Stereoselective synthesis of oxiranes using oxazolidines derived from 2-amino-2-deoxy-D-allose as chiral auxiliaries

Article abstract of DOI:10.1016/S0957-4166(01)00562-6

The synthesis of 2,3-epoxyamide derivatives of 2-amino-2-deoxy-D-allose is described. Epoxidation of the corresponding α,β-unsaturated amides with m-CPBA took place with better stereoselectivity when an oxazolidine ring was fused to the 2,3-positions of the sugar molecule. In most cases, both stereoisomers could be isolated and characterized. The stereochemistry of the new stereogenic centers was then determined by cleavage of the oxirane moiety from the chiral auxiliary, which was also recovered.

Full text of DOI:10.1016/S0957-4166(01)00562-6

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 3189–3203
Stereoselective synthesis of oxiranes using oxazolidines derived
from 2-amino-2-deoxy-
-allose as chiral auxiliaries†
D
Jose´ M. Vega-Pe´rez,* Margarita Vega, 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 19 November 2001; accepted 13 December 2001
Abstract—The synthesis of 2,3-epoxyamide derivatives of 2-amino-2-deoxy-D-allose is described. Epoxidation of the correspond-
ing a,b-unsaturated amides with m-CPBA took place with better stereoselectivity when an oxazolidine ring was fused to the
2,3-positions of the sugar molecule. In most cases, both stereoisomers could be isolated and characterized. The stereochemistry
of the new stereogenic centers was then determined by cleavage of the oxirane moiety from the chiral auxiliary, which was also
recovered. © 2002 Elsevier Science Ltd. All rights reserved.
Carbohydrates are polyfunctional molecules with sev-
1. Introduction
eral stereogenic centers, making them important chiral
templates for numerous asymmetric transformations.33
Chiral 1,3-oxazolidines are widely used in asymmetric
As part of our work, we have used 2-aminosugars with
synthesis. They are usually prepared by reaction of
gluco-, allo- and altro-configuration as chiral starting
carbonyl compounds (mainly aldehydes) with chiral
materials in the synthesis of numerous compounds (2-
b-amino alcohols—ephedrine, norephedrine, phenylgly-
aminoglycals, 2-nitrosugars, compounds with potential
cinol, prolinol are among the most commonly used.2–7
anti-cancer activity).34–39 In previous papers, we have
Bicyclic oxazolidines have also been prepared by con-
densation of a chiral b-amino alcohol with dialkyl g-
reported the synthesis of oxazolidines from 2-amino-2-
deoxy-D-glucose and D-allose derivatives with different
groups on C(2) of the oxazolidine ring, and the reactiv-
ity of these compounds with nucleophiles.1,40–43 We
have also reported the stereoselective epoxidation of
allyl glucopyranoside derivatives and their reactivity
with different nucleophiles.44
and d-chloroketones8 and with keto-acids,9–12 generat-
ing in the process a new stereogenic center with high
stereoselectivity. Many authors have studied the reac-
tivity of the oxazolidine ring with nucleophilic agents, a
good approach to the asymmetric synthesis of chiral
nitrogenated compounds (amines, pyrrolidines, pipe-
ridines, a-amino aldehydes, etc.).13–17 At the same time,
various asymmetric transformations (Diels–Alder
cycloadditions, nucleophile addition, epoxidations)
have been carried out on a,b-unsaturated carbonyl
compounds derived from chiral oxazolidines.3,4,18,19
Herein, we describe the use of the oxazolidines derived
from 2-amino-2-deoxy-D-allose as chiral auxiliaries in
the asymmetric synthesis of the oxiranes of a,b-unsatu-
rated amides.
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.20–22 They are pre-
pared by oxidation of the appropriate alkene,23–27 or
alternatively from aldehydes by employing either the
2. Results and discussion
The alkyl 2-acylamino-(R)-4,6-O-benzylidene-2-deoxy-
D
-allopyranosides 4–10 were obtained in excellent yields
from benzyl or dodecyl 2-amino-(R)-4,6-O-benzylidene-
2-deoxy-
-allopyranosides 1,45 245 and 336 by reaction
with the corresponding activated unsaturated acid. We
have used three different methods for these reactions,
depending on the acid derived and the condensing
agent (Scheme 1). The NMR spectra showed signals
corresponding to the unsaturated moiety incorporated
D
Darzens reaction or
a
sulphur ylide-mediated
approach.28–32
* Corresponding authors. Tel./fax: +34 95 4556737; e-mail: vega@
fafar.us.es
1
† Oxazolidines from sugars, Part 6. For Part 5, see: Ref. 1.
to the sugar molecule in the reaction. In the H spectra,
0957-4166/01/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00562-6

3190
J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 12 (2001) 3189–3203
Ph
O
Ph
O
O
O
O
i
O
OR
OR
HN
R1
NH2
OH
OH
O
R2
1 R = β-Bn
2 R = α-Bn
3 R = β-n-C12H25
4 R = β-Bn , R1 = Ph , R2 = H
5 R = β-Bn , R1 = Me , R2 = H
6 R = β-Bn , R1 = Et , R2 = H
7 R = β-Bn , R1 = Me , R2 = Me
8 R = α-Bn , R1 = Ph , R2 = H
ii
Ph
O
O
O
OBn
9 R = β-n-C12H25 , R1 = Ph , R2 = H
HN
OH
O
10
Scheme 1. (i) Method A: trans-PhCHꢁCHCOCl/Py/CH2Cl2 (4, 8, 9); Method B: R1R2CꢁCHCO2H/pentachlorophenol
trichloroacetate/Et3N/THF (5, 6, 7); (ii) Method C: CH2ꢁCHCH2CO2H/DCC/DMAP/CH2Cl2.
two doublets at 6.4 and 7.6 ppm for compounds 4, 8
and 9, two multiplets at 5.7 and 6.9 ppm for 5 and 6, a
multiplet at 5.53 ppm for 7 and two multiplets at 5.80
and 5.14 ppm for 10 were observed. The 13C spectra
showed two signals at approximately 120 and 145 ppm
for each one of these compounds.
showed signals at 60–55 ppm for 11, 12, and 13 and at
48.7 and 39.7 ppm for 14. The results of this reaction,
shown in Table 1, indicate that the de is low when the
reaction is carried out at room temperature (entries 1,
3, 4, 5) and somewhat better when the reaction is
performed at −10°C (entry 2), although at the cost of a
considerable increase in reaction time. Moreover, the
We have studied the effect of the stereogenic centers of
the sugar in the stereofacial differentiation of the
diastereotopic faces of the double bond in the epoxida-
tion reaction, and used 1H NMR to determine the
diastereomeric excess (de) in each case. The reaction of
4, 5, 9 and 10 with m-chloroperbenzoic acid (m-CPBA)
in dichloromethane at room temperature gave the cor-
responding oxiranes 11–14, which were isolated as mix-
tures of stereoisomers (Scheme 2, Table 1). The 1H
NMR spectrum for 11 contained two doublets at 3.62
and 3.51 ppm, corresponding to the oxirane protons of
the major isomer. For the minor isomer, an isolated
doublet was observed at 3.55 ppm, corresponding to
the oxirane proton in a-position to the carbonyl group.
Compounds 12, 13 and 14 showed signals between 3.5
and 2.3 ppm for the oxirane system. The 13C spectra
solubility of compounds 4, 5,
9
and 10 in
dichloromethane at −10°C is much lower than at room
temperature, which means having to use greater
amounts of solvent and oxidant for the same amount of
starting material.
Epoxides 11, 12 and 14, used as stereoisomeric mix-
tures, were ring-opened with lithium aluminum hydride,
giving the hydroxylamides 15, 16 and 17 (Scheme 3).
The reaction of 11 gave only one regioisomer 15, which
was characterized as its diacetyl derivative 18. The
reaction of 12 gave 16 and 17 in 1:3 ratio. The 1H
NMR spectrum shows two signals for methyl group, a
triplet at 0.87 ppm for 16, and a doublet at 1.17 ppm
for 17, with relative integral of 1:3. Compound 14
afforded 17 as the sole product.
Ph
Ph
O
O
O
O
O
O
i
OBn
OBn
O
O
4
+
HN
Ph
HN
Ph
S
R
OH
OH
R
S
O
O
11a
11b
Ph
Ph
O
O
O
O
O
O
i
i
OR
OBn
10
5, 9
O
HN
R1
HN
OH
OH
O
O
O
14
12 R = Bn , R1 = Me
13 R = n-C12H25 , R1 = Ph
Scheme 2. (i) m-CPBA/CH2Cl2.

J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 12 (2001) 3189–3203
3191
Table 1. Epoxidation of unsaturated amides 4, 5, 9, 10, 19–22, 24 and 26 with m-CPBA at room temperature
Entry
Starting compound
Reaction timea (days)
Reaction product
Yieldb (%)
Dec (%)
1
2
3
4
5
6
7
8
4
4
5
2
10d
3
3
2
2
2
2
3
11
11
12
13
14
27
28
29
30
32
33
80
71
95
91
85
85
80
83
78
94
75
26
40
16
0
12
94
44
46
48
76
50
9
10
19
20
21
22
24
26
9
10
11
3
2
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 integration in 1H NMR spectra of reaction mixtures.
d Reaction at −10°C.
Ph
Ph
O
O
O
O
O
O
OBn
O
OBn
O
ii
i
OAc
OH
11
HN
HN
Ph
Ph
OAc
OH
18
15
Ph
Ph
O
O
O
O
O
O
OBn
O
OBn
OH
i
+
12
14
HN
HN
OH
OH
O
OH
17
16
i
17
Scheme 3. (i) LiAlH4/THF/−10°C; (ii) Ac2O/Py/CH2Cl2.
With the aim of demonstrating the regiochemistry of
the oxirane ring opening reaction of 11, 12, and 14, and
the stereochemistry of the major stereoisomer of oxi-
ranes 11, we obtained compounds 15a, 15b and 17a by
unequivocal synthesis from compound 1 and the corre-
sponding enantiomerically pure acid, and their diacetyl
derivatives 18a and 18b (Scheme 4). The NMR data,
shown in Tables 2 and 3, indicates that in the stereoiso-
meric mixture 15 (Table 2) and 18 (Table 3), the major
isomer has (S)-configuration at the stereogenic carbon
in the a-position of the amide group (15a and 18a), and
thus the major stereoisomer in the oxirane 11 has
(2S,3R)-configuration (11a) (Scheme 2).
viously by our research group1,41,42 (Scheme 5). The
NMR spectra showed signals corresponding to the
methylidene group introduced in the reaction. In the 1H
spectra, two doublets between 5.35 and 5.15 ppm were
observed in each case. The 13C spectra contained a
signal at 82–80 ppm for each compound.
The synthesis of compound 26 was carried out from 10
in two steps (Scheme 5). The treatment of 10 with
acetone–dichloromethane (1:1) containing magnesium
sulphate as a dehydrating agent gave the oxazolidine
25, characterized by its mass spectrum {MS (CI) m/z
398 (100%) [M+H]+}. It was used without further
purification because of its low stability (oxazolidine X
imine equilibrium has been described for compounds
with this structure).2 The reaction of 25 with crotonyl
chloride/pyridine in dichloromethane at 0°C yielded
compound 26 (65% from 10). The NMR data confirm
the presence of the isopropylidene group (1.64 and 1.58
We have also studied the epoxidation of a,b-unsatu-
rated amides derived from sugar-oxazolidines. The for-
mation of a new ring between positions 2 and 3 of the
sugar increases the rigidity of the chiral auxiliary, and
thus enables greater stereoselectivity in the epoxidation
reaction. The alkyl 2-N-acyl-2-amino-(R)-4,6-O-benzyl-
1
ppm in H spectrum, 26.5 and 23.8 ppm in 13C spec-
idene-2-deoxy-2-N-3-O-methylidene-D-allopyranosides
trum) and the crotonyl group (three signals at 6.90, 6.48
19–24 were obtained in good yield from compounds
4–9 by reaction with dibromomethane under phase-
transfer conditions, using a methodology described pre-
1
and 1.75 ppm in H spectrum, 163.3, 140.9, 124.5 and
17.7 ppm in 13C spectrum).

