-isopropylidene-b-
(1?4)-2,3:5,6-di-O-isopropylidene-aldehydo-
D
-talopyranosyl-
-glucose
4.29 (ddd, 1H, J5,6a 6.0 Hz, J4,5 2.0 Hz, H-5), 4.17 (m, 1H, H-4),
4.28–4.13 (m, 2H, H-30, H-6a), 4.07 (dd, 1H, J6a,6b 8.7 Hz, J5,6b
D
0
0
dimethyl acetal (8)
6.9 Hz, H-6b), 3.99 (dd, 1H, J3,4 1.5 Hz, H-3), 3.76 (t, 1H, J2 ,3
8.0 Hz, H-20), 3.50, 3.51 (2s, each 3H, 2 ꢂ OMe), 1.60, 1.57, 1.48,
1.47, 1.46, 1.39 (6s, each 3H, 3 ꢂ CMe2); 13C NMR (50 MHz, CDCl3):
d 153.1 (C-50), 110.9, 110.1, 108.1 (3 ꢂ CMe2), 105.0 (C-1), 103.1 (C-
10), 96.8 (C-60), 78.9, 77.8, 77.2 76.9, (C-2, C-3, C-4, C-5), 74.8, 73.8,
72.8 (C-20, C-30, C-40); 64.4 (C-6), 55.9, 52.9 (2 ꢂ OMe), 27.3, 27.7,
26.3, 25.5, 25.4, 23.9 (3 ꢂ CMe2). Anal. Calcd for C23H38O11: C,
56.32; H, 7.81. Found: C, 56.13; H, 7.77.
3.5.1. From 7 with NaH in DMF
To a suspension of pre-washed (hexane) 60% NaH in mineral oil
(90 mg, 1.51 mmol) in dry DMF (2.0 mL) was added, under argon
atmosphere at 0 °C, a solution of 7 (200 mg, 0.30 mmol) in dry
DMF (5 mL). After warming to room temperature and stirring for
1.5 h , TLC analysis (3:7 hexane–EtOAc) showed the disappearance
of the starting material. MeOH (5 mL) and water (13 mL) were
slowly added, and the mixture was extracted with Et2O
(2 ꢂ 30 mL). The collected organic layers were dried, filtered and
concentrated under diminished pressure. The residue (150 mg)
was purified by flash chromatography (3:7 hexane–EtOAc) to give
3.7. Oxidation–reduction of 6-deoxy-3,4-O-isopropylidene-
arabino-hex-5-enopyranosyl-(1?4)-2,3:5,6-di-O-isopropylidene-
aldehydo- -glucose dimethyl acetal (11)
a-L-
D
8 (142 mg, 96% yield) as a colourless syrup; [
a
]
ꢀ19.6 (c 1.2,
D
3.7.1. Oxidation of 11
CHCl3); Rf 0.55 (3:7 hexane–EtOAc); 1H NMR (200 MHz, CD3CN):
A suspension of 11 (1.02 g, 2.08 mmol) in dry 9:1 CH2Cl2–
CH3CN (14 mL) and pre-dried 4-methylmorpholine-N-oxide
(NMO) (410 mg, 3.5 mmol) containing 4Å powdered molecular
sieves (380 mg) was stirred under an argon atmosphere for
30 min at room temperature. Tetrapropylammonium perruthe-
nate (TPAP) (73 mg, 208 mmol, 10%) was added, and the resulting
green mixture was stirred at room temperature. After 2.5 h, TLC
analysis (9:1 CH2Cl2–acetone) showed the complete disappear-
ance of 11, and the reaction mixture was filtered through alter-
nate pads of Celite and silica gel and extensively washed first
with CH2Cl2 and then with EtOAc. The combined organic phases
were concentrated under diminished pressure to give a syrup
(882 mg, combined yield about 84%) consisting of a mixture of
12 and its hydrate 13 in a ratio of 1:4 established on the basis
of the integration of the H-10 signals (d 5.15 and 5.64, respec-
tively). The flash chromatographic purification (7:3 hexane–
EtOAc) of a sample (210 mg), gave a 1:1 mixture of 12 and 13
d 5.04 (d, 1H, J1 ,2 1.7 Hz, H-10), 4.47 (t, 1H, J2,3 6.6 Hz, H-2), 4.36
0
0
0
0
(d, 1H, J1,2 6.6 Hz, H-1), 4.34 (m, 1H, H-5), 4.22 (dd, 1H, J3 ,4
6.1 Hz, H-30), 4.18 (dd, 1H, J4 ,5 4.6 Hz, H-40), 4.08 (dd, 1 H, J3,4
0
0
1.5 Hz, H-3), 4.05–3.90 (m, 5H, H-50, H-60a, H-60b, H-6a, H-6b),
3.89 (dd, 1H, J4,5 4.5 Hz, H-4), 3.79 (t, 1H, J2 ,3 1.7 Hz, H-20), 3.38,
3.36 (2s, each 3H, 2 ꢂ OMe), 1.48, 1.39, 1.34, 1.33, 1.32, 1.28 (6s,
each 3H, 3 x CMe2); 13C NMR (200 MHz, CD3CN): d 112.5, 111.3,
109.0 (3 ꢂ CMe2), 106.4 (C-1), 99.8 (C-10), 78.6, 78.0, 76.8 76.6
(C-2, C-4, C-3, C-5), 74.7, 71.3, (C-20, C-30), 69.8, 68.0 (C-40, C-50),
65.8 (C-6), 63.3 (C-60), 56.5, 54.0 (2 ꢂ OMe), 27.7, 26.9, 26.7, 26.1,
25.3, 24.9 (3 ꢂ CMe2). Anal. Calcd for C23H38O11: C, 56.32; H,
7.81. Found: C, 56.41; H, 7.90.
0
0
3.5.2. From 10 with NaH, Im2SO2 in DMF
To a suspension of pre-washed (hexane) 60% NaH in mineral oil
(95 mg, 2.37 mmol) in dry DMF (2.4 mL) was added, under argon
atmosphere at 0 °C, a solution of 10 (284 mg, 0.47 mmol) in dry
DMF (9.5 mL). The mixture was warmed to room temperature
and stirred for 30 min, then cooled to ꢀ30 °C and treated with
N,N-sulfonyldiimidazole (Im2SO2) (142 mg, 0.71 mmol, 1.5 equiv).
