Alkyloxycarbonyl group migration in furanosides

Article abstract of DOI:10.1016/j.tet.2012.05.117

A migration of methyloxycarbonyl group from secondary to primary hydroxyl was observed in furanosides (ribosides and xylosides) under usual desilylation conditions using tetrabutylammonium fluoride. The migration was studied further on several alkyloxycarbonyl furanosides under either basic or acidic conditions. As follows from ¹³C labelling experiments and product distribution, the migration in xylosides, proceeds intramolecularly via six-membered cyclic carbonate, whereas in ribosides, the migration is intermolecular. Acidic conditions prevented the migration in ribosides whereas the migration in xylosides was circumvented under neutral conditions.

Full text of DOI:10.1016/j.tet.2012.05.117

Tetrahedron 68 (2012) 6701e6711
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Alkyloxycarbonyl group migration in furanosides
,
,
*
Marcela Dvorakova a b, Marie Pribylova a, Radek Pohl c, Marie E. Migaud d, Tomas Vanek a
a Laboratory of Plant Biotechnologies, Joint Laboratory of Institute of Experimental Botany, Academy of Sciences of the Czech Republic, v.v.i., and Research Institute of Crop Production,
v.v.i., Rozvojova 263, 165 02 Prague 6, Czech Republic
b Department of Organic and Nuclear Chemistry, Faculty of Science, Charles University in Prague, Albertov 6, 128 43 Prague 2, Czech Republic
c Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo nam. 2, 166 10 Prague 6, Czech Republic
d School of Pharmacy, Queen’s University of Belfast, 97 Lisburn Rd., Belfast, BT9 7BL, Northern Ireland, United Kingdom
a r t i c l e i n f o
a b s t r a c t
Article history:
A migration of methyloxycarbonyl group from secondary to primary hydroxyl was observed in furano-
sides (ribosides and xylosides) under usual desilylation conditions using tetrabutylammonium fluoride.
The migration was studied further on several alkyloxycarbonyl furanosides under either basic or acidic
conditions. As follows from 13C labelling experiments and product distribution, the migration in xylo-
sides, proceeds intramolecularly via six-membered cyclic carbonate, whereas in ribosides, the migration
is intermolecular. Acidic conditions prevented the migration in ribosides whereas the migration in xy-
losides was circumvented under neutral conditions.
Received 22 February 2012
Received in revised form 11 May 2012
Accepted 28 May 2012
Available online 6 June 2012
Keywords:
Alkyloxycarbonyl group
Carbonate
Ó 2012 Elsevier Ltd. All rights reserved.
Desilylation
Furanoside
Migration
1. Introduction
Previously, we synthesized a series of OAADPR derivatives in
which the northern ribose was replaced by either xylose or arabi-
The synthesis of substituted carbohydrates is based on the
regioselective introduction of protecting groups allowing the sub-
sequent substitution of specific hydroxyl. Carbonates are utilized in
carbohydrate and peptide synthesis as alcohol as well as amine
protecting groups.1e7 They are susceptible to aqueous basic hy-
drolysis and in this respect, they are very similar to esters, but in
general, are considered much less prone to hydrolysis and migra-
tion because of the resonance effect of the second oxygen.1,8,9 For
example, Zhang et al. has prepared a series of glucopyranose acetyl
and ethyloxycarbonyl derivatives, from which only in acetate de-
rivatives a migration was observed under mild basic conditions.9 In
addition, éstergaard and Larsen investigated the stability of phenol
carbonates in aqueous buffer solutions throughout the pH range.10
They concluded that carbonates are more stable than esters to-
wards acid and base catalysis. Hence, we have explored the possi-
bility of using the methyloxycarbonyl group as a mimic of acetate
group in the synthesis of non-hydrolyzable acetyl adenosinedi-
phosphoribose derivatives (OAADPR).
nose.11 While synthesizing those analogues, a migration of the
acetyl group was observed under various conditions.12 Therefore,
we decided to employ the methyloxycarbonyl group instead to
avoid the migration. We have synthesized xylosyl and ribosyl
methylcarbonate derivatives, key intermediates for subsequent
synthesis of OAADPR analogues. However, during the approach, we
have noticed a migration of the carbonate moiety under conditions
analogous to those under which acetate migration occurred. Due to
its expected higher stability, the methylcarbonate migration was
rather surprising. Especially, as migration from 3-OH to 5-OH was
observed also in ribosides, in which the acetyl migration does not
occur due to the unfavourable stereochemistry of the hydroxyls.12
In contrast to acetates, whose migration around free hydroxyls
on sugar scaffolds was extensively studied, especially in
pyranosides,12e16 the information on such behaviour of carbonates
is sparse. Even though some carbonate rearrangements were also
reported, they usually happened under aqueous conditions,17 or in
certain types of compounds under nucleophilic catalysis, such as
OeC rearrangement in oxazolines and OeN rearrangement in
carbamates,18e22 or in alkenyl enol carbonates under transition
metal catalysis.23e26
* Corresponding author. Tel./fax: þ420 233 022 479; e-mail addresses: dvor-
akova@ueb.cas.cz (M. Dvorakova), pribylova@ueb.cas.cz (M. Pribylova), pohl@
uochb.cas.cz (R. Pohl), m.migaud@qub.ac.uk (M.E. Migaud), vanek@ueb.cas.cz
(T. Vanek).
In our case, we have observed carbonate migration from sec-
ondary to primary hydroxyls under mild basic conditions. When
mild acidic conditions were employed instead, the migration
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.05.117

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M. Dvorakova et al. / Tetrahedron 68 (2012) 6701e6711
occurred to some extent, but only in xylosides, and could be pre-
cluded by neutral conditions. Herein, we report the conditions
causing the migration and the products thereupon formed. We
compare the migration of three aliphatic carbonate groups: methyl,
ethyl and isobutylcarbonates, and we also compare the results to
those previously obtained for acetyl migration in furanosides.
We have prepared a series of xylofuranosyl and ribofuranosyl
aliphatic carbonates with the primary hydroxyl group protected
with a tert-butyldimethylsilyl (TBDMS) group, one of the most
frequently used protective groups for the alcohol functionality.27
We have selected methylcarbonate as isoster of the acetyl group
present in OAADPR and ethylcarbonate and isobutylcarbonate as
presumably more stable carbonate functions and isosters of re-
cently discovered ADPR propionate and butyrate.28
Table 1
The preparation of carbonates
ROCOCl
Si O
RO
Si O
O
O
DMAP, Py
O
O
dry DCM, 0 °C
overnight
O
O
HO
O
O
Entry
1
Substrate
Reagent
Product (product yield)a
Si O
O
Si O
HO
O
O
O
MeOCOCl
O
O
O
O
1a
1b (68%)
O
Si O
2. Results and discussion
O
O
EtOCOCl
O
O
The synthesis started from unprotected
steps gave 5-O-tert-butyldimethylsilyl-1,2-O-isopropylidene-
-xylofuranoside 1a,29,30 the substrate for the xylofuranosyl car-
D-xylose, which in two
O
1c (85%)
a
-
O
D
Si O
bonates syntheses. The synthesis of the ribofuranoside 2a, the
precursor of the ribofuranosyl carbonates, was achieved from the
xylofuranoside 1a by a standard oxidation/reduction sequence.31
This lengthy sequence was prioritized over the low yielding acid
catalyzed acetone condensation on ribose, which tends to mainly
favour the 2,3-O-isopropylidene ribose formation.32,33
Finally, the furanosyl carbonates were synthesized under basic
conditions using corresponding chloroformates. 3-O-Methylox-
ycarbonyl, ethyloxycarbonyl and isobutyloxycarbonyl xylofurano-
sides (entry 1) and ribofuranosides (entry 2) were thus generated
(Table 1).
To access the free 5-OH group in the furanosyl carbonates and
carry out subsequent phosphorylation reactions required in the
synthetic sequence to attain the targetted AcADPR analogues, the
TBDMS group had to be deprotected. Firstly, the desilylation was
accomplished with tetrabutylammonium fluoride (TBAF), the most
commonly used reagent for TBDMS deprotection.
Under these basic conditions, however, a migration of the
methylcarbonate function to the primary hydroxyl position was
observed, in both xyloside and riboside derivatives 1b and 2b
(entries 3 and 6, Tables 2 and 3). Although, the migration could be
expected for the xyloside derivative 1b, it was rather surprising in
riboside 2b due to the anti-configuration of the two hydroxyl
groups. Moreover, unlike in xylosides, the acetyl group in ribosides
was quite stable under the same conditions.12
O
O
IsobutylOCOCl
O
O
O
1d (96%)
O
Si O
O
O
Si O
HO
O
O
2
MeOCOCl
O
O
O
O
O
O
2a
2b (83%)
O
Si O
O
O
EtOCOCl
O
O
2c (75%)
O
Si O
O
O
IsobutylOCOCl
O
O
2d (94%)
O
a
Following column chromatography.
approximately 0.90 ppm upfield, and of H-5a and H-5b signals by
0.62 and 0.53 ppm downfield (Table 4) in comparison with starting
material. The H,H-COSY NMR experiment also revealed the cou-
pling between H-5 and OH protons. On the other hand, in non-
migrated compounds, the coupling between H-3 and OH protons
was observed.
To confirm the mechanism, the reaction was carried out also in
the presence of 13C labelled methanol. In case of xyloside 1b, a 50%
incorporation of 13CH3OH was observed (Fig. 1A) to form 5-O-13C-
The desilylation of 1b with TBAF was completed within minutes
when carried out under room temperature or 0 ꢀC, and gave two
major products, the migrated xyloside 3a, and the xyloside 3b, in
which the carbonate moiety was also hydrolyzed. Similar outcomes
were observed for the riboside 2b, when migrated riboside 6a and
the deprotected riboside 6b were obtained.
In addition, when the reaction was followed by 1H NMR, the
formation of three other minor products was detected only in case
of ribofuranoside 2b (entry 6). These products were identified as 3-
methylcarbonate-1,2-O-isopropylidene-
a
-D
-xylofuranoside
3c,
owing to the presence of 13CH3OH and CH3OH in 1:1 ration in the
reaction mixture. On the contrary, only minor incorporation oc-
curred in riboside 2b to give 5-O-13C-methylcarbonate-1,2-O-iso-
O-methylcarbonate-1,2-O-isopropylidene-
1,2-O-isopropylidene-3,5-O-di(methylcarbonate)-
side 6d and bis (1,2-O-isopropylidene- -ribofuranoside)-5-
a-
D-ribofuranoside 6c,
a-D
-ribofurano-
a
-D
propylidene-a-D-ribofuranoside 6f (Fig. 1B).
carbonate 6e. This observation confirmed that the migration from
3-OH to 5-OH in xylofuranosides proceeds by intramolecular
mechanism (via cyclic carbonate intermediate), whereas in ribo-
furanosides the migration is intermolecular. It is due to the rigid
ribofuranose ring conformation in which the substituents at posi-
tions 3 and 5 are in an anti-configuration, which forestalls the six-
membered cyclic carbonate formation.
On the grounds of the results obtained for TBDMS removal by
TBAF, acidic conditions using ceric ammonium nitrate (CAN) were
employed for this reaction instead. These conditions previously
prevented completely the acetyl migration in ribofuranosides, even
though they failed to avert the acetyl migration in xylofuranosides.12
Nevertheless, all the furanosyl carbonates were subjected not only to
TBDMS removal under basic conditions, but also under acidic con-
ditions to see if there is any difference between acetate and carbonate
group behaviour under such conditions (Tables 2 and 3).
