Regioselective synthesis and biological evaluation of spiro-sulfamidate glycosides from exo-glycals

Article abstract of DOI:10.1016/j.tetasy.2009.07.012

We report the synthesis of spiro-sulfamidate glycosides from exo-glycals. This route is regioselective and furnishes an original class of spiro-hydantoin glycoside analogues. A biological evaluation of this family on a range of glycosidases shows that these compounds are weak but very selective inhibitors of α-glucosidase and amyloglucosidase.

Full text of DOI:10.1016/j.tetasy.2009.07.012

Tetrahedron: Asymmetry 20 (2009) 1817–1823
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Regioselective synthesis and biological evaluation of spiro-sulfamidate
glycosides from exo-glycals
Mahmoud Benltifa a, Miklos De Kiss b, Maria Isabel Garcia-Moreno c, Carmen Ortiz Mellet c,
a,
David Gueyrard b, , Anne Wadouachi
*
*
a Laboratoire des Glucides, UMR CNRS 6219, Université de Picardie Jules Verne, 33 Rue Saint-Leu, F-80039 Amiens, France
b Université de Lyon, ICBMS, Laboratoire de Chimie Organique 2-Glycochimie, UMR 5246, Université Claude Bernard Lyon 1-CNRS, Bâtiment 308(CPE),
43 Boulevard du 11 novembre 1918, F-69622 Villeurbanne, France
c Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, C/ Profesor García González,1, E-41012 Sevilla, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
We report the synthesis of spiro-sulfamidate glycosides from exo-glycals. This route is regioselective and
furnishes an original class of spiro-hydantoin glycoside analogues. A biological evaluation of this family
Received 9 June 2009
Accepted 7 July 2009
Available online 10 August 2009
on a range of glycosidases shows that these compounds are weak but very selective inhibitors of
cosidase and amyloglucosidase.
a-glu-
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
the case of the b-anomer, leading to the corresponding b-spiro-sul-
famidates. Furthermore, these syntheses were only limited to 2-
deoxysugar derivatives.
Glycosylidene-spiro-heterocycles are compounds of interest and
have attracted considerable attention.1 For example, the natural
spiro-nucleoside (+)-hydantocidin A, isolated from a culture of
Streptomyces hygroscopicus, exhibits non-toxically herbicidal and
regulatory plant growth activities,2 and an inhibitory activity of its
50-phosphorylated metabolite against adenylosuccinate synthase
has been observed.3 Other sugar heterocycles related to hydantoci-
din A havebeen synthesized. Spiro-oxathiazole B,4 spiroisoxazolines
C,5 spiro-hydantoin D,6 and spiro-(thio)hydantoin E7 glucosides
have shown good inhibitory activities on glycogen phosphorylase
(Fig. 1). More recently spiro-isoxazoline-C-disaccharides have
Considering the potential biological activities of spiro-heterocy-
clic glycosides, we focused our interest on the synthesis of spiro-sul-
famidate glycosides via a synthetic pathway involving activation by
the Burgess reagent of an intermediate diol obtained from methy-
lene exo-glycals. This reagent is known as a mild and selective
dehydrating agent of secondary and tertiary alcohols to afford the
corresponding olefins.11 It has been used in the synthesis of hetero-
cyclic systems,12 and as a source of heteroatoms in the synthesis of
urethanes,13 sulfamidates,14 sulfamides,15 and disulfides.16
Thus, exo-glycals,17 which are useful intermediates for the syn-
thesis of C-glycosides,18 C-disaccharides,19 and natural products,2d
can be readily obtained using our recently reported methodol-
ogy.20 We recently developed the synthesis of methylene20a or
substituted20b exo-glycals from sugar-derived lactones by employ-
ing Julia-Kocienski reagents.21
shown inhibitions against a-amylase, and other a- and b-glucosi-
dases.8 The synthesis of spirobicyclic compounds requires regio-
and stereoselective reactions that can be induced by the structure
and the natural chirality of sugars. For example, intramolecular
radical-based cyclization involving the anomeric center and the
nucleobase of a modified nucleoside9 or 1,3-dipolar cycloaddition
of exo-glycals5 has been studied for such transformation.
2. Results and discussion
Intramolecular metal-catalyzedaminationof the pseudo-anomer-
ic C–H bond in C-glycoside carbamate and sulfamate esters has been
usedtosynthesize spiro-oxazolidinesandspiro-sulfamidates, respec-
tively.10 Whereas the cyclization of carbamoyloxymethyl glycosides
The starting materials, hept-2-ulopyranoses 2a–c22 and hex-2-
ulofuranoses 2d–e, were prepared by a dihydroxylation reaction
of the corresponding methylene exo-glycals 1a–e, using a combina-
tion of OsO4 and N-methylmorpholidine N-oxide (NMO) as co-oxi-
dant (Scheme 1).23
gives the corresponding
a- and b-spirooxazolidines, the analogous
cyclization of sulfamoyloxymethyl glycosides was successful only in
The osmylation of the benzylated pyranosidic exo-glycals 1a and
1c was performed, the 1H NMR and 13C NMR indicate that the result-
ing products are a-epimers. In the case of acetylated exo-glucal 1b
and furanic exo-glycals 1d–e, C-2 epimeric mixtures were obtained
which could not been separated by chromatography. We first
* Corresponding authors. Tel.: +33 4 72 44 83 49; fax: +33 4 72 44 81 83 (D.G.);
tel.: +33 3 22 82 75 27; fax: +33 3 22 82 75 60 (A.W.).
E-mail addresses: david.gueyrard@univ-lyon1.fr (D. Gueyrard), anne.wadouachi@
u-picardie.fr (A. Wadouachi).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.07.012

1818
M. Benltifa et al. / Tetrahedron: Asymmetry 20 (2009) 1817–1823
Table 1
O
HO
HN
HO
HO
HO
Optimization of the synthesis of spiro-sulfamidates 5a and 6a from 2a
O
O
O
S
NH
HO
BnO
BnO
BnO
Ar
Ar
HO
HO
O
O
BnO
BnO
BnO
+
O
HO
HO
O
O
O
O
S
N
N
S
OH
HO
OH
Et3N
NR
O
BnO
BnO
RN
A
B
C
OH
S
O
O
5a R=CO2tBu
6a R=CO2Me
3 R=CO2tBu
4 R=CO2Me
2a
HO
HO
HO
H
N
H
O
O
N
HO
HO
HO
O
HO
O
HO
O
Entry
Burgess reagent
Equiv
Ta (°C)
Time
Product (yield%)
N
N
H
H
1
2
3
4
5
6
3
3
3
4
4
4
2.5
2.5
4
2.5
2.5
4
rt
24
2
2
24
2
2
5a (10)
5a (35)
5a (73)
6a (17)
6a (41)
6a (93)
D
E
Reflux
Reflux
rt
Reflux
Reflux
Figure 1.
R1
O
R1
O
R3O
R3O
R3O
R3O
R3O
R3O
a
The reactions were conducted in THF.