After 3 h at ꢀ30 °C, TLC analysis (EtOAc) showed the disappearance
of the starting material, and the mixture was cooled to ꢀ40 °C,
treated with MeOH and water (5 mL) and extracted with Et2O
(2 ꢂ 20 mL). The organic extracts collected, dried, filtered and con-
centrated under diminished pressure afforded a residue (240 mg)
which was subjected to a filtration over silica gel (3:7 hexane–
EtOAc) to give pure 8 (221 mg, 96% yield) as a colourless syrup,
identical to the above-described sample.
(135 mg, combined yield about 55%); as a clear syrup; [a]
D
ꢀ19.4 (c 1.18, CHCl3); Rf 0.09 (7:3 hexane–EtOAc); Selected 1H
NMR (200 MHz, C6D6) signals component 12: d 5.17, 4.85 (2 br
s, each 1H, H-60a, H-60b), 5.15 (s, 1H, H-10), 4.76 (dd, 1H, J2,3
7.5 Hz, H-2), 4.28 (d, 1H, J1,2 5.7 Hz, H-1), 4.15 (dd, 1H, J3,4
1.5 Hz, H-3), 3.30, 3.19 (2s, each 3H, 2 ꢂ OMe-1); component 13:
d 5.64 (s, 1H, H-10), 4.96 (dd, 1H, J2,3 7.9 Hz, H-2), 4.37 (d, 1H,
J1,2 5.7 Hz, H-1), 4.08 (dd, 1H, J3,4 1.7 Hz, H-3), 4.85, 4.69 (2 br
s, each 1H, H-60a, H-60b), 3.25, 3.17 (2s, each 3H, 2 ꢂ OMe-1); se-
lected 13C NMR (50 MHz, C6D6) signals: component 12: d 197.8 (C-
20), 152.6 (C-50), 111.6, 110.3, 108.3 (3 ꢂ CMe2), 105.7 (C-1), 102.4
(C-60), 100.4 (C-10), 78.3, 78.1, 77.0, 76.4, 76.3, 75.3 (C-3, C-2, C-4,
C-5, C-30, C-40), 65.3 (C-6), 56.6, 53.7 (2 ꢂ OMe-1); component 13:
d 154.7 (C-50), 112.2, 110.6, 108.5 (3 ꢂ CMe2), 106.1 (C-1), 103.0
(C-10), 94.2 (C-60), 91.4 (C-20), 78.6, 78.4, 78.2, 77.6 (C-2, C-4, C-
5, C-30), 75.6, 73.1 (C-3, C-40), 65.3 (C-6), 56.7, 53.3 (2 ꢂ OMe-
3.6. 6-Deoxy-3,4-O-isopropylidene-a-L-arabino-hex-5-enopyran-
osyl-(1?4)-2,3:5,6-di-O-isopropylidene-aldehydo-D-glucose
dimethyl acetal (11)
1); Cluster of signals for both components:
d 27.5–24.9
A suspension of pre-washed (hexane) 60% NaH in mineral oil
(1.91 g, 47.4 mmol) in dry DMF (60 mL) was cooled to 0 °C and
treated under argon atmosphere with a solution of 47c (6.30 g,
9.51 mmol) in dry DMF (45 mL). The mixture was gently warmed
to room temperature, left under stirring until 4 was consumed
(TLC: 3:7 hexane–EtOAc). After 3.2 h, the reaction mixture was
cooled to 0 °C, treated with crushed ice (50 mL) and extracted with
Et2O (5 ꢂ 40 mL). The collected organic extracts were dried, fil-
tered and concentrated under diminished pressure to give a resi-
due (4.83 g), which was directly subjected to flash
chromatographic purification (7:3 hexane–EtOAc + 0.1% Et3N) to
(3 ꢂ CMe2). The crude mixture was directly used in the reduction,
which follows (Section 3.7.2).
3.7.2. Reduction of the mixture of 12 and 13
A solution of the crude mixture of 12 and 13 in dry MeOH
(15 mL) was treated, under argon atmosphere, at ꢀ40 °C with
NaBH4 (132 mg, 3.5 mmol) and then stirred at the same tempera-
ture until TLC analysis (9:1 CH2Cl2–Me2CO) revealed the complete
disappearance of the starting material (2.5 h). The mixture was di-
luted with CH2Cl2 (20 mL) and treated with water (20 mL), warmed
to room temperature and then extracted with CH2Cl2 (4 ꢂ 30 mL).
The combined organic extracts were dried (Na2SO4), filtered and
concentrated under diminished pressure. The residue (642 mg)
was subjected to flash chromatography (3:1 hexane–EtOAc) to give
14 (390 mg) in 50% yield calculated from 11.
give 11 (3.96 g, 85% yield); as a clear syrup; [
a
]
ꢀ22.8 (c 1.3,
D
CHCl3); Rf 0.22 (7:3 hexane–EtOAc); 1H NMR (200 MHz, CDCl3): d
4.85 (d, 1H, J1 ,2 8.0 Hz, H-10), 4.82 (br t, 1H, J6 a,6 b = J4 ,6 a 1.0 Hz,
0
0
0
0
0
0
H-60a), 4.73 (br t, 1H, J6 a,6 b = J4 ,6 b 1.1 Hz, H-60b), 4.67 (dd, 1H,
J1,2 6.2 Hz, J2,3 7.7 Hz, H-2), 4.65 (m, 1H, H-40), 4.48 (d, 1H, H-1),
0
0
0
0

374
L. Guazzelli et al. / Carbohydrate Research 345 (2010) 369–376
3.7.2.1. 6-Deoxy-3,4-O-isopropylidene-
anosyl-(1?4)-2,3:5,6-di-O-isopropylidene-aldehydo-
a
-
L
-ribo-hex-5-enopyr-
-glucose
] +18.6 (c 0.97, CHCl3);