3192
J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 12 (2001) 3189–3203
Ph
Ph
O
O
O
O
O
O
OBn
OBn
iv
OH
OAc
HN
HN
Ph
Ph
Ph
Ph
OH
OH
OAc
S
S
i
O
O
15a
18a
Ph
Ph
O
O
O
O
O
O
OBn
OBn
iv
ii
OH
OAc
1
HN
HN
OAc
R
R
iii
O
O
15b
18b
Ph
O
O
O
OBn
HN
S
OH
O
OH
17a
Scheme 4. (i) (S)-(−)-3-Phenyllactic acid/DCC/NHS/dioxane; (ii) (R)-(+)-3-phenyllactic acid/DCC/NHS/dioxane; (iii) (S)-(+)-3-
hydroxybutyric acid/DCC/NHS/dioxane; (iv) Ac2O/Py/CH2Cl2.
Table 2. Comparison of the NMR data (l, ppm) for the stereoisomeric mixture 15 and the diastereomerically pure
compounds 15a and 15b
Entry
Signal assigned
15 major isomer/minor isomer
15a (S-configuration)
15b (R-configuration)
1
2
3
4
5
NH
6.93/6.83
4.57/4.55
2.75/2.87
73.1/72.8
41.0/40.7
6.88
4.57
2.77
73.0
41.0
6.79
4.56
2.89
72.8
40.7
OCHAHB
CH(OH)CHAHB
H(OH)CH2Ph
CH(OH)CH2Ph
6 Ph
6
Ph
C6
6
Table 3. Comparison of the NMR data (l, ppm) for the stereoisomeric mixture 18 and the diastereomerically pure
compounds 18a and 18b
Entry
Signal assigned
18 major isomer/minor isomer
18a (S-configuration)
18b (R-configuration)
1
2
3
4
5
NH
H-3
2CH3CO
5.96/6.05
5.67/5.63
2.05, 1.90/2.04, 1.94
74.3/74.1
37.2/36.8
6.00
5.68
2.05, 1.91
74.3
6.06
5.64
2.05, 1.95
74.1
C
6
H(OAc)CH2Ph
CH(OAc)CH2Ph
6
37.2
36.8
The reaction of 19–24 and 26 with m-CPBA in
dichloromethane at room temperature gave the corre-
sponding oxiranes 27–33 as mixtures of stereoisomers
with good yields and with de of between 44 and 94%
(Scheme 6, Table 1). In most cases, both stereoisomers
were isolated by column chromatography, the major
isomer always having the higher Rf. The NMR data for
the oxirane system in compounds 27–33 are shown in
The absolute stereochemistry of the 2,3-epoxyamides
was deduced by correlation with the (2R,3R)-(+)-3-
phenylglycidol obtained from 27 or 32. The reaction of
the major isomer of 27 or 32 with sodium borohydride
in THF at room temperature yielded a sugar derivative
identified by MS as compound 1 or 3, and another
identified by MS, NMR, and [h]D data as (2R,3R)-(+)-
3-phenylglycidol 34 (Scheme 7). The results indicate
that the major stereoisomer of the a,b-epoxyamides has
(2S,3R)-configuration at the oxirane ring.
1
Table 4. In the H NMR spectra of these compounds,
the signal corresponding to the a-protons of the oxirane
ring appears with a greater chemical shift in the minor
isomer, while the chemical shift of the b-proton is
greater for the major isomer. In all 13C spectra of these
compounds, the two signals corresponding to the oxi-
rane carbons appear with the greater chemical shift in
the major isomer.
3. Conclusions
In conclusion, we have presented a stereoselective syn-
thesis of a,b-epoxyamides derived from alkyl allopyran-

J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 12 (2001) 3189–3203
4−9 10
3193
ii
i
Ph
O
O
O
OBn
NH
Ph
O
O
O
O
OR
N
R1
25
O
O
R2
iii
19 R = β-Bn , R1 = Ph , R2 = H
20 R = β-Bn , R1 = Me , R2 = H
21 R = β-Bn , R1 = Et , R2 = H
22 R = β-Bn , R1 = Me , R2 = Me
23 R = α-Bn , R1 = Ph , R2 = H
24 R = β-n-C12H25 , R1 = Ph , R2 = H
Ph
O
O
O
OBn
N
O
O
26
Scheme 5. (i) CH2Br2/CH2Cl2/TBABr/50% NaOH/H2O/reflux; (ii) acetone/CH2Cl2/MgSO4; (iii) trans-CH3CHꢁCHCOCl/Py/
CH2Cl2/0°C.
19−24, 26
m-CPBA/CH2Cl2
Ph
Ph
O
O
O
O
O
O
OR
OR
O
O
+
N
R1
N
R1
S
R
O
O
R
S
R3
R3
O
R2
R3
27a−33a
R3
27b−33b
O
R2
27 R = β-Bn , R1 = Ph , R2 = H , R3 = H
28 R = β-Bn , R1 = Me , R2 = H , R3 = H
29 R = β-Bn , R1 = Et , R2 = H , R3 = H
30 R = β-Bn , R1 = Me , R2 = Me , R3 = H
31 R = α-Bn , R1 = Ph , R2 = H , R3 = H
32 R = β-n-C12H25 , R1 = Ph , R2 = H , R3 = H
33 R = β-Bn , R1 = Me , R2 = H , R3 = Me
Scheme 6.
Table 4. NMR data (l, ppm) for the oxiranes 27–30, 32 and 33
Entry
Compound
CH6
(O)CHR1
CH(O)CH
6
R1
C6
H(O)CHR1
CH(O)C6
HR1
1
2
3
4
5
6
7
8
9
27a
28a
28b
29a
29b
30
32a
32b
33a
33b
3.95
3.43
3.75
3.49
4.0–3.7
3.33
3.97
4.09
3.47
4.23
3.24
3.22
3.19
3.15
–
4.3–4.2
4.15
3.23
3.17
58.2
54.5
54.4
58.7
58.6
60.7
58.8
58.5
55.0
54.3
56.6
53.9
53.8
52.5
52.4
56.8
58.1
57.8
54.5
54.3
10
4.0–3.7

3194
J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 12 (2001) 3189–3203
Ph
O
O
O
O
i
27 (major isomer)
32 (major isomer)
OR
HO
Ph
+
R
R
NH2
OH
1 R = Bn
3 R = n-C12H25
(2R,3R)-(+)-3-phenylglycidol (34)
Ph
O
O
O
O
OR
O
HO
Ph
R
N
Ph
R
S
O
R
(2R,3R)-(+)-3-phenylglycidol (34)
O
27a R = Bn
32a R = n-C12H25
Scheme 7. (i) NaBH4/THF.
osides, with good yields, in which the 2-amino-2-deoxy-
D
-
saturated aqueous sodium bicarbonate and water, dried
(MgSO4), filtered and the filtrate evaporated to dryness
togiveasolidwhichwaspurifiedbyflashchromatography
on silica gel.
allose moiety acts as an effective chiral auxiliary. When
positions 2 and 3 of the sugar participate in an oxazolidine
ring, (a) the starting compounds are more soluble in
dichloromethane, (b) the stereoselectivity of the epoxida-
tion reaction increases considerably, (c) both stereoiso-
mers can be separated and isolated using column
chromatography, (d) the a,b-epoxyamide can be sepa-
rated from the sugar moiety and e) the chiral auxiliary
(sugar) can be recovered.
4.2.1.1. Benzyl (R)-4,6-O-benzylidene-2-deoxy-2-
(trans-3-phenyl-2-propenamido)-b-
D
-allopyranoside
4.
Column chromatography using dichloromethane-
methanol (150:1) as eluent yielded 1.24 g (85%). Mp
238–239°C; [h]D1−74.1 (c 0.5, CH2Cl2); MS (CI): m/z 488
(43%) [M+H]+. H NMR (200 MHz, CDCl3): l 7.65 (d,
1H, Jtrans 15.6 Hz, CHꢁCH
6.35 (d, 1H, Jtrans 15.6 Hz, CH
9.3 Hz, NH), 5.60 (s, 1H, PhCH
Hz, OCHAHBPh), 4.74 (d, 1H, J1,2 8.4 Hz, H-1), 4.59 (d,
1H, Jgem 12.5 Hz, OCHAHBPh), 4.5–4.3 (m, 2H, H-2,
H-6e), 4.29 (t, 1H, J2,3=J3,4 2.7 Hz, H-3), 3.97 (dt, 1H,
6
Ph), 7.5–7.2 (m, 15H, 3Ph),
ꢁCHPh), 6.06 (d, 1H, J2,NH
), 4.90 (d, 1H, Jgem 12.5
4. Experimental
4.1. General
6
6
6
6
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 polar-
imeter at 25°C. Infrared (IR) spectra were obtained on
a Jasco FT/IR-410 spectrophotometer. Mass spectra were
recorded on a Micromass AUTOSPECQ mass spectrom-
eter, 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
J
J
4,5=J5,6a 10.0 Hz, J5,6e 4.5 Hz, H-5), 3.82 (t, 1H,
5,6a=J6e,6a 10.0 Hz, H-6a), 3.70 (dd, 1H, J3,4 2.7 Hz, J4,5
9.2 Hz, H-4). 13C NMR (50 MHz, CDCl3): l 164.5 (CꢁO),
138.8
(CHꢁCHPh), 100.7 (PhC
(OCH2Ph), 68.3 (C-6), 67.5 (C-3), 63.0 (C-5), 52.9 (C-2).
(CHꢁC
6
HPh),
137.7–126.4
6 H), 99.4 (C-1), 78.5 (C-4), 70.2
(3Ph),
122.4
6
6
Anal. calcd for C29H29NO6: C, 71.44; H, 6.00; N, 2.87.
Found: C, 71.48; H, 6.13; N, 2.86%.
4.2.1.2. Benzyl (R)-4,6-O-benzylidene-2-deoxy-2-
(trans-3-phenyl-2-propenamido)-a-
D
-allopyranoside
8.
1
spectrometer at 200 MHz for H and 50 MHz for 13C,
Column chromatography using hexane–ethyl acetate
(15:10) as eluent yielded 1.31 g (90%). Mp 207–208°C;
[h]D +92.0 (c 0.4, Cl2CH2); MS (CI): m/z 488 (75%)
[M+H]+. 1H NMR (200 MHz, CDCl3): l 7.62 (d, 1H, Jtrans
and on a Bruker AMX-500 spectrometer at 500 MHz for
1H and 125 MHz for 13C. The chemical shifts are reported
in ppm on the l scale relative to TMS, COSY, DEPT
and CHCOOR experiments were performed to assign the
signals in the NMR spectra.
15.6 Hz, COCHꢁCH
1H, J2,NH 7.6 Hz, NH), 6.42 (d, 1H, Jtrans 15.6 Hz,
COCHꢁCHPh), 5.62 (s, 1H, PhCH), 5.02 (d, 1H, J1,2 4.0
Hz, H-1), 4.78 (d, 1H, Jgem 11.9 Hz, OCHAHBPh), 4.53
(d, 1H, Jgem 11.9 Hz, OCHAHBPh), 4.44 (dd, 1H, J5,6e 4.0
6 Ph), 7.5–7.3 (m, 15H, 3Ph), 6.44 (d,
6
6
4.2. Alkyl 2-acylamino-(R)-4,6-O-benzylidene-2-deoxy-
6
D
-allopyranosides 4–10, 15a, 15b, 17a
6
Hz, J6e,6a 9.4 Hz, H-6e), 4.3–4.1 (m, 3H, H-2, H-3, H-5),
3.79 (t, 1H, J5,6a=J6e,6a 9.4 Hz, H-6a), 3.69 (dd, 1H, J3,4
2.8 Hz, J4,5 9.4 Hz, H-4). 13C NMR (50 MHz, CDCl3):
4.2.1. Method A. To a solution of either alkyl 2-amino-
(R)-4,6-O-benzylidene-2-deoxy-b- -allopyranoside 1–3
D
(3.0 mmol) and dry pyridine (15 mL) in distilled
dichloromethane (300 mL), cooled to 0°C, cinnamoyl
chloride (1.0 g, 6.0 mmol) was added slowly and the
reaction mixture was stirred overnight at room temper-
ature. The reaction mixture was diluted with
dichloromethane and washed successively with water,
l 165.3 (CꢁO), 141.9 (CHꢁC
120.0 (CHꢁCHPh), 101.9 (PhCH
70.7 (OCH2Ph), 69.1 (C-6), 68.3 (C-3), 57.8 (C-5), 49.4
6
HPh), 137.0–126.2 (3Ph),
6
6
), 97.5 (C-1), 78.5 (C-4),
6
+
’
(C-2). HRMS (EI): [M] , found 487.200556. C29H29NO6
requires487.199488. Anal. calcdforC29H29NO6:C, 71.44;
H, 6.00; N, 2.87. Found: C, 71.19; H, 6.22; N, 2.78%.

