Stereoselective synthesis of oxiranes as a source of isoserine analogues using D-glucosamine and D-glucose derivatives as chiral templates

Article abstract of DOI:10.1016/j.tetasy.2004.09.034

The synthesis of alkyl (R)-4,6-O-(2,3-epoxypropylidene) hexopyranoside derivatives from N-acetyl-d-glucosamine and d-glucose is described. The reaction of epoxidation with m-CPBA of the corresponding alkenylidene derivatives took place with different ster

Full text of DOI:10.1016/j.tetasy.2004.09.034

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 3617–3633
Stereoselective synthesis of oxiranes as a source of
isoserine analogues using D-glucosamine and D-glucose
derivatives as chiral templatesI
*
Jose M. Vega-Perez, Margarita Vega, Eugenia Blanco and Fernando Iglesias-Guerra
*
´
´
´ ´ ´
Departamento de Quımica Organica y Farmaceutica, Facultad de Farmacia, Universidad de Sevilla, E-41071 Sevilla, Spain
Received 6 September 2004; accepted 27 September 2004
Abstract—The synthesis of alkyl (R)-4,6-O-(2,3-epoxypropylidene) hexopyranoside derivatives from N-acetyl-D-glucosamine and
D-glucose is described. The reaction of epoxidation with m-CPBA of the corresponding alkenylidene derivatives took place with
different stereoselectivities depending upon the substitution of the unsaturated system, the protecting groups of the hydroxyl group
at carbon three of the sugar moiety, and its configuration. The ring-opening reaction of these oxiranes with nitrogen nucleophiles
gave phenylisoserine precursors.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
Our primary interest in the synthesis of sugar-derived
oxiranes is twofold. On the one hand, they are interest-
ing in themselves, because compounds, which have an
oxirane ring are reactive substances that act as alkylat-
ing agents, making them potential anti-cancer drugs.
Moreover, as the oxirane fragment is joined to a sugar
molecule, lipophilic moieties can bond, modulating the
hydrophilic–lipophilic balance of the compound, en-
abling greater selectivity in the transport and localiza-
tion of the drug.10–12 In addition, the lability of the
bond between the oxirane moiety and sugar provides
ready release of the active fraction in the organism.
Stereoselective transformations from natural products
are one of the most-effective procedures for the prepara-
tion of enantiomerically pure compounds of biological
and pharmacological interest. Carbohydrates are impor-
tant chiral templates for numerous asymmetric transfor-
mations.2 Our group has been using 2-aminosugars as
chiral templates in the stereoselective synthesis of differ-
ent compounds (2,3-diaminoglucoses,3 chiral oxazol-
idines,4 and compounds with potential anti-cancer
activity3,5,6). Due to the important role of oxiranes
as intermediates in the asymmetric synthesis of chiral
1,2-difunctionalized compounds, we have recently devel-
oped a method for the stereoselective epoxidation of ole-
fins. The olefinic chain was joined to different positions
of a sugar molecule, acting as chiral inductor via various
functions (glycoside, amide). The chiral epoxyalkyl gly-
cosides1,7 and the chiral epoxyamides8 obtained can be
transformed into different types of compounds. This
method has enabled us to synthesize derivatives of gly-
cosyl glycerol analogues that have been used as alkylat-
ing-agent carrier systems.9 Our current aim is to obtain
chiral oxiranes on a moiety that can be easily separated
from the sugar.
On the other hand, the oxiranes are compounds suitable
for transformation into other compounds of biological
interest. Those worthy of note are the a-hydroxy-b-ami-
noacids derived from isoserine, which are nonproteino-
genic aminoacids, and important members of the
b-aminoacid family. Isoserine derivatives constitute the
essential fragment in natural products of high therapeu-
tic value,13 such as taxol (an anti-cancer agent), whose
side chain is N-acyl-(2R,3S)-phenylisoserine, bestatin
(a dipeptide modifier of the immune response), in which
one of the aminoacids is (2S,3R)-2-hydroxy-3-amino-3-
phenylbutyric acid, and the kinostatins (potent inhibitors
of the HIV-1 protease), in which one of the constituent
aminoacids is (2S,3S)-2-hydroxy-3-amino-3-phenylbu-
tyric acid. Due to the b-aminoalcohol properties of these
q Potential anti-cancer drugs, Part 7. For Part 6, see: Ref. 1.
*
Corresponding authors. Tel./fax: +34 95 4556737; e-mail: vega@us.es
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.09.034

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J. M. Vega-Perez et al. / Tetrahedron: Asymmetry 15 (2004) 3617–3633
3618
compounds, one procedure that can be used for their
synthesis is regio- and stereoselective opening with
amines of chiral oxirane—linking this method with our
line of research. Consequently, we began the synthesis
of modified, enantiomerically pure isoserines, using sug-
ars as chiral inductors, in order to study the effect of
stereochemistry and the formation of alkyl analogues
on their biological activity.
in (a) the anomeric configuration and the nature of the
aglycon; (b) the substituent on carbon two of the sugar,
N-acetyl-D-glucosamine, and D-glucose; (c) the protec-
tion of the hydroxyl group on carbon three; and (d)
the configuration of carbon three: gluco and allo
configuration.
The new compounds obtained are capable of being con-
verted into new phenylisoserine analogues. We report
the preliminary studies of the ring-opening reaction of
an oxirane with two nitrogen nucleophiles, sodium
azide, and piperidine.
The aim was to obtain chiral oxiranes on a skeleton that
could be transformed easily into modified isoserines,
joined to a modified sugar moiety that acts as chiral
inductor (and transporter in such case) via a labile bond
enabling easy separation, chemically or enzymatically.
2. Results and discussion
We believe that a straightforward manner to achieve this
might be the oxidation of cinnamal acetals formed be-
tween positions 4 and 6 of a sugar molecule, for the fol-
lowing reasons: (a) these acetals are readily obtained
compounds, and the reaction of oxidation of alkenes
to oxiranes is well known and easy to perform; (b) to
the best of our knowledge, there are no published pre-
cendents on the oxidation of cinnamal acetals of sugars;
(c) we have used 2-aminosugars as chiral templates in
the stereoselective synthesis of numerous compounds
(2-aminoglycals,14 2-nitrosugars,15 chiral oxazolidines,4
chiral epoxyamides,8 compounds with potential anti-
cancer activity,3,5,6 and epoxyalkyl glycosides1,7), and
we think that the glucosamine moiety could serve as a
chiral inductor in the oxidation reaction and as a carrier
agent in derivatives with potential biological activity;
and (d) the acetalic bond is labile, and the chiral induc-
tor can be separated easily.
(R)-4,6-O-Alkenylidene hexopyranosides, whose oxida-
tion has been studied are compounds 6–10 and 12–24
(Schemes 1–4). An attempt was made to study the effect
of their different structural features on the stereofacial
differentiation of the diastereotopic faces of the double
bond in the epoxidation reaction. They can be divided
into three groups: compounds with a gluco configura-
tion and the C-3 hydroxyl group free 6–10, 12, and 13;
compounds with the C-3 hydroxyl group blocked 14–
23, and the compound with an allo configuration 24.
(R)-4,6-O-Alkenylidene glucopyranosides 6–10 were
obtained by reaction of alkyl 2-acetamido-2-deoxy-D-
glucopyranosides5,16 1–3 and trans-cinnamaldehyde
dimethyl acetal 4 or a-methyl-trans-cinnamaldehyde di-
methyl acetal 5 in good yields using the procedure
described by Murphy et al.17 for the formation of acetals
using aldehyde dimethyl acetal as reagent. The same
method was used for the preparation of compounds 12
and 13 from methyl a-D-glucopyranoside 11 (Scheme
1). The reagent a-methyl-trans-cinnamaldehyde di-
methyl acetal 5, obtained by the procedure described
in the preparation of trans-cinnamaldehyde dimethyl
acetal18 4, was characterized by its mass and NMR
spectra.
Herein, we report the epoxidation of the double bond of
trans-cinnamaldehyde and a-methyl-trans-cinnamalde-
hyde, which have previously formed an acetal with the
4- and 6-hydroxyls of the alkyl glycoside of N-acetyl-
D-glucosamine and D-glucose. Additionally, in order to
find the substrate giving the best yields and diastereo-
meric excesses, we have used chiral substrates varying
OMe
OMe
HO
O
Ph
O
MeCN
CSA
O
OR1
HO
OR1
O
R2
HO
HO
+
Ph
NHAc
NHAc
R2
1 R1 = c-C6H11
2 R1 = n-C12H25
3 R1 = Bn
6 R1 = c-C6H11 , R2 = H
7 R1 = n-C12H25 , R2 = H
8 R1 = Bn, R2 = H
4 R2 = H
5 R2 = Me
9 R1 = c-C6H11 , R2 = Me
10 R1 = n-C12H25 , R2 = Me
OMe
HO
HO
HO
O
Ph
O
MeCN
CSA
O
O
R2
HO
+
Ph
OMe
HO
HO
R2
OMe
OMe
4 R2 = H
12 R2 = H
11
5 R2 = Me
13 R2 = Me
Scheme 1.

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J. M. Vega-Perez et al. / Tetrahedron: Asymmetry 15 (2004) 3617–3633
3619
O
R3O
BnBr/KOH
Ph
O
6, 7, 9
OR1
Cl
O
R2
18-crown-6/THF
6, 7
NHAc
Et3N/CH2Cl2
14 R1 = c-C6H11 , R2 = H , R3 = Bn
15 R1 = n-C12H25 , R2 = H , R3 = Bn
16 R1 = c-C6H11 , R2 = Me , R3 = Bn
17 R1 = c-C6H11 , R2 = H, R3 = 5-dibenzosuberyl
18 R1 = n-C12H25 , R2 = H, R3 = 5-dibenzosuberyl
O
Ph
O
O
CH2Br2/CH2Cl2/50% NaOH/H2O/TBABr
O(c-C6H11
)
O
6
NAc
19
Scheme 2.
7
ClCO2Bn/Py/THF-CH2Cl2
O
R3O
Ph
Ac2O/Py/CH2Cl2
O
MeSO2Cl/Py
OR1
O
6
7, 10
R2
NHAc
20 R1 = c-C6H11 , R2 = H , R3 = Ac
21 R1 = n-C12H25 , R2 = H , R3 = CO2Bn
22 R1 = n-C12H25 , R2 = H , R3 = MeSO2
23 R1 = n-C12H25 , R2 = Me , R3 = MeSO2
Scheme 3.
O
Ph
O
NaAcO/MeOCH2CH2OH-H2O
O
O(n-C12H25
)
22
NHAc
OH
24
Scheme 4.
The NMR spectra for compounds 6–10, 12, and 13
showed signals corresponding to the unsaturated moiety
incorporated into the sugar molecule in the acetalation
reaction. The 1H spectra showed a signal at 5.2–
5.0ppm corresponding to the acetal proton, and another
at 6.8–6.6ppm corresponding to the olefinic proton at
the a-position to the phenyl group. Compounds 6–8
and 12 showed a signal at 6.2–6.1ppm corresponding
to the other olefinic proton, while compounds 9, 10,
and 13 showed a singlet at 1.9–1.8ppm corresponding
to the methyl group on the double bond. Compounds
6–10, 12, and 13 showed a doublet at 4.7–4.0ppm for
H-1 as characteristic signal of the sugar moiety.
of the C-3 hydroxyl group as indicated in Scheme 2. The
1H NMR spectra of these compounds showed the sig-
nals corresponding to the protecting group introduced:
two doublets at 4.88 and 4.63ppm for 14, 15, and 16,
a singlet at 5.65ppm corresponding to the suberyl group
for 17 and 18, and two doublets at 5.52 and 4.73ppm for
19.
Compounds 6, 7, and 10 were acylated with different
reagents, giving compounds 20–23 (Scheme 3). Com-
pound 20 showed a singlet at 1.74ppm in 1H and a signal
at 20.6ppm in the 13C NMR spectra, corresponding to
the acetyl group. The 13C NMR spectrum of 21 gave a
signal at 155.1ppm for the new carbonyl group intro-
duced. Compounds 22 and 23 showed characteristic sig-
nals corresponding to the methanosulfonyl group at
The syntheses of compounds 14–18 were carried out
from 6, 7, or 9 by means of several alkylation processes

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J. M. Vega-Perez et al. / Tetrahedron: Asymmetry 15 (2004) 3617–3633
3620
1
3.03ppm in the H and at 38.5ppm in the 13C NMR
spectra.
Table 1. Epoxidation of (R)-4,6-O-propenylidene derivatives 6–10, 12–
24 with m-CPBA at ꢀ15ꢁC
Entry Starting
Reaction Yielda Deb Major oxirane
compound product
(%)
(%) configuration
Compound 24 was synthesized from compound 22 by
the same procedure described for similar compounds4
(Scheme 4). 1H NMR showed mayor chemical shifts
for the signals corresponding to H-2 (4.10ppm) and
H-3 (4.21ppm), and a change in the multiplicity, with re-
spect to compound 7, the isomer of gluco configuration.
1
625
7
84
77
58
81
72
77
78
82
86
89c
86
72
80c
69
65
68
72
75
68
60
42
34
42
74
56
46
72
28
22
13c
34
36
32c
24
0
2R,3S
2R,3S
2R,3S
2R,3S
2R,3S
2R,3S
2R,3S
2S,3R
2S,3R
2S,3R
2S,3R
2S,3R
2S,3R
2S,3R
2
26
27
28
29
30
31
32
33
33
3
8
4
9
5
10
12
13
14
15
15
1634
17
17
18
19
20
21
22
23
24
6
7
The reaction of 6–10 and 12–24 with m-CPBA in chloro-
form at different temperatures gave the corresponding
oxiranes 25–42. The compounds were isolated and puri-
fied by flash chromatography on silica gel (Scheme 5,
8
9
10
11
12
13
14
15
16
17
18
19
20
1
Table 1). The H NMR spectra for these compounds
35
35
36
37
38
39
40
41
42
showed the characteristic signals of the oxirane system
at 3.9 and 3.3ppm for 25–27, 30, 32, 33, 35–40, and
42, and at 4.15 and 1.10ppm for the other compounds.
The 13C NMR spectra showed signals between 62 and
54ppm for each of the compounds 25–42.
0
12
2
2S,3R
2R,3S
2R,3S
2S,3R
1
The diastereomeric excesses (de), determined using H
12
66
NMR, are shown in Table 1, from which certain infer-
ences can be drawn. For their analysis, the starting
(R)-4,6-O-propylidene acetals can be grouped into the
three groups defined above. The first group comprises
of the compounds with the 3-hydroxyl group free (6–
10, 12, and 13); the second group is the compounds with
the 3-hydroxyl group blocked (14–23), and the third is
compound 24 with an allo configuration. As expected,
in the oxidation of a compound, the de is higher when
the reaction temperature is lower. With regard to the de-
a Yields refer to compounds obtained in each reaction after isolation
and purification.
1
b Determined by integration in H NMR spectra of reaction mixtures.
c Reaction at room temperature.
gree of substitution of the double bond, the results show
that the de obtained when the substituent on the double
bond is R2 = Me (entries 4, 5, 7, 11, and 19) is higher
O
O
O
O
Ph
Ph
O
O
NAc
OR1
O
O
O(c-C6H11
)
R2
HO
O
NHAc
25 R1 = c-C6H11 , R2 = H
37
26 R1 = n-C12H25 , R2 = H
i
i
27 R1 = Bn, R2 = H
28 R1 = c-C6H11 , R2 = Me
29 R1 = n-C12H25 , R2 = Me
O
O
O
R3O
Ph
i
O
i
O
OR1
6−10,
O
Ph
O
R2
12−24
O
R2
HO
NHAc
HO
38 R1 = c-C6H11 , R2 = H , R3 = Ac
OMe
30 R2 = H
40 R1 = n-C12H25 , R2 = H , R3 = MeSO2
i
31 R2 = Me
41 R1 = n-C12H25 , R2 = Me , R3 = MeSO2
i
O
O
O
Ph
O
OR1
NHAc
R3O
R2
O
O
Ph
O
32 R1 = c-C6H11 , R2 = H , R3 = Bn
O
O(n-C12H25
NHAc
)
33 R1 = n-C12H25 , R2 = H , R3 = Bn
34 R1 = c-C6H11 , R2 = Me , R3 = Bn
OH
35 R1 = c-C6H11 , R2 = H, R3 = 5-dibenzosuberyl
36 R1 = n-C12H25 , R2 = H, R3 = 5-dibenzosuberyl
39 R1 = n-C12H25 , R2 = H , R3 = CO2Bn
42
Scheme 5. Reagent: (i) m-CPBA/CHCl3.

