Efficient synthesis of a series of novel fructose-based 3-acetyl-5-alkyl-2,3-dihydro-1,3,4-oxadiazole derivatives and studies of the reaction mechanism

Article abstract of DOI:10.1016/j.tetasy.2008.12.033

A series of novel alkyl substituted fructose-based oxadiazoles were synthesized and their cytotoxic activities toward tumor cells were investigated. We studied the reaction mechanism and the stereochemistry of the reaction. Tautomerization between isomers

Full text of DOI:10.1016/j.tetasy.2008.12.033

Tetrahedron: Asymmetry 20 (2009) 399–410
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Tetrahedron: Asymmetry
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Efficient synthesis of a series of novel fructose-based 3-acetyl-5-alkyl-2,3-
dihydro-1,3,4-oxadiazole derivatives and studies of the reaction mechanism
Dong Han b, Xiang-Bao Meng a,b, Lin-Na Wang b, Hong Liu b, Yun Yao b, Zhuo Wang a, Zhen-Jun Yang a,
Zhen-Min Liu a, Zhong-Jun Li a,b,
*
a State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, People’s Republic of China
b Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of novel alkyl substituted fructose-based oxadiazoles were synthesized and their cytotoxic activ-
ities toward tumor cells were investigated. We studied the reaction mechanism and the stereochemistry
of the reaction. Tautomerization between isomers 2 and 3 was observed in solution. The tautomerization
was accelerated by heating or in the presence of acetic acid. An intermediate 6 during the heterocycliza-
tion was isolated, and two different pathways for the heterocyclization were suggested. On the basis of
these findings, an efficient method, with the assistance of microwave irradiation was developed for the
synthesis of 4 and 5. The yields were satisfactory and no by-products were found. We also proposed that
the (R/S)-configurations of oxadiazoles were determined by the E/Z configurations of hydrazones.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 6 November 2008
Accepted 22 December 2008
Available online 25 March 2009
1. Introduction
diastereomers with (R)- and (S)-configurations at C-3 were ob-
tained, and the possible mechanism of the stereoselective synthe-
1,3,4-Oxadiazole derivatives have attracted significant attention
in the field of drug discovery because of their wide array of phar-
macological activities, including antibacterial, anti-fungal, analge-
sic, anti-inflammatory, anti-hypertension, and muscle relaxing
activities.1–7 Various modifications of the structure of 1,3,4-oxadi-
azole have been carried out.8–10 As an important group of 1,3,4-
oxadiazole derivatives, 3-acetyl-2,3-dihydro-1,3,4-oxadiazoles
have also been well documented with biological activities such
as anti-cancer and anti-bacterial activities.11–13
We have concentrated on the synthesis of carbohydrate-based
heterocyclic derivatives because of their unique biological activi-
ties and metabolic properties. In previous works, we synthesized
a series of fructose-based 1,3,4-oxadiazole derivatives 1 with anti-
tumor activities (Scheme 1).14–16 The configuration of 1 is (R) at C-
3. The diastereomer of 1 with (S)-configuration at C-3 was not ob-
tained due to the stereoselectivity of the heterocyclization reac-
sis of these compounds was investigated.
O
O
N
O
O
O
O
N
O
Ac
O
O
O
N
O
Ac
O
R
N
R
R=linear alkyl
1a
R=H
1b R=Br
1c
R=OMe
Scheme 1. Structures of compound 1 and designed alkyl substituted derivatives.
tion.
A
bioactivity assay showed that 1b inhibited the
transmembrane water absorption mediated by aquaporin-1
(AQP1) water channel (Y. Pan, X.J. Li, unpublished data). Molecular
modeling confirmed that 1b could bind to AQP1 and inhibit the
AQP1 water channel (Fig. 1). Molecular docking modeling sug-
gested that modification of the hydrophobic 5-aryl substitution
of 1 could affect the affinity to aquaporin-1. Based on these find-
ings, we designed and synthesized a series of 5-alkyl substituted
fructose-based 1,3,4-oxadiazole derivatives (Scheme 1). Both
Substituted 3-acetyl-2,3-dihydro-1,3,4-oxadiazoles are gener-
ally obtained from hydrazones in acetic anhydride or acetyl chlo-
ride under heating.17–27 The reaction can be promoted by the
addition of trifluoroacetic acid, sodium acetate, pyridine, or zinc
chloride, and by an increase in the reaction temperature. However,
the current synthesis procedures have the shortcomings of long
reaction time, low yields, and significant formation of by-prod-
ucts.13 Therefore, further investigation of the reaction mechanisms
including the by-product formation mechanism was needed to
improve the synthesis of this type of 1,3,4-oxadiazole derivatives.
* Corresponding author. Tel.: +86 10 8280 1714; fax: +86 10 6236 7134.
E-mail address: zjli@bjmu.edu.cn (Z.-J. Li).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.12.033