(i)
OH
R2
R2
OH
1a R1=H, R2=OBn, R3=Bn
1b R1=H, R2=OAc, R3=Ac
1c R1=OBn, R2=H, R3=Bn
2a R1=H, R2=OBn, R3=Bn 94 % (α)
Comparison of the 1H NMR spectra of 6c-
a
and 6c-b revealed
2b R1=H, R2=OAc, R3=Ac 90% (α+β)
2c R1=OBn, R2=H, R3=Bn 90% (α)
that the latter adopts a conformation of the pyranose ring from
5C8, due to a probable equilibrium between the 5H4 and 4H5 half-
chair conformations of oxocarbenium ions (Scheme 6). This change
of conformation has already been reported in guanofosfocin ana-
logues25 and glycosylations of restricted mannuronate esters.26
Glycosidation of heptulopyranose donors has been reported from
TBDPSO
O
TBDPSO
OH
O
(i)
OH
O
O
O
O
benzylated compounds27 and exclusively gave
a-linked ketodisac-
2d 88% (α+β)
1d
charide. The authors concluded that the stereochemical course of
the glycosylation is neither governed by the type of promoter,
nor by the nature of the leaving or protecting group at the C-2
and O-1 positions. They evaluated the effect of the ester group at
C-3 and obtained an anomeric mixture. They proposed that these
reactions proceed via an intermediate oxonium ion. The stereo-
chemical outcome is mainly determined by the anomeric effect
and steric factors.
BnO
BnO
O
OH
(i)
O
BnO
BnO
OH
BnO
BnO
2e 96% (α+β)
1e
Scheme 1. Osmylation of exo-glycals. Reagents and condition: (i) OsO4/NMO,
acetone–H2O (5/2), rt.
The acetylated hept-2-ulopyranose 2b furnished a complex
mixture when reacted with the Burgess-type reagent 3 or 4.
The two hex-2-ulofuranose derivatives 2d and 2e also gave the
corresponding spiro-sulfamidates as diastereoisomeric mixture
optimized the cyclic sulfamidation of the diol 2a (Table 1) with tert-
butyl and methyl N-(triethylammoniumsulfonyl)carbamates 314a
and 4, respectively.
The Burgess reagents 3 and 4 are oxidation and moisture sensi-
tive.24 Reactions were carried out at room temperature for very
long time and furnished the corresponding spiro-sulfamidates 5a
and 6a in very low yields (entries 1 and 4). In refluxing THF for
2 h, the yields increased and reached to 73% and 93%, respectively,
with 4 equiv of Burgess reagents (entries 3 and 6). The sulfamida-
(Scheme 3). The
a,b mixture resulted in a nucleophilic attack by
the nitrogen anion on a five-membered ring oxocarbenium ion
which adopts a folded conformation28 but showed no stereoselec-
tive nucleophilic substitution.
The full assignment of the protons has been performed using
the combination of standard 2D experiments such as COSY, HSQC,
and HMBC. Furthermore, the anomeric configuration has been
tion of 3,4,5,7-tetra-O-benzyl-
was selective and gave only the corresponding
a
-
D
-gluco-hept-2-ulopyranose 2a
-spiro-sulfami-
a
determined by 2D NMR spectroscopy. For example, in the D-gluco
series, NOESY experiment shows a correlation between H-1, H-10
and H-3 which prove that the nitrogen atom is axial.
dates. The heterocyclization involves a di-sulfonated intermediate
I as shown in Scheme 2, which undergoes an intramolecular nucle-
ophilic attack of the nitrogen anion on the more electrophilic cen-
ter of the cyclic sulfamidate. The heterocyclization proceeds most
likely by an SN1-type mechanism, with the formation of an
oxocarbenium ion II.
Similarly, the stereochemistry at the anomeric center has been
proven by NOESY experiments for each series of compounds.
NOESY correlations are listed in Figure 2.
From compound 5a, deprotection of N-Boc with TFA in dichloro-
methane gave compound 7, which was debenzylated by catalytic
hydrogenation to afford the spiro-sulfamidate 8 in quantitative
yield. The N-methoxycarbonyl protected spiro-sulfamidate 6a
Under the above-mentioned optimal conditions, spiro-sulfami-
date 6c was synthesized in 66% yield as a separable mixture of
and b anomers (Scheme 2).
a
O
O
O
O
BnO
S
OBn
BnO
BnO
BnO
OBn
O
N
BnO
BnO
BnO
O
OBn
O
O
(i)
+
O
OH
OBn
S
O
N
O
OH
OBn
O
2c
O
6c α (53%)
6c β (13%)
Scheme 2. Reagents: (i) 4 (4 equiv)/THF, reflux.

M. Benltifa et al. / Tetrahedron: Asymmetry 20 (2009) 1817–1823
1819
O
N
O
S
O
O
TBDPSO
TBDPSO
TBDPSO
+
OH
OH
O
O
O
(i)
O
O
S
O
N
O
O
O
O
O
O
O
O
O
2d
6d- β 15%
6d- α 35%
O
O
S
O
BnO
BnO
OH
O
O
O
O
BnO
BnO
N
(ii)
O
BnO
O
S
+
OH
N
BnO
O
O
BnO
BnO
O
BnO
O
2e
5e- α 42%
5e- β 45%
Scheme 3. Reagents: (i) 4 (4 equiv)/THF, reflux; (ii) 3 (4 equiv)/THF, reflux.
(b-glucosidase/
sults confirm that compound 8 behaves as glucomimetic. This
selectivity toward the -glucosidases is in agreement with the
a-L-rhamnosidase, Penicillium decumbes). These re-
OBn
H
H
S
O
H
O
BnO
BnO
a
D-glucopyrano
BnO
linkage specificity previously encountered in spiro-glycosides.29
Interestingly, the inhibition was totally abolished for the N-
methoxycarbonyl derivative 9, a strong influence of the presence
of N-substituent on the biological activity was observed. This fact
pointed out that the anomeric NH group can be establishing hydro-
gen bond interactions with complementary groups in the active
site of glucosidases. On the other hand, the five-membered cyclic
sulfamide group seems to be particularly well adapted for interact-
ing with amino acids of proteins, which offers a possibility for fur-
ther improvement of the molecular design (see Scheme 5).
N
O
O
O
O
O
O
S
O
O
OBn N
H
OBn
OBn
O
O
OBn
H
H
H
O
H
BnO
O
D-mannopyrano
H
BnO
OBn
H
H
H
N
OBn
H
S
H
O
O
O
O
H
H
3. Conclusion
O
BnO
D-arabinofurano
O
O
BnO
We have developed an original and regioselective route to
spiro-sulfamidate glycosides from exo-glycals. This method was
shown to occur with diverse sugar series (furanose and pyranose)
and different types of protective groups, such as silyl and benzyl
ethers and/or isopropylidene. In each case, the stereochemistry at
the anomeric center has been determined by NMR experiments. Fi-
nally, two spiro-sulfamidates were tested on a range of glycosi-
dases and they have shown a weak but very selective activity
O
O
O
O
S
H
BnO
O
N
S
N
O
BnO
H
O
H
OBn
H
H
O
O
H
H
H
H
OBn
H
H
O
against a-glucosidase and amyloglucosidase.