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J. M. Vega-Perez et al. / Tetrahedron: Asymmetry 15 (2004) 3617–3633
3621
than when R2 = H (entries 1, 2, 6, 8, and 18). Thus, com-
pounds 28, 29, 31, 34, and 41 were obtained with des of
74%, 56%, 72%, 34%, and 12%, respectively, while com-
pounds 25, 26, 30, 32, and 40 were obtained with des of
42%, 34%, 46%, 28%, and 2%, respectively. With regard
to the functionalization of position three of the sugar,
the results show that the compounds of the first group
(gluco configuration, hydroxyl 3 free) present des higher
than those for the corresponding compounds of the sec-
ond group (same configuration, hydroxyl 3 blocked).
Thus, the de for 25 was 42%, while the des for com-
pounds 32, 35, and 38 were 28%, 36%, and 0%, respec-
tively; for 28 the de was 74%, while that for 34 was
34%. These results support the idea of the formation
of a hydrogen bond between the 3-OH group and the
peroxyacid in the transition state related to the electro-
philic addition to the double bond that controls the ste-
reochemical course of the reaction, and are similar to
those found in the epoxidation reaction of alkenyl glyco-
sides1,7,19 with m-CPBA. In the case of the alkenyl glyco-
sides, it has been demonstrated that the reactive face in
the epoxidation reaction is the Re face (see, e.g., Ref. 1).
Given that the distance between the 2-NH and the dou-
ble bond of the glycoside and their relative disposition
are the same as those observed between the 3-OH and
the double bond of the propylidene acetals presented
herein, we tentatively propose that the more-reactive
face of the double bond is the same in both types of
compound—that is the Re,Re face of the propylidene
acetals with the 3-hydroxyl group free.
42, with a de of 66%, the highest de obtained for the oxi-
dation of a compound derived from cinnamaldehyde.
At the same time, it is important to analyze the chemical
shifts of the protons corresponding to the oxidized acet-
1
al system in the H NMR spectra (Table 2). The signal
for H-30 is easily identifiable in the 1H spectra at approx-
imately 4ppm, as a doublet for compounds with
R2 = H and as a singlet for compounds with R2 = Me.
In all spectra for the compounds of the first group (3-
hydroxyl group free) with R2 = H (25, 26, 27, and 30),
the doublet corresponding to H-30 of the major isomer
appeared at lower chemical shift than that of the minor
isomer (entries 1, 2, 3, and 6), so that we assign the same
configuration in the oxirane ring (2R,3S) to the major
isomer for each of these compounds, bearing in mind
the above remarks.
Comparison of the signal for H-30 of compounds 25 and
26 with that of the compounds in the second group (3-
hydroxyl group blocked) showed changes in the previ-
ously described pattern. Compounds 32 and 35 present
the doublet of the major isomer at higher chemical shift
than that of the minor isomer (a different profile to that
presented by compound 25). Compounds 33, 36, and 39
present a profile for the H-30 doublets similar to that
presented by compounds 32 and 35, but different to that
presented by compound 26. We assigned the (2S,3R)-
configuration for the oxirane ring of the major isomer
of compounds 32, 33, 35, 36, and 39, which have the
3-hydroxyl group blocked with an aromatic protecting
group (see below). Compound 40, however, (in which
the hydroxyl group on three is blocked with a nonaro-
matic protecting group) presents the same profile as
With regard to the configuration of position three of the
sugars, it is remarkable that the epoxidation of com-
pound 24, with an allo configuration, led to compound
Table 2. 1H NMR data (d, ppm) for the acetalic group in compounds with the oxirane ring 25–42
O
1'
O
3'
Ph
2'
R2
O
Entry
Compound
H-10
H-20
CH3
H-30
1
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
4.62(M)/4.60(m)
4.63(M)/4.62(m)
4.67(M)/
3.29(M)/
—
—
3.99(m)/3.98(M)
3.99(m)/3.98(M)
4.00(m)/3.94(M)
2
3
3.24(M)/
—
—
1.00(M)/0.99(m)
4
4.47(M)/4.43(m)
4.47(M)/4.44(m)
4.69(M)/4.65(m)
4.47(M)/4.41(m)
5
—
3.22(M)/
—
1.11(M)/1.09(m)
—
4.14(M)/4.13(m)
3.99(m)/3.97(M)
4.16(M)/4.11(m)
4.00(M)/3.97(m)
3.96(M)/3.93(m)
4.15(M)/4.10(m)
3.97(M)/3.93(m)
3.96(M)/3.93(m)
3.99/3.93
6
7
1.10(M)/1.09(m)
—
8
3.30(M)/3.27(m)
3.20(M)/
—
9
4.70(M)/4.64(m)
4.47(M)/4.40(m)
4.61(M)/4.59(m)
4.60(M)/
—
1.12(M)/1.10(m)
10
11
12
13
14
15
16
17
18
—
—
—
—
—
—
4.65
4.59
3.14
3.89/3.87
4.64(M)/4.56(m)
4.63(m)/4.53(M)
4.52(m)/4.34(M)
4.68(M)/4.65(m)
3.16(M)/
3.15(M)/
—
3.92(M)/3.88(m)
3.91(m)/3.89(M)
1.08(m)/1.04(M)
3.93(M)/3.91(m)
3.19(M)/
—
(M) For the major isomer.
(m) For the minor isomer.

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J. M. Vega-Perez et al. / Tetrahedron: Asymmetry 15 (2004) 3617–3633
3622
compound 26, meaning that we assigned a (2R,3S)-con-
figuration for the major isomer of compound 40.
44. The results confirm that the major isomer of com-
pound 43 has a different configuration to that of the
major isomer of compound 44, implying that the com-
pounds derived from 26 and 33 have different
configurations.
Comparison of the H-30 signal for compound 42 (third-
group compound) with that for compound 26 shows
that the profiles for the two compounds are different.
We assign the (2S,3R)-configuration for the oxirane ring
of the major isomer of compound 42.
We also studied the ring-opening reactions of oxirane 28
with two different nitrogen nucleophiles (sodium azide
and piperidine), giving compounds 45 and 46, in good
yield and diastereomeric excess (Scheme 7). In both
cases, the oxirane ring reacted regioselectively via the
least-substituted carbon (benzylic carbon). The 13C
NMR spectra showed the characteristic signals corre-
sponding to CHN3 at 69.0ppm (for 45), to CHNR2 at
73.4ppm, and to CH2NCH2 at 53.1ppm (for 46). Com-
pounds 45 and 46 have an a-hydroxy-b-aminoacetal
structure, and can be used as precursors of phenylisoser-
ine analogues.
In order to demonstrate that the 1H spectra profiles
for the compounds of the first and second groups are
different because the face of the double bond is more
reactive in the epoxidation is different in the two groups
of compounds, we carried out the hydrogenolysis of
compounds 26 and 33 (Scheme 6). The hydrogenolysis
of 26 led to compound 43, and that of 33 to 44. Table
3 shows the chemical shift for the most-characteristic
1
protons in the H NMR spectra of compounds 43 and
O
O
O
Ph
Ph
O
O
H2/Pd(C)
O
O
O(n-C12H25
NHAc
)
O(n-C12H25
NHAc
)
HO
HO
OH
OH
43
44
26
33
O
O
O
Ph
Ph
O
O
H2/Pd(C)
O
O
O(n-C12H25
)
O(n-C12H25
NHAc
)
HO
BnO
NHAc
Scheme 6.
Table 3. 1H NMR data (d, ppm) for compounds 43 and 44
Entry
Compd
H-10
HA-30
HB-30
H-1
H-6e
1
2
43
44
4.46(M)/4.41(m)
4.45(m)/4.43(M)
2.94(m)/2.89(M)
2.96(M)/2.91(m)
2.79(M)/2.75(m)
2.82(m)/2.73(M)
4.61(M)/4.59(m)
4.65(m)/4.62(M)
4.22(M)/4.18(m)
4.25(m)/4.20(M)
(M) For the major isomer.
(m) For the minor isomer.
N3
O
Ph
O
O
O(c-C6H11
)
HO
OH
NHAc
45
i
O
O
Ph
O
O
O(c-C6H11
NHAc
)
HO
ii
28
N
O
Ph
O
O
O(c-C6H11
)
HO
OH
NHAc
46
Scheme 7. Reagents: (i) NaN3/LiClO4/CH3CN; (ii) piperidine/LiClO4/CH3CN.

´
J. M. Vega-Perez et al. / Tetrahedron: Asymmetry 15 (2004) 3617–3633
3623
3. Experimental
(500MHz, DMSO-d6): d 7.8 (d, 1H, J2,NH 9.0Hz,
NH), 7.5–7.3 (m, 5H, Ph), 6.76 (d, 1H, Jtrans 16.1Hz,
3.1. General
PhCH@CHCH), 6.23 (dd, 1H, Jtrans 16.1Hz, J
5.1Hz, PhCH@CHCH), 5.22 (d, 1H, J3,OH 5.8Hz,
OH), 5.19 (d, 1H, J 5.1Hz, PhCH@CHCH), 4.53 (d,
1H, J1,2 8.4Hz, H-1), 4.10 (dd, 1H, J5,6e 4.9Hz, J6e,6a
10.1Hz, H-6e), 3.6–3.5 (m, 3H, H-3, H-6a, OCHR),
3.38 (m, 1H, H-2), 3.28 (t, 1H, J3,4 = J4,5 9.2Hz, H-4),
3.22 (dd, 1H, J4,5 = J5,6a 9.5Hz, J5,6e 4.8Hz, H-5),
1.79 (s, 3H, CH3CON), 1.7–1.2 [m, 10H, (CH2)5].
13C NMR (50MHz, DMSO-d6): d 169.0 (C@O),
135.6–126.7 (Ph), 133.1 (PhCH@CHCH), 125.3
(PhCH@CHCH), 100.3, 100.0 (C-1, PhCH@CHCH),
81.1 (C-4), 75.9 (OCHR), 70.3 (C-3), 67.6 (C-6), 65.8
(C-5), 56.6 (C-2), 32.9–22.8 [(CH2)5], 23.1 (CH3CON).
HRMS(CI): [M+H] +, found 418.221858. C23H32NO6
requires 418.222963. Anal. Calcd for C23H31NO6: C,
66.17; H, 7.48; N, 3.35. Found: C, 65.88; H, 7.33; N,
3.33.
Evaporations were conducted under reduced pressure.
Preparative chromatography was performed on Silica
Gel 60 (E. Merck). Kieselgel 60 F254 (E. Merck) was
used for TLC. Melting points were obtained on a Stuart
Melting Point Apparatus SMP 10 and are uncorrected.
Optical rotations were obtained on a Perkin Elmer Polar-
imeter Model 341 at 25ꢁC. Mass spectra were recorded
on a Micromass AUTOSPECQ mass spectrometer,
EI at 70eV and CI at 150eV; HR mass measurements
with resolutions of 10,000. FAB mass spectra were
recorded on a Kratos MS-80-RFA, using a thioglycerol
matrix. NMR spectra were recorded at 25ꢁC on a
1
Bruker AC-200 spectrometer at 200MHz for H and
50MHz for 13C, and on a Bruker AMX-500 spectro-
1
meter at 500MHz for H and 125MHz for 13C. The
chemical shifts are reported in ppm on the d scale rela-
tive to TMS. COSY, DEPT, and CHCORR experiments
were performed to assign the signals in the NMR
spectra.
3.2.2. 1-Dodecyl 2-acetamido-2-deoxy-(R)-4,6-O-(E-3-
phenyl-2-propenylidene)-b-D-glucopyranoside 7. Yield
5.7g (75%); mp 252–254ꢁC; [a]D = ꢀ68.0 (c 1.0, EtOH);
1
MS(CI): m/z 504 (19%) [M+H]+. H NMR (500MHz,
3.1.1. a-Methyl-trans-cinnamaldehyde dimethyl acetal
DMSO-d6): d 7.71 (d, 1H, J2,NH 8.9Hz, NH), 7.5–7.3
(m, 5H, Ph), 6.76 (d, 1H, Jtrans 16.2Hz, PhCH@CHCH),
6.21 (dd, 1H, Jtrans 16.2Hz, J 5.0Hz, PhCH@CHCH),
5.20 (d, 1H, J 5.0Hz, PhCH@CHCH), 5.13 (d, 1H,
J3,OH 5.6Hz, OH), 4.43 (d, 1H, J1,2 8.4Hz, H-1), 4.11
(dd, 1H, J5,6e 4.8Hz, J6e,6a 10.1Hz, H-6e), 3.66 (m,
1H, OCHAHBR), 3.61 (t, 1H, J5,6a = J6e,6a 10.1Hz, H-
6a), 3.58 (m, 1H, H-3), 3.47 (m, 1H, H-2), 3.38 (m,
1H, OCHAHBR), 3.30 (t, 1H, J3,4 = J4,5 9.3Hz, H-4),
3.2 (m, 1H, H-5), 1.80 (s, 3H, CH3CON), 1.4–1.2 [m,
20H, (CH2)10], 0.85 (t, 3H, J 6.8Hz, CH3). 13C NMR
(125MHz, DMSO-d6): d 169.0 (C@O), 135.6–126.7
(Ph), 133.1 (PhCH@CHCH), 125.3 (PhCH@CHCH),
101.4 (C-1), 100.1 (PhCH@CHCH), 81.0 (C-4), 70.4
(C-3), 68.5 (OCH2R), 67.5 (C-6), 65.8 (C-5), 56.2 (C-
2), 31.1–21.9 [(CH2)10], 22.8 (CH3CON), 13.7 (CH3).
HRMS(EI): [M] +Æ, found 503.324320. C29H45NO6
requires 503.324689. Anal. Calcd for C29H45NO6:
C, 69.15; H, 9.00; N, 2.78. Found: C, 69.24; H, 8.99;
N, 2.79.
5.
A
mixture of a-methyl-trans-cinnamaldehyde
(35mL, 0.25mol), trimethylorthoformate (33mL,
0.30mol), anhydrous methanol (225mL), and anhy-
drous camphorsulfonic acid (0.25g) was stirred at room
temperature for 4days. At the end of this time, the alco-
hol was removed with a rotary evaporator, and the res-
idue was distilled, yielding 36g (75%); MS(FAB): m/z
215 (10%) [M+Na]+. H NMR (200MHz, CDCl3): d
1
7.4–7.2 (m, 5H, Ph), 6.67 [s, 1H, PhCH@ C(CH3)-
CH(OCH3)2], 4.66 [s, 1H, PhCH@C(CH3)CH(OCH3)2],
3.39 [s, 6H, PhCH@C(CH3)CH(OCH3)2], 1.90 [s, 3H,
PhCH@C(CH3)CH(OCH3)2]. 13C NMR (50MHz,
CDCl3): d 136.4–127.5 (Ph), 133.8 [PhCH@C(CH3)-
CH(OCH3)2], 126.1 [PhCH@C(CH3)CH(OCH3)2],
106.7
[PhCH@C(CH3)CH(OCH3)2],
52.5
[PhCH@C(CH3)- CH(OCH3)2], 12.5 [PhCH@C(CH3)-
CH(OCH3)2]. HRMS(FAB): [M+Na] ,
215.104763. C12H16O2 Na requires 215.104800.
+
found
3.2. Alkyl 2-acetamido-(R)-4,6-O-alkenylidene-2-deoxy-
b-D-glucopyranosides 6–10
3.2.3. Benzyl 2-acetamido-2-deoxy-(R)-4,6-O-(E-3-phen-
yl-2-propenylidene)-b-D-glucopyranoside 8. Yield 3.9g
(61%); mp 268–269ꢁC; [a]D = ꢀ54.2 (c 1.0, DMF); MS
(CI): m/z 426 (100%) [M+H]+. 1H NMR (200MHz,
CDCl3): d 7.4–7.3 (m, 10H, 2Ph), 6.80 (d, 1H, Jtrans
16.0Hz, PhCH@CHCH), 6.19 (dd, 1H, Jtrans 16.0Hz,
J 4.7Hz, PhCH@CHCH), 5.47 (d, 1H, J2,NH 5.4Hz,
NH), 5.21 (d, 1H, J 4.7Hz, PhCH@CHCH), 4.90 (d,
1H, Jgem 12.0Hz, OCHAHBPh), 4.62 (d, 1H, J1,2
8.2Hz, H-1), 4.57 (d, 1H, Jgem 12.0Hz, OCHAHBPh),
4.31 (dd, 1H, J6e,6a 10.2Hz, J5,6e 4.7Hz, H-6e), 4.00 (t,
1H, J2,3 = J3,4 8.2Hz, H-3), 3.73 (t, 1H, J5,6a = J6e,6a
10.2Hz, H-6a), 3.6–3.3 (m, 3H, H-2, H-4, H-5), 1.95
(s, 3H, CH3CON). 13C NMR (50MHz, DMSO-d6): d
169.2 (C@O), 138.0–126.8 (Ph), 133.2 (PhCH@CHCH),
125.2 (PhCH@CHCH), 101.5, 100.4 (PhCH@CHCH,
C-1), 81.0 (C-4), 70.4 (C-3), 70.0 (OCH2Ph), 67.5
To a suspension of alkyl 2-acetamido-2-deoxy-b-D-
glucopyranoside 1–3 (15.0mmol) in acetonitrile (90
mL) was added the corresponding aldehyde dimethyl-
acetal 4, 5 (25.0mmol), and anhydrous camphorsulfonic
acid (15mg). The mixture was stirred at room tempera-
ture until the reaction was complete (1–2weeks, TLC).
The reaction mixture was then filtered, the solid stirred
in hexane and the mixture filtered again; the solid was
stirred in water, and the product obtained by filtration.
The product was recrystallized from 96% ethanol.
3.2.1. c-Hexyl 2-acetamido-2-deoxy-(R)-4,6-O-(E-3-phe-
nyl-2-propenylidene)-b-D-glucopyranoside
6. Yield
4.4g (71%); mp 260–262ꢁC; [a]D = ꢀ108.0 (c 0.5,
1
MeOH); MS(CI): m/z 418 (57%) [M+H]+. H NMR

