Spiro-sulfamidate and sulfate nucleosides via 2′ and 3′-C-branched-chain sugars and nucleosides

Article abstract of DOI:10.1016/j.tet.2011.06.030

C-branched-chain sugars and nucleosides were obtained by organocatalysis from ulose derivatives. After a reduction step, the corresponding 1,3-diol was derivatized into 3′-spiro-sulfamidates and unexpected sulfates by treatment with a Burgess reagent. Dep

Full text of DOI:10.1016/j.tet.2011.06.030

Tetrahedron 67 (2011) 6006e6017
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Tetrahedron
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Spiro-sulfamidate and sulfate nucleosides via 20 and 30-C-branched-chain sugars
and nucleosides
ˇ
*
ꢀ
Jerome Lalot, Tony Tite, Anne Wadouachi, Denis Postel, Albert Nguyen Van Nhien
ꢀ
ꢀ
Laboratoire des Glucides-UMR6219, Universite de Picardie Jules Verne, Faculte des sciences, 33 rue Saint Leu, 80039 Amiens, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 April 2011
Received in revised form 31 May 2011
Accepted 10 June 2011
Available online 16 June 2011
C-branched-chain sugars and nucleosides were obtained by organocatalysis from ulose derivatives. After
a reduction step, the corresponding 1,3-diol was derivatized into 30-spiro-sulfamidates and unexpected
sulfates by treatment with a Burgess reagent. Deprotection of the Boc-derivatives was carried out while
preserving the cyclic sulfate. An example of ring opening of the cyclic sulfate derivative with sodium
azide leading to the corresponding 30-C-azidoalkyl branched-chain nucleosides is given.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
30-C-Nucleoside
1,3-Diol
Spiro-sulfate
Sulfamidate
Carbohydrate
Burgess reagent
1. Introduction
branched-chain nucleosides and investigate their use for the syn-
thesis of spiro-sulfamidate derivatives.
Branched-chain sugars and particularly branched-chain nucle-
osides have received much attention as potential chemotherapeutic
agent as well as in antisense oligonucleotide research. Some of
these analogues have been shown to display a very interesting
spectrum of antiviral and anticancer activities.1 The key step in the
total synthesis of these branched-chain sugar nucleosides is the
stereocontrolled quaternization of 20-C or 30-C by the formation of
a new CeC bond. One of the most used methods consists in adding
the C-nucleophile to the corresponding ketonucleoside. However,
ketonucleosides give generally moderate yields of the carbonyl
addition product upon reaction with Grignard,2 organolithium2e4
and organoaluminium reagents.5 The carbonyl addition reaction
involving 20-ketonucleosides with basic reagents is particularly
2. Results and discussion
In continuation of our search for new spiro sugar-modified
nucleosides of antiviral potential,8 we first investigated the re-
activity of the 4,6-O-benzylidene ketopyranose 1 (Scheme 1).
Compound 1 was obtained after a Swern oxidation of methyl 3-O-
benzyl-4,6-O-benzylidene-
a
-
D
-glucopyranoside.9 The crude 2-
-proline (30 mol %) in
ulose 1 was submitted to acetone and
DMSO and led exclusively to aldol 2 in 97% yield over two steps.
L
O
O
O
L-proline
Ph
O
Ph
O
(30 mol%)
O
O
OMe
+
OMe
problematic because b-elimination of the nucleobase readily oc-
DMSO, rt
curs.6,7 Organocatalysis is now widely used for stereocontrolled
CeC bond formation, and its utility is well recognized in a plethora
of organic reaction and synthesis of natural products. To the best of
our knowledge, no direct metal-free aldol reaction involving nu-
cleosides has been described, even if considerable attention has
been devoted to the synthesis of C-30-(20)-branched-chain nucleo-
sides.6 Here, we introduce the synthesis of a new class of C-30-(20)-
97%
BnO
HO
BnO
O
O
1
2
O
O
O
O
L-proline
Ph
O
Ph
O
(30 mol%)
O
OMe
+
OMe
DMSO, rt
65%
OBn
OH
O
OBn
O
3
4
* Corresponding author. Tel.: þ33 322827569; fax: þ33 322827568; e-mail
Scheme 1. Branched-chain sugars synthesis on pyranose ring.
address: albert.nguyen-van-nhien@u-picardie.fr (A. Nguyen Van Nhien).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.06.030

J. Lalot et al. / Tetrahedron 67 (2011) 6006e6017
6007
Similarly, starting from known ulose 3,10 the aldol 4 was obtained in
Ph
O
Ph
Ph
O
65% yield. In both cases, the attack took place from the
sugar moiety.
b-face of the
O
O
O
O
O
O
O
Next, we investigated the reactivity of the stereocontrolled
proline-aldolisation in the 1,2-O-isopropylidene ketopentofura-
noses series 5e7 with 5-O-trityl,11 5-O-tert-butyldimethylsilyl12
and 5,6-O-isopropylidene13 protecting groups (Table 1). Under
similar conditions and using ulose 5,6 in acetone at room temper-
ature, the desired aldol derivatives were obtained as mixture of
isomers for 8a/8b and 9a/9b in 49% and 65%, respectively. In 1989,
Camarasa14 and co-workers have already described the stereo-
selective addition of acetone to various furanos-3-ulose using
K2CO3. Despite a modest yield obtained for ulose 6 (58%), the au-
thors only obtained the acetonyl derivative 8a in 15% yield. This low
yield was partially attributed to the acidity of the proton H-4
leading among others to a polycyclic derivative. In our conditions,
such derivatives have not been detected. Finally, compounds 8a and
9a showed analytical and spectroscopic data in accordance to lit-
erature.14 The reaction carried out from the trityl derivative 7 led to
the only C-derivative 10a in 86% yield. The proposed proline-aldol
transition state clearly shows the preferential Si-facial attack for
compound 7 (Fig. 1) oriented by the bulky 1,2-O-isopropylidene
group. In contrast, transition state of ulose 5 does not show
a preferential facial attack. Similar steric hindrance from both iso-
propylidene was observed and was confirmed by the isolated ratio
of compounds 8a (27%) and 8b (22%).
O
Ph
Ph
O
Ph
O
H
H
N
O
N
O
7
Re-facial attack
Si-facial attack
O
O
O
O
O
O
O
O
O
O
O
O
H
H
N
O
O
N
O
O
5
Re-facial attack
Si-facial attack
Fig. 1. Aldol transition state.
obtained using the classical PDC reagent for oxidation from nu-
cleosides 11, 12 and 13, respectively. Using the proline-aldol con-
densation conditions, the 20-C-branched-chain nucleosides were
obtained with low yields (23%e44%) and weak selectivity except
for nucleoside 15a, which only gave the diastereoisomer 18a in 26%
yield (Table 2).
Table 2
Table 1
20-C-Branched-chain nucleosides synthesisa
Effect of organocatalysts and protecting group in aldol reactiona
TBSO
TBSO
O
O
O
B
B
O
O
L-proline
PDC, Ac2O,
molecular sieves,
CH2Cl2
catalyst
O
O
O
O
O
R
R
(30 mol%)
O
(30 mol%)
R
HO
+
+
O
DMSO, rt
acetone,
OH
8-10a
O
O
DMSO, rt
O
TBSO
OH
11-13
TBSO
O
5-7
8-10b
14-16
TBSO
B
Entry
1
Substrate
Catalyst
Product (yield%)b
TBSO
O
B
O
OH
+
L-Proline
8a (27%)/8b (22%)
TBSO
O
TBSO
17b-19b
OH
O
2
3
6 R¼CH2OTBS
7 R¼CH2OTrt
L
-Proline
-Proline
9a (60%)/9b (5%)
10a (86%)
17a-19a
L
Entry
1
Substrate
B
Product (yield%)b
Ratioc
63/37
4
5
8aþ8b (45%)
9aþ9b (68%)
O
NH
O
14
15
17a/17b (44%)
6 R¼CH2OTBS
7 R¼CH2OTrt
N
O
NH
O
2
18a (26%)
100/0
76/24
N
6
10a (70%)
NH2
N
N
a
Reaction conditions: ulose (1 equiv), catalyst (30 mol %) in DMSO at room
temperature for 24 h.
N
N
3
16
19a/19b (23%)
b
Isolated yield after column chromatography.
a
Reaction conditions: ulose (1 equiv), catalyst (30 mol %) in DMSO at room
temperature for 24 h.
We then applied the proline-aldol reaction to 20- and 30-keto-
nucleosides towards the synthesis of spiro sugar-modified nucle-
osides. These compounds should represent good candidate as
potent mimics of ATSAO8a derivatives or 20-C-methyl cytidine with
potential antiviral activities on the HIV-1 reverse transcriptase and
the NS5B HCV polymerase, respectively.15 The use of organo-
catalysis for aldolisation on nucleosides represent a soft quaterni-
zation method, especially for the 20-ketonucleosides, which are
known to be very sensitive and unstable due to the easy removal of
the nucleic base.12 20-Ketonucleosides 14,16 1517 and 1617 were
b
Isolated yield after column chromatography.
Determined by NMR.
c
Finally, we investigated the direct aldol reaction on the 30-
ketonucleosides. Starting from the known 30-ketonucleosides uri-
dine 2018 and thymidine 21,16 we were delighted to obtain stereo-
selectively the 30-C-branched-chain nucleosides 23 and 24 in 72%
and 90% yield, respectively (Table 3). In the same way, the purine
adenosine 2219 led to the aldol derivative 25 in 87% yield.

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J. Lalot et al. / Tetrahedron 67 (2011) 6006e6017
Table 3
O
O
30-C-Branched-chain nucleosides synthesisa
S
Boc
TBSO
O
O
O
Et3N
N
TBSO
B
1) NaBH4, MeOH
O
TBSO
L-proline
B
O
2) Dowex resin 50W-X8
THF, 80°C
(30 mol%)
O
9a
HO
O
+
OH
DMSO, rt
84%
OH
OTBS
dr 9.5:0.5
O
OTBS
26a/26b
23-25
20-22
TBSO
O
O
TBSO
Entry
1
Substrate
B
Product (yield%)b
O
O
O
O
O
O
NH
O
O
N
S
20
23 (72%)
O
SO2
Boc
SO2
O2
N
O
H
N
N
Boc
Boc
O
A
B
2
21
22
NH
O
24 (90%)
25 (87%)
N
14% Yield
44% Yield
NH2
N
N
N
N
3
TBSO
TBSO
O
O
O
O
O
O
O
S
O
27
a
+
Reaction conditions: ulose (1 equiv), catalyst (30 mol %) in DMSO at room
temperature for 24 h.
O
S
O
28
O
O
b
N
O
Isolated yield after column chromatography.
Boc
Cyclic sulfamidates represent synthetically versatile electro-
philes. Their synthesis and reactivity have been described in de-
tail.20 Although the reactivity of cyclic sulfamidates is well known,
especially in carbohydrate chemistry21 where they were useful
Scheme 2. Reactivity of Burgess reagent with 1,3-diol.
after an intramolecular displacement with inversion of configura-
tion. This result clearly showed that this step is dependent on the
steric constraint generated by the N-Boc Burgess reagent.
intermediates to synthesize various a- and b-glycosylamines, their
application to nucleoside chemistry has received little attention22
and to our knowledge, no spiro-sulfamidate of a pyrimidine nu-
cleoside has been reported so far. In order to extend the molecular
library of potent NNRTI (Non Nucleosidic Reverse Transcriptase
Inhibitor) similar to ATSAO compounds, we decided to undertake
the synthesis of these electrophile spiro derivatives.
Considering this interesting result and in order to synthesize
a 30-spiro-sulfamidate nucleoside 33 and 35, the aldol nucleoside
23 was first functionalized to avoid the reactivity between the ni-
trogen atom of the nucleic base and the Burgess reagent. Some
attempts to directly use the Burgess reagent with the unprotected
N-3 led to a complex mixture of compounds and degradation. The
uridine 23 was either alkylated in presence of K2CO3 and MeI in
acetone to afford 29 in 93% yield or protected with a Boc protecting
group to afford 30 in 74% yield (Scheme 3). We choosed the Boc
Before synthesizing 30-spiro nucleosides, we initially conducted
the reaction in a monosaccharide series. Compound 9a was chosen
as model because of the presence of the 5-OTBS protecting group
(Scheme 2). The carbonyl group was reduced using NaBH4 in MeOH,
which led to the mixture of diastereomers 26a/26b in 84% yield
(ratio 9.5/0.5). These latter were submitted to the N-Boc Burgess-
type reagent (4 equiv) in THF. As expected, the sulfamidate 27
was obtained but, in a modest yield (44%) via the double alcohol
activation of the 1,3-diol. Surprisingly, the sulfamidate was ac-
companied by a cyclic sulfate 28 in 14% yield. No spiro-derivatives
were isolated from the minor diastereoisomer 26. Cyclic sulfate
byproducts have never been described using a Burgess reagent in
literature. In-depth analysis of the 13C NMR clearly shows that the
carbon atom bearing the nitrogen atom in sulfamidate 27 presents
a chemical shift at 52.5 ppm, whereas the same carbon atom in the
sulfate 28 deshielded at 80.7 ppm. Moreover, the HRMS found for
both compounds are in accordance with the expected calculated
HRMS (See Experimental section. Compound 28: [MþH]þ
C17H36NO8SiS calcd 442.1931, found 442.1946; Compound 27:
[MþNa]þ C22H41NO9SiSNa calcd 546.2169, found 546.2183). The
plausible mechanism to explain the competition between the for-
mation of the cyclic sulfamidate and sulfate probably involved the
initial formation of a mono-sulfonated intermediate A. Before the
second addition of the Burgess reagent leading to intermediate B,
the restricted conformation imposed by the glucidic scaffold could
facilitate the concerted nucleophilic attack of the hydroxyl group on
the SO2 electrophilic centre and the alcohol deprotonation to afford
28. Concurrently, the intermediate A could react one more time
with the Burgess reagent to afford the expected sulfamidate 27
Scheme 3. Burgess reagent reactivity with pyrimidine nucleosides. Reagents and
conditions: (i) MeI, K2CO3, acetone; (ii) Boc2O, pyridine, CH2Cl2; (iii) (a) NaBH4, MeOH,
(b) Dowex resin 50W-X8.