H
O
O
O
H
H
O
TBDPSO
D-ribofurano
O
TBDPSO
O
N
S
O
O
O
4. Experimental
4.1. General
S
O
H
H
H
H
N
H
H
H
O
O
O
O
O
All chemicals were purchased from Aldrich or Acros (France).
Thin-layer chromatography (TLC) was performed on Silica Gel 60
F254 (Merck) plates with visualization by UV light (254 nm) and/
or charring with a vanillin-H2SO4 reagent. Preparative column
chromatography was performed using 230–400 mesh Merck silica
gel (purchased from Aldrich). Optical rotations were determined
with a Jasco Dip 370 electronic micropolarimeter (10 cm cell). 1H
and 13C NMR spectra were recorded on a Bruker 300 WB spectrom-
eter at 300 MHz and 75 MHz, respectively, and Noesy experiments
were recorded using Bruker Avance DRX500. Chemical shifts are
given as d values with reference to tetramethylsilane (TMS). Low
resolution electrospray mass spectra (ESI-MS) in the positive ion
mode were obtained on a Waters-Micromass ZQ quadrupole
instrument, equipped with an electrospray (Z-spray) ion source
(Waters-Micromass, Manchester, UK). High resolution electrospray
Figure 2. Noesy correlations of spiro-sulfamidates 5a, 6c, 6d, and 5e.
was also debenzylated using the same conditions to furnish 9 in
93% yield (Scheme 4).
The two spiro-sulfamidates 8 and 9 were assayed against a pa-
nel of glycosidases. The spiro-sulfamidate 8 behaved as a selective
but weak competitive inhibitor of both
(maltase, Ki 190 M) and amyloglucosidase from Aspergillus Niger
(Ki 258 M). No inhibition was observed against b-glucosidase
a-glucosidase from yeast
l
l
(from almonds), b-glucosidase/b-galactosidase (from bovine liver,
cytosolic), trehalase (from pig kidney), isomaltase (from yeast),
a
-galactosidase (from green coffee beans),
a-mannosidase (from
Jack beans), b-mannosidase (from Helix pomatia), or naringinase

1820
M. Benltifa et al. / Tetrahedron: Asymmetry 20 (2009) 1817–1823
BnO
BnO
BnO
HO
HO
HO
BnO
BnO
BnO
O
O
O
(i)
(ii)
O
O
O
BnO
HO
BnO
S
N
S
N
N
S
O
O
O
O
H
H
O
O
O
O
7
8
5a
HO
HO
HO
BnO
O
O
(ii)
BnO
BnO
O
O
HO
BnO
O
S
N
S
N
O
O
O
O
O
O
O
6a
9
Scheme 4. Reagents and conditions: (i) TFA–CH2Cl2 (1/3), rt, quant; (ii) H2, Pd/C, MeOH, rt, quant.
O
S
O
S
BnO
BnO
BnO
O
O
+
BnO
BnO
O
OBn
SN1
O
O
OBn
O
O
S
BnO
O
O
BnO
OH
O
BnO
BnO
Et3N
NR
BnO
BnO
BnO
NR
NR
BnO
OH
5H4
BnO
O
O
2a
NR
S
RN
S
O
O
O
O
I
II
BnO
O
BnO
BnO
O
BnO
RN
S
O
O
5a-6a
Scheme 5.
OBn
BnO
BnO
BnO
OBn
O
BnO
4
OBn
8
7
O 6
OBn
O 3
5
10
9
N
1
S
O 2
O
O
5H4
O
O
O
S
NR
S
O
O
Et3N
NR
O
OBn
O
α53%
BnO
BnO
BnO
4 R=CO2Me
+
OH
SN1
2c
manno
OH
5C2
O
O
O
O
OBn
BnO
S
OBn
N
BnO
O
OBn
O
O
OBn
4H5
OBn
RNO2SO
OBn
β 13%
Scheme 6.
experiments (ESI-HRMS) were performed on a Waters-Micromass
Q-TOF Ultima Global hybrid quadrupole time-of-flight instrument,
equipped with an electrospray (Z-spray) ion source (Waters-
Micromass, Manchester, UK). All solvents were distilled before use.
against the respective o- (for b-glucosidase/b-galactosidase from
bovine liver) or p-nitrophenyl - or b- -glycopyranoside or
trehalose (for trehalase), in the presence of the corresponding
a
D
a, -
a0
spiro-sulfamidate derivative. Each assay was performed in phos-
The glycosidases
a-glucosidase (from yeast), b-glucosidase
phate buffer or phosphate-citrate buffer (for a- or b-mannosidase
(from almonds), b-glucosidase/b-galactosidase (from bovine liver,
and amyloglucosidase) at the optimal pH for each enzyme. The
cytosolic), trehalase (from pig kidney), isomaltase (from yeast),
Km values for the different glycosidases used in the tests and the
amyloglucosidase (from A. Niger),
a
-galactosidase (from green cof-
corresponding working pHs are listed herein: a-glucosidase
fee beans), -mannosidase (from Jack beans), b-mannosidase (from
a
(yeast), Km = 0.35 mM (pH 6.8); isomaltase (yeast) Km = 1.0 mM
(pH 6.8), b-glucosidase (almonds), Km = 3.5 mM (pH 7.3); b-gluco-
sidase/b-galactosidase (bovine liver), Km = 2.0 mM (pH 7.3);
H. pomatia), and naringinase (P. decumbes) used in the inhibition
studies, as well as in the corresponding o- and p-nitrophenyl
glycoside substrates were purchased from Sigma Chemical Co.
Inhibitory potencies were determined by spectrophotometrically
measuring the residual hydrolytic activities of the glycosidases
a-galactosidase (coffee beans), Km = 2.0 mM (pH 6.8); trehalase
(pig kidney), Km = 4.0 mM (pH 6.2); amyloglucosidase (A. niger),
Km = 3.0 mM (pH 5.5); b-mannosidase (H. pomatia), Km = 0.6 mM

M. Benltifa et al. / Tetrahedron: Asymmetry 20 (2009) 1817–1823
1821
(pH 5.5);
a
-mannosidase (jack bean), Km = 2.0 mM (pH 5.5); narin-
4 (264 mg, 1.1 mmol), 178.1 mg (93%) of 6a was obtained as a col-
ginase (P. decumbes), Km = 2.7 mM (pH 6.8). The reactions were ini-
tiated by the addition of the enzyme to a solution of the substrate
in the absence or presence of various concentrations of the inhib-
itor. After the mixture was incubated for 10–30 min at 37 or
55 °C, the reaction was quenched by the addition of 1 M Na2CO3
or a solution of Glc-Trinder (Sigma, for trehalase). The absorbance
of the resulting mixture was determined at 405 nm or 505 nm. The
Ki value and enzyme inhibition mode were determined from the
slope of Lineweaver–Burk plots and double reciprocal analysis
using a Microsoft Office Excel 2003 program.