D
(C-1), 98.4 (C-50), 98.2 (C-10), 77.9 (C-3), 77.8 (C-5), 76.8 (C-4),
D
74.5 (C-2), 73.2 (C-40), 72.5 (C-30), 65.5 (C-20), 64.9 (C-6); 60.7 (C-
60), 56.2, 52.8 (2 ꢂ OMe-1), 48.7 (OMe-50), 26.9, 26.2, 26.0, 25.7,
25.0, 24.5 (3 ꢂ CMe2). Anal. Calcd for C24H42O13: C, 53.52; H,
7.86. Found: C, 53.61; H, 7.90.
dimethyl acetal (14). Colourless syrup; [
a
Rf 0.56 (3:7 hexane–EtOAc); 1H NMR (200 MHz, C6D6): d 5.39 (d,
1H, J1 ,2 3.3 Hz, H-10), 4.85 (br s, 1H, H-60b), 4.83 (d, 1H, J2 ,OH
10.5 Hz, OH), 4.78 (dd, 1H, J2,3 8.0 Hz, H-2), 4.70 (br s, 1H, H-60a),
4.35 (m, 1H, H-4), 4.32 (d, 1H, J1,2 5.6 Hz, H-1), 4.26 (m, 1H, H-5),
0
0
0
3.9. (5R)-2,6-Di-O-benzyl-3,4-O-isopropylidene-5-C-methoxy-
4.23–4.03 (m, 2H, H-6a, H-6b), 4.15 (d, 1H, J3 ,4 6.7 Hz, H-40),
a-L
-ribo-hexopyranosyl-(1?4)-2,3:5,6-di-O-isopropylidene-
0
0
4.05 (dd, 1H, J2 ,3 4.2 Hz, H-30), 4.00 (dd, 1H, J3,4 1.6 Hz, H-3), 3.67
(b dt, 1H, H-20), 3.26, 3.15 (2s, each 3H, 2 ꢂ OMe), 1.58, 1.57,
1.44, 1.33, 1.26, 1.20 (6s, each 3H, 3 ꢂ CMe2); 13C NMR (50 MHz,
C6D6): d 154.2 (C-50), 110.9, 109.8, 108.3 (3 ꢂ CMe2), 105.7 (C-1),
101.4 (C-10), 97.5 (C-60), 78.5, 78.4, 77.9, 75.5 (C-2, C-3, C-4, C-5),
74.1, 72.6 (C-30, C-40), 67.3 (C-20), 65.7 (C-6); 56.2, 53.3 (2 ꢂ OMe),
27.3, 27.2, 27.0, 26.4, 25.6, 25.5 (3 ꢂ CMe2). Anal. Calcd for
C23H38O11: C, 56.32; H, 7.81. Found: C, 56.41; H, 7.92.
aldehydo- -glucose dimethyl acetal (17)
D
0
0
To a solution of 16 (276 mg, 0.51 mmol) in THF containing 0.5%
of water (4.1 mL) were added 18-crown-6 (14 mg) and powdered
KOH (230 mg, 4.09 mmol), and the mixture was stirred at room
temperature for 30 min. BnBr (0.24 mL, 2.05 mmol) was added,
and the suspension was stirred at room temperature until TLC
analysis (3:7 hexane–EtOAc) revealed the complete disappearance
of the starting material (4.5 h, Rf 0.20) and the formation of a major
faster moving product (Rf 0.64). MeOH (10 mL) was added, and the
reaction mixture was further stirred at room temperature for
30 min. Solvents were removed under diminished pressure, and
the residue was partitioned between CH2Cl2 (50 mL) and water
(15 mL). The aq phase was extracted with CH2Cl2 (3 ꢂ 50 mL),
and the combined organic extracts were dried, filtered and concen-
trated under diminished pressure. The residue (630 mg) was sub-
jected to flash chromatography (first hexane, then 3:1 hexane–
3.8. Epoxidation of 6-deoxy-3,4-O-isopropylidene-a-L-ribo-hex-
5-enopyranosyl-(1?4)-2,3:5,6-di-O-isopropylidene-aldehydo-D-
glucose dimethyl acetal (14)
A solution of 14 (655 mg, 1.32 mmol) in MeOH (12 mL) was
cooled to 0 °C, treated with 70% commercial MCPBA (Fluka,
407 mg, 1.98 mmol), warmed to room temperature and left stir-
ring. After 4.5 h, TLC analysis (3:7 hexane–EtOAc) showed the com-
plete disappearance of the starting material and the formation of
three spots at Rf 0.56, 0.40 and 0.29. Satd aq NaHCO3 (40 mL)
was added, and the solution was further stirred for 15 min and
concentrated under diminished pressure. The residue was parti-
tioned between water (30 mL) and CH2Cl2 (75 mL), the aq phase
was extracted with CH2Cl2 (2 ꢂ 50 mL), and the combined organic
extracts were dried, filtered and concentrated under diminished
pressure. The residue (623 mg) was subjected to flash chromatog-
raphy (7:3 hexane–EtOAc) to give 15 (87 mg, 13% yield) and 16
(337 mg, 47% yield).
EtOAc) to give 17 (345 mg, 94% yield) as a colourless syrup; [
a]
D
+0.9 (c 1.12, CHCl3); Rf 0.64 (3:7 hexane–EtOAc); 1H NMR
0
0
(200 MHz, CDCl3): d 7.43–7.23 (m, 10H, Ar–H), 4.91 (d, 1H, J1 ,2
1.4 Hz, H-10), 4.82 (s, 2H, CH2Ph), 4.68, 4.50 (AB system, 2H, JA,B
12.3 Hz, CH2Ph), 4.54 (dd, 1H, J1,2 6.5 Hz, J2,3 7.6 Hz, H-2), 4.33 (d,
1H, H-1), 4.31 (dd, 1H, J2 ,3 5.0 Hz, J3 ,4 6.1 Hz H-30), 4.15 (d, 1H,
H-40), 4.20 (dt, 1H, J 3.3 Hz, J 6.6 Hz, H-5), 4.02 (dd, 1H, J6a,6b
8.9 Hz, J5,6a 6.7 Hz, H-6b), 3.96–3.88 (m, 3H, H-3, H-4, H-6a), 3.75
(d, 1H, H-20), 3.67, 3.57 (AB system, 2H, JA,B 10.3 Hz, H-60a, H-6b),
3.30, 3.29, 3.23 (3s, each 3H, 2 ꢂ OMe-1, OMe-50), 1.50, 1.36,
1.33, 1.30, 1.28, 1.25 (6s, each 3H, 3 ꢂ CMe2); 13C NMR (50 MHz,
CDCl3): d 138.2, 137.9 (2 ꢂ Ar–C), 128.2–127.2 (Ar–CH), 109.9,
109.7, 107.8 (3 ꢂ CMe2), 105.1 (C-1), 99.0 (C-50), 96.9 (C-10), 77.9,
77.7, 76.6 (C-3, C-4, C-5), 73.9, 73.3 (2 ꢂ CH2Ph), 73.3, 73.0 (C-2,
C-40), 72.5, 72.0 (C-20, C-30), 66.2 (C-60), 64.9 (C-6), 55.9, 51.6
(2 ꢂ OMe-1), 47.8 (OMe-50), 26.8, 26.7, 26.4, 25.7, 25.5, 25.0
(3 ꢂ CMe2). Anal. Calcd for C38H54O13: C, 63.49; H, 7.57. Found: C,
63.51; H, 7.58.