´
J. M. Vega-Perez et al. / Tetrahedron: Asymmetry 15 (2004) 3617–3633
3624
(C-6), 66.0 (C-5), 56.1 (C-2), 23.1 (CH3CON). HRMS
(CI): [M+H]+, found 426.190361. C24H28NO6 requires
426.191663. Anal. Calcd for C24H27NO6: C, 67.76; H,
6.35; N, 3.29. Found: C, 67.63; H, 6.41; N, 3.24.
ylamine was added until pH7. The reaction mixture was
evaporated to a reduced volume (ffi15mL) and left over-
night at 5ꢁC. Compound 6 precipitated and was
obtained by filtration and purified by column
chromatography. In the case of 7, after neutralization
of the acidic medium, the reaction mixture was evapo-
rated and a syrup obtained. Column chromatography
gave the pure compound 7 in good yield.
3.2.4. c-Hexyl 2-acetamido-2-deoxy-(R)-4,6-O-(E-2-
methyl-3-phenyl-2-propenylidene)-b-D-glucopyranoside 9.
Yield 5.2g (81%); mp 174–175ꢁC; [a]D = ꢀ155.6 (c 0.3,
EtOH); MS(EI): m/z 431 (26%) [M]+Æ. 1H NMR
(500MHz, DMSO-d6): d 7.8 (d, 1H, J2,NH 9.0Hz,
NH), 7.5–7.3 (m, 5H, Ph), 6.65 [s, 1H,
PhCH@C(CH3)CH, 5.23 (d, 1H, J3,OH 5.8Hz, OH),
5.04 [s, 1H, PhCH@C(CH3)CH], 4.56 (d, 1H, J1,2
8.4Hz, H-1), 4.12 (dd, 1H, J5,6e 4.9Hz, J6e,6a 10.2Hz,
H-6e), 3.61 (dd, 1H, J2,3 = J3,4 9.5Hz, J3,OH 5.6Hz, H-
3), 3.59 (t, 1H, J5,6a = J6e,6a 10.1Hz, H-6a), 3.52 (m,
1H, OCHR), 3.36 (dd, 1H, J1,2 8.4Hz, J2,3 9.3Hz, H-
2), 3.28 (t, 1H, J3,4 = J4,5 9.2Hz, H-4), 3.22 (m, 1H,
H-5), 1.83 [d, 3H, 4J 1.2Hz, PhCH@C(CH3)CH],
1.72 (s, 3H, CH3CON), 1.7–1.2 [m, 10H, (CH2)5].
13C NMR (125MHz, DMSO-d6): d 168.2 (C@O),
135.5–127.4 (Ph), 133.4 [PhCH@C(CH3)CH], 126.2
[PhCH@C(CH3)CH], 103.1 [PhCH(CH3)CH], 99.2 (C-
1), 80.3 (C-4), 75.1 (OCHR), 69.5 (C-3), 66.9 (C-6),
65.1 (C-5), 56.0 (C-2), 32.1–22.0 [(CH2)5], 22.3
(CH3CON), 12.3 (CH3). HRMS(EI): [M] +Æ, found
431.230877. C24H33NO6 requires 431.230788. Anal.
Calcd for C24H33NO6: C, 66.80; H, 7.71; N, 3.25.
Found: C, 66.55; H, 7.52; N, 3.39.
3.3.1. Methyl (R)-4,6-O-(E-3-phenyl-2-propenylidene)-a-
D-glucopyranoside 12. Column chromatography using
dichloromethane–methanol (30:1) yielded 4.2g (90%);
mp 152–153ꢁC; [a]D = +97.2 (c 1.4, CH2Cl2); MS(CI):
1
m/z 309 (55%) [M+H]+. H NMR (200MHz, CDCl3):
d 7.5–7.3 (m, 5H, Ph), 6.79 (d, 1H, Jtrans 16.2Hz,
PhCH@CHCH), 6.18 (dd, 1H, Jtrans 16.2Hz, J 4.8Hz,
PhCH@CHCH), 5.15 (dd, 1H, J 4.8Hz, 4J 0.8Hz,
PhCH@CHCH), 4.8 (d, 1H, J1,2 3.8Hz, H-1), 4.15
(dd, 1H, J5,6e 3.8Hz, J6e,6a 9.2Hz, H-6e), 3.90 (t, 1H,
J2,3 = J3,4 9.2Hz, H-3), 3.7–3.5 (m, 3H, H-2, H-5, H-
6a), 3.4–3.3 (m, 4H, H-4, OCH3). 13C NMR (50MHz,
CDCl3): d 135.6–126.8 (Ph), 134.2 (PhCH@CHCH),
124.0 (PhCH@CHCH), 100.9 (PhCH@CHCH), 99.8
(C-1), 80.4 (C-4), 72.7 (C-2), 71.1 (C-3), 68.4 (C-6),
62.2 (C-5), 55.3 (OCH3). HRMS(EI): [M] +Æ, found
308.125585. C16H20O6 requires 308.125989. Anal. Calcd
for C16H20O6: C, 62.33; H, 6.54. Found: C, 62.17; H,
6.49.
3.3.2. Methyl (R)-4,6-O-(E-2-methyl-3-phenyl-2-propenyl-
idene)-a-D-glucopyranoside 13. Column chromatogra-
phy using dichloromethane–methanol (30:1) yielded
3.2g (67%); mp 105–106ꢁC; [a]D = +119.1 (c 1.1,
3.2.5. 1-Dodecyl 2-acetamido-2-deoxy-(R)-4,6-O-(E-2-
methyl-3-phenyl-2-propenylidene)-b-D-glucopyranoside 10.
Yield 5.4g (70%); mp 214–215ꢁC; [a]D = ꢀ53.3 (c 0.8,
1
1
EtOH); MS(CI): m/z 518 (100%) [M+H]+. H NMR
CH2Cl2); MS(CI): m/z 323 (75%) [M+H]+. H NMR
(200MHz, CDCl3): d 7.3–7.2 (m, 5H, Ph), 6.66 [s, 1H,
PhCH@C(CH3)CH], 5.75 (d, 1H, J2,NH 5.4Hz, NH),
5.01 [s, 1H, PhCH@C(CH3)CH], 4.67 (d, 1H, J1,2
8.3Hz, H-1), 4.26 (dd, 1H, J5,6e 4.3Hz, J6e,6a 10.1Hz,
H-6e), 4.12 (dd, 1H, J2,3 = J3,4 8.9Hz, H-3), 3.9–3.8
(m, 1H, OCHAHBR), 3.69 (t, 1H, J5,6a = J6e,6a 9.8Hz,
H-6a), 3.5–3.3 (m, 4H, H-2, H-4, H-5, OCHAHBR),
2.04 (s, 3H, CH3CON), 1.90 [d, 3H, 4J 1.4Hz,
PhCH@C(CH3)CH], 1.6–1.2 [m, (CH2)10], 0.86 (t, 3H,
J 6.5Hz, CH3). 13C NMR (50MHz, DMSO-d6): d
169.1 (C@O), 136.3–128.3 (Ph), 134.1 [PhCH@
C(CH3)CH], 127.1 [PhCH@C(CH3)CH], 104.0 101.6
[(C-1), PhCH(CH3)CH], 81.0 (C-4), 70.4 (C-3), 68.7
(OCH2R), 67.6 (C-6), 66.0 (C-5), 56.3 (C-2), 31.4–22.2
(200MHz, CDCl3): d 7.5–7.3 (m, 5H, Ph), 6.64 [d, 1H,
4J 1.2Hz, PhCH@C(CH3)CH], 4.96 [s, 1H,
PhCH@C(CH3)CH], 4.73 (d, 1H, J1,2 3.8Hz, H-1),
4.18 (dd, 1H, J5,6e 3.6Hz, J6e,6a 8.9Hz, H-6e), 3.90 (t,
1H, J2,3 = J3,4 9.2Hz, H-3), 3.7–3.5 (m, 3H, H-2, H-5,
H-6a), 3.4–3.3 (m, 4H, H-4, OCH3), 1.90 [d, 3H, 4J
1.2Hz, PhCH@C(CH3)CH]. 13C NMR (50MHz,
CDCl3): d 136.5–128.0 (Ph), 133.6 [PhCH@C(CH3)CH],
126.9 [PhCH@C(CH3)CH], 105.2 [PhCH@C(CH3)CH],
99.8 (C-1), 80.4 (C-4), 72.8 (C-2), 71.4 (C-3), 68.5 (C-
6), 62.3 (C-5), 55.4 (OCH3), 13.0 [PhCH@C(CH3)CH].
HRMS(EI): [M] +Æ, found 322.141336. C17H22O6 re-
quires 322.141639. Anal. Calcd for C17H22O6: C,
63.34; H, 6.88. Found: C, 63.57; H, 6.87.
[(CH2)10], 23.0 (CH3CON), 14.0 (CH3), 13.1
,
517.340208. C30H47NO6 requires 517.340339. Anal.
Calcd for C30H47NO6: C, 69.60; H, 9.15; N, 2.71.
Found: C, 69.27; H, 8.90; N, 2.71.
+Æ
[PhCH@C(CH3)CH]. HRMS(EI): [M]
found
3.4. Alkyl 2-acetamido-(R)-4,6-O-alkenylidene-3-O-
alkyl-2-deoxy-b-D-glucopyranosides 14–18
Method A: To a cooled solution (5ꢁC) of alkyl 2-aceta-
mido-(R)-4,6-O-alkenylidene-2-deoxy-b-D-glucopyrano-
sides 6, 7, 9 (6.0mmol) in fresh distilled THF (60mL)
were added, successively, freshly powdered potassium
hydroxide (2.0g, 35.7mmol), 18-crown-6 (120mg,
0.4mmol), and benzyl bromide (8.4mmol). The reaction
mixture was stirred at this temperature for 3h, and left
overnight at room temperature, then diluted with
dichloromethane (60mL) and washed successively with
water and an aqueous saturated solution of sodium
bicarbonate, dried over MgSO4, filtered, and the filtrate
3.3. Methyl (R)-4,6-O-alkenylidene-a-D-glucopyranosides
12 and 13
To a solution of methyl a-D-glucopyranoside 11
(15.0mmol) in acetonitrile (90mL) was added the corre-
sponding aldehyde dimethylacetal 4, 5 (25.0mmol) and
camphorsulfonic acid (15mg). The mixture was stirred
at room temperature for 3days. After checking by
TLC that all of the starting material had reacted, trieth-

