Stereoselective synthesis of epoxyalkyl glycoside precursors of glycosyl glycerol analogues from alkenyl glycosides of N-acetyl-D-glucosamine derivatives

Article abstract of DOI:10.1016/S0957-4166(02)00649-3

The synthesis of epoxyalkyl glycoside derivatives of N-acetyl-D-glucosamine is described. Epoxidation of the corresponding alkenyl glycosides with m-CPBA took place with different stereoselectivity depending on the nature of the unsaturated system and the protecting groups on the sugar moiety. The configuration of the newly formed stereogenic centres has been confirmed unequivocally by chemical correlation.

Full text of DOI:10.1016/S0957-4166(02)00649-3

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 2471–2483
Stereoselective synthesis of epoxyalkyl glycoside precursors of
glycosyl glycerol analogues from alkenyl glycosides of
N-acetyl-
-glucosamine derivatives†
D
Jose´ M. Vega-Pe´rez,* Jose´ I. Candela, Eugenia Blanco and Fernando Iglesias-Guerra*
Departamento de Qu´ımica Orga´nica y Farmace´utica, Facultad de Farmacia, Universidad de Sevilla, E-41071 Sevilla, Spain
Received 23 September 2002; accepted 10 October 2002
Abstract—The synthesis of epoxyalkyl glycoside derivatives of N-acetyl-D-glucosamine is described. Epoxidation of the corre-
sponding alkenyl glycosides with m-CPBA took place with different stereoselectivity depending on the nature of the unsaturated
system and the protecting groups on the sugar moiety. The configuration of the newly formed stereogenic centres has been
confirmed unequivocally by chemical correlation. © 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
of lysozyme,15 while epoxyalkyl cellobiosides have been
synthesized as inhibitors of cellulases.16,17 It has also
been reported that the inhibition of several endoglu-
canases by oligosaccharidic epoxyalkyl glycosides
shows a remarkable specificity not only with respect to
the sugar moiety but also with respect to the chain
length and the configuration of the aglycone.18,19 Fur-
thermore, it is noteworthy that certain glycosyl glyc-
erols, an important class of compounds widely
distributed in plants, animals and bacteria,20 have
shown tumour inhibitory activity;21–25 and they can be
obtained from epoxyalkyl glycosides and subsequent
ring opening reaction.16 Thus, we became very inter-
ested in investigating a good method to obtain the
epoxyalkyl glycosides of aminosugars with high
stereoselectivity.
Oxiranes are important intermediates in organic synthe-
sis, because their electrophilic or nucleophilic opening
leads to 1,2-difunctionalized systems or to the forma-
tion of new carbonꢀcarbon bonds.2–4 This chemical
reactivity is responsible for the biological activity exhib-
ited by compounds bearing an oxirane moiety. Thus,
they can present cytotoxic activity, and hence have been
studied for use as anti-cancer agents.5 It is noteworthy
that in a strategy to obtain new highly selective drugs
against carcinoma cells in rapid growth, which have a
great demand for primary metabolites such as carbohy-
drates, the latter are used as antitumour agent carrier.6–8
This line of research is one of the components of our
work, and previously we have described the synthesis of
compounds with potential antitumour activity by link-
age of the alkylating moiety—chlorambucil or
cyclophosphamide—widely used clinically in the treat-
ment of different types of cancer9,10—to different posi-
tions of various aminosugars.1,11–14 We want to
broaden this approach and use oxiranes as alkylating
moiety. At the same time, the epoxyalkyl glycosides of
some sugars have been studied as potential inhibitors of
several endoglycosidases. Thus, epoxypropyl glycosides
We believe that a straightforward means to achieve this
might be the oxidation of alkenyl glycosides, for the
following (and other) reasons.
(a) Alkenyl glycosides are readily obtained, and the
oxidation of alkenes to oxiranes is very well known
and easily performed;
(b) published precedent works on the oxidation of
alkenyl glycosides are scarce, and refer mostly to allyl
glycosides of sugars;26–28 those referring to the epoxi-
of N-acetyl-D-glucosamine, di-N-acetylchitobiose and
tri-N-acetylchitotriose have been prepared as inhibitors
dation of alkenyl glycosides derived from N-acetyl-D-
glucosamine are even fewer in number;29 and
(c) we have used 2-aminosugars as chiral templates in
the stereoselective synthesis of numerous compounds
(2-aminoglycals,30 2-nitrosugars,14 chiral oxazolidi-
* Corresponding authors. Tel./fax: +34 95 4556737; e-mail:
vega@fafar.us.es, vega@us.es
† Potential anticancer drugs, Part 6. For Part 5, see: Ref. 1.
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00649-3

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J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 13 (2002) 2471–2483
nes,31 chiral epoxyamides,32 compounds with poten-
2. Results and discussion
tial anti-cancer activity11–13), and we anticipated that
the glucosamine moiety could serve as a chiral induc-
tor in the oxidation reaction and as carrier agent in
the derivatives with potential biological activity.
The oxidation of the alkenyl glucopyranosides 1–18 was
studied (Schemes 1 and 2) in an attempt to determine
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 two groups, according to their higher or
lower conformational flexibility: the peracetylated
derivatives 1, 2, 4, 5, and those possessing a benzylidene
group between positions 4 and 6 of the tetrahydropyran
ring, resulting in a more rigid structural model 7–18.
This was important to study because the only work
published on oxidations of the alkenyl glycosides of
We have already published preliminary assays for the
preparation of epoxyalkyl glycosides by oxidation of
alkenyl glycosides of D
-glucosamine,1 and observed that
the reaction takes place with high stereoselectivity. We
have also explored the preparation of glycosyl amino-
glycerols by further ring opening reaction with nitrogen
nucleophiles.33
Herein, we report on a study of the oxidation of a wide
range of alkenyl glycosides derived from D-glucosamine
D
-glucosamine deals solely with the oxidation of 1,29
and we ourselves have observed greater stereoselectivity
in the oxidation of the more rigid compounds.33
Because of the possible influence of the group at posi-
tion 3 of the sugar on the stereochemical course of the
reaction, we have further divided the benzylidene
derivatives into two groups: compounds with the C-3
hydroxyl group free (7–12), and compounds with the
C-3 hydroxyl group blocked with protecting groups, in
analogy to the peracetylated derivatives (13–18).
Finally, within each group, the glycosides are differenti-
ated by the number and type of substituents on the
double bond.
with m-chloroperoxybenzoic acid (m-CPBA), aiming to
analyze the influence that the different groups on the
double bond and the protecting groups of the sugar
hydroxyls have on the stereoselectivity of the reaction.
We also present unequivocal chemical proof of the
configuration of the major diastereoisomer obtained in
the oxidation reaction. The new compounds obtained
can be converted into new glycosyl glycerols represent-
ing a pool of compounds, of differing—but related—
structure, with
a potentially broad spectrum of
biological activity.
Scheme 1. Reagents: (i) AcCl; (ii) Unsaturated alcohol/Hg(CN)2; (iii) NaMeO/MeOH; (iv) PhCHO/ZnCl2.
Scheme 2. Reagents: (i) Ac2O/Py; (ii) MeI/KOH/18-crown-6/THF or BnBr/CH2Cl2/50% NaOH/H2O/TBABr; (iii) TBSCl/imida-
zole/DMF; (iv) CH2Br2/CH2Cl2/50% NaOH/H2O/TBABr/reflux.

J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 13 (2002) 2471–2483
2473
1
The alkenyl glucopyranoses 1–12 were obtained from
N-acetyl- -glucosamine in excellent yields using the
procedure
The diastereomeric excess (d.e.), determined using H
NMR, is shown in Table 1, from which certain infer-
ences can be drawn. For their analysis, the starting
alkenyl glycosides can be grouped into the three groups
defined above. The first comprises the peracetylated
derivatives (compounds 1, 2, 4, 5); the second is the
benzylidene derivatives with the 3-hydroxyl group free
(compounds 7–12); and the third is the benzylidene
derivatives with the 3-hydroxyl group blocked (com-
pounds 13–18). As expected, the d.e. of the oxidation
reaction is higher when the reaction temperature is
lowered. The d.e. obtained for the compounds of the
first group (entries 1–8) are lower than those for the
corresponding compounds of the second group with the
same aglycone (entries 9–20) measured at the same
temperature, probably because of the greater rigidity of
the latter compounds. So, at 10°C, compounds 23, 24,
26 and 27 are obtained with d.e. of 93, 82, 70 and 49%,
respectively, while compounds 19, 20, 21 and 22 are
obtained with d.e. of 72, 74, 60 and 34%, respectively.
The d.e. of the alkenyl glycosides of the third group
(entries 21–26) are again lower than those for the
corresponding compounds of the second group with the
same aglycone (entries 10 and 12) measured at the same
temperature. This effect is very marked for the oxida-
tion of 18, a compound in which, besides not having
the hydroxyl group at position 3 of the sugar, also does
not have the N–H bond by formation of an oxazolidine
bridge between these two positions. This supports the
idea of the formation of a hydrogen bond between the
NH group and the peroxyacid, preferentially stabilizing
the transition state related to electrophilic addition to
the Re-face (see below) of the double bond,33 and
further suggests additional stabilization of this transi-
tion state, probably by formation of a hydrogen bridge
between the hydroxyl group at position 3 and the
acetamido group. At the same time, intra-group com-
parison of the different alkenyl glycosides by the degree
of substitution of the double-bond carbons shows that
diastereoselectivity generally decreases slightly when a
D
previously
described
for
alkyl
glucopyranosides11,12,34 (Scheme 1). The compounds 1,
6 and 7 have been described previously in the litera-
ture.15,35,36 The reaction of 2-acetamide-3,4,6-tri-O-ace-
tyl-2-deoxy-a-D
-glucopyranosyl chloride37 with the
corresponding unsaturated alcohol gave compounds 1–
6, which were transformed into the compounds 7–12 by
deacetylation, and subsequent reaction with benzalde-
hyde. The NMR spectra showed signals corresponding
to the unsaturated moiety incorporated into the sugar
1
molecule in the glycosidation reaction. The H NMR
spectra showed signals at 6.60–4.80 ppm corresponding
to the double bond, the characteristic signals corre-
sponding to the sugar moiety, a doublet for H-1 at
4.70–4.50 ppm for the compounds 1–12, two triplets for
H-3 and H-4 at 5.20 and 4.90 ppm, respectively, for
1–6, and a singlet at 5.50 ppm corresponding to the
benzylidene group in compounds 7–12.
The syntheses of compounds 13–18 were carried out
1
from 7 or 8 as indicated in Scheme 2. The H NMR
spectra of these compounds showed the signals corre-
sponding to the protecting group present: a singlet at
2.07 ppm for 13, a singlet at 3.35 ppm for 14, two
signals at 4.70–4.50 ppm for 15, three singlets at 0.79,
−0.03 and −0.10 for 16 (similar for 17), and two signals
at 5.48 and 4.80–4.70 for 18.
The reaction of 1, 2, 4, 5, 7–18 with m-CPBA in
dichloromethane at different temperatures gave the cor-
responding oxiranes 19–34. In all cases, the major
isomer was isolated and purified by recrystallization
from ethanol or by flash chromatography on silica gel
1
(Scheme 3, Table 1). The H NMR spectra for these
compounds showed the characteristic signals of the
oxirane system at 3.85 and 3.20 ppm for 21 and 26, and
at 3.10–2.50 for the other compounds (Table 2). The
13C NMR spectra showed signals between 62 and 44
ppm for every one the compounds 19–34.
Scheme 3. Reagents: (i) m-CPBA/CH2Cl2.