0
0
0
0
3.8.1. (5S)-2,5-Anhydro-3,4-O-isopropylidene-a-L-ribo-hexopy-
ranosyl-(1?4)-2,3:5,6-di-O-isopropylidene-aldehydo-D-glucose
dimethyl acetal (15)
Colourless syrup; [
a
]
D ꢀ48.3 (c 1.0, CHCl3); Rf 0.40 (3:7 hexane–
EtOAc); 1H NMR (600 MHz, CDCl3): d 5.09 (s, 1H, H-10), 4.60 (s, 1H,
H-20), 4.40 (dd, 1H, J2,3 7.2 Hz, H-2), 4.35 (d, 1H, J1,2 6.0 Hz, H-1),
4.34 (d, 1H, J3 ,4 5.5 Hz, H-30), 4.26 (d, 1H, H-40), 4.25 (m, 1H, H-
5), 4.09, 4.08 (AB system, 2H, JA,B 13.0 Hz, H-60a, H-60b), 4.00 (m,
3H, H-4, H-6a, H-6b), 3.91 (dd, 1H, J3,4 2.1 Hz, H-3), 3.46, 3.45
(2s, each 3H, 2 ꢂ OMe), 1.44, 1.40, 1.37, 1.36, 1.34, 1.28 (6s, each
0
0
3.10. 2,6-Di-O-benzyl-4-deoxy-a-L-erythro-hex-4-enopyranosyl-
(1?4)-2,3:5,6-di-O-isopropylidene-aldehydo-D-glucose dimethyl
acetal (19)
13
3H, 3 ꢂ CMe2); C NMR (50 MHz, CDCl3): d 113.9 (C-50), 110.3,
108.3, 107.8 (3 ꢂ CMe2), 105.6 (C-1), 98.3 (C-10), 82.7 (C-20), 80.8
(C-40), 80.1 (C-30), 80.0, 77.9 (C-3, C-5), 75.9 (C-2), 73.5 (C-4),
64.7 (C-6); 58.4 (C-60), 56.6, 54.2 (2 ꢂ OMe), 27.7, 26.3, 26.1,
25.9, 25.4, 24.9 (3 ꢂ CMe2). Anal. Calcd for C23H38O12: C, 54.54;
H, 7.56. Found: C, 54.48; H, 7.52.
A solution of 1810 (5.45 g, 7.90 mmol) in dry THF (100 mL) was
warmed to reflux and treated with solid t-BuOK (9.70 g,
79.2 mmol). After 15 min, TLC analysis (1:1 hexane–EtOAc)
showed the complete disappearance of the starting material, and
satd aq NaHCO3 (100 mL) was then added. The aq phase was ex-
tracted with CH2Cl2 (3 ꢂ 200 mL), and the collected organic ex-
tracts were dried, filtered and concentrated under diminished
pressure. The residue (5.35 g) was subjected to flash chromatogra-
phy (3:2 hexane–EtOAc, 0.1% Et3N) to give 19 (4.04 g, 81% yield) as
3.8.2. (5R)-3,4-O-Isopropylidene-5-C-methoxy-a-L-ribo-hexopy-
ranosyl-(1?4)-2,3:5,6-di-O-isopropylidene-aldehydo-D-glucose
dimethyl acetal (16)
Colourless syrup; [
a
]
ꢀ15.8 (c 1.25, CHCl3); Rf 0.29 (3:7 hex-
0 0
D
ane–EtOAc); 1H NMR (600 MHz, CDCl3): d 5.10 (d, 1H, J1 ,2 3.1 Hz,
a colourless syrup; [
a
]
ꢀ25.1 (c 1.0, CHCl3); Rf 0.4 (3:2 hexane–
D
H-10), 4.53 (dd, 1H, J2,3 7.8 Hz, H-2), 4.40 (dd, 1H, J2 ,3 4.5 Hz, J3 ,4
EtOAc); 1H NMR (250 MHz, CD3CN): d 7.43–7.27 (m, 10H, Ar–H),
0
0
0
0
7.2 Hz, H-30), 4.38 (d, 1H, J1,2 6.4 Hz, H-1), 4.25 (dt, 1H, J 6.8 Hz, J
2.4 Hz, H-5), 4.16 (d, 1H, H-40), 4.08 (m, 3H, H-4, H-6a, H-6b),
4.00 (m, 1H, H-20), 3.91 (dd, 1H, J3,4 1.6 Hz, H-3), 3.80, 3.72 (AB sys-
tem, 2H, JA,B 12.0 Hz, H-60a, H-60b), 3.44, 3.43 (2s, each 3H,
2 ꢂ OMe-1), 3.37 (s, 3H, OMe-50), 2.99 (br d, 1H, OH), 2.21 (br s,
1H, OH), 1.56, 1.44, 1.40, 1.37, 1.35, 1.34 (6s, each 3H, 3 ꢂ CMe2);
13C NMR (50 MHz, CDCl3): d 109.9, 109.8, 107.9 (3 ꢂ CMe2), 105.4
5.62 (dd, 1H, J1 ,2 2.3 Hz J1 ,3 1.1 Hz, H-10), 5.17 (dt, 1H, J3 ,4
0
0
0
0
0
0
5.3 Hz, J4 ,6 a = J4 ,6 b 0.8 Hz, H-40), 4.77, 4.64 (AB system, 2H, JA,B
11.6 Hz, CH2Ph), 4.52 (s, 2H, CH2Ph), 4.32 (d, 1H, J1,2 6.6 Hz, H-1),
4.23 (ddd, 1H, J4,5 3.8 Hz, J5,6a 6.3 Hz, J5,6b 7.0 Hz, H-5), 4.18 (m,
0
0
0
0
1H, J2 ,3 4.0 Hz, H-30), 4.12 (dd, 1H, J2,3 7.1 Hz, J3,4 1.4 Hz, H-3),
4.07 (dd, 1H, H-4), 4.05- 3.88 (m, 4H, H-6a, H-6b, H-60a, H-60b),
4.02 (dd, 1 H, H-2), 3.73 (dd, 1H, H-20), 3.38, 3.34 (2s, each 3H,
0
0

L. Guazzelli et al. / Carbohydrate Research 345 (2010) 369–376
375
H-6b), 3.95 (d, 1H, 1H, J3 ,4 10.0 Hz, H-40), 3.89 (dd, 1H, J2 ,3
0
0
0
0
0
2 ꢂ OMe), 3.12 (d, 1H, J3 ,OH 10.1 Hz, OH), 1.37, 1.31, 1.30, 1.28 (4s,
13
each 3H, 2 ꢂ CMe2); C NMR (62.9 MHz, CD3CN): d 149.0 (C-50),
3.2 Hz, H-20), 3.75, 3.58 (AB system, 2H, JA,B 10.5, H-60a, H-60b),
3.67 (dd, 1H, H-30), 3.36, 3.31 (2s, each 3H, 2 ꢂ OMe-1), 3.29 (s,
3H, OMe-50), 1.36, 1.30, 1.28, 1.23 (4s, each 3H, 2 ꢂ CMe2); 13C
NMR (50 MHz, CD3CN): d 140.1, 139.4 (2 ꢂ Ar–C), 129.2–128.2
(Ar–CH), 110.3, 108.2 (2 ꢂ CMe2), 106.7 (C-1), 100.3 (C-50), 99.4
(C-10), 79.4 (C-20), 78.7, 78.5, 78.1, 76.3 (C-2, C-3, C-4, C-5), 75.2,
74.3 (2 ꢂ CH2Ph), 70.8, 71.8 (C-30, C-40), 70.7 (C-60), 65.6 (C-6),
56.7, 54.0 (2 ꢂ OMe-1), 49.0 (OMe-50), 27.1, 27.0, 26.9, 25.1
(2 ꢂ CMe2). Anal. Calcd for C35H50O13: C, 61.93; H, 7.42. Found: C,
61.97; H, 7.44.