J. Lalot et al. / Tetrahedron 67 (2011) 6006e6017
6009
protecting group, known to be readily cleaved under mild condi-
tions and in fact, probably compatible with the cyclic sulfate or
cyclic sulfamidate moieties. After a reduction step with NaBH4 in
MeOH, a mixture of isomers 1,3-diols 31a/31b (ratio 91/9) was
obtained in 71% yield from 23 and 32a/32b in 96% yield from 30.
When the mixture of 1,3-diols 31a/b was submitted to the N-Boc
Burgess reagent (4 equiv) in refluxing THF, a mixture of two six-
membered ring compounds were obtained. In a similar fashion,
as observed with the monosaccharide 26a/b, HPLC purification
provided the sulfamidate 33 and the cyclic sulfate 34 in 16% and
62% yield, respectively. Increasing the equivalents in N-Boc Burgess
reagent (6 equiv vs 4 equiv) led to 33 and 34 in 23% and 36% yield,
respectively. Moreover, very recently, Hudlicky and co-workers23
have studied the thermal stability by NMR experiments of several
Burgess reagents. They observed that some Burgess reagents
decomposed in less than an hour in refluxing THF and led us con-
sequently, to use 4 equiv of Burgess reagent in this study. This in-
teresting result emphasized a decrease in the overall yield (59% vs
78%) and a ratio increasing of 33 versus 34 (6 equiv: 34/33¼1.56;
4 equiv: 34/33¼3.8) and thus confirmed the previous proposed
mechanism as well as the relationship between the bulky Burgess
reagent’s and the favoured mono or bis-sulfonated intermediate.
The same conditions (4 equiv of Burgess reagent) applied to puri-
fied and isolated 32a also led to sulfamidate 35 in 22% yield and
sulfate 36 in 43% yield. These examples represent a direct method
towards the synthesis of spiro-sulfate on nucleoside diol. Usually,
cyclic sulfate were fused with the furanose ring.24 The few exam-
ples25 described in the literature were mostly used the two-step
sequences: formation of the cyclic sulfite intermediate followed
by a Sharpless oxidation.26 Cyclic sulfates are useful intermediates
in organic synthesis, one of their advantage consists in activating
a position (here, C-400) for nucleophilic attack and to generate an
acyclic sulfate.20b,27a
Fig. 2. NOESY experiment with spiro-sulfate 34.
H-500 and H-40/H-400, thereby ruling out the C-40 configuration as
well as the presence of the methylene group below the sugar ring.
The same result was also observed with the N-protected thy-
mine derivative 41 obtained from compound 24 (Scheme 5).
Compound 41 was obtained in 92% (Boc2O, pyridine, CH2Cl2) and
after a reduction step by NaBH4, compound 42a was separated and
isolated from 42b by HPLC for the next reaction step. Under the
same reaction conditions used for the synthesis of 27, the sole cyclic
sulfate 43 was isolated in 84% yield. The cyclic sulfamidate de-
rivative observed in the case of 33 has been scarcely detected by
mass spectrometry in this case.
O
O
R
Boc
N
N
TBSO
HO
TBSO
HO
N
N
1) NaBH4, MeOH
O
O
O
O
2) Dowex resin 50W-X8
72%
OTBS
OTBS
dr 86:14
O
HO
42a/42b
24
Boc2O, pyridine,
CH2Cl2, rt
92%
, R = H
The choice of Boc as protecting group proved to be suitable since
conditions used for its cleavage preserves the cyclic sulfate and
sulfamidate moieties for derivatives 35 and 36. Using classical
standard conditions (TFA, CH2Cl2), sulfamidate 35 led to depro-
tected compound 37 in 47% yield and N-Boc derivative 38 in 24%
yield. Using the same conditions, sulfate 36 led to deprotected
compound 39 in 40% yield and partially desilylated compound 40
(24%) (Scheme 4).
41
, R = Boc
O
N
Boc
N
NEt3
Boc
S
TBSO
O
O2
N
O
O
THF, 80°C
84%
O
42a
S
To confirm the configuration of the stereochemistry of C-400 in
the 1,3-diol 31a (the major product obtained after reduction of the
carbonyl group) and 34, a NOESY experiment was realized on the
cyclic sulfate 34 (Fig. 2). Two correlations were observed for H-40/
O
OTBS
O
43
Scheme 5. Synthesis of spiro-sulfate.
O
O
NH
NH
Finally, if we keep in mind that the formation of the cyclic sulfate
was due to the bulkiness of the Burgess reagent, which preferen-
tially attacks the alcoholic hydrogen than the SN2 displacement,
a less bulky Burgess reagent (Scheme 6), such as methyl N-(triethyl-
ammoniumsulfonyl)carbamate (Et3NeSO2eNCO2Me) would lead
preferentially to the sulfamidate ring. Remarkably, when the uri-
dine derivative 31a/b was submitted to the commercially available
TBSO
TBSO
N
N
TFA, CH2Cl2
50°C
O
O
O
O
35
+
O
O
O2S
HN
O2S
N
OTBS
OTBS
O
OtBu
38 (24%)
37 (47%)
O
O
O
N
NH
O
NH
TBSO
O2S
HO
N
N
O
TFA, CH2Cl2
50°C
TBSO
N
O
36
O
+
O
O
THF, 80°C
N
NEt3
O
O
31a/b
+
MeO2C
S
O
O
O2S
O2
42%
OTBS
OTBS
S
O
O
O
OTBS
N
MeO2C
39
40
(40%)
(24%)
44
Scheme 4. Deprotection of uridine compounds.
Scheme 6. Chimioselectivity with Burgess reagent.

6010
J. Lalot et al. / Tetrahedron 67 (2011) 6006e6017
NCO2Me Burgess reagent, we nicely isolated the sole sulfamidate
derivative 44 in 42% yield.
(230 mesh) or using an automatic flash chromatography apparatus.
Cyclohexane and ethyl acetate were distilled before use.
To confirm the sulfate structures, we took advantage of the good
electrophilic nature of the cyclic sulfate to open the ring with
a nucleophile, such as sodium azide (Scheme 7). Firstly, the treat-
ment of cyclic sulfate 34 with sodium azide in DMF at room tem-
perature and subsequent aqueous H2SO4 hydrolysis of the
generated acyclic sulfate gave the corresponding azidonucleosides
45 and 46 in 24% and 61% yield, respectively. Compound 46 was the
result of the deprotection of the 50-OTBS protecting group of
compound 45.
4.2. Synthesis
4.2.1. Methyl 3-O-benzyl-4,6-O-benzylidene-2-C-acetonyl-a-D-glu-
copyranose (2). To a solution of compound 1 (916 mg, 2.47 mmol)
in distilled CH2Cl2 (20 mL) at ꢀ78 ꢂC was added DMSO (0.53 mL,
7.42 mmol) and oxalyl chloride (0.42 mL, 4.94 mmol). After stirring
for 3 h, Et3N (1.04 mL, 7.42 mmol) was added and the reaction was
cooled at room temperature. After usual work-up, the crude ulose
was dissolved in DMSO (20 mL) and acetone (5 mL) and L-proline
O
(85 mg, 0.74 mmol) was added. After stirring for 40 h at room
temperature, the reaction mixture was extracted with EtOAc and
water. The organic phase was washed with a saturated solution of
NaCl, dried over Na2SO4, filtered and concentrated under reduced
pressure. After flash chromatography (EtOAc/cyclohexane, 20/80),
compound 2 was isolated as a colourless syrup (1.03 g, 97% over two
CH3
N
NaN3, DMF
rt
H2SO4,
H2O/THF
rt
TBSO
N
34
O
O
-O3S
N3
O
24% for 45
46
61% for
OTBS
steps). [a 20
]
þ50 (c 0.11, CHCl3); IR (ATR)
n
3417, 2927, 2857, 1706,
1662, 1470, 1454, 1361, 1118, 1073, 1045 cmꢀ1 1H NMR (CDCl3,
300 MHz):
7.56e7.27 (m, 10H, 2ꢁ C6H5), 5.61 (s,1H, CHPh), 4.89 (s,
D
O
;
CH3
N
d
2H, OCH2Ph), 4.79 (s, 1H, H-1), 4.33 (dd, 1H, J5,6b¼4 Hz,
J6a,6b¼9.6 Hz, H-6a), 3.98 (d, 1H, J3,4¼9.9 Hz, H-3), 3.90 (dt, 1H,
J4,5¼J5,6b¼9.5 Hz, J5,6a¼4.5 Hz, H-5), 3.82 (t, 1H, J5,6b¼J6a,6b¼9.5 Hz,
H-6b), 3.64 (t, 1H, J3,4¼J4,5¼9.5 Hz, H-4), 3.46 (s, 3H, OCH3), 3.33 (d,
1H, JA,B¼15 Hz, H-A (CH2CO)), 2.52 (d, 1H, JA,B¼15 Hz, H-B (CH2CO)),
RO
N
O
O
HO
N3
OTBS
2.26 (s, 3H, CH3); 13C NMR (CDCl3, 75 MHz):
d 209.9 (CO), 138.6,
45
, R = TBS
46, R = H
137.7, 128.2e126.0 (2ꢁ C6H5), 101.9, 101.1 (C-1, CHPh), 80.8, 80.4 (C-
4, C-3), 76.8 (C-2), 75.5 (OCH2Ph), 69.0 (C-6), 62.9 (C-5), 55.5
(OCH3), 43.3 (CH2e), 32.7 (eCH3). HRMS [MNaþ] C24H28O7Na calcd
451.1733, found 451.1729.
Scheme 7. Spiro-sulfate ring opening with NaN3.
3. Conclusions
We have synthesized various branched-chain sugars and nu-
cleosides under mild conditions using -proline as catalyst. After
4.2.2. Methyl 2-O-benzyl-4,6-O-benzylidene-3-C-acetonyl-
pyranose (4). To a solution of 3 (133 mg, 0.36 mmol) in DMSO
(3 mL) and acetone (0.5 mL) was added -proline (12.4 mg,
0.107 mmol). After stirring for 40 h at room temperature, water and
EtOAc were added. The organic layer was separated by extraction
and washed with a saturated solution of NaCl and water. The or-
ganic phase was dried over Na2SO4, filtered and evaporated to
dryness. After flash chromatography on silica gel (Cyclohexane/
EtOAc, 15/85), compound 4 (100 mg, 65%) was successively isolated
a-D-gulo-
L
a reduction step, the 1,3-diol has been easily converted into cyclic
sulfamidate or sulfate. Their stabilities were proved in N-Boc acidic
deprotection conditions. The activation of 1,3-diols via cyclic sul-
famidate and sulfate would give rise to two types of compound: (a)
a nucleophilic opening of cyclic sulfamidate on the C-30 and (b)
a nucleophilic ring opening of the cyclic sulfate on the C-400. Similar
studies on the 20-position, variation of the nucleophiles and also the
biological evaluation of the nucleosides is under investigation and
will be reported in due course.
L
as a solid: mp¼78e79 ꢂC; [
a
]
20 þ120 (c 0.11, CHCl3); IR (ATR)
n 3418,
D
3389, 2920, 2855, 1668, 1446, 1413, 1357, 1165, 1113, 1059, 1041,
1025 cmꢀ1
;
1H NMR (CDCl3, 300 MHz):
d
7.56e7.29 (m, 10H, 2ꢁ
C6H5), 5.49 (s, 1H, CHPh), 4.79 (d, 1H, JA,B¼12 Hz, H-A OCH2Ph), 4.74
(s, 1H, H-1), 4.69 (d, 1H, JA,B¼12 Hz, H-B OCH2Ph), 4.32 (d, 1H,
J6a,6b¼12 Hz, H-6a), 4.24 (dd, 1H, J4,5¼6 Hz, J5,6b¼3 Hz, H-5), 4.10
(dd, 1H, H-6b), 3.91 (d, 1H, H-4), 3.69 (d, 1H, JA,B¼15 Hz, H-A
(CH2CO)), 3.68 (s, 1H, H-2), 3.48 (s, 3H, OCH3), 2.64 (d, 1H,
JA,B¼15 Hz, H-B (CH2CO)), 2.08 (s, 3H, CH3); 13C NMR (CDCl3,
4. Experimental
4.1. Materials and methods
Melting points are uncorrected. Optical rotations were recorded
in CHCl3 solution. 1H NMR (300.13 MHz) and 13C NMR (75.47 MHz)
spectra were recorded in CDCl3 (internal Me4Si), respectively. 1H
assignments were deduced from 2D 1He1H NMR COSY experi-
ments. 13C assignments were deduced from 2D 13Ce1H NMR HSQC
experiments. Stereochemical assignments were deduced by anal-
ysis of the corresponding NOESY graph (NOESY graph 2D homo-
nuclear correlation via dipolar coupling. Dipolar coupling may be
due to NOE or chemical exchange. Phase sensitive with gradient
pulses in mixing time). TLC was performed on Silica F254 and de-
tection by UV light at 254 nm or by charring with p-anisaldehy-
deeH2SO4eAcOHeEtOH reagent. FTIR spectra were obtained using
ATR or NaCl and are reported in cmꢀ1. High-resolution mass spectra
(HRMS) were recorded on a Q-TOF spectrometer. HPLC analysis was
75 MHz):
d
212.5 (CO), 138.4, 137.9, 129.1e126.2 (2ꢁ C6H5), 103.3 (C-
1), 101.1 (CHPh), 78.3 (C-4), 74.3 (C-3), 73.7 (C-5), 72.7 (OCH2Ph),
69.3 (C-6), 61.9 (C-2), 55.8 (OCH3), 44.3 (CH2e), 32.1 (eCH3). HRMS
[MNaþ] C24H28O7Na calcd 451.1733, found 451.1729.
4.2.3. 1,2:5,6-Di-O-isopropylidene-3-C-acetonyl-
(8a) and 1,2:5,6-di-O-isopropylidene-3-C-acetonyl-
(8b). To a solution of 5 (100 mg, 0.39 mmol) in DMSO (4 mL) and
acetone (1 mL) was added -proline (0.0134 g, 0.12 mmol). After
a
-
D
-ribofuranose
a-D-xylofuranose
L
stirring for 24 h at room temperature, water (20 mL) was added.
The aqueous phase was then extracted with EtOAc (3ꢁ15 mL) and
the organic layers were combined, washed with water (20 mL) and
brine (20 mL), dried over Na2SO4, filtered and evaporated to dry-
ness. After flash chromatography on silica gel (Cyclohexane/EtOAc,
8/2e7/3), compound 8b (26.8 mg, 22%) was successively isolated as
a syrup followed by compound 8a (32.5 mg, 27%) as a syrup.
performed using a C18 5
alytical part and a C18 5
preparative. Column chromatography was effected on Silica Gel 60
m
(250mmꢁ4.6 mm) column for the an-
m
(250mmꢁ22 mm) column for HPLC