J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 12 (2001) 3189–3203
3195
4.2.1.3. 1-Dodecyl (R)-4,6-O-benzylidene-2-deoxy-2-
(trans-3-phenyl-2-propenamido)-b- -allopyranoside 9.
4.2.2.2. Benzyl 4,6-O-benzylidene-2-deoxy-2-(trans-2-
-allopyranoside 6. Column chromatog-
D
pentenamido)-b-
D
Column chromatography using dichloromethane–
methanol (180:1) as eluent yielded 1.44 g (85%). Mp
232–233°C; [h]D −80.0 (c 0.5, DMF); MS (CI): m/z 566
raphy using dichloromethane–methanol (120:1) as
eluent yielded 1.19 g (90%). Mp 243–244°C; [h]D −77.1
1
(c, 0.7, CHCl3); MS (CI): m/z 440 (20%) [M+H]+. H
1
(100%) [M+H]+. H NMR (200 MHz, CDCl3): l 7.66
NMR (200 MHz, CDCl3): l 7.5–7.3 (m, 10H, 2Ph),
(d, 1H, Jtrans 15.6 Hz, CHꢁCH
2Ph), 6.45 (d, 1H, Jtrans 15.6, CH
J2,NH 9.2 Hz, NH), 5.56 (s, 1H, PhCH
6
Ph), 7.5–7.3 (m, 10H,
ꢁCHPh), 6.32 (d, 1H,
), 4.73 (d, 1H, J1,2
6.92 (dt, 1H, Jtrans 15.3 Hz, J 6.3 Hz, CHꢁCH6 CH2CH3),
6
5.86 (d, 1H, J2,NH 9.2 Hz, NH), 5.72 (dt, 1H, Jtrans 15.3
4
6
Hz, J 1.7 Hz, CH
4.88 (d, 1H, Jgem 12.5 Hz, OCHA
J1,2 8.4 Hz, H-1), 4.58 (d, 1H, Jgem 12.5 Hz,
OCHAHBPh), 4.40 (dd, 1H, J5,6e 4.5 Hz, J6e,6a 9.9 Hz,
6
ꢁCHCH2CH3), 5.59 (s, 1H, PhCH
6 ),
8.3 Hz, H-1), 4.4–4.3 (m, 3H, H-2, H-3, H-6e), 3.98 (m,
1H, J4,5=J5,6a 9.6 Hz, J5,6e 4.6 Hz, H-5), 3.9–3.7 (2H,
6
HBPh), 4.69 (d, 1H,
H-6a, OCHA
Hz, H-4), 3.44 (m, 1H, OCHAHB
(CH2)10], 0.85 (t, 3H, J 6..6 Hz, CH3). 13C NMR (50
MHz, CDCl3): l 165.4 (CꢁO), 141.6 (CHꢁCHPh),
137.0–126.1 (2Ph), 120.4 (CHꢁCHPh), 101.6 (PhCH),
100.4 (C-1), 78.7 (C-4), 70.1 (OCH2R), 69.1 (C-6), 68.8
6
HBR), 3.66 (dd, 1H, J3,4 2.2 Hz, J4,5 9.3
6
6
R), 1.5–1.1 [m, 20H,
H-6e), 4.3–4.2 (m, 2H, H-2, H-3), 3.95 (m, 1H, H-5),
3.80 (t, 1H, J5,6a=J6e,6a 9.9 Hz, H-6a), 3.67 (dd, 1H, J3,4
2.4 Hz, J4,5 9.2 Hz, H-4), 2.21 (m, 2H,
6
6
6
CHꢁCHCH2
CHꢁCHCH2CH3
166.6 (CꢁO), 146.9 (CHꢁC
(2Ph), 122.4 (CHꢁCHCH2CH3), 101.7 (PhC
(C-1), 78.7 (C-4), 70.4 (OCH2Ph), 69.1 (C-6), 68.8
(C-3), 63.3 (C-5), 51.7 (C-2), 25.1 (CHꢁCHCH2CH3),
H3). HRMS (CI): [M+H]+, found
6
CH3), 1.06 (t, 3H,
). 13C NMR (50 MHz, CDCl3): l
HCH2CH3), 137.3–126.1
H), 99.1
J
7.4 Hz,
6
6
(C-3), 63.3 (C-5), 52.2 (C-2), 31.9–22.6 [(CH2)10], 14.1
(CH3). HRMS (CI): [M+H]+, found 566,348086.
C34H48NO6 requires 566,348164. Anal. calcd for
C34H47NO6: C, 72.18; H, 8.37; N, 2.48. Found: C,
71.93; H, 8.42; N, 2.55%.
6
6
6
6
6
12.4 (CHꢁCHCH2C
6
440.207031. C25H30NO6 requires 440.207313. Anal.
calcd for C25H29NO6: C, 68.32; H, 6.65; N, 3.19.
Found: C, 68.00; H, 6.79; N, 3.29%.
4.2.2. Method B. To a solution of the corresponding
a,b-unsaturated acid (4.5 mmol) in distilled and dry
THF (75 mL), was added triethylamine (9 mL) and the
mixture was stirred at room temperature for 30 min.
Then pentachlorophenol trichloroacetate (2.80 g, 6.8
mmol) was added, and the mixture was stirred for 3 h.
After this time, a solution of alkyl 2-amino-(R)-4,6-O-
4.2.2.3. Benzyl (R)-4,6-O-benzylidene-2-deoxy-2-(3-
methyl-2-butenamido)-b-D-allopyranoside 7. Column
chromatography using dichloromethane–methanol
(135:1) as eluent yielded 1.25 g (95%). Mp 208–209°C;
[h]D −91.1 (c 0.5, CH2Cl2); MS (CI): m/z 440 (99%)
benzylidene-2-deoxy-b- -allopyranoside 1 or 3 (3.0
D
1
mmol) in distilled and dry THF (75 mL) was added and
the reaction mixture was stirred for a further 8 h. The
solvent was evaporated to a volume of 10–15 mL and
the mixture was poured into ice-water. The precipitate
obtained was isolated by filtration, washed with water
and dissolved in dichloromethane. The solution was
washed successively with 5% aqueoussodium hydroxide
and water, dried (MgSO4), filtered and the filtrate was
evaporated to dryness to give a solid, which was
purified by flash chromatography on silica gel.
[M+H]+. H NMR (200 MHz, CDCl3): l 7.5–7.2 (m,
10H, 2Ph), 5.78 (d, 1H, J2,NH 9.1 Hz, NH), 5.59 (s, 1H,
PhCH
12.5 Hz, OCHA
4.57 (d, 1H, Jgem 12.5 Hz, OCHAHB
6
), 5.53 [m, 1H, CH
6
ꢁC(CH3)2], 4.89 (d, 1H, Jgem
HBPh), 4.68 (d, 1H, J1,2 8.2 Hz, H-1),
Ph), 4.39 (dd, 1H,
6
6
J5,6e 4.5 Hz, J6e,6a 9.9 Hz, H-6e), 4.3–4.2 (m, 2H, H-2,
H-3), 3.93 (dt, 1H, J4,5=J5,6a 9.9 Hz, J5,6e 4.5 Hz, H-5),
3.80 (t, 1H, J5,6a=J6e,6a 9.9 Hz, H-6a), 3.66 (dd, 1H, J3,4
4
2.3 Hz, J4,5 9.2 Hz, H-4), 2.15, 1.84 [2d, 6H, J 1.3 Hz,
CHꢁC(CH3 2
(CꢁO), 151.7 [CHꢁC
[CHꢁC(CH3)2], 101.7 (PhC
70.4 (OCH2Ph), 69.1 (C-6), 68.9 (C-3), 63.3 (C-5), 51.4
(C-2), 27.2, 19.9 [CHꢁC(C
H3)2]. HRMS (CI): [M+H]+,
6
) ]. 13C NMR (50 MHz, CDCl3): l 166.3
6
(CH3)2], 137.4–126.1 (2Ph), 118.4
H), 99.3 (C-1), 78.7 (C-4),
4.2.2.1. Benzyl (R)-4,6-O-benzylidene-2-(trans-2-bute-
6
6
namido)-2-deoxy-b-
D
-allopyranoside 5. Column chro-
6
matography using dichloromethane–methanol (100:1)
as eluent yielded 1.17 g (90%). Mp 234–235°C; [h]D
−92.3 (c 0.4, CH2Cl2); MS (CI): m/z 426 (92%) [M+H]+.
1H NMR (200 MHz, CDCl3): l 7.5–7.3 (m, 10H, 2Ph),
6
found 440.204192. C25H30NO6 requires 440.207313.
Anal. calcd for C25H29NO6: C, 68.32; H, 6.65; N, 3.19.
Found: C, 68.03; H, 6.62; N, 3.15%.
6.86 (m, 1H, CHꢁCH
NH), 5.75 (dq, 1H, Jtrans 15.2 Hz, 4J 1.6 Hz,
CHꢁCHCH3), 5.58 (s, 1H, PhCH), 4.88 (d, 1H, Jgem
12.5 Hz, OCHAHBPh), 4.70 (d, 1H, J1,2 8.2 Hz, H-1),
4.57 (d, 1H, Jgem 12.5 Hz, OCHAHBPh), 4.39 (dd, 1H,
6 CH3), 5.85 (d, 1H, J2,NH 9.1 Hz,
4.2.3. Method C. To a solution of benzyl 2-amino-(R)-
6
6
4,6-O-benzylidene-2-deoxy-b- -allopyranoside 1 (1.07
D
6
g, 3.0 mmol) in distilled dichloromethane (100 mL)
were sequentially added vinylacetic acid (0.3 mL, 3.5
mmol), 4-(N,N-dimethylamino)pyridine (0.01 g, 0.08
mmol), and N,N%-dicyclohexylcarbodiimide (0.7 g, 3.3
mmol), and the mixture was stirred at room tempera-
ture for 4 h. The solid was removed by filtration, and
the filtrate was diluted with dichloromethane and
washed successively with 1 N aqueous acetic acid,
saturated aqueous sodium bicarbonate, and water,
dried (MgSO4), filtered, and the filtrate evaporated to
dryness. The solid was purified by flash chromatogra-
phy on silica gel, using dichloromethane–methanol
(130:1) as eluent, to give 10.
6
J5,6e 4.7 Hz, J6e,6a 9.7 Hz, H-6e), 4.3–4.0 (m, 2H, H-2,
H-3), 3.95 (dt, 1H, J4,5=J5,6a 9.7 Hz, J5,6e 4.7 Hz, H-5),
3.80 (t, 1H, J5,6a=J6e,6a 9.7 Hz, H-6a), 3.67 (dd, 1H, J3,4
4
2.4 Hz, J4,5 9.7 Hz, H-4), 1.85 (dd, 3H, J 6.7 Hz, J 1.6
Hz, CHꢁCHCH3
165.4 (CꢁO), 140.7 (CHꢁC
120.0 (CHꢁCHCH3), 101.7 (PhC
(C-4), 70.5 (OCH2Ph), 69.1 (C-6), 68.7 (C-3), 63.3
H3). Anal. calcd for
6
). 13C NMR (50 MHz, CDCl3): l
6
HCH3), 137.3–124.9 (2Ph),
H), 99.1 (C-1), 78.7
6
6
6
(C-5), 51.6 (C-2), 17.8 (CHꢁCHC
C24H27NO6: C, 67.75; H, 6.40; N, 3.29. Found: C,
67.46; H, 6.20; N, 3.33%.
6