139.7, 139.6 (2 ꢂ Ar–C), 129.3–128.5 (Ar–CH), 110.7, 108.9
(2 ꢂ CMe2), 106.6 (C-1), 102.9 (C-40), 98.8 (C-10), 78.5, 78.5 (C-4,
C-5), 77.3 (C-2), 75.3 (C-20), 75.0 (C-3), 73.1, 71.7 (2 ꢂ CH2Ph),
69.6 (C-60), 65.8 (C-6), 61.3 (C-30), 56.8, 54.7 (2 ꢂ OMe-1), 27.3,
27.2, 26.8, 25.4 (2 ꢂ CMe2). Anal. Calcd for C34H46O11: C, 64.75;
H, 7.35. Found: C, 64.77; H, 7.38.
3.11. Epoxidation–methanolysis of 2,6-di-O-benzyl-deoxy-
erythro-hex-4-enopyranosyl-(1?4)-2,3:5,6-di-O-isopropylidene-
aldehydo- -glucose dimethyl acetal (19)
a-L-
D
3.12. 2,3,6-Tri-O-benzyl-deoxy-a-L-erythro-hex-4-enopyranosyl-
(1?4)-2,3:5,6-di-O-isopropylidene-aldehydo-D-glucose dimethyl
acetal (22)
A solution of 19 (5.81 g, 9.21 mmol) in MeOH (180 mL) was
cooled to 0 °C and treated with 70% commercial MCPBA (2.95 g,
11.9 mmol,). After 5 min the reaction mixture was gently warmed
to room temperature and left under stirring until 19 was consumed
(TLC, 1:1 hexane–EtOAc, 24 h). Satd aq NaHCO3 (50 mL) was added,
the solution was further stirred for 30 min and the solvent was re-
moved under diminished pressure. The residue was partitioned be-
tween water (60 mL) and CH2Cl2 (150 mL), the aq phase was
extracted with CH2Cl2 (2 ꢂ 150 mL), and the collected organic ex-
tracts were dried, filtered and concentrated under diminished
pressure. The residue (5.4 g) was subjected to flash chromatogra-
phy (3:2 hexane–EtOAc) to give 20 (3.63 g, 58% yield) and the 40-
epimer 21 (920 mg, 15% yield).
A solution of 19 (317 mg, 0.50 mmol) in dry DMF (8 mL) was
treated at 0 °C with a 60% NaH in mineral oil (60 mg, 2.50 mmol),
and the mixture was stirred for 15 min at 0 °C. Benzyl bromide
(160 lL, 0.65 mmol) was added, and the reaction mixture was
warmed to room temperature and further stirred. After 30 min,
TLC analysis (3:2 hexane–EtOAc) showed the disappearance of
the starting material (Rf 0.31) and the formation of a major faster
moving product (Rf 0.51). Excess NaH was decomposed with MeOH
(0.5 mL) under stirring for 10 min at 0 °C, CH2Cl2 (15 mL) and H2O
(8 mL) were added, and the aq phase was further extracted with
CH2Cl2 (2 ꢂ 15 mL). The combined organic extracts were dried, fil-
tered and concentrated under diminished pressure, and the crude
product (350 mg) was subjected to flash chromatography (7:3 hex-
ane–EtOAc) to give pure 22 (318 mg, 88% yield) as a colourless syr-
3.11.1. (5R)-2,6-Di-O-benzyl-5-C-methoxy-a-L-ribo-
hexopyranosyl-(1?4)-2,3:5,6-di-O-isopropylidene-aldehydo-D-
glucose dimethyl acetal (20)
D ꢀ25.0 (c 1.04, CHCl3); 1H NMR
Colourless syrup, [
a
]
D ꢀ22.8 (c 1.3, CHCl3); Rf 0.33 (1:1 hexane–
up, Rf 0.31 (3:2 hexane–EtOAc); [a]
(250 MHz, CD3CN): d 7.41–7.24 (m, 15H, Ar–H), 5.32 (t, 1H,
EtOAc); 1H NMR (200 MHz, CD3CN): d 7.39–7.31 (m, 10H, Ar H),
4.97, 4.69 (AB system, 2H, JA,B 11.4 Hz, CH2Ph), 4.60, 4.45 (AB sys-
J1 ,2 = J1 ,3 1.0 Hz, H-10), 4.94 (dt, 1H, J3 ,4 2.8 Hz, J4 ,6 a = J4 ,6 b
0.8 Hz, H-40), 4.86, 4.73 (AB system, 2H, JA,B 11.6 Hz, CH2Ph), 4.56,
4.52 (AB system, 2H, JA,B 12.0 Hz, CH2Ph), 4.53, 4.47 (AB system,
2H, JA,B 11.8 Hz, CH2Ph), 4.43 (dd, 1H, J1,2 6.3 Hz, J2,3 7.2 Hz, H-2),
4.35 (d, 1H, H-1), 4.26 (dt, 1H, J4,5 3.8 Hz, J5,6a = J5,6b 6.3 Hz, H-5),
0
0
0
0
0
0
0
0
0
0
tem, 2H, JA,B 11.9 Hz, CH2Ph), 4.88 (d, 1H, J1 ,2 0.9 Hz, H-10), 4.44
(dd, 1H, J1,2 6.5 Hz, J2,3 7.0 Hz, H-2), 4.34 (d, 1H, H-1), 4.25 (m,
1H, H-5), 4.10–3.90 (m, 5H, H-3, H-4, H-6a, H-6b, H-40), 3.99 (dd,
0
0
1H, J2 ,3 1.5 Hz, H-20), 3.85 (dt, 1H, J3 ,4 3.0 Hz, J3 ,OH 2.3 Hz, H-30),
3.67, 3.53 (AB system, 2H, JA,B 10.2, H-60a, H-60b), 3.30, 3.26, 3.24
(3s, each 3H, 2 ꢂ OMe-1, OMe-50), 1.36, 1.31, 1.30, 1.26 (4s, each
0
0
0
0
0
4.24 (m, 1H, J2 ,3 5.4 Hz, H-30), 4.08 (dd, 1H, J6a,6b 10.5 Hz, H-6b),
4.07 (dd, 1H, J3,4 2.0 Hz, H-3), 4.04 (dd, 1H, H-4), 3.97 (m, 2H, H-
6a, H-20), 3.90 (m, 2H, H-60a, H-60b), 3.35, 3.33 (2s, each 3H,
2 ꢂ OMe), 1.34, 1.31, 1.30, 1.29 (4s, each 3H, 2 ꢂ CMe2); 13C NMR
(62.9 MHz, CD3CN): d 150.4 (C-50), 139.8, 139.7, 139.5 (3 ꢂ Ar–C),
129.2–128.4 (Ar–CH), 110.6, 108.7 (2 ꢂ CMe2), 106.3 (C-1), 101.0
(C-10), 100.4 (C-40), 78.7 (C-3), 78.5 (C-5), 76.9 (C-4), 76.0 (C-2),
73.9, 72.8, 71.4 (3 ꢂ CH2Ph), 73.6 (C-20), 71.8 (C-30), 69.9 (C-60),
65.9 (C-6), 56.2, 53.8 (2 ꢂ OMe-1), 27.3, 27.2, 26.9, 25.1 (2 ꢂ CMe2).