The migration products were identified by 1H NMR spectros-
copy, which revealed the change in shift of H-3 signal by

M. Dvorakova et al. / Tetrahedron 68 (2012) 6701e6711
6703
Table 2
TBDMS deprotection in xylosides
Si O
RO
RO
O
O
O
O
O
O
RO
R = H or alkyl
O
O
,
b
Entry
3
Substrate
Reagent
TBAF
Product (product yield)a
O
Si O
O
O
O
O
HO
O
O
O
O
+
O
O
O
HO
1b
O
HO
O
O
3b (25%)
3a (73%)
O
H313C
HO
+
O
O
O
O
TBAFþ13C-MeOH
O
O
HO
O
HO
O
3b (23%)
3c (76%)
O
HO
+
O
O
O
O
O
O
O
O
O
O
+
CAN
O
HO
O
O
O
O
O
3d (0%)
3e (3%)
3a (92%)
O
b
(mixture 3a:3d, 1:1; 100%)
O
HO
O
O
O
O
O
O
O
+
CuCl2$2H2O
O
O
HO
O
3d (0%)
3a (95%)
O
b
(3a:3d, 0:1; 100%)
O
Si O
O
O
O
O
O
O
O
4
TBAF
+ 3b (4%)
O
O
HO
1c
O
O
4a (92%)
O
HO
O
O
O
O
O
O
+
CAN
O
O
HO
O
O
4a
4b (100%)b
O
(mixture 4a:4b, 1:2; 97%)a
O
Si O
O
O
O
O
O
O
5
TBAF
O
O
O
HO
1d
O
O
5a (96%)
O
HO
O
O
O
O
O
+
O
CAN
O
O
O
5b (100%)b
HO
O
5a
(mixture 5a:5b, 1:3; 94%)a
O
a
Following column chromatography.
The product yields from reaction before purification.
b

6704
M. Dvorakova et al. / Tetrahedron 68 (2012) 6701e6711
Table 3
TBDMS deprotection in ribosides
Si O
RO
RO
RO
O
O
O
O
O
O
O
R = H or alkyl
O
Entry
Substrate
Reagent
Product (product yield)a
O
O
HO
O
HO
O
O
O
O
O
O
+
+
Si O
O
HO
O
O
O
O
HO
O
O
O
6b (34%)
6c (11%)
6a (50%)
O
6
TBAF
O
O
O
OH
O
O
O
O
2b
O
O
O
+
O
O
+
O
O
O
O
O
O
O
O
6d (1%)
6e (2%)
HO
O
O
O
13
H
C
3
HO
O
O
O
TBAFþ13C-MeOH
O
O
+
HO
HO
O
O
6b (37%)
6f (60%)
HO
O
O
O
CAN
O
O
6c (95%)
O
O
O
Si O
O
O
HO
O
O
O
O
O
O
O
O
O
O
O
O
O
+
7
TBAF
+
+ 6b
(19%)
O
O
O
O
HO
O
2c
O
O
7c (8%)
7b (11%)
7a (60%)
O
O
O
HO
O
O
CAN
O
O
O
7b (96%)
O
O
O
O
Si O
O
O
O
O
O
HO
O
O
O
O
O
O
O
O
O
8
TBAF
+
+
+ 6b
(8%)
O
O
O
O
O
O
HO
O
2d
8c (6%)
O
8b (1%)
8a (82%)
O
O
HO
O
O
O
CAN
O
O
8b (96%)
O
a
Following column chromatography.
The deprotection of TBDMS group in xyloside 1b with CAN did
not completely prevent the carbonate migration and led to a for-
mation of a mixture of two compounds, migrated 3a and non-
migrated 3d xylosides, in 1:1 ratio (entry 3). This result suggests
that there is a difference in liability to migration between the ace-
tate and carbonate functional group, as acetyl migration was not
prevented at all when using CAN, whilst methylcarbonate migration
was prevented partly. It appears that in xylofuranosides, the six-
membered ring orthoacetate formation is facilitated under acidic
conditions, whereas the formation of cyclic carbonate is dis-
favoured. It seems that, under acidic conditions, the resonance effect
of carbonates’ second oxygen averts the orthocarbonate formation.
Noticibly, no migration was observed when the products were
kept in organic solvent (CDCl3), however when the mixture of 3a

M. Dvorakova et al. / Tetrahedron 68 (2012) 6701e6711
6705
Table 4
When xylofuranosides 1c and 1d were subjected to TBDMS
deprotection with TBAF (entries 4e5), also a complete migration of
carbonate occurred to form 5-O-ethylcarbonate xyloside 4a and 5-
O-isobutylcarbonate xyloside 5a, respectively. On the other hand,
these xylosides 1c and 1d were less susceptible to hydrolysis than
1b, and thus only 4% of 3b was formed from xyloside 1c and no such
product was observed in case of xyloside 1d.
The deprotection of xylosides 1c and 1d with CAN led only to
a formation of non-migrated products, 4b and 5b, respectively.
Nevertheless, the purification of these compounds by silica gel
column chromatography gave rise to migrated products again. The
ratio in favour of non-migrated xyloside was 2:1 for ethylcarbonate,
and 3:1 for isobutylcarbonate derivative.
1H NMR comparison of reactants to products
Reactant
H-3 (ppm)
H-5 (ppm)
Product
H-3 (ppm)
H-5 (ppm)
1a
2a
1b/1c/1d
4.32
3.98
5.14
4.12
1b/1c/1d
2b/2c/2d
3a/4a/5a
3b
5.14
4.78
4.19
4.34
5.09
4.88
3.98e3.89
4.13
4.80
3.85þ3.78
3.89þ3.75
4.49þ4.30
4.11þ4.00
3.86þ3.73
4.63þ4.54
4.49þ4.29
3.82
3.96þ3.68
4.47þ4.25
4.51þ4.30
3.89þ3.80
3.85þ3.78
3d/4b/5b
3e
2b/2c/2d
4.78
3.89þ3.75
6a/7a/8a
6b
6c/7b/8b
6d/7c/8c
6e
4.70
3.98e3.89
From these results, it is obvious that the higher alkyl group, the
less prone to migration it is. It may be caused either by the bulki-
ness of the alkyl group as well as by the positive inductive effect of
the alkyl groups.
To avoid the migration on silica gel column, some pre-
cautions were taken and tested on the purification of 3-O-eth-
ylcarbonate-1,2-O-isopropylidene-
a-D-xylofuranoside 4b. Firstly,
the pretreatment of silica gel column with eluent containing 1%
of Et3N followed by washing with eluent free of Et3N (five col-
umn volumes) was tried. This afforded only pure migrated
product 4a due to remaining basicity of column. Secondly, the
use of neutral alumina instead of silica gel for column chro-
matography was tested. Alike, it gave again the migrated prod-
uct 4a, containing 10% of non-migrated xyloside 4b according to
1H NMR. As a result, no conditions were found to afford pure
xylofuranoside 4b by column chromatography. Even though, the
xylofuranoside 4b could be used in further synthesis without
purification.
From the deprotection of ribofuranosides 2c and 2d with TBAF
were isolated four products, migrated ribosides 7a and 8a, non-
migrated ribosides 7b and 8b, dicarbonate ribosides 7c and 8c,
and ribofuranoside 6b (entries 7 and 8). On the contrary, CAN
deprotection of these ribosides 2c and 2d gave rise to non-migrated
ribofuranosides 7b and 8b, as expected following on from the
outcomes of the 3-O-methylcarbonate ribofuranoside 2b desilyla-
tion. Thus, these acidic conditions completely forestalled the mi-
gration in ribofuranosides.
In order to obtain pure 3-O-methylcarbonate xyloside 3d, neu-
tral catalytic conditions were employed for the desilylation of
TBDMS.34 Thus, a treatment of 1b with a catalytic amount of
CuCl2$2H2O in acetone/H2O (95/5) mixture under reflux gave rise
to a pure 3d (entry 3). However, the attempt of purification of the
compound by alumina column chromatography led again to a mi-
gration of methyloxycarbonyl moiety towards primary hydroxyl to
form 3a.
From the results obtained, it is obvious that the stability of
carbonate versus acetate depends on the reaction conditions. Un-
der basic conditions, the migration of carbonate proceeds promptly
from secondary to primary hydroxyl independently on migration
mechanism. It occurred also intermolecularly in ribosides, in which
the acetyl migration was disfavoured. Under acidic conditions, the
carbonate migration was almost completely prevented, except for
the methyloxycarbonyl group present on xylosides, which migrated
partly. The methyloxycarbonyl migration could however be totally
prevented under neutral conditions. Though the migration was
precluded during the reaction and work-up, the purification by
column chromatography caused migration in xylosyl carbonates,
which could not be forestalled. The absorption of compound on
column sorbent is probably the accelerator of the isomerisation.
Therefore, for the utilization of 3-alkyloxycarbonylxylosides in the
synthesis of AcADPR derivatives would be necessary to use them
directly in phosphorylation step and omit the intermediate’s
purification.
Fig. 1. A: Expanded 1H NMR spectrum of xylofuranoside 3c; B: Expanded 1H NMR
spectrum of ribofuranoside 6f.
and 3d was subjected to a silica gel column chromatography,
a conversion of 3d to 3a was observed. In addition, a minor com-
pound was isolated, which was identified as cyclic 3,5-O-carbon-
ate-1,2-O-isopropylidene-a-D-xylofuranoside 3e. This product
confirms the intramolecular migration mechanism via the cyclic
carbonate.
In riboside 2b, the intermolecular migration was disfavoured
under acidic conditions and thus the TBDMS deprotection with CAN
afforded only pure non-migrated 3-O-methylcarbonate ribofur-
anoside 6c (entry 6).
These results show that carbonate is more prone to in-
termolecular migration under basic conditions than acetate is, and
that intermolecular migration is completely precluded under acidic
conditions.

6706
M. Dvorakova et al. / Tetrahedron 68 (2012) 6701e6711
The difference in stability of carbonates depending on the size of
Bruker DPX 400 MHz or Bruker DRX 600 MHz. Trimethylsilane
(0 ppm, 1H NMR) and CDCl3 (77 ppm, 13C NMR) were used as in-
ternal references. The chemical shifts (d) are reported in ppm (parts
per millions) and the coupling constants (J values) are recorded in
Hz (hertz). The hydrogen and carbon assignments were done
according to 2D experiments (1He1H COSY and 1He13C HMQC).
Mass spectra were recorded on a LTQ Orbitrap XL spectrometer.
Optical rotations were measured on a PerkineElmer 341 polarim-
alkyl group was not very significant. Some difference could be
observed only in xylosides in which the higher alkyl group was, the
lower hydrolysis under basic conditions occurred and the higher
stability towards migration during column chromatography was
observed. The results correspond with those reported by Streidl
et al. who compared the leaving group abilities of organic car-
bonates and found that this ability decreases from methyl to iso-
butyl group revealing the isobutylcarbonate more stable.35 In
addition, Ogilvie and Letsinger stated that isobutylcarbonate’s
stability as alkali-labile protecting group is superior to acetate and
comparable to pivaloate.36
€
eter at 589 nm. Melting points were recorded on Buchi Melting
Point apparatus B-540. The elementar analyses were performed on
PerkineElmer 2400 Series II CHNS/O analyzer.
Overall, the carbonate migration is forestalled under acidic
conditions in both furanoside classes, which may be caused by the
enhanced stability of carbonates’ resonance forms. On the contrary,
under basic conditions, it seems that the electronegativity of sec-
ond oxygen surpasses its resonance effect, and thus the carbonate
undergoes the migration more easily than the ester functionality.