orless syrup: [
a]
D = ꢁ8 (c 0.1, CHCl3). 1H NMR (300 MHz, CDCl3): d
7.40–7.23 (m, 20H, Harom), 4.98 (d, 1H, J = 9.6 Hz, H-4a), 4.92–4.55
(m, 8H, 4 ꢀ CH2Ph), 4.61 (d, 1H, J = 9.6 Hz, H-4b), 3.90–3.3 (m, 4H,
CH3O, CHOBn, H8), 3.77 (dd, 1H, J = 11.5 Hz, J = 1.5 Hz, CHOBn),
3.61 (m, 1H, H-7), 3.53 (t, 1H J = 9.7 Hz, H-9). 13C NMR (75 MHz,
CDCl3): d 149.3 (C@O (CO2Me)), 138.2, 137.9, 137.7, 137.1 (4 ꢀ CAr),
128.5, 128.4, 128.2, 128.1, 128.0, 127.8, 127.7 (CArH), 92.4 (C-5),
83.3 (C-9), 76.8 (C-8), 76.3 (C-10), 75.9, 75.5, 75.4 (3 ꢀ CH2Ph),
75.2 (C-7), 73.6 (CH2Ph), 68.2 (CH2OBn), 67.7 (C-4), 54.5 (OCH3).
HRMS: [M+Na]+ calcd for C37H39NO10NaS: 712.2192, found
[M+Na]+ m/z 712.2193.
4.2. 2,4-O-Isopropylidene-6-tert-butyldiphenylsilyl-D-ribo-hex-
2-ulofuranose 2d
4.5. (5S,7R,8R,9S,10S)-8,9,10-Tribenzyloxy-7-benzyloxymethyl-3,6-
dioxa-1-methoxycarbonyl-2-thia-1-azaspiro[4.5]decan-2,2-dioxide
Following the procedure of osmylation as described in Ref. 23b,
compound 2d was isolated with 88% yield as a mixture of anomers
(522.6 mg from 550 mg of 1d). Colorless amorphous solid. 1H NMR
(300 MHz, CDCl3): d 7.78–7.65 (m, 4H, Ph), 7.53–7.38 (m, 6H, Ph),
6c-a and (5R,7R,8R,9S,10S)-8,9,10-tribenzyloxy-7-benzyloxymethyl-
3,6-dioxa-1-methoxycarbonyl-2-thia-1-azaspiro-[4.5]decan-2,2-di
oxide 6c-b
4.91 (dd, 1H, J = 6.92 Hz, J = 4.1 Hz, H-4
J = 1.1 Hz, H-4b), 4.80 (d, 1H, J = 6.95 Hz, H-3
5.9 Hz, H-3b), 4.32 (m, 1H, H-5 ), 4.26 (m, 1H, H-5b), 3.93–3.68
, H1ab, H1bb, H6a , H6b , Y6ab, H6bb), 1.64,
), 1.53, 1.36 ((2CH3, b)), 1.15 (s, 9H, tBu b), 1.15 (s,
). 13C NMR (75 MHz, CDCl3): d 135.8–135.6 (CArH),
), 112.7 (CIVb),
), 86.5 (C-3b), 86.2 (C-5b), 82.8 (C-4b),
), 65.8, 63.8 (C-1 , C-6 ), 65.3, 64.5 (C-1b,
,b), 26.7 (CH3 , 26.4 (CH3b, 25.1 (CH3
a
), 4.86 (dd, 1H, J = 5.9 Hz,
Using the general procedure for preparing 5a from 3,4,5,7-
tetra-O-benzyl-a-D-manno-hept-2-ulopyranose 2c (130.7 mg,
0.23 mmol) and commercial methyl N-(triethylammoniumsulfo-
nyl)carbamate 4 (218.3 mg, 0.91 mmol), 84.6 mg (53%) of the epi-
a
), 4.67 (d, 1H, J =
a
(m, 8H, H1a
1.45 (2CH3,
a
a
, H1b
a
a
a
mer 6c-
a
and 20 mg (13%) of the epimer 6c-b were obtained as
: [
D = +36 (c 0.1, CHCl3). 1H
9H, tBu
132.0, 129.9 (Cipso), 128.0–127.9 (CArH), 115.0 (CIV
106.1 (C-2b), 103.1 (C-2
81.2 (C-3 ), 81.0 (C-4
a
colorless syrups: Compound 6c-
a
a]
a
NMR (300 MHz, CDCl3): d 7.23–7.43 (m, 20H, Harom), 5.35 (d,
1H, J = 9.8 Hz, H-4a), 4.96 (d, 1H, J = 2.4 Hz, H-10), 4.68–4.50 (m,
8H, H-4b, H-7, 3CH2Ph), 4.39 (m, 2H, CH2Ph), 3.95 (d, 1H
J = 2.5 Hz, H-9), 3.82 (s, 3H, OCH3), 3.80 (d, 1H, J = 8.6 Hz, H-8),
3.67 (dd, 1H, J = 11.5 Hz, J = 2.6 Hz, CHOBn), 3.60 (dd, 1H,
J = 11.5 Hz, J = 4.5 Hz, CHOBn). 13C NMR (75 MHz, CDCl3): d 150.7
(C@O (CO2Me)), 138.3, 137.6, 137.5, 137.0 (4 ꢀ CAr), 128.6, 128.6,
128.5, 128.4, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7 (CArH), 93.7
(C-5), 76.4 (C-8), 75.6 (C-9), 75.2 (C-7), 74.9 (C-4), 73.2, 72.6,
72.5 (3 ꢀ CH2Ph), 71.7 (C-10), 71.5 (CH2Ph), 69.4 (CH2OBn), 54.4
(OCH3). HRMS: [M+Na] calcd for C37H39NO10NaS: 712.2192, found
a
a
a
a
a
a
C-6b), 26.9 (3 ꢀ CH3
a
a,
24.9 (CH3b. HRMS: [M+Na]+ calcd for C25H34NO6NaSi: 481.2022,
found [M+Na]+ m/z 481.2024.
4.3. (5S,7R,8R,9S,10R)-8,9,10-Tribenzyloxy-7-benzyloxymethyl-
1-tert-butoxycarbonyl-3,6-dioxa-2-thia-1-azaspiro [4.5]decan-
2,2-dioxide 5a
To a solution of 3,4,5,7-tetra-O-benzyl-
a-
D-gluco-hept-2-ulo-
[M+Na] m/z 712.2186. Compound 6c-b: [a]
D = +12 (c 0.1, CHCl3). 1H
pyranose 2a (127.7 mg, 0.22 mmol) in anhydrous THF (5 mL)
was added tert-butyl N-(triethyl-ammoniumsulfonyl)carbamate
322 (251 mg, 0.89 mmol) at room temperature in a single portion.