400
D. Han et al. / Tetrahedron: Asymmetry 20 (2009) 399–410
2. Results and discussion
1,2:4,5-Di-O-isopropylidene-b-D-erythro-2,3-hexodiulo-2,6-
pyranose reacted with hydrazides in methanol catalyzed by acetic
acid to afford a mixture of hydrazones 2 and 3 (around a 2:1 ratio,
Scheme 2),14 which are a pair of Z/E isomers. The E/Z configurations
of 2 and 3 were confirmed by 1H, 13C, and NOESY spectra.22 The
NOESY spectra of 2 showed a correlation between H-4 and –
NHCO–, indicating that 2 is in the E configuration. The NOESY spec-
tra of 3 showed a correlation between H-2 and –NHCO–, indicating
3 is in the Z configuration. In addition, we succeeded in obtaining a
single crystal of 2a from 1:2 AcOEt-cyclohexane for X-ray diffrac-
tion analysis.31 The 3D-structure of 2a (Fig. 2) clearly indicated
an E configuration, which verified the NOESY results.
Figure 1. Molecular modeling of 1b docked into the AQP1 water channel.
We also investigated the effect of microwave irradiation on the
reaction. Microwave irradiation has been widely used for the dis-
tribution of heat energy in organic synthesis. Unlike conventional
heating methods, microwave irradiation administer selective,
instantaneous heat to materials allowing, in many cases, faster
reaction rates, cleaner chemical transformations, and higher yields
with a concomitant decrease in the formation of by-products.28–30
Figure 2. The crystal structure ORTEP plot of 2a.
When the pure isomer of 2 or 3 was dissolved in solution with
MeOH or ethyl acetate for more than 24 h, a new spot was always
O
O
O
O
O
O
O
O
N
O
O
N
O
O
O
O
a
+
b
c
O
Ac
O
Ac
O
R
O
R
N
N
O
N
O
O
N
O
O
O
O
O
4a-l
+
(R)-isomer
5a-l (S)-isomer
O
O
ROCHN
2a-l
NHCOR
3a-l Z-isomer
O
O
N
O
O
N
O
O
N
E-isomer
O
O
O
O
O
O
+
+
O
Ac
O
Ac
O
O
Ac
O
R
O
R
N
N
N
a
R= CH3
4a 5a*
+
4a-l
e
f
(R)-isomer
5a-l (S)-isomer
R= n-C5H11
R= n-C6H13
R= n-C7H15
i
R= n-C9H19
R= n-C11H23
R= n-C15H31
R= n-C17H35
b R= C2H5
j
c
R= n-C3H7
g
k
l
*byproducts 4a and 5a were detected when R=b-l
d R= n-C4H9
h R= n-C8H17
Scheme 2. Reagents and condition: (a) hydrazide, MeOH, AcOH, 82–95%; (b) Ac2O, microwave irradiation, 160 °C, 30 min, 83–94%; (c) Ac2O, 120 °C, oil bath heating, 12–48 h,
40–58% (81% for 4a + 5a).