Anal. Calcd for C41H52O11: C, 68.31; H, 7.27. Found: C, 68.28; H,
7.29.
0
0
3H, 2 ꢂ CMe2); 13C NMR (50 MHz, CD3CN):
d 139.2, 139.1
(2 ꢂ Ar–C), 128.8–128.6 (Ar–CH), 110.3, 108.7 (2 ꢂ CMe2), 106.3
(C-1), 102.6 (C-50), 99.1 (C-10), 80.3 (C-20), 78.6, 78.5, 77.7, 75.6
(C-2, C-3, C-4, C-5), 76.0, 73.8 (2 ꢂ CH2Ph), 71.1 (C-30), 66.8 (C-
40), 65.9, 65.5 (C-6, C-60), 56.4, 53.1 (2 ꢂ OMe-1), 48.8 (OMe-50),
27.1, 27.0, 26.9, 25.2 (2 ꢂ CMe2). Anal. Calcd for C35H50O13: C,
61.93; H, 7.42. Found: C, 61.96; H, 7.45.
The structure of 20 was confirmed by transformation into 17 by
treatment of 20 (0.112 g, 0.165 mmol) with TsOH (3 mg,
0.0167 mmol) in DMP (3 mL) at room temperature. After 4 h, the
TLC (1:1 hexane–EtOAc) revealed the complete disappearance of
the starting material, Et3N (0.4 mL) was added, and the solution
was stirred at room temperature. After 15 min the solution was
concentrated under diminished pressure and the residue
(125 mg) was subjected to flash chromatography (7:3 hexane–
EtOAc) to give 17 (0.110 g, 93% yield) as a colourless syrup, identi-
cal to the sample described above.
3.13. Epoxidation–methanolysis of 2,3,6-tri-O-benzyl-deoxy-
-erythro-hex-4-enopyranosyl-(1?4)-2,3:5,6-di-O-
isopropylidene-aldehydo- -glucose dimethyl acetal (22)
a-
L
D
A solution of 22 (233 mg, 0.323 mmol) in MeOH (12 mL) was
cooled to 0 °C and treated with 70% commercial MCPBA
(111.4 mg, 0.388 mmol). After 5 min, the reaction mixture was
gently warmed to room temperature and left under stirring until
22 was consumed (TLC, 1:1 hexane–EtOAc, 14 h). Satd aq NaHCO3
(10 mL) was added, the solution was further stirred for 10 min, and
the solvent was removed under diminished pressure. CH2Cl2
(20 mL) was added, the aq phase was extracted with CH2Cl2
(2 ꢂ 20 mL), and the collected organic extracts were dried, filtered
and concentrated under diminished pressure. The residue was sub-
jected to flash chromatography (3:2 hexane–EtOAc) to give 23
(42.8 mg, 17% yield) and the 40-epimer 24 (120 mg, 48% yield).
3.11.2. (5S or 5R)-2,6-Di-O-benzyl-5-C-methoxy-b-D-lyxo-
hexopyranosyl-(1?4)-2,3:5,6-di-O-isopropylidene-aldehydo-D-
glucose dimethyl acetal (21)
Colourless syrup; [
a
]
ꢀ42.0 (c 1.07, CHCl3); Rf 0.13 (1:1 hex-
D
ane–EtOAc); 1H NMR (200 MHz, CD3CN): d 7.39–7.25 (m, 10H,
Ar–H), 4.95, 4.69 (AB system, 2H, JA,B 11.8 Hz, CH2Ph), 4.72, 4.45
(AB system, 2H, JA,B 11.7 Hz, CH2Ph), 4.53 (dd, 1H, J1,2 6.3 Hz, J2,3
7.6 Hz, H-2), 4.39 (d, 1H, J1 ,2 1.0 Hz, H-10), 4.35 (d, 1H, H-1), 4.25
(dt, 1H, J 3.4 Hz, J 6.6 Hz, H-5), 4.05–3.94 (m, 4H, H-3, H-4, H-6a,
0
0

376
L. Guazzelli et al. / Carbohydrate Research 345 (2010) 369–376
3.13.1. (5R)-2,3,6-Tri-O-benzyl-5-C-methoxy-
osyl-(1?4)-2,3:5,6-di-O-isopropylidene-aldehydo-D-glucose
dimethyl acetal (23)
a
-
L
-ribo-hexopyran-
subjected to the workup described above, and the crude reaction
product was flash chromatographated (2:3 hexane–EtOAc) to give
25 (175 mg, 73% yield) as an amorphous solid, identical to the sam-
ple described above.
