Ring contraction of glycopyranosyl enamines: An easy route to furanoid thioglycosides of 5-aminosugars

Article abstract of DOI:10.1016/j.tetasy.2004.05.027

The reaction of glycohexapyranosyl enamines, having 2- and 3-hydroxyl groups in a cis-relationship with 2,2-dimethoxypropane, induces ring contraction of the sugar ring with formation of 2,3-O-isopropylidene furanoid glycosylenamines. 5-O-Mesylation of th

Full text of DOI:10.1016/j.tetasy.2004.05.027

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 2003–2010
Ring contraction of glycopyranosyl enamines: an easy route to
furanoid thioglycosides of 5-aminosugars
ꢀ
M. Angeles Pradera, Francisco J. Sayago, Jose M. Illangua, Manuel Angulo,
ꢀ
Consolacion Gasch and Jose Fuentes
*
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Departamento de Quımica Organica, Facultad de Quımica y Servicio de RMN. Univ. de Sevilla, Aptdo 553, E-41071 Sevilla, Spain
Received 23 April 2004; accepted 24 May 2004
Available online 19 June 2004
Abstract—The reaction of glycohexapyranosyl enamines, having 2- and 3-hydroxyl groups in a cis-relationshipwith 2,2-dimeth-
oxypropane, induces ring contraction of the sugar ring with formation of 2,3-O-isopropylidene furanoid glycosylenamines. 5-O-
Mesylation of these compounds, followed by formation of anhydroazasugars and nucleophilic ring opening, with thiols, produces
alkyl and aryl thiofuranosides of 5-aminosugars.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
furanose moieties are important constituents in the cell
walls of lower organisms such as bacteria,10 fungi,11 and
plants,12 and are crucial for the survival of these
organisms. Consequently, there has been increasing
interest in the syntheses of furanose oligosaccharides,
although the bibliographic data are more scarce than in
the case of the pyranose counterparts. Several alkyl and
aryl 1-thiofuranosides,13 useful as glycofuranosyl donors
in the preparation of di- and oligofuranosides, have
recently been described.14 The thioglycosides have also
been used to prepare poly-O-protected 1-hydroxysugars,
as the thioalkyl and thiophenyl groups can be selectively
removed from poly-O-protected sugars with different
O-protecting groups.15 From a pharmaceutical point of
view, the thioglycosides are useful as antithrombotic
agents.16 Recently, we have reported the preparation of
monocyclic17 and bicyclic17;18 azasugar thioglycosides, in
which the oxygen atom of the sugar ring is substituted
by a nitrogen atom. The method is based on the nucleo-
philic opening of intermediate anhydroazasugar deriv-
atives. As far as we are aware, there are no data on
furanoid thioglycosides having an amino groupon the
Glycosylenamines can be easily and stereoselectively
transformed into anhydroazasugars;1 and, in this way,
they are versatile starting materials for preparing five-,2
six-,3 and seven4-membered polyhydroxyiminocyclitols
with enzyme inhibitory activity.5
Dialkoxycarbonyl vinyl groups have also been used as
temporary N-protecting groups of aminosugars and
glycosylamines, in the preparation of isothiocyanatosu-
gars, thioureidosugars, and other derivatives6 useful in
glycoconjugate synthesis. We have found no data on
anomeric equilibria or ring contraction of glycopyr-
anosyl enamines.
At the same time, thioglycosides, a type of glycoside in
which the anomeric oxygen atom has been substituted
by a sulfur atom, have been widely used as efficient
glycosyl donors in glycosylation reactions for the syn-
theses of complex carbohydrates.7 Over the last few
years, several new syntheses of aryl and alkyl thioglyco-
pyranosides and their use in programmable8 and non-
programmable9 preparations of pyranoid oligosacchar-
ides have been reported. Oligosaccharide-containing
sugar chain, while in the case of pyranoid analogues the
8
amino groupis found only on the two position
and -galacto configurations).
(D-gluco
D
Herein we report the synthesis of the first alkyl 6 and
12–14 and aryl 15 1-thioglycosides of furanoid 5-amino-
sugars starting from glycosyl enamines 1 and 7. This
method involves a ring contraction reaction of the
starting enaminosugar derivative.
* Corresponding author. Tel.: +34-954557150; fax: +34-954624960;
e-mail: jfuentes@us.es
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.05.027

ꢀ
2004
M. A. Pradera et al. / Tetrahedron: Asymmetry 15 (2004) 2003–2010
2. Results and discussion
expected range for furanoid sugar derivatives, which is
deshielded (5–12 ppm) as expected for pyranoid ana-
logues.20 In fact, these deshieldings are observed in the
comparison of the data for 3 and 4 with the data for 2
(Table 1 and Experimental). Moreover, the resonance
for H-5 in 4 was at 5.24, 0.9 ppm deshielded with respect
to the signal for the same proton in 3, indicating that
esterification took place at position five, and conse-
quently confirming the furanoid structure. The anomeric
b configuration of 3 and 4 is supported by the formation
of the azaanhydroderivative 5 (see below), which is only
possible if the enamino group and the exocyclic sugar
backbone are in a cis-relationship.
The primary hydroxyl group of the inexpensive b-D-
mannopyranosylenamine 119 was regioselectively O-
benzoylated (Scheme 1) by treatment with benzoyl
chloride and pyridine at )40 ꢁC for 24 h, to obtain 2
(36% yield). The chemical shifts of H-6a and H-6b (4.53
and 4.30 ppm, respectively) were indicative of the
esterification.
Treatment of 2 with dimethoxypropane in acetone in the
presence of 10-camphor sulfonic acid (CAS) at 60 ꢁC for
1 h produced the 2,3-O-isopropylidene D-mannofur-
anosylenamine 3 in high yield. Compound 3 was O-
mesylated by reaction with mesyl chloride in pyridine at
rt for 24 h under argon to obtain the 5-O-mesyl deriv-
ative 4 in 82% yield. The furanoid structure of 3 and 4
was supported by NMR spectroscopic data (Table 1 and
Experimental). Thus the J3;4 value was in the range 3.4–
3.6 Hz, suggesting a cis-relationshipbetween the corre-
sponding protons, which is possible in the furanoid
structure but not in a pyranoid structure. The reso-
nances for C-1, C-2, C-3, and C-4 in 3 and 4 were in the
Although neither ring contraction nor anomeric equi-
libria have been described for glycohexopyranosyl-
amines, we presume that in the acid medium, oxo-cation
16 is formed, which evolves to the key intermediate
stabilized iminium cation 17. On neutralization, the
[3.3.0] bicyclic acetal 3 is preferentially formed. Small
amounts of the [4.3.0] bicyclic acetal 18 were detected,
but they evolved to 3 in the reaction medium (Scheme
2).