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J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 13 (2002) 2471–2483
Table 1. Epoxidation of alkenyl glucosides 1, 2, 4, 5, 7–18 with m-CPBA
Entry
Starting compound
Temperature (°C)
Reaction timea (days)
Reaction product
Yieldb (%)
D.e.c (%)
1
2
3
4
5
6
7
8
1
1
2
2
4
4
5
5
7
7
8
8
9
10
−15
10
−15
10
−15
10
−15
10
−15
10
−15
10
−15
10
−15
10
5
55
4
60
6
80
6
90
2
90
6
33
1
30
2
24
6
19d
19
20
20
21
21
22
22
23
23
24
24
25
25
26
26
27
27
28
28
29
30
31
32
33
34
75
42
68
57
69
67
71
52
74
48
69
49
81
66
72
65
73
58
70
59
82
47
85
83
76
62
72
80
78
95
60
88
35
43
93
100
86
97
66
82
75
87
49
61
27
36
70
74
68
64
74
23
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
9
10
10
11
11
12
12
13
14
15
16
17
18
−15
10
70
2
−15
−15
−15
−15
−15
−15
−15
35
20
60
14
30
14
72
a Reaction time approximated (TLC showed that all starting compound had been consumed).
b Yields refer to compounds obtained in each reaction after isolation and purification.
c Determined by relative integration in the 1H NMR spectra of reaction mixtures.
d Literature: temperature 20°C; yield 71%; d.e. 68% (Ref. 29).
Table 2. NMR data (l, ppm) in CDCl3 for the oxirane protons, and anomeric proton and carbon in compounds 19–34
Entry
Compound
H-2%
HA-3%; HB-3%
H-1 minor/major
C-1 major/minor
1
2
3
4
5
6
7
8
19a
19
20
3.12
3.12
–
3.17
2.92
3.05
–
3.10
3.24
2.99
3.06
3.06
3.11
3.10
3.11
–
2.75; 2.67
2.76; 2.68/2.53b
2.82; 2.55
3.85; –
4.75/4.63
4.74/4.62
4.67/4.54
4.81/4.65
4.79/4.70
4.54/4.51
4.67/4.44
4.68/4.49
4.59/4.55
4.75/4.67
4.62/4.53
4.55/4.43
5.05/4.95
4.96/4.9–4.8
4.98/4.90
4.92/4.80
4.96/4.95
101.3/100.7
101.6/101.2
101.6/100.8
101.8/100.2
101.8/101.6
102.9/102.8
101.7/101.6
102.0/101.9
101.7/101.3
101.7/101.4
102.5/102.1
101.2/101.1
101.0/100.7
100.8/100.5
101.2/100.8
103.5/103.3
21
22
–; –
23c,d
24
2.70; 2.56
2.95; 2.66
2.89; –
3.85; –
–; –
2.81; 2.56
2.76; 2.64/2.51b
2.77; 2.65/2.55b
2.76; 2.64/2.52b
2.76; 2.66/2.52b
2.81; 2.57
2.73; 2.50
25
9
26d
27
10
11
12
13
14
15
16
17
28
29
30
31
32
33
34d,e
3.15
a Reference 29.
b l HB for the major/minor isomers.
c Reference 33.
d NMR spectrum recorded in DMSO-d6.
e 1H NMR spectrum recorded at 80°C.

J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 13 (2002) 2471–2483
2475
Scheme 4. Reagents: (i) NaN3/LiClO4/CH3CN; (ii) NaMeO/MeOH; (iii) PhCHO/ZnCl2; (iv) Ac2O/Py.
single substituent is introduced at the unsaturated car-
bons (see, for example, the entries for compounds
24–26 with respect to 23) and decreases notably when
the allylic system is doubly substituted (see the entry for
22 with respect to 19, and 27 with respect to 23).
Finally, when the aglycone is a homoallylic system
(compound 12, entries 19 and 20), the oxidation
product 28 is obtained with very low stereoselectivity.
formed (compounds 23–34), we went on to the chemical
assignment of the stereochemistry of one of the benzyl-
idene oxiranes (23) of defined stereochemistry (by cor-
relation here with 19).29 Thus, 36 was synthesized
independently from 19 and 2333 (Scheme 4). The chem-
1
ical displacement values shown in its H and 13C NMR
spectra were identical to the signals for the major
diastereoisomer. Both compounds 36 were transformed
independently into 37; again, the NMR spectra were
1
identical. The H and 13C NMR spectra of a mixture of
In conclusion, the structural features favouring high
stereoselectivity in the oxidation of alkenyl glycosides
of N-acetyl-D-glucosamine derivatives by m-CPBA,
compound 37 obtained by the two routes present a
single set of signals. The foregoing proves the R-
configuration at position 2% of 23, and by extension,
recognizes the Re-face as the more reactive in all cases.
are, probably in this order: the fact that the alkenyl
glycoside is an allyl glycoside; the existence of the N–H
bond in the acetamido group; the presence of an acetal
group between positions 4 and 6 of the pyranose ring,
making the system rigid; and the presence of a free
hydroxyl group at position 3. The existence of all these
features in compound 7 explains why, at low tempera-
ture, its oxidation product—compound 23—can be
obtained with total diastereoselectivity.
3. Experimental
3.1. General
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 are uncorrected. Optical
rotations were obtained on a Bellingham+Stanley Ltd
P-20 polarimeter at 25°C. Mass spectra were recorded
on a Micromass AUTOSPECQ mass spectrometer, CI
at 150 eV, and HR mass measurements with resolutions
of 10000. FAB mass spectra were recorded on a Kratos
MS-80-RFA using a thioglycerol matrix. NMR spectra
were recorded at 25°C on a Bruker AC-200 spectrome-
Regarding the stereochemistry of the new stereogenic
centre created in the formation of the oxirane, Peter et
al.29 demonstrated unequivocally that, in compound 19
(the major diastereoisomer), the configuration is R at
position 2% (see Table 2). They also observe that the
anomeric proton of this major compound 19 (C-2% R)
resonates at higher field (or possesses a lower l) than
the minor diastereoisomer, (C-2% S), and on this basis,
assign the R-configuration for the other oxiranes (dif-
ferent to those presented here) described in their work.
1
ter at 200 MHz for H and 50 MHz for 13C, and on a
1
Bruker AMX-500 spectrometer at 500 MHz for H and
125 MHz for 13C. The chemical shifts are reported in
ppm on the l scale relative to TMS. COSY, DEPT, and
CHCORR experiments were performed to assign the
signals in the NMR spectra.
In all of the cases examined (as shown in Table 2) the
major stereoisomer also presents a lower chemical shift
1
in H NMR for the value of the anomeric proton (as in
19) and a higher chemical displacement value for the
anomeric carbon in 13C NMR. Thus, it can be tenta-
tively stated that the Re-face of the double bond is the
more reactive to the electrophilic agent.
3.2. Alkenyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-b-
D
-glucopyranosides, 1–6
To rule out the possibility that the presence of the
benzylidene ring condensed with the tetrahydropyran
ring in compounds 7–18 might invert the reactivity of
the diastereotopic faces of the alkene and the chemical
displacement of the anomeric protons of the oxiranes
A solution of 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-a-
-glucopyranosyl chloride37 (18.3 g, 50 mmol) in dry
nitromethane (40 mL) was added dropwise, with exclu-
sion of moisture, to a stirred mixture of the correspond-
ing unsaturated alcohol (25 mL) in anhydrous toluene
D