J. Lalot et al. / Tetrahedron 67 (2011) 6006e6017
6011
20
D
Compound 8a: [
a
]
þ45 (c 0.105, CHCl3); IR (ATR)
n
2998, 1708,
5.59
brine (20 mL), dried over Na2SO4, filtered and evaporated to dry-
ness. After flash chromatography on silica gel (Cyclohexane/EtOAc,
1374, 1205, 1045, 1011, 850 cmꢀ1; 1H NMR (CDCl3, 300 MHz):
d
(d, 1H, J1,2¼3.8 Hz, H-1), 4.44 (d,1H, J1,2¼3.8 Hz, H-2), 3.95e3.87 (m,
2H, H-6a, H5), 3.77 (dd, 1H, J4,6a¼5.2 Hz, J6a,6b¼8.0 Hz, H-6a), 3.65
(dd, 1H, J5,6b¼5.2 Hz, J6a,6b¼8.0 Hz, H-6b), 3.65 (d, 1H, J4,6a¼8.1 Hz,
1/0e7/3), compound 10a (98.1 mg, 86%) was isolated as a white
20
solid. Mp¼67 ꢂC; [
a]
þ3 (c 0.10, CHCl3); IR (ATR)
n 3299, 1706,
D
1372, 1213, 1050, 1002, 759, 690 cmꢀ1; 1H NMR (CDCl3, 300 MHz):
H-4), 3.23 (br s, 1H, OH), 2.95 (d, 1H, J3 a,3 b¼15.0 Hz, H-30a
d
7.55e7.26 (m, 15H, 3ꢁ C6H5), 5.87 (d, 1H, J1,2¼3.9 Hz, H-1), 4.60 (d,
0
0
(CH2CO)), 2.24 (d, 1H, J3 a,3 b¼15.0 Hz, H-30b (CH2CO)), 2.16 (s, 3H,
1H, J1,2¼3.9 Hz, H-2), 4.16 (t, 1H, J4,5a¼J4,5b¼5.3 Hz, H-4), 3.38 (m,
2H, H-5a, OH), 3.24 (dd, 1H, J4,5b¼4.9 Hz, J5a,5b¼10 Hz, H-5b), 2.65
(d, 1H, JA,B¼15 Hz, H-A (CH2CO)), 2.25 (d, 1H, JA,B¼15 Hz, H-B
(CH2CO)), 2.14 (s, 3H, CH3), 1.67, 1.42 (s, 6H, 2ꢁ CH3); 13C NMR
0
0
CH3), 1.44, 1.31, 1.23, 1.20 (s, 12H, 4ꢁ CH3); 13C NMR (CDCl3,
75 MHz):
d
208.2 (CO), 112.6, 109.8 [2ꢁ OC(CH3)2], 103.5 (C-1), 82.0
(C-4), 80.9 (C-2), 78.5 (C-3), 73.3 (C-5), 67.8 (C-6), 44.5 (CH2CO),
32.5 (CH3), 26.6, 26.5, 26.4, 25.2 (4ꢁ CH3). HRMS [MNaþ]
(CDCl3, 75 MHz): d 208.5 (CO), 143.7, 128.8e127.3 (C6H5), 112.7
20
C15H24O7Na calcd 339.1420, found 339.1413. Compound 8b: [
a]
[OC(CH3)2], 104.0 (C-1), 87.1 (Cq trityl), 81.1 (C-4), 80.9 (C-2), 78.4
(C-3), 61.7 (C-5), 43.9 (CH2CO), 32.5 (CH3), 26.7 (2ꢁ CH3). HRMS
[MNaþ] C30H32O6Na calcd 511.2097, found 511.2092.
D
þ10 (c 0.085, CHCl3); IR (ATR)
n
2987, 1700, 1372, 1213, 1165, 1063,
5.70 (d, 1H, J1,2¼3.7 Hz, H-
845 cmꢀ1; 1H NMR (CDCl3, 300 MHz):
d
1), 4.36 (d, 1H, J1,2¼3.7 Hz, H-2), 4.20 (m, 1H, H-5), 4.02 (br s, 1H,
OH), 3.93 (dd, 1H, J5,6a¼6.3 Hz, J6a,6b¼8.7 Hz, H-6a), 3.82 (dd, 1H,
J5,6b¼5.3 Hz, J6a,6b¼8.7 Hz, H-6b), 3.49 (d, 1H, J4,5¼8.2 Hz, H-4), 2.88
(d, 1H, JA,B¼18.3 Hz, H-A (CH2CO)), 2.79 (d, 1H, JA,B¼18.3 Hz, H-B
4.2.6. 1-(30,50-Bis-O-tert-butyldimethylsilyl-20-C-acetonyl-
ofuranosyl)uracil (17a) and 1-(30,50-bis-O-tert-butyldimethylsilyl-20-
C-acetonyl- -ribofuranosyl)uracil (17b). To a solution of 14 (1.71 g,
b-D-lyx-
b-D
(CH2CO)), 2.07 (s, 3H, CH3), 1.32, 1.18, 1.28, 1.12 (s, 12H, 4ꢁ CH3); 13
C
3.53 mmol) in DCM (25 mL) over molecular sieves (4 A), was added
PDC (0.929 g, 2.47 mmol) and Ac2O (1.26 mL, 12.34 mmol). The
reaction was allowed to stir at reflux for 2 h. EtOAc (50 mL) wad
added, the mixture was filtered over a pad of silica gel and washed
with EtOAc. The solvent was then removed at room temperature
under reduced pressure. To a solution of this crude product (1.7 g,
ꢁ
NMR (CDCl3, 75 MHz):
d
210.7 (CO), 112.0, 109.1 [2ꢁ OC(CH3)2],
104.6 (C-1), 85.4 (C-4), 82.8 (C-2), 79.3 (C-3), 72.2 (C-5), 67.4 (C-6),
43.7 (CH2CO), 30.9 (CH3), 26.9, 26.7, 26.3, 25.2 (4ꢁ CH3). HRMS
[MNaþ] C15H24O7Na calcd 339.1420, found 339.1412.
4.2.4. 5-O-tert-Butyldimethylsilyl-1,2-O-isopropylidene-3-C-ace-
3.53 mmol) in DMSO (35 mL) and acetone (10 mL) was added L-
tonyl-
isopropylidene-3-C-acetonyl-
6 (2.00 g, 6.61 mmol) in DMSO (60 mL) and acetone (15 mL) was
added -proline (0.22 g, 1.98 mmol). After stirring for 24 h at room
a
-
D
-ribofuranose (9a) and 5-O-tert-butyldimethylsilyl-1,2-O-
proline (122 mg, 1.06 mmol). After stirring for 48 h at room tem-
perature, water (60 mL) was added. The aqueous phase was then
extracted with EtOAc (3ꢁ50 mL) and the organic layers were
combined, washed with water (50 mL) and brine (50 mL), dried
over Na2SO4, filtered and evaporated to dryness. The residue was
the purified by flash chromatography to afford 837 mg (44%) of
a mixture of 17a and 17b (63/37 ratio). Pure fraction of separated
a-D-xylofuranose (9b). To a solution of
L
temperature, water and EtOAc were added. The organic layer was
separated by extraction and washed with a saturated solution of
NaCl and water. The organic phase was dried over Na2SO4, filtered
and evaporated to dryness. After flash chromatography on silica gel
(Cyclohexane/EtOAc, 15/85), compound 9b (112 mg, 5%) was suc-
cessively isolated as a syrup followed by compound 9a (1.33 g, 60%)
17a and 17b have been isolated for analysis. Compound 17a:
20
mp¼155e156 ꢂC; [
a
]
þ38 (c 0.12, CHCl3); IR (ATR)
n 2955, 2929,
D
2857, 1712, 1675, 1474, 1464, 1280, 1251, 1095, 1080 cmꢀ1; 1H NMR
as a syrup. Compound 9a: [
a
]
20 þ41 (c 0.55, CHCl3); IR (ATR)
n
2929,
(CDCl3, 300 MHz): d
7.41 (s, 1H, H-6), 5.99 (s, 1H, H-10), 4.30 (s, 1H,
D
1704, 1372, 1258, 1069, 1004, 836 cmꢀ1; 1H NMR (CDCl3, 300 MHz):
H-20), 3.97e3.83 (m, 4H, H-30, H-40, H-50a, H-50b), 2.96 (d, 1H,
J2 a,2 b¼18 Hz, H-200a), 2.75 (d, 1H, J2 a,2 b¼18 Hz, H-200b), 2.17 (s, 3H,
CH3), 1.92 (s, 3H, CH3), 0.95, 0.90 (s, 18H, 2ꢁ t-Bu), 0.14, 0.13, 0.06 (s,
00
00
00
00
d
5.70 (d, 1H, J1,2¼6 Hz, H-1), 4.43 (d, 1H, J1,2¼6 Hz, H-2), 3.81 (dd,
1H, J4,5a¼6 Hz, J5a,5b¼9 Hz, H-5a), 3.74 (dd, 1H, J4,5b¼6 Hz,
J5a,5b¼9 Hz, H-5b), 3.68 (t, 1H, J4,5a¼J4,5b¼6 Hz, H-4), 3.43 (br s, 1H,
OH), 2.83 (d, 1H, JA,B¼15 Hz, H-A (CH2CO)), 2.35 (d, 1H, JA,B¼15 Hz,
H-B (CH2CO)), 2.16 (s, 3H, CH3),1.49,1.26 (s, 6H, 2ꢁ CH3), 0.83 (s, 9H,
12H, 4ꢁ SiCH3); 13C NMR (CDCl3, 75 MHz):
d 209.3 (CO), 164.1, 151.1
(C-4, C2), 138.0 (C-6), 109.1 (C-5), 87.2 (C-10), 86.2 (C-40), 80.3 (C-30),
78.2 (C-20), 63.4 (C-50), 43.0 (C-200), 31.0 (CH3), 25.7 (2ꢁ t-Bu), 18.4,
17.8 (2ꢁ Cq t-Bu), 12.5 (CH3), ꢀ4.3, ꢀ4.7, ꢀ5.3, ꢀ5.4 (4ꢁ SiCH3).
HRMS [MNaþ] C25H46N2O7Si2Na calcd 565.2741, found 565.2728.
t-Bu), 0.01 (s, 6H, 2ꢁ SiCH3); 13C NMR (CDCl3, 75 MHz):
d 208.2
(CO), 112.4 [OC(CH3)2], 103.6 (C-1), 82.4 (C-4), 81.1 (C-2), 78.0 (C-3),
60.9 (C-5), 44.2 (CH2CO), 32.3 (CH3), 26.5 (2ꢁ CH3), 25.8 (t-Bu), 18.1
Compound 17b: mp¼64e65 ꢂC; [
a
]
20 þ60 (c 0.09, CHCl3); IR (ATR)
D
(Cq t-Bu), ꢀ5.4 (2ꢁ SiCH3). HRMS [MNH4þ] C17H36NO6Si calcd
n
2955, 2929, 2857, 1685, 1471, 1253, 1128, 1066 cmꢀ1 1H NMR
;
20
378.2312, found 378.2308. Compound 9b: [
a
]
þ10 (c 0.165,
(CDCl3, 300 MHz): d 9.12 (s, 1H, NH), 7.47 (s, 1H, H-6), 6.04 (s, 1H, H-
D
2929,1706,1374,1251,1098,1004, 835, 734 cmꢀ1
5.88 (d, 1H, J1,2¼3 Hz, H-1), 4.51 (d, 1H,
;
10), 5.00 (d, 1H, J3 ,4 ¼7.0 Hz, H-3 ), 4.46 (s, 1H, OH), 4.24 (dt, 1H,
0
0
0
CHCl3); IR (ATR)
n
1H NMR (CDCl3, 300 MHz):
d
J3 ,4 ¼7.0 Hz, J4 ,5 a¼3.7 Hz, H-40), 3.94 (dd, 1H, J5 a,5 b¼11.2 Hz,
0
0
0
0
0
0
0
0
0
0
0
0
0
J1,2¼3 Hz, H-2), 4.40 (s, 1H, OH), 4.01 (dd, 1H, J4,5a¼6 Hz,
J5a,5b¼12 Hz, H-5a), 3.87 (dd, 1H, J4,5b¼6 Hz, J5a,5b¼12 Hz, H-5b),
3.82 (t, 1H, J4,5a¼J4,5b¼6 Hz, H-4), 2.96 (d, 1H, JA,B¼18 Hz, H-A
(CH2CO)), 2.89 (d, 1H, JA,B¼18 Hz, H-B (CH2CO)), 2.23 (s, 3H, CH3),
1.44, 1.30 (s, 6H, 2ꢁ CH3), 0.90 (s, 9H, t-Bu), 0.03 (s, 6H, 2ꢁ SiCH3);
J5 a,4 ¼3.7 Hz, H-5 a), 3.85 (dd, 1H, J5 a,5 b¼11.2 Hz, J5 b,4 ¼3.9 Hz, H-
50b), 2.91 (d, 1H, J2 a,2 b¼18 Hz, H-200a), 2.77 (d, 1H, J2 a,2 b¼18 Hz,
H-200b), 2.24 (s, 3H, CH3), 1.93 (s, 3H, CH3), 0.97, 0.90 (s, 18H, 2ꢁ t-
Bu), 0.19, 0.17, 0.13, 0.10 (s, 12H, 4ꢁ SiCH3); 13C NMR (CDCl3,
00
00
00
00
75 MHz): d 207.4 (CO), 164.1, 151.1 (C-4, C2), 137.6 (C-6), 109.2 (C-5),
13C NMR (CDCl3, 75 MHz):
d
209.6 (CO), 111.9 [OC(CH3)2], 104.4 (C-
86.8 (C-10), 80.2 (C-40), 76.7 (C-20), 73.4 (C-30), 62.0 (C-50), 45.4 (C-
200), 31.7 (CH3), 26.0, 25.9 (2ꢁ t-Bu), 18.4, 18.3 (2ꢁ Cq t-Bu), 12.7
(CH3), ꢀ4.5, ꢀ4.7, ꢀ5.2, ꢀ5.3 (4ꢁ SiCH3). HRMS [MNaþ]
C25H46N2O7Si2Na calcd 565.2741, found 565.2730.
1), 85.6 (C-2), 81.4 (C-4), 79.7 (C-3), 60.5 (C-5), 44.4 (CH2CO), 31.2
(CH3), 26.9, 26.4 (2ꢁ CH3), 25.8 (t-Bu), 18.2 (Cq t-Bu), -5.5 (2ꢁ
þ
SiCH3). HRMS [MNH4
378.2309.
] C17H36NO6Si calcd 378.2312, found
4.2.7. 1-(30,50-Bis-O-tert-butyldimethylsilyl-20-C-acetonyl-
b-D-lyx-
4.2.5. 1,2-O-Isopropylidene-3-C-acetonyl-5-O-trityl-
anose (10a). To a solution of 7 (0.1 g, 0.23 mmol) in DMSO (4 mL)
and acetone (1 mL) was added -proline (0.008 g, 0.07 mmol). After
stirring for 24 h at room temperature, water (20 mL) was added.
The aqueous phase was then extracted with EtOAc (3ꢁ15 mL) and
the organic layers were combined, washed with water (20 mL) and
a
-
D
-ribofur-
ofuranosyl)thymine (18a). A solution of CrO3 (4.23 g, 42.4 mmol) in
pyridine (6.9 mL) was stirred for 20 min at ꢀ5 ꢂC then CH2Cl2
(10 mL) was added and Ac2O (4.2 mL, 44.52 mmol). After stirring for
5 min, compound 10 (6.26 g, 13.25 mmol) dissolved in CH2Cl2
(90 mL) was added. The reaction mixture was cooled at room
temperature for 3 h. EtOAc (100 mL) was then added and the
L