This finding is in contrast with the typical behaviour of carbonates,
which are considered more stable than esters under basic
conditions.1,8
4.2. 5-O-tert-Butyldimethylsilyl-1,2-O-isopropylidene-a-D-
xylofuranoside (1a)
1,2-O-isopropylidene-a-D-xylofuranoside (5.60 g, 29.5 mmol)
dissolved in dry pyridine/dry DCM (40 mL/40 mL) was added
dropwise to a solution of TBDMSCl (4.90 g, 32.5 mmol) and DMAP
(0.38 g, 3.00 mmol) in dry DCM (50 mL) at 0 ꢀC. The resulting so-
lution was allowed to warm up to room temperature and was
stirred overnight. The solvent was then removed under vacuum.
The white residue was dissolved in CHCl3 (100 mL), washed with
a saturated solution of NaHCO3 (2ꢂ50 mL). The aqueous layer was
then extracted with CHCl3 (3ꢂ50 mL). The combined organic layers
were washed with water and brine, dried, filtered and evaporated.
Purification by flash chromatography on silica gel (gradient from
8/2 to 6/4, v/v, hexane/EtOAc) gave the title compound 1a (8.45 g,
3. Conclusion
In summary, the carbonate migration from secondary to pri-
mary hydroxyl in furanosides occurs under mild basic conditions
and could be prevented under acidic conditions in ribosides. In
xylosides, non-migrated products can be obtained during desily-
lation under acidic or neutral conditions; however, when purified
by column chromatography, a prompt migration to primary hy-
droxyl occurs. In xylosides, the migration proceeds in-
tramolecularly through a six-membered cyclic carbonate, while in
ribosides, the migration is intermolecular due to unfavourable
stereochemistry of 3- and 5-OH. In comparison with acetyl group,
methyloxycarbonyl group seems more stable under acidic condi-
tions and less stable under basic conditions under, which also an
intermolecular migration in ribosides is facilitated.
94%) as a colourless oil. Rf (25% EtOAc/hexane) 0.74; ½a D20
ꢁ8.7
ꢃ
(c 0.4, CHCl3); nmax (CHCl3) 3411, 2932, 2859, 1257, 1120, 1074,
840 cmꢁ1
; dH (400 MHz, CDCl3) 5.96 (1H, d, J 3.7 Hz, H-1), 4.51 (1H,
d, J 3.7 Hz, H-2), 4.32 (1H, br s, H-3), 4.14e4.10 (3H, m, H-4, H-5a, H-
5b), 1.49 (3H, s, C(CH3)2), 1.32 (3H, s, C(CH3)2), 0.89 (9H, s,
SiC(CH3)3), 0.11 (3H, s, SiCH3), 0.11 (3H, s, SiCH3); dC (100 MHz,
CDCl3) 111.5 (C(CH3)2), 105.0 (C-1), 85.6 (C-2), 78.3 (C-4), 77.1 (C-3),
62.3 (C-5), 26.8 (C(CH3)2), 26.2 (C(CH3)2), 25.7 (SiC(CH3)3), 18.1
(SiC(CH3)3), ꢁ5.5 (SiCH3), ꢁ5.6 (SiCH3); HRMS (ESI): MNaþ, found
327.15986. C14H28NaO5Si requires 327.15982.
4.3. 5-O-tert-Butyldimethylsilyl-1,2-O-isopropylidene-a-D-
4. Experimental section
4.1. General
ribofuranoside (2a)
Dimethylsulfoxide (16.8 mL, 236 mmol) diluted in dry DCM
(50 mL) was added dropwise to a solution of oxalyl chloride
(10.0 mL, 118 mmol) in dry DCM (20 mL) at ꢁ78 ꢀC
and the resulting solution was stirred for 40 min. A solution of 5-O-
All reactions requiring anhydrous or inert conditions were car-
ried out under a positive atmosphere of argon in oven-dried
glassware. Solutions or liquids were introduced in round bottom
flasks using oven-dried syringes through rubber septa. All reactions
were stirred magnetically using Teflon-coated stirring bars. If
needed, reactions were warmed up using electrically-heated silicon
oil bath, and the stated temperature corresponds to the tempera-
ture of the bath. When reactions required cooling to ꢁ78 ꢀC, dry ice/
acetone bath was used. Organic solutions obtained after aqueous
work-up were dried over MgSO4. The removal of solvents was ac-
complished using a rotary evaporator at water aspirator pressure.
Chemicals were purchased from SigmaeAldrich Chemical
Company. Solvents for extractions and chromatography were pur-
chased of technical grade from Penta Chemicals s.r.o., Czech Re-
public. Solvents used in reactions were distilled from appropriate
tert-butyldimethylsilyl-1,2-isopropylidene-a-D-xylofuranoside 1a
(9.00 g, 29.5 mmol) in dry DCM (40 mL) was then added dropwise
to the reaction mixture, and stirring was continued at ꢁ78 ꢀC for
2 h. Et3N (60.0 mL, 472 mmol) was added at ꢁ78 ꢀC and, after
10 min, the reaction mixture was allowed to warm up to room
temperature. Water (60 mL) was then added and the aqueous layer
was extracted with Et2O (3ꢂ60 mL). The combined organic layers
were washed with a solution of NH4Cl (2ꢂ50 mL) and brine, dried,
filtered and concentrated under vacuum to afford the crude ketone
as an yellow oil. The residue was dissolved in THF/H2O (9/1) (80 mL)
and to this solution NaBH4 (1.13 g, 30.0 mmol) was added. The
resulting reaction mixture was stirred at room temperature for 2 h.
The reaction was quenched with a solution of NH4Cl and the
aqueous layer was then extracted with CHCl3 (3ꢂ30 mL). The
combined organic layers were washed with brine, dried, filtered
and evaporated under vacuum to afford the crude ribofuranoside as
an oil. Purification by flash chromatography on silica gel (gradient
from 85/15 to 65/45, v/v, hexane/EtOAc) afforded the title com-
pound 2a (3.90 g, 47%) as a colourless oil. Rf (25% EtOAc/hexane)
ꢀ
drying agents and stored under argon over activated Linde 4 A
molecular sieves. Column and flash chromatography was carried
out using Merck Silica (60e200
mm) or Merck neutral Alumina 90
(63e200 m). Analytical TLC was performed with Merck Silica gel
m
60 F254 plates. Visualization was accomplished by UV-light
(254 nm) and staining with a vanillin solution, followed by heat-
ing. IR spectra were recorded on Nicolet 6700 FT-IR spectrometer.
1H, 13C and 2D (H-COSY, HMQC) NMR spectra were all recorded on
0.72; ½a 2D0
ꢃ
þ30.7 (c 1.1, CHCl3); nmax (CHCl3) 3561, 2931, 2858, 1257,
1119, 1074, 1019, 936, 837 cmꢁ1
;
dH (400 MHz, CDCl3) 5.79 (1H, d, J

M. Dvorakova et al. / Tetrahedron 68 (2012) 6701e6711
6707
3.9 Hz, H-1), 4.56 (1H, dd, J 5.0, 3.9 Hz, H-2), 3.98 (1H, ddd, J 10.0,
8.0, 5.0 Hz, H-3), 3.89 (1H, dd, J 12.8, 4.0 Hz, H-5a), 3.82e3.79 (2H,
m, H-4, H-5b), 2.38 (1H, d, J 8.0 Hz, OH), 1.56 (3H, s, C(CH3)2), 1.36
(3H, s, C(CH3)2), 0.89 (9H, s, SiC(CH3)3), 0.07 (3H, s, SiCH3), 0.06 (3H,
s, SiCH3); dC (100 MHz, CDCl3) 112.5 (C(CH3)2), 104.1 (C-1), 81.1 (C-
4), 78.7 (C-2), 71.2 (C-3), 61.7 (C-5), 26.5 (C(CH3)2), 25.9 (SiC(CH3)3),
18.4 (SiC(CH3)3), ꢁ5.4 (SiCH3), ꢁ5.4 (SiCH3); HRMS (ESI): MNaþ,
found 327.15986. C14H28NaO5Si requires 327.15982.
column chromatography (gradient from 95/5 to 9/1, v/v, hexane/
EtOAc) afforded the title compound 1d (0.25 g, 96%) as a colourless
oil. Rf (10% EtOAc/hexane) 0.60; ½a D20
ꢃ
ꢁ32.7 (c 0.4, CHCl3); nmax
(CHCl3) 2960, 2858, 1746, 1472, 1258, 1092, 1022, 970, 840 cmꢁ1
;
dH
(400 MHz, CDCl3) 5.91 (1H, d, J 3.8 Hz, H-1), 5.13 (1H, d, J 3.1 Hz, H-
3), 4.57 (1H, d, J 3.8 Hz, H-2), 4.36 (1H, ddd, J 7.6, 5.6, 3.1 Hz, H-4),
3.92 (2H, d, J 6.7 Hz, CH2CH(CH3)2), 3.84 (1H, dd, J 10.0, 5.6 Hz, H-
5a), 3.80 (1H, dd,
J 10.0, 7.6 Hz, H-5b), 2.02e1.91 (1H, m,
CH2CH(CH3)2),1.52 (3H, s, C(CH3)2),1.31 (3H, s, C(CH3)2), 0.94 (6H, d,
J 6.7 Hz, CH2CH(CH3)2), 0.87 (9H, s, SiC(CH3)3), 0.05 (3H, s, SiCH3),
0.03 (3H, s, SiCH3); dC (100 MHz, CDCl3) 154.4 (CO), 112.2
(CH(CH3)2), 104.8 (C-1), 83.3 (C-2), 79.3 (C-4), 79.1 (C-3), 74.5
(CH2CH(CH3)2), 59.7 (C-5), 27.7 (CH2CH(CH3)2), 26.7 (C(CH3)2), 26.3
4.4. General procedure for carbonate formation
Methylchloroformate or ethylchloroformate or isobutyl chlor-
oformate (5ꢂn) was added dropwise to a stirred solution of
5-O-tert-butyldimethylsilyl-1,2-O-isopropylidene-
a
-
D
-xylofurano-
(C(CH3)2),
25.8
(SiC(CH3)3),
18.9
(CH2CH(CH3)2),
18.9
side 1a or 5-O-tert-butyldimethylsilyl-1,2-O-isopropylidene-
a
-
D
-
(CH2CH(CH3)2), 18.2 (SiC(CH3)3), ꢁ5.4 (SiCH3), ꢁ5.6 (SiCH3); HRMS
ribofuranoside 2a (1ꢂn), DMAP (0.1ꢂn) and dry pyridine (5ꢂn) in
dry DCM at 0 ꢀC. After stirring for 1 h at 0 ꢀC, the reaction mixture
was allowed to warm up to room temperature and left stirring
overnight. The reaction was quenched with a saturated solution of
Cu(SO4)2, solids formed were filtered off and washed with DCM.
The aqueous layer was extracted with Et2O and the combined or-
ganic layers were washed with water and brine, dried and
evaporated.
(ESI): MNaþ, found 427.21219. C19H36NaO7Si requires 427.21225.
4.4.4. 5-O-tert-Butyldimethylsilyl-1,2-O-isopropylidene-3-O-methyl-
carbonate-
(3.30 mmol) of 5-O-tert-butyldimethylsilyl-1,2-O-isopropylidene-
-ribofuranoside 2a. Purification by silica gel column chroma-
a-D-ribofuranoside (2b). For the reaction was used 1.00 g
a-D
tography (gradient from 85/15 to 65/45, v/v, hexane/EtOAc) affor-
ded the title compound 2b (1.00 g, 83%) as a white solid, mp
57e58 ꢀC; Rf (10% EtOAc/hexane) 0.36; ½a 2D0
ꢃ
þ91.0 (c 1.2, CHCl3);
4.4.1. 5-O-tert-Butyldimethylsilyl-1,2-O-isopropylidene-3-O-methyl-
nmax (CHCl3) 2958, 2858, 1753, 1444, 1279, 1128, 1020, 837 cmꢁ1
; dH
carbonate-
(4.92 mmol) of 5-O-tert-butyldimethylsilyl-1,2-O-isopropylidene-
-xylofuranoside 1a.