3196
J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 12 (2001) 3189–3203
4.2.3.1.
Benzyl
(R)-4,6-O-benzylidene-2-(3-bute-
-allopyranoside 10. Yield 1.15 g
calcd for C29H31NO7: C, 68.90; H, 6.18; N, 2.77.
Found: C, 69.00; H, 6.23; N, 2.82%.
namido)-2-deoxy-b-
D
(90%). Mp 241–242°C; [h]D −117.7 (c 0.5, CH2Cl2); MS
(CI): m/z 426 (100%) [M+H]+. H NMR (200 MHz,
4.2.4.2. Benzyl (R)-4,6-O-benzylidene-2-deoxy-2-[(R)-
2-hydroxy-3-phenylpropanamido]-b-D-allopyranoside 15b.
1
CDCl3): l 7.5–7.2 (m, 10H, 2Ph), 6.00 (d, 1H, J2,NH 8.6
Hz, NH), 5.80 (m, 1H, CH2CH
PhCH), 5.14 (m, 2H, CH2CHꢁCH2
12.5 Hz, OCHAHBPh), 4.68 (d, 1H, J1,2 8.0 Hz, H-1),
4.57 (d, 1H, Jgem 12.5 Hz, OCHAHBPh), 4.39 (dd, 1H,
6
ꢁCH2), 5.58 (s, 1H,
6 ), 4.88 (d, 1H, Jgem
Column chromatography using dichloromethane–
methanol (65:1) as eluent yielded 0.34 g (67%). Mp
270–271°C; [h]D −48.7 (c 0.6, DMF); MS (FAB): m/z
6
6
1
6
528 (13%) [M+Na]+. H NMR (200 MHz, CDCl3): l
J5,6e 4.4 Hz, J6e,6a 9.8 Hz, H-6e), 4.25–4.20 (m, 2H, H-2,
H-3), 3.95 (m, 1H, J4,5=J5,6a 9.8 Hz, J5,6e 4.4 Hz, H-5),
3.78 (t, 1H, J5,6a=J6e,6a 9.8 Hz, H-6a), 3.65 (dd, 1H, J3,4
7.5–7.2 (m, 15H, 3Ph), 6.79 (d, 1H, J2,NH 8.6 Hz, NH),
5.59 (s, 1H, PhCH
OCHAHBPh), 4.70 (d, 1H, J1,2 8.2 Hz, H-1), 4.56 (d,
1H, Jgem 12.4 Hz, OCHAHBPh), 4.39 (dd, 1H, J5,6e 4.5
Hz, J6e,6a 9.8 Hz, H-6e), 4.30 (dd, 1H, J1,2 8.2 Hz, J2,3
4.2 Hz, H-2), 4.2–4.1 [m, 2H, H-3, CH(OH)CH2Ph],
6 ), 4.90 (d, 1H, Jgem 12.4 Hz,
6
4
2.2 Hz, J4,5 9.2 Hz, H-4), 2.99 (dt, 2H, J 7.1 Hz, J 1.2
6
Hz, CH2
170.0 (CꢁO), 137.3–126.1 (2Ph), 131.1 (CH2C
119.8 (CH2CHꢁCH2), 101,7 (PhCH), 99.0 (C-1), 78.7
(C-4), 70.5 (OCH2Ph), 69.1 (C-6), 68.7 (C-3), 63.3
(C-5), 51.9 (C-2), 41.6 (C
6
CHꢁCH2). 13C NMR (50 MHz, CDCl3): l
6
HꢁCH2),
6
6
6
3.93 (m, 1H, H-5), 3.80 (t, 1H, J5,6a=J6e,6a 10.0 Hz,
H-6a), 3.65 (dd, 1H, J3,4 2.3 Hz, J4,5 9.2 Hz, H-4), 3.18
6
6
H2CHꢁCH2). Anal. calcd for
[dd, 1H, Jgem 14.0 Hz, J 4.0 Hz, CH(OH)CHA
2.89 [dd, 1H, Jgem 14.0 Hz, 8.1 Hz,
CH(OH)CHAHB
Ph], 2.17 (m, 2H, 2OH). 13C NMR (50
MHz, CDCl3): l 172.1 (CꢁO), 136.9–126.1 (3Ph), 101.8
(PhCH), 99.0 (C-1), 78.7 (C-4), 72.8 [CH(OH)CH2Ph],
70.7 (OCH2Ph), 69.1 (C-6), 68.6 (C-3), 63.3 (C-5), 51.8
(C-2), 40.7 [CH(OH)CH2Ph]. Anal. calcd for
6 HBPh],
C24H27NO6: C, 67.75; H, 6.40; N, 3.29. Found: C,
67.50; H, 6.36; N, 3.27%.
J
6
6
6
4.2.4. Method D. To a solution of the hydroxyacid
[(S)-(–)-3-phenyllactic acid, (R)-(+)-3-phenyllactic acid
or (S)-(+)-3-hydroxybutyric acid] (1.2 mmol) in dry
dioxane (20 mL) N-hydroxysuccinimide (0.17 g, 1.5
mmol), N,N%-dicyclohexylcarbodiimide (0.30 g, 1.5
mmol) were added and the mixture was stirred at room
temperature for 2 h. The solid was removed by filtra-
tion, and to the filtrate, a solution of benzyl 2-amino-
6
6
C29H31NO7: C, 68.90; H, 6.18; N, 2.77. Found: C,
68.57; H, 6.44; N, 2.78%.
4.2.4.3. Benzyl (R)-4,6-O-benzylidene-2-deoxy-2-[(S)-
3-hydroxybutanamido]-b-D-allopyranoside 17a. Column
chromatography using dichloromethane–methanol
(20:1) as eluent yielded 0.32 g (72%). Mp 221–222; [h]D
−96.2 (c 0.4, DMF); MS (CI): m/z 444 (16%) [M+H]+.
1H NMR (200 MHz, CDCl3): l 7.5–7.2 (m, 10H, 2Ph),
(R)-4,6-O-benzylidene-2-deoxy-b-
D
-allopyranoside
1
(0.36 g, 1.0 mmol) and triethylamine (0.2 mL, 1.4
mmol) in dry dioxane (20 mL) was added and the
mixture was stirred overnight at room temperature. The
solution was poured into water, and the precipitate was
filtered and washed with water. The solid was dissolved
in dichloromethane and washed successively with satu-
rated aqueous sodium bicarbonate and water, dried
(MgSO4), filtered and the filtrate evaporated to dryness.
The solid obtained was purified by flash chromatogra-
phy on silica gel.
6.08 (d, 1H, J2,NH 9.2 Hz, NH), 5.59 (s, 1H, PhCH
4.90 (d, 1H, Jgem 12.4 Hz, OCHAHBPh), 4.70 (d, 1H,
J1,2 8,2 Hz, H-1), 4.57 (d, 1H, Jgem 12.4 Hz,
OCHAHBPh), 4.40 (dd, 1H, J5,6e 4,4 Hz, J6e,6a 99 Hz,
H-6e), 4.24 (m, 2H, H-2, H-3), 4.17 [m, 1H,
CH2CH(OH)CH3], 3.94 (dt, 1H, J5,6e 4.4 Hz, J4,5=J5,6a
6 ),
6
6
6
9.5 Hz, H-5), 3.81 (t, 1H, J5,6a=J6e,6a 10.0 Hz, H-6a),
3.66 (dd, 1H, J3,4 2.3 Hz, J4,5 9.3 Hz, H-4), 2.3–2.2 [m,
2H, CH2
CH2CH(OH)CH3
171.8 (CꢁO), 129.3–126.1 (2Ph), 101.8 (PhC
(C-1), 78.6 (C-4), 70.7 (OC
(C-3), 64.8 [CH2CH(OH)CH3], 63.4 (C-5), 51.7 (C-2),
44.1 [CH2CH(OH)CH3], 22.7 [CH2CH(OH)C6 H3].
6
CH(OH)CH3], 1.18 [d, 3H,
J
6.3 Hz,
6
]. 13C NMR (50 MHz, CDCl3): l
4.2.4.1. Benzyl (R)-4,6-O-benzylidene-2-deoxy-2-[(S)-
6
H), 99.1
2-hydroxy-3-phenylpropanamido]-b-D-allopyranoside 15a.
6
H2Ph), 69.0 (C-6), 68.6
Column chromatography using dichloromethane–
methanol (55:1) as eluent yielded 0.39 g (77%). Mp
248–249°C; [h]D −142.3 (c 0.5, DMF); MS (CI): m/z
506 (22%) [M+H]+. 1H NMR (200 MHz, CDCl3): l
7.5–7.2 (m, 15H, 3Ph), 6.88 (d, 1H, J2,NH 9.0 Hz, NH),
6
6
HRMS (CI): [M+H]+, found 444.201102. C24H30NO7
requires 444.202228. Anal. calcd for C24H29NO7: C,
65.00; H, 6.59; N, 3.16. Found: C, 64.89; H, 6.61; N,
3.28%.
5.60 (s, 1H, CH
OCHAHBPh), 4.73 (d, 1H, J1,2 7.9 Hz, H-1), 4.57 (d,
1H, Jgem 12.4 Hz, OCHAHBPh), 4.40 (dd, 1H, J5,6e 4.5
Hz, J6e,6a 9.8 Hz, H-6e), 4.3–4.2 [m, 3H, H-2, H-3,
CH(OH)CH2Ph], 3.94 (m, 1H, H-5), 3.80 (t, 1H, J5,6a
6 Ph), 4.89 (d, 1H, Jgem 12.4 Hz,
6
6
4.2.5. Acetyl derivatives from 15a and 15b. To a solution
of 15a or 15b (0.25 g, 0.5 mmol) in distilled
dichloromethane (20 mL), pyridine (0.5 mL) and acetic
anhydride (0.5 mL) were added and the reaction mix-
ture was stirred overnight at room temperature. The
solution was washed successively with water, 1N solu-
tion of acetic acid, saturated aqueous sodium bicarbon-
ate and water, then dried (MgSO4) and filtered and the
filtrate evaporated to dryness. The solid obtained was
purified by flash chromatography on silica gel.
6
=
J6e,6a 10.0 Hz, H-6a), 3.67 (dd, 1H, J3,4 2.3 Hz, J4,5 9.2
Hz, H-4), 3.23 [dd, 1H, Jgem 14.0 Hz, J 4.2 Hz,
CH(OH)CHA
Hz, CH(OH)CHAHB
(50 MHz, CDCl3): l 172.6 (CꢁO), 138.8–126.0 (3Ph),
100.7 (CHPh), 99.5 (C-1), 78.6 (C-4), 73.0
[CH(OH)CH2Ph], 70.0 (OCH2Ph), 68.3 (C-6), 67.6 (C-
3), 63.0 (C-5), 51.7 (C-2), 41.0 [CH(OH)CH2Ph]. Anal.
6
HBPh], 2.77 [dd, 1H, Jgem 14.0 Hz, J 8.9
6
Ph], 2.38 (m, 2H, 2OH). 13C NMR
6
6
6
6

J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 12 (2001) 3189–3203
3197
4.2.5.1.
anamido]-3-O-acetyl-(R)-4,6-O-benzylidene-2-deoxy-b-
-allopyranoside 18a. Column chromatography using
Benzyl
2-[(S)-2-acetoxy-3-phenylprop-
4.3.1. Benzyl 2-amino-(R)-4,6-O-benzylidene-2-deoxy-2-
N-3-O-methylidene-2-N-(trans-3-phenyl-2-propenoyl)-b-
D
D-allopyranoside 19. Column chromatography using
dichloromethane–methanol (120:1) as eluent yielded
0.26 g (88%). Mp 216–217°C; [h]D −95.6 (c 0.6,
dichloromethane–methanol (220:1) as eluent yielded
1.00 g (80%). Mp 194–195°C; [h]D +73.9 (c 0.6,
1
1
CH2Cl2); MS (CI): m/z 590 (22%) [M+H]+. H NMR
CH2Cl2); MS (CI): m/z 500 (100%) [M+H]+. H NMR
(200 MHz, CDCl3): l 7.4–7.1 (m 15H, 3Ph), 6.00 (d,
1H, J2,NH 8.4 Hz, NH), 5.68 (t, 1H, J2,3=J3,4 2.6 Hz,
(500 MHz, CDCl3): l 7.69 (d, 1H, Jtrans 15.6 Hz,
CHꢁCH
15.6 Hz, CH
Jgem 5.6 Hz, OCH2N), 4.98 (d, 1H, Jgem 10.7 Hz,
OCHAHBPh), 4.77 (d, 1H, J1,2 7.4 Hz, H-1), 4.56 (d,
1H, Jgem 10.7 Hz, OCHAHBPh), 4.50–4.45 (m, 2H, H-3,
6
Ph), 7.5–7.2 (m, 15H, 3Ph), 7.05 (d, 1H, Jtrans
H-3), 5.52 (s, 1H, PhCH
Hz, CH(OAc)CH2Ph], 4.88 (d, 1H, Jgem 12.2 Hz,
OCHAHBPh), 4.68 (d, 1H, J1,2 8.6 Hz, H-1), 4.58 (d,
1H, Jgem 12.2 Hz, OCHAHBPh), 4.4–4.3 (m, 2H, H-2,
H-6e), 3.9–3.7 (m, 3H, H-4, H-5, H-6a), 3.22 [dd, 1H,
Jgem 14.3 Hz, J 4.9 Hz, CH(OAc)CHAHB Ph], 3.06 [dd,
Ph], 2.05,
6
), 5.32 [dd, 1H, J 4.9 Hz, J 7.6
6
ꢁCHPh), 5.62 (s, 1H, PhCH), 5.32 (2d, 2H,
6
6
6
6
6
6
H-6e), 4.18 (dd, 1H, J1,2 7.4 Hz, J2,3 4.3 Hz, H-2), 4.05
(dt, 1H, J5,6e 5.1 Hz, J4,5=J5,6a 9.8 Hz, H-5), 3.91 (dd,
6
1H, Jgem 14.3 Hz, J 7.6 Hz, CH(OAc)CHAHB
6
1H, J3,4 3.1 Hz, J4,5 9.6 Hz, H-4), 3.84 (t, 1H, J5,6a
J6e,6a 10.2 Hz, H-6a). 13C NMR (125 MHz, CDCl3): l
164.7 (CꢁO), 142.9 (CHꢁCHPh), 136.7–126.2 (3Ph),
118.7 (CHꢁCHPh), 102.7 (PhCH), 101.2 (C-1), 80.8
(OCH2N), 76.8 (C-3), 76.4 (C-4), 72.3 (OCH2Ph), 69.0
=
1.91 (2s, 6H, 2CH3CO). 13C NMR (50 MHz, CDCl3): l
169.6, 169.3, 169.2 (3CꢁO), 136.9–125.8 (3Ph), 101.2
6
(PhC
70.1 (OC
(C-2), 37.2 [CH(OAc)C
6
H), 98.5 (C-1), 76.8 (C-4), 74.3 [C
6
H(OAc)CH2Ph],
6
6
6
H2Ph), 69.3 (C-3), 68.8 (C-6), 64.3 (C-5), 51.0
H2Ph], 20.6, 20.5 (2CH3CO).
Anal. calcd for C33H35NO9: C, 67.22; H, 5.98; N, 2.38.
Found: C, 67.08; H, 6.01; N, 2.51.
6
6
6
(C-6), 63.4 (C-5), 59.1 (C-2). Anal. calcd for
C30H29NO6: C, 72.13; H, 5.85; N, 2.80. Found: C,
71.97; H, 5.69; N, 2.90%.
4.2.5.2.
anamido]-3-O-acetyl-(R)-4,6-O-benzylidene-2-deoxy-b-
-allopyranoside 18b. Column chromatography using
Benzyl
2-[(R)-2-acetoxy-3-phenylprop-
4.3.2. Benzyl 2-amino-(R)-4,6-O-benzylidene-2-N-(trans-
2-butenoyl)-2-deoxy-2-N-3-O-methylidene-b-D-allopyrano-
D
side 20. Column chromatography using dichloro-
methane–methanol (180:1) as eluent yielded 0.76 g
(70%). Mp 155–156°C; [h]D −7.8 (c 0.8, CH2Cl2); MS
(CI): m/z 438 (66%) [M+H]+. 1H NMR (200 MHz,
CDCl3): l 7.5–7.2 (m, 10H, 2Ph), 6.96 (m, 1H,
dichloromethane–methanol (100:1) as eluent yielded
0.27 g (92%). Mp 197–198°C; [h]D −91.5 (c 0.6,
1
CH2Cl2); MS (CI): m/z 590 (32%) [M+H]+. H NMR
(200 MHz, CDCl3): l 7.4–7.1 (m, 15H, 3Ph), 6.06 (d,
1H, J2,NH 8.8 Hz, NH), 5.64 (t, 1H, J2,3=J3,4 2.6 Hz,
CHꢁCH
5.58 (s, 1H, PhCH
Jgem 11.2 Hz, OCHA
H-1), 4.55 (d, 1H, Jgem 11.2 Hz, OCHAHB
(m, 2H, H-3, H-6e), 4.1–3.7 (m, 4H, H-2, H-4, H-5,
H-6a), 1.75 (d, 3H, J 6.7 Hz, CHꢁCHCH3
). 13C NMR
(50 MHz, CDCl3): l 164.6 (CꢁO), 142.6 (CHꢁCHCH3);
136.6–126.3 (2Ph), 123.1 (CHꢁCHCH3), 102.7 (PhCH),
101.0 (C-1), 80.6 (OCH2N), 76.7 (C-4), 76.4 (C-3), 72.1
(OCH2Ph), 69.0 (C-6), 63.4 (C-5), 59.0 (C-2), 17.9
(CHꢁCHCH3). Anal. calcd for C25H27NO6: C, 68.64; H,
6
CH3), 6.43 (d, 1H, Jtrans 15.1 Hz, CH
), 5.21 (bs, 2H, OCH2N), 4.92 (d, 1H,
HBPh), 4.66 (d, 1H, J1,2 7.2 Hz,
Ph), 4.5–4.4
6 ꢁCHCH3),
H-3), 5.54 (s, 1H, PhCH
Hz, CH(OAc)CH2Ph], 4.86 (d, 1H, Jgem 12.2 Hz,
OCHAHBPh), 4.67 (d, 1H, J1,2 8.6 Hz, H-1), 4.56 (d,
1H, Jgem 12.2 Hz, OCHAHBPh), 4.4–4.3 (m, 2H, H-2,
H-6e), 3.9–3.7 (m, 3H, H-4, H-5, H-6a), 3.23 [dd, 1H,
Jgem 14.3 Hz, J 5.4 Hz, CH(OAc)CHAHBPh], 3.06 [dd,
Ph], 2.05,
6
), 5.29 [dd, 1H, J 7.4 Hz, J 5.4
6
6
6
6
6
6
6
6
6
1H, Jgem 14.3 Hz, J 7.4 Hz, CH(OAc)CHAHB
6
6
6
1.95 (2s, 6H, 2CH3CO). 13C NMR (50 MHz, CDCl3): l
169.9, 169.2, 168.2 (3CꢁO), 136.9–125.9 (3Ph), 101.2
6
(PhC
70.3 (OC
(C-2), 36.8 [CH(OAc)C
6
H), 98.6 (C-1), 77.6 (C-4), 74.1 [C
6
H(OAc)CH2Ph],
6
6
H2Ph), 69.0 (C-3), 68.9 (C-6), 64.3 (C-5), 50.9
H2Ph], 20.7 (2CH3CO). Anal.
calcd for C33H35NO9: C, 67.22; H, 5.98; N, 2.38.
Found: C, 67.14; H, 6.03; N, 2.41%.
6.22; N, 3.20. Found: C, 68.44; H, 6.14; N, 3.11%.
6
6
4.3.3. Benzyl 2-amino-(R)-4,6-O-benzylidene-2-deoxy-2-
N-3-O-methylidene-2-N-(trans-2-pentenoyl)-b-
D
-allopyr-
anoside
21.
Column
chromatography
using
4.3. Alkyl 2-N-acyl-2-amino-(R)-4,6-O-benzylidene-2-
dichloromethane–methanol (200:1) as eluent yielded
1.00 g (90%). Mp 68–69°C; [h]D −32.7 (c 0.6, CHCl3);
deoxy-2-N-3-O-methylidene-
D
-allopyranosides 19–24,
1
26
MS (CI): m/z 452 (82%) [M+H]+. H NMR (200 MHz,
CDCl3): l 7.6–7.2 (m, 10H, 2Ph), 7.00 (m, 1H,
To a solution of either alkyl 2-acylamino-(R)-4,6-O-
benzylidene-2-deoxy- -allopyranoside 4–9 (2.5 mmol)
CHꢁCH
CHꢁCHCH2CH3), 5.57 (s, 1H, PhCH
OCH2N), 4.91 (d, 1H, Jgem 11.1 Hz, OCHA
(d, 1H, J1,2 7.3 Hz, H-1), 4.53 (d, 1H, Jgem 11.1 Hz,
OCHAHBPh), 4.5–4.4 (m, 2H, H-6e, H-3), 4.1–3.7 (m,
4H, H-2, H-4, H-5, H-6a), 2.09 (m, 2H,
CHꢁCHCH2CH3), 0.88 (t, 3H, 7.4 Hz,
CHꢁCHCH2CH3
). 13C NMR (50 MHz, CDCl3): l
164.9 (CꢁO), 148.8 (CHꢁCHCH2CH3), 136.7–126.2
(2Ph), 120.5 (CHꢁCHCH2CH3), 102.7 (PhCH), 101.0
(C-1), 80.7 (OCH2N), 76.7 (C-4), 76.4 (C-3), 72.1
6
CH2CH3), 6.37 (d, 1H, Jtrans 15.3 Hz,
), 5.21 (bs, 2H,
HBPh), 4.66
D
6
6
in distilled 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.
6
6
6
J
6
6
6
6