6012
J. Lalot et al. / Tetrahedron 67 (2011) 6006e6017
reaction mixture was filtered through a silica pad and eluate with
EtOAc. After elimination of the solvent under reduced pressure, the
ulose derivative was obtained (4.3 g, 69%) and used in the next step
without further purification. To a solution of crude ulose (1.5 g,
152.6, 140.8 (C-2, C-6), 86.1 (C-10), 80.2 (C-40), 76.2 (C-20), 73.7 (C-
30), 62.0 (C-50), 45.1 (CH2CO), 31.6 (CH3), 26.1, 25.9 (2ꢁ t-Bu), 18.5,
18.3 (2ꢁ Cq t-Bu), ꢀ4.4, ꢀ4.6, ꢀ5.2, ꢀ5.3 (4ꢁ SiCH3). HRMS [MNaþ]
C25H45N5O5Si2Na calcd 574.2911, found 574.2871.
3.19 mmol) in DMSO (25 mL) and acetone (10 mL) was added L-
proline (0.110 g, 0.95 mmol). After stirring for 48 h at room tem-
perature, water (50 mL) was added. The aqueous phase was then
extracted with EtOAc (3ꢁ30 mL) and the organic layers were
combined, washed with water (30 mL) and brine (30 mL), dried
over Na2SO4, filtered and evaporated to dryness. After flash chro-
4.2.9. 1-(20,50-Bis-O-tert-butyldimethylsilyl-30-C-acetonyl-
furanosyl)uracil (23). To a solution of 20 (5.00 g, 10.6 mmol) in
DMSO (92 mL) and acetone (23 mL) was added -proline (0.37 g,
3.18 mmol). After stirring for 24 h at room temperature, water
(150 mL) was added. The aqueous phase was then extracted with
EtOAc (3ꢁ100 mL) and the organic layers were combined, washed
with water (100 mL) and brine (100 mL), dried over Na2SO4, filtered
and evaporated to dryness. The residue was triturated in hexane
b-D-xylo-
L
matography (Cyclohexane/EtOAc, 85/15), compound 18a was iso-
20
lated as a white solid (0.443 g, 26%). Mp¼68 ꢂC; [
a
]
þ5 (c 0.12,
D
CHCl3); IR (ATR) n
2929, 1688, 1463, 1252, 1098, 840 cmꢀ1; 1H NMR
(CDCl3, 300 MHz):
d
9.96 (br s, 1H, NH), 7.52 (d, 1H, J5,6¼8.2 Hz, H-
and filtered to afford 4.04 g (72%) of compound 23 as a white solid.
20
6), 5.94 (s, 1H, H-10), 5.62 (d, 1H, J5,6¼8.2 Hz, H-5), 4.61 (s, 1H, OH),
Mp¼68 ꢂC; [
a
]
þ5 (c 0.12, CHCl3); IR (ATR)
n
2930, 1690, 1470,
D
4.22 (s, 1H, H-30), 3.92 (m, 1H, H-40), 3.84 (dd, 1H, J4 ,5 a¼6.7 Hz,
1264, 1090, 840 cmꢀ1
;
1H NMR (CDCl3, 300 MHz):
d
7.84 (d, 1H,
0
0
J5 a,5 b¼9.9 Hz, H-50a), 3.76 (dd, 1H, J4 ,5 b¼4.3 Hz, J5 a,5 b¼9.9 Hz, H-
J5,6¼9 Hz, H-5), 5.75 (s,1H, H-10), 5.68 (d,1H, J5,6¼9 Hz, H-6), 4.33 (s,
1H, H-20), 4.16e3.97 (m, 3H, H-40, H-50a, H-50b), 3.01 (d, 1H,
JA,B¼18 Hz, H-A (CH2CO)), 2.91 (d, 1H, JA,B¼18 Hz, H-B (CH2CO)),
2.21 (s, 3H, CH3), 0.95, 0.90 (s, 18H, 2ꢁ t-Bu), 0.24, 0.15, 0.14, 0.08 (s,
0
0
0
0
0
0
50b), 2.92 (d, 1H, J2 a,2 b¼18 Hz, H-200a), 2.71 (d, 1H, J2 a,2 b¼18 Hz,
00
00
00
00
H-200b), 2.12 (s, 3H, CH3), 0.87, 0.83 (s, 18H, 2ꢁ t-Bu), 0.06, 0.01 (s,
12H, 4ꢁ SiCH3); 13C NMR (CDCl3, 75 MHz):
d 209.9 (CO), 163.9, (C-
4), 151.3 (C-2), 142.4 (C-6), 101.1 (C-5), 87.7 (C-10), 86.3 (C-40), 80.5
(C-20), 78.2 (C-30), 63.4 (C-50), 43.2 (C-200), 31.2 (CH3), 26.0, 25.8 (2ꢁ
t-Bu), 18.5, 17.9 (2ꢁ Cq t-Bu), ꢀ4.3, ꢀ5.0, ꢀ5.3 (4ꢁ SiCH3). HRMS
[MNaþ] C24H44N2O7Si2Na calcd 551.2585, found 551.2590.
12H, 4ꢁ SiCH3); 13C NMR (CDCl3, 75 MHz):
d 209.2 (CO), 150.5 (C-2,
C-4), 141.2 (C-6), 101.0 (C-5), 91.4 (C-10), 84.5 (C-40), 82.3 (C-20), 79.5
(C-30), 60.8 (C-50), 44.2 (CH2CO), 30.9 (CH3), 25.9, 25.8 (2ꢁ t-Bu),
18.3, 17.9 (2ꢁ Cq t-Bu), ꢀ4.4, ꢀ5.4, ꢀ5.5, ꢀ5.6 (4ꢁ SiCH3). HRMS
[MHþ] C24H45N2O7Si2 calcd 529.2765, found 529.2762.
4.2.8. 1-(30,50-Bis-O-tert-butyldimethylsilyl-20-C-acetonyl-
furanosyl)adenine (19a) and 1-(30,50-bis-O-tert-butyldimethylsilyl-20-
C-acetonyl- -arabinofuranosyl)adenine (19b). To a solution of 16
b-D-ribo-
4.2.10. 1-(20,50-Bis-O-tert-butyldimethylsilyl-30-C-acetonyl-
furanosyl)thymine (24). To a solution of 21 (2.00 g, 4.12 mmol) in
DMSO (36 mL) and acetone (9 mL) was added -proline (0.14 g,
b-D-xylo-
b-D
ꢁ
(1.3 g, 2.62 mmol) in DCM (20 mL) over molecular sieves (4 A), was
added PDC (0.690 g, 1.8 mmol) and Ac2O (0.9 mL, 9.2 mmol). The
reaction was allowed to stir at reflux for 2 h. EtOAc (50 mL) wad
added, the mixture was filtered over a pad of silica gel and washed
with EtOAc. The solvent was then removed at room temperature
under reduced pressure. To a solution of this crude product (1.3 g,
L
1.24 mmol). After stirring for 24 h at room temperature, water
(50 mL) was added. The aqueous phase was then extracted with
EtOAc (3ꢁ50 mL) and the organic layers were combined, washed
with water (50 mL) and brine (50 mL), dried over Na2SO4, filtered
and evaporated to dryness. Hexane was added and after filtration,
compound 24 was obtained as a white solid (2.02 g, 90%).
2.62 mmol) in DMSO (20 mL) and acetone (10 mL) was added L-
proline (90.6 mg, 7.9 mmol). After stirring for 48 h at room tem-
perature, water (60 mL) was added. The aqueous phase was then
extracted with EtOAc (3ꢁ50 mL) and the organic layers were
combined, washed with water (50 mL) and brine (50 mL), dried
over Na2SO4, filtered and evaporated to dryness. The residue was
purified by flash chromatography to afford 0.34 g (23%) of a mixture
Mp¼69 ꢂC; [
a
]
20 ꢀ3.5 (c 0.335, CHCl3); IR (ATR)
n
2929, 1683, 1471,
7.64 (s, 1H,
D
1257, 1105, 839, 778 cmꢀ1; 1H NMR (CDCl3, 300 MHz):
d
0
0
0
H-6), 5.77 (d, 1H, J1 ,2 ¼3 Hz, H-1 ), 4.33 (br s, 1H, OH), 4.30 (d, 1H,
J1 ,2 ¼3 Hz, H-2 ), 4.08 (dd,1H, J4 ,5 a¼6 Hz, J5 a,5 b¼12 Hz, H-50a), 3.96
0
0
0
0
0
0
0
(dd, 1H, J4 ,5 b¼6 Hz, J5 a,5 b¼12 Hz, H-50b), 3.89 (t, 1H,
0
0
0
0
J4 ,5 a¼J4 ,5 b¼6 Hz, H-40), 2.99 (d, 1H, JA,B¼18 Hz, H-A (CH2CO)), 2.90
(d, 1H, JA,B¼18 Hz, H-B (CH2CO)), 2.19 (s, 3H, CH3), 1.97 (s, 3H, CH3),
0.93, 0.82 (s, 18H, 2ꢁ t-Bu), 0.18, 0.13, 0.12, 0.03 (s, 12H, 4ꢁ SiCH3);
0
0
0
0
of 19a and 19b (76/24). Pure fraction of separated 19a and 19b have
20
D
been isolated for analysis. Compound 19a: mp¼92e93 ꢂC; [
a]
þ9 (c 0.13, CHCl3); IR (ATR)
n
3304, 3159, 2953, 2929, 2856, 1706,
13C NMR (CDCl3, 75 MHz):
d 209.3 (CO), 164.3, 150.6 (C-2, C-4), 137.0
1633, 1597, 1471, 1250, 1092 cmꢀ1
;
1H NMR (CDCl3, 300 MHz):
(C-6),109.6 (C-5), 91.1 (C-10), 84.1 (C-40), 82.4 (C-20), 79.4 (C-30), 60.9
(C-50), 44.3 (CH2CO), 30.9 (CH3), 25.9, 25.8 (2ꢁ t-Bu), 17.8, 17.9 (2ꢁ
Cq t-Bu), 12.6 (CH3), ꢀ4.5, ꢀ4.4, ꢀ5.4, ꢀ5.5 (4ꢁ SiCH3). HRMS
[MHþ] C25H47N2O7Si2 calcd 543.2922, found 543.2936.
d
8.30, 8.15 (s, 2H, H-2, H-6), 6.30 (br s, 2H, NH2), 6.09 (s, 1H, H-10),
4.85 (br s, 1H, OH), 4.45 (d, 1H, J4 ,5 a¼1.2 Hz, H-30), 4.02 (m, 1H, H-
0
0
40), 3.94 (dd, 1H, J4 ,5 a¼5.7 Hz, J5 a,5 b¼10.4 Hz, H-50a), 3.84 (dd, 1H,
0
0
0
0
J4 ,5 b¼4.1 Hz, J5 a,5 b¼10.4 Hz, H-50b), 3.02 (d,1H, J2 a,2 b¼18.2 Hz, H-
0
0
0
0
00
00
200a (CH2CO)), 2.49 (d, 1H, J2 a,2 b¼18.2 Hz, H-200b (CH2CO)), 2.05 (s,
4.2.11. 1-(20,50-Bis-O-tert-butyldimethylsilyl-30-C-acetonyl-
furanosyl)adenine (25). To a solution of 22 (2.30 g, 4.65 mmol) in
DMSO (40 mL) and acetone (10 mL) was added -proline (0.16 g,
b-D-xylo-
00
00
3H, CH3), 0.90, 0.89, 0.88, 0.87 (s, 18H, 2ꢁ t-Bu), 0.11, 0.10, 0.03 (s,
12H, 4ꢁ SiCH3); 13C NMR (CDCl3, 75 MHz):
d
208.3 (CO),155.7, 150.1,
L
119.1 (C-4, C-8, C-9), 153.0, 140.1 (C-2, C-6), 87.4 (C-10), 86.6 (C-40),
79.9 (C-20), 78.1 (C-30), 63.8 (C-50), 42.9 (CH2CO), 31.2 (CH3), 26.1,
25.9 (2ꢁ t-Bu), 18.6, 18.0 (2ꢁ Cq t-Bu), ꢀ4.2, ꢀ4.9, ꢀ5.2, ꢀ5.3 (4ꢁ
1.39 mmol). After stirring for 24 h at room temperature, water
(50 mL) was added. The aqueous phase was then extracted with
EtOAc (3ꢁ50 mL) and the organic layers were combined, washed
with water (50 mL) and brine (50 mL), dried over Na2SO4, filtered
and evaporated to dryness. The organic phase was dried over
Na2SO4, filtered and evaporated to dryness. The residue was tritu-
SiCH3). HRMS [MNaþ] C25H45N5O5Si2Na calcd 574.2911, found
20
574.2836. Compound 19b: mp¼60e61 ꢂC; [
a
]
D
þ49 (c 0.11,
CHCl3); IR (ATR)
n 3308, 3154, 2953, 2929, 2856, 1707, 1637, 1597,
1471, 1251, 1144, 1070 cmꢀ1; 1H NMR (CDCl3, 300 MHz):
d
8.24, 8.16
rated in hexane and filtered to afford 2.22 g (87%) of compound 25
20
(s, 2H, H-2, H-6), 6.31 (s, 1H, H-10), 6.01 (br s, 2H, NH2), 05.07 (d, 1H,
as a white solid. Mp¼164 ꢂC; [
a]
ꢀ21(c 0.125, CHCl3); IR (ATR)
n
D
J3 ,4 ¼7.4 Hz, H-3 ), 4.94 (br s, 1H, OH), 4.28 (m, 1H, H-4 ), 3.91 (dd,
2928, 1659, 1472, 1251, 1083, 842 cmꢀ1; 1H NMR (CDCl3, 300 MHz):
0
0
0
1H, J4 ,5 a¼3.2 Hz, J5 a,5 b¼11.1 Hz, H-50a), 3.81 (dd, 1H, J4 ,5 b¼2.0 Hz,
d
8.32, 8.19 (s, 2H, H-2, H-6), 5.99 (s, 1H, H-10), 4.73 (s, 1H, H-20), 4.15
0
0
0
0
0
0
J5 a,5 b¼11.1 Hz, H-50b), 2.73 (d, 1H, JA,B¼18.1 Hz, H-A (CH2CO)), 2.67
(d, 1H, JA,B¼18.1 Hz, H-B (CH2CO)), 2.17 (s, 3H, CH3), 0.92, 0.90 (s,
18H, 2ꢁ t-Bu), 0.15, 0.12, 0.08, 0.04 (s, 12H, 4ꢁ SiCH3); 13C NMR
(dd, 1H, J4 ,5 a¼6 Hz, J5 a,5 b¼9 Hz, H-5 a), 4.03 (t, 1H, J4 ,5 b¼9 Hz,
0
0
0
0
0
0
0
0
0
J5 a,5 b¼9 Hz, H-50b), 3.98 (dd, 1H, J4 ,5 a¼6 Hz, J4 ,5 b¼9 Hz, H-40),
3.07 (d, 1H, JA,B¼18 Hz, H-A (CH2CO)), 3.00 (d, 1H, JA,B¼18 Hz, H-B
(CH2CO)), 2.21 (s, 3H, CH3), 0.92, 0.90 (s, 18H, 2ꢁ t-Bu), 0.20, 0.14,
0
0
0
0
0
0
(CDCl3, 75 MHz):
d 207.2 (CO), 155.3, 150.1, 119.3 (C-4, C-8, C-9),