Purification by silica gel column chromatography (gradient
a
-
D
-xylofuranoside (1b). For the reaction was used 1.50 g
(400 MHz, CDCl3) 5.82 (1H, d, J 3.7 Hz, H-1), 4.83e4.78 (2H, m, H-2,
H-3), 4.17 (1H, td, J 8.0, 2.7 Hz, H-4), 3.89 (1H, dd, J 11.9, 2.5 Hz, H-
5a), 3.83 (3H, s, CH3), 3.74 (1H, dd, J 11.9, 3.0 Hz, H-5b), 1.55 (3H, s,
C(CH3)2), 1.35 (3H, s, C(CH3)2), 0.88 (9H, s, SiC(CH3)3), 0.055 (3H, s,
SiCH3), 0.044 (3H, s, SiCH3); dC (100 MHz, CDCl3) 154.9 (CO), 113.3
(C(CH3)2), 104.5 (C-1), 78.6 (C-4), 77.6 (C-2), 74.5 (C-3), 61.2 (C-5),
55.1 (CH3), 26.8 (C(CH3)2), 26.7 (C(CH3)2), 25.9 (SiC(CH3)3), 18.3
(SiC(CH3)3), ꢁ5.36 (SiCH3), ꢁ5.46 (SiCH3); HRMS (ESI) MNaþ, found
385.16530. C16H30NaO7Si requires 385.16530.
a-D
from 85/15 to 65/45, v/v, hexane/EtOAc) afforded the title com-
pound 1b (1.20 g, 68%) as a colourless oil. Rf (10% EtOAc/hexane)
0.45; ½a 2D0
ꢃ
ꢁ32.3 (c 1.0, CHCl3); nmax (CHCl3) 2958, 2858, 1753, 1443,
1274, 1093, 1023, 957, 840 cmꢁ1
;
dH (400 MHz, CDCl3) 5.91 (1H, d, J
3.7 Hz, H-1), 5.14 (1H, d, J 3.1 Hz, H-3), 4.57 (1H, d, J 3.7 Hz, H-2),
4.36 (1H, ddd, J 7.6, 5.5, 3.1 Hz, H-4), 3.85 (1H, dd, J 10.0, 5.5 Hz, H-
5a), 3.80 (3H, s, CH3), 3.78 (1H, dd, J 10.0, 7.6 Hz, H-5b), 1.52 (3H, s,
C(CH3)2), 1.31 (3H, s, C(CH3)2), 0.87 (9H, s, SiC(CH3)3), 0.05 (3H, s,
SiCH3), 0.03 (3H, s, SiCH3); dC (100 MHz, CDCl3) 154.8 (CO), 112.2
(CH(CH3)2), 104.8 (C-1), 83.2 (C-2), 79.4 (C-4), 79.3 (C-3), 59.8 (C-5),
55.0 (CH3), 26.7 (C(CH3)2), 26.3 (C(CH3)2), 25.8 (SiC(CH3)3), 18.2
(SiC(CH3)3), ꢁ5.5 (SiCH3), ꢁ5.7 (SiCH3); HRMS (ESI): MNaþ, found
385.16528. C16H30NaO7Si requires 385.16530.
4.4.5. 5-O-tert-Butyldimethylsilyl-1,2-O-isopropylidene-3-O-ethyl-
carbonate-
510 mg (1.70 mmol) of 5-O-tert-butyldimethylsilyl-1,2-O-iso-
propylidene- -ribofuranoside 2a.
a-D-ribofuranoside (2c). For the reaction was used
a-D
Purification by silica gel column chromatography (gradient from
95/5 to 9/1, v/v, hexane/EtOAc) afforded the title compound 2c
(460 mg, 75%) as a colourless oil. Rf (10% EtOAc/hexane) 0.43; ½a D20
ꢃ
þ86.9 (c 0.9, CHCl3); nmax (CHCl3) 2957, 2858,1749,1375,1269,1129,
4.4.2. 5-O-tert-Butyldimethylsilyl-1,2-O-isopropylidene-3-O-ethyl-
1022, 939, 837 cmꢁ1
; dH (400 MHz, CDCl3) 5.81 (1H, d, J 3.6 Hz, H-
carbonate-
665 mg (2.20 mmol) of 5-O-tert-butyldimethylsilyl-1,2-O-iso-
propylidene- -xylofuranoside 1a. Purification by silica gel col-
a
-
D
-xylofuranoside (1c). For the reaction was used
1), 4.82e4.78 (2H, m, H-2, H-3), 4.27e4.17 (3H, m, CH2CH3, H-4),
3.89 (1H, dd, J 11.8, 2.6 Hz, H-5a), 3.75 (1H, dd, J 11.8 3.0 Hz, H-5b),
1.55 (3H, s, C(CH3)2), 1.35 (3H, s, C(CH3)2), 1.33 (3H, t, J 7.1 Hz,
CH2CH3), 0.88 (9H, s, SiC(CH3)3), 0.06 (3H, s, SiCH3), 0.05 (3H, s,
SiCH3); dC (100 MHz, CDCl3) 154.3 (CO), 113.3 (CH(CH3)2), 104.4 (C-
1), 78.6 (C-4), 77.6 (C-2), 74.2 (C-3), 64.5 (CH2CH3), 61.2 (C-5), 26.8
(C(CH3)2), 26.7 (C(CH3)2), 25.9 (SiC(CH3)3), 18.3 (SiC(CH3)3), 14.2
(CH2CH3), ꢁ5.4 (SiCH3), ꢁ5.5 (SiCH3); HRMS (ESI): MNaþ, found
399.18096. C17H32NaO7Si requires 399.18095.
a-D
umn chromatography (gradient from 95/5 to 9/1, v/v, hexane/
EtOAc) afforded the title compound 1c (0.70 g, 85%) as a colourless
oil. Rf (10% EtOAc/hexane) 0.53; ½a D20
ꢃ
ꢁ30.8 (c 0.44, CHCl3); nmax
(CHCl3) 2957, 2858, 1748, 1375, 1264, 1092, 1022, 840 cmꢁ1
;
dH
(400 MHz, CDCl3) 5.90 (1H, d, J 3.7 Hz, H-1), 5.14 (1H, d, J 3.0 Hz, H-
3), 4.57 (1H, d, J 3.7 Hz, H-2), 4.36 (1H, ddd, J 7.6, 5.6, 3.0 Hz, H-4),
4.21 (2H, q, J 7.1 Hz, CH2CH3), 3.85 (1H, dd, J 10.0, 5.6 Hz, H-5a), 3.79
(1H, dd, J 10.0, 7.6 Hz, H-5b),1.52 (3H, s, C(CH3)2),1.31 (6H, t, J 7.1 Hz,
CH2CH3, C(CH3)2), 0.87 (9H, s, SiC(CH3)3), 0.05 (3H, s, SiCH3), 0.04
(3H, s, SiCH3); dC (100 MHz, CDCl3) 154.2 (CO), 112.1 (CH(CH3)2),
104.8 (C-1), 83.3 (C-2), 79.3 (C-4), 79.1 (C-3), 64.4 (CH2CH3), 59.8 (C-
5), 26.7 (C(CH3)2), 26.3 (C(CH3)2), 25.8 (SiC(CH3)3), 18.2 (SiC(CH3)3),
14.2 (CH2CH3), ꢁ5.5 (SiCH3), ꢁ5.7 (SiCH3); HRMS (ESI): MNaþ,
found 399.18100. C17H32NaO7Si requires 399.18095.
4.4.6. 5-O-tert-Butyldimethylsilyl-1,2-O-isopropylidene-3-O-iso-
butylcarbonate-
330 mg (1.08 mmol) of 5-O-tert-butyldimethylsilyl-1,2-O-iso-
propylidene- -ribofuranoside 2a. Purification by silica gel col-
a-D-ribofuranoside (2d). For the reaction was used
a-D
umn chromatography (gradient from 95/5 to 9/1, v/v, hexane/
EtOAc) afforded the title compound 2d (0.41 g, 94%) as a colourless
oil. Rf (10% EtOAc/hexane) 0.51; ½a D20
ꢃ
þ85.2 (c 0.53, CHCl3); nmax
(CHCl3) 2959, 2858, 1744, 1472, 1259, 1129, 1020, 837 cmꢁ1
;
dH
4.4.3. 5-O-tert-Butyldimethylsilyl-1,2-O-isopropylidene-3-O-iso-
(400 MHz, CDCl3) 5.82 (1H, d, J 3.7 Hz, H-1), 4.82 (1H, dd, J 4.9,
3.7 Hz, H-2), 4.78 (1H, dd, J 8.1, 4.9 Hz, H-3), 4.20 (1H, td, J 8.1,
2.7 Hz, H-4), 3.96 (2H, d, J 6.7 Hz, CH2CH(CH3)2), 3.89 (1H, dd, J 11.8,
2.4 Hz, H-5a), 3.75 (1H, dd, J 11.8, 3.0 Hz, H-5b), 2.05e1.94 (1H, m,
butylcarbonate-
197 mg (0.65 mmol) of 5-O-tert-butyldimethylsilyl-1,2-O-iso-
propylidene- -xylofuranoside 1a. Purification by silica gel
a-D-xylofuranoside (1d). For the reaction was used
a-D

6708
M. Dvorakova et al. / Tetrahedron 68 (2012) 6701e6711
CH2CH(CH3)2), 1.55 (3H, s, C(CH3)2), 1.35 (3H, s, C(CH3)2), 0.95 (6H,
d, J 6.7 Hz, CH2CH(CH3)2), 0.88 (9H, s, SiC(CH3)3), 0.04 (3H, s, SiCH3),
0.04 (3H, s, SiCH3); dC (100 MHz, CDCl3) 154.5 (CO), 113.2 (C(CH3)2),
104.5 (C-1), 78.6 (C-4), 77.6 (C-2), 74.6 (CH2CH(CH3)2), 74.2 (C-3),
61.2 (C-5), 27.7 (CH2CH(CH3)2), 26.8 (C(CH3)2), 26.7 (C(CH3)2), 25.9
(SiC(CH3)3), 18.9 (CH2CH(CH3)2), 18.9 (CH2CH(CH3)2), 18.4
(SiC(CH3)3), ꢁ5.4 (SiCH3), ꢁ5.5 (SiCH3); HRMS (ESI): MNaþ, found
427.21218. C19H36NaO7Si requires 427.21225.
64.2 (C-5), 55.2 (CH3), 26.8 (C(CH3)2), 26.2 (C(CH3)2); HRMS (ESI):
MNaþ, found 271.07890. C10H16NaO7 requires 271.07882.
Compound 3b: The spectroscopic data corresponded to those
given above.
4.5.3. 1,2-O-Isopropylidene-5-O-ethylcarbonate-
(4a). For the reaction was used 89.0 mg (0.24 mmol) of 5-O-tert-
butyldimethylsilyl-1,2-O-isopropylidene-3-O-ethylcarbonate-
a-D-xylofuranoside
a-D-
xylofuranoside 1c. The purification by silica gel column chroma-
tography (gradient from 100/0 to 99/1, v/v, DCM/EtOH) afforded
the title compound 4a (57.0 mg, 92%) as a white solid and 3b
(2.00 mg, 4%) as an oil.