3198
J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 12 (2001) 3189–3203
(OC
(CHꢁCHC
6
H2Ph), 69.0 (C-6), 63.4 (C-5), 59.0 (C-2), 25.2
H3). HRMS
(d, 1H, Jgem 5.8 Hz, NCHA
6 HBO), 5.27 (d, 1H, Jgem
6
H2CH3), 12.0 (CHꢁCHCH2C6
5.8 Hz, NCHAHBO), 4.59 (d, 1H, J1,2 7.4 Hz, H-1),
6
+
’
(EI): [M] , found 451.198802. C26H29NO6 requires
451.199488. Anal. calcd for C26H29NO6: C, 69.16; H,
6.47; N, 3.10. Found: C, 68.88; H, 6.64; N, 3.14%.
4.5–4.4 (m, 2H, H-3, H-6e), 4.13 (dd, 1H, J1,2 7.4 Hz,
J2,3 4.3 Hz, H-2), 4.1–3.8 (m, 3H, H-4, H-5,
OCH
3.44 (m, 1H, OCHAHB
0.86 (t, 3H, J 6.5 Hz, CH3). 13C NMR (50 MHz,
CDCl3): l 164.7 (CꢁO), 142,6 (CHꢁCHPh), 136.7–
126.3 (Ph), 118.7 (CHꢁCHPh), 102.8, 102.1 (C-1,
PhCH), 80.9 (NCH2O), 76.8 (C-4), 76.5 (C-3), 71.1
(OC
6
AHBR), 3.78 (t, 1H, J5,6a=J6e,6a 10.0 Hz, H-6a),
6
R), 1.6–1.1 [m, 20H, (CH2)10],
4.3.4. Benzyl 2-amino-(R)-4,6-O-benzylidene-2-deoxy-2-
N-(3-methyl-2-butenoyl)-2-N-3-O-methylidene-b-D-allo-
pyranoside 22. Column chromatography using hex-
ane–ethyl acetate (3:1) as eluent yielded 0.85 g (75%).
Mp 136–137°C; [h]D −14.2 (c 0.7, CH2Cl2); MS (CI):
m/z 452 (100%) [M+H]+. 1H NMR (200 MHz,
CDCl3): l 7.5–7.3 (m, 10H, 2Ph), 6.19 [s, 1H,
6
6
6
6
H2R), 69.1 (C-6), 63.4 (C-5), 59.2 (C-2), 31.9–22.7
[(CH2)10], 14.1 (CH3). HRMS (CI): [M+H]+, found
578.347399. C35H48NO6 requires 578.348164. Anal.
calcd for C35H47NO6: C, 72.76; H, 8.20; N, 2.42.
Found: C, 72.54; H, 8.31; N, 2.47%.
CH
OCH2N), 4.92 (d, 1H, Jgem 11.2 Hz, OCHA
4.66 (d, 1H, J1,2 7.3 Hz, H-1), 4.55 (d, 1H, Jgem 11.2
Hz, OCHAHBPh), 4.5–4.4 (m, 2H, H-3, H-6e), 4.1–3.7
(m, 4H, H-2, H-4, H-5, H-6a), 2.12, 1.70 [2s, 6H,
CHꢁC(CH3 2
) ]. 13C NMR 50 MHz, CDCl3): l 165.9
(CꢁO), 153.6 [CHꢁC(CH3)2], 136.7–126.3 (2Ph), 116.8
[CHꢁC(CH3)2], 102.8 (PhCH), 101.2 (C-1), 80.5
(OCH2N), 76.7 (C-4), 76.5 (C-3), 72.1 (OCH2Ph), 69.1
(C-6), 63.4 (C-5), 59.4 (C-2), 27.3, 20,3
[CHꢁC(CH3)2]. Anal. calcd for C26H29NO6: C, 69.16;
6
ꢁC(CH3)2], 5.57 (s, 1H, PhCH
6
), 5.19 (m, 2H,
6
HBPh),
4.4. Benzyl 2-amino-(R)-4,6-O-benzylidene-2-N-(trans-
6
2-butenoyl)-2-deoxy-2-N-3-O-isopropylidene-b-D-allopyr-
anoside 26
6
6
A solution of benzyl 2-amino-(R)-4,6-O-benzylidene-
2-deoxy-b- -allopyranoside 1 (1.0 g, 2.8 mmol) in dry
6
6
D
6
acetone (100 mL) was stirred at room temperature for
3 h. Distilled dichloromethane (100 mL) and anhy-
drous magnesium sulphate (2.0 g) were added, and
the suspension was stirred for two weeks. Then, the
reaction mixture was filtered through a pad of kiesel-
guhr (4 cm diameter×0.5 cm height) and the filtrate
was evaporated to dryness. The compound obtained,
benzyl 2-amino-(R)-4,6-O-benzylidene-2-deoxy-2-N-3-
6
H, 6.47; N, 3.10. Found: C, 68.96; H, 6.43; N, 3.09%.
4.3.5. Benzyl 2-amino-(R)-4,6-O-benzylidene-2-deoxy-2-
N-3-O-methylidene-2-N-(trans-3-phenyl-2-propenoyl)-a-
D
-allopyranoside 23. Column chromatography using
O-isopropylidene-b-
398 (100%) [M+1]+}, was used without further purifi-
cation. To solution of 25 in distilled
D
-allopyranoside 25 {MS (CI) m/z
hexane–ethyl acetate (15:10) as eluent yielded 1.11 g
(89%). Mp 108–109°C; [h]D +196.1 (c 0.5, CH2Cl2);
MS (CI): m/z 500 (37%) [M+H]+. 1H NMR (200
MHz, CDCl3): l 7.75, 7.68 (2d, 1H, Jtrans 15.4 Hz,
a
dichloromethane (100 mL) at 0°C, dry pyridine (10
mL) and crotonyl chloride (0.5 mL, 5.2 mmol) were
added. The reaction mixture was stirred overnight at
room temperature, and then poured into ice water.
The organic phase was washed successively with
water, saturated aqueous sodium bicarbonate and
water. The solution was dried (MgSO4), filtered and
evaporated to dryness. The solid obtained was
purified by column chromatography using hexane–
ethyl acetate (32:10) as eluent, yield: 0.72 g (55%).
Mp 86–87°C; [h]D −16.9 (c 0.7, CH2Cl2); EM (CI):
m/z 466 (100%) [M+H]+. 1H NMR (200 MHz,
CDCl3): l 7.6–7.3 (m, 10H, 2Ph), 6.90 (m, 1H,
CH
6
ꢁCHPh), 7.6–7.1 (m, 15H, 3Ph), 6.34, 6.30 (2d,
1H, Jtrans 15.4 Hz, CHꢁCH
5.38 (d, 1H, J1,2 5.4 Hz, H-1), 5.30, 5.21 (2d, 2H, J
2.0 Hz, OCH2N), 4.71, 4.70 (2d, 1H, Jgem 11.9 Hz,
6
Ph), 5.62 (s, 1H, PhCH),
6
OCHA
6
HBPh), 4.63 (dd, 1H, J5,6e 5.0 Hz, J6e,6a 9.8 Hz,
Ph), 4.4–
H-6e), 4.48 (d, 1H, Jgem 11.9 Hz, OCHAHB
6
4.2 (m, 3H, H-2, H-3, H-5), 3.89 (dd, 1H, J3,4 3.4 Hz,
J4,5 9.5 Hz, H-5), 3.73 (t, 1H, J5,6a=J6e,6a 10.0 Hz,
H-6a). 13C NMR (50 MHz, CDCl3): l 162.5 (CꢁO),
143.6, 143.3 (C
117.1 (CHꢁCHPh), 102.7 (PhC
82.0, 80.5 (OCH2N), 76.5, 76.4 (C-4), 73.9 (C-3), 70.6
(OCH2Ph), 69.6, 69.2 (C-6), 56.7 (C-5), 56.0, 55.8 (C-
6
HꢁCHPh), 137.5–126.3 (Ph), 117.2,
6
6
H), 95.7, 94.8 (C-1),
6
CHꢁCH
CHꢁCHCH3), 5.56 (s, 1H, PhCH
11.4 Hz, OCHAHBPh), 4.65 (d, 1H, J1,2 7.4 Hz, H-1),
4.52 (d, 1H, Jgem 11.4 Hz, OCHAHBPh), 4.5–4.4 (m,
2H, H-3, H-6e), 4.1–3.7 (m, 3H, H-2, H-5, H-6a), 1.75
(d, 3H, J 6.6, CHꢁCHCH3), 1.64, 1.58 [2s, 6H,
OC(CH
3)2N]. 13C NMR (50 MHz, CDCl3): l 163.3
(CꢁO), 140.9 (CHꢁCHCH3), 136.7–126.2 (2Ph), 124.5
(CHꢁCHCH3), 102.5 (PhCH), 100.7 (C-1), 96.9
[OC(CH3)2N], 76.5 (C-4), 72.3 (C-3), 71.4 (OCH2Ph),
68.9 (C-6), 63.1 (C-5), 60.4 (C-2), 26.5, 23.8
6
CH3), 6.48 (d, 1H, Jtrans 15.0 Hz,
+
’
2). HRMS (EI): [M] , found 499.199545. C30H29NO6
requires 499.199488. Anal. calcd for C30H29NO6: C,
72.13; H, 5.85; N, 2.80. Found: C, 72.02; H, 5.90; N,
2.78%.
6
6
), 4.88 (d, 1H, Jgem
6
6
6
6
4.3.6.
deoxy-2-N-3-O-methylidene-2-N-(trans-3-phenyl-2-prop-
enoyl)-b- -allopyranoside 24. Column chromatography
using hexane–ethyl acetate (34:10) as eluent yielded
1.17 g (81%). Mp 109–110°C; [h]D −32.4 (c 0.6,
CH2Cl2); MS (CI): m/z 578 (100%) [M+H]+. 1H
NMR (200 MHz, CDCl3): l 7.69 (d, 1H, Jtrans 15.6
1-Dodecyl
2-amino-(R)-4,6-O-benzylidene-2-
6
6
6
D
6
6
+
’
[OC(C6 H3)2N], 17.7 (CHꢁCHC6 H3). HRMS (EI): [M] ,
found 465.214076. C27H31NO6 requires 465.215138.
Anal. calcd for C27H31NO6: C, 69.66; H, 6.71; N,
3.01. Found: C, 69.61; H, 6.78; N, 3.07%.
Hz, CHꢁCH
Jtrans 15.6 Hz, CH
6
Ph), 7.6–7.3 (m, 10H, 2Ph), 7.10 (d, 1H,
ꢁCHPh), 5.58 (s, 1H, PhCH), 5.35
6
6