´
J. M. Vega-Perez et al. / Tetrahedron: Asymmetry 15 (2004) 3617–3633
3625
evaporated to dryness. The solid obtained was purified
by flash chromatography on silica gel.
OCHAHBPh), 4.39 (t, 1H, J2,3 = J3,4 8.5Hz, H-3), 4.27
(dd, 1H, J5,6e 4.4Hz, J6e,6a 10.2Hz, H-6e), 3.69 (t, 1H,
J5,6a = J6e,6a 10.2Hz, H-6a), 3.6–3.4 (m, 3H, H-4, H-5,
OCHR), 3.04 (m, 1H, H-2), 1.92 [d, 3H, 4J 1.4Hz,
PhCH@C(CH3)CH], 1.86 (s, 3H, CH3CON), 1.8–
1.2 [m, 10H, (CH2)5]. 13C NMR (50MHz, CDCl3): d
170.3 (C@O), 138.4, 136.7, 129.1, 128.3, 128.1, 127.7
(Ph), 133.8 [PhCH@C(CH3)CH], 126.9 [PhCH@
C(CH3)CH], 104.2 [PhCH@C(CH3)CH], 98.2 (C-1),
82.6 (C-4), 77.6 (C-3), 76.0 (OCHR), 74.5 (OCH2Ph),
68.6 (C-6), 65.8 (C-5), 58.7 (C-2), 33.4–24.1 [(CH2)5],
23.8 (CH3CON), 13.4 [PhCH@C(CH3)CH]. HRMS
(CI): [M+H]+, found 522.282827. C31H40NO6 requires
522.285563. Anal. Calcd for C31H39NO6: C, 71.38; H,
7.54; N, 2.69. Found: C, 71.10; H, 7.32; N, 2.40.
3.4.1. c-Hexyl 2-acetamido-3-O-benzyl-2-deoxy-(R)-4,6-
O-(E-3-phenyl-2-propenylidene)-b-D-glucopyranoside 14.
Column chromatography using dichloromethane–meth-
anol (120:1) yielded 2.2g (73%); mp 245–246ꢁC;
[a]D = +5.5 (c 1.1, CHCl3); MS(CI): m/z 508 (22%)
1
[M+H]+. H NMR (200MHz, CDCl3): d 7.4–7.3 (m,
10H, 2Ph) 6.78 (d, 1H, Jtrans 16.1Hz, PhCH@CHCH),
6.18 (dd, 1H, J 4.4Hz, Jtrans 16.1Hz, PhCH@CHCH),
5.73 (d, 1H, J2,NH 7.4Hz, NH), 5.16 (dd, 1H, J 4.5Hz,
4J 0.9Hz, PhCH@CHCH), 5.11 (d, 1H, J1,2 8.3Hz, H-
1), 4.88 (d, 1H, Jgem 11.8Hz, OCHAHBPh), 4.64 (d,
1H, Jgem 11.8Hz, OCHAHBPh), 4.36 (t, 1H, J2,3 = J3,4
8.5Hz, H-3), 4.25 (dd, 1H, J5,6e 4.5Hz, J6e,6a 10.2Hz,
H-6e), 3.68 (t, 1H, J5,6a = J6e,6a 10.2Hz, H-6a), 3.6–3.4
(m, 3H, H-4, H-5, OCHR), 3.1 (m, 1H, H-2), 1.9–1.2
[m, 13H, CH3CON, (CH2)5]. 13C NMR (50MHz,
CDCl3): d 170.3 (C@O), 136.7–126.8 (Ph), 133.7
(PhCH@CHCH), 124.5 (PhCH@CHCH), 100.6, 98.4
(PhCH@CHCH, C-1), 82.5 (C-4), 77.7 (C-3), 76.3
(OCHR), 74.5 (OCH2Ph), 68.5 (C-6), 65.7 (C-5),
58.5 (C-2), 33.4–24.0 [(CH2)5], 23.8 (CH3CON). HRMS
(CI): [M+H]+, found 508.268461. C30H38NO6 requires
508.269913. Anal. Calcd for C30H37NO6: C, 70.98; H,
7.35; N, 2.76. Found: C, 70.72; H, 7.41; N, 2.72.
Method B: To a cooled solution (5ꢁC) of alkyl 2-acetam-
ido-2-deoxy-(R)-4,6-O-(E-3-phenyl-2-propenylidene)-b-
D-glucopyranosides 6, 7 (2.0mmol) in distilled dichloro-
methane (200mL) were added triethylamine (20mL) and
5-chlorodibenzosuberane (6.0mmol). The reaction mix-
ture was stirred at this temperature for 3h and left at
room temperature for 48h. The mixture was washed
with water, dilute hydrochloric acid, and aqueous satu-
rated solution of sodium bicarbonate, dried over
MgSO4, and evaporated. The pure product was ob-
tained by column chromatography in good yield.
3.4.4. c-Hexyl 2-acetamido-2-deoxy-3-O-(5-dibenzosu-
beryl)-(R)-4,6-O-(E-3-phenyl-2-propenylidene)-b-D-gluco-
pyranoside 17. Column chromatography using
hexane–ethyl acetate (3.2:1) yielded 0.75g (62%); mp
221–222ꢁC; [a]D = ꢀ44.1 (c 1.0, CHCl3); MS(FAB):
3.4.2. 1-Dodecyl 2-acetamido-3-O-benzyl-2-deoxy-(R)-
4,6-O-(E-3-phenyl-2-propenylidene)-b-D-glucopyranoside
15. Column chromatography using dichloromethane–
methanol (140:1) yielded 2.9g (81%); mp 189–190ꢁC;
[a]D = +48.0 (c 0.5, CHCl3); MS(EI): m/z 593 (26%)
[M]+Æ. 1H NMR (200MHz, CDCl3): d 7.4–7.3 (m,
10H, 2Ph) 6.79 (d, 1H, Jtrans 16.1Hz, PhCH@CHCH),
6.18 (dd, 1H, J 4.4Hz, Jtrans 16.1Hz, PhCH@CHCH),
5.56 (d, 1H, J2,NH 7.7Hz, NH), 5.18 (dd, 1H, J
4.4Hz, 4J 0.8Hz, PhCH@CHCH), 4.93 (d, 1H, J1,2
8.4Hz, H-1), 4.88 (d, 1H, Jgem 11.5Hz, OCHAHBPh),
4.62 (d, 1H, Jgem 11.8Hz, OCHAHBPh), 4.3–4.2 (m,
2H, H-3, H-6e), 3.8–3.4 (m, 5H, H-4, H-5, H-
6aOCH2R), 3.24 (t, 1H, J1.2 = J2,3 8.3Hz, H-2), 1.86
(s, 3H, CH3CON), 1.5–1.2 [m, 20H, (CH2)10], 0.86 (t,
3H, J 6.5Hz, CH3). 13C NMR (50MHz, CDCl3): d
170.3 (C@O), 138.5–126.9 (Ph), 133.8 (PhCH@CHCH),
124.5 (PhCH@ CHCH), 100.7, 100.3 (PhCH@CHCH,
C-1), 82.5 (C-4), 76.4 (C-3), 74.5 (OCH2Ph), 70.2
(OCH2R), 68.5 (C-6), 65.8 (C-5), 58.0 (C-2), 31.9–22.7
[(CH2)10], 23.6 (CH3CON), 14.1 (CH3). HRMS(CI):
[M+H]+, found 594.379054. C36H52NO6 requires
594.379464. Anal. Calcd for C36H51NO6: C, 72.82; H,
8.66; N, 2.36. Found: C, 73.06; H, 7.8.54; N, 2.15.
1
m/z 632 (63%) [M+Na]+. H NMR (200MHz, CDCl3):
d 7.5–7.2 (m, 13H, Ph) 6.80 (d, 1H, Jtrans 16.1Hz,
PhCH@CHCH), 6.22 (dd, 1H, Jtrans 16.1Hz, J 5.5Hz,
PhCH@CHCH), 5.65 (s, 1H, CH suberyl group), 5.13
(m, 2H, NH, PhCH@CHCH), 4.88 (d, 1H, J1,2 8.3Hz,
H-1), 4.3–4.1 (m, 2H, H-3, H-6e), 3.7–2.8 [m, 9H, H-2,
H-4, H-5, H-6a, OCHR, (CH2)2 suberyl group], 1.61
(s, 3H, CH3CON). 13C NMR (50MHz, CDCl3): d
169.7 (C@O), 135.9–125.8 (Ph), 133.9 (PhCH@CHCH),
124.6
(PhCH@CHCH),
101.0,
99.1
(C-1,
PhCH@CHCH), 82.7 (C-4), 77.6 (C-3), 76.4 (OCHR,
CH suberyl group), 68.6 (C-6), 65.8 (C-5), 57.5 (C-2),
33.3–23.7 [(CH2)5, (CH2)2 suberyl group], 23.3
(CH3CON). HRMS(EI): [M] +Æ, found 609.310537.
C38H43NO6 requires 609.309039. Anal. Calcd for
C38H43NO6: C, 74.85; H, 7.11; N, 2.30. Found: C,
74.72; H, 7.09; N, 2.26.
3.4.5. 1-Dodecyl 2-acetamido-2-deoxy-3-O-(5-dibenzosu-
beryl)-(R)-4,6-O-(E-3-phenyl-2-propenylidene)-b-D-gluco-
pyranoside 18. Column chromatography using
hexane–ethyl acetate (3.4:1) yielded 0.9g (64%); mp
217–218ꢁC; [a]D = ꢀ41.6 (c 1.1, CHCl3); MS(CI): m/z
696 (10%) [M+H]+. 1H NMR (200MHz, CDCl3): d
7.5–7.2 (m, Ph) 6.81 (d, 1H, Jtrans 16.4Hz,
PhCH@CHCH), 6.23 (dd, 1H, J 4.8Hz, Jtrans 16.4Hz,
PhCH@CHCH), 5.64 (s, 1H, CH suberyl group), 5.13
(d, 1H, J 4.8Hz, PhCH@CHCH), 4.97 (d, 1H, J2,NH
7.0Hz, NH), 4.67 (d, 1H, J1,2 8.3Hz, H-1), 4.25 (dd,
1H, J5,6e 4.8Hz, J6e,6a 10.3Hz, H-6e), 4.05 (t, 1H,
3.4.3. c-Hexyl 2-acetamido-3-O-benzyl-2-deoxy-(R)-4,
6-O-(E-2-methyl-3-phenyl-2-propenylidene)-b-D-glucopyr-
anoside 16. Column chromatography using dichloro-
methane–methanol (120:1) yielded 2.5g (80%); mp
233–234ꢁC; [a]D = +17.5 (c 1.1, CHCl3); MS(CI): m/z
522 (20%) [M+H]+. 1H NMR (200MHz, CDCl3): d
7.4–7.3 (m, 10H, 2Ph) 6.70 [s, 1H, PhCH@C(CH3)CH],
5.68 (d, 1H, J2,NH 7.3Hz, NH), 5.15 (d, 1H, J1,2 8.3Hz,
H-1), 4.99 [s, 1H, PhCH@C(CH3)CH], 4.87 (d, 1H, Jgem
11.7Hz, OCHAHBPh), 4.63 (d, 1H, Jgem 11.7Hz,

´
J. M. Vega-Perez et al. / Tetrahedron: Asymmetry 15 (2004) 3617–3633
3626
J2,3 = J3,4 9.4Hz, H-3), 3.8–2.9 [m, 10H, H-4, H-5, H-2,
H-6a, OCH2R, (CH2)2 suberyl group], 1.63 (s, 3H,
CH3CON), 1.5–1.2 [m, 20H, (CH2)10], 0.86 (t, 3H, J
6.5Hz, CH3). 13C NMR (50MHz, CDCl3): d 169.7
(C@O), 135.8–125.8 (Ph), 134.1 (PhCH@CHCH),
124.5 (PhCH@CHCH), 101.1 (PhCH@CHCH, C-1),
82.7 (C-4), 76.4 (C-3, CH suberyl group), 70.0
(OCH2R), 68.6 (C-6), 65.8 (C-5), 56.4 (C-2), 32.8–22.6
dried over MgSO4, filtered, and the filtrate evaporated
to dryness. The solvent was removed under reduced
pressure to give a solid, which was purified by flash
chromatography on silica gel using diethyl ether–hexane
(10:1) as eluent. Yield 0.60g (63%); mp 251–252ꢁC;
[a]D = ꢀ70.4 (c 1.1, CHCl3); MS(CI): m/z 460 (27%)
[M+H]+. 1H NMR (500MHz, DMSO-d6): d 7.92 (d,
1H, J2,NH 9.3Hz, NH), 7.5–7.3 (m, 5H, Ph) 6.71 (d,
1H, Jtrans 16.1Hz, PhCH@CHCH), 6.20 (dd, 1H, J
5.1Hz, Jtrans 16.1Hz, PhCH@CHCH), 5.22 (d, 1H, J
5.1Hz, PhCH@CHCH), 5.11 (t, 1H, J2,3 = J3,4 9.9Hz,
H-3), 4.69 (d, 1H, J1,2 8.4Hz, H-1), 4.15 (dd, 1H, J5,6e
5.0Hz, J6e,6a 10.2Hz, H-6e) 3.7–3.6 (m, 3H, H-2, H-4,
H-6a), 3.44 (m, 1H, OCHR), 3.38 (m, 1H, J4,5 = J5,6a
10.0Hz, J5,6e 5.1Hz, H-5), 1.96 (s, 3H, CH3CON),
1.74 (s, 3H, CH3COO), 1.7–1.2 [m, 10H, (CH2)5]. 13C
NMR (50MHz, DMSO-d6): d 169.7, 169.0 (2C@O),
135.4–126.8 (Ph), 133.3 (PhCH@CHCH), 124.8
(PhCH@CHCH), 100.2, 99.6 (PhCH@CHCH, C-1),
77.8 (C-4), 76.3 (OCHR), 71.9 (C-3), 67.4 (C-6), 65.6
[(CH2)10, (CH2)2 suberyl group], 23.2 (CH3CON), 14.1
(CH3). HRMS(CI): [M+H]
+
, found 696.425146.
C44H58NO6 requires 696.426414. Anal. Calcd for
C44H57NO6: C, 75.94; H, 8.26; N, 2.01. Found: C,
76.05; H, 8.14; N, 1.94.
3.5. c-Hexyl 2-acetamido-2-deoxy-2-N-3-O-methylidene-
(R)-4,6-O-(E-3-phenyl-2-propenylidene)-b-D-glucopyrano-
side 19
To a solution of c-hexyl 2-acetamido-2-deoxy-(R)-4,6-
O-(E-3-phenyl-2-propenylidene)-b-D-glucopyranoside 6
(2.5mmol) in distilled dichloromethane (50mL) were
added dibromomethane (50mL), 50% aqueous sodium
hydroxide solution (100mL), and tetrabutylammonium
bromide (6.5mg, 0.02mmol). The reaction mixture was
stirred vigorously under reflux for 2days, then cooled
to room temperature. The organic phase was washed
with water until neutral, dried over MgSO4, and the sol-
vent removed under reduced pressure to give a solid,
which was purified by flash chromatography on silica
gel using hexane–ethyl acetate (3.2:1) as eluent, yielding
0.80g (82%); mp 151–152ꢁC; [a]D = ꢀ17.9 (c 1.3,
(C-5), 54.1 (C-2), 32.9–22.9 [(CH2)5], 22.7 (CH3CON),
20.6 (CH3COO). HRMS(EI): [M]
+Æ
,
found
459.224705. C25H33NO7 requires 459.225703. Anal.
Calcd for C25H33NO7: C, 65.35; H, 7.24; N, 3.05.
Found: C, 65.37; H, 7.23; N, 3.00.
3.6.2. 1-Dodecyl 2-acetamido-3-O-benzyloxycarbonyl-2-
deoxy-(R)-4,6-O-(E-3-phenyl-2-propenylidene)-b-D-gluco-
pyranoside 21. To a cooled solution of 1-dodecyl
2-acetamido-2-deoxy-(R)-4,6-O-(E-3-phenyl-2-propenyli-
dene)-b-D-glucopyranoside 7 (2.0mmol) in THF–dichlo-
romethane (5:3) (80mL) were very slowly added dry
pyridine (7mL), and benzyl chloroformate (1.5mL,
10mmol). The reaction mixture was stirred at room tem-
perature for 2days, then diluted with dichloromethane
(20mL), washed successively with water, dilute aqueous
solution of hydrochloric acid (3 · 20mL), saturated
aqueous solution of sodium bicarbonate (3 · 20mL),
and water, dried over MgSO4, filtered, and the filtrate
evaporated to dryness. The solvent was removed under
reduced pressure to give a solid, which was purified by
recrystallization from 96% ethanol. Yield 0.93g (73%);
mp 151–152ꢁC; [a]D = ꢀ58.2 (c 0.8, CHCl3); MS(CI):
1
CHCl3); MS(CI): m/z 430 (100%) [M+H]+. H NMR
(200MHz, CDCl3): d 7.4–7.2 (m, 5H, Ph), 6.79 (d, 1H,
Jtrans 16.2Hz, PhCH@CHCH), 6.16 (dd, 1H, J 4.6Hz,
Jtrans 16.4Hz, PhCH@CHCH), 5.52 (d, 1H, Jgem 5.5Hz,
4
OCHAHBN), 5.23 (dd, 1H, J 4.6Hz, J 0.9Hz, PhCH@
CHCH), 4.77 (d, 1H, J1,2 7.8Hz, H-1), 4.73 (d, 1H, Jgem
5.5Hz, OCHAHBN), 4.29 (dd, 1H, J5,6e 4.7Hz, J6e,6a
10.4Hz, H-6e), 3.9–3.8 (m, 3H, H-3, H-4, H-6a), 3.7 (m,
1H, OCHR), 3.5–3.3 (m, 2H, H-2, H-5), 2.25 (s, 3H,
CH3CON), 2.0–1.2 [m, 10H, (CH2)5]. 13C NMR
(50MHz, CDCl3): d 173.9 (C@O), 135.7–126.9 (Ph),
134.4 (PhCH@CHCH), 123.6 (PhCH@CHCH), 102.2,
100.8 (PhCH@CHCH, C-1), 82.5 (C-4), 82.3 (OCH2N),
78.9, 78.4 (C-3, OCHR), 69.1 (C-2), 68.4 (C-6), 62.2 (C-
5), 33.6–23.2 [(CH2)5], 24.0 (CH3CON). HRMS(EI):
[M]+Æ, found 429.216742. C24H31NO6 requires
429.215138. Anal. Calcd for C24H31NO6: C, 67.11; H,
7.27; N, 3.26. Found: C, 66.86; H, 7.37; N, 3.21.
1
m/z 638 (26%) [M+H]+. H NMR (200MHz, CDCl3):
d 7.5–7.3 (m, 10H, 2Ph) 6.72 (d, 1H, Jtrans 16.1Hz,
PhCH@CHCH), 6.11 (dd, 1H, J 4.7Hz, Jtrans 16.1Hz,
PhCH@CHCH), 5.73 (d, 1H, J2,NH 8.7Hz, NH), 5.3–
4
5.1 (m, 3H, H-3, OCH2Ph), 5.09 (d, 1H, J 0.8Hz, J
4.7Hz, PhCH@CHCH), 4.68 (d, 1H, J1,2 8.3Hz, H-1),
4.27 (dd, 1H, J5,6e 4.3Hz, J6e,6a 10.2Hz, H-6e) 3.9–3.2
(m, 6H, H-2, H-4, H-5, H-6a, OCH2R), 1.87 (s, 3H,
CH3CON), 1.5–1.2 [m, 20H, (CH2)10], 0.86 (t, 3H, J
6.5Hz, CH3). 13C NMR (50MHz, CDCl3): d 170.1,
3.6. Alkyl 2-acetamido-3-O-acyl-2-deoxy-(R)-4,6-O-(E-3-
phenyl-2-propenylidene)-b-D-glucopyranosides 20 and 21.
3.6.1. c-Hexyl 2-acetamido-3-O-acetyl-2-deoxy-(R)-4,6-
O-(E-3-phenyl-2-propenylidene)-b-D-glucopyranoside 20.
To a solution of c-hexyl 2-acetamido-2-deoxy-(R)-4,6-
O-(E-3-phenyl-2-propenylidene)-b-D-glucopyranoside 6
(2.0mmol) in distilled dichloromethane (250mL) were
added acetic anhydride (6mL) and dry pyridine
(6mL). The reaction mixture was stirred overnight at
room temperature and then washed successively with
water, dilute aqueous solution of acetic acid, saturated
aqueous solution of sodium bicarbonate, and water,
155.1
(2C@O),
135.7–126.8
(Ph),
134.1
(PhCH@CHCH), 123.9 (PhCH@CHCH), 101.3, 100.9
(PhCH@CHCH, C-1), 78.5 (C-4), 75.4 (C-3), 70.2,
69.9 (OCH2Ph, OCH2R), 68.3 (C-6), 65.9 (C-5), 55.3
(C-2), 31.9–22.6 [(CH2)10], 23.1 (CH3CON), 14.1
, found 638.369213.
+
(CH3). HRMS(CI): [M+H]
C37H52NO8 requires 638.369293. Anal. Calcd for
C37H51NO8: C, 69.68; H, 8.06; N, 2.20. Found: C,
69.75; H, 7.95; N, 2.07.