2476
J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 13 (2002) 2471–2483
,
(40 mL) containing 4 A molecular sieves (30 g) and
mercury(II) cyanide (12.5 g). The mixture was stirred at
room temperature for 1–2 days. When TLC showed that
all of the chloride had reacted, the mixture was diluted
with ethyl acetate and filtered through a pad (12 cm
diameter×1 cm height) of alumina. The organic layer was
washed with an aqueous saturated solution of sodium
bicarbonate and water, then dried (Na2SO4) and concen-
trated. Suspension of the residue with stirring in hexane
for 1 h gave a solid that was filtered off and washed with
hexane. Recrystallization from ethanol gave the pure
peracetate.
(OCH2R), 68.6 (C-5), 62.1 (C-6), 54.8 (C-2), 23.4
(CH3CON), 20.7, 20.6, 20.5 (3CH3COO). Anal. calcd for
C23H29NO9: C, 59.60; H, 6.31; N, 3.02. Found: C, 59.37;
H, 6.19; N, 2.97%.
6
6
3.2.4. 3-Methyl-2-butenyl 2-acetamido-3,4,6-tri-O-acetyl-
2-deoxy-b-D-glucopyranoside, 5. Yield 15.1 g (73%); mp
138–139°C; [h]D +50.0 (c 0.6, CHCl3); MS (CI): m/z 416
1
(27%) [M+H]+. H NMR (200 MHz, CDCl3): l 5.96 (d,
1H, J2,NH 8.8 Hz, NH), 5.3–5.1 [m, 2H, H-3,
CH6 ꢁC(CH3)2], 4.98 (t, 1H, J3,4=J4,5 9.6 Hz, H-4), 4.65
(d, 1H, J1,2 8.3 Hz, H-1), 4.2–4.0 (m, 4H, H-6, H-6%,
OCH2R), 3.78 (m, 1H, H-2), 3.64 (m, 1H, H-5), 2.01, 1.96,
1.95, 1.88(4s, 4CH3CO), 1.68, 1.60[2s, 6H, CHꢁC(CH3 2
13C NMR (50 MHz, CDCl3): l 170.7, 170.6, 170.5, 169.3
(4CꢁO), 139.0 [CHꢁC(CH3)2], 119.5 [CHꢁC(CH3)2], 98.8
(C-1), 72.3 (C-4), 71.6 (C-3), 68.8 (C-5), 65.0 (OCH2R),
62.2 (C-6), 54.6 (C-2), 25.7, 23.2, 20.6, 20.5, 20.4, 17.8
(6CH3). HRMS (CI): [M+H]+, found 416.192050.
C19H30NO9 requires 416.192057. Anal. calcd for
C19H29NO9: C, 54.93; H, 7.04; N, 3.37. Found: C, 54.93;
H, 6.98; N, 3.37%.
6 ) ].
3.2.1. 2-Methyl-2-propenyl 2-acetamido-3,4,6-tri-O-ace-
tyl-2-deoxy-b-D-glucopyranoside, 2. Yield 17.0 g (85%);
6
6
mp 165–166°C; [h]D +36.9 (c 0.6, CH2Cl2); MS (CI): m/z
402 (65%) [M+H]+. 1H NMR (200 MHz, CDCl3): l 5.84
(d, 1H, J2,NH 8.9 Hz, NH), 5.24 (t, 1H, J2,3=J3,4 9.4 Hz,
H-3), 5.02 (t, 1H, J3,4=J4,5 9.5 Hz, H-4), 4.90, 4.85 (2bs,
2H, CꢁCH2), 4.60 (d, 1H, J1,2 8.3 Hz, H-1), 4.3–3.8 (m,
5H, H-2, H-6, H-6%, OCH2R), 3.65 (m, 1H, H-5), 2.03,
1.98, 1.97, 1.89 (4s, 4CH3CO), 1.66 (s, 3H, CH3). 13C
NMR (50 MHz, CDCl3): l 170.9, 170.7, 170.2, 169.3
3.3. Alkenyl 2-acetamido-(R)-4,6-O-benzylidene-2-
deoxy-b-D-glucopyranosides, 7–12
(4CꢁO), 140.9 (C
(OCH2R), 72.4 (C-4), 71.6 (C-3), 68.7 (C-5), 62.1 (C-6),
54.5 (C-2), 23.2 (CH3CON), 20.7, 20.6, 20.5 (3CH3COO),
6 ꢁCH2), 113.2 (CꢁC6 H2), 99.5 (C-1), 72.8
6
6
To a solution of 1–6 (25 mmol) in methanol (100 mL)
was added a solution of sodium methoxide (2.0 mmol)
in methanol (20 mL). After 30 min at room temperature,
the mixture was neutralized by addition of Dowex 50 resin
(H+ form), filtered, and evaporated. The solid obtained
wasdissolvedinbenzaldehyde(100mL), andzincchloride
(5 g) was added. The mixture was stirred for 2 days and
then poured into hexane/water (1:1) (500 mL) with
stirring. The precipitate was filtered off, washed with
water and with hexane, and then recrystallized from
ethanol.
+
’
19.2 (CH3). HRMS (EI): [M] , found 401.167637.
C18H27NO9 requires 401.168582. Anal. calcd for
C18H27NO9: C, 53.86; H, 6.78; N, 3.49. Found: C, 53.81;
H, 6.67; N, 3.53%.
3.2.2. trans-2-Butenyl 2-acetamido-3,4,6-tri-O-acetyl-2-
deoxy-b-D-glucopyranoside, 3. Yield 13.6 g (68%); mp
163–164°C; [h]D1−28.3 (c 0.8, CH2Cl2); MS (CI): m/z 402
(40%) [M+H]+. H NMR (200 MHz, CDCl3): l 5.8–5.6
(m, 3H, NH, CHꢁCH), 5.28 (t, 1H, J2,3=J3,4 9.6 Hz, H-3),
5.02 (t, 1H, J3,4=J4,5 9.4 Hz, H-4), 4.69 (d, 1H, J1,2 8.3
Hz, H-1), 4.3–3.9 (m, 4H, H-6, H-6%, OCH2R), 3.80 (m,
1H, H-2), 3.66 (m, 1H, H-5), 2.05, 1.99, 1.98, 1.91 (4s,
4CH3CO), 1.67 (d, 3H, J 6.5 Hz, CH3). 13C NMR (50
MHz, CDCl3): l 170.8, 170.7, 170.3, 169.4 (4CꢁO), 130.7,
126.2 (CH=CH), 99.2 (C-1), 72.3 (C-4), 71.6 (C-3), 69.8
(OCH2R), 68.6 (C-5), 62.1 (C-6), 54.7 (C-2), 23.3
3.3.1. 2-Methyl-2-propenyl 2-acetamido-(R)-4,6-O-ben-
zylidene-2-deoxy-b-D-glucopyranoside, 8. Yield 6.1 g
(67%); mp 262–264°C; [h]D −50.0 (c 1.0, DMF); MS (CI):
m/z 364 (85%) [M+H]+. 1H NMR (200 MHz, DMSO-d6):
l 7.84 (d, 1H, J2,NH 8.2 Hz, NH), 7.5–7.3 (m, 5H, Ph),
5.59 (s, 1H, PhCH6 ), 5.28 (d, 1H, J3,OH 4.9 Hz, OH), 4.92,
(C6 H3CON), 20.7, 20.6, 20.5 (3C6 H3COO), 17.8 (CH3).
4.83 (2bs, 2H, CꢁCH2), 4.45 (d, 1H, J1,2 7.8 Hz, H-1),
4.20 (dd, 1H, J5,6e 4.6 Hz, J6e,6a 10.1 Hz, H-6e), 4.08 (d,
HRMS (CI): [M+H]+, found 402.176338. C18H28NO9
requires402.176407. Anal. calcdforC18H27NO9:C, 53.86;
H, 6.78; N, 3.49. Found: C, 53.53; H, 6.79; N, 3.48%.
1H, Jgem 13.0 Hz, OCHA
6 HBR), 3.87 (d, 1H, Jgem 13.0 Hz,
OCHAHBR), 3.73 (t, 1H, J5,6a=J6e,6a 9.9 Hz, H-6a),
6
3.6–3.3 (m, 4H, H-2, H-3, H-4, H-5), 1.81 (s, 3H,
CH3CON), 1.64 (s, 3H, CH3). 13C NMR (50 MHz,
3.2.3. trans-3-Phenyl-2-propenyl 2-acetamido-3,4,6-tri-O-
acetyl-2-deoxy-b-D-glucopyranoside, 4. Yield 18.7 g
DMSO-d6): l 169.0 (CꢁO), 141.5 (C
128.0, 126.3 (Ph), 111.8 (CꢁCH2), 101.0 (C-1), 100.7
(PhCH), 81.3 (C-4), 71.9 (OCH2R), 70.3 (C-3), 67.9 (C-6),
6 ꢁCH2), 137.7, 128.8,
(81%); mp 175–176°C; [h]D −24.0 (c 1.0, DMF); MS (CI):
6
1
m/z 464 (5%) [M+H]+. H NMR (200 MHz, CDCl3): l
6
7.4–7.2 (m, 5H, Ph), 6.58 (d, 1H, Jtrans 16.0 Hz,
65.9 (C-5), 56.1 (C-2), 23.0 (C6 H3CON), 19.0 (CH3).
HRMS (CI): [M+H]+, found 364.176046. C19H26NO6
requires364.176013. Anal. calcdforC19H25NO6:C, 62.80;
H, 6.93; N, 3.85. Found: C, 62.69; H, 6.77; N, 4.06%.
CH2CHꢁCH6 Ph), 6.20 (m, 1H, CH2CH6 ꢁCHPh), 5.49 (d,
1H, J2,NH 8.8 Hz, NH), 5.28 (t, 1H, J2,3=J3,4 9.3 Hz, H-3),
5.07 (t, 1H, J3,4=J4,5 9.6 Hz, H-4), 4.76 (d, 1H, J1,2 8.3
4
Hz, H-1), 4.48 (ddd, 1H, Jgem 12.8 Hz, J 5.6 Hz, J 1.4
Hz,
CHAHB
CHA
6
HBCHꢁCHPh),
4.3–4.1
(m,
3H,
3.3.2. trans-2-Butenyl 2-acetamido-(R)-4,6-O-benzyli-
6
CHꢁCHPh, H-6, H-6%), 3.87 (m, 1H, H-2), 3.69
dene-2-deoxy-b-D-glucopyranoside, 9. Yield 8.5 g (94%);
(m, 1H, H-5), 2.06, 2.01, 2.00, 1.93 (4s, 4CH3CO). 13C
NMR (50 MHz, CDCl3): l 170.9, 170.7, 170.2, 169.4
(4CꢁO), 136.3, 133.3, 128.6, 127.9, 126.5, 124.6
(CHꢁCHPh), 99.6 (C-1), 72.3 (C-4), 71.8 (C-3), 69.7
mp 236–238°C; [h]D1−57.7 (c 1.0, DMF); MS (CI): m/z
364 (45%) [M+H]+. H NMR (200 MHz, DMSO-d6): l
7.82 (d, 1H, J2,NH 8.5 Hz, NH), 7.5–7.3 (m, 5H, Ph),
5.7–5.4 (m, 3H, PhCH6 , CHꢁCH), 5.28 (d, 1H, J3,OH 5.3

J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 13 (2002) 2471–2483
2477
Hz, OH), 4.47 (d, 1H, J1,2 8.0 Hz, H-1), 4.3–4.1 (m, 2H,
H-6e, OCHAHBR), 3.91 (dd, 1H, J 6.0 Hz, Jgem 12.3 Hz,
OCHAHBR), 3.72 (t, 1H, J5,6a=J6e,6a 9.9 Hz, H-6a),
3.6–3.2 (m, 4H, H-2, H-3, H-4, H-5), 1.80 (s, 3H,
CH3CON), 1.65 (d, 3H, J 6.2 Hz, CH3). 13C NMR (50
MHz, DMSO-d6): l 169.2 (CꢁO), 137.8, 128.9, 128.1,
(m, 2H, OCH2CH2
NMR (50 MHz, CDCl3): l 172.2 (CꢁO), 137.0, 129.2,
128.3, 126.3 (Ph), 134.9 (CHꢁCH2), 117.0 (CHꢁCH2),
101.9 (C-1), 100.5 (PhCH), 81.5 (C-4), 71.2 (C-3), 68.8
(OCH2CH2R), 68.5 (C-6), 66.3 (C-5), 59.2 (C-2), 33.8
(OCH2CH2R), 23.6 (C
H3CON). HRMS (CI): [M+H]+,
found 364.175683. C19H26NO6 requires 364.176013.
Anal. calcd for C19H25NO6: C, 62.80; H, 6.93; N, 3.85.
Found: C, 62.73; H, 6.93; N, 3.86%.
6
R), 2.02 (s, 3H, CH3CON). 13C
6
6
6
6
6
6
6
6
126.4 (Ph), 128.2, 127.4 (C
6
HꢁC
6
H), 100.8 (C-1), 100.7
(PhC
6
H), 81.3 (C-4), 70.4 (C-3), 68.9 (OCH2R), 67.9
(C-6), 66.0 (C-5), 56.2 (C-2), 23.1 (C6 H3CON), 17.6
(CH3). HRMS (CI): [M+H]+, found 364.175819.
C19H26NO6 requires 364.176013. Anal. calcd for
C19H25NO6: C, 62.80; H, 6.93; N, 3.85. Found: C,
62.63; H, 6.87; N, 3.88%.
3.4. Allyl 2-acetamido-3-O-acetyl-(R)-4,6-O-benzyli-
dene-2-deoxy-b-D-glucopyranosides, 13
Allyl 2-acetamido-(R)-4,6-O-benzylidene-2-deoxy-b-D-
3.3.3. trans-3-Phenyl-2-propenyl 2-acetamido-(R)-4,6-O-
glucopyranoside 7 (3.5 g, 10 mmol) was acetylated in
the usual way with acetic anhydride/pyridine (1:1) (40
mL). The reaction mixture was kept overnight at room
temperature and then poured into ice–water. The pre-
cipitate obtained was isolated by filtration and, recrys-
benzylidene-2-deoxy-b-D-glucopyranoside, 10. Yield 9.2 g
(87%); mp 252–253°C; [h]D −90.0 (c 1.2, DMF); MS
1
(FAB): m/z 448 (100%) [M+Na]+. H NMR (200 MHz,
DMSO-d6): l 7.90 (d, 1H, J2,NH 8.4 Hz, NH), 7.5–7.2
(m, 10H, 2Ph), 6.59 (d, 1H, Jtrans 16.0 Hz,
tallized from ethanol, yielded 3.7
g (95%); mp
CH2CHꢁCH
CH2CHꢁCH), 5.60 (s, 1H, PhCH
5.2 Hz, OH), 4.56 (d, 1H, J1,2 7.9 Hz, H-1), 4.37 (ddd,
1H, Jgem 12.3 Hz,
6.0 Hz, 4J 1.3 Hz,
OCHAHBCHꢁCH), 4.2–4.1 (m, 2H, H-6e,
OCHAHB
6
), 6.27 (dt, 1H, J 5.4 Hz, Jtrans 16.0 Hz,
283–284°C; [h]D −77.1 (c 0.7, CH2Cl2); MS (CI): m/z
392 (60%) [M+H]+. 1H NMR (200 MHz, CDCl3): l
7.5–7.3 (m, 5H, Ph), 5.98 (d, 1H, J2,NH 9.5 Hz, NH),
6
6
), 5.32 (d, 1H, J3,OH
J
5.77 (m, 1H, CH
3H, H-3, CHꢁCH
4.3–4.05 (m, 3H, H-2, H-6e, OCHA
OCHAHBR), 3.8–3.65 (m, 2H, H-4, H-6a), 3.52 (dt, 1H,
6
ꢁCH2), 5.48 (s, 1H, PhCH
2), 4.44 (d, 1H, J1,2 8.4 Hz, H-1),
HBR), 3.89 (m, 1H,
6 ), 5.3–5.1 (m,
6
6
6
CHꢁCH), 3.75 (t, 1H, J5,6a=J6e,6a 9.9 Hz,
6
H-6a), 3.6–3.3 (m, 4H, H-2, H-3, H-4, H-5), 1.83 (s, 3H,
CH3CON). 13C NMR (50 MHz, DMSO-d6): l 169.2
(CꢁO), 137.7, 131.0, 128.9, 128.7, 128.0, 127.6, 126.3,
6
J
4,5=J5,6a 9.6 Hz, J5,6e 4.7 Hz, H-5), 2.07 (s, 3H,
CH3COO), 1.95 (s, 3H, CH3CON). 13C NMR (50
126.0 (Ph, CHꢁCHPh), 101.0 (C-1), 100.7 (PhC
6
H), 81.3
MHz, CDCl3): l 171.4, 170.2 (2CꢁO), 136.9, 129.1,
(C-4), 70.4 (C-3), 68.7 (OCH2R), 67.9 (C-6), 66.0 (C-5),
128.2, 126.0 (Ph), 133.5 (C6 HꢁCH2), 117.4 (CHꢁC6 H2),
56.2 (C-2), 23.2 (C
6
H3CON), 17.6 (CH3). HRMS (CI):
101.2 (C-1), 101.1 (PhC
(OCH2R), 68.6 (C-6), 66.2 (C-5), 54.3 (C-2), 23.3
(CH3CON), 20.9 (C
H3COO). HRMS (CI): [M+H]+,
6 H), 78.6 (C-4), 72.0 (C-3), 70.0
[M+H]+, found 426.191285. C24H28NO6 requires
426.191663. Anal. calcd for C24H27NO6: C, 67.75; H,
6.40; N, 3.29. Found: C, 67.53; H, 6.41; N, 3.16%.
6
6
found 392.170795. C20H26NO7 requires 392.170928.
Anal. calcd for C20H25NO7: C, 61.37; H, 6.44; N, 3.58.
Found: C, 61.21; H, 6.35; N, 3.62%.
3.3.4. 3-Methyl-2-butenyl 2-acetamido-(R)-4,6-O-benzyl-
idene-2-deoxy-b-D-glucopyranoside, 11. Yield 7.1 g
(75%); mp 164–166°C; [h]D −34.6 (c 1.0, DMF); MS
(CI): m/z 378 (20%) [M+H]+. 1H NMR (200 MHz,
DMSO-d6): l 7.80 (d, 1H, J2,NH 8.6 Hz, NH), 7.5–7.3
3.5. Alkenyl 2-acetamido-3-O-alkyl-(R)-4,6-O-benzyli-
dene-2-deoxy-b-D-glucopyranosides, 14 and 15
(m, 5H, Ph), 5.58 (s, 1H, PhCH
6
), 5.3–5.1 [m, 2H, OH,
3.5.1. Allyl 2-acetamido-(R)-4,6-O-benzylidene-2-deoxy-
3-O-methyl-b- -glucopyranoside, 14. To a solution of 7
CH
6
ꢁC(CH3)2], 4.49 (d, 1H, J1,2 8.1 Hz, H-1), 4.2–3.9
D
(m, 3H, H-6e, OCH2R), 3.75 (t, 1H, J5,6a=J6e,6a 9.9 Hz,
H-6a), 3.6–3.3 (m, 4H, H-2, H-3, H-4, H-5), 1.81 (s, 3H,
(3.5 g, 10 mmol) in dry THF (50 mL) were added,
successively, freshly powdered potassium hydroxide (1.0
g, 17.9 mmol), 18-crown-6 (150 mg, 0.5 mmol), and
methyl iodide (20.8 mmol). The mixture was stirred at
room temperature, and the reaction was monitored by
TLC at the end of the reaction. The mixture was then
diluted with dichloromethane, and washed several time
with water and dried (Na2SO4). Evaporation of the
organic phase gave the pure methylated product. The
solid obtained, purified by crystallization from ethanol,
yielded 2.3 g (64%); mp 290–291°C; [h]D −103.4 (c 0.7,
CH3CON), 1.69, 1.59 [2s, 6H, CHꢁC(CH3 2
(50 MHz, DMSO-d6): l 169.1 (CꢁO), 137.8, 128.9,
128.0, 126.4 (Ph), 136.6 [CHꢁC(CH3)2], 120.5
[CHꢁC(CH3)2], 100.7 (PhCH), 100.5 (C-1), 81.3 (C-4),
70.5 (C-3), 67.9 (OCH2R), 66.0 (C-5), 64.6 (C-6), 56.2
6
) ]. 13C NMR
6
6
6
(C-2), 23.1 (C6 H3CON), 25.5, 19.0 [CHꢁC(C6 H3)2].
HRMS (CI): [M+H]+, found 378.191480. C20H28NO6
requires 378.191663. Anal. calcd for C20H27NO6: C,
63.65; H, 7.21; N, 3.71. Found: C, 63.39; H, 6.99; N,
3.97%.
1
DMF); MS (CI): m/z 364 (100%) [M+H]+. H NMR
(200 MHz, DMSO-d6): l 7.96 (d, 1H, J2,NH 8.7 Hz,
3.3.5. 3-Butenyl 2-acetamido-(R)-4,6-O-benzylidene-2-
NH), 7.5–7.3 (m, 5H, Ph), 5.82 (m, 1H, CH
(s, 1H, PhCH), 5.15 (m, 2H, CHꢁCH2), 4.52 (d, 1H, J1,2
8.0 Hz, H-1), 4.3–4.1 (m, 2H, H-6e, OCHAHBR), 4.00
(m, 1H, OCHAHBR), 3.77 (t, 1H, J5,6a=J6e,6a 10.1 Hz,
H-6a), 3.6–3.4 (m, 4H, H-2, H-3, H-4, H-5), 3.35 (s, 3H,
OCH3), 1.82 (s, 3H, CH3CON). 13C NMR (50 MHz,
DMSO-d6): l 169.0 (CꢁO), 137.6, 128.8, 128.1, 126.0
6 ꢁCH2), 5.65
deoxy-b-
D
-glucopyranoside, 12. Yield 6.0 g (66%); mp
6
6
235–236°C; [h]D −44.4 (c 0.9, DMF); MS (CI): m/z 364
6
1
(100%) [M+H]+. H NMR (200 MHz, CDCl3): l 7.5–
6
7.3 (m, 5H, Ph), 6.0–5.7 (m, 2H, NH, CH
(s, 1H, PhCH), 5.08 (m, 2H, CHꢁCH2), 4.64 (d, 1H, J1,2
8.2 Hz, H-1), 3.6–3.4 (m, 4H, H-2, H-3, H-4, H-5), 2.34
6
ꢁCH2), 5.51
6
6