J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 12 (2001) 3189–3203
3199
4.5. Epoxidation of the unsaturated amides with m-
(CꢁO), 137.1–126.2 (2Ph), 101.74, 101.71 (PhC
99.2, 98.8 (C-1), 78.7, 78.6 (C-4), 70.8, 70.7
(OCH2Ph), 69.0 (C-6), 68.6, 68.5 (C-3), 63.34, 63.29
(C-5), 56.2 [CH(O)CHCH3], 55.8, 55.6
[CH(O)CHCH3], 51.6, 51.2 (2C-2), 17.5, 17.4
[CH(O)CHC found
441.178846. C24H27NO7 requires 441.178753. Anal.
calcd for C24H27NO7: C, 65.29; H, 6.16; N, 3.17.
Found: C, 64.98; H, 6.35; N, 3.14%.
6 H),
chloroperoxybenzoic acid
6
To a solution of either 4, 5, 9, 10, 19–24, 26 (1.5
mmol) in distilled dichloromethane (300 mL), m-
chloroperoxybenzoic acid (Aldrich 57–86%) (3.0 g)
was added and the suspension was stirred at room
temperature. When TLC showed that all starting com-
pound had been consumed (2–3 days), the reaction
mixture was washed successively with 5% aqueous
sodium hydroxide and water, dried (MgSO4), filtered
and the filtrate evaporated to dryness. The solid
obtained was purified by flash chromatography on sil-
ica gel.
6
6
+
’
6
H3].
HRMS
(EI):
[M] ,
4.5.3. 1-Dodecyl (R)-4,6-O-benzylidene-2-deoxy-2-[(E)-
2,3-epoxy-3-phenylpropanamido]-b-D-allopyranoside 13.
Two stereoisomers were obtained in 1:1 ratio. Column
chromatography using dichloromethane–methanol
(100:1) as eluent allowed the purification of two
stereoisomers but not their separation. Yield 0.79 g
(91%). Mp 189–190°C; [h]D −147.8 (c 0.3, DMF); MS
4.5.1. Benzyl (R)-4,6-O-benzylidene-2-deoxy-2-[(E)-2,3-
epoxy-3-phenylpropanamido]-b-
D
-allopyranoside
11.
Two stereoisomers were obtained in 63:37 ratio (26%
de). Column chromatography using dichloromethane–
methanol (125:1) as eluent allowed the purification of
two stereoisomers but not their separation. Yield 0.60
g (80%). Mp 255–256°C; [h]D −61.5 (c 0.5, DMF); MS
(CI): m/z 504 (22%) [M+H]+. 1H NMR (200 MHz,
CDCl3) (for the major isomer 11a): l 7.5–7.1 (m 15H,
3Ph), 6.71 (d, 1H, J2,NH 9.2 Hz, NH), 5.61 (s, 1H,
(CI): m/z 582 (16%) [M+H]+ 1H NMR (200 MHz,
’
CDCl3): l 7.5–7.3 (m, 10H, 2Ph), 6.73, 6.69 (2d, 1H,
J2,NH 8.7 Hz, NH), 5.59 (s, 1H, PhCH6 ), 4.69, 4.68 (2d,
1H, J1,2 8,4 Hz, H-1), 4.38 (dd, 1H, J5,6e 4.8 Hz, J6e,6a
10.0 Hz, H-6e), 4.28 (m, 1H, H-3), 4.2–3.7 [m, 5H,
H-2, H-5, H-6a, OCHA
1H, J3,4 2.5 Hz, J4,5 9.3 Hz, H-4), 3.56, 3.54 [2d, 1H,
Jtrans 2.0 Hz CH(O)CHPh], 3.44 (m, 1H, OCHAHBR),
6 HBR, CH(O)CH6 Ph], 3.66 (dd,
6
6
PhCH
(d, 1H, J1,2 8.2 Hz, H-1), 4.57 (d, 1H, Jgem 12.3 Hz,
OCHAHBPh), 4.42 (dd, 1H, J5,6e 4.6 Hz, J6e,6a 10.0
Hz, H-6e), 4.3–4.2 (m, 2H, H-2, H-3), 3.99 (dt, 1H,
6 ), 4.93 (d, 1H, Jgem 12.3 Hz, OCH6 AHBPh), 4.77
1.6–1.2 [m, 10H, (CH2)10], 0.85 (t, 3H, J 6.4 Hz, CH3).
13C NMR (50 MHz, CDCl3): l 167.1 (CꢁO), 136.9–
125.7 (Ph), 101.6 (PhC
4), 70.2, 70.0 (OC
(C-5), 58.9 [CH(O)CHPh], 58.6 [CH(O)C
(C-2), 31.8–22.6 [(CH2)10], 14.1 (CH3). HRMS (EI):
[M] , found 581.334319. C34H47NO7 requires
6
6 H), 100.0, 99.9 (C-1), 78.6 (C-
6
H2R), 69.0 (C-6), 68.5 (C-3), 63.3
HPh], 51.6
J
J
4,5=J5,6a 9.6 Hz, J5,6e 4.6 Hz, H-5), 3.82 (t, 1H,
5,6a=J6e,6a 10.0 Hz, H-6a), 3.68 (m, 1H, H-4), 3.62,
6
6
[d, 1H, Jtrans 1.9 Hz, CH(O)CH
1.9 Hz, CH
(O)CHPh]. 13C NMR (50 MHz, CDCl3)
(for the major isomer 11a): l 167.2 (CꢁO), 136.9–
125.7 (Ph), 101.8 (PhCH), 99.2 (C-1), 78.7 (C-4), 70.9
(OCH2Ph), 69.0 (C-6), 68.6 (C-3), 63.5 (C-5), 58.9,
[CH(O)CHPh], 58.7 [CH(O)CHPh], 51.4 (C-2). HRMS
6 Ph], 3.51 [d, 1H, Jtrans
+
’
6
581.335253. Anal. calcd for C23H47NO7: C, 70.20; H,
8.14; N, 2.41. Found: C, 70.11; H, 8.12; N, 2.38%.
6
6
6
6
4.5.4. Benzyl (R)-4,6-O-benzylidene-2-deoxy-2-(3,4-
+
’
(EI): [M] , found 503.193733. C29H29NO7 requires
503.194403. Anal. calcd for C29H29NO7: C, 69.17; H,
5.80; N, 2.78. Found: C, 68.96; H, 5.80; N, 2.70%.
epoxybutanamido)-b-
D
-allopyranoside
14.
Two
stereoisomers were obtained in 56:44 ratio (12% de).
Column chromatography using dichloromethane–
methanol (100:1) as eluent allowed the purification of
two stereoisomers but not their separation. Yield 0.56
g (85%). Mp 240–241°C; [h]D −110.3 (c 0.6, DMF);
MS (CI): m/z 442 (19%) [M+H]+. 1H NMR (200
MHz, CDCl3): l 7.5–7.3 (m, 10H, 2Ph), 6.26 (m, 1H,
When an identical reaction was carried out at −10°C,
compound 11 was obtained with a de of 40%.
4.5.2. Benzyl (R)-4,6-O-benzylidene-2-deoxy-2-[(E)-2,3-
epoxybutanamido]-b-
D
-allopyranoside
12.
Two
NH), 5.60 (s, 1H, PhCH
OCHAHBPh), 4.73, 4.72 (2d, 1H, J1,2 7.9 Hz, H-1),
4.59, 4.57 (2d, 1H, Jgem 12.3 Hz, OCHAHBPh), 4.40
6 ), 4.90 (d, 1H, Jgem 12.3 Hz,
stereoisomers were obtained in 58:42 ratio (16% de).
Column chromatography using dichloromethane–
methanol (125:1) as eluent allowed the purification of
two stereoisomers but not their separation. Yield 0.63
g (95%). Mp 243–244°C; [h]D −101.1 (c 0.5, DMF);
MS (CI): m/z 442 (10%) [M+H]+. 1H NMR (200
MHz, CDCl3): l 7.5–7.2 (m, 10H, 2Ph), 6.53 (m, 1H,
6
6
(dd, 1H, J5,6e 4.5 Hz, J6e,6a 9.9 Hz, H-6e), 4.3–4.2 (m,
2H, H-2, H-3), 3.95 (dt, 1H, J4,5=J5,6a 9.7 Hz, J5,6e
4.5 Hz, H-5), 3.81 (t, 1H, J 5,6a=J6e,6a 9.9 Hz, H-6a),
3.67 (dd, 1H, J3,4 2.4 Hz, J4,5 9.2 Hz, H-4), 3.21, 3.12
[2m, 1H, CH2CH
(O)CH2], 2.6–2.5 [m, 2H, CHAHB
2.41 (bs, 1H, OH), 2.34, 2.26 [2dd, 1H, Jgem 6.8 Hz,
Jtrans 3.1 Hz, CH2CH(O)CHcisHtrans
]. 13C NMR (50
MHz, CDCl3): l 168.7 (CꢁO), 129.3–126.1 (2Ph),
101.7 (PhCH), 99.2 (C-1), 78.6 (C-4), 70.8 (OCH2Ph),
69.1 (C-6), 68.7 (C-3), 63.3 (C-5), 51.9 (C-2), 48.7
[CH2CH(O)CH2], 47.1 [CH2CH(O)CH2], 39.8, 39.6
[CH2CH(O)CH2]. Anal. calcd for C24H27NO7: C,
6
(O)CH2], 2.80 [m, 1H, CHA
6
HBCH-
Htrans],
J2,NH 6.7 Hz, NH), 5.58, 5.57 (2s, 1H, PhCH
4.86 (2d, 1H, Jgem 12.3 Hz, OCHAHBPh), 4.70, 4.67
(2d, 1H, J1,2 8.3 Hz, H-1), 4.59, 4.51 (2d, 1H, Jgem
12.3 Hz, OCHAHBPh), 4.39 (dd, 1H, J5,6e 4.4 Hz,
6
), 4.90,
6
CH(O)CHcis
6
6
6
6
J6e,6a 9.9 Hz, H-6e), 4.3–4.1 (m, 2H, H-2, H-3), 3.96
(m, 1H, H-5), 3.79 (t, 1H, J5,6a=J6e,6a 9.9 Hz, H-6a),
3.66 (m, 1H, H-4), 3.21, 3.17 [2d, 1H, Jtrans 2.1 Hz,
6
6
6
6
CH
5.1 Hz, CH(O)CH
CH(O)CHCH3
]. 13C NMR (50 MHz, CDCl3): l 168.3
6
(O)CHCH3], 3.00, 2.64 [2dq, 1H, Jtrans 2.1 Hz, J
6
6
CH3], 1.38, 1.29 [2d, 3H, J 5.1 Hz,
65.29; H, 6.16; N, 3.17. Found: C, 65.05; H, 6.24; N,
3.27%.
6