P
BzOCH2
HOH2C
H
O
OEt
NHP
H
N
O
O
i
BzO
HO
O
ii
iii
HO
HO
O
O
NHP
HO
HO
CO2Et
OH
OH
3
1
2
H
BzOCH2
P
NHP
O
O
BzO
MsO
NHP
N
O
SEt
O
BzO
v
H
O
O
iv
O
H
O
O
4
6
5
Scheme 1. Reagents and conditions: (i) ClBz/Py, )40 ꢁC, 24 h; (ii) 2,2-dimethoxypropane, CAS, 60 ꢁC, 1 h; (iii) ClMs/Py, rt, 24 h; (iv) NaOMe/DMF,
45 ꢁC/20 mmHg, 8 h; (v) EtSH/Cl2CH2/PTSA, rt, 15 min.
Table 1. Selected NMR spectroscopic data (d ppm, J Hz) for compounds 2–6 and 8–15 at 500 (1H) and 125 (13C) MHz
Sugar ring
Enamino moiety
d values
Ja values
dNH
d@CH d@CH d@C
H-1
H-2
H-4
H-5
C-1
C-4
C-5
1,2
3,4
4,5
2b
4.93
4.81
4.82
5.84
4.66
4.79
4.83
5.15
5.76
4.64
4.62
4.62
4.71
3.74
4.71
4.75
4.63
4.80
4.69
4.28
4.75
4.57
4.79
4.79
4.79
4.89
3.54
3.66
3.92
5.03
3.68
3.37
3.45
3.70
4.65
3.35
3.35
3.35
3.33
3.54
4.33
5.24
4.45
4.07
4.09
3.40
4.85–4.82
4.19
3.80
3.80
3.80
3.86
85.3
89.4
89.4
91.1
87.7
89.3
83.9
87.7
92.9
87.5
87.7
88.0
90.8
66.1
76.7
76.0
82.1
80.2
82.1
73.7
78.2
85.4
84.3
84.1
84.5
84.4
75.6
68.5
76.3
55.4
58.3
66.1
73.2
76.0
52.1
54.2
54.5
54.8
54.3
––
––
––
9.39
9.43
9.44
––
8.09
8.05
8.01
7.63
8.16
8.06
8.06
8.11
7.52
8.13
8.13
8.12
8.23
158.9
157.4
157.1
144.6
160.0
157.5
158.0
157.7
144.4
159.3
159.1
159.4
159.4
91.0
94.0
94.5
93.9
90.8
93.8
93.2
92.2
92.0
89.4
89.4
89.8
89.6
3c
3.8
3.9
2.9
4.0
3.8
2.4
3.5
2.8
4.0
4.0
3.9
4.0
3.6
3.4
4.9
3.5
3.7
6.6
3.2
5.0
3.5
3.4
3.5
3.5
8.2
7.5
0.0
8.5
7.7
9.0
6.8
0.0
8.8
8.9
8.9
9.0
4c
5b
6c
9.54
9.42
9.34
9.20
––
8c
9c
10b
11b
12c
13c
14c
15c
9.27
9.27
9.29
9.30
a Only the values directly measured on the spectra are indicated.
b In DMSO-d6.
c In CDCl3.

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M. A. Pradera et al. / Tetrahedron: Asymmetry 15 (2004) 2003–2010
2005
P
BzOCH2
HO
BzOCH2
BzOH2C
HO
O
OEt
H
N
O
O
Me2C(OMe)2
H
OH
H+
NHP
NHP
NHP
NHP
HO
HO
CO2Et
O
HO
O
OH
OH
16
2
18
BzOCH2
H
OH
BzO
HO
O
HO
HO
Me2C(OMe)2
H
O
O
OH
17
3
Scheme 2. Mechanism of the formation of 3.
Treatment of 4 with sodium methoxide in DMF at 40 ꢁC
and under reduced pressure for 8 h produced the anhy-
droazasugar derivative 5 in 73% yield. The reaction took
place through the stabilized intermediate amide anion
19,2 which by internal nucleophilic displacement of the
selective excitation of this proton revealed a strong NOE
effect with H-1, similar to that observed with the vicinal
H-3, showing a close proximity between these nuclei and
thus suggesting that both protons should be on the same
face of the sugar ring. Also in agreement with this
configuration at C-1 is the observation of a small NOE
contact between the methylene groupof the aglycon and
the endo methyl of the isopropylidene group.
1
5-OMs groupafforded 5. The H NMR spectrum of 5
contained no signal for NH, and showed a singlet for the
HC@ of the enamino moiety (@CHNR2) instead of the
doublet (@CHNHR) of the spectrum of 4. The signal
for H-1 was strongly (1.02 ppm) shifted downfield,
whereas the resonances for H-5 and C-5 were shifted
upfield (0.79 and 20.9 ppm, respectively) as expected for
the substitution of a sulfonyloxy groupby an enamino
group. The NMR data for the enamino moiety of 5 were
similar to those previously described4 for related N-
protected anhydroazasugars. Very marked changes were
observed in all the coupling constants of the sugar ring
of 5, in accordance with the conformational change by
the formation of the tricyclic system.
The formation of 6 is stereoselective with only the a-
L
anomer being isolated. Under the reaction conditions, 5
can be protonated (Scheme 3) on the endocyclic oxygen
atom (fi 20) or on the nitrogen atom (fi 21). The
cleavage of the C1–N bond to form ion 22 is preferential
with respect to the cleavage of the C1–O bond; as in the
first case the cis [3.3.0] stable bicyclic system is retained.
The conformation of the furanose ring of 22 is close to
2
0T1 ꢀ E1 ꢀ T1, while the attack of the ethanethiol on
si face of 21 produces 6. The presence of the isopropyl-
idene groupdetermines the course of the reaction; the
[3.3.0] ring favors the cleavage of the C–N bond,
whereas in absence of the isopropylidene group, the
cleavage of the C–O bond is predominant.18
O
OEt
H
BzO
MsO
N
O
O
O
O
OEt
Similarly with the aim of obtaining information from
another glycosylenamine with the same relative config-
uration and to easily form a 2,3-isopropylidene deriva-
19
tive, we started from the b-L-rhamnopyranosylenamine
719 (Scheme 4). This compound has no primary hydr-
oxyl group, and consequently the first low-yielding
benzoylation is not necessary, thus increasing the overall
yield. Reaction of 7 with dimethoxypropane under the
same conditions described above for 2 afforded 8 (ma-
jor) and 9 (minor). When the pyranosyl derivative 9 was
placed in acetone, CAS produced a 1:1 mixture of 8 and
9. The spectroscopic data of 8 were very close to those
for 3 (Table 1 and Experimental) as the furanoid moiety
of both compounds are enantiomers. In the case of 9,
the measured vicinal coupling constants of the sugar
ring, together with a shielding20 in the resonances of the
carbons of the same ring, confirmed the pyranoid
structure.
Reaction of 5 with ethanethiol in dichloromethane in the
presence of p-toluenesulfonic acid (PTSA) at rt for
15 min produced ethyl a-L-gulo thiofuranoside 6. The
1H NMR spectrum of 6 showed again the signal for NH,
and the resonance for HC@ was a doublet; the data for
the enamino moiety were close to those for 2–4 (Table 1
and Experimental). The chemical shift for the reso-
nances of C-1 (87.7 ppm) was similar to that described
for ethyl 1-thioglycopyranosides20 and ethyl 1-thiogly-
cofuranosides.13 The ethylthio groupwas also evident
from MS data and from the resonances of the S–CH2
group.13;18 An HMBC correlation spectrum21 showed a
3-bond connection between C-1 and S-CH2, and be-
tween H-1 and S-CH2 groups.