4.5. General procedure for TBDMS group removal with TBAF
TBAF (1ꢂn, 1 M in THF) was added to a stirred solution of fu-
ranoside 1bed and 2bed (1ꢂn), respectively, in dry THF at room
temperature. After stirring for 10 min or 12 h (when stated), the
reaction mixture was diluted with CHCl3 and washed with a satu-
rated solution of NH4Cl (15 mL). The aqueous layer was extracted
(3ꢂ15 mL) with CHCl3, then evaporated and extracted with CHCl3
(5ꢂ5 mL) as solid. The combined organic layers were dried and
evaporated. The longer reaction time was used for the successful
isolation and identification of minor products.
Compound 4a: mp 105e107 ꢀC; Rf (10% EtOH/CHCl3) 0.70; ½a 2D0
ꢃ
þ13.2 (c 0.3, CHCl3); nmax (CHCl3) 3619, 3491, 2992,1740, 1375, 1274,
1164, 1077, 1012, 878, 860 cmꢁ1
; dH (400 MHz, CDCl3) 5.91 (1H, d, J
3.6 Hz, H-1), 4.54 (1H, d, J 3.6 Hz, H-2), 4.48 (1H, ddd, J 13.5, 5.7, 4.1,
H-5a), 4.32 (1H, dd, J 5.1, 2.5 Hz, H-4), 4.27e4.30 (1H, m, H-5b), 4.22
(2H, q, J 7.2 Hz, CH2CH3), 4.18 (1H, dd, J 4.6, 2.1 Hz, H-3), 3.08 (1H, d,
J 4.6 Hz, OH), 1.48 (3H, s, C(CH3)2), 1.30 (6H, t, J 7.2 Hz, CH2CH3,
C(CH3)2); dC (100 MHz, CDCl3) 155.6 (CO), 111.9 (CH(CH3)2), 104.7
(C-1), 85.1 (C-2), 78.0 (C-4), 74.4 (C-3), 64.9 (CH2CH3), 63.9 (C-5),
26.6 (C(CH3)2), 26.2 (C(CH3)2), 14.1 (CH2CH3); HRMS (ESI): MNaþ,
found 285.09451. C11H18NaO7 requires 285.09447.
4.5.1. 1,2-O-Isopropylidene-5-O-methylcarbonate-a-D-xylofurano-
side (3a). For the reaction was used 100 mg (0.28 mmol)
of 5-O-tert-butyldimethylsilyl-1,2-O-isopropylidene-3-O-meth-
Compound 3b: The spectroscopic data corresponded to those
obtained previously.
ylcarbonate-
column chromatography (CHCl3/EtOH, 98/2, v/v) afforded 1,2-
O-isopropylidene-5-O-methylcarbonate- -xylofuranoside 3a
a-D-xylofuranoside 1b. Purification by silica gel
4.5.4. 1,2-O-Isopropylidene-5-O-isobutylcarbonate-
side (5a). For thereactionwas used70.0 mg(0.17 mmol) of5-O-tert-
butyldimethylsilyl-1,2-O-isopropylidene-3-O-isobutylcarbonate-
-xylofuranoside 1d. The purification by silica gel column chroma-
a-D-xylofurano-
a-D
(50.0 mg, 73%) as a white solid and 1,2-O-isopropylidene-
xylofuranoside 3b (13.0 mg, 25%) as an oil.
a
-
D
-
a-
D
Compound 3a: mp 130e131 ꢀC; Rf (10% EtOH/CHCl3) 0.67; ½a 2D0
ꢃ
tography (gradient from 100/0 to 99/1, v/v, DCM/EtOH) afforded the
þ12.6 (c 0.94, CHCl3); nmax (CHCl3) 3619, 3497, 2994, 2937, 1746,
title compound 5a (48.0 mg, 96%) as a colourless oil. Rf (10% EtOH/
1444, 1282, 1163, 1077, 1016, 970, 860 cmꢁ1
;
dH (400 MHz, CDCl3)
CHCl3) 0.76; ½a 2D0
ꢃ
þ12.9 (c 0.22, CHCl3); nmax (CHCl3) 3619, 3495,
5.92 (1H, d, J 3.6 Hz, H-1), 4.55 (1H, d, J 3.6 Hz, H-2), 4.49 (1H, dd, J
12.8, 8.8 Hz, H-5a), 4.36e4.27 (2H, m, H-4, H-5b), 4.19 (1H, q, J
2.2 Hz, H-3), 3.80 (3H, s, CH3), 2.79 (1H, d, J 4.5 Hz, OH), 1.49 (3H, s,
C(CH3)2), 1.31 (3H, s, C(CH3)2); dC (100 MHz, CDCl3) 156.2 (CO), 111.9
(CH(CH3)2), 104.7 (C-1), 85.1 (C-2), 78.0 (C-4), 74.5 (C-3), 64.2 (C-5),
55.2 (CH3), 26.8 (C(CH3)2), 26.2 (C(CH3)2); HRMS (ESI): MNaþ, found
271.07887. C10H16NaO7 requires 271.07882.
2964, 1739, 1463, 1276, 1077, 1016, 973, 860 cmꢁ1
; dH (400 MHz,
CDCl3) 5.92 (1H, d, J 3.6 Hz, H-1), 4.55 (1H, d, J 3.6 Hz, H-2), 4.48 (1H,
dd, J 10.1, 6.3 Hz, H-5a), 4.35e4.26 (2H, m, H-4, H-5b), 4.22 (2H, dd, J
4.1, 1.9 Hz, H-3), 3.93 (2H, d, J 6.7 Hz, CH2CH(CH3)2), 3.01 (1H, d, J
4.5 Hz, OH), 2.02e1.91 (1H, m, CH2CH(CH3)2), 1.49 (3H, s, C(CH3)2),
1.31 (3H, s, C(CH3)2), 0.94 (6H, d, J 6.7 Hz, CH2CH(CH3)2); dC
(100 MHz, CDCl3) 155.9 (CO), 111.9 (CH(CH3)2), 104.7 (C-1), 85.1 (C-
2), 78.1 (C-4), 74.7 (CH2CH(CH3)2), 74.4 (C-3), 63.9 (C-5), 27.8
(CH2CH(CH3)2), 26.8 (C(CH3)2), 26.2 (C(CH3)2), 18.8 (CH2CH(CH3)2);
HRMS (ESI): MHþ, found 291.14375. C13H23O7 requires 291.14383.
Compound 3b: Rf (10% EtOH/CHCl3) 0.54; ½a D20
ꢁ13.9 (c 0.34,
ꢃ
CHCl3); nmax (CHCl3) 3589, 3450, 3029, 2937, 1105, 1076, 1013,
860 cmꢁ1
; dH (400 MHz, CDCl3) 5.97 (1H, d, J 3.6 Hz, H-1), 4.53 (1H,
d, J 3.6 Hz, H-2), 4.34 (1H, d, J 2.7 Hz, H-3), 4.17 (1H, td, J 4.5, 2.7 Hz,
H-4), 4.11 (1H, dd, J 12.3, 4.5 Hz, H-5a), 4.00 (1H, dd, J 12.3, 2.7 Hz,
H-5b), 1.48 (3H, s, C(CH3)2), 1.32 (3H, s, C(CH3)2); dC (100 MHz,
CDCl3) 111.7 (CH(CH3)2), 104.9 (C-1), 85.7 (C-2), 78.9 (C-4), 77.2 (C-
3), 60.9 (C-5), 26.8 (C(CH3)2), 26.2 (C(CH3)2); HRMS (ESI): MNaþ,
found 213.07327. C8H14NaO5 requires 213.07334.
4.5.5. 1,2-O-Isopropylidene-5-O-methylcarbonate-a-D-ribofurano-
side (6a). For the reaction was used 150 mg (0.41 mmol) of
5-O-tert-butyldimethylsilyl-1,2-O-isopropylidene-3-O-methylcar-
bonate-a-D-ribofuranoside 2b. The reaction was stirred for 12 h.
Purification by silica gel column chromatography (CHCl3/EtOH,
98/2, v/v) afforded as major products 1,2-O-isopropylidene-5-O-
4.5.2. 1,2-O-Isopropylidene-5-O-13C-methylcarbonate-
a
-
D
-xylofur-
methylcarbonate-
solid), and 1,2-O-isopropylidene-
34%, oil). Minor products isolated were: 1,2-O-isopropylidene-3-
O-methylcarbonate- -ribofuranoside 6c (11.0 mg, 11%, white
solid), 1,2-O-isopropylidene-3,5-O-di(methylcarbonate)- -ribo-
a
-
D
-ribofuranoside 6a (51.0 mg, 50%, white
anoside (3c). For the reaction was used 535 mg (1.48 mmol)
of 5-O-tert-butyldimethylsilyl-1,2-O-isopropylidene-3-O-methyl-
a-D
-ribofuranoside 6b (27.0 mg,
carbonate-
a
-
D
-xylofuranoside 1b and 56.0
m
L
of 13C-CH3OH
a-D
(1ꢂn). Purification by silica gel column chromatography (CHCl3/
EtOH, 98/2, v/v) afforded the title compound 3c (278 mg, 76%) as
a white solid, and 3b (64.0 mg, 23%) as an oil.
a-D
furanoside 6d (1.00 mg, 1%, oil) and bis (1,2-O-isopropylidene-
ribofuranoside)-3-carbonate 6e (3.00 mg, 2%, oil).
a-D-
Compound 3c: A 50% incorporation of 13C-CH3OH was observed.
Compound 6a: mp 108e109 ꢀC; [found: C, 48.54; H, 6.66.
C10H16O7 requires C, 48.39; H 6.50%]; Rf (10% EtOH/CHCl3) 0.74;
Mp 130e131 ꢀC; Rf (10% EtOH/CHCl3) 0.67; ½a 2D0
þ8.6 (c 0.9, CHCl3);
ꢃ
nmax (CHCl3) 3619, 3497, 2994, 2938, 1746, 1442, 1282, 1164, 1077,
½
a 2D0
ꢃ
þ43.2 (c 1.1, CHCl3); nmax (CHCl3) 3560, 3027, 2959, 1753, 1444,
1015, 968, 860 cmꢁ1
;
dH (400 MHz, CDCl3) 5.92 (1H, d, J 3.6 Hz, H-1),
1279, 1166, 1117, 1011, 873 cmꢁ1
;
dH (400 MHz, CDCl3) 5.83 (1H, d, J
4.55 (1H, d, J 3.6 Hz, H-2), 4.49 (1H, dd, J 12.8, 8.8 Hz, H-5a),
4.36e4.27 (2H, m, H-4, H-5b), 4.19 (1H, q, J 2.2 Hz, H-3), 3.80 (1.5H,
d, J 65.6 Hz, 13C-CH3), 3.80 (1.5H, s, CH3), 2.79 (1H, d, J 4.5 Hz, OH),
1.49 (3H, s, C(CH3)2),1.31 (3H, s, C(CH3)2); dC (100 MHz, CDCl3) 156.2
(CO), 111.9 (CH(CH3)2), 104.7 (C-1), 85.1 (C-2), 78.0 (C-4), 74.5 (C-3),
3.9 Hz, H-1), 4.58 (1H, t, J 4.3 Hz, H-2), 4.49 (1H, dd, J 12.0, 2.2 Hz, H-
5a), 4.29 (1H, dd, J 12.0, 4.5 Hz, H-5b), 3.98e3.88 (2H, m, H-3, H-4),
3.80 (3H, s, CH3), 2.39 (1H, d, J 6.2 Hz, OH), 1.57 (3H, s, C(CH3)2), 1.37
(3H, s, C(CH3)2); dC (100 MHz, CDCl3) 155.6 (CO), 112.8 (C(CH3)2),
104.0 (C-1), 78.2 (C-4, C-2), 71.6 (C-3), 65.9 (C-5), 54.9 (CH3), 26.5

M. Dvorakova et al. / Tetrahedron 68 (2012) 6701e6711
6709
(C(CH3)2), 26.4 (C(CH3)2); HRMS (ESI): MNaþ, found 271.07884.
ribofuranoside 2c. The reaction was stirred for 12 h. Purification
by silica gel column chromatography (CH2Cl2/EtOH, 999/1e99/
1e95/5, v/v) afforded 1,2-O-isopropylidene-5-O-ethylcarbonate-
C10H16NaO7 requires 271.07882.