2478
J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 13 (2002) 2471–2483
(Ph), 134.5 (C
100.2 (PhCH), 80.6 (C-4), 79.5 (C-3), 69.0 (OCH2R),
67.8 (C-6), 65.6 (C-5), 59.0 (OCH3), 54.2 (C-2), 22.9
(C
H3CON). HRMS (CI): [M+H]+, found 364.175979.
C19H26NO6 requires 364.176013. Anal. calcd for
C19H25NO6: C, 62.80; H, 6.93; N, 3.85. Found: C,
62.49; H, 6.70; N, 3.85%.
6
HꢁCH2), 116.2 (CHꢁC
6
H2), 101.0 (C-1),
OSi(CH3 2
168.8 (CꢁO), 137.6, 128.8, 128.0, 126.2 (Ph), 134.6
(CHꢁCH2), 116.2 (CHꢁCH2), 100.8 (C-1), 100.7
(PhCH), 81.5 (C-4), 72.3 (C-3), 68.9 (OCH2R), 67.8
(C-6), 65.6 (C-5), 56.0 (C-2), 25.6 [OSi(CH3)2C(CH3)3],
23.1 (CH3CON), 17.9 [OSi(CH3)2C(CH3)3], −4.2, −5.0
[OSi(C
H3)2C(CH3)3]. HRMS (CI): [M+H]+, found
464.246313. C24H38NO6Si requires 464.246842. Anal.
calcd for C24H37NO6Si: C, 62.17; H, 8.04; N, 3.02.
Found: C, 62.11; H, 7.90; N, 3.15%.
6
) C(CH3)3]. 13C NMR (50 MHz, DMSO-d6): l
6
6
6
6
6
6
6
6
6
3.5.2. Allyl 2-acetamido-3-O-benzyl-(R)-4,6-O-benzyli-
dene-2-deoxy-b-D-glucopyranoside, 15. To a solution of
7 (3.5 g, 10 mmol) in distilled dichloromethane (200
mL), benzyl bromide (2.5 mL, 21.0 mmol), 50%
aqueous sodium hydroxide solution (200 mL) and tetra-
butylammonium bromide (32 mg, 0.10 mmol) were
added. The reaction mixture was stirred vigorously at
room temperature for 3 h. The organic phase was
washed with water until neutral, dried (MgSO4), and
the solvent was removed under reduced pressure to give
a solid which, purified by crystallization from ethyl
acetate–ethanol, yielded 3.1 g (71%); mp 270–272°C;
[h]D −37.6 (c 1.0, DMF); MS (CI): m/z 440 (10%)
3.6.2. 2-Methyl-2-propenyl 2-acetamido-(R)-4,6-O-ben-
zylidene-2-deoxy-3-O-tert-butyldimethylsilyl-b-D-gluco-
pyranoside, 17. Yield 3.4 g (71%); mp 132–133°C; [h]D
−30.4 (c 0.9, CH2Cl2); MS (CI): m/z 478 (75%) [M+H]+.
1H NMR (200 MHz, CDCl3): l 7.5–7.3 (m, 5H, Ph),
5.87 (d, 1H, J2,NH 8.1 Hz, NH), 5.46 (s, 1H, PhCH
4.90 (m, 3H, CꢁCH2, H-1), 4.3–4.2 (m, 2H, H-6e,
OCHAHBR), 3.95 (d, 1H, Jgem 12.6 Hz, OCHAHBR),
6 ),
6
6
3.73 (t, 1H, J5,6a=J6e,6a 10.0 Hz, H-6a), 3.5–3.3 (m, 4H,
H-2, H-3, H-4, H-5), 1.95 (s, 3H, CH3CON), 1.69 (s,
1
[M+H]+. H NMR (200 MHz, DMSO-d6): l 8.00 (d,
3H, CH3), 0.79 [s, 9H, OSi(CH3)2C(CH3 3
−0.08 [2s, 6H, OSi(CH3 2
) C(CH3)3]. 13C NMR (50 MHz,
CDCl3): l 170.0 (CꢁO), 141.1 (CꢁCH2), 137.2, 128.9,
128.1, 126.2 (Ph), 112.8 (CꢁCH2), 101.7 (C-1), 99.5
(PhCH), 82.5 (C-4), 73.0 (OCH2R), 71.1 (C-3), 68.7
(C-6), 65.8 (C-5), 59.2 (C-2), 25.7 [OSi(CH3)2C(CH3)3],
23.7 (CH3CON), 19.3 (CH3), 18.1 [OSi(CH3)2C(CH3)3],
−4.2, −5.0 [OSi(C
H3)2C(CH3)3]. HRMS (CI): [M+H]+,
6 ) ], −0.02,
1H, J2,NH 8.4 Hz, NH), 7.5–7.2 (m, 10H, 2Ph), 5.81 (m,
6
1H, CH
CHꢁCH2), 4.72 (d, 1H, Jgem 11.9 Hz, PhCHA
4.6–4.5 (m, 2H, PhCHAHBO, H-1), 4.3–4.15 (m, 2H,
H-6e, OCHAHBR), 4.01 (m, 1H, OCHAHBR), 3.8–3.6
6
ꢁCH2), 5.70 (s, 1H, PhCH
6
), 5.18 (m, 2H,
6
6
6
HBO),
6
6
6
6
6
6
(m, 4H, H-2, H-3, H-4, H-6a), 3.46 (m, 1H, H-5), 1.81
(s, 3H, CH3CON). 13C NMR (50 MHz, DMSO-d6): l
169.1 (CꢁO), 138.7, 137.6, 129.7, 128.8, 128.1, 128.0,
127.4, 126.0 (2Ph), 134.5 (C
100.9 (C-1), 100.1 (PhC
(PhCH2O), 69.0 (OCH2R), 67.8 (C-6), 65.6 (C-5), 54.6
(C-2), 23.0 (C
H3CON). HRMS (CI): [M+H]+, found
440.207175. C25H30NO6 requires 440.207313. Anal.
calcd for C25H29NO6: C, 68.32; H, 6.65; N, 3.19.
Found: C, 68.15; H, 6.97; N, 3.34%.
6
6
6
found 478.261653. C25H40NO6Si requires 478.262492.
Anal. calcd for C25H39NO6Si: C, 62.86; H, 8.23; N,
2.93. Found: C, 62.79; H, 8.18; N, 3.01%.
6
HꢁCH2), 116.3 (CHꢁC
6 H2),
6
H), 80.9 (C-4), 78.6 (C-3), 73.2
6
6
3.7. Allyl 2-acetamido-(R)-4,6-O-benzylidene-2-deoxy-2-
N-3-O-methylidene-b-D-glucopyranoside, 18
To a solution of allyl 2-acetamido-(R)-4,6-O-benzyli-
dene-2-deoxy-b- -glucopyranoside 7 (10 mmol) in dis-
3.6. Alkenyl 2-acetamido-(R)-4,6-O-benzylidene-2-
D
deoxy-3-O-tert-butyldimethylsilyl-b-
D
-glucopyranosides,
tilled dichloromethane (50 mL), dibromomethane (50
mL), 50% aqueous sodium hydroxide solution (100
mL), and tetrabutylammonium bromide (6.5 mg, 0.02
mmol) were added. The reaction mixture was vigor-
ously stirred under reflux for 2 days, then cooled to
room temperature. The organic phase was washed with
water until neutral, dried (MgSO4), and the solvent was
removed under reduced pressure to give a solid which
was purified by flash chromatography on silica gel
using hexane–ethyl acetate (15:10) as eluent, yielding
3.5 g (97%); mp 94–95°C; [h]D −21.5 (c 1.0, CH2Cl2);
MS (CI): m/z 362 (100%) [M+H]+. 1H NMR (200 MHz,
CDCl3): l 7.96 (d, 1H, J2,NH 8.7 Hz, NH), 7.5–7.3 (m,
16 and 17
To a solution of 7, 8 (10 mmol) in dry DMF (30 mL),
imidazole (3.4 g, 50 mmol) and tert-butyldimethylsilyl
chloride (3.8 g, 25 mmol) were added and the mixture
was stirred at room temperature for 2 h. The reaction
mixture was diluted with dichloromethane, washed with
water, dried (Na2SO4), filtered and the filtrate evapo-
rated to dryness to give a white solid, which was
purified by flash chromatography on silica gel using
hexane–ethyl acetate (7:1).
3.6.1. Allyl 2-acetamido-(R)-4,6-O-benzylidene-2-deoxy-
5H, Ph), 5.90 (m, 1H, CH
5.48 (d, 1H, Jgem 5.3 Hz, OCHA
CHꢁCH2), 4.8–4.7 (m, 2H, OCHAHB
(m, 2H, OCHAHBR, H-6e), 4.14 (m, 1H, OCHAHB
6
ꢁCH2), 5.60 (s, 1H, PhCH
HBN), 5.28 (m, 2H,
N, H-1), 4.5–4.3
R),
6 ),
3-O-tert-butyldimethylsilyl-b-
D
-glucopyranoside,
16.
6
Yield 3.8 g (82%); mp 98–99°C; [h]D −66.3 (c 1.0,
6
6
1
CH2Cl2); MS (CI): m/z 464 (60%) [M+H]+. H NMR
6
6
(200 MHz, DMSO-d6): l 7.91 (d, 1H, J2,NH 9.0 Hz,
4.0–3.8 (m, 3H, H-3, H-4, H-6a), 3.50 (m, 1H, H-5),
3.37 (dd, 1H, J1,2 7.9 Hz, J2,3 9.2 Hz, H-2), 2.22 (s, 3H,
CH3CON). 13C NMR (50 MHz, CDCl3): l 173.3
(CꢁO), 136.5, 129.3, 128.3, 126.2 (Ph), 132.8
NH), 7.5–7.3 (m, 5H, Ph), 5.82 (m, 1H, CH
(s, 1H, PhCH), 5.17 (m, 2H, CHꢁCH2), 4.50 (d, 1H, J1,2
8.3 Hz, H-1), 4.3–4.1 (m, 2H, H-6e, OCHAHBR), 3.99
(m, 1H, OCHAHBR), 3.8–3.4 (m, 5H, H-2, H-3, H-4,
H-5, H-6a), 1.78 (s, 3H, CH3CON), 0.75 [s, 9H,
OSi(CH3)2C(CH3)3], −0.03, −0.10 [2s, 6H,
6 ꢁCH2), 5.63
6
6
6
6
(C
(PhC
(OCH2R), 69.1 (C-5), 68.5 (C-6), 62.0 (C-2), 23.2
6
HꢁCH2), 118.7 (CHꢁC
6 H2), 102.8 (C-1), 101.6
6
H), 82.4 (OCH2N), 82.0 (C-4), 79.2 (C-3), 70.6
6