For the assignment of the stereochemistry of C-1 in 6,
DPFGSE-NOE22 experiments were performed. Such
experiments were crucial in the case of H-4, since
The anomeric configurational symbol changes due to the inversion at
C-5.

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M. A. Pradera et al. / Tetrahedron: Asymmetry 15 (2004) 2003–2010
P
EtSH
si
BzOCH2
BzOCH2
P
NHP
O
O
NH
O
N
O
BzO
H
H
H
H
5
O
H
6
H
O
O
O
O
20
21
22
Scheme 3.
P
Me
HO
O
H3C
HO
HO
O
OEt
O
H
N
O
HO
Me
NHP
i
+
NHP
CO2Et
O
O
H
O
O
OH
7
8
9
ii
O
H3C
P
O
H
N
O
SR
iii
MsO
Me
iv
Me
PHN
NHP
O
O
O
O
H
O
O
12 R = Et
13 R = Bu
10
11
R = BuSH
14
15R = PhOMe
Scheme 4. Reagents and conditions: (i) 2,2-dimethoxypropane, CAS, 60 ꢁC, 1 h; (ii) ClMs/Py, rt, 24 h; (iii) NaOMe/DMF, 45 ꢁC/20 mmHg, 15 min;
(iv) RSH/Cl2CH2/PTSA, rt, 15 min.
Treatment of 8 with mesyl chloride gave 10, which by
reaction with sodium methoxide in DMF produced the
anhydrosugar derivative 11 in high yield. The formation
of 10 involves (Table 1) a considerable deshielding in the
resonance for H-5, while compound 11 had similar
structural supports to those discussed above for 5.
Finally, reaction of 10 with ethanethiol, 1-butanethiol,
1,4-butanedithiol, and 4-methoxythiophenol in the
presence of PTSA yielded the corresponding furanoid
alkyl 12–14 or 4-methoxyphenyl 15 1-thiofuranoside. In
the case of the 1,4-butanedithiol, the monoglycosyl
derivative 14 was the only product isolated. The chem-
ical shifts and the coupling constants for the sugar ring
and for the enamino moiety of 12–15 were very close
(Table 1 and Experimental) to the corresponding data
for 6, and confirmed the proposed structures. The ano-
meric configuration of 12 and 15 (Fig. 1) was established
through 1D NOESY experiments similar to those dis-
cussed above for 6. The NOE contact H-4 and H-1 was
determinant; an NOE between S–CH2 and the endo
methyl of the isopropylidene group for 12 and a NOE
between aromatic protons (ortho) and CH@ of the
enamino moiety for 15, were also observed.
Figure 1. 1H NMR and DPFGSE-NOE spectra of 15.
L
-rhamno configuration as examples). The furanoid
glycohexofuranosylenamines, which have the enamino
moiety and the exocyclic sugar backbone in a cis-rela-
tionship( 3 and 8), can be transformed in three steps into
alkyl (aryl) 1-thioglycofuranosides of 5-aminosugars 6
and 12–15. The key intermediate of this transformation
is an anhydroazasugar derivative 5 or 11. Herein
the dialkoxycarbonylvinyl groupwas used to protect
the amino groupand to stabilize a negative charge in the
formation of the azaanhydrocompounds. The dialk-
oxycarbonylvinylamino groupstabilized the opsitive
charge in the ring contraction reaction. All the reactions
are highly stereoselective.
3. Conclusion
In conclusion, the pyranoid ring of glycohexopyr-
anosylenamines can be transformed into a furanoid ring,
if the sugar configuration permits the formation of
a cis-2,3-O-isopropylidene derivative (D-manno and

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M. A. Pradera et al. / Tetrahedron: Asymmetry 15 (2004) 2003–2010
2007
4. Experimental
4.1. General methods
2CH2CH3); 13C NMR (125.7 MHz, DMSO-d6) d 167.4
(C@O benzoyl), 165.8, 164.9 (2C@O), 158.9 (CH@),
133.3–128.8 (Ar), 91.0 (C@), 85.3 (C-1), 75.6 (C-5), 73.4
(C-3), 69.9 (C-2), 66.1 (C-4), 64.4 (C-6), 59.3, 59.1
(2CH2CH3), 14.3, 14.2 (2CH2CH3); Anal Calcd for
C21H27NO10: C, 55.62; H, 6.00; N, 3.09. Found: C,
55.25; H, 5.91; N, 3.18.
Melting points were determined with a Gallenkamp
apparatus and are uncorrected. A Perkin–Elmer Model
141 MC polarimeter, 1-cm tubes, and solutions in
CH2Cl2, at 589 nm, were used for measurement of spe-
cific rotations. IR spectra were recorded for KBr discs
on a Bomen Michelson MB-120 FTIR spectrophoto-
meter. Mass spectra (EI, CI, and FAB) were recorded
with a Kratos MS-80RFA or a Micromass AutoSpecQ
instrument with a resolution of 1000 or 60,000 (10%
valley definition). For the FAB spectra, ions were pro-
duced by a beam of xenon atoms (6–7 keV), using 3-
nitrobenzyl alcohol or thioglycerol as matrix and NaI as
salt. TLC was performed on silica gel HF254, with
detection by UV light or charring with H2SO4. Silica gel
60 (Merck, 70–230 and 230–400 mesh) was used for
preparative chromatography.
4.3. Preparation of compounds 3, 8, and 9
A solution of the corresponding compound 2 or 7
(0.312 mmol), dimethoxypropane dimethyl acetal
(0.624 mmol), and CAS (0.027 mmol) in acetone (1 mL)
was stirred at 60 ꢁC for 1 h. The solution was poured
into cool aq NaHCO3 (saturated), extracted with
CH2Cl2, dried over MgSO4, and concentrated. From 2,
the residue was purified by column chromatography
(CH2Cl2/MeOH 60:1) to give compound 3. From 7, the
residue was purified by column chromatography (diethyl
ether) to give compounds 8 and 9. Compound 9 was
treated with acetone/CAS at 60 ꢁC to yield a mixture 1:1
of 8 and 9.
NMR experiments were recorded on a Bruker AMX or
1
Avance AV 500 spectrometer (500.13 MHz for H and
125.75 MHz for 13C). Sample concentrations were typi-
cally in the range 10–15 mg per 0.6 mL of CDCl3.
Chemical shifts are given in ppm, using the residual
protonated solvent signal as reference. 1H and 13C
assignments were confirmed by 2D conventional COSY,
HMQC, or HSQC and HMBC experiments. For the
HMQC experiment, the null time following the BIRD
pulse was 400 ms. The HMBC experiments were opti-
mized for long-range coupling constants of 10 Hz. 1D
NOESY experiments were carried out on a 5 mm inverse
detection probe operating at 303 K, by using the double-
pulsed field gradient spin-echo technique (DPFGSE-
NOE).22 A mixing time of 400 ms, a recycle delay of 2 s,
and 1024 transients per spectrum, were used in all cases.
Selective inversions were performed by using Gaussian-
shaped soft pulses (50 ms).