J. Lalot et al. / Tetrahedron 67 (2011) 6006e6017
6013
0.13, 0.05 (s, 12H, 4ꢁ SiCH3); 13C NMR (CDCl3, 75 MHz):
d
208.4
(C-4), 84.9 (C-3), 62.3 (C-5), 52.5 (CH(CH3)), 33.2 (CH2), 28.0 (t-Bu),
27.9, 26.9 (2ꢁ CH3), 25.9 (t-Bu), 19.6 (CH3), 18.17 (Cq t-Bu), -5.39,
-5.55 (2ꢁ SiCH3). HRMS [MNaþ] C22H41NO9SiSNa calcd 546.2169,
found 546.2183.
(CO), 155.3, 149.2, 119.3 (C-4, C-8, C-9), 152.5, 140.1 (C-2, C-6), 90.9
(C-10), 85.2 (C-40), 82.8 (C-20), 79.5 (C-30), 61.1 (C-50), 44.9 (CH2CO),
31.0 (CH3), 25.9, 25.8 (2ꢁ t-Bu), 18.3, 17.8 (2ꢁ Cq t-Bu), ꢀ4.1, ꢀ5.3,
ꢀ5.4 (4ꢁ SiCH3). HRMS [MHþ] C25H46N5O5Si2 calcd 552.3038,
found 552.3029.
4.2.14. 1-(20,50-Bis-O-tert-butyldimethylsilyl-30-C-acetonyl-
b-D-xylo-
furanosyl)-3-N-methyluracil (29). To a solution of compound 23
(1.0 g, 1.89 mmol) in acetone (100 mL) was added K2CO3 (523 mg,
3.78 mmol) and methyl iodide (1.17 mL, 18.9 mmol). After stirring
for 4 h under reflux, the reaction mixture was cooled at room
temperature then filtered and the solvent eliminated under re-
duced pressure. Hexane was added to precipitate the potassium
carbonate residue. After filtration and elimination of the solvent,
4.2.12. 5-O-tert-Butyldimethylsilyl-1,2-O-isopropylidene-3-C-(20-hy-
droxypropyl)-a-D-ribofuranose (26a/26b). To a solution of com-
pound 9a (1.03 g, 3.10 mmol) in MeOH (10 mL) maintained between
ꢀ5 and ꢀ10 ꢂC was added portionwise NaBH4 (234 mg, 6.20 mmol).
After stirring for 1 h, the reaction mixture was neutralized with
a Dowex 50W-X8 resin until pH 7. After filtration and elimination of
the solvent under reduced pressure, 870 mg (84%) of a mixture of
compound 26a/26b (91/9 ratio) was isolated. The 1,3-diol was used
compound 29 was obtained as a white solid (950 mg, 93%).
20
Mp¼105e106 ꢂC; [
a]
þ6 (c 0.15, CHCl3); IR (ATR)
n 3440, 2929,
D
in the next step without further purification. IR (NaCl)
2931, 2885, 2857, 1471, 1416, 1375, 1254, 1216, 1098, 1020, 998,
838 cmꢀ1; 1H NMR (CDCl3, 300 MHz):
n
3454, 2955,
2856, 1710, 1700, 1664, 1655, 1470, 1250, 1100, 1076 cmꢀ1; 1H NMR
(CDCl3, 300 MHz):
d
7.80 (d, 1H, J5,6¼8.1 Hz, H-5), 5.75 (d, 1H,
0
0
0
d
5.70 (d, 1H, J1,2¼6.0 Hz, H-
J1 ,2 ¼0.9 Hz, H-1 ), 5.70 (d, 1H, J5,6¼8.1 Hz, H-6), 4.31 (d, 1H,
0
0
0
0
0
0
0
0
1), 4.35 (d, 1H, J1,2¼6.0 Hz, H-2), 4.12 (m, 1H, eCHOH), 3.82 (m, 2H,
H-4, H-5a), 3.68 (dd, 1H, J4,5b¼9.0 Hz, J5a,5b¼12.0 Hz, H-5b), 1.71 (d,
1H, JA,B¼12.0 Hz, H-A (CH2CH)), 1.66 (d, 1H, JA,B¼12.0 Hz, H-B
(CH2CH)), 1.52, 1.30 (s, 6H, 2ꢁ CH3), 1.13 (d, 3H, JCH,CH3¼6.0 Hz, CH3),
0.83 (s, 9H, t-Bu), 0.02 (s, 6H, 2ꢁ SiCH3); 13C NMR (CDCl3, 75 MHz):
J1 ,2 ¼0.9 Hz, H-2 ), 4.10 (dd, 1H, J4 ,5 a¼5.1 Hz, J5 a ,5 b¼10.2 Hz, H-
50a), 3.98 (m, 2H, H-40, H-50b), 3.34 (s, 3H, NCH3), 2.99 (d, 1H,
JA,B¼18 Hz, H-A (CH2CO)), 2.89 (d, 1H, JA,B¼18 Hz, H-B (CH2CO)),
2.19 (s, 3H, CH3), 0.89, 0.86 (s, 18H, 2ꢁ t-Bu), 0.23, 0.15, 0.13, 0.08 (s,
12H, 4ꢁ SiCH3); 13C NMR (CDCl3, 75 MHz):
d 209.1 (CO), 163.1, 151.1
d
112.4 [OC(CH3)2], 103.6 (C-1), 83.0 (C-4), 80.6 (C-2), 79.9 (C-3),
(C-2, C-4), 138.9 (C-6), 100.3 (C-5), 91.9 (C-10), 84.4 (C-40), 82.3 (C-
20), 79.5 (C-30), 60.8 (C-50), 44.2 (CH2CO), 30.9 (CH3), 27.5 (NCH3),
25.9, 25.8 (2ꢁ t-Bu), 18.2, 17.9 (2ꢁ Cq t-Bu), ꢀ4.3, ꢀ5.4, ꢀ5.5, ꢀ5.6
(4ꢁ SiCH3). HRMS [MNaþ] C25H46N2O7Si2Na calcd 565.2741, found
565.2747.
64.5 (eCHOH), 61.3 (C-5), 37.9 (eCH2e), 25.8 (2ꢁ CH3), 25.6 (t-Bu),
23.9 (CH3), 18.2 (Cq t-Bu), ꢀ5.3, ꢀ5.4 (2ꢁ SiCH3). HRMS [MNaþ]
C17H34O6SiNa calcd 385.2022, found 385.2010.
4.2.13. 1,2-O-Isopropylidene-5-O-tert-butyldimethylsilyl-b- -ribofur-
anosyl-3-spiro-60-(40-R-methyl-10,30,20-dioxathiane-20,20D-dioxide)
4.2.15. 1-(20,50-Bis-O-tert-butyldimethylsilyl-30-C-acetonyl-
b-D-xylo-
(28) and 1,2-O-isopropylidene-5-O-tert-butyldimethylsilyl-
b
-
D
-ribo-
furanosyl)-3-N-tert-butoxycarbonyluracil (30). To a solution of 23
(1.14 g, 2.15 mmol) in 20 mL of a mixture of pyridine/CH2Cl2 (8/2)
was added Boc2O (1.88 g, 8.62 mmol). The reaction mixture was
stirred at room temperature for overnight. After elimination of the
solvent under reduced pressure and flash chromatography, com-
pound 30 was isolated as a white solid (1.0 g, 74%). Mp¼51e52 ꢂC;
furanosyl-3-spiro-60-(30-N-tert-butoxycarbonyl-40-S-methyl-10,20,30-
oxathiazinone-20,20-dioxide) (27). To a solution of alcohol 26a/
b (333 mg, 0.92 mmol) in anhydrous THF (20 mL) was added tert-
butyl
N-(triethyl-ammoniumsulfonyl)carbamate
(1.04
g,
3.70 mmol) at room temperature in a single portion. The resulting
solution was placed immediately in an oil bath at 75 ꢂC and stirred
for 2 days. Upon completion of the reaction, the solvent was re-
moved under reduced pressure and the residue was diluted in
CH2Cl2, then washed with saturated aqueous NH4Cl. The organic
phase was dried (Na2SO4) and concentrated. The crude orange oil
was purified by flash chromatography using first as eluent CH2Cl2
to afford the sulfate 28 as a clear oil (57 mg, 14.5%), then a mixture
[a
]
20þ20 (c 0.49, CH2Cl2); IR (ATR)
n
2930, 2857, 1786, 1718, 1678,
1H NMR (CDCl3,
D
1445, 1371, 1252, 1149, 1113, 1086, 837 cmꢀ1
;
0
0
300 MHz):
d
7.84 (d, 1H, J5,6¼8.3 Hz, H-6), 5.76 (d, 1H, J1 ,2 ¼1.2 Hz,
H-10), 5.70 (d, 1H, H-5), 4.30 (d, 1H, H-20), 4.10 (dd, 1H, J4 ,5 a¼5.3 Hz,
0
0
J5 a,5 b¼10.5 Hz, H-50a), 4.01e3.92 (m, 2H, H-40, H-50b), 3.01 (d, 1H,
JA,B¼18.2 Hz, H-A CH2CO), 2.89 (d, 1H, JA,B¼18.2 Hz, H-B CH2CO),
2.21 (s, 3H, CH3), 1.63 (s, 9H, t-Bu), 0.95, 0.91 (s, 18H, 2ꢁ t-Bu), 0.20,
0
0
of CH2Cl2/EtOAc (30/1) to afford 212 mg (44%) of the sulfamidate 27
0.16, 0.12, 0.07 (s, 12H, 4ꢁ SiCH3); 13C NMR (CDCl3, 75 MHz):
d 208.8
20
as a pale yellow oil. Compound 28: [
(NaCl)
838 cmꢀ1; 1H NMR (CDCl3, 300 MHz):
a
]
þ34.9 (c 1.0, CHCl3); IR
(CO), 160.1, 147.9, 147.3 (C-2, C-4, CO), 139.9 (C-6), 100.2 (C-5), 90.8
(C-10), 86.4 (Cq t-Bu), 83.8 (C-40), 81.9 (C-20), 79.0 (C-30), 60.4 (C-50),
43.7 (CH2CO), 30.5 (CH3), 27.5, 25.6 (3ꢁ t-Bu),17.7,17.0 (2ꢁ Cq t-Bu),
ꢀ4.9, ꢀ5.9, ꢀ6.0, ꢀ6.1 (4ꢁ SiCH3). HRMS [MNaþ] C29H52N2O9Si2Na
calcd 651.3109, found 651.3088.
D
n
2955, 2931, 2858, 1721, 1397, 1257, 1168, 1099, 1016, 929,
5.74 (d, 1H, J1,2¼3.8 Hz, H-
d
1), 5.13e5.27 (m, 1H, CHeCH3), 4.42 (d, 1H, J1,2¼3.8 Hz, H-2),
4.37e4.41 (m, 1H, H-4), 4.21 (dd, 1H, J4,5a¼1.4 Hz, J5a,5b¼12.8 Hz, H-
5a), 4.01 (dd, 1H, J4,5b¼3.4 Hz, J5a,5b¼12.8 Hz, H-5b), 2.51 (dd, 1H,
JCH,A¼1.9 Hz, JA,B¼14.4 Hz, H-A CH2CH), 1.98 (d, 1H, CH2,
JCH,B¼11.8 Hz, JA,B¼14.4 Hz, H-B CH2CH), 1.59 (s, 3H, CH3), 1.48, 1.46
(s, 3H, CH3), 1.36 (s, 3H, CH3), 0.88 (s, 9H, t-Bu), 0.08, 0.07 (s, 6H, 2ꢁ
4.2.16. 1-(20,50-Bis-O-tert-butyldimethylsilyl-30-(S)-C-isopropanoyl-
b-D
-xylofuranosyl)-30-N-methyluracil (31a) and 1-(20,50-bis-O-tert-
butyldimethylsilyl-30-(R)-C-isopropanoyl- -xylofuranosyl)-30-N-
b-D
SiCH3). 13C NMR (CDCl3, 75 MHz):
d
114.4 (Cq C(CH3)2), 102.3 (C-1),
methyluracil (31b). To a solution of compound 29 (950 mg,
1.75 mmol) in MeOH (20 mL) maintained between ꢀ5 and ꢀ10 ꢂC
was added portionwise NaBH4 (132 mg, 3.5 mmol). After stirring for
1 h, the reaction mixture was neutralized with a Dowex 50W-X8
resin until pH 7. After filtration and elimination of the solvent under
reduced pressure, the crude was triturated in hexane then filtered
to afford 750 mg (79%) of a mixture of compound 31a/31b (91/9
ratio). Separation by HPLC (CH3CN, 20 mL/min, 254 nm, prevail C18
90.7 (C-3), 86.1 (C-2), 80.7 [CH(CH3)], 79.4 (C-4), 60.7 (C-5), 33.5
(CH2), 27.0, 26.7 [OC(CH3)2], 25.9 (t-Bu), 21.1 (CH3), 18.4 (Cq t-Bu),
ꢀ5.1, ꢀ5.5 (2ꢁ SiCH3). HRMS [MHþ] C17H36NO8SiS calcd 442.1931,
found 442.1946. Compound 27: [
n
a
]
20 þ28.7 (c 1.0, CHCl3); IR (NaCl)
D
2956, 2933, 2858, 1731, 1385, 1312, 1218, 1146, 878 cmꢀ1; 1H NMR
(CDCl3, 300 MHz):
d
5.89 (d, 1H, J1,2¼4.4 Hz, H-1), 4.63 (t, 1H,
J4,5¼2.3 Hz), 4.48e4.58 (m, 2H, H-2, CHCH3), 3.75e3.86 (m, 2H, H-
5a, H-5b), 2.72 (dd, 1H, JCH,A¼4.3 Hz, JA,B¼15.2 Hz H-A eCH2CH),
2.15 (dd, 1H, JCH,B¼5.03 Hz, JA,B¼15.2 Hz, H-A eCH2CH), 1.58 (s, 3H,
CH3), 1.51 (s, 9H, t-Bu),1.49 (s, 3H, CH3),1.38 (s, 3H, CH3), 0.87 (s, 9H,
5 m) afforded, respectively, compound 31a and 31b as white solid.
20
Compound 31a: mp¼164e165 ꢂC; [
a
]
þ33 (c 0.14, CHCl3); IR
D
(ATR)
n 3577, 3422, 2956, 2931, 2856, 1706, 1661, 1470, 1462, 1247,
t-Bu), 0.05, 0.06 (s, 6H, 2ꢁ SiCH3). 13C NMR (CDCl3, 75 MHz):
d
150.2
1114, 1108, 1075 cmꢀ1
; d 7.89 (d, 1H,
1H NMR (CDCl3, 300 MHz):
0
0
0
(CO), 115.4 [OC(CH3)2], 105.1 (C-1), 91.2 (Cq t-Bu), 87.0 (C-2), 85.4
J5,6¼8.2 Hz, H-6), 5.73 (d, 1H, J1 ,2 ¼2.3 Hz, H-1 ), 5.70 (d, 1H, H-5),