Colourless syrup, [
a
]
ꢀ14.6 (c 0.96, CHCl3); Rf 0.33 (3:2 hex-
D
ane–EtOAc); 1H NMR (250 MHz, CD3CN): d 7.43–7.26 (m, 15H, Ar
H), 4.88, 4.74 (AB system, 2H, JA,B 11.4 Hz, CH2Ph), 4.63, 4.50 (AB
system, 2H, JA,B 11.9 Hz, CH2Ph), 4.60, 4.44 (AB system, 2H, JA,B
3.15. 2,6-Di-O-benzyl-D-lyxo-hexos-5-ulose (26)
11.8 Hz, CH2Ph), 4.81 (d, 1H, J1 ,2 1.1 Hz, H-10), 4.42 (dd, 1H, J1,2
6.5 Hz, J2,3 7.5 Hz, H-2), 4.33 (d, 1H, H-1), 4.24 (dt, 1H, J4,5 3.4 Hz,
J5,6a = J5,6b 6.6 H-5), 4.09 (m, 1H, H-20), 4.01 (dd, 1H, J6a,6b 8.5 Hz,
Compound 26 was obtained by the method described above for
25, with the following reagents: 331 mg of 21 (0.49 mmol) in 2:1
(v/v) CH3CN–H2O (18 mL) and 90% aq CF3COOH (1.4 mL). After
1.5 h at 60 °C, TLC analysis showed the complete disappearance
of the starting material, and the reaction mixture was subjected
to the workup described above for 25. The residue (135 mg) was
subjected to a flash chromatographic purification, eluted with 3:7
hexane–EtOAc, to give 26 (126 mg, 72% yield) as a white solid; con-
0
0
0
0
H-6b), 3.96 (m, 3H, H-3, H-4, H-6a), 3.82 (ddd, 1H, J3 ,4 3.1 Hz,
J4 ,OH 9.9 Hz, J2 ,4 1.2 Hz, H-30), 3.81 (d, 1H, OH-40),3.74 (dd, 1H,
0
0
0
J2 ,3 2.9 Hz, H-30), 3.70, 3.50 (AB system, 2H, JA,B 10.2, H-60a, H-
60b), 3.28, 3.25, (2s, each 3H, 2 ꢂ OMe-1), 3.19 (s, 3H, OMe-50),
1.30 (s, 12H, 2 ꢂ CMe2); 13C NMR (62.9 MHz, CD3CN): d 139.5,
139.3, 139.2 (3 ꢂ Ar–C), 129.3–128.6 (Ar–CH), 110.4, 108.7
(2 ꢂ CMe2), 106.3 (C-1), 102.9 (C-50), 98.8 (C-10), 78.6 (C-3), 78.5
(C-5), 78.2 (C-20), 77.7 (C-4), 75.9, 73.9, 70.5 (3 ꢂ CH2Ph), 75.6 (C-
2), 74.0 (C-30), 68.5 (C-40), 65.9 (C-60), 65.5 (C-6), 56.4, 53.1
(2 ꢂ OMe-1), 48.9 (OMe-50), 27.1, 27.0, 26.9, 25.1 (2 ꢂ CMe2). Anal.
Calcd for C42H56O13: C, 65.61; H, 7.34. Found: C, 65.58; H, 7.28.
0
0
stituted (13C NMR, CD3CN) by a mixture of
anomers in a ratio of about 65:35 estimated on the basis of the rel-
a- and b-1,4-furanose
ative C-1 signal intensities (d 101.6 and 97.4, respectively); [a]
D
ꢀ15.5 (c 1.0, CHCl3); Rf 0.29 (4:1 CH2Cl2–Et2O); lit.16 for the
L-enan-
tiomer [
a]
+15.1 (c 0.96, CHCl3).
D1
Acknowledgement
3.13.2. (5S or 5R)-2,3,6-Tri-O-benzyl-5-C-methoxy-b-D-lyxo-
hexopyranosyl-(1?4)-2,3:5,6-di-O-isopropylidene-aldehydo-
glucose dimethyl acetal (24)
D
-
This research was partly supported by Ministero dell’Università
e della Ricerca (MIUR, Rome, Italy) in the frame of the COFIN na-
tional project.
Colourless syrup; [
a
]
ꢀ54.6 (c 0.99, CHCl3); Rf 0.44 (3:2 hex-
D
ane–EtOAc); 1H NMR (250 MHz, CD3CN): d 7.39–7.236 (m, 15H,
Ar–H), 4.93, 4.70 (AB system, 2H, JA,B 11.8 Hz, CH2Ph), 4.73, 4.47
(AB system, 2H, JA,B 11.7 Hz, CH2Ph), 4.59 (s, 2H, CH2Ph), 4.90 (d,
References
1H, J1 ,2 0.7 Hz, H-10), 4.53 (dd, 1H, J1,2 6.2 Hz, J2,3 7.5 Hz, H-2),
4.35 (d, 1H, H-1), 4.26 (dt, 1H, J 3.2 Hz, J 6.7 Hz, H-5), 4.18 (d, 1H,
1. Bonaccorsi, F.; Catelani, G.; Oscarson, S. Carbohydr. Res. 2009, 344, 1442–1448.
2. (a) Theander, O. Acids and other oxidation products. In The Carbohydrates:
Chemistry and Biochemistry, 2nd ed.; Pigman, W., Horton, D., Eds., Academic
Press: New York, 1980; Vol. 1B, pp 1013–1099; (b) De Lederkremer, R. M.;
Marino, C. Adv. Carbohydr. Chem. Biochem. 2003, 58, 199–306.
3. (a) Baxter, E. W.; Reitz, A. B. J. Org. Chem. 1994, 59, 3175–3185; (b) Barili, P. L.;
Berti, G.; Catelani, G.; D’Andrea, F.; De Rensis, F.; Puccioni, L. Tetrahedron 1997,
53, 3407–3416.
4. (a) Pistarà, V.; Barili, P. L.; Catelani, G.; Corsaro, A.; D’Andrea, F.; Fisichella, S.
Tetrahedron Lett. 2000, 41, 3253–3256; (b) Catelani, G.; Corsaro, A.; D’Andrea,
F.; Mariani, M.; Pistarà, V. Bioorg. Med. Chem. Lett. 2002, 12, 3313–3315.
5. Adinolfi, M.; Barone, G.; Iadonisi, A.; Mangoni, L. Tetrahedron Lett. 1998, 39,
2021–2024.
6. (a) Barili, P. L.; Berti, G.; Catelani, G.; D’Andrea, F. Gazz. Chim. Ital. 1992, 122,
135–142; (b) Barili, P. L.; Berti, G.; Catelani, G.; D’Andrea, F.; De Rensis, F.