The resulting solution was placed immediately in an oil bath at
75 °C and stirred for 2 h. Upon completion of the reaction, the sol-
vent was removed under reduced pressure and the residue was di-
luted in CH2Cl2 (30 mL), then washed with saturated aqueous
NH4Cl (15 mL). The organic phase was dried (MgSO4) and concen-
trated. The crude product was purified by flash chromatography
(cyclohexane/ethyl acetate = 7:3) to afford 5a (86 mg, 73%) as a
NMR (300 MHz, CDCl3): d 7.40–7.25 (m, 20H, Harom), 5.04 (d, 1H,
J = 10.5 Hz, CHPh), 4.93 (d, 1H, J = 10.7 Hz, CHPh), 4.77–4.54 (m, 6H,
3CH2Ph), 4.40 (2d, 2H, J = 9.5 Hz, H-4a, H-4b), 4.16 (m, 2H, H-8, H-
10), 3.98 (dd, 1H, J = 11.5 Hz, J = 4.3 Hz, CHOBn), 3.77 (m, 2H, H-9,
CHOBn) 3.53 (m, 1H, H-7), 3.41 (s, 3H, OCH3). 13C NMR (75 MHz,
CDCl3): d 150.2 (C@O (CO2Me)), 138.3, 137.8, 137.4, 137.3 (4 ꢀ CAr),
128.7, 128.6, 128.5, 128.4, 128.3, 128.1, 128.0, 127.8, 127.6 (CArH),
91.7 (C-5), 80.1 (C-9), 77.7 (C-8), 76.7 (C-7), 76.4, 75.3, 73.5, 73.3
(4 ꢀ CH2Ph), 73.1 (C-10), 71.8 (C-4), 68.9 (CH2OBn), 53.8 (OCH3).
HRMS: [M+Na]+ calcd for C37H39NO10NaS: 712.2192, found
[M+Na]+ m/z 712.2202.
colorless syrup: [a]
D = +30 (c 0.1, CHCl3). 1H NMR (300 MHz,
CDCl3): d 7.40–7.21 (m, 20H, Harom), 4.94 (d, 1H, J = 9.5 Hz, H-
4a), 4.90–4.52 (m, 9H, 4 ꢀ CH2Ph, H-10), 4.56 (d, 1H, J = 9.5 Hz,
H-4b), 3.91–3.76 (m, 3H, CH2OBn, H-8),3.57 (m, 1H, H-7), 3.46(t,
1H, J = 9.9 Hz, H-9) 1.59 (s, 9H, 3 ꢀ CH3). 13C NMR (75 MHz, CDCl3):
d 147.6 (C@O (Boc)), 138.2, 138.1, 137.7, 137.2 (4 ꢀ CAr), 128.5,
128.4, 128.2, 128.0, 127.9, 127.8, 127.7 (CArH), 92.0 (C-5), 86.4
(CIV (Boc)), 83.0 (C-9), 77.0 (C-10), 76.7 (C-8), 75.7, 75.7, 75.4
(3 ꢀ CH2Ph), 75.1 (C-7), 72.6 (CH2Ph), 68.0 (CH2OBn), 67.3 (C-4),
27.9 (3 ꢀ CH3(Boc)). HRMS: [M+Na]+ calcd for C40H45NO10NaS:
754.2662, found [M+Na]+ m/z 754.2640.
4.6. (5S,7R,8S,9S)-8,9-Dimethylmethylenedioxy-7-tert-butyldiphe
nylsilyloxymethyl-3,6-dioxa-1-methoxycarbonyl-2-thia-1-aza-
spiro[4.4]nonan-2,2-dioxide 6d-a and (5R,7R,8S,9S)-8,9-dimethyl-
methylenedioxy-7-tert-butyldiphenylsilyloxymethyl-3,6-dioxa-1-
methoxycarbonyl-2-thia-1-azaspiro[4.4]nonan-2,2-dioxide 6d-b
Using the general procedure for preparing 5a from 3,4-O-iso-
propylidene-7-O-tert-butyldiphenylsilyl-D-ribo-hex-2-ulopyranose
2d (239.3 mg, 0.52 mmol) and commercial methyl N-(triethy-
lammoniumsulfonyl)carbamate 4 (497.4 mg, 2.08 mmol) in THF
4.4. (5S,7R,8R,9S,10R)-8,9,10-Tribenzyloxy-7-benzyloxymethyl-
1-methoxycarbonyl-3,6-dioxa-2-thia-1-aza-spiro-[4.5]decan-
2,2-dioxide 6a
(10 mL), 112.8 mg (35%) of the epimer 6d-a and 49 mg (15%) of
the epimer 6d-b were obtained as colorless syrups: Compound
6d-
a
: [
a
]
D = ꢁ28 (c 0.1, CHCl3). 1H NMR (300 MHz, CDCl3): d 7.67
(m, 5H, Ph), 7.47 (m, 5H, Ph), 5.11 (dd, 1H, J = 7.2 Hz, J = 3.7 Hz,
H-8), 4.84 (d, 1H, J = 7.2 Hz, H-9), 4.76 (m, 1H, H-7), 4.43 (d, 1H,
J = 9.5 Hz, H-4a), 4.33 (d, 1H, J = 9.5 Hz, H-4b), 3.89 (m, 4H, CHOSi,
OCH3), 3.82 (dd, 1H, J = 1.9 Hz, J = 11.7 Hz, CHOSi), 1.57 (CH3), 1.43
Using the general procedure for preparing 5a from 3,4,5,7-tetra-
O-benzyl-a-D-gluco-hept-2-ulopyranose 2a (158 mg, 0.27 mmol)
and commercial methyl N-(triethylammoniumsulfonyl)carbamate

1822
M. Benltifa et al. / Tetrahedron: Asymmetry 20 (2009) 1817–1823
(CH3), 1.12 (s, 9H, tBu). 13C NMR (75 MHz, CDCl3): d 149.3 (C@O),
132.8, 132.5 (2 ꢀ CAr), 130.2, 130.1, 128.03, 128.0 (CArH), 116.2
(CIV), 98.9 (C-5), 88.8 (CIV tBu), 88.2 (C-7), 84.9 (C-9), 80.8 (C-8),
74.0 (C-4), 63.7 (CH2OSi), 54.2 (OCH3), 27.0 (3 ꢀ CH3), 25.3, 24.6
(2 ꢀ CH3). HRMS: [M+Na]+ calcd for C27H35NO9NaSSi: 600.1700,
4.9. (5S,7R,8R,9S,10R)-3,6-Dioxa-8,9,10-trihydro-xy-7-hydroxymethyl-
2-thia-1-azaspiro[4.5]decan-2,2-dioxide 8
A solution of 7 (49 mg, 0.07 mmol) in MeOH (7 mL) was hydro-
genated at atmospheric pressure for 18 h using Pd/C (10 mg) as a
catalyst. The suspension was filtered through Celite and concen-
trated. The residual syrup was purified by flash column chromatog-
raphy (ethyl acetate/methanol 4:1) to afford 8 as a colorless syrup
found [M+Na]+ m/z 600.1706. Compound 6d-b: [
a]D = ꢁ56 (c 0.1,
CHCl3). 1H NMR (300 MHz, CDCl3): d 7.69 (m, 5H, Ph), 7.44 (m,
5H, Ph), 5.14 (d, 1H, J = 6.2 Hz, H-9), 4.93 (m, 2H, H-8, H-4a), 4.57
(d, 1H, J = 10.3 Hz, H-4b), 4.31 (dd, 1H, J = 5.2 Hz, J = 11.3 Hz, H-
7), 3.77 (m, 2H, CH2OSi), 3.77 (OCH3), 1.55 (CH3), 1.38 (CH3), 1.09
(s, 9H, tBu). 13C NMR (75 MHz, CDCl3): d 149.3 (C@O), 135.7,
133.2 (2 ꢀ CAr), 129.7–127.7 (CArH), 114.3 (CIV), 98.1 (C-5), 88.8
(C-7), 86.8 (CIV tBu), 84.4 (C-9), 81.5 (C-8), 73.5 (C-4), 64.1 (CH2O-
Si), 54.6 (OCH3), 26.8 (4 ꢀ CH3), 25.3 (CH3). HRMS: [M+Na]+ calcd
for C27H35NO9NaSSi: 600.1700, found [M+Na]+ m/z 600.1683.