Compound 6b: Rf (10% EtOH/CHCl3) 0.50; ½a D20
þ29.3 (c 0.16,
ꢃ
CHCl3); nmax (CHCl3) 3600, 3561, 3029, 2932, 1456, 1385, 1165, 1115,
a
-
D
-ribofuranoside 7a (84.0 mg, 60%), 1,2-O-isopropylidene-3-
1067, 1011, 873 cmꢁ1
;
dH (400 MHz, CDCl3) 5.71 (1H, d, J 3.6 Hz, H-
O-ethylcarbonate- -ribofuranoside 7b (15.0 mg, 11%) 1,2-
a-D
1), 4.54 (1H, t, J 4.2 Hz, H-2), 4.16e4.10 (1H, m, H-3), 3.85e3.80 (3H,
m, H-4, H-5), 1.52 (3H, s, C(CH3)2), 1.30 (3H, s, C(CH3)2); dC
(100 MHz, CDCl3) 112.3 (CH(CH3)2), 103.5 (C-1), 80.2 (C-4), 79.5 (C-
2), 70.6 (C-3), 60.0 (C-5), 26.6 (C(CH3)2), 26.3 (C(CH3)2); HRMS (ESI):
MNaþ, found 213.07335. C8H14NaO5 requires 213.07334.
O-isopropylidene-3,5-O-di(ethylcarbonate)-
(15.0 mg, 8%) and 6b (19.0 mg, 19%) as oils.
a-D-ribofuranoside 7c
Compound 7a: Rf (10% EtOH/CHCl3) 0.80; ½a D20
þ38.4 (c 0.68,
ꢃ
CHCl3); nmax (CHCl3) 3559, 3027, 2968, 1747, 1456, 1385, 1270, 1165,
1121, 1077, 1010, 873 cmꢁ1
; dH (400 MHz, CDCl3) 5.83 (1H, d, J
Compound 6c: mp 104e105 ꢀC; [found: C, 48.49; H, 6.56.
C10H16O7 requires C, 48.39; H, 6.50%]; Rf (10% EtOH/CHCl3) 0.67;
3.8 Hz, H-1), 4.57 (1H, t, J 4.2 Hz, H-2), 4.47 (1H, dd, J 12.1, 2.3 Hz, H-
5a), 4.28 (1H, dd, J 12.1, 4.5 Hz, H-5b), 4.20 (2H, q, J 7.1 Hz, CH2CH3),
3.97e3.88 (2H, m, H-4, H-3), 2.47 (1H, d, J 10.2 Hz, OH), 1.55 (3H, s,
C(CH3)2), 1.36 (3H, s, C(CH3)2), 1.29 (3H, t, J 7.1 Hz, CH2CH3); dC
(100 MHz, CDCl3) 155.0 (CO), 112.8 (C(CH3)2), 104.0 (C-1), 78.2 (C-4,
C-2), 71.5 (C-3), 65.7 (C-5), 64.3 (CH2CH3), 26.5 (C(CH3)2), 14.2
(CH2CH3); HRMS (ESI): MNaþ, found 285.09468. C11H18NaO7 re-
quires 285.09447.
½
a 2D0
ꢃ
þ118.4 (c 0.35, CHCl3); nmax (CHCl3) 3601, 2960, 1753, 1668,
1444, 1279, 1111, 1036, 1012, 873 cmꢁ1
;
dH (400 MHz, CDCl3) 5.83
(1H, d, J 3.7 Hz, H-1), 4.86e4.83 (1H, m, H-2), 4.80 (1H, dd, J 9.0,
4.7 Hz, H-3), 4.18 (1H, td, J 9.0, 2.6 Hz, H-4), 3.96 (1H, qd, J 12.8,
2.3 Hz, H-5a), 3.83 (3H, s, CH3), 3.68 (1H, ddd, J 12.8, 8.4, 2.9 Hz, H-
5b), 1.97 (1H, dd, J 8.4, 4.8 Hz, OH), 1.56 (3H, s, C(CH3)2), 1.35 (3H, s,
C(CH3)2); dC (100 MHz, CDCl3) 155.0 (CO), 113.5 (C(CH3)2), 104.1 (C-
1), 77.7 (C-4), 77.5 (C-2), 73.8 (C-3), 60.1 (C-5), 55.3 (CH3), 26.7
(C(CH3)2), 26.6 (C(CH3)2); HRMS (ESI): MNaþ, 271.07886.
C10H16NaO7 requires 271.07882.
Compound 6d: Rf (10% EtOH/CHCl3) 0.90; dH (400 MHz, CDCl3)
5.83 (1H, d, J 3.7 Hz, H-1), 4.85e4.82 (1H, m, H-2), 4.71 (1H, dd, J 9.0,
4.8 Hz, H-3), 4.47 (1H, dd, J 12.0, 2.5 Hz, H-5a), 4.32 (1H, ddd, J 9.0,
4.0, 2.5 Hz, H-4), 4.25 (1H, dd, J 12.0, 4.0 Hz, H-5b), 3.83 (3H, s, CH3),
3.79 (3H, s, CH3), 1.56 (3H, s, C(CH3)2), 1.35 (3H, s, C(CH3)2); HRMS
(ESI): MNaþ, found 329.08420. C12H18NaO9 requires 329.08430.
Due to low amount of material was not possible to measure 13C
NMR, so this compound was synthesized separately to confirm the
spectroscopic data obtained.
Compound 7b: Rf (10% EtOH/CHCl3) 0.76; ½a D20
þ115.4 (c 0.54,
ꢃ
CHCl3); nmax (CHCl3) 3602, 3027, 2937, 1749, 1376, 1270, 1167, 1112,
1036, 1017, 872 cmꢁ1
; dH (400 MHz, CDCl3) 5.83 (1H, d, J 3.6 Hz, H-
1), 4.85e4.78 (1H, m, H-2, H-3), 4.25 (1H, dq, J 7.2, 1.8 Hz, CH2CH3),
4.19 (1H, dt, J 8.8, 2.6 Hz, H-4), 3.95 (1H, ddd, J 12.8, 5.1, 2.3 Hz, H-
5a), 3.68 (1H, ddd, J 12.8, 8.3, 3.0 Hz, H-5b), 1.99 (1H, dd, J 8.3,
2.1 Hz, OH), 1.56 (3H, s, C(CH3)2), 1.35 (3H, s, C(CH3)2), 1.33 (3H, t, J
7.1 Hz, CH2CH3); dC (100 MHz, CDCl3) 154.4 (CO), 113.5 (CH(CH3)2),
104.0 (C-1), 77.7 (C-4), 77.6 (C-2), 73.6 (C-3), 64.8 (CH2CH3), 60.1 (C-
5), 26.6 (C(CH3)2), 26.6 (C(CH3)2),14.1 (CH2CH3); HRMS (ESI): MNaþ,
found 285.09456. C11H18NaO7 requires 285.09447.
Compound 7c: Rf (10% EtOH/CHCl3) 0.93; ½a D20
þ92.2 (c 0.22,
ꢃ
CHCl3); nmax (CHCl3) 3027, 2929, 1750, 1456, 1376, 1258, 1034, 1013,
Compound 6e: Rf (10% EtOH/CHCl3) 0.60; nmax (CHCl3) 2928,
873 cmꢁ1
; dH (400 MHz, CDCl3) 5.83 (1H, d, J 3.7 Hz, H-1),
1724, 1461, 1271, 1122, 1076, 1010, 873, 651 cmꢁ1
;
dH (400 MHz,
4.85e4.82 (1H, m, H-2), 4.72 (1H, dd, J 9.0, 4.8 Hz, H-3), 4.46 (1H,
dd, J 12.1, 2.5 Hz, H-5a), 4.33 (1H, ddd, J 9.0, 4.0, 2.5 Hz, H-4),
4.27e4.18 (5H, m, H-5b, 2ꢂ CH2CH3), 1.56 (3H, s, C(CH3)2), 1.35 (3H,
s, C(CH3)2), 1.33 (3H, t, J 7.1 Hz, CH2CH3), 1.31 (3H, t, J 7.1 Hz,
CH2CH3); dC (100 MHz, CDCl3) 154.8 (CO), 154.1 (CO), 113.5
(C(CH3)2), 104.1 (C-1), 77.2 (C-2), 75.2 (C-4), 74.3 (C-3), 64.9
(CH2CH3), 64.8 (CH2CH3), 64.4 (C-5), 26.6 (C(CH3)2), 26.6 (C(CH3)2),
14.2 (CH2CH3), 14.1 (CH2CH3); HRMS (ESI): MNaþ, found 357.11556.
C14H22NaO9 requires 357.11560.
CDCl3) 5.82 (1H, d, J 3.9 Hz, H-1), 4.57 (1H, t, J 4.3 Hz, H-2), 4.51 (1H,
dd, J 12.1, 2.3 Hz, H-5a), 4.30 (1H, dd, J 12.1, 4.5 Hz, H-5b), 3.98e3.89
(2H, H-4, H-3), 2.41 (1H, d, J 9.9 Hz, 3-OH), 1.57 (3H, s, C(CH3)2), 1.37
(3H, s, C(CH3)2); dC (100 MHz, CDCl3) 154.9 (CO), 112.8 (C(CH3)2),
103.9 (C-1), 77.9 (C-4, C-2), 71.3 (C-3), 65.9 (C-5), 25.9 (C(CH3)2),
25.8 (C(CH3)2); HRMS (ESI): MNaþ, found 429.13672. C17H26NaO11
requires 429.13673.
4.5.6. 1,2-O-Isopropylidene-5-O-13C-methylcarbonate-
a
-
D
-ribofur-
Compound 6b: The spectroscopic data corresponded to those
given above.
anoside (6f). For the reaction was used 200 mg (0.55 mmol) of
5-O-tert-butyldimethylsilyl-1,2-O-isopropylidene-3-O-methylcar-
bonate-
a
-
D
-ribofuranoside 2b and 23.0
m
L of 13C-CH3OH (1ꢂn).
4.5.8. 1,2-O-Isopropylidene-5-O-isobutylcarbonate-a-D-ribofur-
anoside (8a). For the reaction was used 170 mg (0.17 mmol)
of 5-O-tert-butyldimethylsilyl-1,2-O-isopropylidene-3-O-isobut
ylcarbonate-a-D-ribofuranoside 2d. The reaction was stirred for
12 h. The purification by silica gel column chromatography
(gradient from 100/0 to 99/1, v/v, DCM/EtOH) afforded 1,2-O-
Purification by silica gel column chromatography (CHCl3/EtOH,
98/2, v/v) afforded 6f (82.0 mg, 60%, white solid) and 6b (39.0 mg,
37%, oil).
Compound 6f: Only the minor incorporation of 13C-CH3OH was
observed.