6014
J. Lalot et al. / Tetrahedron 67 (2011) 6006e6017
4.24 (dd, 1H, J4 ,5 a¼2.3 Hz, J5 a,5 b¼12.0 Hz, H-50a), 4.20 (m, 1H, H-
Compound 33: mp¼59e60 ꢂC; [
a
]
20 þ25 (c 0.13, CHCl3); IR (ATR)
n
0
0
0
0
D
3000), 4.12 (d, 1H, J1 ,2 ¼2.3 Hz, H-2 ), 4.08 (dd, 1H, J4 ,5 b¼2.3 Hz,
2954, 2930, 2858, 1732, 1709, 1664, 1461, 1409, 1291, 1253, 1146,
0
0
0
0
0
J5 a,5 b¼12.0 Hz, H-50b), 3.99 (t, 1H, J4 ,5 a¼J4 ,5 b¼2.3 Hz, H-40), 2.00
1109 cmꢀ1; 1H NMR (CDCl3, 300 MHz):
d
7.61 (d, 1H, J5,6¼8.20Hz, H-
0
0
0
0
0
0
(dd, 1H, J3 a,3 ¼10.2 Hz, J3 a,3 b¼14.8 Hz, H-300a), 1.65 (dd, 1H,
6), 5.81 (d, 1H, J5,6¼8.2 Hz,0H-5), 5.76 (d, 1H, J1 ,2 ¼1.6 Hz, H-1 ), 4.66
00
000
00
00
0
0
J3 b,3 ¼2.5 Hz, J3 a,3 b¼14.8 Hz, H-300b), 1.27 (d, 3H, JCH,3 ¼6.2 Hz,
(d, 1H, J1 ,2 ¼1.6 Hz, H-2 ), 4.63 (m, 1H, CHCH3), 4.19 (dd, 1H,
00
000
00
00
000
0
0
0
0
0
0
0
0
CH3), 0.92, 0.89 (s, 18H, 2ꢁ t-Bu), 0.18, 0.17, 0.15, 0.10 (s, 12H, 4ꢁ
J4 ,5 a¼5.4 Hz, J4 ,5 b¼4.4 Hz, H-40), 4.13 (dd, 1H, J4 ,5 a¼5.4 Hz,
SiCH3); 13C NMR (CDCl3, 75 MHz):
d 163.2, 151.1 (C-2, C-4), 138.6 (C-
J5 a,5 b¼10.9 Hz, H-50a), 4.03 (dd, 1H, J4 ,5 b¼4.4 Hz, J5 a,5 b¼10.9 Hz,
H-50b), 3.35 (s, 3H, NCH3), 2.58 (dd, 1H, JA,CH¼6.7 Hz, JA,B¼15.0 Hz,
H-A (CH2CH)), 2.49 (dd, 1H, JB,CH¼8.3 Hz, JA,B¼15.0 Hz, H-B
(CH2CH)), 1.51 (s, 3H, CH3), 1.40 (d, 3H, JCH,CH3¼6.5 Hz, CH3), 0.95,
0.94 (s, 18H, 2ꢁ t-Bu), 0.26, 0.22, 0.17, 0.16 (s, 12H, 4ꢁ SiCH3); 13C
0
0
0
0
0
0
6), 100.3 (C-5), 90.7 (C-10), 83.6, 83.1 (C-40, C-20), 81.3 (C-30), 64.9 (C-
3000), 62.7 (C-50), 39.5 (C-300), 27.5 (NCH3), 25.8, 24.3 (2ꢁ t-Bu), 24.3
(CH3), 18.1, 18.0 (2ꢁ Cq t-Bu), ꢀ4.7, ꢀ5.0, ꢀ5.5, ꢀ5.6 (4ꢁ SiCH3).
HRMS [MNaþ] C25H48N2O7Si2Na calcd 567.2898, found 567.2920.
20
Compound 31b: mp¼104e105 ꢂC; [
a
]
þ65 (c 0.07, CHCl3); IR
NMR (CDCl3, 75 MHz): d 162.8, 151.2, 149.4 (C-2, C-4, CO), 137.1 (C-
D
(ATR)
n
3359, 2955, 2929, 2857, 1705, 1655, 1462, 1251, 1102 cmꢀ1
;
6), 101.2 (C-5), 93.7 (C-30), 90.9 (C-10), 85.4 (C-40), 79.0 (C-20), 60.1
(C-50), 52.0 (eCHeCH2), 28.9 (CH2eCHe), 27.8 (t-Bu), 27.5 (NCH3),
25.8, 25.7 (2ꢁ t-Bu), 20.7 (CH3), 18.3, 17.9 (2ꢁ Cq t-Bu), ꢀ4.1, ꢀ5.4,
1H NMR (CDCl3, 300 MHz):
d
7.90 (d, 1H, J5,6¼8.2 Hz, H-6), 5.71 (d,
1H, J5,6¼8.2 Hz, H-5), 5.70 (s, 1H, H-10), 4.29 (dd, 1H, J4 ,5 a¼2.9 Hz,
0
0
J5 a,5 b¼12.0 Hz, H-50a), 4.25 (s, 1H, H-20), 4.15 (dd, 1H, J4 ,5 b¼2.9 Hz,
ꢀ5.5, ꢀ5.7 (4ꢁ SiCH3). HRMS [MNaþ] C30H55N3O10Si2SNa calcd
0
0
0
0
20
J5 a,5 b¼12.0 Hz, H-50b), 4.14 (m, 1H, H-3000), 3.94 (t, 1H,
728.3044, found 728.3064. Compound 34: mp¼59e60 ꢂC; [
a
]
D
0
0
J4 ,5 a¼J4 ,5 b¼2.9 Hz, H-40), 3.37 (s, 3H, CH3), 1.93 (dd, 1H,
þ13 (c 0.1, CHCl3); IR (ATR)
n 2955, 2930, 2857, 1708, 1665, 1458,
0
0
0
0
J3 a,3 ¼0.7 Hz, J3 a,3 b¼14.2 Hz, H-300a), 1.60 (dd, 1H, J3 b,3 ¼10.3 Hz,
1403, 1253, 1203, 1093 cmꢀ1; 1H NMR (CDCl3, 300 MHz):
d 7.40 (d,
00
000
00
00
00
000
J3 a,3 b¼14.2 Hz, H-300b), 1.23 (d, 3H, JCH,3 ¼6.1 Hz, CH3), 0.95, 0.94
1H, J5,6¼8.2 Hz, H-6), 5.83 (d,1H, J5,6¼8.2 Hz, H-5), 5.78 (s,1H, H-10),
00
00
000
(s, 18H, 2ꢁ t-Bu), 0.32, 0.19, 0.18, 0.14 (s, 12H, 4ꢁ SiCH3); 13C NMR
5.19 (s, 1H, H-20), 4.93 (ddq, 1H, JCH,A¼12.4 Hz, JCH,B¼2.3 Hz,
0
0
0
0
(CDCl3, 75 MHz):
d
163.3, 151.0 (C-2, C-4), 138.7 (C-6), 100.0 (C-5),
JCH,CH3¼6.2 Hz, eCHeCH2), 4.22 (dd, 1H, J4 ,5 a¼7.6 Hz, J4 ,5 b¼5.0 Hz,
92.5 (C-10), 83.4 (C-30), 83.4 (C-40), 81.2 (C-20), 66.1 (C-3000), 61.9 (C-
50), 38.4 (C-300), 27.5 (NCH3), 25.8, 25.7 (2ꢁ t-Bu), 23.9 (CH3), 18.1,
17.9 (2ꢁ Cq t-Bu), ꢀ3.7, ꢀ5.5, ꢀ5.7, ꢀ5.8 (4ꢁ SiCH3). HRMS [MNaþ]
C25H48N2O7Si2Na calcd 567.2898, found 567.2918.
H-40), 4.06 (dd, 1H, J4 ,5 a¼7.6 Hz, J5 a ,5 b¼10.3 Hz, H-50a), 3.98 (dd,
0
0
0
0
0
1H, J4 ,5 b¼5.0 Hz, J5 a ,5 b¼10.3 Hz, H-50b), 2.45 (dd, 1H,
JCH,A¼12.5 Hz, JA,B¼15 Hz, H-A CH2CHe), 2.33 (d, 1H, JCH,B¼2.3 Hz,
JA,B¼15 Hz, H-B CH2CHe), 1.49 (m, 3H, JCH,CH3¼6.2 Hz, CH3CHe),
0.95, 0.94 (s, 18H, 2ꢁ t-Bu), 0.30, 0.22, 0.16, 0.15 (s, 12H, 4ꢁ SiCH3);
0
0
0
0
0
4.2.17. 1-(20,50-Bis-O-tert-butyldimethylsilyl-30-(S)-C-isopropanoyl-
13C NMR (CDCl3, 75 MHz):
d 162.7, 151.0 (C-2, C-4), 136.7 (C-6), 101.5
b-
D
-xylofuranosyl)-3-N-tert-butoxycarbonyluracil (32a) and 1-(20,50-
(C-5), 96.1 (C-30), 92.0 (C-10), 83.9 (C-40), 79.8 (eCHCH3), 77.2 (C-30),
59.4 (C-50), 29.6 (CH2CHe), 27.9 (NCH3), 25.9, 25.7 (2ꢁ t-Bu), 20.6
(CH3), 18.2, 17.9 (2ꢁ Cq t-Bu), ꢀ4.2, ꢀ5.5, ꢀ5.6 (4ꢁ SiCH3). HRMS
[MNaþ] C25H46N2O9SSi2Na calcd 629.2360, found 629.2358.
bis-O-tert-butyldimethylsilyl-30-(R)-C-isopropanoyl-
b-D-xylofur-
anosyl)-3-N-tert-butoxycarbonyluracil (32b). To a solution of 30
(930 mg, 1.48 mmol) in MeOH (15 mL) maintained between ꢀ5 and
ꢀ10 ꢂC was added portionwise NaBH4 (56 mg, 1.48 mmol). After
stirring for 1 h, the reaction mixture was neutralized with a Dowex
50W-X8 resin until pH 7. After filtration and elimination of the
solvent under reduced pressure, the crude was triturated in hexane
then filtered to afford 895 mg (96%) of a mixture of compound
32a/32b (78/22 ratio). Purification by HPLC (CH32C0N, 20 mL/min,
4.2.19. 1-[(20,50-Bis-O-tert-butyldimethylsilyl-
b-D-xylofuranosyl)-3-
N-tert-butoxycarbonyluracil]-30-spiro-600-(300-N-tert-butoxycarbonyl-
400-R-methyl-100,200,300-oxathiazinone-200,200-dioxide) (35) and 1-
[(20,50-bis-O-tert-butyldimethylsilyl-
b-D-xylofuranosyl)-3-N-tert-bu-
toxycarbonyluracil]-30-spiro-600-(400-R-methyl-100,300,200-dioxathiane-
200,200-dioxide) (36). To a solution of 32a (400 mg, 0.63 mmol) in
distilled THF (15 mL) was added Burgess reagent (708 mg,
2.52 mmol). After stirring overnight at 80 ꢂC under a nitrogen at-
mosphere, the solvent was eliminated under reduced pressure and
the crude was purified by flash chromatography (EtOAc/cyclohex-
ane,10/90) to afford 300 mg of an unseparable mixture of sulfate 36
(43%) and sulfamidate 35 (22%) (1.7/1 ratio). The mixture was
254 nm) afforded 32a as an incolor liquid. [
a
]
þ25 (c 0.40,
D
CH2Cl2); IR (ATR)
n 3390, 2930, 2858, 1786, 1719, 1670, 1452, 1372,
1253, 1148, 1062, 837 cmꢀ1
;
1H NMR (CDCl3, 3000MHz):
d 7.90 (d,
0
0
1H, J5,6¼8.2 Hz, H-6), 5.70 (d, 1H, J1 ,2 ¼2.9 Hz, H-1 ), 5.67 (d, 1H, H-
5), 4.20 (m, 2H, H-3000, H-50a), 4.10 (d, 1H, H-20), 4.06 (dd, 1H,
J4 ,5 b¼2.4 Hz, J5 a,5 b¼11.8 Hz, H-50a), 3.99 (t,1H, J4 ,5 b¼J4 ,5 a¼2.4 Hz,
0
0
0
0
0
0
0
0
H-40), 2.00 (dd, 1H, J3 a,3 ¼10.2 Hz, J3 a,3 b¼14.9 Hz, H-300a), 1.66 (m,
1H, H-300b), 1.60 (s, 9H, t-Bu), 1.27 (d, 3H, JCH,CH3¼6.2 Hz, CH3), 0.95,
0.91 (s, 18H, 2ꢁ t-Bu), 0.17, 0.16, 0.15, 0.14 (s, 12H, 4ꢁ SiCH3); 13C
00
000
00
00
separated by HPLC (CH3CN, 20 mL/min, 254 nm). Compound 35:
20
mp¼79e80 ꢂC; [
a
]
þ36 (c 0.15, CH2Cl2); IR (ATR)
n
2932, 2858,
1H NMR
7.54 (d, 1H, J5,6¼8.3 Hz, H-6), 5.62 (d, 1H,
D
NMR (CDCl3, 75 MHz):
d
160.1, 147.9, 147.3 (C-2, C-4, CO), 139.5 (C-
1787, 1726, 1680, 1442, 1388, 1371, 1253, 1147, 837 cmꢀ1
;
(CDCl3, 300 MHz): d
6), 100.3 (C-5), 89.1 (C-10), 86.0 (Cq t-Bu), 83.4, 83.1 (C-20, C-40), 80.7
(C-30), 64.3 (C-3000), 62.3 (C-50), 39.0 (C-300), 26.9, 25.3, 25.2 (3ꢁ t-
Bu), 23.9 (CH3), 17.6, 17.5 (2ꢁ Cq t-Bu), ꢀ5.0, ꢀ5.5, ꢀ6.1, ꢀ6.2 (4ꢁ
SiCH3). HRMS [MNaþ] C29H54N2O9Si2Na calcd 653.3266, found
653.3238.
0
0
0
0
J1 ,2 ¼2.8 Hz, H-1 ), 5.60 (d, 1H, H-5), 4.44 (m, 2H, CHCH3, H-2 ), 3.98
(t, 1H, J4 ,5 a¼J4 ,5 b¼4.3 Hz, H-40), 3.92 (dd, 1H, J5 a,5 b¼11.2 Hz, H-
50a), 3.86 (dd, 1H, H-50b), 2.41 (dd, 1H, JA,CH¼6.6 Hz, JA,B¼15.0 Hz, H-
A (CH2CH)), 2.34 (dd, 1H, JB,CH¼8.8 Hz, JA,B¼15.0 Hz, H-B (CH2CH)),
1.43, 1.36 (s, 18H, 2ꢁ t-Bu), 1.22 (d, 3H, JCH,CH3¼6.4 Hz, CH3), 0.78,
0
0
0
0
0
0
4.2.18. 1-[(20,50-Bis-O-tert-butyldimethylsilyl-
b
-
D
-xylofuranosyl)-3-
0.75 (s,18H, 2ꢁ t-Bu), 0.02, 0.01, ꢀ0.01, ꢀ0.02 (s,12H, 4ꢁ SiCH3); 13
C
N-methyluracil]-30-spiro-600-(300-N-tert-butoxycarbonyl-400-R-methyl-
NMR (CDCl3, 75 MHz):
d
159.7, 148.9, 148.0, 147.0 (C-2, C-4, 2ꢁ CO),
100,200,300-oxathiazinone-200,200-dioxide) (33) and 1-[(20,50-bis-O-tert-
138.3 (C-6), 101.3 (C-5), 92.6 (C-30), 89.0 (C-10), 86.0 (Cq t-Bu), 84.7
(C-40), 78.7 (C-20), 60.0 (C-50), 51.6 (eCHeCH2), 29.2 (CH2eCHe),
27.3, 26.9, 25.3,25.2 (4ꢁ t-Bu), 20.2 (CH3), 17.8, 17.4 (2ꢁ Cq t-Bu),
ꢀ4.9, ꢀ5.8, ꢀ6.1 (4ꢁ SiCH3). HRMS [MNaþ] C34H61N3O12Si2SNa
calcd 814.3412, found 814.3406. Compound 36: mp¼67e68 ꢂC;
butyldimethylsilyl-b-
-xylofuranosyl)-3-N-methyluracil]-30-spiro-600-
(400-R-methyl-100,300,20D0-dioxathiane-200,200-dioxide) (34). To a solution
of 31a/31b (300 mg, 0.55 mmol) in distilled THF (15 mL) was added
Burgess reagent (620 mg, 2.2 mmol). After stirring overnight at
80 ꢂC under a nitrogen atmosphere, the solvent was eliminated
under reduced pressure and the crude was purified by flash chro-
matography (EtOAc/cyclohexane, 10/90) to afford 266 mg of an
unseparable mixture of 34 (62%) and 33 (16%) (3.4/1 ratio). The
mixture was separated by HPLC (CH3CN, 20 mL/min, 254 nm).
[a
]
20 þ28 (c 0.16, CH2Cl2); IR (ATR)
n 2931, 2858, 1787, 1719, 1679,
D
1442, 1405, 1252, 1205, 1149, 1101, 870 cmꢀ1 1H NMR (CDCl3,
;
300 MHz):
d
7.40 (d, 1H, J5,6¼9.0 Hz, H-6), 5.80 (m, 2H, H-5, H-10),
0
0
0
5.14 (d, 1H, J1 ,2 ¼1.4 Hz, H-2 ), 4.94 (ddq, 1H, JCH,A¼12.3 Hz,
0
0
JCH,B¼2.2 Hz, JCH,CH3¼6.1 Hz, eCHeCH2), 4.17 (dd, 1H, J4 ,5 a¼7.4 Hz,