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J. M. Vega-Perez et al. / Tetrahedron: Asymmetry 15 (2004) 3617–3633
3627
3.7. 1-Dodecyl 2-acetamido-(R)-4,6-O-(E-2-alkyl-3-phen-
yl-2-propenylidene)-2-deoxy-3-O-methanosulfonyl-b-D-gluco-
pyranosides 22 and 23
3.8. 1-Dodecyl 2-acetamido-2-deoxy-(R)-4,6-O-(E-3-
phenyl-2-propenylidene)-b-D-allopyranoside 24
A solution of 1-dodecyl 2-acetamido-2-deoxy-3-O-meth-
anosulfonyl-(R)-4,6-O-(E-3-phenyl-2-propenylidene)-b-
D-glucopyranoside 22 (1.16g, 2.0mmol) and anhydrous
sodium acetate (1.10g) in 96:4 2-methoxyethanol-water
(15mL) was heated at reflux temperature for 12h. After
cooling, the mixture was poured into water and the
precipitate collected by filtration and recrystallized
from ethanol. Yield 0.81g (81%); mp 231–233ꢁC;
[a]D = +20.0 (c 1.0, EtOH); MS(CI): m/z 504 (73%)
To a cooled solution (0ꢁC) of 1-dodecyl 2-acetamido-2-
deoxy-(R)-4,6-O-(E-3-phenyl-2-propenylidene)-b-D-glu-
copyranoside 7 or 1-dodecyl 2-acetamido-2-deoxy-(R)-
4,6-O-(E-2-methyl-3-phenyl-2-propenylidene)-b-D-gluc-
opyranoside 10 (2.0mmol) in dry pyridine (25mL)
was slowly added methanosulfonyl chloride (0.4mL,
5.0mmol). The reaction mixture was kept overnight at
5ꢁC, then poured into water (150mL) with stirring,
and the precipitate isolated by filtration. The pure com-
pounds were obtained by recrystallization from 96%
ethanol.
1
[M+H]+. H NMR (200MHz, CDCl3): d 7.4–7.3 (m,
5H, Ph), 6.77 (d, 1H, Jtrans 16.2Hz, PhCH@CHCH),
6.16 (dd, 1H, Jtrans 16.2Hz, J 4.8Hz, PhCH@CHCH),
6.00 (d, 1H, J2,NH 9.0Hz, NH), 5.21 (d, 1H, J 4.8Hz,
PhCH@CHCH), 4.62 (d, 1H, J1,2 8.5Hz, H-1), 4.3–4.2
(m, 2H, H-3, H-6e), 4.10 (ddd, 1H, J5,6e 4.5Hz,
J1,2 = J2,NH 8.8Hz, J2,3 2.9Hz, H-2) 3.9–3.3 (m, 5H,
H-4, H-5, H-6a, OCH2R), 2.00 (s, 3H, CH3CON), 1.5–
1.1 [m, 20H, (CH2)10], 0.85 (t, 3H, J 6.1Hz, CH3). 13C
NMR (50MHz, CDCl3): d 169.8 (C@O), 135.5–126.8
(Ph), 134.3 (PhCH@CHCH), 124.0 (PhCH@CHCH),
101.1, 100.1 (PhCH@CHCH, C-1), 78.4, (C-4), 69.8
(OCH2R), 68.8 (C-6), 68.6 (C-3), 65.2 (C-5), 52.2 (C-
2), 31.8–22.6 [(CH2)10], 23.3 (CH3CON), 14.1 (CH3).
HRMS(CI): [M+H] +, found 504.330959. C29H46NO6
requires 504.332514. Anal. Calcd for C29H45NO6: C,
69.15; H, 9.00; N, 2.78. Found: C, 68.83; H, 9.09; N,
2.77.
3.7.1. 1-Dodecyl 2-acetamido-2-deoxy-3-O-methanosulfo-
nyl-(R)-4,6-O-(E-3-phenyl-2-propenylidene)-b-D-gluco-
pyranoside 22. Yield 0.91g (78%); mp 161–163ꢁC;
[a]D = ꢀ68.0 (c 1.0, EtOH); MS(CI): m/z 582 (36%)
1
[M+H]+. H NMR (200MHz, CDCl3): d 7.5–7.3 (m,
5H, Ph) 6.75 (d, 1H, Jtrans 16.1Hz, PhCH@CHCH),
6.10 (dd, 1H, J 5.0Hz, Jtrans 16.1Hz, PhCH@CHCH),
5.90 (d, 1H, J2,NH 7.7Hz, NH), 5.2–5.1 (m, 2H, H-3,
PhCH@CHCH), 5.06 (d, 1H, J1,2 8.2Hz, H-1), 4.30
(dd, 1H, J5,6e 4.5Hz, J6e,6a 10.2Hz, H-6e) 3.9–3.3 (m,
6H, H-2, H-4, H-5, H-6a, OCH2R), 3.04 (s, 3H,
CH3SO3), 2.00 (s, 3H, CH3CON), 1.5–1.2 [m, 20H,
(CH2)10], 0.86 (t, 3H, J 6.5Hz, CH3). 13C NMR
(50MHz, CDCl3): d 171.2 (C@O), 135.4–126.9 (Ph),
134.7 (PhCH@CHCH), 123.6 (PhCH@CHCH), 101.1,
100.3 (PhCH@CHCH, C-1), 78.9, 78.8 (C-4, C-3), 70.5
(OCH2R), 68.3 (C-6), 65.4 (C-5), 57.1 (C-2), 38.6
3.9. Epoxidation with m-chloroperoxybenzoic acid
To a solution of the different (R)-4,6-O-propenylidene
derivatives 6–10, 12–24 (2.0mmol) in chloroform
(150mL) was added a solution of m-chloroperoxyben-
zoic acid (Aldrich 57–86%) (3.0g) in chloroform
(50mL), previously dried over MgSO4. The reaction
mixture was kept at ꢀ15ꢁC until TLC showed that all
of the starting compound had been consumed (2-
months), after which the solution was washed succes-
sively with 5% aqueous sodium hydroxide (7 · 30mL)
and water, dried over MgSO4, filtered, and the filtrate
evaporated to dryness. The diastereomeric excess (de)
(CH3SO3), 31.9–22.6 [(CH2)10], 23.0 (CH3CON), 14.1
(CH3). HRMS(CI): [M+H]
C30H48NO8Srequires 582.310065. Anal. Calcd for
C30H47NO8S: C, 61.97; H, 8.15; N, 2.41; S, 5.50. Found:
C, 61.72; H, 7.95; N, 2.32; S, 5.50.
+
, found 582.308948.
3.7.2. 1-Dodecyl 2-acetamido-2-deoxy-3-O-methanosulf-
onyl-(R)-4,6-O-(E-2-methyl-3-phenyl-2-propenylidene)-b-
D-glucopyranoside 23. Yield 0.90g (76%); mp 162–
163ꢁC; [a]D = ꢀ19.4 (c 0.8, CH2Cl2); MS(FAB): m/z
1
1
618 (36%) [M+Na]+. H NMR (200MHz, CDCl3): d
was determined by H NMR. The solids obtained were
purified by recrystallization from either ethanol or by
flash chromatography on silica gel.
7.3–7.2 (m, 5H, Ph), 6.63 [br s, 1H, PhCH@C(CH3)CH],
5.97 (d, 1H, J2,NH 7.6Hz, NH), 5.21 (t, 1H, J2,3 9.4Hz,
H-3), 5.11 (d, 1H, J1,2 8.2Hz, H-1), 4.98 [s, 1H,
PhCH@C(CH3)CH], 4.31 (dd, 1H, J5,6e 4.5Hz, J6e,6a
10.2Hz, H-6e) 3.8–3.3 (m, 6H, H-2, H-4, H-5, H-6a,
OCH2R), 3.02 (s, 3H, CH3 SO3), 2.00 (s, 3H, CH3CON),
3.9.1. c-Hexyl 2-acetamido-2-deoxy-(R)-4,6-O-[(2R,3S)-
2,3-epoxy-3-phenylpropylidene]-b-D-glucopyranoside 25.
Two stereoisomers were obtained in 71:28 ratio (42%
de). The pure diastereoisomeric mixture was obtained
by recrystallization from 96% ethanol. Yield 0.70g
(84%); mp 209–210ꢁC; [a]D = ꢀ123.6 (c 0.3, DMF);
4
1.87 [d, 3H, J 1.4Hz, PhCH@C(CH3)CH], 1.5–1.2 [m,
20H, (CH2)10], 0.86 (t, 3H, J 6.2Hz, CH3). 13C NMR
(50MHz, CDCl3): d 171.4 (C@O), 136.2–128.2 (Ph),
133.1 [PhCH@C(CH3)CH], 127.2 [PhCH@C(CH3)CH],
104.9, 100.2 [PhCH@C(CH3)CH, C-1], 78.9, 78.6 (C-4,
C-3), 70.9 (OCH2R), 68.3 (C-6), 65.4 (C-5), 57.3 (C-2),
38.4 (CH3SO3), 31.9–22.7 [(CH2)10], 23.4 (CH3CON),
14.1 (CH3), 13.1 [PhCH@C(CH3)CH]. HRMS(CI):
[M+H]+, found 596.324272. C31H50NO8Srequires
596.325715. Anal. Calcd for C31H49NO8S: C, 62.49; H,
8.29; N, 2.35; S, 5.38. Found: C, 62.77; H, 8.49; N,
2.42; S, 5.40.
MS(CI):
m/z 434 (100%) [M+H]+. 1H NMR
(500MHz, DMSO-d6): d 7.80 (d, 1H, J2,NH 9.0Hz,
NH), 7.5–7.3 (m, 5H, Ph), 5.24 (br s, 1H, OH), 4.62
[d, J 4.6Hz, PhCH(O)CHCH major], 4.60 [d, J 4.6Hz,
PhCH(O)CHCH minor], 4.53 (d, 1H, J1,2 8.4Hz, H-1),
4.11 (m, 1H, H-6e), 3.99 [d, Jtrans 2,0Hz, PhCH(O)-
CHCH minor], 3.98 [d, Jtrans 2,0Hz, PhCH(O)CHCH
major], 3.6–3.5 (m, 2H, H-3, OCHR), 3.37 (t, J5,6a
J6e,6a 9.5Hz, H-6a major), 3.29 [dd, Jtrans 2.0Hz, J
=

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J. M. Vega-Perez et al. / Tetrahedron: Asymmetry 15 (2004) 3617–3633
3628
4.6Hz, PhCH(O)CHCH major], 3.25 (m, 3H, H-2, H-4,
H-5), 1.81 (s, CH3CON minor), 1.79 (s, CH3CON ma-
jor), 1.7–1.2 [m, 10H, (CH2)5]. 13C NMR (125MHz,
DMSO-d6): d 169.0 (C@O minor), 168.9 (C@O major),
136.0–126.0 (Ph), 100.0 (C-1), 99.6 [PhCH(O)CHCH
minor], 99.4 [PhCH(O)CHCH major], 81.0 (C-4 major),
80.8 (C-4 minor), 75.9 (OCHR), 70.2 (C-3 minor), 70.1
(C-3 major), 67.5 (C-6 minor), 67.3 (C-6 major),
65.6 (C-5), 60.2 [PhCH(O)CHCH minor], 60.1
d6): d 169.2 (C@O), 137.9–126.1 (Ph), 101.5 (C-1), 99.6
[PhCH(O)CHCH minor], 99.5 [PhCH(O)CHCH major],
80.9 (C-4), 70.7 (C-3), 70.2 (OCH2Ph), 67.3 (C-6), 65.9
(C-5), 60.1 [PhCH(O)CHCH], 56.1 (C-2), 54.8
[PhCH(O)CHCH major], 54.5 [PhCH(O)CHCH minor],
23.1 (CH3CON). HRMS(EI): [M] +Æ, found 441.175649.
C24H27NO7 requires 441.178753. Anal. Calcd for
C24H27NO7: C, 65.30; H, 6.18; N, 3.17. Found: C,
65.19; H, 6.34; N, 2.98.
[PhCH(O)CHCH
[PhCH(O)CHCH major], 54.4 [PhCH(O)CHCH minor],
major],
56.5
(C-2),
54.7
3.9.4. c-Hexyl 2-acetamido-2-deoxy-(R)-4,6-O-[(2R,3S)-
2,3-epoxy-2-methyl-3-phenylpropylidene]-b-D-glucopyr-
anoside 28. Two stereoisomers were obtained in 87:13
ratio (74% de). The pure diastereoisomeric mixture
was obtained by recrystallization from 96% ethanol.
Yield 0.72g (81%); mp 184–185ꢁC; [a]D = ꢀ83.3 (c 0.5,
DMF); MS(CI): m/z 448 (46%) [M+H]+. 1H NMR
(200MHz, DMSO-d6): d 7.79 (d, 1H, J2,NH 8.8Hz,
NH), 7.4–7.2 (m, 5H, Ph), 5.29 (d, 1H, J3,OH 5.5Hz,
OH), 4.57 (d, 1H, J1,2 8.4Hz, H-1), 4.47 [s, PhCH(O)-
C(CH3)CH major], 4.43 [s, PhCH(O)C(CH3)CH minor],
4.2–4.1 [m, 2H, H-6e, PhCH(O)C(CH3)CH], 3.6–3.5 (m,
3H, OCHR, H-3, H-6a), 3.3–3.2 (m, 3H, H-2, H-4, H-5),
1.79 (s, 3H, CH3CON), 1.7–1.2 [m, 10H, (CH2)5], 1.00
[s, PhCH(O)C(CH3)CH major], 0.99 [s, PhCH(O)-
C(CH3)CH minor]. 13C NMR (50MHz, DMSO-d6): d
169.0 (C@O), 134.7–126.4 (Ph), 102.5 [PhCH(O)-
C(CH3)CH minor], 102.2 [PhCH(O)C(CH3)CH major],
99.8 (C-1), 80.9 (C-4 major), 80.7 (C-4 minor), 75.8
(OCHR), 70.0 (C-3), 67.5 (C-6 minor), 67.4 (C-6 major),
65.8 (C-5), 62.2 [PhCH(O)C(CH3)CH], 59.8 [PhCH(O)-
C(CH3)CH major], 59.6 [PhCH(O)C(CH3)CH minor],
56.8 (C-2), 32.9–22.8 [(CH2)5], 23.1 (CH3CON), 10.7
32.9–23.0 [(CH2)5], 23.1 (CH3CON major), 23.1
(CH3CON minor). HRMS(EI): [M]
+Æ
,
found
433.210378. C23H31NO7 requires 433.210053. Anal.
Calcd for C23H31NO7: C, 63.73; H, 7.21; N, 3.23.
Found: C, 63.80; H, 6.95; N, 3.30.
3.9.2. 1-Dodecyl 2-acetamido-2-deoxy-(R)-4,6-O-[(2R,3S)-
2,3-epoxy-3-phenylpropylidene]-b-D-glucopyranoside 26.
Two stereoisomers were obtained in 67:33 ratio (34%
de). The pure diastereoisomeric mixture was obtained
by recrystallization from 96% ethanol. Yield 0.80g
(77%); mp 251–252ꢁC; [a]D = ꢀ62.0 (c 1.2, DMF);
MS(CI): m/z 520 (40%) [M+H]+. 1H NMR (200
MHz, DMSO-d6):
d 7.84 (d, 1H, J2,NH 9.4Hz,
NH), 7.4–7.3 (m, 5H, Ph), 5.34 (br s, 1H, OH), 4.63
[d, J 4.6Hz, PhCH(O)CHCH major], 4.62 [d, J 4.5Hz,
PhCH(O)CHCH minor], 4.41 (d, 1H, J1,2 8.0Hz, H-1),
4.11 (m, 1H, H-6e), 3.99 [d, Jtrans 1.9Hz, PhCH(O)-
CHCH minor], 3.98 [d, Jtrans 1.9Hz, PhCH(O)CHCH
major], 3.7–3.2 [m, 8H, PhCH(O)CHCH, OCH2R, H-
2, H-3, H-4, H-5, H-6a], 1.79 (s, CH3CON minor),
1.78 (s, CH3CON major), 1.5–1.2 [m, 20H, (CH2)10],
0.84 (t, 3H, J 6.4Hz, CH3). 13C NMR (50MHz,
DMSO-d6): d 169.0 (C@O), 136.0–126.1 (Ph), 101.6
(C-1), 99.5 [PhCH(O)CHCH minor], 99.4 [PhCH(O)-
CHCH major], 80.9 (C-4 major), 80.8 (C-4 minor),
70.3 (C-3), 68.7 (OCH2R), 67.4 (C-6 minor), 67.3 (C-6
major), 65.8 (C-5), 60.1 [PhCH(O)CHCH], 56.1 (C-2),
54.7 [PhCH(O)CHCH major], 54.5 [PhCH(O)CHCH
[PhCH(O)C(CH3)CH
major],
10.5
C(CH3)CH minor]. HRMS(CI): [M+H]
[PhCH(O)-
,
+
found
448.233465. C24H34NO7 requires 448.233528. Anal.
Calcd for C24H33NO7: C, 64.41; H, 7.43; N, 3.13.
Found: C, 64.14; H, 7.47; N, 3.30.
3.9.5. 1-Dodecyl 2-acetamido-2-deoxy-(R)-4,6-O-[(2R,3S)-
2,3-epoxy-2-methyl-3-phenylpropylidene]-b-D-glucopyra-
noside 29. Two stereoisomers were obtained in 78:22
ratio (56% de). The pure diastereoisomeric mixture
was obtained by recrystallization from 96% ethanol.
Yield 0.77g (72%); mp 221–222ꢁC; [a]D = ꢀ57.1 (c 0.7,
minor], 31.3–22.1 [(CH2)10], 23.0 (CH3CON), 14.0
found 519.322610.
+Æ
(CH3). HRMS(EI): [M]
,
C29H45NO7 requires 519.319603. Anal. Calcd for
C29H45NO7: C, 67.03; H, 8.73; N, 2.69. Found: C,
66.74; H, 8.58; N, 2.63.
1
CHCl3); MS(CI): m/z 534 (72%) [M+H]+. H NMR
3.9.3. Benzyl 2-acetamido-2-deoxy-(R)-4,6-O-[(2R,3S)-
2,3-epoxy-3-phenylpropylidene]-b-D-glucopyranoside 27.
Two stereoisomers were obtained in 71:29 ratio (42%
de). The pure diastereoisomeric mixture was obtained
by column chromatography using dichloromethane–
methanol (50:1) as eluent. Yield 0.5g (58%); mp 254–
256ꢁC; [a]D = ꢀ52.0 (c 1.0, DMF); MS(CI): m/z 442
(200MHz, CDCl3): d 7.4–7.2 (m, 5H, Ph), 5.86 (d, 1H,
J2,NH 5.4Hz, NH), 4.69 (d, 1H, J1,2 8.3Hz, H-1), 4.47
[s, PhCH(O)C(CH3)CH major], 4.44 [s, PhCH(O)-
C(CH3)CH minor], 4.25 (dd, 1H, J5,6e 4.2Hz, J6e,6a
10.3Hz, H-6e), 4.14 [s, PhCH(O)C(CH3)CH major],
4.13 [s, PhCH(O)C(CH3)CH minor], 3.82 (m, 1H,
OCHAHBR), 3.7–3.3 (m, 5H, H-2, H-4, H-5, H-6a,
OCHAHBR), 2.03 (s, 3H, CH3CON), 1.6–1.2 [m, 20H,
(CH2)10], 1.11 [s, PhCH(O)C(CH3)CH major, 1.09 [s,
PhCH(O)C(CH3)CH minor], 0.86 (t, 3H, J 6.5Hz,
CH3). 13C NMR (50MHz, DMSO-d6): d 169.0 (C@O),
134.7–126.5 (Ph), 102.6 [PhCH(O)C(CH3)CH minor],
102.3 [PhCH(O)C(CH3)CH major], 101.5 (C-1), 80.9
(C-4 major), 80.6 (C-4 minor), 70.2 (C-3), 68.7
(OCH2R), 67.4 (C-6 minor), 67.3 (C-6 major), 65.9 (C-
5 major), 65.6 (C-5 minor), 62.2 [PhCH(O)C(CH3)CH],
59.8 [PhCH(O)C(CH3)CH major], 59.7 [PhCH(O)-
1
(11%) [M+H]+. H NMR (200MHz, CDCl3): d 7.4–7.3
(m, 10H, 2Ph), 5.5 (m, 1H, NH), 4.89 (d, 1H, Jgem
12.1Hz, OCHAHBPh), 4.67 [d, J 4.0Hz, PhCH(O)-
CHCH major], 4.62 (d, 1H, J1,2 8.3Hz, H-1), 4.56 (d,
1H, Jgem 12.1Hz, OCHAHBPh), 4.27 (m, 1H, H-6e),
4.00 (m, 1H, H-3), 4.00 [d, Jtrans 1.9Hz, PhCH(O)-
CHCH minor], 3.94 [d, Jtrans 1.9Hz, PhCH(O)CHCH
major], 3.7–3.4 [m, 4H, H-2, H-4, H-5, H-6a], 3.24 [dd,
1H, Jtrans 1.7Hz, J 4.0Hz, PhCH(O)CHCH major],
1.95 (s, 3H, CH3CON). 13C NMR (50MHz, DMSO-