Mp 108e109 ꢀC; Rf (10% EtOH/CHCl3) 0.74; ½a 2D0
ꢃ
þ43.0 (c 0.35,
isopropylidene-5-O-isobutylcarbonate-
(100 mg, 82%) as a white solid, 1,2-O-isopropylidene-3-O-iso-
butylcarbonate- -ribofuranoside 8b (1.00 mg, 1%), 1,2-O-iso-
propylidene-3,5-O-di(isobutylcarbonate)- -ribofuranoside 8c
(10.0 mg, 6%) and 6b (12.0 mg, 8%) as oils.
a
-
D
-ribofuranoside
8a
CHCl3); nmax (CHCl3) 3559, 3027, 2958, 1752, 1443, 1279, 1165, 1121,
1077, 1009, 873 cmꢁ1
;
dH (400 MHz, CDCl3) 5.83 (1H, d, J 3.9 Hz, H-
a-D
1), 4.58 (1H, t, J 4.3 Hz, H-2), 4.49 (1H, dd, J 12.0, 2.2 Hz, H-5a), 4.29
(1H, dd, J 12.0, 4.5 Hz, H-5b), 3.98e3.88 (2H, m, H-3, H-4), 3.80
(0.5H, d, J 65.6 Hz, 13C-CH3), 3.80 (2.5H, s, CH3), 2.39 (1H, d, J 6.2 Hz,
OH), 1.57 (3H, s, C(CH3)2), 1.37 (3H, s, C(CH3)2); dC (100 MHz, CDCl3)
155.6 (CO), 112.8 (C(CH3)2), 104.0 (C-1), 78.2 (C-4, C-2), 71.6 (C-3),
65.9 (C-5), 54.9 (CH3), 26.5 (C(CH3)2), 26.4 (C(CH3)2); HRMS (ESI):
MNaþ, found 271.07881. C10H16NaO7 requires 271.07882.
Compound 6b: The spectroscopic data corresponded to those
given above.
a-D
Compound 8a: mp 65e66 ꢀC; [found: C, 54.08; H, 7.74. C13H22O7
requires C, 53.78; H, 7.64%]; Rf (10% EtOH/CHCl3) 0.87; ½a D20
þ29.9 (c
ꢃ
0.45, CHCl3); nmax (CHCl3) 3559, 3028, 2968, 1746, 1471, 1385, 1270,
1165, 1121, 1077, 1010, 977, 873 cmꢁ1
; dH (400 MHz, CDCl3) 5.82 (1H,
d, J 3.8 Hz, H-1), 4.57 (1H, dd, J 4.5, 3.8 Hz, H-2), 4.49 (1H, dd, J 12.1,
2.3 Hz, H-5a), 4.28 (1H, dd, J 12.1, 4.7 Hz, H-5b), 3.98e3.88 (4H, m,
H-4, CH2CH(CH3)2, H-3), 2.45 (1H, d, J 10.1 Hz, OH), 2.01e1.90 (1H,
m, CH2CH(CH3)2), 1.56 (3H, s, C(CH3)2), 1.37 (3H, s, C(CH3)2), 0.94
(6H, d, J 6.7 Hz, CH2CH(CH3)2); dC (100 MHz, CDCl3) 155.3 (CO),
112.8 (CH(CH3)2), 104.0 (C-1), 78.2 (C-2, C-4), 74.4 (CH2CH(CH3)2),
71.6 (C-3), 65.8 (C-5), 27.7 (CH2CH(CH3)2), 26.5 (C(CH3)2), 26.5
4.5.7. 1,2-O-Isopropylidene-5-O-ethylcarbonate-
(7a). For the reaction was used 200 mg (0.53 mmol) of 5-O-tert-
butyldimethylsilyl-1,2-O-isopropylidene-3-O-ethylcarbonate-
a-D-ribofuranoside
a-D-

6710
M. Dvorakova et al. / Tetrahedron 68 (2012) 6701e6711
(C(CH3)2), 18.9 (CH2CH(CH3)2); HRMS (ESI): MNaþ, found
59.7 (C-5), 55.4 (CH3), 26.6 (C(CH3)2), 26.2 (C(CH3)2). For a full
313.12575. C13H22NaO7 requires 313.12577.
characterization see below.
Compound 8b: Rf (10% EtOH/CHCl3) 0.82; ½a D20
ꢃ
þ97.0 (c 0.95,
Compound 3e: Rf (10% EtOH/CHCl3) 0.78; ½a D20
þ16.7 (c 0.05,
ꢃ
CHCl3); nmax (CHCl3) 3601, 2966, 1745, 1471, 1384, 1267, 1167, 1111,
CHCl3); nmax (CHCl3) 2927, 2855, 1728, 1465, 1276, 1164, 1077, 1013,
1032, 1010, 873 cmꢁ1
1), 4.83 (1H, dd, J 4.7, 3.7 Hz, H-2), 4.79 (1H, dd, J 8.9, 4.7 Hz, H-3),
4.19 (1H, td, 8.9, 2.6 Hz, H-4), 3.97e3.92 (2H, m, H-5a,
;
dH (400 MHz, CDCl3) 5.82 (1H, d, J 3.7 Hz, H-
880 cmꢁ1
; dH (400 MHz, CDCl3) 6.02 (1H, d, J 3.7 Hz, H-1), 4.88 (1H,
d, J 2.9 Hz, H-3), 4.77 (1H, d, J 3.7 Hz, H-2), 4.65e4.61 (1H, m, H-5a),
4.54 (1H, m, H-4, H-5a),1.52 (3H, s, C(CH3)2),1.34 (3H, s, C(CH3)2); dC
(100 MHz, CDCl3) 146.8 (CO), 113.6 (CH(CH3)2), 105.7 (C-1), 84.4 (C-
2), 82.6 (C-3), 69.6 (C-4), 67.1 (C-5), 26.6 (C(CH3)2), 26.3 (C(CH3)2);
HRMS (ESI): MNaþ, found 239.05254. C9H12NaO6 requires
239.05261.
J
CH2CH(CH3)2), 3.68 (1H, d, J 12.6 Hz, H-5b), 2.10 (1H, br s, OH),
2.01e1.90 (1H, m, CH2CH(CH3)2), 1.56 (3H, s, C(CH3)2), 1.34 (3H, s,
C(CH3)2), 0.94 (6H, d, J 6.7 Hz, CH2CH(CH3)2); dC (100 MHz, CDCl3)
154.6 (CO), 113.4 (CH(CH3)2), 104.1 (C-1), 77.8 (C-4), 77.6 (C-2), 74.8
(CH2CH(CH3)2), 73.6 (C-3), 60.1 (C-5), 27.7 (CH2CH(CH3)2), 26.6
(C(CH3)2), 26.6 (C(CH3)2), 18.9 (CH2CH(CH3)2), 18.8 (CH2CH(CH3)2);
HRMS (ESI): MNaþ, found 313.12575. C13H22NaO7 requires
313.12577.
4.6.2. 1,2-O-Isopropylidene-3-O-ethylcarbonate-
(4b). For the reaction was used 99.0 mg (0.26 mmol) of 5-O-tert-
butyldimethylsilyl-1,2-O-isopropylidene-3-O-ethylcarbonate-
xylofuranoside 1c. The NMR of crude compound revealed almost
pure title compound 4b. However, the purification by silica gel
column chromatography (gradient from 100/0 to 99/1, v/v, DCM/
a-D-xylofuranoside
a-D-
Compound 8c: Rf (10% EtOH/CHCl3) 0.96; ½a D20
ꢃ
þ68.3 (c 0.87,
CHCl3); nmax (CHCl3) 3029, 2965, 1747, 1471, 1385, 1251, 1109, 1030,
1002, 975, 873 cmꢁ1
; dH (400 MHz, CDCl3) 5.84 (1H, d, J 3.8 Hz, H-
1), 4.84 (1H, dd, J 4.8, 3.8 Hz, H-2), 4.69 (1H, dd, J 9.0, 4.8 Hz, H-3),
4.46 (1H, dd, J 12.0, 2.5 Hz, H-5a), 4.34 (1H, ddd, J 9.0, 4.2, 2.6 Hz, H-
4), 4.25 (5H, dd, J 12.0, 4.2 Hz, H-5b), 3.94 (2H, d, J 6.7 Hz,
CH2CH(CH3)2), 3.92 (2H, d, J 6.7 Hz, CH2CH(CH3)2), 2.04e1.92 (1H,
m, CH2CH(CH3)2), 1.56 (3H, s, C(CH3)2), 1.35 (3H, s, C(CH3)2), 0.94
(12H, m, CH2CH(CH3)2); dC (100 MHz, CDCl3) 155.1 (CO), 154.3 (CO),
113.5 (C(CH3)2), 104.2 (C-1), 77.2 (C-2), 75.3 (C-4), 74.8 (C-3), 74.5
(CH2CH(CH3)2), 74.4 (CH2CH(CH3)2), 65.2 (C-5), 27.7 (CH2CH(CH3)2),
26.6 (C(CH3)2), 18.9 (CH2CH(CH3)2), 18.9 (CH2CH(CH3)2), 18.8
(CH2CH(CH3)2); HRMS (ESI): MNaþ, found 413.17816. C18H30NaO9
requires 413.17820.
EtOH) afforded
carbonate- -xylofuranoside 4b and 1,2-O-isopropylidene-5-O-
ethylcarbonate- -xylofuranoside 4a (67.0 mg, 97%) as a colour-
less oil in 2:1 ratio. The pretreatment of silica gel column with el-
uent containing 1% of Et3N followed by washing with eluent free of
Et3N (five column volumes) afforded pure 4a. The use of alumina
instead of silica gel for column chromatography gave again the
migrated product 4a, containing 10% of non-migrated 4b according
to 1H NMR.
a mixture of 1,2-O-isopropylidene-3-O-ethyl-
a-D
a-D
Compound 4a: The spectroscopic data are given above.
Compound 4b: Rf (10% EtOH/CHCl3) 0.74; ½a D20
þ9.4 (c 0.3,
ꢃ
Compound 6b: The spectroscopic data corresponded to those
given above.
CHCl3); nmax (CHCl3) 3606, 3510, 2930, 1742, 1376, 1269, 1164, 1093,
1018, 957 cmꢁ1
; dH (400 MHz, CDCl3) 5.93 (1H, d, J 3.7 Hz, H-1), 5.10
(1H, d, J 2.8 Hz, H-3), 4.63 (1H, d, J 3.7 Hz, H-2), 4.39 (1H, dt, J 6.0,
2.8 Hz, H-4), 4.23 (2H, q, J 7.2 Hz, CH2CH3), 3.86 (1H, p, J 6.0 Hz, H-
5a), 3.73 (1H, p, J 6.0 Hz, H-5b), 2.2 (1H, t, J 6.8 Hz, OH), 1.52 (3H, s,
C(CH3)2), 1.32 (6H, t, J 7.2 Hz, CH2CH3, C(CH3)2); dC (100 MHz, CDCl3)
154.7 (CO), 112.3 (CH(CH3)2), 104.5 (C-1), 83.4 (C-2), 79.6 (C-3), 79.5
(C-4), 64.9 (CH2CH3), 59.6 (C-5), 26.7 (C(CH3)2), 26.2 (C(CH3)2), 14.1
(CH2CH3); HRMS (ESI): MNaþ, found 285.09456. C11H18O7Na re-
quires 285.09447.
4.6. General procedure for TBDMS group removal with CAN
CAN (1.1ꢂn) was added to a stirred solution of furanoside 1bed
and 2bed (1ꢂn), respectively, dissolved in a mixture of AcCN/H2O
(9/1, 20 mL). The reaction mixture was stirred at room temperature
for 2 h. After dilution with CHCl3 (10 mL), a solution of NaHCO3
(15 mL) was added. The aqueous layer was extracted with CHCl3
(3ꢂ10 mL) and the combined organic fractions were dried, filtered
and evaporated.