J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 13 (2002) 2471–2483
2479
(C
6
H3CON). Anal. calcd for C19H23NO6: C, 63.15; H,
C23H29NO10 requires 479.179147. Anal. calcd for
C23H29NO10: C, 57.61; H, 6.10; N, 2.92. Found: C,
57.38; H, 6.00; N, 3.10%.
6.41; N, 3.88. Found: C, 62.88; H, 6.55; N, 3.82%.
3.8. Epoxidation of alkenyl glucosides with m-chloro-
peroxybenzoic acid
3.8.1.3. (S)-2,3-Epoxy-3-methylbutyl 2-acetamido-
3,4,6-tri-O-acetyl-2-deoxy-b-D-glucopyranoside, 22. Mp
To a solution of either 1, 2, 4, 5 or 7–18 (1.5 mmol) in
distilled dichloromethane (300 mL), m-chloroperoxy-
benzoic acid (Aldrich 57–86%) (3.0 g) was added and
the suspension was stirred. When TLC showed that all
starting compound had been consumed, the reaction
mixture was washed successively with a 5% aqueous
solution of sodium hydroxide and water, dried
(MgSO4), filtered, and the filtrate evaporated to dry-
156–158°C; [h]D 1+13.9 (c 0.9, DMF); MS (CI): m/z 432
(65%) [M+H]+. H NMR (200 MHz, CDCl3): l 5.82
(2d, 1H, J2,NH 8.4 Hz, 9.0 Hz, NH), 4.79 (d, J1,2 8.3 Hz,
H-1 minor), 4.70 (d, J1,2 8.4 Hz, H-1 major), 2.92 [m,
1H, OCH2CH
(4s, 12H, 4CH3CO), 1.28, 1.24 [2s, 6H, OCH2CH(O)-
C(CH
3)2]. 13C NMR (50 MHz, CDCl3): l 170.9, 170.7,
6 (O)C(CH3)2], 2.04, 1.99, 1.98, 1.92, 1.90
6
170.3, 169.4, 169.3 (4CꢁO), 101.8 (C-1 major), 100.2
1
ness. Diastereomeric excess (d.e.) was determined by H
(C-1 minor) 72.5, 72.1, 71.9, 71.8 (C-4, C-3), 68.6 (C-5
NMR. The solids obtained were purified by recrystal-
lization from ethanol or by flash chromatography on
silica gel.
minor), 68.4 (C-5 major), 68.3 [OC
major], 67.9 [OCH2CH(O)C(CH3)2 minor], 62.1 (C-6
minor), 62.0 (C-6 major), 62.2 [OCH2CH(O)C(CH3)2
major], 61.1 [OCH2CH(O)C(CH3)2 minor], 58.2
[OCH2CH(O)C(CH3)2 minor], 57.7 [OCH2CH(O)C-
(CH3)2 major], 54.8 (C-2 minor), 54.3 (C-2 major), 24.6,
6 H2CH(O)C(CH3)2
6
6
6
3.8.1. Epoxidation of peracetyl derivatives
6
3.8.1.1. (R)-2,3-Epoxy-2-methylpropyl 2-acetamido-
6
3,4,6-tri-O-acetyl-2-deoxy-b-D-glucopyranoside, 20. Mp
24.5, 23.3, 20.7, 20.6, 18.9, 18.7 (6CH3). HRMS (CI):
[M+H]+, found 432.185043. C19H30NO10 requires
432.186972. Anal. calcd for C19H29NO10: C, 52.89; H,
6.78; N, 3.25. Found: C, 52.66; H, 6.57; N, 3.39%.
152–154°C; [h]D +16.6 (c 0.8, DMF); MS (CI): m/z 418
1
(15%) [M+H]+. H NMR (200 MHz, CDCl3): l 5.64 (d,
1H, J2,NH 8.8 Hz, NH major), 5.53 (d, J2,NH 8.6 Hz,
NH minor), 4.67 (d, J1,2 8.4 Hz, H-1 minor), 4.54 (d,
J1,2 8.5 Hz, H-1 major), 2.82, 2.55 [2d, 2H, Jgem 5.1 Hz,
OCH2C(CH3)(O)CH2
6
], 2.06, 2.01, 2.00, 1.99, 1.94 (4s,
3.8.2. Epoxidation of 4,6-O-benzylidene derivatives
3.8.2.1. (R)-2,3-Epoxy-2-methylpropyl 2-acetamido-
12H, 4CH3CO), 1.33 (s, CH3 minor), 1.29 (s, CH3
major). 13C NMR (50 MHz, CDCl3): l 170.9, 170.7,
170.3, 170.2, 169.3 (4CꢁO), 101.6 (C-1 major), 101.2
(C-1 minor) 72.7, 72.5, 71.9, 71.8 (C-4, C-3), 69.6 (C-5
(R)-4,6-O-benzylidene-2-deoxy-b-D-glucopyranoside, 24.
Mp 274–276°C; [h]D −69.1 (c 1.0, DMF); MS (CI): m/z
1
380 (100%) [M+H]+. H NMR (200 MHz, CDCl3): l
minor), 68.4 (C-5 major), 70.6 [OC
minor], 69.8 [OCH2C(CH3)(O)CH2 major], 62.0 (C-6
major), 61.5 (C-6 minor), 56.1 [OCH2C(CH3)(O)CH2
minor], 56.0 [OCH2C(CH3)(O)CH2 major], 54.2 (C-2
major), 51.0 (C-2 minor), 51.6 [OCH2C(CH3)(O)CH2
minor], 50.4 [OCH2C(CH3)(O)CH2 major], 23.2, 23.0,
6 H2C(CH3)(O)CH2
7.5–7.3 (m, 5H, Ph), 6.85 (d, 1H, J2,NH 3.8 Hz, NH),
6
5.54 (s, 1H, PhCH6 ), 4.67 (d, J1,2 8.4 Hz, H-1 minor),
6
4.44 (d, J1,2 8.4 Hz, H-1 major), 4.31 (dd, 1H, J5,6e 4.9
Hz, J6e,6a 10.3 Hz, H-6e), 3.40 (m, 1H, H-5), 2.95, 2.66
6
6
[2d, 2H, Jgem 4.9 Hz, OCH2C(CH3)(O)CH6 2], 2.05 (s,
6
3H, CH3CON), 1.39 (s, CH3 minor), 1.34 (s, CH3
major). 13C NMR (50 MHz, CDCl3): l 173.1 (CꢁO),
137.0, 129.1, 128.2, 126.3 (Ph), 102.9 (C-1 major), 102.8
20.9, 20.7, 20.6, 20.5, 18.3, 18.1 (5CH3). HRMS (CI):
[M+H]+, found 418.171028. C18H28NO10 requires
418.171322. Anal. calcd for C18H27NO10: C, 51.79; H,
6.52; N, 3.36. Found: C, 51.52; H, 6.33; N, 3.48%.
(C-1 minor), 101.9 (PhC
[OCH2C(CH3)(O)CH2], 68.4 (C-6), 66.3 (C-5), 59.6 (C-
2), 57.1 [OCH2C(CH3)(O)CH2], 49.6 [OCH2C(CH3)(O)-
H2], 23.0 (C6 H3CON), 18.2 [OCH2C(C6 H3)(O)CH2].
6 H), 81.3 (C-4), 73.3 (C-3), 69.5
6
6
3.8.1.2. (2S,3S)-2,3-Epoxy-3-phenylpropyl 2-acetam-
ido-3,4,6-tri-O-acetyl-2-deoxy-b-D-glucopyranoside, 21.
Mp 141–142°C; [h]D −32.0 (c 1.0, DMF); MS (CI): m/z
480 (35%) [M+H]+. 1H NMR (200 MHz, CDCl3): l
7.4–7.2 (m, 5H, Ph), 5.78 (d, 1H, J2,NH 8.9 Hz, NH),
C6
HRMS (CI): [M+H]+, found 380.171042. C19H26NO7
requires 380.170928. Anal. calcd for C19H25NO7: C,
60.15; H, 6.64; N, 3.69. Found: C, 60.10; H, 6.70; N,
3.71%.
5.18 (t, 1H, J2,3=J3,4 9.5 Hz, H-3), 5.06 (t, 1H, J3,4
=
J4,5 9.4 Hz, H-4), 4.81 (d, J1,2 8.5 Hz, H-1 minor), 4.65
(d, J1,2 8.4 Hz, H-1 major), 4.25 [dd, 1H, Jgem 12.2 Hz,
3.8.2.2. (2S,3S)-2,3-Epoxybutyl 2-acetamido-(R)-4,6-
J 4.6 Hz, OCH
12.5 Hz, J 2.2 Hz, OCHAHB
(m, 3H, H-2, H-6, H-6%), 3.85 [d, 1H, J 2.0 Hz,
OCH2CH(O)CHPh], 3.68 (m, 1H, H-5), 3.17 [m, 1H,
OCH2CH
6
AHBCH(O)CHPh], 4.14 [dd, 1H, Jgem
O-benzylidene-2-deoxy-b-D-glucopyranoside, 25. Mp
6
CH(O)CHPh], 4.05–3.95
258–260°C; [h]D −76.7 (c 0.7, DMF); MS (CI): m/z 380
1
(100%) [M+H]+. H NMR (200 MHz, CDCl3): l 7.5–
6
7.3 (m, 5H, Ph), 6.70 (d, 1H, J2,NH 4.8 Hz, NH), 5.54 (s,
6
(O)CHPh], 2.07, 2.02, 2.01, 1.93 (4s,
1H, PhCH6 ), 4.68 (d, J1,2 8.3 Hz, H-1 minor), 4.49 (d,
4CH3CO). 13C NMR (50 MHz, CDCl3): l 170.9, 170.7,
170.3, 169.3 (4CꢁO), 136.4, 134.5, 128.5, 128.4, 125.6
(Ph), 101.6 (C-1 major), 100.8 (C-1 minor), 72.5 (C-4),
J1,2 8.4 Hz, H-1 major), 4.31 (dd, 1H, J5,6e 4.9 Hz, J6e,6a
10.4 Hz, H-6e), 4.08 [dd, 1H, Jgem 13.3 Hz, J 2.1 Hz,
OCHA
Hz, H-6a), 3.40 (m, 1H, H-5), 3.10 [m, 1H,
OCH2CH(O)CHCH3], 2.89 [m, 1H, OCH2CH(O)-
CHCH3], 2.05 (s, 3H, CH3CON), 1.40 [d, J 5.3 Hz,
OCH2CH(O)CHCH3 major]. NMR (50
13C
6 HBCH(O)CHCH3], 3.74 (t, 1H, J5,6a=J6e,6a 10.0
71.9 (C-3), 68.3 (C-5), 67.0 [OC
(C-6), 60.8 [OCH2CH(O)CHPh], 55.1 (C-2), 54.3
[OCH2CH(O)CHPh], 23.3 (C
(3C
6 H2CH(O)CHPh], 62.0
6
6
6
6
H3CON), 20.8, 20.7, 20.6
6
’
6
H3COO). HRMS (EI): [M]+ , found 479.177804.
6