4.3.1. 6-O-Benzoyl-N-(2,2-diethoxycarbonylvinyl)-2,3-O-
isopropylidene-b-D-mannofuranosylamine, 3. Amorphous
22
solid. Yield 85%; ½aŠ ¼ þ88 (c 0.9, CH2Cl2); FABMS
D
m=z 516 [(M+Na)þ]; IR 3466, 3345, 3304, 2982, 2945,
1717, 1665, 1605, 1452, 1377, 1269, 1225, 1105, 1032,
1
806, 714 cmꢀ1; H NMR (500 MHz, CDCl3) d 9.43 (dd,
1H, JNH;1 ¼ 9:3, JNH;HC ¼ 13:6, NH), 8.05 (d, 1H,
HC@), 8.09–7.42 (m, 5H, Ar), 4.93 (dd, 1H, J2;3 ¼ 6:0,
J3;4 ¼ 3:6, H-3), 4.81 (dd, 1H, J1;2 ¼ 3:8, H-1), 4.71 (dd,
1H, H-2), 4.65 (dd, 1H, J5;6a ¼ 2:9, J6a;6b ¼ 11:8, H-6a),
4.44 (dd, 1H, J5;6b ¼ 5:9, H-6b), 4.33 (m, 1H, H-5), 4.26,
4.19 (each q, each 2H, JH;H ¼ 7:1, 2CH2CH3), 3.66 (dd,
1H, J4;5 ¼ 8:2, H-4), 1.63, 1.40 (each s, each 3H,
2(CH3)2C), 1.33, 1.28 (each t, each 3H, 2CH2CH3); 13C
NMR (125.7 MHz, CDCl3) d 167.8 (2C@O benzoyl),
167.0, 165.7 (2C@O), 157.4 (CH@), 133.2–128.4 (Ar),
113.9 (C(CH3)2), 94.0 (C@), 89.4 (C-1), 80.3 (C-3), 79.0
(C-2), 76.7 (C-4), 68.5 (C-5), 66.9 (C-6), 60.1, 59.9
(2CH2CH3), 25.9, 24.8 [(CH3)2C], 14.4, 14.3
(2CH2CH3); Anal Calcd for C24H31NO10: C, 58.41; H,
6.33; N, 2.84. Found: C, 58.60; H, 6.33; N, 2.85.
4.2. 6-O-Benzoyl-N-(2,2-diethoxycarbonylvinyl)-b-D-
mannopyranosylamine, 2
To a stirred solution of 1 (1.03 g, 2.88 mmol) in pyridine
(8 mL) at )40 ꢁC was gradually added benzoyl chloride
(680 lL, 5.82 mmol). The mixture was kept for 24 h, the
reaction controlled by TLC (CH2Cl2/MeOH, 15:1) and
then 5 mL of water added. The mixture was twice
evaporated to dryness with toluene. The residue was
4.3.2. N-(2,2-Diethoxycarbonylvinyl)-2,3-O-isopropylid-
ene-b-L-rhamnofuranosylamine, 8. Amorphous solid.
24
Yield 55%; ½aŠ ¼ ꢀ81 (c 1.0, CH2Cl2); FABMS m=z
purified by column chromatography (CH2Cl2/MeOH,
30:1) to give an amorphous solid. Yield 36%; ½aŠ
D
22
D
¼
396 [(M+Na)þ]; IR 3384, 3306, 2984, 2938, 1697, 1669,
1614, 1449, 1384, 1324, 1261, 1226, 1172, 1044,
þ52 (c 1.0, MeOH); FABMS m=z 476 [(M+Na)þ]; IR
1
3524, 3385, 2982, 2901, 1703, 1640, 1593, 1452, 1377,
757 cmꢀ1; H NMR (500 MHz, CDCl3) d 9.42 (dd, 1H,
1
1289, 1248, 1092, 1022, 868, 797, 712 cmꢀ1; H NMR
JNH;1 ¼ 9:3, JNH;HC@ ¼ 13:6, NH), 8.06 (d, 1H, HC@),
4.87 (dd, 1H, J2;3 ¼ 6:1, J3;4 ¼ 3:7, H-3), 4.79 (dd, 1H,
J1;2 ¼ 3:8, H-1), 4.69 (dd, 1H, H-2), 4.26, 4.19 (each q,
each 2H, JH;H ¼ 7:0, 2CH2CH3), 4.09 (m, 1H, H-5), 3.37
(dd, 1H, J4;5 ¼ 7:7, H-4), 2.09 (d, 1H, J5;OH ¼ 5:2, OH-
H5), 1.60, 1.39 (each s, each 3H, (CH3)2C), 1.33 (d, 3H,
J5;6 ¼ 7:7, H-6), 1.33, 1.29 (each t, each 3H, 2CH2CH3);
13C NMR (125.7 MHz, CDCl3) d 167.9, 165.9 (2C@O),
157.5 (CH@), 113.8 (C(CH3)2), 93.8 (C@), 89.3 (C-1),
(500 MHz, DMSO-d6) d 9.39 (dd, 1H, JNH;1 ¼ 8:9,
JNH;HC ¼ 14:1, NH), 8.09 (d, 1H, HC@), 7.96–7.50 (m,
5H, Ar), 5.36 (d, 1H, J2;OH ¼ 5:3, OH-H2), 5.15 (d, 1H,
J4;OH ¼ 3:9, OH-H4), 5.06 (d, 1H, J3;OH ¼ 5:3, OH-H3),
4.93 (d, 1H, H-1), 4.53 (d, 1H, J6a;6b ¼ 11:8, H-6a), 4.30
(dd, 1H, J5;6b ¼ 5:3, H-6b), 4.09, 4.03 (each q, each 2H,
JH;H ¼ 7:1, 2CH2CH3), 3.74 (m, 1H, H-2), 3.54 (m, 2H,
H-4,H-5), 3.41 (m, 1H, H-3), 1.18, 1.15 (each t, each 3H,

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M. A. Pradera et al. / Tetrahedron: Asymmetry 15 (2004) 2003–2010
82.1 (C-4), 80.3 (C-3), 79.3 (C-2), 66.1 (C-5), 60.1, 60.0
(2CH2CH3), 25.9, 24.9 [(CH3)2C], 20.7 (C-6), 14.5, 14.4
(2CH2CH3); Anal Calcd for C17H27NO8: C, 54.68; H,
7.29; N, 3.75. Found: C, 54.76; H, 7.47; N, 3.81.
4.4.2. N-(2,2-Diethoxycarbonylvinyl)-2,3-O-isopropylid-
ene-5-O-mesyl-b- -rhamnofuranosylamine, 10. Column
chromatography (AcOEt/hexane, 1:2) yields an amor-
L
24
phous solid, 90%; ½aŠ ¼ ꢀ40 (c 0.9, CH2Cl2); FABMS
D
m=z 474 [(M+Na)þ]; IR 3383, 3330, 2995, 2948, 1705,
1675, 1607, 1458, 1356, 1237, 812 cmꢀ1
;
1H NMR
4.3.3. N-(2,2-Diethoxycarbonylvinyl)-2,3-O-isopropylid-
ene-b-L-rhamnopyranosylamine, 9. Amorphous solid.