Tetrahedron 1997, 53, 8665–8674.
7. (a) Enright, P. M.; O’Boyle, K. M.; Murphy, P. V. Org. Lett. 2000, 2, 3929–3932;
(b) Enright, P. M.; Tosin, M.; Nieuwenhuyzen, M.; Cronin, L.; Murphy, P. V. J.
Org. Chem. 2002, 67, 3733–3741; (c) Catelani, G.; Corsaro, A.; D’Andrea, F.;
Mariani, M.; Pistarà, V.; Vittorino, E. Carbohydr. Res. 2003, 338, 2349–2358; (d)
Corsaro, A.; Catelani, G.; D’Andrea, F.; Fisichella, S.; Mariani, M.; Pistarà, V.
Environ. Sci. Pollut. Res. 2003, 10, 325–328; (e) Guazzelli, L.; Catelani, G.;
D’Andrea, F.; Pistarà, V. Carbohydr. Res. 2009, 344, 717–724.
0
0
1H, J3 ,4 10.1 Hz, H-40), 4.05 (m, 1H, H-6b), 4.04 (dd, 1H, J2 ,3
0
0
0
0
3.0 Hz, H-20), 3.98 (dd, 1H, J3,4 1.3 Hz, H-3), 3.96 (m, 2H, H-4, H-
6a,), 3.59 (dd, 1H, H-30), 3.78, 3.61 (AB system, 2H, JA,B 10.5,
H-60a, H-60b), 3.37, 3.32 (2s, each 3H, 2 ꢂ OMe-1), 3.30 (s, 3H,
OMe-50), 1.31, 1.30, 1.29, 1.27 (4s, each 3H, 2 ꢂ CMe2); 13C NMR
(62.9 MHz, CD3CN): d 140.2, 139.9, 139.5 (3 ꢂ Ar–C), 129.2–128.1
(Ar–CH), 110.4, 108.7 (2 ꢂ CMe2), 106.7 (C-1), 100.3 (C-50), 99.3
(C-10), 78.8 (C-5), 78.6 (C-3), 78.5 (C-30), 77.9 (C-4), 76.9 (C-20),
76.3 (C-2), 75.0, 74.3, 72.4 (3 ꢂ CH2Ph), 68.8 C-40), 70.7 (C-60),
65.5 (C-6), 56.7, 54.0 (2 ꢂ OMe-1), 49.0 (OMe-50), 27.2, 27.1, 26.9,
25.2 (2 ꢂ CMe2). Anal. Calcd for C42H56O13: C, 65.61; H, 7.34.
Found: C, 65.58; H, 7.31.
3.14. 2,6-Di-O-benzyl-L-ribo-hexos-5-ulose (25)
A solution of 17 (344 mg, 0.479 mmol) in a 4:1 CH3CN–H2O
(8.5 mL) was treated with 90% aq CF3COOH (24.2 mL) and stirred
at 50 °C until the TLC analysis (EtOAc) showed the complete disap-
pearance of the starting material (5 h). The mixture was concen-
trated under diminished pressure and repeatedly co-evaporated
with toluene (4 ꢂ 30 mL). The crude residue was partitioned be-
tween brine (20 mL) and EtOAc (40 mL) and the aq phase was ex-
tracted with EtOAc (3 ꢂ 40 mL). The organic phases were collected,
dried and concentrated under diminished pressure to give a resi-
due that was directly subjected to a flash chromatographic purifi-
cation, eluting with 3:7 hexane–EtOAc, to give 25 (113 mg, 66%
yield) as an amorphous solid constituted (NMR) by a mixture of
8. Barili, P. L.; Bergonzi, M. C.; Berti, G.; Catelani, G.; D’Andrea, F.; De Rensis, F. J.
Carbohydr. Chem. 1999, 18, 1037–1049.
9. Barili, P. L.; Berti, G.; D’Andrea, F.; Di Bussolo, V.; Gaudiosi, A. Tetrahedron Lett.
1992, 33, 7061–7064.
10. Attolino, E.; Catelani, G.; D’Andrea, F. Eur. J. Org. Chem. 2006, 5279–5292.
11. Hanessian, S. Preparative Carbohydrate Chemistry; Marcel Dekker: New York,
1997. pp 127–149.
12. (a) Martin, O. R.; Yang, F.; Xie, F. Tetrahedron Lett. 1995, 36, 47–50; (b) Cipolla,
L.; Lay, L.; Nicotra, F. J. Org. Chem. 1997, 62, 6678–6681; (c) Juers, S.; Thiem, J. J.
Carbohydr. Chem. 2009, 28, 293–297.
13. Ley, S. V.; Griffith, W. P.; Norman, J.; Marsden, S. P. Synthesis 1994, 639–666.
14. Stevens, J. D. Carbohydr. Res. 1975, 45, 143–150.
15. (a) Berti, G. Top. Stereochem. 1972, 7, 130–152; (b) Barili, P. L.; Berti, G.;
Catelani, G.; Colonna, F.; D’Andrea, F. Carbohydr. Res. 1989, 190, 13–21.
16. Barili, P. L.; Catelani, G.; D’Andrea, F.; De Rensis, F.; Goracci, G. J. Carbohydr.
Chem 1998, 17, 1167–1180.
17. (a) O’Brien, J. L.; Tosin, M.; Murphy, P. V. Org. Lett. 2001, 3, 3353–3356; (b)
Steiner, A. J.; Stütz, A. E.; Tarling, C. A.; Withers, G. S.; Wrodnigg, T. M.
Carbohydr. Res. 2007, 342, 1850–1858.
18. 18. Catelani, G.; D’Andrea, F.; Guazzelli, L.; Masi, L.; Pistarà, V. XI Conference-
School on Carbohydrate Chemistry, 22-26 June 2008, Siena (Italy); OR 15.
19. Attolino, E.; Bonaccorsi, F.; Catelani, G.; D’Andrea, F. Carbohydr. Res. 2008, 343,
2545–2556.
a
- and b-1,4-furanose anomers in a ratio of about 7:3, estimated
on the basis of the relative C-10 NMR signal intensities (d 100.9
and 97.4, respectively); Rf 0.31 (1:1 hexane–EtOAc); mp 121–
125 °C; lit.8 mp 120–124 °C; [
a
]
D
ꢀ20.5 (c 0.7; CHCl3).
Hydrolysis of 20 (456 mg, 0.67 mmol) was performed in 4:1 (v/
v) CH3CN–H2O (11 mL) with 90% aq CF3COOH (2.3 mL) according to
the procedure described above. After 4 h, the reaction mixture was