(20 mg, quant.): [a]
D = +26 (c 0.1, MeOH). 1H NMR (300 MHz,
CD3OD): d 4.66 (d, 1H, J 8.8 Hz, H-4b), 4.49 (d, 1H, J 8.8 Hz, H-
4a), 3.80 (m, 2H, CH2OH), 3.65 (m, 1H, H-7), 3.44 (m, 3H, H-10,
H-9, H-2). 13C NMR (75 MHz, CD3OD): d 92.9 (C-5), 76.7, 74.8 (C-
9, C-10), 74.3 (C-7), 70.7 (C-8), 69.1 (C-4), 60.4 (CH2OH). HRMS:
[M+Na]+ calcd for C7H13NO8NaS: 294.0260, found [M+Na]+ m/z
294.0268.
4.7. (5S,7R,8S,9R)-8,9-Dibenzyloxy-7-benzyloxymethyl-1-tert-butox
4.10. (5S,7R,8R,9S,10R)-8,9,10-Trihydroxy-7-hydroxymethyl-3,6-
ycarbonyl-3,6-dioxa-2-thia-1-azaspiro[4.4]nonan-2,2-dioxide 5e-
a
dioxa-1-methoxycarbonyl-2-thia-1-azaspiro[4.5]decan-2,2-dioxide 9
and (5S,7R,8S,9R)-8,9-dibenzyloxy-7-benzyloxymethyl-1-tert-butoxy
carbonyl-3,6-di-oxa-2-thia-1-azaspiro[4.4]nonan-2,2-dioxide 5e-b
Using the general procedure for preparing 8 from 6a (54.3 mg,
0.07 mmol), 34 mg of 9 was obtained as a colorless syrup: [a] =
D
Using the general procedure for preparing 5a from 3,4,6-tri-O-
+19 (c 0.1, MeOH). 1H NMR (300 MHz, CD3OD): d 4.87 (m, 2H, H-
4a et H-4b), 3.90 (s, 3H, CH3), 4.45 (d, 1H, J = 9.8 Hz, H-10), 3.86
(dd, 1H, J = 2.1 Hz, J = 12.2 Hz, CHOH), 3.71 (dd, 1H, J = 5.2 Hz,
J = 12.2 Hz, CHOH), 3.51 (ddd, 1H, J = 9.6 Hz, J = 5.2 Hz, J = 2.1 Hz,
H-7), 3.38 (m, 1H, H-8), 3.32 (m, 1H, H-9). 13C NMR (75 MHz,
CD3OD): d 151.8 (C@O), 95.8(C-5), 78.6 (C-7), 76.0 (C-9), 71.5 (C-
8), 70.9 (C-10), 69.6 (C-4), 63.4 (CH2OH), 55.5 (OCH3). HRMS:
[M+Na]+ calcd for C9H15NO10NaS: 352.0314, found [M+Na]+ m/z
352.0316.
benzyl-D-arabino-hex-2-ulopyranose 2e (206 mg, 0.46 mmol)
and tert-butyl N-(triethyl-ammoniumsulfonyl)carbamate 322
(511.8 mg, 1.83 mmol) in THF (10 mL), 117.6 mg (42%) of the epi-
mer 5e-
a
and 126 mg (45%) of the epimer 5e-b were obtained as
a colorless syrup: Compound 5e-
a: [a]
D = +36 (c 0.1, CHCl3). 1H
NMR (300 MHz, CDCl3): d 7.36 (m, 15H, Harom), 5.13 (d, 1H,
J = 8.1 Hz, H-9), 4.94 (d, 1H, J = 9.6 Hz, H-4a), 4.82–4.44 (m, 6H,
3 ꢀ CH2Ph), 4.38 (m, 2H, H-4b, H-7), 4.19 (dd, 1H, J = 8.1 Hz,
J = 8.8 Hz, H-8), 3.67 (dd, 1H, J = 2.0 Hz, J = 11.2 Hz, CHOBn), 3.46
(dd, 1H, J = 2.6 Hz, J = 11.2 Hz, CHOBn), 1.61 (s, 9H, 3 ꢀ CH3). 13C
NMR (75 MHz, CDCl3): d 147.7 (C@O), 138.9, 138.8, 136.7 (3 ꢀ CAr),
128.7, 128.5, 128.4, 128.4, 128.0, 127.8, 127.7 (CArH), 95.9 (C-5),
86.2 (CIV Boc), 83.3 (C-9), 79.8 (C-7), 79.4 (C-8), 73.6, 73.4, 72.9
(3 ꢀ CH2Ph), 71.8 (C-4), 60.0 (CH2OBn), 28.1 (3 ꢀ CH3). HRMS:
[M+Na]+ calcd for C32H37NO9NaS: 643.2087, found [M+Na]+ m/z
Acknowledgments
The authors would like to thank Dr. B. Fenet for NMR experi-
ments and Professor A. Vasella for his helpful discussion about
manno-conformers
634.2075. Compound 5e-b: [
(300 MHz, CDCl3): 7.34 (m, 15H, Harom), 4.83 (d, 1H,
a]
D = +12 (c 0.1, CHCl3). 1H NMR
References
d
J = 11.2 Hz, CHPh), 4.68–4.52 (m, 7H, H-4a, H-8, CH2Bn), 4.42 (d,
1H, J = 9.1 Hz, H-4b), 4.13 (m, 2H, H-7, H-9), 3.86 (dd, 1H,
J = 7.3 Hz, J = 10.6 Hz, CHOBn), 3.73 (dd, 1H, J = 3.6 Hz, J = 10.6 Hz,
CHOBn), 1.56 (s, 9H, 3 ꢀ CH3). 13C NMR (75 MHz, CDCl3): d 147.5
(C@O), 137.9, 137.7, 136.8 (3 ꢀ CAr), 128.5, 128.4, 128.3, 128.2,
127.8, 127.7 (CArH), 94.8 (C-5), 86.4 (C-9), 85.6 (CIV Boc), 83.4 (C-
8), 80.9 (C-7), 74.8 (C-4), 73.4, 73.2, 72.9 (3 ꢀ CH2Ph), 70.7
(CH2OBn), 27.9 (3 ꢀ CH3). HRMS: [M+Na]+ calcd for C32H37NO9NaS:
643.2087, found [M+Na]+ m/z 634. 2103.