2480
J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 13 (2002) 2471–2483
MHz, DMSO-d6): l 169.2 (CꢁO), 137.7, 128.9, 128.0,
56.1 (C-2 major), 24.4, 18.6 [OCH2CH(O)C(C
6
H3)2],
’
126.4 (Ph), 101.7 (C-1 major), 101.6 (C-1 minor), 100.7
23.1 (C6 H3CON). HRMS (EI): [M]+ , found
(PhC
CHCH3 minor], 68.8 [OC
(C-6), 66.0 (C-5), 56.9 [OCH2C
56.7 [OCH2CH(O)CHCH3 major], 56.1 (C-2), 51.3
[OCH2CH(O)CHCH3 minor], 51.2 [OCH2CH(O)-
CHCH3 major], 23.1 (CH3CON), 17.1 [OCH2CH(O)-
CHC
H3]. HRMS (CI): [M+H]+, found 380.171278.
6
H), 81.2 (C-4), 70.3 (C-3), 69.0 [OC
H2CH(O)CHCH3 major], 67.8
H(O)CHCH3 minor],
6
H2CH(O)-
393.178388. C20H27NO7 requires 393.178753. Anal.
calcd for C20H27NO7: C, 61.06; H, 6.92; N, 3.56.
Found: C, 61.00; H, 6.86; N, 3.61%.
6
6
6
6
6
6
3.8.2.5. 3,4-Epoxybutyl 2-acetamido-(R)-4,6-O-ben-
6
zylidene-2-deoxy-b-
D
-glucopyranoside,
28.
Two
C19H26NO7 requires 380.170928. Anal. calcd for
C19H25NO7: C, 60.15; H, 6.64; N, 3.69. Found: C,
59.88; H, 6.64; N, 3.82%.
stereoisomers were obtained. Reaction at 10°C: mp
251–253°C; [h]D −64.5 (c 0.9, DMF); MS (CI): m/z 380
1
(100%) [M+H]+. H NMR (200 MHz, CDCl3): l 7.5–
7.3 (m, 5H, Ph), 6.70 (2d, 1H, J2,NH 4.7 Hz, NH), 5.55
(s, 1H, PhCH
J1,2 8.3 Hz, H-1 major), 4.30 (m, 1H, H-6e), 3.06 [m,
1H, OCH2CH2CH(O)CH2], 2.81, 2.56 [2m, 2H,
OCH2CH2CH(O)CH2], 2.04 (s, 3H, CH3CON), 1.60 [m,
2H, OCH2CH2
CH(O)CH2]. 13C NMR (50 MHz,
DMSO-d6): l 169.1 (CꢁO), 137.8, 128.9, 128.0, 126.4
(Ph), 101.7 (C-1 major), 101.4 (C-1 minor), 100.7
6 ), 4.62 (d, J1,2 8.3 Hz, H-1 minor), 4.53 (d,
3.8.2.3. (2S,3S)-2,3-Epoxy-3-phenylpropyl 2-acetam-
ido-(R)-4,6-O-benzylidene-2-deoxy-b-D-glucopyranoside,
6
26. Mp 248–250°C; [h]D −88.3 (c 1.2, DMF); MS
6
1
(FAB): m/z 464 (100%) [M+Na]+. H NMR (500 MHz,
6
DMSO-d6): l 7.84 (d, 1H, J2,NH 8.8 Hz, NH), 7.5–7.2
(m, 10H, 2Ph), 5.59 (s, 1H, PhCH6 ), 5.28 (d, 1H, J3,OH
5.5 Hz, OH), 4.59 (d, J1,2 8.2 Hz, H-1 minor), 4.55 (d,
J1,2 8.2 Hz, H-1 major), 4.19 (dd, J5,6e 5.0 Hz, J6e,6a 10.2
Hz, H-6e major), 4.11 (dd, J5,6e 4.9 Hz, J6e,6a 10.2 Hz,
(PhC
CH2], 66.0 (C-5), 65.8 (C-6), 56.0 (C-2), 49.2
[OCH2CH2CH(O)CH2], 46.3 [OCH2CH2CH(O)CH2
major], 46.2 [OCH2CH2CH(O)CH2 minor], 32.3
[OCH2CH2CH(O)CH2 major], 32.1 [OCH2CH2CH(O)-
CH2 minor], 23.0 (C
H3CON). HRMS (CI): [M+H]+,
6 H), 81.3 (C-4), 70.4 (C-3), 67.9 [OC6 H2CH2CH(O)-
6
6
H-6e minor), 3.85 [m, 2H, OCHA
[dd, 1H, Jgem 12.3 Hz, J 5.0 Hz, OCHAHB
CHPh], 3.73 (t, 1H, J5,6a=J6e,6a 10.0 Hz, H-6a), 3.62 (m,
1H, H-3), 3.56 (m, 1H, H-2), 3.44 (t, 1H, J3,4=J4,5 9.6
Hz, H-4), 3.35 (dt, 1H, J4,5=J5,6a 9.8 Hz, J5,6e 4.9 Hz,
6
HBCH(O)CH
6
Ph], 3.78
CH(O)-
6
6
6
6
6
found 380.170892. C19H26NO7 requires 380.170928.
Anal. calcd for C19H25NO7: C, 60.15; H, 6.64; N, 3.69.
Found: C, 60.09; H, 6.66; N, 3.96%.
H-5), 3.24 [m, 1H, OCH2CH6 (O)CHPh], 1.82 (s, 3H,
CH3CON major), 1.80 (s, 3H, CH3CON minor). 13C
NMR (125 MHz, DMSO-d6): l 169.3 (CꢁO), 137.7,
137.0, 128.9, 128.5, 128.2, 128.1, 126.4, 125.9 (2Ph),
3.8.3. Epoxidation of 4,6-O-benzylidene-3-O-protected
derivatives
102.0 (C-1 major), 101.9 (C-1 minor), 100.7 (PhC
81.2 (C-4), 70.4 (C-3), 68.8 [OCH2CH(O)CHPh minor],
68.3 [OCH2CH(O)CHPh major], 67.8 (C-6), 66.0 (C-5),
60.3 [OCH2CH(O)CHPh minor], 60.1 [OCH2CH(O)-
CHPh major], 56.1 (C-2), 55.3 [OCH2CH(O)CHPh
minor], 54.9 [OCH2CH(O)CHPh major], 23.1
(C
H3CON). HRMS (CI): [M+H]+, found 442.185556.
6 H),
6
6
3.8.3.1. (R)-2,3-Epoxypropyl 2-acetamido-3-O-acetyl-
6
6
(R)-4,6-O-benzylidene-2-deoxy-b-D-glucopyranoside, 29.
6
From 13: Yield 0.50 g (82%); mp 279–280°C; [h]D −64.0
6
1
(c 1.0, CH2Cl2); MS (CI): m/z 408 (15%) [M+H]+. H
6
NMR (200 MHz, CDCl3): l 7.5–7.3 (m, 5H, Ph), 5.96,
C24H28NO7 requires 442.186578. Anal. calcd for
C24H27NO7: C, 65.29; H, 6.16; N, 3.17. Found: C,
65.13; H, 6.11; N, 3.11%.
5.94 (2d, 1H, J2,NH 9.5 Hz, NH), 5.48 (s, 1H, PhCH6 ),
5.21 (m, 1H, H-3), 4.55 (d, J1,2 8.5 Hz, H-1 minor), 4.43
(d, J1,2 8.4 Hz, H-1 major), 4.30 (dd, 1H, J5,6e 4.7 Hz,
J6e,6a 10.3 Hz, H-6e), 3.06 [m, 1H, OCH2CH
2.76 [m, 1H, OCH2CH(O)CHcisHtrans], 2.64 [dd, Jtrans
2.7 Hz, Jgem 5.2 Hz, OCH2CH(O)CHcisHtrans major],
2.51 [dd, Jtrans 2.6 Hz, Jgem 4.8 Hz, OCH2CH(O)-
6 (O)CH2],
3.8.2.4. (S)-2,3-Epoxy-3-methylbutyl 2-acetamido-(R)-
6
4,6-O-benzylidene-2-deoxy-b-
D
-glucopyranoside, 27. Mp
6
188–190°C; [h]D −64.9 (c 1.0, DMF); MS (CI): m/z 394
1
(80%) [M+H]+. H NMR (200 MHz, CDCl3): l 7.5–7.3
CHcisH6 trans minor], 2.06 (s, 3H, CH3COO), 1.97 (s,
(m, 5H, Ph), 6.35 (d, J2,NH 5.7 Hz, NH minor), 6.18 (d,
CH3CON major), 1.96 (s, CH3CON minor). 13C NMR
(50 MHz, CDCl3): l 171.3, 170.3 (CꢁO), 136.9, 129.1,
128.2, 126.0 (Ph), 102.5 (C-1 major), 102.1 (C-1 minor),
J2,NH 5.8 Hz, NH major), 5.53 (s, 1H, PhCH6 ), 4.75 (d,
J1,2 8.3 Hz, H-1 minor), 4.67 (d, J1,2 8.3 Hz, H-1
major), 4.30 (dd, 1H, J5,6e 4.9 Hz, J6e,6a 10.3 Hz, H-6e),
3.76 (t, 1H, J5,6a=J6e,6a 10.1 Hz, H-6a), 2.99 [dd, 1H, J
101.3 (PhC
[OCH2CH(O)CH2 minor], 68.5 [OC
major], 67.7 (C-6), 66.3 (C-5), 54.3 (C-2), 50.8
[OCH2CH(O)CH2 minor], 50.4 [OCH2CH(O)CH2
major], 44.2 [OCH2CH(O)CH2 minor], 43.8
[OCH2CH(O)CH2 major], 23.3 (CH3CON), 20.9
(C
H3COO). HRMS (CI): [M+H]+, found 408.165674.
6
H), 78.5 (C-4), 71.9 (C-3), 70.7
6
6
H2CH(O)CH2
3.5 Hz, 7.9 Hz, OCH2CH
CH3CON major), 2.02 (s, CH3CON minor), 1.34, 1.31
[2s, OCH2CH(O)C(CH3 2 minor], 1.33, 1.29 [2s,
OCH2CH(O)C(CH3 2
major]. 13C NMR (50 MHz,
6 (O)C(CH3)2], 2.04 (s,
6
6
6
)
6
6
)
6
6
DMSO-d6): l 169.2 (CꢁO), 137.7, 128.8, 128.0, 126.3
6
(Ph), 101.7 (C-1 major), 101.3 (C-1 minor), 100.7
C20H26NO8 requires 408.165842. Anal. calcd for
C20H25NO8: C, 58.96; H, 6.19; N, 3.44. Found: C,
58.92; H, 6.13; N, 3.51%.
(PhC
67.8 [OC
[OCH2CH(O)C(CH3)2 major], 60.6 [OCH2C
C(CH3)2 minor], 57.3 [OCH2CH(O)C(CH3)2 minor],
57.2 [OCH2CH(O)C(CH3)2 major], 56.2 (C-2 minor),
6
H), 81.2 (C-4), 70.4 (C-3 major), 70.3 (C-3 minor),
H2CH(O)C(CH3)2], 67.5 (C-6), 66.0 (C-5), 61.1
H(O)-
6
6
6
6
From 23: An aliquot of compound 23 (0.75 mmol) was
acetylated in the usual way with acetic anhydride/pyri-
6