J. Lalot et al. / Tetrahedron 67 (2011) 6006e6017
6015
J4 ,5 b¼4.9 Hz, H-40), 4.04 (dd, 1H, J4 ,5 a¼7.4 Hz, J5 a ,5 b¼10.4 Hz, H-
J4 ,5 a¼7.1 Hz, J4 ,5 b¼5.1 Hz, H-40), 4.08 (dd, 1H, J5 a,5 b¼10.6 Hz, H-
50a), 3.97 (dd, 1H, H-50b), 3.75 (m, 1H, eCHCH3), 2.24 (dd, 1H,
JA,B¼14.7 Hz, JCH,A¼2.4 Hz, H-A CH2CHe), 1.90 (dd, 1H, JCH,B¼2.4 Hz,
H-B CH2CHe), 1.31 (d, 3H, JCH3,CH¼6.5 Hz, CH3), 0.97, 0.95 (s, 9H, t-
Bu), 0.31, 0.22, 0.16 (s, 12H, 4ꢁ SiCH3); 13C NMR (CDCl3, 75 MHz):
0
0
0
0
0
0
0
0
0
0
0
0
0
50a), 3.96 (dd, 1H, J4 ,5 b¼4.9 Hz, J5 a ,5 b¼10.4 Hz, H-50b), 2.46 (dd,
1H, JCH,A¼11.8 Hz, JA,B¼15.0 Hz, H-A CH2CHe), 2.31 (d, 1H,
JCH,B¼2.2 Hz, JA,B¼15.0 Hz, H-B CH2CHe), 1.60 (s, 9H, t-Bu), 1.48 (d,
3H, JCH,CH3¼6.2 Hz, CH3CHe), 0.94, 0.91 (s, 18H, 2ꢁ t-Bu), 0.24, 0.20,
0
0
0
0
0
0.14, 0.13 (s, 12H, 4ꢁ SiCH3); 13C NMR (CDCl3, 75 MHz):
d
159.6,
d
163.1, 150.1 (C-2, C-4), 139.5 (C-6), 101.6 (C-5), 95.4 (C-30), 91.9 (C-
147.9, 146.9 (C-2, C-4, CO), 137.7 (C-6), 101.6 (C-5), 95.6 (C-30), 90.9
(C-10), 86.0 (Cq t-Bu), 83.2 (C-40), 79.4 (eCHCH3), 77.1 (C-20), 58.9
(C-50), 29.2 (CH2CHe), 26.9, 25.3, 25.1 (3ꢁ t-Bu), 20.1 (CH3), 17.7,
17.4 (2ꢁ Cq t-Bu), ꢀ4.9, ꢀ6.0, ꢀ6.1 (4ꢁ SiCH3). HRMS [MNaþ]
C29H52N2O11SSi2Na calcd 715.2728, found 715.2729.
10), 84.7 (C-40), 77.1 (C-20), 59.6 (C-50), 48.9 (eCHCH3), 30.0
(eCHCH2), 25.7 (2ꢁ t-Bu), 20.9 (CH3), 18.2, 17.9 (2ꢁ Cq t-Bu), ꢀ4.2,
ꢀ5.4, ꢀ5.5 (4ꢁ SiCH3). HRMS [MNaþ] C24H44N2O9SSi2Na calcd
20
615.2204, found 615.2194. Compound 40: mp¼103e104 ꢂC; [
a]
D
þ16 (c 0.11, CH2Cl2); IR (ATR)
n 2933, 2859, 1685, 1458, 1399, 1263,
1204, 1122, 1070 cmꢀ1 1H NMR (CDCl3, 300 MHz):
; d 7.68 (d, 1H,
4.2.20. 1-[(20,50-Bis-O-tert-butyldimethylsilyl-
cil]-30-spiro-600-(400-R-methyl-100,200,300-oxathiazinone-200,200-dioxide)
b
-
D
-xylofuranosyl)ura-
J5,6¼8.2 Hz, H-6), 5.77 (0dd, 1H, J5,6¼8.2 Hz, J5,NH¼1.7 Hz, H-5), 5.75
0
0
0
(d, 1H, J1 ,2 ¼1.7 Hz, H-1 ), 4.71 (d, 1H, H-2 ), 4.67 (m, 1H, eCHCH3),
(37) and 1-[(20,50-bis-O-tert-butyldimethylsilyl-
b-D-xylofuranosyl)
4.20 (dd, 1H, J4 ,5 a¼5.3 Hz, J4 ,5 b¼4.5 Hz, H-40), 4.14 (dd, 1H,
0
0
0
0
uracil]-30-spiro-600-(300-N-tert-butoxycarbonyl-400-R-methyl-100,200,300-
J5 a,5 b¼11.0 Hz, H-50a), 4.04 (dd, 1H, H-50b), 2.59 (dd, 1H,
JA,B¼15.0 Hz, JCH,A¼6.7 Hz, H-A CH2CHe), 2.48 (dd, 1H, JCH,B¼8.2 Hz,
H-B CH2CHe), 1.54 (s, 9H, t-Bu), 1.42 (d, 3H, JCH3,CH¼6.5 Hz, CH3),
0.97, 0.95 (s, 18H, 2ꢁ t-Bu), 0.25, 0.22, 0.18, 0.17 (s, 12H, 4ꢁ SiCH3);
0
0
oxathiazinone-200,200-dioxide) (38). To a solution of 35 (52 mg,
0.066 mmol) in CH2Cl2 (10 mL) was added TFA (97.6 mL, 1.31 mmol).
After stirring at 50 ꢂC overnight, the solvent was eliminated under
reduced pressure and the crude was purified by flash chromatog-
raphy (EtOAc/cyclohexane, 30/70) to afford 29 mg of an unsepar-
able mixture of 37 and 38. The mixture was separated by HPLC
(CH3CN, 20 mL/min, 254 nm) to afford successively 37 (18 mg, 47%)
13C NMR (CDCl3, 75 MHz):
d 162.7, 150.1, 149.4 (C-2, C-4, CO), 139.5
(C-6), 101.8 (C-5), 93.6 (C-30), 90.3 (C-10), 85.5, 85.4 (C-40, Cq t-Bu),
78.9 (C-20), 60.1 (C-50), 52.0 (eCHCH3), 29.0 (eCHCH2), 27.8, 25.8,
25.7 (3ꢁ t-Bu), 20.7 (CH3), 18.3, 17.9 (2ꢁ Cq t-Bu), ꢀ4.2, ꢀ5.3, ꢀ5.5,
ꢀ5.6 (4ꢁ SiCH3). HRMS [MNaþ] C18H30N2O9SSi2Na calcd 501.1339,
found 501.1329.
and 38 (11 mg, 24%). Compound 37: mp¼108e109 ꢂC; [
a]
20 þ25 (c
D
0.14, CH2Cl2); IR (ATR)
n 2930, 2857, 1683, 1462, 1376, 1255, 1099,
836 cmꢀ1; 1H NMR (CDCl3, 300 MHz):
d
7.45 (d, 1H, J5,6¼8.2 Hz, H-
0
6), 5.81 (d, 1H, H-5), 5.77 (d, 1H, J1 ,2 ¼0.8 Hz, H-1 ), 5.21 (d, 1H, H-
4.2.22. 1-(20,50-Bis-O-tert-butyldimethylsilyl-30-C-acetonyl-
b-D-xylo-
0
0
20), 4.94 (ddq, 1H, JCH,CH3¼6.1 Hz, JCH,A¼12.3 Hz, JCH,B¼2.3 Hz,
furanosyl)-3-N-tert-butoxycarbonylthymine (41). To a solution of 24
(1.80 g, 3.33 mmol) in 50 mL of a mixture of pyridine/CH2Cl2 (8/2)
was added Boc2O (1.45 g, 6.67 mmol). The reaction mixture was
stirred at room temperature for overnight. After elimination of the
solvent under reduced pressure and flash chromatography, com-
eCHCH3), 4.23 (dd, 1H, J4 ,5 a¼7.6 Hz, J4 ,5 b¼5.0 Hz, H-40), 4.07 (dd,
0
0
0
0
1H, J5 a,5 b¼10.3 Hz, H-50a), 3.99 (dd, 1H, H-50b), 2.46 (dd, 1H,
JA,B¼14.9 Hz, H-A CH2CHe), 2.33 (dd, 1H, H-B CH2CHe), 1.49 (d, 3H,
CH3), 0.96, 0.93 (s, 18H, 2ꢁ t-Bu), 0.30, 0.21, 0.16, 0.14 (s, 12H, 4ꢁ
0
0
SiCH3); 13C NMR (CDCl3, 75 MHz):
d
162.6, 149.7 (C-2, C-4), 138.5 (C-
pound 41 was isolated as a white solid (1.98 g, 92%). Mp¼55e56 ꢂC;
20
D
6), 101.7 (C-5), 95.6 (C-30), 91.0 (C-10), 83.4 (C-40), 79.3 (eCHCH3),
76.1 (C-20), 58.9 (C-50), 29.1 (eCHCH2), 25.3, 25.2 (3ꢁ t-Bu), 20.1
(CH3), 17.7, 17.4 (2ꢁ Cq t-Bu), ꢀ4.7, ꢀ6.0 (4ꢁ SiCH3). HRMS [MNaþ]
[
a
]
ꢃ5 (c 0.12, CHCl3); IR (ATR)
n 2954, 2929, 2857, 2359, 1785,
1710, 1665, 1462, 1442, 1370, 1255, 1235, 1140, 1109, 1084 cmꢀ1; 1H
NMR (CDCl3, 600 MHz):
d
7.63 (s, 1H, H-6), 5.77 (s, 1H, H-10), 4.33
C24H45N3O8SSi2Na calcd 614.2364, found 614.2358. Compound 38:
(br s, 1H, OH), 4.24 (s, 1H, H-20), 4.05 (dd, 1H, J4 ,5 a¼5.0 Hz,
0
0
20
Mp¼81e82 ꢂC; [
a
]
þ24 (c 0.09, CH2Cl2); IR (ATR)
n
2931, 2858,
J5 a,5 b¼10.8 Hz, H-50a), 3.94 (dd, 1H, J4 ,5 b¼5.0 Hz, J5 a,5 b¼10.8 Hz,
0
0
0
0
0
0
D
1728, 1686, 1462, 1392, 1296, 1258, 1186, 1147, 1120, 837 cmꢀ1
;
1H
H-50b), 3.86 (t,1H, J4 ,5 a¼J4 ,5 b¼5.0 Hz, H-40), 2.97 (d,1H, JA,B¼18 Hz,
H-A (CH2CO)), 2.87 (d, 1H, JA,B¼18 Hz, H-B (CH2CO)), 2.18 (s, 3H,
CH3), 1.91 (s, 3H, CH3), 1.59 (s, 9H, t-Bu), 0.92, 0.85 (s, 18H, 2ꢁ t-Bu),
0.16, 0.12, 0.08, 0.01 (s, 12H, 4ꢁ SiCH3); 13C NMR (CDCl3, 150 MHz):
0
0
0
0
NMR (CDCl3, 300 MHz):
d
7.53 (d, 1H, J5,6¼8.2 Hz, H-6), 5.81 (d, 1H,
0
0
0
0
H-5), 5.79 (d, 1H, J1 ,2 ¼0.8 Hz, H-1 ), 5.24 (d, 1H, H-2 ), 4.96 (ddq,
1H, JCH,CH3¼6.2 Hz, JCH,A¼12.4 Hz, JCH,B¼2.0 Hz, eCHCH3), 4.30 (t,
1H, J4 ,5 a¼J4 ,5 b¼5.7 Hz, H-40), 4.09 (d, 2H, H-50a, H-50b), 2.41 (dd,
1H, JA,B¼14.9 Hz, H-A CH2CHe), 2.22 (dd, 1H, H-B CH2CHe), 1.53 (d,
3H, CH3), 0.94 (s, 9H, t-Bu), 0.31, 0.22 (s, 6H, 2ꢁ SiCH3); 13C NMR
d
209.3 (CO), 161.4, 148.4, 147.9 (C-2, C-4, CO), 136.3 (C-6), 109.3 (C-
0
0
0
0
5), 91.0 (C-10), 86.2 (Cq t-Bu), 83.9 (C-40), 82.6 (C-30), 79.4 (C-20),
60.9 (C-50), 44.1 (CH2CO), 30.8 (CH3), 27.4, 25.8, 25.7 (3ꢁ t-Bu), 18.2,
17.8 (2ꢁ Cq t-Bu), 12.5 (CH3), ꢀ4.5, ꢀ5.4, ꢀ5.5, ꢀ5.6 (4ꢁ SiCH3).
HRMS [MNaþ] C30H54N2O9Si2Na calcd 665.3266, found 665.3281.
(CDCl3, 75 MHz):
d 163.0, 150.1 (C-2, C-4), 139.1 (C-6), 102.1 (C-5),
96.6 (C-30), 91.6 (C-10), 84.5 (C-40), 79.9 (eCHCH3), 77.1 (C-20), 59.4
(C-50), 29.6 (eCHCH2), 25.6 (t-Bu), 20.6 (CH3), 17.9 (Cq t-Bu), ꢀ4.2,
ꢀ5.5 (2ꢁ SiCH3). HRMS [MNaþ] C29H53N3O10SSi2Na calcd 714.2888,
found 714.2911.
4.2.23. 1-(20,50-Bis-O-tert-butyldimethylsilyl-30-(S)-C-isopropanoyl-
b-D
-xylofuranosyl)-30-N-tert-butoxycarbonylthymine (42a) and 1-
(20,50-bis-O-tert-butyldimethylsilyl-30-(R)-C-isopropanoyl-
b-D-xylo-
4.2.21. 1-[(20,50-Bis-O-tert-butyldimethylsilyl-
cil]-30-spiro-600-(400-R-methyl-100,300,200-dioxathiane-200,200-dioxide)
(39) and 1-[(20-O-tert-butyldimethylsilyl-
-xylofuranosyl)uracil]-
b
-
D
-xylofuranosyl)ura-
furanosyl)-30-N-tert-butoxycarbonylthymine (42b). To a solution of
compound 41 (720 mg, 1.12 mmol) in MeOH (10 mL) maintained
between ꢀ5 and ꢀ10 ꢂC was added portionwise NaBH4 (43 mg,
1.12 mmol). After stirring for 1 h, the reaction mixture was neu-
tralized with a Dowex 50W-X8 resin until pH 7. After filtration and
elimination of the solvent under reduced pressure, the crude was
triturated in hexane then filtered to afford 518 mg (72%) of a mix-
ture of compound 42a/42b (84/16 ratio). Separation by HPLC
(CH3CN, 20 ml/min, 254 nm) afforded, respectively, compound 42a
b-D
30-spiro-600-(400-R-methyl-100,300,200-dioxathiane-200,200-dioxide)
(40). To a solution of 36 (73 mg, 0.105 mmol) in CH2Cl2 (15 mL) was
added TFA (0.15 mL, 2.10 mmol). After stirring at 50 ꢂC overnight,
the solvent was eliminated under reduced pressure and the crude
was purified by flash chromatography (EtOAc/cyclohexane, 30/70)
to afford 59 mg of an unseparable mixture of 39 and 40. The mix-
ture was separated by HPLC (CH3CN, 20 mL/min, 254 nm) to afford
and 42b as white solid. Compound 42a: mp¼179e180 ꢂC; [
a
]
20 þ25
D
successively 40 (12 mg, 24%) and 39 (25 mg, 40%). Compound 39:
(c 0.12, CHCl3); IR (ATR) n 3562, 3436, 2958, 2931, 2856, 1780, 1707,
20
D
mp¼85e87 ꢂC; [
a]
þ19 (c 0.17, CH2Cl2); IR (ATR)
n
2930, 2858,
1649, 1464, 1369, 1254, 1152, 1137, 1114, 1094 cmꢀ1; 1H NMR (CDCl3,
1685, 1458, 1405, 1254, 1205, 1089 cmꢀ1
;
1H NMR (CDCl3,
300 MHz):
d
7.60 (s, 1H, H-6), 5.77 (d, 1H, J1 ,2 ¼3.7 Hz, H-1 ), 4.20
0
0
0
300 MHz):
d
7.50 (d, 1H, J5,6¼8.2 Hz, H-6), 5.80 (dd, 1H, J5,6¼8.2 Hz,
(m, 1H, H-3000), 4.19 (dd, 1H, J4 ,5 a¼2.6 Hz, J5 a,5 b¼11.7 Hz, H-50a),
0
0
0
0
J5,NH¼1.9 Hz, H-5), 5.74 (s, 1H, H-10), 5.24 (s, 1H, H-20), 4.21 (dd, 1H,
4.06 (dd, 1H, J4 ,5 b¼2.6 Hz, J5 a,5 b¼11.7 Hz, H-50b), 4.04 (d, 1H,
0
0
0
0