(500 MHz, DMSO-d6, 50 ꢁC) d 9.20 (dd, 1H, JNH;1 ¼ 9:2,
JNH;HC@ ¼ 13:6, NH), 8.11 (d, 1H, HC@), 5.15 (dd, 1H,
J1;2 ¼ 3:5, H-1), 4.85–4.82 (m, 2H, H-3, H-5), 4.75 (dd,
1H, J2;3 ¼ 6:0, H-2), 4.13, 4.07 (each q, each 2H,
JH;H ¼ 7:0, 2CH2CH3), 3.70 (dd, 1H, J3;4 ¼ 3:2,
J4;5 ¼ 6:8, H-4), 3.18 (s, 3H, Ms), 1.47, 1.32 [each s, each
3H, (CH3)2C], 1.42 (d, 3H, J5;6 ¼ 6:0, H-6), 1.21, 1.20
(each t, each 3H, 2CH2CH3); 13C NMR (125.7 MHz,
DMSO-d6, 50 ꢁC) d 167.2, 164.7 (2C@O), 157.7 (CH@),
112.4 [C(CH3)2], 92.2 (C@), 87.7 (C-1), 79.1 (C-3), 78.5
(C-2), 78.2 (C-4), 76.0 (C-4), 59.4, 59.2 (2CH2CH3), 38.0
(Ms), 25.6, 24.6 [(CH3)2C], 18.7 (C-6), 14.2 (2CH2CH3);
Anal Calcd for C18H29NO10S: C, 47.88; H, 6.47; N, 3.10;
S, 7.10. Found: C, 47.75; H, 6.44; N, 3.18; S, 6.96.
24
Yield 45%; ½aŠ ¼ ꢀ58 (c 1.0, CH2Cl2); FABMS
D
m=z 396 [(M+Na)þ]; IR 3449, 3385, 3298, 2984, 2937,
1
1678, 1603, 1449, 1379, 1247, 1023, 804 cmꢀ1; H NMR
(500 MHz, CDCl3)
d
9.34 (dd, 1H, JNH;1 ¼ 8:9,
JNH;HC@ ¼ 13:6, NH), 8.06 (d, 1H, HC@), 4.83 (dd, 1H,
J1;2 ¼ 2:4, H-1), 4.28 (dd, 1H, J2;3 ¼ 5:8, H-2), 4.28–4.17
(m, 4H, 2CH2CH3), 4.10 (dd, 1H, J3;4 ¼ 6:6, H-3), 3.45
(ddd, 1H, J4;5 ¼ 9:0, J4;OH ¼ 3:8, H-4), 3.40 (dq, 1H,
J5;6 ¼ 6:1, H-5), 2.40 (d, 1H, OH-H4), 1.56, 1.39 (each s,
each 3H, (CH3)2C), 1.33, 1.29 (each t, each 3H,
JH;H ¼ 7:0, 2CH2CH3), 1.33 (d, 3H, H-6); 13C NMR
(125.7 MHz, CDCl3) d 167.3, 165.8 (2C@O), 158.0
(CH@), 110.5 (C(CH3)2), 93.2 (C@), 83.9 (C-1), 79.3 (C-
2), 73.7 (C-3), 73.2 (C-4), 73.0 (C-5), 59.9, 59.8
(2CH2CH3), 27.6, 26.1 ((CH3)2C), 17.7 (C-6), 14.2, 14.0
(2CH2C3); HREIMS m=z obsd 373.1735 calcd for
C17H27NO8 373.1737.
4.5. Preparation of compounds 5 and 11
To a stirred solution of the corresponding mesyl com-
pound 4 or 10 (0.27 mmol) in DMF (5.0 mL) at 40 ꢁC
and 20 mmHg, sodium methoxide (16 mg, 0.27 mmol)
was added. The reaction was stirred for 8 h for 5 and
15 min for 11. The mixture was poured into ice-water
and extracted with CH2Cl2. The organic layer was sep-
arated, washed with water, dried over MgSO4, filtered,
and evaporated to dryness. The residue was purified as
described.
4.4. Preparation of compounds 4 and 10
Into a cooled (0 ꢁC) stirred solution of the correspond-
ing compound 3 or 8 (0.894 mmol) in pyridine (3.1 mL)
under argon, mesyl chloride (248 lL, 3.12 mmol) was
dropped. The mixture was stirred at rt for 24 h and the
reaction controlled by TLC (CH2Cl2/MeOH, 100:1).
The solution was poured into ice-water and extracted
with CH2Cl2; the organic layer was separated, washed
with 1 M sulfuric acid, satd aq NaHCO3, and water,
dried over MgSO4, filtered, and evaporated to dryness.
The residue was purified as described.
4.5.1. 1,5-Anhydro-6-O-benzoyl-N-(2,2-diethoxycarbon-
ylvinyl)-2,3-O-isopropylidene-a-L-gulofuranosylamine, 5.
Column chromatography (CH2Cl2/MeOH, 100:1) yields
24
D
an amorphous solid, 73%; ½aŠ ¼ þ109 (c 1.1, CH2Cl2);
FABMS m=z 498 [(M+Na)þ]; IR 3063, 2982, 2936, 1721,
1686, 1597, 1447, 1383, 1267, 714 cmꢀ1
;
1H NMR
4.4.1. 6-O-Benzoyl-N-(2,2-diethoxycarbonylvinyl)-2,3-O-
isopropylidene-5-O-mesyl-b-D-mannofuranosylamine, 4.
Column chromatography (CH2Cl2) yields an amor-
(500 MHz, DMSO-d6, 60 ꢁC) d 7.97–7.50 (m, 5H, Ar),
7.63 (br s, 1H, HC@), 5.84 (br s, 1H, H-1), 5.03 (d, 1H,
J3;4 ¼ 4:9, H-4), 4.78 (dd, 1H, J2;3 ¼ 8:1, H-3), 4.63 (dd,
1H, J1;2 ¼ 2:9, H-2), 4.45 (m, 1H, H-5), 4.19 (br s, 2H,
H-6a, H-6b), 4.14–4.04 (m, 4H, 2CH2CH3), 1.51, 1.31
(each s, each 3H, [(CH3)2C]), 1.18, 1.16 (each t, each 3H,
JH;H ¼ 7:0, 2CH2CH3); 13C NMR (125.7 MHz, DMSO-
d6, 60 ꢁC) d 165.9 (C@O), 165.0 (2C@O), 144.6 (CH@),
133.1–128.4 (Ar), 118.8 [C(CH3)2], 93.9 (C@), 91.1 (C-
1), 82.1 (C-4), 80.5 (C-2), 75.9 (C-3), 61.2 (C-6), 59.8,
59.1 (2CH2CH3), 55.4 (C-5), 25.0, 24.9 [(CH3)2C], 13.9,
13.6 (2CH2CH3); Anal Calcd for C24H29NO9: C, 60.62;
H, 6.15; N, 2.95. Found: C, 60.24; H, 6.09; N, 2.92.