J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 13 (2002) 2471–2483
2481
dine (1:1) (4 mL). The reaction mixture was kept
overnight at room temperature and then poured into
ice–water. The precipitate obtained was isolated by
filtration and, recrystallized from ethanol–water, gave
29 as only one stereoisomer. Yield 0.28 g (92%); MS
74.4 (PhC
[OC
(C-2), 50.8 [OCH2C
(O)CH2 major], 44.2 [OCH2CH(O)C
(C
H3CON). HRMS (CI): [M+H]+, found 456.201254.
C25H30NO7 requires 456.202228. Anal. calcd for
C25H29NO7: C, 65.92; H, 6.42; N, 3.07. Found: C,
65.67; H, 6.46; N, 3.12%.
6
H2O), 70.8 [OC
6
H2CH(O)CH2 minor], 68.9
6
H2CH(O)CH2 major], 68.7 (C-6), 66.0 (C-5), 57.1
H(O)CH2 minor], 50.3 [OCH2CH-
H2], 23.6
6
6
6
6
1
(FAB): m/z 430 (100%) [M+Na]+. H NMR (200 MHz,
CDCl3): l 7.5–7.3 (m, 5H, Ph), 5.95 (d, 1H, J2,NH 9.3
Hz, NH), 5.48 (s, 1H, PhCH
Hz, H-3), 4.46 (d, 1H, J1,2 8.4 Hz, H-1), 4.31 (dd, 1H,
J5,6e 4.7 Hz, J6e,6a 10.3 Hz, H-6e), 3.50 (dt, 1H, J4,5
J5,6a 9.6 Hz, J5,6e 4.7 Hz, H-5), 3.08 [m, 1H,
OCH2CH(O)CH2], 2.76 [m, 1H, OCH2CH(O)-
CHcisHtrans], 2.64 [dd, 1H, Jtrans 2.7 Hz, Jgem 5.2 Hz,
6 ), 5.20 (t, 1H, J2,3=J3,4 9.9
=
3.8.3.4. (R)-2,3-Epoxypropyl 2-acetamido-(R)-4,6-O-
benzylidene-2-deoxy-3-O-tert-butyldimethylsilyl-b-D-
6
6
glucopyranoside, 32. Yield 0.60 g (83%); mp 125–127°C;
[h]D −66.0 (c 1.0, CH2Cl2); MS (CI): m/z 480 (100%)
OCH2CH(O)CHcisHtrans], 2.06 (s, 3H, CH3COO), 1.97
6
(s, 3H, CH3CON). 13C NMR (50 MHz, CDCl3): l
171.3, 170.3 (CꢁO), 136.9, 129.1, 128.2, 126.1 (Ph),
[M+H]+. H NMR (200 MHz, CDCl3): l 7.5–7.3 (m,
1
5H, Ph), 5.67 (d, 1H, J2,NH 8.1 Hz, NH), 5.46 (s, 1H,
102.5 (C-1), 101.3 (PhC
[OC
50.4 [OCH2C
(CH3CON), 20.9 (C
6
H), 78.5 (C-4), 71.8 (C-3), 68.5
PhCH
1H, J1,2 8.5 Hz, H-1 major), 3.11 [m, 1H,
OCH2CH(O)CH2], 2.76 [m, 1H, OCH2CH(O)-
CHcisHtrans], 2.66 [dd, Jtrans 2.7 Hz, Jgem 5.2 Hz,
OCH2CH(O)CHcisHtrans major], 2.52 [dd, Jtrans 2.7 Hz,
Jgem 5.2 Hz, OCH2CH(O)CHcisHtrans minor], 2.01 (s,
CH3CON minor), 1.96 (s, CH3CON major), 0.79 [s,
9H, OSi(CH3)2C(CH3)3], −0.01, −0.07 [2s, 6H,
OSi(CH
3)2C(CH3)3]. 13C NMR (50 MHz, CDCl3): l
170.3 (CꢁO), 137.1, 129.0, 128.1, 126.3 (Ph), 101.8
(PhCH), 100.8 (C-1 major), 100.5 (C-1 minor), 82.4
(C-4), 71.2 (C-3), 70.5 [OCH2CH(O)CH2 minor], 68.7
[OCH2CH(O)CH2 major, C-6], 66.0 (C-5), 59.1 (C-2),
50.8 [OCH2CH(O)CH2 minor], 50.4 [OCH2CH(O)CH2
major], 44.2 [OCH2CH(O)CH2 minor],
[OCH2CH(O)CH2 major], 25.7 [OSi(CH3)2C(C
23.8 (CH3CON), 18.1 [OSi(CH3)2C
[OSi(C
H3)2C(CH3)3]. HRMS (CI): [M+H]+, found
6 ), 4.98 (d, 1H, J1,2 8.5 Hz, H-1 minor), 4.90 (d,
6
H2CH(O)CH2], 67.7 (C-6), 66.4 (C-5), 54.4 (C-2),
H(O)CH2], 43.8 [OCH2CH(O)CH2], 23.3
H3COO).
6
6
6
6
6
6
6
6
3.8.3.2. (R)-2,3-Epoxypropyl 2-acetamido-(R)-4,6-O-
benzylidene-2-deoxy-3-O-methyl-b-
D
-glucopyranoside,
6
30. Yield 0.27 g (47%); mp 211–212°C; [h]D +102.2 (c
6
0.5, CH2Cl2); MS (CI): m/z 380 (100%) [M+H]+. H
NMR (200 MHz, CDCl3): l 7.5–7.3 (m, 5H, Ph), 5.83
1
6
(d, 1H, J2,NH 7.7 Hz, NH), 5.52 (s, 1H, PhCH
J1,2 8.2 Hz, H-1 minor), 4.95 (d, J1,2 8.2 Hz, H-1
major), 4.31 (dd, 1H, J5,6e 4.3 Hz, J6e,6a 10.3 Hz, H-6e),
6
), 5.05 (d,
6
6
6
6
3.11
OCH2CH(O)CHcis
5.1 Hz, OCH2CH(O)CHcisHtrans
[m,
1H,
6
OCH2CH
Htrans], 2.65 [dd, Jtrans 2.7 Hz, Jgem
major], 2.55 [dd, Jtrans
6
(O)CH2],
2.77
[m,
6
44.1
H3)3],
6
6
6
6
6 (CH3)3], −4.1, −5.0
2.6 Hz, Jgem 5.2 Hz, OCH2CH(O)CHcisHtrans
6
minor],
6
2.01 (s, 3H, CH3CON). 13C NMR (50 MHz, CDCl3): l
170.1 (CꢁO), 137.2, 129.0, 128.2, 126.0 (Ph), 101.2 (C-1
480.241486. C24H38NO7Si requires 480.241756. Anal.
calcd for C24H37NO7Si: C, 60.10; H, 7.78; N, 2.92.
Found: C, 60.14; H, 7.80; N, 3.03%.
major), 101.1 (C-1 minor), 100.6 (PhC
6
H), 82.3 (C-4),
H2CH(O)CH2], 68.7 (C-6), 65.9
(C-5), 57.6 (C-2), 50.7 [OCH2CH(O)CH2 minor], 50.3
[OCH2CH(O)CH2 major], 44.2 [OCH2CH(O)CH2], 29.7
(CH3O), 23.7 (C
H3CON). HRMS (CI): [M+H]+, found
78.4 (C-3), 69.2 [OC
6
6
6
6
3.8.3.5. (R)-2,3-Epoxy-2-methylpropyl 2-acetamido-
(R)-4,6-O-benzylidene-2-deoxy-3-O-tert-butyldimethyl-
silyl-b-D-glucopyranoside, 33. Yield 0.56 g (76%); mp
137–139°C; [h]D −42.5 (c 0.8, CH2Cl2); MS (CI): m/z
494 (50%) [M+H]+. 1H NMR (200 MHz, CDCl3): l
7.5–7.3 (m, 5H, Ph), 5.64 (d, 1H, J2,NH 8.3 Hz, NH),
6
380.169608. C19H26NO7 requires 380.170928. Anal.
calcd for C19H25NO7: C, 60.15; H, 6.64; N, 3.69.
Found: C, 59.90; H, 6.62; N, 3.80%.
5.46 (s, 1H, PhCH6 ), 4.92 (d, J1,2 8.4 Hz, H-1 minor),
3.8.3.3. (R)-2,3-Epoxypropyl 2-acetamido-3-O-benzyl-
4.80 (d, J1,2 8.5 Hz, H-1 major), 4.29 (dd, 1H, J5,6e 4.2
Hz, J6e,6a 10.2 Hz, H-6e), 2.81, 2.57 [2d, 2H, Jgem 5.1
(R)-4,6-O-benzylidene-2-deoxy-b-D-glucopyranoside, 31.
Yield 0.58 g (85%); mp 263–264°C; [h]D −54.0 (c 1.0,
CH2Cl2); MS (FAB): m/z 478 (97%) [M+Na]+. 1H
NMR (200 MHz, CDCl3): l 7.5–7.3 (m, 10H, 2Ph),
Hz, OCH2C(CH3)(O)CH2
[s, OCH2C(CH3)(O)CH2
OCH2C(CH3)(O)CH2 major], 0.79 [s, 9H, OSi(CH3)2-
C(CH3)3], −0.14, −0.07 [2s, 6H, OSi(CH3 2
) C(CH3)3]. 13
NMR (50 MHz, CDCl3): l 170.1 (CꢁO), 137.1, 129.0,
128.1, 126.2 (Ph), 101.8 (PhCH), 101.2 (C-1 major),
100.8 (C-1 minor), 82.3 (C-4), 73.2
[OCH2C(CH3)(O)CH2 minor], 71.5 (C-3 major), 71.4
(C-3 minor), 70.6 [OCH2C(CH3)(O)CH2 major], 68.7
(C-6), 66.0 (C-5), 58.9 (C-2 minor), 58.7 (C-2 major),
55.8 [OCH2C(CH3)(O)CH2], 51.6 [OCH2C(CH3)(O)-
H2 minor], 50.9 [OCH2C(CH3)(O)CH2 major], 25.7
[OSi(CH3)2C(CH3)3], 23.7 (CH3CON),
[CH2C(CH3)(O)CH2], 18.1 [OSi(CH3)2C
–5.0 [OSi(C
6
], 1.98 (s, 3H, CH3CON), 1.35
6
minor], 1.30 [s,
6
5.6–5.5 (m, 2H, NH, PhCH
minor), 4.9–4.8 (m, H-1 major, PhCHA
1H, Jgem 11.9 Hz, PhCHAHBO), 4.33 (dd, 1H, J5,6e 4.9
Hz, J6e,6a 10.3 Hz, H-6e), 3.10 [m, 1H, OCH2CH(O)-
CH2], 2.76 [m, 1H, OCH2CH(O)CHcisHtrans], 2.64 [dd,
Jtrans 2.7 Hz, Jgem 5.2 Hz, OCH2CH(O)CHcisHtrans
major], 2.52 [dd, Jtrans 2.6 Hz, Jgem 5.2 Hz,
6
), 4.96 (d, J1,2 8.3 Hz, H-1
6
6
C
6
HBO), 4.62 (d,
6
6
6
6
6
6
6
OCH2CH(O)CHcisHtrans
6
minor], 1.89 (s, CH3CON
6
major), 1.87 (s, CH3CON minor). 13C NMR (50 MHz,
C6
6
CDCl3): l 170.5 (CꢁO), 138.3, 137.3, 129.0, 128.4,
6
6
18.3
(CH3)3], –4.1,
128.3, 128.2, 127.8, 126.0 (2Ph), 101.2 (PhC
(C-1 major), 100.7 (C-1 minor), 82.6 (C-4), 76.5 (C-3),
6
H), 101.0
6
6
6
H3)2C(CH3)3]. HRMS (CI): [M+H]+, found