´
J. M. Vega-Perez et al. / Tetrahedron: Asymmetry 15 (2004) 3617–3633
3629
C(CH3)CH minor], 56.3 (C-2), 31.3–22.1 [(CH2)10], 23.0
(CH3CON), 14.0 (CH3), 10.7 [PhCH(O)C(CH3)CH ma-
jor], 10.5 [PhCH(O)C(CH3)CH minor]. HRMS(CI):
[M+H]+, found 534.342345. C30H48NO7 requires
534.343078. Anal. Calcd for C30H47NO7: C, 67.51; H,
8.88; N, 2.62. Found: C, 67.36; H, 8.96; N, 2.58.
0.6, CHCl3); MS(CI): m/z 524 (83%) [M+H]+. 1H
NMR (500MHz, DMSO-d6): d 7.96 (d, 1H, J2,NH
8.9Hz, NH), 7.4–7.2 (m, 10H, 2Ph), 4.7–4.5 [m, 4H,
H-1, OCH2Ph, PhCH(O)CHCH], 4.14 (dd, 1H, J5,6e
4.9Hz, J6e,6a 9.9Hz, H-6e), 4.00 [d, Jtrans 2.0Hz,
PhCH(O)CHCH major], 3.97 [d, Jtrans 2.0Hz,
PhCH(O)CHCH minor], 3.7–3.5 (m, 5H, OCHR, H-2,
H-3, H-4, H-6a), 3.37 (m, 1H, H-5), 3.30 [dd, Jtrans
2.0Hz, J 4.1Hz, PhCH(O)CHCH major], 3.27 [dd,
1H, Jtrans 2.0Hz, J 4.3Hz, PhCH(O)CHCH minor],
1.80 (s, 3H, CH3CON), 1.7–1.2 [m, 10H, (CH2)5]. 13C
NMR (125MHz, DMSO-d6): d 169.2 (C@O), 1368.0–
125.2 (Ph), 99.0 (C-1), 98.6 [PhCH(O)CHCH minor],
98.4 [PhCH(O)CHCH major], 79.9 (C-4 minor), 79.8
(C-4 major), 77.6 (C-3 major), 77.5 (C-3 minor), 75.2
(OCH2Ph), 72.3 (OCHR), 66.8 (C-6 major), 66.6 (C-6
minor), 64.6 (C-5), 59.4 [PhCH(O)CHCH minor],
59.3 [PhCH(O)CHCH major], 54.3 (C-2 minor), 54.2
(C-2 major), 53.8 [PhCH(O)CHCH major], 53.7
[PhCH(O)CHCH minor], 32.1–22.1 [(CH2)5], 23.1
(CH3CON). HRMS(CI): [M+H] +, found 524.264828.
C30H38NO7 requires 524.264904. Anal. Calcd for
C30H37NO7: C, 68.81; H, 7.12; N, 2.67. Found: C,
68.57; H, 6.95; N, 2.62.
3.9.6. Methyl (R)-4,6-O-[(2R,3S)-2,3-epoxy-3-phenylpro-
pylidene]-a-D-glucopyranoside 30. Two stereoisomers
were obtained in 73:27 ratio (46% de). The pure diaste-
reoisomeric mixture was obtained by column chromato-
graphy using dichloromethane–methanol (30:1) as
eluent. Yield 0.50g (77%); mp 76–78ꢁC; [a]D = +61.4
1
(c 1.0, CHCl3); MS(EI): m/z 324 (7%) [M]+Æ. H NMR
(200MHz, CDCl3): d 7.4–7.2 (m, 5H, Ph), 4.75 (d, 1H,
J1,2 3.8Hz, H-1), 4.69 [d, J 3.6Hz, PhCH(O)CHCH ma-
jor], 4.65 [d, J 3.6Hz, PhCH(O)CHCH minor], 4.18 (dd,
1H, J5,6e 4.3Hz, J6e,6a 9.7Hz, H-6e), 3.99 [d, Jtrans 2.1Hz,
PhCH(O)CHCH minor], 3.97 [d, Jtrans 2.1Hz,
PhCH(O)CHCH major], 3.90 (t, J2,3 = J3,4 9.2Hz, H-3
minor), 3.88 (t, J2,3 = J3,4 9.2Hz, H-3 major), 3.7–3.5
(m, 3H, H-2, H-5, H-6a), 3.39 (s, 3H, OCH3), 3.31 (t,
J3,4 = J4,5 9.2Hz, H-4), 3.22 [dd, 1H, Jtrans 2.1Hz, J
3.6Hz, PhCH(O)CHCH]. 13C NMR (50MHz, CDCl3):
d 135.8–125.9 (Ph), 99.8, 99.3 [PhCH(O)CHCH, C-1],
80.5 (C-4), 72.7 (C-2), 71.2 (C-3), 68.4 (C-6), 62.1 (C-
3.9.9. 1-Dodecyl 2-acetamido-3-O-benzyl-2-deoxy-(R)-
4,6-O-[(2S,3R)-2,3-epoxy-3-phenylpropylidene]-b-D-gluco-
pyranoside 33. Two stereoisomers were obtained in a
61:39 ratio (22% de). The pure diastereoisomeric mix-
ture was obtained by column chromatography using
dichloromethane–methanol (100:1) as eluent. Yield
1.0g (86%); mp 159–160ꢁC; [a]D = ꢀ0.5 (c 1.7, CH2Cl2);
5), 60.5 [PhCH(O)CHCH], 55.4 [OCH3, PhCH(O)-
,
+Æ
CHCH]. HRMS(EI): [M]
found 324.210381.
C16H20O7 requires 324.120903. Anal. Calcd for
C16H20O7: C, 59.25; H, 6.22. Found: C, 59.04; H, 6.25.
3.9.7. Methyl (R)-4,6-O-[(2R,3S)-2,3-epoxy-2-methyl-3-
phenylpropylidene]-a-D-glucopyranoside 31. Two stereo-
isomers were obtained in an 86:14 ratio (72% de). The
pure diastereoisomeric mixture was obtained by column
1
MS(CI): m/z 610 (95%) [M+H]+. H NMR (200MHz,
CDCl3): d 7.3–7.2 (m, 10H, 2Ph), 5.54 (d, 1H, J2,NH
7.7Hz, NH), 4.96 (d, 1H, J1,2 8.3Hz, H-1), 4.87 (d, Jgem
11.7Hz, OCHAHBPh major), 4.83 (d, 1H, Jgem 11.7Hz,
OCHAHBPh minor), 4.70 [d, J 3.3Hz, PhCH(O)CHCH
major], 4.64 [d, J 3.3Hz, PhCH(O)CHCH minor], 4.61
(d, Jgem 11.7Hz, OCHAHBPh major), 4.59 (d, Jgem
11.7Hz, OCHAHBPh minor), 4.3–4.2 (m, 2H, H-3, H-
6e), 3.96 [d, Jtrans 2.0Hz, PhCH(O)CHCH major], 3.93
[d, Jtrans 2.0Hz, PhCH(O)CHCH minor], 3.20 [dd, Jtrans
2.0Hz, J 3.3Hz, PhCH(O)CHCH major], 1.86 (s,
CH3CON minor), 1.85 (s, CH3CON major), 1.5–1.2
[m, 10H, (CH2)10], 0,86 (t, 3H, J 6.5Hz, CH3). 13C
NMR (50MHz, CDCl3): 170.3 (C@O), 138.4–125.7
(Ph), 100.2 (C-1), 99.7 [PhCH(O)CHCH minor], 99.4
[PhCH(O)CHCH major], 82.6 (C-4), 76.2 (C-3), 74.5
(OCH2Ph), 70.2 (OCH2 R), 68.4 (C-6), 65.6 (C-5), 60.8
[PhCH(O)CHCH], 58.1 (C-2), 55.2 [PhCH(O)CHCH
minor], 55.0 [PhCH(O)CHCH major], 31.9–22.6
[(CH2)10], 23.5 (CH3CON), 14.1 (CH3). HRMS(CI):
[M+H]+, found 609.371674. C36H51NO7 requires
609.366554. Anal. Calcd for C36H51NO7: C, 70.91; H,
8.43; N, 2.30. Found: C, 70.79; H, 7.8.22; N, 2.28.
chromatography
using
dichloromethane–methanol
(30:1) as eluent. Yield 0.53g (78%); mp 87–89ꢁC;
[a]D = +66.2 (c 0.9, CHCl3); MS(EI): m/z 338 (8%)
1
[M]+Æ. H NMR (200MHz, CDCl3): d 7.4–7.2 (m, 5H,
Ph), 4.75 (d, 1H, J1,2 3.9Hz, H-1), 4.47 [s, PhCH(O)-
C(CH3)CH major], 4.41 [s, 1H, PhCH(O)C(CH3)CH
minor], 4.20 (dd, 1H, J5,6e 4.1Hz, J6e,6a 9.4Hz, H-6e),
4.16 [s, PhCH(O)C(CH3)CH major], 4.11 [s,
PhCH(O)C(CH3)CH minor], 3.89 (t, 1H, J2,3 = J3,4
9.2Hz, H-3), 3.7–3.5 (m, 3H, H-2, H-5, H-6a), 3,40 (s,
3H, OCH3), 3.31 (t, 1H, J3,4 9.2Hz, H-4), 1.10 [s,
PhCH(O)C(CH3)CH major], 1.09 [s, PhCH(O)-
C(CH3)CH minor]. 13C NMR (50MHz, CDCl3): d
134.6–126.6 (Ph), 102.8, 99.8 PhCH(O)C(CH3)CH, C-
1], 80.6 (C-4), 72.7 (C-2), 71.4 (C-3), 68.5 (C-6), 62.5
[PhCH(O)C(CH3)CH], 62.2 (C-5), 60.5 [PhCH(O)-
C(CH3)CH], 55.4 (OCH3), 11.3 [PhCH(O)C(CH3)CH
major], 11.0 [PhCH(O)C(CH3)CH minor]. HRMS
(EI): [M]+Æ, found 338.136406. C17H22O7 requires
338.136553. Anal. Calcd for C17H22O7: C, 60.35; H,
6.55. Found: C, 60.05; H, 6.57.
3.9.10. c-Hexyl 2-acetamido-3-O-benzyl-2-deoxy-(R)-4,
6-O-[(2S,3R)-2,3-epoxy-2-methyl-3-phenylpropylidene]-b-
D-glucopyranoside 34. Two stereoisomers were
obtained in a 67:33 ratio (34% de). The pure diastereo-
isomeric mixture was obtained by column chromatogra-
phy using dichloromethane–methanol (120:1) as eluent.
Yield 0.88g (86%); mp 199–200ꢁC; [a]D = +9.7 (c 0.5,
3.9.8. c-Hexyl 2-acetamido-3-O-benzyl-2-deoxy-(R)-4,
6-O-[(2S,3R)-2,3-epoxy-3-phenylpropylidene]-b-D-gluco-
pyranoside 32. Two stereoisomers were obtained in a
64:36 ratio (28% de). The pure diastereoisomeric mix-
ture was obtained by recrystallization from 96% etha-
nol. Yield 0.86g (82%); mp 225–226ꢁC; [a]D = ꢀ29.3 (c