1. (a) Gasch, C.; Pradera, M. A.; Salameh, B. A. B.; Molina, J. L.; Fuentes, J.
Tetrahedron: Asymmetry 2001, 12, 1267–1277; (b) Chang, C. F.; Yang, W. B.;
Chang, C. C.; Lin, C. H. Tetrahedron Lett. 2002, 43, 6515–6519; (c) Sayago, F. J.;
Pradera, M. A.; Gasch, C.; Fuentes, J. Tetrahedron 2006, 62, 915–921; (d) Taylor,
R. J. K.; McAllister, G. D.; Franck, R. W. Carbohydr. Res. 2006, 341, 1298–1311;
(e) Li, X.; Wang, R.; Wang, Y.; Chen, H.; Li, Z.; Ba, C.; Zhang, J. Tetrahedron 2008,
64, 9911–9920; (f) Somsak, L.; Nagy, V.; Hadady, Z.; Felfödi, N.; Docsa, T.;
Gergely, P. Front. Med. Chem. 2005, 2, 253–272.
2. (a) Haruyama, H.; Takayama, T.; Kinoshita, T.; Kondo, M.; Nakajima, M.;
Haneishi, T. J. Chem. Soc., Perkin Trans. 1 1991, 1637–1640; (b) Nakajima, M.;
Itoi, K.; Takamatsu, Y.; Kinoshita, T.; Okazaki, T.; Kawakubo, K.; Shindo, M.;
Honma, T.; Tohjigamori, M.; Haneishi, T. J. Antibiot. 1991, 44, 293–300.
3. (a) Heim, D. R.; Cseke, C.; Gerwick, B. C.; Murdoch, M. G.; Green, S. B. Pestic.
Biochem. Physiol. 1995, 53, 138–145; (b) Poland, B. W.; Lee, S. F.; Subramanian,
M. V.; Siehl, D. L.; Anderson, R. J.; Fromm, H. J.; Honzatko, R. B. Biochemistry
1996, 35, 15753–15759.
4.8. (5S,7R,8R,9S,10R)-8,9,10-Tribenzyloxy-7-benzyl-oxymethyl-
3,6-dioxa-2-thia-1-azaspiro[4.5]decan-2,2-di-oxide 7
4. (a) Praly, J. P.; Boyé, S.; Joseph, B.; Rollin, P. Tetrahedron Lett. 1993, 34, 3419–
3420; (b) Praly, J. P.; Faure, R.; Joseph, B.; Kiss, L.; Rollin, P. Tetrahedron 1994,
50, 6559–6568; (c) Elek, R.; Kiss, L.; Praly, J. P.; Somsak, L. Carbohydr. Res. 2005,
340, 1397–1402; (d) Somsak, L.; Nagy, V.; Vidal, S.; Czifrak, K.; Berzsenyi, E.;
Praly, J. P. Bioorg. Med. Chem. Lett. 2008, 18, 5680–5683.
Spiro-sulfamidate 5a (57 mg, 0.08 mmol) was treated with TFA-
CH2Cl2 (3 mL, 3:1) at rt for 2 h, then concentrated under reduced
pressure and chromatographed on silica gel (cyclohexane/ethyl
acetate = 7:3) to afford 7 (49 mg, quant.) as a colorless syrup:
5. Benltifa, M.; Vidal, S.; Gueyrard, D.; Goekjian, P. G.; Msaddek, M.; Praly, J. P.
Tetrahedron Lett. 2006, 47, 6143–6147.
[a
]
D = ꢁ18 (c 0.1, CHCl3). 1H NMR (300 MHz, CDCl3): d 7.39–7.21
6. (a) Bichard, C. J. F.; Mitchell, E. P.; Wormald, M. R.; Watson, K. A.; Johnson, L. N.;
Zographos, S. E.; Koutra, D. D.; Oikonomakos, N. G.; Fleet, G. W. J. Tetrahedron
Lett. 1995, 36, 2145–2148; (b) Watson, K. A.; Chrysina, E. D.; Tsitsanou, K. E.;
Zographos, S. E.; Archontis, G.; Fleet, G. W. J.; Oikonomakos, N. G. Proteins:
Struct. Funct. Bioinform. 2005, 61, 966–983; (c) Archontis, G.; Watson, K. A.; Xie,
Q.; Andreou, G.; Chrysina, E. D.; Zographos, S. E.; Oikonomakos, N. G.; Karplus,
M. Proteins: Struct. Funct. Bioinform. 2005, 61, 984–998; (d) Gregoriou, M.;
Noble, M. E. M.; Watson, K. A.; Garman, E. F.; Krulle, T. M.; De La Fuente, C.;
Fleet, G. W. J.; Oikonomakos, N. G.; Johnson, L. N. Protein Sci. 1998, 7, 915–927.
7. (a) Somsak, L.; Kovacs, L.; Toth, M.; Osz, E.; Szilagyi, L.; Gyorgydeak, Z.; Dinya,
Z.; Docsa, T.; Toth, B.; Gergely, P. J. Med. Chem. 2001, 44, 2843–2848; (b)
(m, 20H, Harom), 5.18 (s, 1H, NH), 5.01–4.49 (m, 8H, 4 ꢀ CH2Ph),
4.32 (d, 1H, J = 8.8 Hz, H-4a), 4.05 (d, 1H, J = 8.8 Hz, H-4b), 3.97
(m, 1H, H-7), 3.86 (m, 2H, H-8, CHOBn), 3.73 (m, 2H, H-9, CHOBn),
3.55 (d, 1H, J 9.1 Hz, H-10). 13C NMR (75 MHz, CDCl3): d 137.8,
137.7, 136.2 (4 ꢀ CAr), 128.9, 128.7, 128.6, 128.5, 128.1, 128.0,
127.9, 127.8 (CArH), 92.8 (C-5), 84.5 (C-9), 77.3 (C-8), 77.0 (C-4),
76.3 (C-10), 75.9, 75.3, 75.0, 73.7 (4 ꢀ CH2Ph), 73.0 (C-7), 67.8
(CH2OBn). HRMS: [M+Na]+ calcd for C35H37NO8NaS: 654.2138,
found [M+Na]+ m/z 654.2159.