20
D
phous solid, 82%; ½aŠ ¼ þ75 (c 0.8, CH2Cl2); FABMS
m=z 594 [(M+Na)þ]; IR 3297, 2984, 2940, 1725, 1665,
1
1605, 1454, 1371, 1267, 1103, 802, 714 cmꢀ1; H NMR
(500 MHz, CDCl3)
d
9.44 (dd, 1H, JNH;1 ¼ 9:4,
JNH;HC@ ¼ 13:5, NH), 8.01 (d, 1H, HC@), 8.09–7.42 (m,
5H, Ph), 5.24 (ddd, 1H, J4;5 ¼ 7:5, J5;6a ¼ 2:3, J5;6b ¼ 6:2,
H-5), 4.87 (m, 1H, H-6a), 4.86 (m, 1H, H-3), 4.82 (dd,
1H, J1;2 ¼ 3:9, H-1), 4.75 (dd, 1H, J2;3 ¼ 5:9, H-2), 4.51
(dd, 1H, J6a;6b ¼ 12:7, H-6b), 4.27, 4.19 (each m, each
2H, 2CH2CH3), 3.92 (dd, 1H, J3;4 ¼ 3:4, H-4), 3.09 (s,
3H, Ms), 1.64, 1.40 (each s, each 3H, (CH3)2), 1.34, 1.29
(each t, each 3H, JH;H ¼ 7:0, 2CH2CH3); 13C NMR
(125.7 MHz, CDCl3) d 167.7 (C@O), 165.9, 165.5
(2C@O), 157.1 (CH@), 133.2–128.4 (Ph), 114.2
(C(CH3)2), 94.5 (C@), 89.4 (C-1), 79.3 (C-3), 78.8 (C-2),
76.3 (C-5), 76.0 (C-4), 63.8 (C-6), 60.1, 59.9 (2CH2CH3),
38.7 (Ms), 25.8, 24.9 ((CH3)2C), 14.3, 14.2 (2CH2CH3);
Anal Calcd for C25H33NO12 S: C, 52.53; H, 5.82; N,
2.45. Found: C, 52.29; H, 5.81; N, 2.46.
4.5.2.
1,5-Anhydro-6-deoxy-N-(2,2-diethoxycarbonyl-
-gulofuranosylamine, 11.
Column chromatography (ether/hexane, 4:1) yields an
vinyl)-2,3-O-isopropylidene-a-
D
24
amorphous solid, 77%; ½aŠ ¼ ꢀ17 (c 1.0, CH2Cl2);
D
FABMS m=z 378 [(M+Na)þ]; IR, 2988, 2936, 1690,
1
1597, 1420, 1374, 1269, 740 cmꢀ1; H NMR (500 MHz,
DMSO-d6, 30 ꢁC) d 7.52 (br s, 1H, HC@), 5.76 (br s, 1H,

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M. A. Pradera et al. / Tetrahedron: Asymmetry 15 (2004) 2003–2010
2009
H-1), 4.70 (dd, 1H, J3;4 ¼ 5:0, J4;5 ¼ 8:0, H-4), 4.65 (m,
1H, H-3), 4.57 (dd, 1H, J1;2 ¼ 2:8, J2;3 ¼ 8:5, H-2), 4.19
(m, 1H, H-5), 4.11–4.06 (m, 4H, 2CH2CH3), 1.50, 1.28
(each s, each 3H, [(CH3)2C]), 1.21, 1.17 (each t, each 3H,
(each q, each 2H, JH;H ¼ 7:1, 2CH2CH3), 3.80 (m, 1H,
H-5), 3.35 (dd, 1H, J4;5 ¼ 8:8, H-4), 2.68 (m, 2H,
SCH2CH3), 1.53, 1.32 (each s, each 3H, [(CH3)2C], 1.38
(d, 3H, J5;6 ¼ 6:4, H-6), 1.34, 1.28 (each t, each 3H,
2CH2CH3), 1.27 (t, 3H, JH;H ¼ 7:5, SCH2CH3); 13C
NMR (125.7 MHz, CDCl3) d 169.5, 166.0 (2C@O),
159.3 (CH@), 113.2 (C(CH3)2), 89.4 (C@), 87.5 (C-1),
84.3 (C-4), 82.6 (C-2), 79.9 (C-3), 59.7, 59.4 (2
CH2CH3), 54.5 (C-5), 29.0 (SCH2CH3), 25.8, 25.0
[(CH3)2C], 17.3 (C-6), 15.4 (SCH2CH3), 14.4, 14.3
(2CH2CH3); HREIMS m=z obsd 417.1828 calcd for
C19H31NO7S 417.1821.
JH;H ¼ 7:0, 2CH2CH3), 0.94 (d, 3H, J5;6 ¼ 6:0, H-6); 13
C
NMR (125.7 MHz, DMSO-d6, 30 ꢁC) d 166.6, 166.4
(2C@O), 144.4 (CH@), 118.9 [C(CH3)2], 92.7 (C-1), 92.0
(C@), 85.4 (C-4), 80.0 (C-2), 76.2 (C-3), 60.0, 59.3
(2CH2CH3), 52.1 (C-5), 25.3, 25.2 [(CH3)2C], 15.7 (C-6),
14.4, 14.2 (2CH2CH3). HRCIMS m=z obsd 356.1689
calcd for C17H25NO7 356.1709.
4.6. Preparation of compounds 6, 12–14
4.6.3. Buthyl 5,6-di-deoxy-5-N-(2,2-diethoxycarbonyl-
vinylamine)-2,3-O-isopropylidene-1-thio-a-D-gulofurano-
side, 13. Column chromatography (CH2Cl2, CH2Cl2/
To a stirred solution of the corresponding compound 5
ꢁ
or 11 (0.270 mmol) in dry CH2Cl2 (4.0 mL), over 3 A
molecular sieves, ethanethiol (5 fi 6), and (11 fi 12), 1-
butanethiol, (11 fi 13), 1,4-butanedithiol, (11 fi 14), and
4-methoxythiophenol (11 fi 15) (6.775 mmol), and
PTSA (0.393 mmol) were added. The reaction was con-
trolled by TLC (CH2Cl2/MeOH, 100:1). The solution
was poured into a stirred mixture of ice and satd aq
NaHCO3, extracted with CH2Cl2, washed with water,
and dried over MgSO4. The residue was purified as
indicated.