6016
J. Lalot et al. / Tetrahedron 67 (2011) 6006e6017
0
J1 ,2 ¼3.7 Hz, H-2 ), 3.95 (t, 1H, J4 ,5 a¼J4 ,5 b¼2.6 Hz, H-40), 2.00 (dd,
(dd, 1H, JB,CH¼8.2 Hz, JA,B¼15.1 Hz, H-B (CH2CH)), 1.43 (d, 3H,
JCH,CH3¼6.5 Hz, CH3), 0.96, 0.95 (s, 18H, 2ꢁ t-Bu), 0.27, 0.21, 0.17, 0.16
0
0
0
0
0
0
1H, J3 a,3 ¼10.2 Hz, J3 a,3 b¼15.0 Hz, H-300a), 1.95 (s, 3H, CH3), 1.66
00
000
00
00
(dd, 1H, J3 b,3 ¼2.2 Hz, J3 a,3 b¼15.0 Hz, H-300b), 1.64 (s, 9H, t-Bu),
(s, 12H, 4ꢁ SiCH3); 13C NMR (CDCl3, 75 MHz):
d
163.0, 151.8, 151.4
00
000
00
00
1.28 (d, 3H, JCH,3 ¼6.2 Hz, CH3), 0.98, 0.92 (s, 18H, 2ꢁ t-Bu), 0.19,
(C-2, C-4, CO), 137.3 (C-6), 101.6 (C-5), 94.5 (C-30), 91.0 (C-10), 85.4
(C-40), 79.4 (C-20), 60.3 (C-50), 55.0 (OCH3), 29.1 (CH2eCHe), 27.8
(CH3), 26.1, 25.9 (2ꢁ t-Bu), 20.8 (CH3), 18.5, 18.2 (2ꢁ Cq t-Bu), ꢀ4.0,
ꢀ5.2, ꢀ5.4, ꢀ5.6 (4ꢁ SiCH3). HRMS [MNaþ] C27H49N3O10Si2SNa
calcd 686.2575, found 686.2579.
000
0.14, 0.11 (s, 12H, 4ꢁ SiCH3); 13C NMR (CDCl3, 75 MHz):
d 161.3,
148.6, 148.5 (C-2, C-4, CO), 135.5 (C-6), 109.9 (C-5), 88.7 (C-10), 86.4
(Cq t-Bu), 83.4, 82.6 (C-20, C-40), 81.3 (C-30), 64.8 (C-3000), 62.9 (C-50),
39.9 (C-300), 27.4, 25.9 (2ꢁ t-Bu), 24.4 (CH3), 18.1, 18.0 (2ꢁ Cq t-Bu),
12.5 (CH3), ꢀ4.6, ꢀ4.9, ꢀ5.4, ꢀ5.5 (4ꢁ SiCH3). HRMS [MNaþ]
C30H56N2O9Si2Na calcd 667.3422, found 667.3395. Compound 42b:
4.2.26. 1-[20,50-Bis-O-tert-butyldimethylsilyl-30-(S)-C-(2-(R)-hydrox-
mp¼184e185 ꢂC; [
a
]
20 þ48 (c 0.07, CHCl3); IR (ATR)
n
3485, 2956,
ypropyl)-
butyldimethylsilyl-30-(S)-C-(2-(R)-hydroxypropyl)-
anosyl]-30-N-methyluracil (46). To
solution of 34 (81.3 mg,
b-D
-xylofuranosyl]-30-N-methyluracil (45) and 1-[20-O-tert-
D
2929, 2857, 1779, 1707, 1662, 1463, 1370, 1256, 1152, 1143,
b-D-xylofur-
1093 cmꢀ1
;
1H NMR (CDCl3, 300 MHz):
d
7.72 (s, 1H, H-6), 5.74 (s,
a
1H, H-10), 5.51 (s, 1H, OH), 4.23 (dd, 1H, J4 ,5 a¼3.0 Hz,
0.13 mmol) in anhydrous DMF (1.2 mL) was added NaN3 (17 mg,
0.27 mmol). After 24 h at room temperature, another 2 equiv of
NaN3 were added and the solution was allowed to stir at room
temperature for an additional 24 h. DMF was then removed under
reduced pressure and the resulting mixture was dissolved into THF
0
0
J5 a,5 b¼12.0 Hz, H-50a), 4.19 (s, 1H, H-20), 4.18 (m, 1H, H-3000), 4.14
0
0
(dd, 1H, J4 ,5 b¼3.0 Hz, J5 a,5 b¼12.0 Hz, H-50b), 3.84 (t, 1H,
0
0
0
0
J4 ,5 a¼J4 ,5 b¼3.0 Hz, H-40), 1.93 (m, 4H, H-300a, CH3), 1.64 (s, 10H, H-
0
0
0
0
300b, t-Bu), 1.24 (d, 3H, JCH,3 ¼6.3 Hz, CH3), 0.96, 0.91 (s, 18H, 2ꢁ t-
000
Bu), 0.23, 0.18, 0.17, 0.16 (s, 12H, 4ꢁ SiCH3); 13C NMR (CDCl3,
(5 mL) and 0.5 mL of a solution of H2SO4 (220 mL) and H2O (70 mL) in
75 MHz):
d
161.5, 148.5,148.0 (C-2, C-4, CO),136.4 (C-6), 109.0 (C-5),
THF (5 mL) was added. The solution was allowed to stir at room
temperature for 30 min, then DCM (10 mL) was added and the
organic phase was washed by a saturated aqueous solution of
NaHCO3, dried over Na2SO4, filtered and evaporated to dryness.
After flash chromatography on silica gel (Cyclohexane/EtOAc, 1/
0e6/4), compound 45 (20.6 mg, 24%) was isolated as a syrup, and
91.8 (C-10), 86.4 (Cq t-Bu), 83.2 (C-30), 82.9 (C-40), 81.7 (C-20), 66.1
(C-3000), 61.8 (C-50), 38.3 (C-300), 27.5, 25.8 (2ꢁ t-Bu), 24.0 (CH3), 18.1,
17.8 (2ꢁ Cq t-Bu), 12.6 (CH3), ꢀ3.9, ꢀ5.4, ꢀ5.5, ꢀ5.6 (4ꢁ SiCH3).
HRMS [MNaþ] C30H56N2O9Si2Na calcd 667.3422, found 667.3442.
4.2.24. 1-[(20,50-Bis-O-tert-butyldimethylsilyl-
b
-
D
-xylofuranosyl)-3-
compound 46 (36.2 mg, 61%) as a white solid. Compound 45:
20
N-tert-butoxycarbonylthymine]-30-spiro-600-(400-R-methyl-100,300,200-
dioxathiane-200,200-dioxide) (43). To a solution of 42a (200 mg,
0.31 mmol) in distilled THF (15 mL) was added Burgess reagent
(349 mg, 1.24 mmol). After stirring overnight at 80 ꢂC under a ni-
trogen atmosphere, the solvent was eliminated under reduced
pressure and the crude was purified by flash chromatography
mp¼54e55 ꢂC; [
a
]
ꢀ13 (c 0.08, CHCl3); IR (ATR)
n 3333, 2955,
D
2929, 2857, 2113, 1702, 1656, 1470, 1249, 1110, 1088 cmꢀ1; 1H NMR
(CDCl3, 300 MHz):
d
7.91 (d, 1H, J5,6¼8.1 Hz, H-5), 5.64 (d, 1H, H-10),
0
0
5.63 (d, 1H, J5,6¼8.1 Hz, H-6), 4.23 (dd, 1H, J5 a,5 b¼12.2 Hz,
J4 ,5 a¼2.5 Hz, H-50a),4.16 (s, 1H, H-20), 4.06 (dd, 1H, J4 ,5 b¼2.0 Hz, H-
0
0
0
0
50b), 3.90 (m, 1H, eCHOH), 3.85 (t, 1H, J4 ,5 b¼J4 ,5 b¼2.0 Hz, H-40),
3.31 (s, 3H, NCH3), 1.96 (dd, 1H, JA,CH¼9.4 Hz, JA,B¼14.4 Hz, H-A
(CH2CH)), 1.66 (br s, 1H, OH),1.46 (dd, 1H, JB,CH¼4.4 Hz, JA,B¼14.4 Hz,
H-B (CH2CH)), 1.35 (d, 3H, JCH3,CH¼6.5 Hz, CH3CHe), 0.90 (s, 18H, 2ꢁ
t-Bu), 0.24, 0.18, 0.14, 0.13 (s, 12H, 4ꢁ SiCH3); 13C NMR (CDCl3,
0
0
0
0
(EtOAc/cyclohexane, 10/90) to afford 43 (184 mg, 84%) as a white
20
D
solid. Mp¼75e76 ꢂC; [
a
]
þ11 (c 0.12, CHCl3); IR (ATR)
n 2950,
2931, 2858, 1787, 1713, 1669, 1440, 1405, 1371, 1250, 1204, 1148,
1092 cmꢀ1
;
1H NMR0(CDCl3, 300 MHz):
d
7.18 (s, 1H, H-6), 5.87 (d,
0
0
0
0
0
1H, J1 ,2 ¼1.8 Hz, H-1 ), 5.10 (d, 1H, J1 ,2 ¼1.8 Hz, H-2 ), 4.96 (m, 1H,
75 MHz): d 163.5, 150.7 (C-2, C-4), 138.9 (C-6), 100.2 (C-5), 92.4 (C-
CHCH3), 4.10 (dd, 1H, J4 ,5 a¼7.4 Hz, J4 ,5 b¼4.2 Hz, H-40), 4.05 (m, 1H,
10), 83.1 (C-20), 81.7 (C-40), 81.2 (C-30), 62.4 (C-50), 53.8 (eCHeCH3),
37.4 (CH2eCHe), 27.7 (NCH3), 26.2, 25.9 (2ꢁ t-Bu), 20.5 (CH3), 18.2
(2ꢁ Cq t-Bu), ꢀ3.7, ꢀ5.5, ꢀ5.6 (4ꢁ SiCH3). HRMS [MHþ]
C25H47N5O6Si2Na calcd 592.2963, found 592.2968. Compound 46:
0
0
0
0
H-50a), 3.95 (dd, 1H, J4 ,5 b¼4.2 Hz, J5 a,5 b¼9.4 Hz, H-50b), 2.48 (dd,
1H, JA,CH¼12.1 Hz, JA,B¼14.9 Hz, H-A (CH2CH)), 2.31 (dd, 1H,
JB,CH¼1.9 Hz, JA,B¼14.9 Hz, H-B (CH2CH)), 1.99 (s, 3H, CH3), 1.60 (s,
9H, t-Bu), 1.49 (d, 3H, JCH,CH3¼6.2 Hz, CH3), 0.95, 0.92 (s, 18H, 2ꢁ t-
Bu), 0.20, 0.18, 0.15, 0.14 (s, 12H, 4ꢁ SiCH3); 13C NMR (CDCl3,
0
0
0
0
mp¼143e144 ꢂC; [
a
]
20 ꢀ23 (c 0.085, CHCl3); IR (ATR)
n 3282, 2953,
D
2929, 2096, 1698, 1649, 1470, 1292, 1250, 1198, 1111, 1100 cmꢀ1; 1H
75 MHz):
d
161.0,148.5 (C-2, C-4),147.6 (CO),134.2 (C-6),111.2 (C-5),
NMR (CDCl3, 300 MHz):
d
8.17 (d, 1H, J5,6¼8.1 Hz, H-5), 5.71 (d, 1H,
96.5 (C-30), 91.0 (C-10), 86.6 (Cq t-Bu), 83.2 (C-40), 80.2 (eCHeCH2),
77.7 (C-20), 59.5 (C-50), 29.8 (CH2eCHe), 27.8, 25.8, 25.6 (3ꢁ t-Bu),
20.6 (CH3), 18.2, 17.8 (2ꢁ Cq t-Bu), 12.8 (CH3), ꢀ4.4, ꢀ5.4, ꢀ5.5 (4ꢁ
SiCH3). HRMS [MNaþ] C30H54N2O11SSi2Na calcd 729.2885, found
729.2897.
H-10), 5.61 (d, 1H, J5,6¼8.1 Hz, H-6), 4.44 (s, 1H, H-20), 4.23 (dd, 1H,
J5 a,5 b¼12.9 Hz, J4 ,5 a¼2.7 Hz, H-50a), 4.15 (dd, 1H, J4 ,5 b¼2.4 Hz, H-
0
0
0
0
0
0
50b), 4.04 (m, 1H, eCHOH), 4.00 (t, 1H, J4 ,5 b¼J4 ,5 b¼2.5 Hz, H-40),
3.34 (s, 3H, NCH3), 2.02 (dd, 1H, JA,CH¼10.7 Hz, JA,B¼14.4 Hz, H-A
(CH2CH)), 1.60 (dd, 1H, JB,CH¼3.4 Hz, JA,B¼14.4 Hz, H-B (CH2CH)),
1.44 (d, 3H, JCH3,CH¼6.5 Hz, CH3CHe), 0.98 (s, 9H, t-Bu), 0.32, 0.29 (s,
0
0
0
0
4.2.25. 1-[(20,50-Bis-O-tert-butyldimethylsilyl-
b
-
D
-xylofuranosyl)-3-
6H, 2ꢁ SiCH3); 13C NMR (CDCl3, 75 MHz):
d 164.5, 150.8 (C-2, C-4),
N-methyluracil]-30-spiro-600-(300-N-methoxycarbonyl-400-R-methyl-
100,200,300-oxathiazinone-200,200-dioxide) (44). To a solution of 31a/
b (512 mg, 0.94 mmol) in distilled THF (20 mL) was added Burgess
reagent (898 mg, 3.77 mmol). After stirring overnight at 80 ꢂC
under a nitrogen atmosphere, the solvent was eliminated under
reduced pressure and the crude was purified by flash chromatog-
140.2 (C-6), 99.4 (C-5), 92.5 (C-10), 84.5 (C-40), 81.7 (C-30), 81.4 (C-
20), 61.4 (C-50), 53.9 (eCHeCH3), 36.8 (CH2eCHe), 27.7 (NCH3), 26.2
(t-Bu), 20.5 (CH3), 18.3 (Cq t-Bu), ꢀ3.8, ꢀ5.3 (2ꢁ SiCH3). HRMS
[MNaþ] C19H33N5O6SiNa calcd 478.2098, found 478.2078.
Acknowledgements
raphy (EtOAc/cyclohexane, 10/90) to afford 262 mg (42%) of 44 as
20
D
a solid. Mp¼59e60 ꢂC; [
a
]
þ13 (c 0.16, CHCl3); IR (ATR)
n 2955,
ꢀ
A.N.V.N. thanks le Conseil Regional de Picardie for financial
2930, 2857, 1738, 1708, 1666, 1461, 1047, 1291, 1254, 1181,
support.
1109 cmꢀ1; 1H NMR (CDCl3, 300 MHz):
d
7.62 (d, 1H, J5,6¼8.20Hz, H-
0
0
6), 5.80 (d, 1H, J5,6¼8.2 Hz, H-5), 5.77 (d, 1H, J10,2 ¼1.8 Hz, H-1 ), 4.69
0
0
0
(m, 1H, CHCH3), 4.67 (d, 1H, J1 ,2 ¼1.7 Hz, H-2 ), 4.21 (m, 1H, H-4 ),
Supplementary data
4.15 (dd, 1H, J4 ,5 a¼5.5 Hz, J5 a,5 b¼11.0 Hz, H-50a), 4.05 (dd, 1H,
0
0
0
0
J4 ,5 b¼4.2 Hz, J5 a,5 b¼11.0 Hz, H-50b), 3.91 (s, 3H, CH3), 3.36 (s, 3H,
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2011.06.030.
0
0
0
0
CH3), 2.68 (dd, 1H, JA,CH¼6.7 Hz, JA,B¼15.1 Hz, H-A (CH2CH)), 2.56

J. Lalot et al. / Tetrahedron 67 (2011) 6006e6017
13. Mazur, A.; Tropp, B. E.; Engel, R. Tetrahedron 1984, 40, 3949e3956.
6017
References and notes
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ꢀ
20. (a) Martínez, A. G.; Fernandez, A. H.; Vilchez, D. M.; Hanack, M.; Subramanian,
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