2482
J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 13 (2002) 2471–2483
494.258167. C25H40NO7Si requires 494.257406. Anal.
calcd for C25H39NO7Si: C, 60.82; H, 7.96; N, 2.84.
Found: C, 60.59; H, 7.80; N, 2.87%.
methoxide (1.0 mmol) in methanol (2 mL). After 30
min at room temperature, the mixture was neutralized
by addition of Dowex 50 resin (H+ form), filtered, and
evaporated. The solid obtained was dissolved in benz-
aldehyde (10 mL), and zinc chloride (0.5 g) was added.
The mixture was stirred for 2 days and then poured
into hexane/water (1:1) (50 mL) with stirring. The
precipitate was filtered off, washed with water and with
hexane, and then recrystallized from ethanol. Yield 0.43
g (70%); mp 228–229; MS (CI): m/z 409 (5%) [M+H]+.
1H NMR (200 MHz, DMSO-d6): l 7.86 (d, J2,NH 8.4
Hz, NH minor), 7.83 (d, J2,NH 8.4 Hz, NH major),
3.8.3.6. (R)-2,3-Epoxypropyl 2-acetamido-(R)-4,6-O-
benzylidene-2-deoxy-2-N-3-O-methylidene-b-D-glucopy-
ranoside, 34. Two stereoisomers were obtained. Yield
0.35 g (62%); mp 198–199°C; [h]D +82.8 (c 1.1,
1
CH2Cl2); MS (CI): m/z 378 (15%) [M+H]+. H NMR
(200 MHz, DMSO-d6, 80°C): l 7.6–7.3 (m, 5H, Ph),
5.70 (s, 1H, PhCH
OCHAHBN), 4.96, 4.95 (2d, 1H, J1,2 8.0 Hz, H-1), 4.72
(d, 1H, Jgem 5.0 Hz, OCHAHBN), 3.15 [m, 1H,
OCH2CH(O)CH2], 2.73, 2.60 [2m, 2H, OCH2CH(O)-
CH
6 ), 5.27 (d, 1H, Jgem 5.0 Hz,
6
7.5–7.3 (m, 5H, Ph), 5.59 (s, 1H, PhCH6 ), 5.28 (m, 2H,
6
2OH), 4.47 (d, J1,2 7.8 Hz, H-1 minor), 4.44 (d, J1,2 7.8
Hz, H-1 major), 4.19 (dd, 1H, J5,6e 4.3 Hz, J6e,6a 10.1
Hz, H-6e), 1.1 (s, 3H, CH3CON). 13C NMR (50 MHz,
DMSO-d6): l 169.3 (CꢁO), 137.7, 129.9, 128.1, 126.4
(Ph), 102.2 (C-1 major), 102.0 (C-1 minor), 100.7
6
6
2], 2.14 (s, CH3CON minor), 2.13 (s, CH3CON
major). 13C NMR (50 MHz, CDCl3): l 179.5 (CꢁO),
136.4, 129.2, 128.2, 126.1 (Ph), 103.5 (C-1 major), 103.3
(C-1 minor), 101.5 (PhC
79.0 (C-3), 71.1 [OC
[OC
(C-2 major), 61.6 (C-2 minor), 50.2 [OCH2C
minor], 50.0 [OCH2CH(O)CH2 major],
[OCH2CH(O)CH2 major], 44.2 [OCH2CH(O)C
minor], 23.2 (C
H3CON). HRMS (CI): [M+H]+, found
6
H), 82.2 (OCH2N), 81.8 (C-4),
H2CH(O)CH2 minor], 70.1
(PhC
(C-3), 68.6 [OCH2C
5), 56.1 (C-2), 53.2 [OCH2CH(OH)C
(C
H3CON). HRMS (CI): [M+H]+, found 409.171958.
6
H), 81.2 (C-4), 70.4 [OC
H(OH)CH2N3], 67.8 (C-6), 66.0 (C-
H2N3], 23.1
6 H2CH(OH)CH2N3], 70.3
6
6
6
H2CH(O)CH2 major], 69.1 (C-5), 68.4 (C-6), 61.9
H(O)CH2
44.3
H2
6
6
6
6
C18H25N4O7 requires 409.172325. Anal. calcd for
C18H24N4O7: C, 52.94; H, 5.92; N, 13.72. Found: C,
52.88; H, 5.87; N, 13.80%.
6
6
6
378.154586. C19H24NO7 requires 378.155277. Anal.
calcd for C19H23NO7: C, 60.47; H, 6.14; N, 3.71.
Found: C, 60.40; H, 6.05; N, 3.80%.
3.9.3. (R)-2-Acetoxy-3-azidopropyl 2-acetamido-3-O-
acetyl-(R)-4,6-O-benzylidene-2-deoxy-b-D-glucopyrano-
3.9. Azide ring-opening reaction
side, 37. Compound 36 (100 mg, 0.25 mmol) was acetyl-
ated in the usual way with acetic anhydride/pyridine
(1:1) (5 mL). The reaction mixture was kept overnight
at room temperature and then poured into ice–water.
The precipitate obtained was isolated by filtration and
recrystallized from ethanol, giving compound 37 as a
white solid. Only one stereoisomer was obtained. Yield
109 mg (89%); mp 218–219°C; [h]D −64.9 (c 1.0,
3.9.1. (R)-3-Azido-2-hydroxypropyl 2-acetamido-3,4,6-
tri-O-acetyl-2-deoxy-b-D-glucopyranoside 35. To a solu-
tion of compound 19 (0.81 g, 2.0 mmol) in acetonitrile
(20 mL), lithium perchlorate (0.43 g, 4.0 mmol) and
sodium azide (0.52 g, 8.0 mmol) were added. The
mixture was stirred at room temperature for 30 days,
with stirring. It was then poured into ice-water, and the
precipitate obtained was filtered off, dried, and recrys-
tallized from ethanol. Two stereoisomers were obtained
in 87:13 ratio (74% d.e.). Yield 0.58 g (65%); mp
104–105°C; [h]D +55.6 (c 0.9, AcOEt); MS (FAB): m/z
1
CH2Cl2); MS (CI): m/z 493 (70%) [M+H]+. H NMR
(200 MHz, CDCl3): l 7.5-7.3 (m, 5H, Ph), 5.90 (d, 1H,
J2,NH 9.4 Hz, NH), 5.49 (s, 1H, PhCH
2,3=J3,4 9.9 Hz, H-3), 5.05
OCH2CH(OAc)CH2N3], 4.40 (d, 1H, J1,2 8.4 Hz, H-1),
4.30 (dd, 1H, J5,6e 4.8 Hz, J6e,6a 10.4 Hz, H-6e), 4.11 (m,
1H, H-2), 3.41 [d, 2H, 4.7 Hz,
6
), 5.20 (t, 1H,
J
[m, 1H,
6
1
469 (100%) [M+Na]+. H NMR (200 MHz, CDCl3): l
5.88 (d, 1H, J2,NH 8.8 Hz, NH), 4.63 (d, J1,2 8.4 Hz, H-1
major), 4.61 (d, J1,2 8.3 Hz, H-1 minor), 3.43 [d, J 4.6
J
OCH2CH(OAc)CH6 2N3], 2.08, 2.07, 1.95 (3s, 9H,
3CH3CO). 13C NMR (50 MHz, CDCl3): l 171.5, 170.2,
170.1, (3CꢁO), 136.8, 129.1, 128.3, 126.0 (Ph), 102.0
Hz, OCH2CH(OH)CH6 2N3 minor], 3.32 [d, J 5.2 Hz,
OCH2CH(OH)CH6 2N3 major], 2.07, 2.02, 2.01, 2.00,
1.94 (4s, 12H, 4CH3CO). 13C NMR (50 MHz, CDCl3):
(C-1), 101.3 (PhC
[OCH2CH(OAc)CH2N3], 68.5 [OC
67.0 (C-6), 66.4 (C-5), 54.1
[OCH2CH(OAc)CH2N3], 23.3 (CH3CON), 20.9, 20.8,
(2CH3COO). Anal. calcd for C22H28N4O9: C, 53.65; H,
6 H), 78.5, (C-4), 71.7 (C-3), 70.5
l 171.1, 170.9, 170.7, 169.3 (4CꢁO), 101.8 (C-1), 72.3
6
6
H2CH(OAc)CH2N3],
(C-2), 50.5
[OC
[OCH2C
CH2N3 minor], 68.3 (C-5), 62.0 (C-6), 54.5 (C-2 minor),
54.3 (C-2 major), 53.1 [OCH2CH(OH)CH2N3 major],
52.8 [OCH2CH(OH)CH2N3 minor], 23.3 (CH3CON),
20.7, 20.6, 20.5 (3C
H3COO). HRMS (CI): [M+H]+,
6 H2CH(OH)CH2N3], 72.2, (C-4), 71.9 (C-3), 69.7
6
H(OH)CH2N3 major], 69.5 [OCH2C6 H(OH)-
6
6
6
6
5.73; N, 11.38. Found: C, 53.82; H, 5.53; N, 11.12%.
6
6
6
found 447.172302. C17H27N4O10 requires 447.172719.
Anal. calcd for C17H26N4O10: C, 45.74; H, 5.87; N,
12.55. Found: C, 45.61; H, 5.70; N, 12.62%.
Acknowledgements
3.9.2. (R)-3-Azido-2-hydroxypropyl 2-acetamido-(R)-
We thank the Ministerio de Ciencia y Tecnolog´ıa
(Spain) and the FEDER program for financial support
(BQU2001-2425), and Jose´ Mart´ın Reina for his collab-
oration in the preparation of the starting material.
4,6-O-benzylidene-2-deoxy-b-D-glucopyranoside, 36. To
a solution of compound 35 (0.67 g, 1.5 mmol) in
methanol (15 mL) was added a solution of sodium

J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 13 (2002) 2471–2483
2483
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