MeOH, 100:1). Yield 65% as amorphous solid;
24
D
½aŠ ¼ ꢀ132 (c 1.0, CH2Cl2); FABMS m=z 468
[(M+Na)þ]; IR 3296, 2984, 2930, 2859, 2149, 1701, 1655,
1
1609, 1429, 1375, 1260, 748 cmꢀ1; H NMR (500 MHz,
CDCl3) d 9.27 (dd, 1H, JNH;5 ¼ 9:0, JNH;HC@ ¼ 14:1,
NH), 8.13 (d, 1H, HC@), 4.79 (dd, 1H, J1;2 ¼ 4:0,
J2;3 ¼ 5:9, H-2), 4.63 (dd, 1H, J3;4 ¼ 3:4, H-3), 4.62 (d,
1H, H-1), 4.23 (q, 2H, JH;H ¼ 7:1, CH2CH3), 4.18 (m,
2H, CH2CH3), 3.80 (m, 1H, H-5), 3.35 (dd, 1H,
J4;5 ¼ 8:9, H-4), 2.66 (m, 2H, SCH2CH2CH2CH3), 1.58
(m, 2H, SCH2CH2CH2CH3), 1.35 (m, 2H,
SCH2CH2CH2CH3), 1.52, 1.32 (each s, each 3H,
(CH3)2C), 1.37 (d, 3H, J5;6 ¼ 6:8, H-6), 1.33, 1.27 (each
t, each 3H, 2CH2CH3), 0.87 (t, 3H, JH;H ¼ 7:4,
SCH2CH2CH2CH3); 13C NMR (125.7 MHz, CDCl3) d
169.4, 166.0 (2C@O), 159.1 (CH@), 113.2 [C(CH3)2],
89.4 (C@), 87.7 (C-1), 84.1 (C-4), 82.6 (C-2), 79.9 (C-3),
59.6, 59.4 (2CH2CH3), 54.5 (C-5), 32.2 (SCH2)CH2),
32.0 (SCH2), 21.7 (SCH2CH2CH2), 25.8, 24.9 [(CH3)2C],
4.6.1. Ethyl 6-O-benzoyl-5-deoxy-5-N-(2,2-diethoxycar-
bonylvinylamine)-2,3-O-isopropylidene-1-thio-a-L-gulo-
furanoside, 6. Column chromatography (CH2Cl2,
CH2Cl2/MeOH, 100:1). Yield 73% as amorphous
23
D
solid; ½aŠ ¼ þ37 (c 1.5, CH2Cl2); EIMS m=z 537 Mþ;
IR 3265, 2980, 2934, 2872, 1723, 1656, 1608, 1451, 1379,
1270, 713 cmꢀ1; 1H NMR (500 MHz, CDCl3) d 9.54 (dd,
1H, JNH;5 ¼ 9:0, JNH;HC@ ¼ 14:0, NH), 8.16 (d, 1H,
HC@), 8.04–7.42 (m, 5H, Ph), 4.80 (dd, 1H, J1;2 ¼ 4:0,
J2;3 ¼ 6:0, H-2), 4.71 (dd, 1H, J3;4 ¼ 3:5, H-3), 4.69 (m,
1H, H-6a), 4.66 (d, 1H, H-1), 4.47 (dd, 1H, J5;6b ¼ 4:0,
J6a;6b ¼ 12:0, H-6b), 4.22, 4.16 (each q, each 2H,
JH;H ¼ 7:5, 2CH2CH3), 4.07 (m, 1H, H-5), 3.68 (dd, 1H,
J4;5 ¼ 8:5, H-4), 2.67 (m, 2H, SCH2), 1.51 (s, 3H,
(CH3)2C), 1.31 (t, 3H, CH2CH3), 1.28 (s, 3H, (CH3)2C),
1.25 (t, 6H, CH2CH3, SCH2CH3); 13C NMR
(125.7 MHz, CDCl3) d 169.3 (C@O benzoyl), 166.2,
165.8 (2C@O), 160.0 (CH@), 133.6–128.6 (Ar), 113.7
(C(CH3)2), 90.8 (C@), 87.7 (C-1), 82.8 (C-2), 80.2 (C-4),
79.8 (C-3), 64.5 (C-6), 60.0, 59.7 (2CH2CH3), 58.3 (C-5),
26.6 (SCH2CH3), 25.9, 24.9 [(CH3)2C], 15.5 (SCH2CH3),
14.6, 14.5 (2CH2CH3); HREIMS m=z obsd 537.2035
calcd for C26H35NO9S 537.2033.
17,3
(C-6),
14.4,
14.3
(2CH2CH3),
13.5
(SCH2CH2CH2CH3); HREIMS m=z obsd 445.2135
calcd for C21H35NO7S 445.2134.
4.6.4. 4-Buthylthio 5,6-di-deoxy-5-N-(2,2-diethoxycar-
bonylvinylamine)-2,3-O-isopropylidene-1-thio-a-D-gulo-
furanoside, 14. Column chromatography (CH2Cl2,
CH2Cl2/MeOH, 100:1). Yield 64% as amorphous
24
D
solid; ½aŠ ¼ ꢀ56 (c 1.0, CH2Cl2); FABMS m=z 500
[(M+Na)þ]; IR 3304, 2988, 2933, 2853, 2147, 1684, 1654,
1
1616, 1426, 1374, 1283, 750 cmꢀ1; H NMR (500 MHz,
CDCl3) d 9.29 (dd, 1H, JNH;5 ¼ 8:0, JNH;HC@ ¼ 14:0,
NH), 8.12 (d, 1H, HC@), 4.79 (dd, 1H, J1;2 ¼ 3:9,
J2;3 ¼ 6:0, H-2), 4.63 (dd, 1H, J3;4 ¼ 3:5, H-3), 4.62 (d,
1H, H-1), 4.22 (q, 2H, JH;H ¼ 7:1, CH2CH3), 4.17 (m,
2H, CH2CH3), 3.80 (m, 1H, H-5), 3.35 (dd, 1H,
J4;5 ¼ 8:9, H-4), 2.67 (m, 2H, SCH2CH2CH2CH2SH),
2.50 (m, 2H, SCH2CH2CH2CH2SH), 1.73–1.69 (m, 4H,
SCH2CH2H2CH2SH), 1.52 (s, 3H, (CH3)2C), 1.38 (d,
3H, J5;6 ¼ 6:7, H-6), 1.34 (t, 3H, 2CH2CH3), 1.32 (s, 3H,
(CH3)2C), 1.29 (t, 3H, 2CH2CH3); 13C NMR
(125.7 MHz, CDCl3) d 169.7, 166.4 (2C@O), 159.4
(CH@), 113.5 [C(CH3)2], 89.8 (C@), 88.0 (C-1), 84.5 (C-
4), 82.8 (C-2), 80.1 (C-3), 59.9, 59.7 (2CH2CH3), 54.8 (C-
5), 33.1 (SCH2CH2), 32.0 (SCH2), 29.1 (SCH2CH2CH2),
26.1, 25.2 [(CH3)2C], 24.3 (SCH2CH2CH2CH2SH), 17.5
4.6.2. Ethyl 5,6-di-deoxy-5-N-(2,2-diethoxycarbonyl-
vinylamine)-2,3-O-isopropylidene-1-thio-a-D-gulofurano-
side, 12. Column chromatography (CH2Cl2, CH2Cl2/
MeOH, 100:1). Yield 73% as amorphous solid;
24
D
½aŠ ¼ ꢀ49 (c 0.9, CH2Cl2); FABMS m=z 440
[(M+Na)þ]; IR 3331, 2984, 2926, 2862, 1701, 1654, 1611,
1424, 1364, 1277, 748 cmꢀ1
;
1H NMR (500 MHz,
CDCl3) d 9.27 (dd, 1H, JNH;5 ¼ 8:0, JNH;HC ¼ 14:0, NH),
8.13 (d, 1H, HC@), 4.79 (m, 1H, H-2), 4.64 (d, 1H,
J1;2 ¼ 4:0, H-1), 4.62 (dd, 1H, J3;4 ¼ 3:5, H-3), 4.23, 4.17

ꢀ
2010
M. A. Pradera et al. / Tetrahedron: Asymmetry 15 (2004) 2003–2010
5. For a recent review see: Lillelund, V. H.; Jensen, H. H.;
Liang, X.; Bols, M. Chem. Rev. 2002, 102, 515–553.