3200
J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 12 (2001) 3189–3203
4.5.5. Benzyl 2-amino-(R)-4,6-O-benzylidene-2-deoxy-2-
N-[(2S,3R)-2,3-epoxy-3-phenylpropanoyl]-2-N-3-O-
68.9 (C-6), 63.6 (C-5), 58.6 (C-2), 54.4 [C
6
H(O)CHCH3],
53.8 [CH(O)C6 HCH3], 17,2 [CH(O)CHC6 H3]. HRMS
methylidene-b-
D
-allopyranoside 27. Two stereoisomers
(CI): [M+H]+, found 454.184981. C25H28NO7 requires
454.186578. Anal. calcd for C25H27NO7: C, 66.21; H,
6.00; N, 3.09. Found: C, 65.98; H, 5.99; N, 3.18%.
were obtained in 97:3 ratio [94% de for the (2S,3R)-iso-
mer]. The major isomer 27a (major Rf) was isolated by
column chromatography using hexane–ethyl acetate
(25:10) as eluent, yield: 0.66 g (85%). Mp 171–172°C;
[h]D +62.5 (c 0.5, CHCl3); MS (CI): m/z 516 (25%)
4.5.7. Benzyl 2-amino-(R)-4,6-O-benzylidene-2-deoxy-2-
N-[(E)-2,3-epoxypentanoyl]-2-N-3-O-methylidene-b-D-
allopyranoside 29. Two stereoisomers were obtained in
73:27 ratio [46% de for the (2S,3R)-isomer]. Both iso-
mers were isolated by column chromatography using
hexane–ethyl acetate (17:10) as eluent, yield: 0.58 g
(83%).
1
[M+H]+. H NMR (200 MHz, CDCl3): l 7.51–6.9 (m,
15H, 3Ph), 5.58 (s, 1H, PhCH
Hz, OCH2N), 4.6–4.3 (m, 6H, H-1, H-2, H-3, H-6e,
OCH2Ph), 4.23 [d, 1H, Jtrans 1.7 Hz, CH(O)CHPh], 3.95
[d, 1H, Jtrans 1.7 Hz, CH(O)CHPh], 3.9–3.7 (m, 3H,
H-4, H-5, H-6a). 13C NMR (50 MHz, CDCl3): l 165.2
(CꢁO), 136.6–126.0 (3Ph), 102.8 (PhCH), 99.7 (C-1),
80.9 (OCH2N), 76.8 (C-3), 76.3 (C-4), 71.4 (OCH2Ph),
68.9 (C-6), 63.7 (C-5), 58.7 (C-2), 58.2 [CH(O)CHPh],
56.6 [CH(O)CHPh]. Anal. calcd for C30H29NO7: C,
6 ), 5.19 (dd, 2H, Jgem 5.7
6
6
6
6
6
4.5.7.1. Major isomer 29a (major Rf). Mp 78–79°C;
[h]D −53.6 (c 0.5; CH2Cl2); MS (CI): m/z 468 (19%)
6
1
6
[M+H]+. H NMR (200 MHz, CDCl3): l 7.5–7.2 (m,
69.89; H, 5.67; N, 2.72. Found: C, 69.83; H, 5.79; N,
2.70%.
10H, 2Ph), 5.59 (s, 1H, PhC
Hz, OCH2N), 4.93 (d, 1H, Jgem 11.4 Hz, OCHA
4.64 (d, 1H, J1,2 7.5 Hz, H-1), 4.54 (d, 1H, Jgem 11.4 Hz,
OCHAHBPh), 4.5–4.4 (m, 2H, H-3, H-6e), 4.29 (dd, 1H,
6
H), 5.17 (dd, 2H, Jgem 5.2
6
HBPh),
6
4.5.6. Benzyl 2-amino-(R)-4,6-O-benzylidene-2-deoxy-2-
N-[(E)-2,3-epoxybutanoyl]-2-N-3-O-methylidene-b-D-
allopyranoside 28. Two stereoisomers were obtained in
72:28 ratio [44% de for the (2S,3R)-isomer]. Both iso-
mers were isolated by column chromatography using
hexane–ethyl acetate (17:10) as eluent, yield: 0.54 g
(80%).
J1,2 7.5 Hz, J2,3 4.2 Hz, H-2), 4.0–3.9 (m, 2H, H-4, H-5),
3.78 (t, 1H, J5,6a=J6e,6a 10.0 Hz, H-6a), 3.49 [d, 1H,
Jtrans 2.0 Hz, CH
Hz, J 4.1 Hz, CH(O)CH
CH(O)CHCH2CH3], 0.76 [t, 3H,
CH(O)CHCH2CH3
166.4 (CꢁO), 136.6–126.3 (2Ph), 102.8 (PhC
6
(O)CHCH2CH3], 3.19 [dt, 1H, Jtrans 2.0
6
CH2CH3], 1.5–1.2 [m, 2H,
6
J
7.5 Hz,
H), 100.4
6
]. 13C NMR (50 MHz, CDCl3): l
6
(C-1), 80.9 (OCH2N), 76.8 (C-3), 76.4 (C-4), 71.8
(OCH2Ph), 69.0 (C-6), 63.9 (C-5), 59.5 (C-2), 58.7
[CH(O)CHCH2CH3], 52.5 [CH(O)CHCH2CH3], 23.7
[CH(O)CHCH2CH3], 9.2 [CH(O)CHCH2CH3]. Anal.
4.5.6.1. Major isomer 28a (major Rf). Mp 113–114°C;
[h]D −21.1 (c 0.6, CH2Cl2); MS (CI): m/z 454 (36%)
6
6
6
1
[M+H]+. H NMR (500 MHz, CDCl3): l 7.5–7.2 (m,
6
6
10H, 2Ph), 5.61 (s, 1H, PhCH
Hz, OCH2N), 4.96 (d, 1H, Jgem 11.4 Hz, OCHA
4.67 (d, 1H, J1,2 7.6 Hz, H-1), 4.56 (d, 1H, Jgem 11.4 Hz,
OCHAHBPh), 4.5–4.4 (m, 2H, H-3, H-6e), 4.28 (dd, 1H,
6
), 5.17 (dd, 2H, Jgem 5.5
calcd for C26H29NO7: C, 66.80; H, 6.25; N, 3.00.
Found: C, 66.56; H, 6.19; N, 3.04%.
6
HBPh),
6
4.5.7.2. Minor isomer 29b (minor Rf). Mp 80–81°C;
[h]D −144.2 (c 0.4; CH2Cl2); MS (CI): m/z 468 (33%)
J1,2 7.6 Hz, J2,3 4.2 Hz, H-2), 3.99 (m, 1H, J4,5=J5,6a 9.9
Hz, J5,6e 5.0 Hz, H-5), 3.91 (dd, 1H, J3,4 3.2 Hz, J4,5 9.9
Hz, H-4), 3.80 (t, 1H, J5,6a=J6e,6a 9.9 Hz, H-6a), 3.43 [d,
1
[M+H]+; H NMR (200 MHz, CDCl3): l 7.5–7.3 (m,
10H, 2Ph), 5.57 (s, 1H, PhCH
2H, OCH2N), 4.91 (d, 1H, Jgem 11.2 Hz, OCHA
4.66 (d, 1H, J1,2 7.5 Hz, H-1), 4.64 (d, 1H, Jgem 11.2 Hz,
OCHAHBPh), 4.5–4.4 (m, 2H, H-3, H-6e), 4.12 (dd, 1H,
J1,2 7.5 Hz, J2,3 4.3 Hz, H-2), 4.0–3.7 [m, 4H, H-4, H-5,
H-6a, CH(O)CHCH2CH3], 3.15 [m, 1H, CH(O)-
CHCH2CH3], 1.61 [m, 2H, CH(O)CHCH2CH3], 0.90 (t,
3H, J 7.5 Hz, CH(O)CHCH2CH3
]. 13C NMR (50 MHz,
CDCl3): 166.7 (CO), 136.6–126.2 (2Ph), 102.8
(PhCH), 100.1 (C-1), 80.8 (OCH2N), 77.0 (C-3), 76.3
(C-4), 71.9 (OCH2Ph), 69.0 (C-6), 63.6 (C-5), 59.3
(C-2), 58.6 [CH(O)CHCH2CH3], 52.4 [CH(O)CHCH2-
CH3], 24.3 [CH(O)CHCH2CH3], 9.4 [CH(O)CHCH2-
H3]. HRMS (CI): [M+H]+, found 468.201746.
6
), 5.14 (dd, Jgem 5.6 Hz,
1H, Jtrans 1.8 Hz, CH
1.8 Hz, J 5.1 Hz, CH(O)CH
CH(O)CHCH
3]. 13C NMR (125 MHz, CDCl3): l 166.1
(CꢁO), 136.6–126.2 (2Ph), 102.7 (PhCH), 100.5 (C-1),
80.8 (OCH2N), 76.8 (C-3), 76.3 (C-4), 71.8 (OCH2Ph),
68.9 (C-6), 63.8 (C-5), 58.7 (C-2), 54.5 [CH(O)CHCH3],
53.9 [CH(O)CHCH3], 16.3 [CH(O)CHCH3]. Anal. calcd
6
(O)CHCH3], 3.24 [dq, 1H, Jtrans
6
HBPh),
6
CH3], 0.96 (d, 3H, J 5.1 Hz,
6
6
6
6
6
6
6
6
6
6
6
for C25H27NO7: C, 66.21; H, 6.00; N, 3.09. Found: C,
66.07; H, 6.18; N, 2.97%.
l
6
6
4.5.6.2. Minor isomer 28b (minor Rf). Mp 83–84°C;
[h]D −102.7 (c 0.4, CH2Cl2); MS (CI): m/z 454 (53%)
6
6
6
1
[M+H]+; H NMR (200 MHz, CDCl3): l 7.5–7.3 (m,
C6
10H, 2Ph), 5.58 (s, 1H, PhCH
Hz, OCH2N), 4.92 (d, 1H, Jgem 11.3 Hz, OCHA
4.7–4.6 (m, 2H, H-1, OCHAHBPh), 4.4–4.2 (m, 2H,
6
), 5.14 (dd, 2H, Jgem 5.6
C26H30NO7 requires 468.202228. Anal. calcd for
C26H29NO7: C, 66.80; H, 6.25; N, 3.00. Found: C,
66.62; H, 6.39; N, 2.88%.
6
HBPh),
6
H-3, H-6e), 4.11 (dd, 1H, J1,2 7.5 Hz, J2,3 4.2 Hz, H-2),
4.0–3.8 (m, 3H, H-4, H-5, H-6a), 3.75 [d, 1H, Jtrans 2.1
Hz, CH
Hz, CH(O)CH
CH(O)CHCH
3]. 13C NMR (50 MHz, CDCl3): l 166.4
(CꢁO), 136.6–126.3 (2Ph), 102.8 (PhCH), 100.0 (C-1),
80.8 (OCH2N), 77.0 (C-3), 76.4 (C-4), 71.9 (OCH2Ph),
6
(O)CHCH3], 3.22 [dq, 1H, Jtrans 2.1 Hz, J 5.1
4.5.8. Benzyl 2-amino-(R)-4,6-O-benzylidene-2-deoxy-2-
N-(2,3-epoxy-3-methylbutanoyl)-2-N-3-O-methylidene-b-
6
CH3], 1.31 [d, 3H, 5.1 Hz,
J
6
D-allopyranoside 30. Two stereoisomers were obtained
6
in 74:26 ratio (48% de). Column chromatography using
hexane–ethyl acetate (15:10) as eluent allowed the
6