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J. M. Vega-Perez et al. / Tetrahedron: Asymmetry 15 (2004) 3617–3633
3630
CHCl3); MS(CI): m/z 538 (32%) [M+H]+. H NMR
(200MHz, CDCl3): d 7.4–7.2 (m, 5H, Ph), 5.80 (d, 1H,
J2,NH 7.2Hz, NH), 5.16 (d, J1,2 8.3Hz, H-1 major),
5.15 (d, J1,2 8.3Hz, H-1 minor), 4.87 (d, 1H, Jgem
11.6Hz, OCHAHBPh), 4.64 (d, Jgem 11.6Hz,
OCHAHBPh minor), 4.63 (d, Jgem 11.6Hz, OCHAHBPh
major), 4.47 [s, PhCH(O)C(CH3)CH major], 4.40 [s,
PhCH(O)C(CH3)CH minor], 4.15 [s, PhCH(O)-
C(CH3)CH major], 4.10 [s, PhCH(O)C(CH3)CH minor],
3.7–3.4 (m, 4H, H-2, H-4, H-6a, OCHR), 3.03 (m, 1H,
H-5), 1.87 (s, CH3CON minor), 1.86 (s, CH3CON ma-
jor), 1.7–1.2 [m, 10H, (CH2)5], 1.12 [s, PhCH(O)-
C(CH3)CH major], 1.10 [s, PhCH(O)C(CH3)CH
minor]. 13C NMR (50MHz, CDCl3): d 170.4 (C@O),
138.2–126.5 (Ph), 102.9 [PhCH(O)C(CH3)CH minor],
102.5 [PhCH(O)C(CH3)CH major], 98.1 (C-1), 82.5,
(C-4), 77.6 (C-3), 75.6 (OCHR), 74.5 (OCH2Ph), 72.3
68.4 (C-6), 65.5 (C-5), 62.4 [PhCH(O)C(CH3)CH],
60.4 [PhCH(O)C(CH3)CH minor], 60.1 [PhCH(O)-
C(CH3)CH major], 58.6 (C-2), 33.3–23.7 [(CH2)5], 23.5
[a]D = ꢀ53.2 (c 0.7, CH2Cl2); MS(CI): m/z 712 (8%)
1
1
[M+H]+. H NMR (200MHz, CDCl3): d 7.5–7.1 (m,
13H, Ph), 5.62 (s, OCH suberyl group major), 5.56 (s,
OCH suberyl group minor), 5.02 (m, 1H, NH), 4.71
(d, J1,2 8.3Hz, H-1 major), 4.68 (d, J1,2 8.3Hz, H-1 min-
or), 4.60 [d, 1H, J 3.8Hz, PhCH(O)CHCH], 4.3–4.0 (m,
2H, H-6e, H-3), 3.96 [d, Jtrans 1.9Hz, PhCH(O)CHCH
major], 3.93 [d, Jtrans 1.9Hz, PhCH(O)CHCH minor],
3.8–2.8 [m, 11H, H-2, H-4, H-5, H-6a, OCH2R, (CH2)2
suberyl group, PhCH(O)CHCH], 1.64 (s, 3H,
CH3CON), 1.5–1.2 [m, 20H, (CH2)10], 0.86 (t, 3H, J
6.8Hz, CH3). 13C NMR (50MHz, CDCl3): d 169.8
(C@O), 130.7–125.9 (Ph), 100.9 (C-1), 99.9 [PhCH(O)-
CHCH], 82.7 (C-4), 75.3 (OCH suberyl group, C-3),
70.1 (OCH2R), 68.5 (C-6), 65.7 (C-5), 60.8
[PhCH(O)CHCH major], 60.6 [PhCH(O)CHCH minor],
56.9 (C-2), 55.4 [PhCH(O)CHCH minor], 55.1
[PhCH(O)CHCH major], 32.8–22.7 [(CH2)10, (CH2)2
suberyl group], 23.4 (CH3CON), 14.1 (CH3). HRMS
(CI): [M+H]+, found 712.419050. C44H58NO7 requires
712.421329. Anal. Calcd for C44H57NO7: C, 74.23; H,
8.07; N, 1.97. Found: C, 73.98; H, 7.90; N, 1.73.
(CH3CON), 11.5 [PhCH(O)C(CH3)CH major], 10.8
[PhCH(O)C(CH3)CH minor]. HRMS(CI): [M+H]
+Æ
,
found 538.280744. C31H40NO7 requires 538.280478.
Anal. Calcd for C31H39NO7: C, 69.25; H, 7.31; N,
2.61. Found: C, 69.20; H, 7.31; N, 2.36.
3.9.13.
c-Hexyl
2-acetamido-2-deoxy-(R)-4,6-O-(2,
3-epoxy-3-phenylpropylidene)-2-N-3-O-methylidene-b-D-
glucopyranoside 37. Two stereoisomers were obtained
without diastereoisomeric excess. The pure diastereoiso-
meric mixture was obtained by recrystallization from
96% ethanol. Yield 0.6g (65%); mp 152–153ꢁC;
[a]D = ꢀ40.7 (c 0.5, CH2Cl2); MS(CI): m/z 446 (100%)
3.9.11. c-Hexyl 2-acetamido-2-deoxy-3-O-(5-dibenzosu-
beryl)-(R)-4,6-O-[(2S,3R)-2,3-epoxy-3-phenylpropylidene]-
b-D-glucopyranoside 35. Two stereoisomers were
obtained in a 68:32 ratio (36% de). The pure diastereoiso-
meric mixture was obtained by recrystallization from
96% ethanol. Yield 0.94g (72%); mp 186–188ꢁC;
[a]D = ꢀ30.0 (c 0.7, DMF); MS(CI): m/z 626 (10%)
[M+H]+. 1H NMR (200MHz, CDCl3): d 7.5–7.1 (m,
13H, Ph), 5.65 (s, OCH suberyl group major), 5.60 (s,
OCH suberyl group minor), 5.19 (d, 1H, J2,NH 7.5Hz,
NH), 4.93 (d, J1,2 8.3Hz, H-1 major), 4.90 (d, J1,2
8.3Hz, H-1 minor), 4.61 [d, J 3.8Hz, PhCH(O)CHCH
major], 4.59 [d, J 3.8Hz, PhCH(O)CHCH minor],
4.3–4.1 (m, 2H, H-3, H-6e), 3.97 [d, Jtrans 2.0Hz,
PhCH(O)CHCH major], 3.93 [d, Jtrans 2.0Hz, PhCH(O)-
CHCH minor], 3.7–2.8 [m, 10H, OCHR, H-4, H-5, H-2,
H-6a, PhCH(O)CHCH, (CH2)2 suberyl group], 2.04 (s,
CH3CON major), 2.00 (s, CH3CON minor), 1.8–1.2 [m,
10H, (CH2)5]. 13C NMR (50MHz, CDCl3): d 169.8
(C@O), 130.7–125.9 (Ph), 99.9 [PhCH(O)CHCH],
98.9 (C-1), 82.7 (C-4), 77.0 (C-3), 76.4 (OCH suberyl
group), 75.0 (OCHR), 68.5 (C-6), 65.6 (C-5), 60.7
[PhCH(O)CHCH minor], 60.6 [PhCH(O)CHCH major],
57.7 (C-2), 55.4 [PhCH(O)CHCH major], 55.2
[M+H]+. H NMR (200MHz, CDCl3): d 7.4–7.2 (m,
1
5H, Ph), 5.49 (d, 1H, Jgem 5.5Hz, OCHAHBN), 4.8–4.7
(m, 2H, OCHAHBN, H-1), 4.65 [d, 1H, J 4.2Hz,
PhCH(O)CHCH], 4.3–4.2 (m, 2H, H-3, H-6e), 3.99,
3.93 [2d, 1H, Jtrans 1.9Hz, PhCH(O)CHCH], 3.8–3.2
[m, 6H, H-2, H-4, H-5, H-6a, OCHR, PhCH(O)CHCH],
2.24 (s, 3H, CH3CON), 1.7–1.2 [m, 10H, (CH2)5]. 13C
NMR (50MHz, CDCl3): d 169.8 (C@O), 135.9–125.8
(Ph), 102.2 (C-1), 100.0, 99.1 [PhCH(O)CHCH], 82.4
(OCH2N), 82.1 (C-4), 78.9, 78.5 (C-3, OCHR), 68.9
(C-2), 68.3 (C-6), 62.2 (C-5), 60.5, 60.4 [PhCH(O)-
CHCH], 55.6, 54.8 [PhCH(O)CHCH], 33.6-23.7
+
[(CH2)5], 23.2 (CH3CON). HRMS(CI): [M+H] , found
446.218439. C24H32NO7 requires 446.217878. Anal.
Calcd for C24H31NO7: C, 64.70; H, 7.01; N, 3.14.
Found: C, 64.44; H, 6.81; N, 2.95.
3.9.14. c-Hexyl 2-acetamido-3-O-acetyl-2-deoxy-(R)-4,
6-O-(2,3-epoxy-3-phenylpropylidene)-b-D-glucopyranoside
38. Two stereoisomers were obtained without diaster-
eoisomeric excess. The pure diastereoisomeric mixture
was obtained by column chromatography using diethyl
ether–hexane–methanol (9:1:0.3) as eluent. Yield 0.6g
(68%); mp 201–202ꢁC; [a]D = ꢀ35.5 (c 0.9, DMF); MS
(CI): m/z 476 (24%) [M+H]+. 1H NMR (200MHz,
CDCl3): d 7.3–7.2 (m, 5H, Ph), 6.20, 6.17 (2d, 1H,
J2,NH 9.4Hz, NH), 5.25 (m, 1H, H-3), 4.63 (d, 1H, J1,2
8.6Hz, H-1), 4.59 [d, 1H, J 3.7Hz, PhCH(O)CHCH],
4.24 (m, 1H, H-6e), 3.98 (t, 1H, J5,6a = J6e,6a 9.4Hz, H-
6a), 3.89, 3.87 [2d, 1H, Jtrans 1.9Hz, PhCH(O)CHCH],
3.7–3.4 (m, 4H, H-2, H-4, H-5, OCHR), 3.14 [m, 1H,
PhCH(O)CHCH], 2.08, 2.06 (2s, 3H, CH3COO), 1.92
(s, 3H, CH3CON), 1.7–1.2 [m, 10H, (CH2)5]. 13C
[PhCH(O)CHCH minor], 33.3–23.4 [(CH2)5, (CH2)2 sub-
eryl group], 23.7 (CH3CON). HRMS(CI): [M+H]
+
,
found 626.308667. C38H44NO7 requires 626.311778.
Anal. Calcd for C38H43NO7: C, 72.94; H, 6.93; N, 2.24.
Found: C, 72.60; H, 6.86; N, 2.28.
3.9.12. 1-Dodecyl 2-acetamido-2-deoxy-3-O-(5-dibenzo-
suberyl)-(R)-4,6-O-[(2S,3R)-2,3-epoxy-3-phenylpropyl-
idene]-b-D-glucopyranoside 36. Two stereoisomers were
obtained in a 62:38 ratio (24% de). The pure diastereo-
isomeric mixture was obtained by recrystallization from
96% ethanol. Yield 1.0g (69%); mp 184–185ꢁC;

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J. M. Vega-Perez et al. / Tetrahedron: Asymmetry 15 (2004) 3617–3633
3631
NMR (50MHz, CDCl3): d 171.1, 169.9 (2C@O), 135.6–
125.4 (Ph), 99.8 (C-1), 99.3, 99.0 [PhCH(O)CHCH], 78.0
(C-4), 77.0 (C-3), 71.5 (OCHR), 68.0 (C-6), 65.5 (C-5),
60.2, 60.1 [PhCH(O)CHCH], 55.0, 54.7 [2PhCH(O)-
CHCH], 54.4 (C-2), 32.8–23.2 [(CH2)5], 23.0
(CH3CON), 20.6 (CH3COO). HRMS(EI): [M] +Æ, found
475.219945. C25H33NO8 requires 475.220617. Anal.
Calcd for C25H33NO8: C, 63.14; H, 6.99; N, 2.95.
Found: C, 62.86; H, 6.83; N, 2.81.
C-3), 70.5 (OCH2R), 68.2 (C-6), 65.2 (C-5), 60.3, 60.2
[PhCH(O)CHCH], 56.9, 56.9 (C-2), 55.6 [PhCH(O)-
CHCH major], 54.7 [PhCH(O)CHCH minor], 38.7,
38.5 (CH3SO2), 31.9–22.6 [(CH2)10], 23.4 (CH3CON),
14.1 (CH3). HRMS(CI): [M+H] +, found 598.305657.
C30H48NO9Srequires 598.304979. Anal. Calcd for
C30H47NO9S: C, 60.28; H, 7.65; N, 2.34. Found: C,
60.55; H, 7.67; N, 2.43.
3.9.17. 1-Dodecyl 2-acetamido-2-deoxy-(R)-4,6-O-[(2R,
3S)-2,3-epoxy-2-methyl-3-phenylpropylidene]-3-O-metha-
nosulfonyl-b-D-glucopyranoside 41. Two stereoisomers
were obtained in a 56:44 ratio (12% de). The pure dia-
stereoisomeric mixture was obtained by column chro-
matography using hexane–ethyl acetate (1.2:1) as
eluent. Yield 0.8g (68%); mp 139–140ꢁC; [a]D = ꢀ30.4
3.9.15. 1-Dodecyl 2-acetamido-3-O-benzyloxycarbonyl-
2-deoxy-(R)-4,6-O-[(2S,3R)-2,3-epoxy-3-phenylpropylid-
ene]-b-D-glucopyranoside 39. Two stereoisomers were
obtained in a 56:44 ratio (12% de). The pure diastereo-
isomeric mixture was obtained by recrystallization from
96% ethanol. Yield 0.9g (72%); mp 103–104ꢁC;
[a]D = ꢀ45.2 (c 0.6, CHCl3); MS(CI): m/z 654 (17%)
1
(c 0.9, CHCl3); MS(CI): m/z 612 (13%) [M+H]+. H
1
[M+H]+. H NMR (200MHz, CDCl3): d 7.3–7.2 (m,
NMR (200MHz, CDCl3): d 7.4–7.2 (m, 5H, Ph), 5.96
(m, 1H, NH), 5.24 (m, 1H, H-3), 5.14 (d, J1,2 8.1Hz,
H-1 major), 5.13 (d, J1,2 8.0Hz, H-1 minor), 4.52 [s,
PhCH(O)C(CH3)CH minor], 4.34 [s, PhCH(O)-
C(CH3)CH major], 4.28 (m, 1H, H-6e), 4.09 [s,
PhCH(O)C(CH3)CH minor], 4.03 [s, PhCH(O)-
C(CH3)CH major], 3.81 (m, 1H, OCHAHBR) 3.7–3.3
(m, 5H, H-2, H-4, H-5, H-6a, OCHAHBR), 3.13 (s,
CH3SO2 major), 3.08 (s, CH3SO2 minor), 2.00 (s, 3H,
CH3CON), 1.5–1.2 [m, 20H, (CH2)10], 1.08 [s,
PhCH(O)C(CH3)CH minor], 1.04 [s, PhCH(O)-
C(CH3)CH major], 0.86 (t, 3H, J 6.4Hz, CH3). 13C
NMR (50MHz, CDCl3): d 171.4 (C@O), 134.4–126.3
(Ph), 103.7 [PhCH(O)C(CH3)CH major], 102.5
[PhCH(O)C(CH3)CH minor], 100.1 (C-1), 78.8, 78.7
(C-4, C-3), 70.6 (OCH2R), 68.2 (C-6), 65.3 (C-5), 62.1
10H, 2Ph), 5.61 (d, J2,NH 8.5Hz, NH major), 5.60 (d,
J2,NH 8.5Hz, NH minor), 5.3–5.1 (m, 2H, PhCH2OCO,
H-3), 4.76 (d, J1,2 8.3Hz, H-1 major), 4.74 (d, J1,2
8.3Hz, H-1 minor), 4.64 [d, J 3.3Hz, PhCH(O)CHCH
major], 4.56 [d, J 3.9Hz, PhCH(O)CHCH minor], 4.27
(m, 1H, H-6e), 3.92 [d, Jtrans 2.0Hz, PhCH(O)CHCH
major], 3.88 [d, Jtrans 2.0Hz, PhCH(O)CHCH minor],
3.8–3.4 (m 6H, H-2, H-4, H-5, H-6a, OCH2R), 3.16
[m, 1H, PhCH(O)CHCH], 1.78 (s, CH3CON major),
1.77 (s, CH3CON minor), 1.5–1.2 [m, 20H, (CH2)10],
0.86 (t, 3H, J 6.5Hz, CH3). 13C NMR (50MHz, CDCl3):
d 170.2, 155.0 (2C@O), 136.0–125.8 (Ph), 101.1 (C-1),
99.7 [PhCH(O)CHCH minor], 99.4 [PhCH(O)CHCH
major], 78.6 (C-4 major), 78.5 (C-4 minor), 74.9 (C-3),
70.3, 70.0 (PhCH2OCO, OCH2R), 68.2 (C-6), 65.8 (C-
5), 60.5 [PhCH(O)CHCH major], 60.4 [PhCH(O)CHCH
[PhCH(O)C(CH3)CH
major],
62.0
[PhCH(O)-
minor],
55.6
[PhCH(O)CHCH
major],
55.4
C(CH3)CH minor], 60.9 [PhCH(O)C(CH3)CH major],
60.0 [PhCH(O)C(CH3)CH minor], 57.4 (C-2), 38.7
(CH3SO2 major), 38.5 (CH3SO2 minor), 31.9–22.7
[(CH2)10], 23.4 (CH3CON), 14.1 (CH3), 11.5 [PhCH(O)-
C(CH3)CH minor], 10.6 [PhCH(O)C(CH3)CH major].
HRMS(CI): [M+H] +, found 612.320568. C31H50NO9S
requires 612.320630. Anal. Calcd for C31H49NO9S : C,
60.87; H, 8.07; N, 2.29. Found: C, 60.65; H, 7.93; N,
2.49.
[PhCH(O)CHCH minor], 54.9 (C-2), 31.9–22.6
[(CH2)10], 23.0 (CH3CON), 14.1 (CH3). HRMS(CI):
[M+H]+, found 654.362872. C37H52NO9 requires
654.364208. Anal. Calcd for C37H51NO9: C, 67.97; H,
7.86; N, 2.14. Found: C, 67.78; H, 7.78; N, 2.10.
3.9.16. 1-Dodecyl 2-acetamido-2-deoxy-(R)-4,6-O-[(2R,
3S)-2,3-epoxy-3-phenylpropylidene]-3-O-methanosulfonyl-
b-D-glucopyranoside 40. Two stereoisomers were
obtained in a 51:49 ratio (2% de). The pure diastereo-
isomeric mixture was obtained by column chro-
matography using hexane–ethyl acetate (1.2:1) as
eluent. Yield 0.9g (75%); mp 125–126ꢁC; [a]D = ꢀ30.8
3.9.18. 1-Dodecyl 2-acetamido-2-deoxy-(R)-4,6-O-[(2S,
3R)-2,3-epoxy-3-phenylpropylidene]-b-D-allopyranoside
42. Two stereoisomers were obtained in an 83:17 ratio
(66% de). The pure diastereoisomeric mixture was ob-
tained by column chromatography using dichlorometh-
ane–methanol (60:1) as eluent. Yield 0.6g (60%); mp
212–213ꢁC; [a]D = ꢀ40.9 (c 1.1, DMF); MS(CI): m/z
520 (18%) [M+H]+. 1H NMR (500MHz, CDCl3): d
7.3–7.2 (m, 5H, Ph), 5.96 (d, 1H, J2,NH 9.1Hz, NH),
4.68 [d, J 3.8Hz, PhCH(O)CHCH major], 4.65 [d, J
3.8Hz, PhCH(O)CHCH minor], 4.61 (d, J1,2 8.5Hz,
H-1 major), 4.57 (d, J1,2 8.5Hz, H-1 minor), 4.3–4.2
(m, 2H, H-3, H-6e), 4.08 (dt, 1H, J1,2 8.5Hz, J2,3
2.8Hz, J2,NH 9.0Hz, H-2), 3.93 [d, Jtrans 2.0Hz,
PhCH(O)CHCH major], 3.91 [d, Jtrans 2.0Hz,
PhCH(O)CHCH minor], 3.87 (dt, 1H, J4,5 = J5,6a
10.0Hz, J5,6e 4.7Hz, H-5), 3.80 (m, 1H, OCHAHBR),
3.61 (t, 1H, J5,6a = J6e,6a 10.2Hz, H-6a minor), 3.60 (t,
1H, J5,6a = J6e,6a 10.2Hz, H-6a major), 3.46 (dd, 1H,
(c 0.9, CH2Cl2); MS(CI): m/z 598 (7%) [M+H]+. H
1
NMR (200MHz, CDCl3): d 7.3–7.2 (m, 5H, Ph), 5.89
(d, J2,NH 7.6Hz, NH major), 5.87 (d, J2,NH 7.6Hz,
NH minor), 5.23 (t, 1H, J2,3 = J3,4 9.4Hz, H-3), 5.10
(d, 1H, J1,2 8.1Hz, H-1), 4,63 [d, J 3.2Hz, PhCH(O)-
CHCH minor], 4.53 [d, J 4.6Hz, PhCH(O)CHCH ma-
jor], 4.28 (m, 1H, H-6e), 3.91 [d, Jtrans 1.9Hz, PhCH(O)-
CHCH minor], 3.89 [d, Jtrans 1.9Hz, PhCH(O)CHCH
major], 3.79 (m, 1H, OCHAHBR), 3.6–3.3 (m, 5H,
H-2, H-4, H-5, H-6a, OCHAHBR), 3.15 [m, 1H,
PhCH(O)CHCH], 3.12 (s, CH3SO2 major), 3.05 (s,
CH3SO2 minor), 2.00 (s, 3H, CH3CON), 1.5–1.2 [m,
20H, (CH2)10], 0.86 (t, 3H, J 6.4Hz, CH3). 13C NMR
(50MHz, CDCl3): d 171.3 (C@O), 135.6–125.6 (Ph),
100.3 (C-1), 99.2 [PhCH(O)CHCH], 78.8, 78.5 (C-4,