6. (a) Fuentes, J.; Olano, D.; Gasch, C.; Pradera, M. A.
Tetrahedron: Asymmetry 2000, 11, 2471–2482; (b) Babiano
(C-6), 14.7, 14.6 (2CH2CH3); HREIMS m=z obsd
477.1848 calcd for C21H35NO7S2 477.1855.
ꢀ
Caballero, R.; Fuentes Mota, J.; Galbis Perez, J. A.
Carbohydr. Res. 1986, 154, 208–288; For a review see: (c)
4.6.5. (4-Methoxy)phenyl 5,6-di-deoxy-5-N-(2,2-dieth-
oxycarbonylvinylamine)-2,3-O-isopropylidene-1-thio-a-D-
gulofuranoside, 15. Amorphous solid. Yield 40%;
ꢀ
Garcıa Fernandez, J. M.; Ortiz Mellet, C. Adv. Carbohydr.
Chem. Biochem. 1999, 55, 35–135.
ꢀ
22
D
½aŠ ¼ þ42 (c 1.3, CH2Cl2); FABMS m=z 518
7. For a review see: Garegg, P. J. Adv. Carbohydr. Chem.
Biochem. 1997, 52, 179–205.
[(M+Na)þ]; IR 3433, 2984, 2936, 1648, 1603, 1489, 1381,
1
1279, 1242, 752 cmꢀ1; H NMR (500 MHz, CDCl3) d
8. Zhang, Z.; Ollmann, I. R.; Ye, X.-S.; Wischnat, R.; Baarov,
T.; Wong, Ch.-H. J. Am. Chem. Soc. 1999, 121, 734–753.
9. See as examples: (a) Crich, D.; Li, H. J. Org. Chem. 2002,
67, 4640–4646; (b) Crich, D.; Mora, M. de la; Vinod, A.
U. J. Org. Chem. 2003, 68, 8142; (c) Das, S. K.; Roy, J.;
Reddy, K. A.; Abbieni, C. Carbohydr. Res. 2003, 338,
2237–2240; (d) Van der Klein, P. A. M.; Boons, G. J. P.
H.; Veeneman, G. H.; Van der Marel, G. A.; Van Boom,
J. H. Synlett 1990, 311–313.
10. (a) Brennan, P. J.; Nikaido, H. Annu. Rev. Biochem. 1995,
64, 29–63; (b) Lederkremer, R. M.; Colli, W. Glycobiology
1995, 5, 547–552.
11. Ayer, W. A.; Kawahara, N. Tetrahedron Lett. 1995, 36,
7953–7956.
12. Kils, F. M. New Compr. Biochem. 1995, 29a, 511.
9.30 (dd, 1H, JNH;5 ¼ 7:5, JNH;HC@ ¼ 14:0, NH), 8.23 (d,
1H, HC@), 7.48–6.77 (m, 4H, Ar), 4.89 (dd, 1H,
J1;2 ¼ 4:0, J2;3 ¼ 6:0, H-2), 4.71 (d, 1H, H-1), 4.65 (dd,
1H, J3;4 ¼ 3:5, H-3), 4.23–4.20 (each q, each 2H,
JH;H ¼ 7:0, 2CH2CH3), 3.86 (m, 1H, H-5), 3.77 (s, 3H,
OMe), 3.33 (dd, 1H, J4;5 ¼ 9:0, H-4), 1.58, 1.35 (each s,
each 3H, [(CH3)2C]), 1.39 (d, 3H, J5;6 ¼ 6:5, H-6), 1.35,
1.28 (each t, each 3H, 2CH2CH3); 13C NMR
(125.7 MHz, CDCl3) d 169.5, 166.1 (2C@O), 159.7–
114.5 (Ar), 159.4 (CH@), 113.5 [C(CH3)2], 90.8 (C-1),
89.7 (C@), 84.4 (C-4), 82.5 (C-2), 80.0 (C-3), 59.7, 59.6
(2CH2CH3), 55.3 (OCH3), 54.3 (C-5), 26.0, 25.2
[(CH3)2C], 16.8 (C-6), 14.5, 14.4 (2CH2CH3); HREIMS
m=z obsd 495.1936 calcd for C24H33NO8S 495.1927.
ꢂ
13. Gelin, M.; Ferrieres, V.; Plusquellec, D. Eur. J. Org.
Chem. 2000, 1423–1431.
14. See as examples: (a) Cociorva, O. M.; Lowary, T. L.
Tetrahedron 2004, 60, 1481–1489; (b) Pathak, A. K.;
Pathak, V.; Kulshrestha, M.; Kinnaird, D.; Suling, W. J.;
Gurcha, S. S.; Besra, G. S.; Reynolds, R. C. Tetrahedron
2003, 59, 10239–10248; (c) D’Souza, F. W.; Cheshev,
P. E.; Ayers, J. D.; Lowary, T. L. J. Org. Chem. 1998, 63,
9037–9044.
15. Misra, A. K.; Agnihotri, G. Carbohydr. Res. 2004, 339,
885–890.
16. Bozo, E.; Boros, S.; Kuszmann, J. Carbohydr. Res. 1998,
311, 191–202.
Acknowledgements
ꢀ
~
We thank the Direccion General de Ensenanza Superior
ꢀ
ꢀ
e Investigacion Cientıfica of Spain and the Junta de
Andalucia for financial support (grant numbers
BQU2001-3740 and FQM-134), and the Ministerio de
ꢀ
Educacion Cultura y Deporte, and the Fundacion
Camara of the University of Seville, for the award of
fellowships to F.J.S., and J.M.I., respectively.
ꢀ
ꢀ
17. Pradera, M. A.; Sayago, F. J.; Illangua, J. M.; Gasch,
C.; Fuentes, J. Tetrahedron Lett. 2003, 44, 6605–
6608.
References and notes
1. Pradera, M. A.; Olano, D.; Fuentes, J. Tetrahedron Lett.
1995, 36, 8653–8656.
2. Fuentes, J.; Olano, D.; Pradera, M. A. Tetrahedron:
Asymmetry 1997, 8, 3443–3456.
3. Pradera, M. A.; Olano, D.; Sayago, F. J.; Gasch, C.;
Illangua, J. M.; Repetto, G.; Fuentes, J. Communicated at
23rd IUPAC International Symposium on the Chemistry of
Natural Products, Florence, Italy, 2002. Book of abstracts,
communication P73, p199.
4. Fuentes, J.; Gasch, C.; Olano, D.; Pradera, M. A.;
Repetto, G.; Sayago, F. J. Tetrahedron: Asymmetry
2002, 13, 1743–1753.
18. Fuentes, J.; Sayago, F. J.; Illangua, J. M.; Gasch, C.;
Angulo, M.; Pradera, M. A. Tetrahedron: Asymmetry
2004, 15, 603–615.
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