M. Benltifa et al. / Tetrahedron: Asymmetry 20 (2009) 1817–1823
1823
Oikonomakos, N. G.; Skamnaki, V. T.; Osz, E.; Szilagyi, L.; Somsak, L.; Docsa, T.;
Toth, B.; Gergely, P. Bioorg. Med. Chem. 2002, 10, 261–268.
Chem. 1993, 12, 349–356; (c) Gervay, J.; Flaherty, T. M.; Holmes, D. Tetrahedron
1997, 53, 16355–16364.
8. Zhang, P. Z.; Li, X. L.; Chen, H.; Li, Y. N.; Wang, R. Tetrahedron Lett. 2007, 48,
7813–7816.
19. (a) Rajanbabu, T. V.; Reddy, G. S. J. Org. Chem. 1986, 51, 5458–5461; (b) Lay,
L.; Nicotra, F.; Panza, L.; Russo, G.; Caneva, E. J. Org. Chem. 1992, 57, 1304–
1306; (c) Rubinstenn, G.; Mallet, J. M.; Sinaÿ, P. Tetrahedron Lett. 1998, 39,
3697–3700.
20. (a) Gueyrard, D.; Haddoub, R.; Salem, A.; Said Bacar, N.; Goekjian, P. G. Synlett
2005, 520–522; (b) Bourdon, B.; Corbet, M.; Fontaine, P.; Goekjian, P. G.;
Gueyrard, D. Tetrahedron Lett. 2008, 49, 747–749.
21. (a) Baudin, J. B.; Hareau, G.; Julia, S. A.; Ruel, O. Tetrahedron Lett. 1991, 32,
1175–1178; (b) Baudin, J. B.; Hareau, G.; Julia, S. A.; Lorne, R.; Ruel, O. Bull. Soc.
Chim. Fr. 1993, 130, 856–878.
22. References for known compounds 2a, 2c: see Ref. 23 for 2e: Yamanoi, T.;
Misawa, N.; Matsuda, S.; Watanabe, M. Carbohydr. Res. 2008, 343, 1366–1372.
23. (a) Aebischer, B.; Bieri, J. H.; Prewo, R.; Vasella, A. Helv. Chim. Acta 1982, 65,
2251–2272; (b) Li, X.; Takahashi, H.; Ohtake, H.; Shiro, M.; Ikegami, S.
Tetrahedron 2001, 57, 8053–8066.
24. Wipf, P.; Venkatraman, S. Tetrahedron Lett. 1996, 37, 4659–4662.
25. (a) Sugimura, H.; Natsui, Y. Tetrahedron Lett. 2003, 44, 4729–4732; (b) George,
T. G.; Szolcsanyi, P.; Koenig, S. G.; Paterson, D. E.; Isshiki, Y.; Vasella, A. Helv.
Chim. Acta 2004, 87, 1287–1298.
26. Codée, J. D. C.; de Jong, A. R.; Dinkelaar, J.; Overkleeft, H. S.; van der Marel, G. A.
Tetrahedron 2009, 65, 3780–3788.
27. Heskamp, B. M.; van der Marel, G. A.; van Boom, J. H. Synlett 1992, 713–715.
28. Hernadez-Garcia, L.; Quintero, L.; Höpfl, H.; Sosa, M.; Sartillo-Piscil, F.
Tetrahedron 2009, 65, 139–144.
9. (a) Gimisis, T.; Chatgilialoglu, C. J. Org. Chem. 1996, 61, 1908–1909; (b) Kittaka,
A.; Tanaka, H.; Kato, H.; Nonaka, Y.; Nakamura, K. T.; Miyasaka, T. Tetrahedron
Lett. 1997, 38, 6421–6424; (c) Gimisis, T.; Chatgilialoglu, C.; Castellari, C. Chem.
Commun. 1997, 2089–2090; (d) Kittaka, A.; Kato, H.; Tanaka, H.; Nonaka, Y.;
Amano, M.; Nakamura, K. T.; Miyasaka, T. Tetrahedron 1999, 55, 5319–5344; (e)
Chatgilialoglu, C.; Gimisis, T.; Spada, G. P. Chem. Eur. J. 1999, 5, 2866–2876; (f)
Chatgilialoglu, C. Farmaco 1999, 54, 321–325.
10. Toumieux, S.; Compain, P.; Martin, O. R. Tetrahedron Lett. 2005, 46, 4731–4735.
11. Burgess, E. M.; Penton, H. R.; Taylor, E. A. J. Am. Chem. Soc. 1970, 92, 5224–5226.
12. (a) Brain, C. T.; Hallett, A.; Ko, S. Y. Tetrahedron Lett. 1998, 39, 127–130; (b) Hua,
G.; Liu, D.; Xie, F.; Zhang, W. Tetrahedron Lett. 2007, 48, 385–399; (c) Li, J. J.; Li, J. J.;
Li, J.; Trehan, A. K.; Wong, H. S.; Krishnananthan, S.; Kennedy, L. J.; Gao, Q.; Ng, A.;
Robl, J. A.; Balasubramanian, B.; Chen, B. C. Org. Lett. 2008, 10, 2897–2900.
13. (a) Wood, M. R.; Kim, J. Y.; Books, K. M. Tetrahedron Lett. 2002, 43, 3887–3890;
(b) Burgess, E. M.; Penton, H. R., Jr.; Taylor, E. A. J. Org. Chem. 1973, 38, 26–31;
(c) Atkins, G. M.; Burgess, E. M. J. Am. Chem. Soc. 1972, 94, 6135–6141.
14. (a) Rinner, U.; Adams, D. R.; dos Santos, M. L.; Abboud, K. A.; Hudlicky, T. Synlett
2003, 1247–1252; (b) Leisch, H.; Saxon, R.; Sullivan, B.; Hudlicky, T. Synlett
2006, 445–449; (c) Nicolaou, K. C.; Huang, X.; Snyder, S. A.; Rao, P. B.; Bella, M.;
Reddy, M. V. Angew. Chem., Int. Ed. 2002, 41, 834–838.
15. Nicolaou, K. C.; Longbottom, D. A.; Snyder, S. A.; Nalbanadian, A. Z.; Huang, X.
Angew. Chem., Int. Ed. 2002, 41, 3866–3870.
16. Banfield,S. C.;Omori, A.T.;Leisch,H.;Hudlicky, T. J.Org.Chem.2007, 72, 4989–4992.
17. Taillefumier, C.; Chapleur, Y. Chem. Rev. 2004, 104, 263–292.
18. (a) Nicotra, F.; Panza, L.; Russo, G. Tetrahedron Lett. 1991, 32, 4035–4038; (b)
Faivre-Buet, V.; Eynard, I.; Nga, H. N.; Descotes, G.; Grouiller, A. J. Carbohydr.
29. (a) Kapferer, P.; Birault, V.; Poisson, J. F.; Vasella, A. Helv. Chim. Acta 2003, 86,
2210–2227; (b) Gonzalez-Bello, C.; Castedo, L.; Canada, F. J. Eur. J. Org. Chem.
2006, 4, 1002–1011.