4.6.3. 1,2-O-Isopropylidene-3-O-isobutylcarbonate-a-D-xylofurano-
side (5b). For the reaction was used 80.0 mg (0.20 mmol) of 5-O-
tert-butyldimethylsilyl-1,2-O-isopropylidene-3-O-iso-
4.6.1. 1,2-O-Isopropylidene-3-O-methylcarbonate-a-D-xylofurano-
side (3d). For the reaction was used 160 mg (0.44 mmol) of 5-O-
tert-butyldimethylsilyl-1,2-O-isopropylidene-3-O-methylcar-
bonate-a-D-xylofuranoside 1b. The reaction led to a formation of
butylcarbonate-a-D-xylofuranoside 1d. The NMR of crude com-
pound revealed almost pure title compound 5b. However, the
purification by silica gel column chromatography (gradient from
100/0 to 99/1, v/v, DCM/EtOH) afforded a mixture of 1,2-O-iso-
a mixture of two compounds (115 mg, white solid, in 1:1 ratio),
which were identified as 1,2-O-isopropylidene-5-O-methylcar-
propylidene-3-O-ethylcarbonate- -xylofuranoside 5b and 1,2-O-
a
-
D
bonate-
methylcarbonate-
a
-
D
-xylofuranoside 3a and 1,2-O-isopropylidene-3-O-
-xylofuranoside 3d. Purification by silica gel
isopropylidene-5-O-ethylcarbonate-a-D-xylofuranoside 5a
(54.0 mg, 94%) in 3:1 ratio as colourless oil.
a-
D
column chromatography (gradient from 100/0 to 99/1, v/v, DCM/
EtOH) led to an isolation of 3.00 mg of cyclic 1,2-O-isopropylidene-
Compound 5a: The spectroscopic data are given above.
Compound 5b: Rf (10% EtOH/CHCl3) 0.79; ½a D20
þ11.8 (c 0.51,
ꢃ
3,5-O-carbonate-
of 1,2-O-isopropylidene-5-O-methylcarbonate-
3a (white solid). The amount of 1,2-O-isopropylidene-5-O-meth-
ylcarbonate- -xylofuranoside 3a was given by the conversion of
a
-D-xylofuranoside 3e (3%, oil) and 101 mg (92%)
CHCl3); nmax (CHCl3) 3608, 3513, 2964, 1741, 1463, 1271, 1164, 1090,
a
-D-xylofuranoside
1019, 946 cmꢁ1
; dH (400 MHz, CDCl3) 5.94 (1H, d, J 3.7 Hz, H-1), 5.09
(1H, d, J 2.7 Hz, H-3), 4.63 (1H, d, J 3.7 Hz, H-2), 4.38 (1H, dt, J 6.0,
2.7 Hz, H-4), 3.99e3.90 (2H, m, CH2CH(CH3)2), 3.88e3.82 (1H, m, H-
5a), 3.75e3.68 (1H, m, H-5b), 2.28 (1H, br s, OH), 2.03e1.92 (1H, m,
CH2CH(CH3)2),1.52 (3H, s, C(CH3)2),1.31 (3H, s, C(CH3)2), 0.94 (6H, d,
J 6.7 Hz, CH2CH(CH3)2); dC (100 MHz, CDCl3) 155.0 (CO), 112.3
(CH(CH3)2), 104.5 (C-1), 83.4 (C-2), 79.5 (C-3, C-4), 74.9
(CH2CH(CH3)2), 59.6 (C-5), 27.7 (CH2CH(CH3)2), 26.6 (C(CH3)2), 26.2
(C(CH3)2), 18.8 (CH2CH(CH3)2), 18.8 (CH2CH(CH3)2); HRMS (ESI):
MNaþ, found 313.12577. C13H22O7Na requires 313.12577.
a-D
1,2-O-isopropylidene-3-O-methylcarbonate-a-D-xylofuranoside 3d
on silica gel column.
Compound 3a: The spectroscopic data correspond to those given
above.
Compound 3d: Rf (10% EtOH/CHCl3) 0.70; dH (400 MHz, CDCl3)
5.93 (1H, d, J 3.7 Hz, H-1), 5.09 (1H, d, J 2.7 Hz, H-3), 4.62 (1H, d, J
3.7 Hz, H-2), 4.38 (1H, dt, J 5.9, 2.7 Hz, H-4), 3.89e3.84 (1H, m, H-
5a), 3.82 (3H, s, CH3), 3.76e3.71 (1H, m, H-5b), 2.21 (1H, br s, OH),
1.51 (3H, s, C(CH3)2), 1.31 (3H, s, C(CH3)2); dC (100 MHz, CDCl3) 155.3
(CO), 112.3 (CH(CH3)2), 104.5 (C-1), 83.4 (C-2), 79.8 (C-3), 79.4 (C-4),
4.6.4. 1,2-O-Isopropylidene-3-O-methylcarbonate-
a-D-ribofurano-
side (6c). For the reaction was used 210 mg (0.58 mmol) of

M. Dvorakova et al. / Tetrahedron 68 (2012) 6701e6711
6711
5-O-tert-butyldimethylsilyl-1,2-O-isopropylidene-3-O-methylcar-
bonate- -ribofuranoside 2b. Purification by silica gel column
EtOH/CHCl3) 0.90; ½a D20
ꢃ
þ83.5 (c 0.26, CHCl3). nmax (CHCl3) 2959,
a-
D
2857, 1755, 1444, 1270, 1033, 1004, 942, 873 cmꢁ1
; dH (400 MHz,
chromatography (gradient from 6/4 to 1/1, v/v, hexane/EtOAc) gave
the title compound 6c (137 mg, 95%) as a white solid. The spec-
troscopic data are given above.
CDCl3) 5.83 (1H, d, J 3.7 Hz, H-1), 4.85e4.82 (1H, m, H-2), 4.71 (1H,
dd, J 9.0, 4.8 Hz, H-3), 4.47 (1H, dd, J 12.0, 2.5 Hz, H-5a), 4.32 (1H,
ddd, J 9.0, 4.0, 2.5 Hz, H-4), 4.25 (1H, dd, J 12.0, 4.0 Hz, H-5b), 3.83
(3H, s, CH3), 3.79 (3H, s, CH3), 1.56 (3H, s, C(CH3)2), 1.35 (3H, s,
C(CH3)2); dC (100 MHz, CDCl3) 155.4 (CO), 154.7 (CO), 113.6
(C(CH3)2), 104.2 (C-1), 77.1 (C-2), 75.2 (C-4), 74.6 (C-3), 65.1 (C-5),
55.3 (CH3), 55.0 (CH3), 26.6 (C(CH3)2), 26.6 (C(CH3)2); HRMS (ESI):
MNaþ, found 329.08429. C12H18NaO9 requires 329.08430.
4.6.5. 1,2-O-Isopropylidene-3-O-ethylcarbonate-
(7b). For the reaction was used 148 mg (0.39 mmol) of 5-O-tert-
butyldimethylsilyl-1,2-O-isopropylidene-3-O-ethylcarbonate-
a-D-ribofuranoside
a-D-
ribofuranoside 2c. Purification by silica gel column chromatography
(gradient from 100/0 to 99/1, v/v, DCM/EtOH) afforded the title
compound 7b (99.0 mg, 96%) as a colourless oil. The spectroscopic
data are given above.
Acknowledgements
The financial support by LH11048 grant from The Ministry of
Education, Youth and Sports, Czech Republic and EST grand from
Marie Curie EC funds are gratefully acknowledged.
4.6.6. 1,2-O-Isopropylidene-3-O-isobutylcarbonate-a-D-ribofurano-
side (8b). For the reaction was used 70.0 mg (0.17 mmol) of 5-O-
tert-butyldimethylsilyl-1,2-O-isopropylidene-3-O-iso-
butylcarbonate-a-D-ribofuranoside 2d. The purification by silica gel
Supplementary data
column chromatography (gradient from 100/0 to 99/1, v/v, DCM/
EtOH) afforded the title compound 8b (48.0 mg, 96%) as a colourless
oil. The spectroscopic data are given above.
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2012.05.117.
These data include MOL files and InChiKeys of the most important
compounds described in this article.
4.7. General procedure for TBDMS group removal with
CuCl2$2H2O
References and notes
CuCl2$2H2O (0.05 mmol) was added to a stirred solution of fu-
ranoside 1b (1.00 mmol), respectively, dissolved in a mixture of
acetone/H2O (95/5, 10 mL). The reaction mixture was stirred under
reflux for 9 h. After completion of the reaction, it was evaporated till
dryness. The residue was then dissolved in eluent (CHCl3/EtOH, 98/
2) and applied directly on column.
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4.7.1. 1,2-O-Isopropylidene-3-O-methylcarbonate-a-D-xylofurano-
side (3d). For the reaction was used 80.0 mg (0.22 mmol) of 5-O-
tert-butyldimethylsilyl-1,2-O-isopropylidene-3-O-methylcar-
bonate-
a-
D-xylofuranoside
1b,
2.00 mg
(0.011 mmol)
of
CuCl2$2H2O and 2.2 mL of acetone/H2O (95/5). The reaction led to
a formation of 3d (55.0 mg, 100%). Purification by neutral alumina
column chromatography of 40 mg (gradient from 98/2 to 95/5, v/v,
CHCl3/EtOH) led to an isolation of 38.0 mg of 1,2-O-isopropylidene-
5-O-methylcarbonate-a-D-xylofuranoside 3a.
Compound 3a: The spectroscopic data correspond to those given
above.
€
ꢀ
Compound 3d: Rf (10% EtOH/CHCl3) 0.67; ½a D20
þ3.3 (c 0.87,
ꢃ
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1021, 949, 859 cmꢁ1
; dH (400 MHz, CDCl3) 5.93 (1H, d, J 3.7 Hz, H-1),
ꢁ
17. Thevenet, S.; Wernicke, A.; Belniak, S.; Descotes, G.; Bouchu, A.; Queneau, Y.
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18. Joannesse, C.; Simal, C.; Concellon, C.; Thomson, J. E.; Campbell, C. D.; Slawin, A.
5.09 (1H, d, J 2.7 Hz, H-3), 4.62 (1H, d, J 3.7 Hz, H-2), 4.38 (1H, dt, J
5.8, 2.7 Hz, H-4), 3.86 (1H, dd, J 11.8, 5.8 Hz, H-5a), 3.82 (3H, s, CH3),
3.74 (1H, dd, J 11.8, 5.8 Hz, H-5b), 1.52 (3H, s, C(CH3)2), 1.31 (3H, s,
C(CH3)2); dC (100 MHz, CDCl3) 155.3 (CO), 112.3 (CH(CH3)2), 104.5
(C-1), 83.4 (C-2), 79.8 (C-3), 79.4 (C-4), 59.6 (C-5), 55.4 (CH3), 26.6
(C(CH3)2), 26.2 (C(CH3)2); HRMS (ESI): MNaþ, found 271.07888.
C10H16NaO7 requires 271.07882.
ꢁ
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4.8. 1,2-O-Isopropylidene-3,5-O-di(methylcarbonate)-a-D-
ribofuranoside (6d)
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To a solution of 1,2-O-isopropylidene-
(35.0 mg, 0.18 mmol) in dry DCM at 0 ꢀC was added DMAP
(7.00 mg, 0.055 mmol), dry pyridine (150 L, 1.80 mmol) and
methyl chloroformate (150 L, 1.80 mmol). The mixture was stirred
a-D-ribofuranoside 6b
m
m
30. Lu, Y.; Just, G. Tetrahedron 2001, 57, 1677e1687.
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of CuSO4, NaHCO3 and brine, and the organic phase was dried, fil-
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matography (gradient from 100/0 to 99/1, v/v, DCM/EtOH) afforded
the title compound 6d (46.0 mg, 82%) as a colourless oil. Rf (10%
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