J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 12 (2001) 3189–3203
3201
purification of two stereoisomers but not their separa-
(C-1), 80.9 (OCH2N), 71.1 (OC
6
H2R), 63.5 (C-5), 58.5
tion. Yield 0.55 g (78%). Mp 82–83°C; [h]D −37.9 (c 0.6,
[CH(O)CHPh], 57.8 [CH(O)C6 HPh], 56.6 (C-2). HRMS
6
1
+
’
CH2Cl2); MS (CI): m/z 468 (40%) [M+H]+; H NMR
(EI): [M] , found 593.334479. C35H47NO7 requires
593.335253.
(500 MHz, CDCl3) (for the major isomer): l 7.5–7.2
(m, 10H, 2Ph), 5.59 (s, 1H, PhCH
OCH2N), 4.97 (d, 1H, Jgem 11.6 Hz, OCHA
(d, 1H, J1,2 7.6 Hz, H-1), 4.58 (d, 1H, Jgem 11.6 Hz,
OCHAHBPh), 4.5–4.4 (m, 3H, H-2, H-3, H-6e), 4.00 (m,
1H, H-5), 3.89 (dd, 1H, J3,4 3.1 Hz, J4,5 9.6 Hz, H-4),
3.81 (t, 1H, J5,6a=J6e,6a 10.0 Hz, H-6a), 3.33 [s, 1H,
6
), 5.14 (m, 2H,
6
HBPh), 4.63
4.5.11.
deoxy-2-N-[(E)-2,3-epoxybutanoyl]-2-N-3-O-isopropyli-
dene-b- -allopyranoside 33. Two stereoisomers were
obtained in 75:25 ratio [50% de for the (2S,3R)-isomer].
Both isomers were isolated by column chromatography
using hexane–ethyl acetate (17:10) as eluent, yield: 0.54
g (75%).
1-Benzyl
2-amino-(R)-4,6-O-benzylidene-2-
6
D
CH
13C NMR (125 MHz, CDCl3) (for the major isomer): l
165.6 (CꢁO), 136.7–126.2 (2Ph), 102.7 (PhCH), 100.1
(C-1), 80.4 (OCH2N), 76.7 (C-3), 76.3 (C-4), 71.6
6 (O)C(CH3)2], 1.29, 1.17 [2s, 6H, CH(O)C(CH6 3)2].
6
4.5.11.1. Major isomer 33a (major Rf). Mp 90–91°C;
[h]D −18.2 (c 0.6, CH2Cl2); MS (CI): m/z 482 (81%)
(OC
[CH(O)C(CH3)2], 58.0 (C-2), 56.8 [CH(O)C
23.7, 19.1 [CH(O)C(C
467.194004. C26H29NO7 requires 467.194403. Anal.
calcd for C26H29NO7: C, 66.80; H, 6.25; N, 3.00.
Found: C, 66.55; H, 6.19; N, 2.95%.
6
H2Ph),
69.0
(C-6),
63.8
(C-5),
60.7
(CH3)2],
6
6
1
[M+H]+. H NMR (500 MHz, CDCl3): l 7.5–7.3 (m,
+
’
6
H3)2]. HRMS (EI): [M] , found
10H, 2Ph), 5.60 (s, 1H, PhCH
Hz, OCHAHBPh), 4.66 (d, 1H, J1,2 7.7 Hz, H-1), 4.61
(d, 1H, Jgem 11.8 Hz, OCHAHBPh), 4.55 (t, 1H, J2,3
6 ), 4.90 (d, 1H, Jgem 11.8
6
6
=
J3,4 3.7 Hz, H-3), 4.46 (dd, 1H, J5,6e 5.1 Hz, J6e,6a 10.2
Hz, H-6e), 4.28 (dd, 1H, J1,2 7.7 Hz, J2,3 3.7 Hz, H-2),
3.96 (dt, 1H, J4,5=J5,6a 9.9 Hz, J5,6e 5.1 Hz, H-5), 3.87
(dd, 1H, J3,4 3.2 Hz, J4,5 9.9 Hz, H-4), 3.81 (t, 1H,
4.5.9. Benzyl 2-amino-(R)-4,6-O-benzylidene-2-deoxy-2-
N-[(E)-2,3-epoxy-3-phenylpropanoyl]-2-N-3-O-methyli-
dene-a-D-allopyranoside 31. MS (CI): m/z 516 (20%)
J
5,6e=J6e,6a 9.9 Hz, H-6a), 3.47 [d, 1H, Jtrans 1.7 Hz,
CH(O)CHCH3], 3.23 [dq, 1H, Jtrans 1.7 Hz, J 5.2 Hz,
CH(O)CHCH3], 1.61, 1.53 [2s, 6H, OC(CH3)2N], 1.09
[d, 3H, J 5.2 Hz, CH(O)CHCH
3]. 13C NMR (125 MHz,
CDCl3): l 165.0 (CꢁO), 136.7–126.3 (2Ph), 102.8
(PhCH), 100.1 (C-1), 97.7 [OC(CH3)2N], 76.9 (C-4),
72.7 (C-3), 71.3 (OCH2Ph), 69.0 (C-6), 63.8 (C-5), 60.1
(C-2), 55.0 [CH(O)CHCH3], 54.5 [CH(O)CHCH3], 26.3,
23.7 [OC(CH3)2N], 16.6 [CH(O)CHCH3]. Anal. calcd
1
[M+H]+. H NMR (200 MHz, CDCl3): complex spec-
trum, stereoisomers, and conformers mixture. Anal.
calcd for C30H29NO7: C, 69.89; H, 5.67; N, 2.72.
Found: C, 69.61; H, 5.92; N, 2.58%.
6
6
6
6
6
4.5.10. 1-Dodecyl 2-amino-(R)-4,6-O-benzylidene-2-
deoxy-2-N-[(E)-2,3-epoxy-3-phenylpropanoyl]-2-N-3-O-
methylidene-b-D-allopyranoside 32. Two stereoisomers
were obtained in 88:12 ratio [76% de for the (2S,3R)-
isomer]. Both isomers were isolated by column chro-
matography using hexane–ethyl acetate (32:10) as
eluent, yield: 0.84 g (94%).
6
6
6
6
6
for C27H31NO7: C, 67.35; H, 6.49; N, 2.91. Found: C,
67.14; H, 6.53; N, 2.91%.
4.5.11.2. Minor isomer 33b (minor Rf). Mp 182–
183°C; [h]D −105.3 (c 0.3, CH2Cl2); MS (CI): m/z 482
4.5.10.1. Major isomer 32a (major Rf). Mp 67–68°C;
[h]D+40.4 (c 0.5, Cl2CH2); MS (CI): m/z 594 (35%)
1
(40%) [M+H]+. H NMR (200 MHz, CDCl3): l 7.5–7.2
(m, 10H, 2Ph), 5.56 (s, 1H, PhCH
11.7 Hz, OCHAHBPh), 4.65 (d, 1H, Jgem 11.7 Hz,
OCHAHBPh), 4.62 (d, 1H, J1,2 7.6 Hz, H-1), 4.5–4.4 (m,
2H, H-3, H-6e), 4.08 (dd, 1H, J1,2 7.6 Hz, J2,3 4.0 Hz,
H-2), 4.0–3.7 [m, 4H, H-4, H-5, H-6a, CH(O)CHCH3],
3.17 [dq, 1H, Jtrans 1.8 Hz, J 5.0 Hz, CH(O)CHCH3],
1.54, 1.36 [2s, 6H, OC(CH3)2N)], 1.35 [d, 3H, J 5.0 Hz,
CH(O)CHCH3
]. 13C NMR (50 MHz, CDCl3): l 165.1
(CꢁO), 136.7–126.4 (2Ph), 102.9 (PhCH), 99.5 (C-1),
97.7 [OC(CH3)2N], 76.7 (C-4), 72.8 (C-3), 71.2
(OCH2Ph), 69.1 (C-6), 63.6 (C-5), 60.0 (C-2), 54.3
[CH(O)CHCH3], 26.2, 23.6 [OC(CH3)2N], 17.2
[CH(O)CHCH3]. HRMS (EI): [M] , found 481.209446.
6 ), 4.91 (d, 1H, Jgem
1
[M+H]+. H NMR (200 MHz, CDCl3): l 7.5–7.3 (m,
6
10H, 2Ph), 5.57 (s, 1H, PhCH
6
), 5.29 (d, 1H, Jgem 5.7
N),
6
Hz, OCHAHBN), 5.18 (d, 1H, Jgem 5.7 Hz, OCHAHB
6
6
4.5–4.4 (m, 2H, H-1, H-3), 4.37 (dd, 1H, J5,6e 4.4 Hz,
J6e,6a 10.0 Hz, H-6e), 4.3–4.2 [m, 2H, H-2,
6
6
CH(O)CH
3.9–3,8 (m, 2H, H-4, H-5), 3.73 (t, 1H, J5,6a=J6e,6a 10.0
Hz, H-6a), 3.56 (m, 1H, OCHAHBR), 3,20 (m, 1H,
OCHAHB
R). 13C NMR (50 MHz, CDCl3): l 165.2
(CꢁO), 136.6–125.9 (2Ph), 102.6 (PhCH), 101.2 (C-1),
80.9 (OCH2N), 76.8 (C-4), 76.1 (C-3), 70.6 (OCH2R),
68.8 (C-6), 63.5 (C-5), 58.8 [CH(O)CHPh], 58.1
[CH(O)CHPh], 56.3 (C-2), 31.8–22.6 [(CH2)10], 14.0
6 Ph], 3.97 [d, 1H, Jtrans 1.7 Hz, CH6 (O)CHPh],
6
6
6
6
6
6
6
6
6
6
6
6
+
’
6
6
C27H31NO7 requires 481.210053. Anal. calcd for
C27H31NO7: C, 67.35; H, 6.49; N, 2.91. Found: C,
67.07; H, 6.51; N, 2.89%.
(CH3). Anal. calcd for C35H47NO7: C, 70.80; H, 7.98;
N, 2.36. Found: C, 70.52; H, 8.14; N, 2.54%.
4.5.10.2. Minor isomer 32b (minor Rf). MS (CI): m/z
594 (40%) [M+H]+. 1H NMR (200 MHz, CDCl3): l
4.6. Reaction of epoxyamides with metallic hydrides
7.5–7.3 (m, 10H, 2Ph), 5.54 (PhCH
5.6 Hz, OCHAHBN), 5.17 (d, 1H, Jgem 5.6 Hz,
OCHAHBN), 4.60 (d, 1H, J1,2 7.5 Hz, H-1), 4.15 [d, 1H,
Jtrans 1.9 Hz, CH(O)CHPh], 4.09 [d, 1H, Jtrans 1.9 Hz,
CH
(O)CHPh]. 13C NMR (50 MHz, CDCl3): l 101.7
6 ), 5.33 (d, 1H, Jgem
6
4.6.1. General procedure for reaction with lithium alu-
minum hydride. A stirred solution of either 11, 12 or 14
(0.5 mmol) in dry THF (30 mL) was cooled to −10°C
under an argon atmosphere. Lithium aluminum hydride
6
6
6

3202
J. M. Vega-Pe´rez et al. / Tetrahedron: Asymmetry 12 (2001) 3189–3203
solution in THF (1 M, 0.8 mmol) was added and the
reaction mixture was stirred for 3–6 h and then allowed
to warm to room temperature. Saturated aqueous
sodium sulphate solution (0.25 mL) was added drop-
wise. The solid was removed by filtration and washed
with anhydrous THF and the filtrate was then concen-
trated to dryness.
9.8 Hz, H-6e), 4.3–4.1 [m, 3H, H-2, H-3,
CH2CH(OH)CH3], 3.96 (dt, 1H, J4,5=J5,6a 9.3 Hz, J5,6e
4.5 Hz, H-5), 3.80 (t, 1H, J5,6a=J6a,6e 10.0 Hz, H-6a),
3.66 (dd, 1H, J3,4 1.9 Hz, J4,5 9.3 Hz, H-4), 2.4–2.1 [m,
6
2H, CH
CH2CH(OH)CH3
171.8 (CꢁO), 136.9–126.1 (2Ph), 101.7 (PhC
(C-1), 78.6 (C-4), 70.6 (OCH2Ph), 69.0 (C-6), 68.7, 68.6
(C-3), 64.8, 64.7 [CH2CH(OH)CH3], 63.3 (C-5), 51.7,
51.6 (C-2), 44.1 [CH2CH(OH)CH3], 22.6
[CH2CH(OH)CH3]. HRMS (EI): [M] , found
6
2CH(OH)CH3], 1.17 [d, 3H,
]. 13C NMR (50 MHz, CDCl3): l
H), 99.0
J 6.3 Hz,
6
6
6
6
4.6.1.1. Benzyl (R)-4,6-O-benzylidene-2-deoxy-2-(2-
6
+
’
hydroxy-3-phenylpropanamido)-b-
D
-allopyranoside
15.
6
Only one regioisomer was obtained as stereoisomeric
444.201322. C24H30NO7 requires 444.202228.
mixture from 11. MS (CI): m/z 506 (20%) [M+H]+. H
NMR (200 MHz, CDCl3): l 6.93 (d, 1H, J2,NH 9.0 Hz,
1
From compound 12, using the described conditions,
two regioisomers were obtained: 16 and 17 in 1:3 ratio.
1H NMR (200 MHz, CDCl3): l 1.17 [d, J 6.3 Hz,
NH), 4.57 (d, 1H, Jgem 12.1 Hz, OCHAHB
1H, Jgem 14.0 Hz, J 8.5 Hz, CH(OH)CHAHB
major isomer); 6.83 (d, 1H, J2,NH 8.7 Hz, NH), 4.55 (d,
1H, Jgem 12.5 Hz, OCHAHBPh), 2.87 [dd, 1H, Jgem 14.0
Hz, J 8.2 Hz, CH(OH)CHAHBPh] (for the minor iso-
mer). 13C NMR (50 MHz, CDCl3):
73.1
[CH(OH)CH2Ph], 41.0 [CH(OH)CH2Ph] (for the major
isomer); 72.8 [CH(OH)CH2Ph], 40.6 [CH(OH)CH2Ph]
6
Ph), 2.75 [dd,
6
Ph] (for the
CH2CH(OH)CH3
CH(OH)CH2CH3
CDCl3): 22.6 [CH2CH(OH)C
[CH(OH)CH2CH3] (for 16).
6
]
(for 17), 0.87 [t,
] (for 16). 13C NMR (50 MHz,
H3] (for 17), 9.1
J 7.2 Hz,
6
6
6
l
6
l
6
6
6
6
6
4.6.2. General procedure for reaction with sodium boro-
hydride. To a solution of 27a or 32a (0.5 mmol) in dry
THF (50 mL) was added sodium borohydride (12 mg,
0.32 mmol) and the reaction mixture was stirred at
room temperature until completion of the reaction.
When TLC showed that all of the starting compound
had been consumed (1 week), the solvent was co-evapo-
rated with methanol to give a solid which was purified
by flash chromatography on silica gel. The elution with
hexane–ethyl acetate (2:1) gave the compound 34,
which was identified as (2R,3R)-(+)-3-phenylglycidol.
The posterior elution with dichloromethane–methanol
(60:1) gave the sugar moiety 1 or 3.
(for the minor isomer). 15 was acetylated for its
characterization.
4.6.1.1.1. Benzyl 2-(2-acetoxy-3-phenylpropanamido)-
3-O-acetyl-(R)-4,6-O-benzylidene-2-deoxy-i-D-allopy-
ranoside 18. Compound 15 was acetylated in the usual
way with acetic anhydride/pyridine/dichloromethane,
and purified by column chromatography using
dichloromethane–methanol (125:1) as eluent, yield: 0.23
1
g (78%); MS (CI): m/z 590 (35%) [M+H]+. H NMR
(200 MHz, CDCl3): l 7.4–7.2 (m, 15H, 3Ph), 6.05 (d,
J2,NH 8.7 Hz, NH minor isomer), 5.96 (d, J2,NH 8.4 Hz,
NH major isomer), 5.67 (bs, H-3 major isomer), 5.63
(bs, H-3 minor isomer), 5.53 (PhCH
CH(OAc)CH2Ph], 4.87, 4.85 (2d, 1H, Jgem 12.3 Hz,
OCHAHBPh), 4.67, 4.65 (2d, 1H, J1,2 8.6 Hz, H-1), 4.57,
4.55 (2d, 1H, Jgem 12.3 Hz, OCHAHBPh), 4.4–4.3 (m,
2H, H-6e, H-2), 3.9–3.7 (m, 3H, H-4, H-5, H-6a), 3.2–
6 ), 5.31 [m, 1H,
6
6
Acknowledgements
6
3.0 [m, 2H, CH(OAc)CH6 2Ph], 2.05, 1.90 (2s, CH3 major
isomer), 2.04, 1.94 (2s, CH3 minor isomer). 13C NMR
We thank the Ministerio de Ciencia y Tecnolog´ıa
(Spain) for financial support (grant BQU2001-2425)
and Ezequiel Arocha Lavado for his collaboration in
the preparation of the starting material.
(50 MHz, CDCl3): l 170.0, 169.7, 169.4, 169.3,169.2,
168.2 (3CꢁO), 137.0–125.4 (3Ph), 101.3, 101.2 (C
98.6, 98,5 (C-1), 76.9 (C-4), 74.3 [CH(OAc)CH2Ph
major isomer], 74.1 [CH(OAc)CH2Ph minor isomer],
70.3, 70.2 (OCH2Ph), 69.4, 69.1 (C-3), 68.8 (C-6), 64.3
(C-5), 51.0 (C-2), 37.2 [CH(OAc)CH2Ph major isomer],
36.8 [CH(OAc)CH2Ph minor isomer], 20.8, 20.7, 20.6,
20.5 (2CH3CO). Anal. calcd for C33H35NO9: C, 67.22;
6 HPh),
6
6
6
6
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