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J. M. Vega-Perez et al. / Tetrahedron: Asymmetry 15 (2004) 3617–3633
3632
J3,4 2.4Hz, J4,5 9.6Hz, H-4), 3.40 (m, 1H, OCHAHBR),
3.19 [dd, 1H, Jtrans 2.0Hz, J 3.8Hz, PhCH(O)CHCH],
2.08 (s, CH3CON minor), 1.99 (s, CH3CON major),
1.5–1.2 [m, 20H, (CH2)10], 0.85 (t, 3H, J 6.9Hz, CH3).
13C NMR (50MHz, CDCl3): d 169.6 (C@O), 135.7–
125.8 (Ph), 100.2 (C-1), 99.8 [PhCH(O)CHCH], 78.4
(C-4), 69.9 (OCH2R), 68.7 (C-6), 68.5 (C-3), 63.1 (C-
5), 60.7 [PhCH(O)CHCH], 55.4 [PhCH(O)CHCH],
522 (35%) [M+H]+. 1H NMR (500MHz, CDCl3): d
7.3–7.2 (m, 5H, Ph), 5.83 (d, J2,NH 6.0Hz, NH major),
5.75 (d, J2,NH 6.2Hz, NH minor), 4.65 (d, J1,2 8.4Hz,
H-1 minor), 4.62 (d, J1,2 8.5Hz, H-1 major), 4.45 [d, J
3.7Hz, PhCH2CH(OH)CH minor], 4.43 [d, J 5.0Hz,
PhCH2CH(OH)CH major], 4.25 (dd, J5,6e 4.5Hz, J6e,6a
10.4Hz, H-6e minor), 4.20 (dd, J5,6e 4.7Hz, J6e,6a
10.4Hz, H-6e major), 2.96 [dd, J 4.1Hz, Jgem 14.0Hz,
PhCHAHBCH(OH)CH major], 2.91 [dd, J 5.4Hz, Jgem
14.0Hz, PhCHAHBCH(OH)CH minor], 2.82 [dd, J
8.3Hz, Jgem 14.0Hz, PhCHAHBCH(OH)CH minor],
2.73 [dd, J 8.6Hz, Jgem 14.0Hz, PhCHAHBCH(OH)CH
major], 2.01 (s, CH3CON minor), 2.00 (s, CH3CON ma-
jor), 1.6–1.2 [m, 20H, (CH2)10], 0.86 (t, 3H, J 6.9Hz,
CH3). 13C NMR (125MHz, CDCl3): d 171.9 (C@O),
137.9–126.4 (Ph), 101.8 (C-1), 100.8 [PhCH2CH-
(OH)CH minor], 100.7 [PhCH2CH(OH)CH major],
81.2 (C-4 major), 81.1 (C-4 minor), 72.8 [PhCH2CH-
(OH)CH minor], 72.5 [PhCH2CH(OH)CH major], 71.0
(C-3 major), 70.8 (C-3 minor), 70.1 (OCH2R), 68.1 (C-
6), 66.2 (C-5 major), 66.0 (C-5 minor), 58.9 (C-2 major),
58.5 (C-2 minor), 38.0 [PhCH2CH(OH)CH minor], 37.8
[PhCH2CH(OH)CH major], 31.9–22.6 [(CH2)10], 23.5
(CH3CON), 14.1 (CH3). HRMS(CI): [M+H] +, found
522.341338. C29H48NO7 requires 522.343078.
52.1 (C-2), 31.9–22.7 [(CH2)10], 23.3 (CH3CON), 14.1
(CH3). HRMS(CI): [M+H]
+
, found 520.326261.
C29H46NO7 requires 520.327428. Anal. Calcd for
C29H45NO7: C, 67.03 H, 8.73; N, 2.55. Found: C,
66.96; H, 8.55; N, 2.45.
3.10. Hydrogenolysis reactions
A solution of compound 26 or 33 (0.5mmol) in metha-
nol (10mL) was hydrogenolyzed over 10% Pd(C)
(50mg) at room temperature and atmospheric pressure.
TLC indicated complete reaction after 2days. The mix-
ture was diluted with methanol, the catalyst filtered off
and washed with methanol, and the filtrate concentrated
to dryness under reduced pressure.
3.10.1. 1-Dodecyl 2-acetamido-2-deoxy-(R)-4,6-O-[(2R)-
2-hydroxy-3-phenylpropylidene]-b-D-glucopyranoside 43.
Two stereoisomers were obtained in a 72:28 ratio
(44% de). The pure diastereoisomeric mixture was ob-
tained by column chromatography using dichlorometh-
ane–methanol (20:1) as eluent. Yield 0.18g (70%); mp
188–190ꢁC; [a]D = ꢀ23.2 (c 0.8, DMF); MS(CI): m/z
522 (41%) [M+H]+. 1H NMR (500MHz, CDCl3): d
7.3–7.1 (m, 5H, Ph), 6.30 (d, J2,NH 6.4Hz, NH minor),
6.09 (d, J2,NH 6.3Hz, NH major), 4.61 (d, J1,2 8.3Hz,
H-1 major), 4.59 (d, J1,2 8.4Hz, H-1 minor), 4.46 [d, J
3.3Hz, PhCH2CH(OH)CH major], 4.41 [d, J 5.6Hz,
PhCH2CH(OH)CH minor], 4.22 (dd, J5,6e 4.5Hz, J6e,6a
10.4Hz, H-6e major), 4.18 (dd, J5,6e 4.5Hz, J6e,6a
10.4Hz, H-6e minor), 2.94 [dd, J 3.6Hz, Jgem 14.0Hz,
PhCHAHBCH(OH)CH minor], 2.89 [dd, J 4.9Hz, Jgem
14.0Hz, PhCHAHBCH(OH)CH major], 2.79 [dd, J
8.5Hz, Jgem 14.0Hz, PhCHAHBCH(OH)CH major],
2.75 [dd, J 8.6Hz, Jgem 14.0Hz, PhCHAHBCH(OH)CH
minor], 1.98 (s, CH3CON major), 1.94 (s, CH3CON
minor), 1.6–1.2 [m, 20H, (CH2)10], 0.84 (t, 3H, J
6.9Hz, CH3). 13C NMR (50MHz, CDCl3): d 172.0
(C@O), 138.0–126.4 (Ph), 101.6 (C-1), 100.8
[PhCH2CH(OH)CH], 81.1 (C-4 major), 80.9 (C-4 min-
or), 72.8 [PhCH2CH(OH)CH minor], 72.5 [PhCH2CH-
(OH)CH major], 70.9 (C-3), 70.1 (OCH2R), 68.1 (C-6),
66.2 (C-5), 58.4 (C-2 major), 57.9 (C-2 minor), 38.0
[PhCH2CH(OH)CH minor], 37.5 [PhCH2 CH(OH)CH
major], 31.9–22.7 [(CH2)10], 23.4 (CH3CON), 14.1
(CH3). Anal. Calcd for C29H47NO7: C, 66.77; H, 9.08;
N, 2.68. Found: C, 66.62; H, 8.96; N, 2.65.
3.11. Ring-opening nucleophilic reactions
3.11.1. c-Hexyl 2-acetamido-(R)-4,6-O-[(2R,3R)-3-azido-
2-hydroxy-2-methyl-3-phenylpropylidene]-2-deoxy-b-D-glu-
copyranoside 45. To a solution of compound 28
(0.26g, 0.58mmol) in acetonitrile (25mL) were added
lithium perchlorate (0.19g, 1.8mmol) and sodium azide
(0.30g, 4.6mmol). The mixture was stirred at 80ꢁC for
9days. The salts were filtered off, and the filtrate concen-
trated to a small volume. Water was added slowly until a
white precipitate was formed. Two stereoisomers were
obtained in a 93:7 ratio (86% de). The solid was isolated
by filtration, and recrystallized from 96% ethanol. Yield
0.20g (70%); mp 228–230ꢁC; [a]D = ꢀ18.1 (c 0.9, DMF);
1
MS(CI): m/z 491 (35%) [M+H]+. H NMR (500MHz,
CDCl3): d 7.5–7.3 (m, 5H, Ph), 6.13 (br s, 1H, NH),
4.8–4.7 [m, 2H, H-1, PhCH(N3)C(CH3)(OH)CH], 4.25
[s, 1H, PhCH(N3)C(CH3)(OH)CH], 4.20 (dd, J5,6e
4.8Hz, J6e,6a 10.4Hz, H-6e), 4.04 (t, 1H, J2,3 = J3,4
9.3Hz, H-3), 3.49 (t, 1H, J5,6a = J6e,6a 10.3Hz, H-6a),
3.4–3.3 (m, 3H, H-2, H-5, OCHR), 3.17 (t, 1H,
J3,4 = J4,5 9.2Hz, H-4), 2.00 (s, CH3CON major), 1.99
(s, CH3CON minor), 1.8–1.1 [m, 13H, (CH2)5,
PhCH(N3)C(CH3)(OH)CH]. 13C NMR (125MHz,
CDCl3): d 172.0 (C@O), 135.8–126.6 (Ph), 102.8 (C-1),
98.9
[PhCH(N3)C(CH3)(OH)CH
major],
98.8
[PhCH(N3)C(CH3)(OH)CH minor], 81.2 (C-4), 77.9
(OCHR), 75.1 [PhCH(N3)C(CH3)(OH)CH], 70.7 (C-3
major),
70.0
(C-3
minor),
69.0
[PhCH-
(N3)C(CH3)(OH)CH], 68.3 (C-6 major), 67.9 (C-6 min-
or), 66.0 (C-5 major), 65.9 (C-5 minor), 59.1 (C-2
major), 58.8 (C-2 minor), 33.4–23.8 [(CH2)5], 23.6
(CH3CON), 18.8 [PhCH(N3)C(CH3)(OH)CH]. HRMS
(CI): [M+H]+, found 491.251897. C24H35N4O7 requires
491.250575. Anal. Calcd for C24H34N4O7: C, 58.76; H,
6.99; N, 11.42. Found: C, 58.63; H, 7.12; N, 11.31.
3.10.2. 1-Dodecyl 2-acetamido-2-deoxy-(R)-4,6-O-[(2S)-
2-hydroxy-3-phenylpropylidene]-b-D-glucopyranoside 44.
Two stereoisomers were obtained in a 62:38 ratio
(24% de). The pure diastereoisomeric mixture was ob-
tained by column chromatography using dichlorometh-
ane–methanol (20:1) as eluent. Yield 0.19g (74%); mp
183–184ꢁC; [a]D = ꢀ29.7 (c 0.7, DMF); MS(CI): m/z

´
J. M. Vega-Perez et al. / Tetrahedron: Asymmetry 15 (2004) 3617–3633
3633
3.11.2. c-Hexyl 2-acetamido-2-deoxy-(R)-4,6-O-[(2R,
References
3R)-2-hydroxy-2-methyl-3-phenyl-3-(1-piperidyl)propylid-
ene]-b-D-glucopyranoside 46. To a solution of com-
pound 28 (0.10g, 0.22mmol) in acetonitrile (10mL) were
added lithium perchlorate (24mg, 0.23mmol) and pip-
eridine (0.30g, 4.6mmol). The mixture was kept at room
temperature for 2-months and then poured into water.
The precipitate obtained was isolated by filtration and
recrystallized from 96% ethanol. Only one stereoisomer
was obtained. Yield 0.75g (63%); mp 209–210ꢁC;
[a]D = ꢀ11.0 (c 0.3, DMF); MS(CI): m/z 533 (15%)
´
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5H, Ph), 5.77 (d, 1H, J2,NH 5.7Hz, NH), 4.80 (d, 1H,
J1,2 8.3Hz, H-1), 4.12 (dd, J5,6e 5.0Hz, J6e,6a 10.3Hz,
H-6e), 4.08 [s, 1H, PhCH(NR2)C(CH3)(OH)CH], 4.04
(t, 1H, J2,3 = J3,4 9.5Hz, H-3), 3.54 [s, 2H,
PhCH(NR2)C(CH3)(OH)CH, OCHR], 3.36 (t, 1H,
J5,6a = J6e,6a 10.3Hz, H-6a), 3.22 (dt, 1H, J5,6e 4.9Hz,
J4,5 = J5,6a 10.3Hz, H-5), 3.09 (m, 1H, H-2), 2.80 (t,
1H, J3,4 = J4,5 9.6Hz, H-4), 2.3–1.1 [m, 20H, 2(CH2)5],
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´
1.98
(s,
3H,
CH3CON),
1.40
[s,
3H,
Vega-Perez, J. M. Chirality 2002, 14, 199–203.
PhCH(NR2)C(CH3)(OH)CH]. 13C NMR (125MHz,
CDCl3): d 171.4 (C@O), 135.8–127.0 (Ph), 103.2 (C-1),
98.5 [PhCH(NR2)C(CH3)(OH)CH], 81.3 (C-4), 77.7
(OCHR), 77.4 [PhCH(NR2)C(CH3)(OH)CH], 73.4
[PhCH(NR2)C(CH3)(OH)CH], 70.4 (C-3), 68.2 (C-6),
66.2 (C-5), 59.3 (C-2), 53.1 (CH2NCH2), 33.4–23.8
[(CH2)3, (CH2)5], 23.6 (CH3CON), 20.4 [PhCH-
(NR2)C(CH3)(OH)CH]. HRMS(CI): [M+H] +, found
533.322800. C29H45N2O7 requires 533.322677. Anal.
Calcd for C29H44N2O7: C, 65.39; H, 8.33; N, 5.26.
Found: C, 65.54; H, 8.20; N, 5.02.
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Acknowledgements
´
We thank the Ministerio de Educacion y Ciencia (Spain)
and the FEDER program for financial support
(BQU2001-2425 and CTU2004-01057/BQU).
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