D. Han et al. / Tetrahedron: Asymmetry 20 (2009) 399–410
401
observed on TLC. The newly generated compound was separated
and characterized as the E/Z isomer of the reactant. Therefore, tau-
tomerization between 2 and 3 was discovered in solution. Pure
hydrazone 2d or 3d was used as the starting isomer to determine
the rate of tautomerization and the final ratio of isomers under dif-
ferent conditions. The results showed that the isomer tautomerized
in less than 5% in different solvents such as MeOH, DCM, and cyclo-
hexane when left at room temperature for more than 24 h. However,
an equilibrium of 2d and 3d (around 2:1 in ratio) in each solvent was
achieved in 2 h at reflux, and the same ratio was achieved in less than
5 min in the presence of 0.1% AcOH. Our syntheses of 2 and 3 were
catalyzed by AcOH, therefore the isomers 2 and 3 should have
reached equilibrium, in a ratio around 2:1.
When a mixture of 2 and 3 was used as the starting material in
acetic anhydride under heating conditions and nitrogen protection,
two oxadiazole isomers 4 and 5 were isolated, which were a pair of
diastereomers (around 2:1 in ratio, Scheme 2). These products
were isomers with different configurations at the spiro carbon C-
3 of the pyran ring. The major isomer 4 showed a smaller Rf value
than 5. The 1H NMR spectra indicated that the chemical shift of the
Ac-group of the major isomer 4 (d 2.03–2.07 ppm) was lower than
that of the minor isomer 5 (d 2.26–2.28 ppm), while the chemical
shift of –CH2@N– of the major isomer 4 (d 2.57–2.62 ppm) was
higher than that of the minor isomer 5 (d 2.33–2.39 ppm). These
facts implied that all the major isomers 4a–4l have the same con-
figuration at C-3, and all the minor isomers 5a–5l have the same
opposite configuration. The C-3 configurations of 4 and 5 were as-
signed by NOESY spectra and crystal structure. In the NOESY spec-
tra, the major isomer 4 showed a correlation between the CH3 of
NAc and H-6, suggesting that the C-3 was (R) configuration. The
same correlation was not observed in the NOESY spectra of 5, indi-
cating that the C-3 was (S) configuration. The 1H NMR and NOESY
results were in agreement with the conclusion of Ashry et al.22
Moreover, compound 4a was crystallized from 1:4 AcOEt–cyclo-
hexane for X-ray diffraction analysis.31 The ORTEP plot (Fig. 3)
clearly indicates that 4a has an (R)-configuration at the spiro C-3,
which is consistent with the NOESY results.
nal yield decreased. The amount of by-products also increased with
an increase in the reaction temperature. Thus, we reasoned that a
better understanding of the reaction mechanism was needed for
further improvement of this synthetic method.
2.1. Mechanism of the heterocyclization
During the cyclization of 2 and 3, a new spot on TLC with high Rf
value was observed after about 2 h, and the spot disappeared after
a certain period of time. This spot could be an intermediate or a by-
product of the heterocyclization reaction, which could provide
clues of the reaction mechanism. To isolate and identify this inter-
mediate, the reactions were quenched in which the substitute R
was methyl a, butyl d, and undecyl k after 5 h. The intermediates
were isolated by column chromatography to obtain compounds
6a, 6d and 6k, respectively. These compounds 6a, 6d and 6k turned
out to be the respective N-acetyl substitutes of the hydrazones
after characterization (Scheme 3). Even though only three interme-
diates were isolated and identified, similar intermediates 6a–l
should be formed in all the reactions with different substitutions
under the same conditions.
The transformation of hydrazone 6 to oxadiazoles 4 and 5 likely
undergoes the same process as the cyclization of hydrazones 2 and
3 to form oxadiazoles. However, because there are two acyl substi-
tutions in hydrazone 6, any one of the two acyl groups could par-
ticipate in the cyclization. When the RCO– group participates in the
cyclization, oxadiazoles 4 and 5 are formed. However, when the
CH3CO– group participates in the cyclization, by-products 4a and
5a are formed (Scheme 3). We found that compounds 6a, 6d, and
6k were not stable, but their degradation products at room tem-
perature or at 100 °C were not 4 and 5, indicating that acetic anhy-
dride or acetyl chloride was required for the cyclization reaction.
The heterocyclization of hydrazones 2 and 3 could undergo di-
rect cyclization or indirect cyclization through the di-acylated
intermediate 6, as shown in Scheme 3. In the direct cyclization
mechanism, compounds 2 and 3 react directly with acetic anhy-
dride through path A. Because intermediate 6 was formed later
in the reaction and products 4 and 5 were already detected before
the formation of 6, direct cyclization should be the dominant
pathway.
Since the generation of by-products 4a and 5a is through the for-
mationof intermediate 6, inhibitionof theformationof 6 couldavoid
the generation of by-product. Because intermediate 6 was formed
only after prolonged heating, ways to accelerate the reaction should
be able to limit by-product formation. Microwave irradiation is one
of the most promising ways to accelerate the reaction.
2.2. Efficient synthesis of 4 and 5 under microwave irradiation
We performed experiments to prepare 4b and 5b with micro-
wave irradiation and optimized the reaction conditions (Table 1).
Under the optimized conditions, target products were prepared
in up to 92% yield at 160 °C for 30 min. Because of the short reac-
tion time, as expected, no traces of by-products were detected.
Using the optimal conditions, oxadiazole derivatives 4a–4l and
5a–5l were prepared efficiently. Results under microwave irradia-
tion and oil bath heating are summarized in Table 2. Under the
microwave irradiation, the isolated yields were obviously im-
proved and no by-products were detected. However, the ratio of
the isomers 4 and 5 was around 2:1 under both heating and micro-
wave conditions.
Figure 3. The crystal structure ORTEP plot for 4a.
The yield of 4a and 5a was high when reacted at 120 °C for 12 h.
However, 4b–l and 5b–l were produced only in 40% yield under the
same conditions, and a considerable amount of by-products 4a and
5a was generated. The amount of by-product increased signifi-
cantly with prolonged reaction time. Efforts were made to opti-
mize the reaction conditions. However, the reaction solution
turned dark after the addition of TFA, pyridine, or ZnCl2, and the fi-
2.3. The stereochemistry of the oxadiazole synthesis
In order to improve the stereospecific synthesis of diastereo-
mers 4 and 5 to obtain a higher proportion of one isomer, we inves-

402
D. Han et al. / Tetrahedron: Asymmetry 20 (2009) 399–410
O
O
O
O
O
O
O
O
N
O
O
O
N
N
O
O
O
O
Ac2O
N
N
O
O
R
Ac
O
O
O
N
H
O
H
R
R
4a-l and 5a-l
(target products)
A
2a-l and 3a-l
O
O
O
O
Ac2O
O
N
N
O
O
O
O
O
CH3
R
O
O
B
O
O
Ac2O
O
N
N
O
O
O
O
O
O
N
O
O
O
N
N
O
O
O
R
CH3
O
O
Ac
O
O
O
O
6 a-l
N
H3C
4a and 5a
(by-products when R=b-l)
R
CH3
C
Scheme 3. Mechanism for the formation of target products and by-products.
tigated the effects of temperature, heating methods (microwave
Table 1
irradiation or oil bath heating), and of catalysts (AcONa, pyridine,
or ZnCl2) on the ratio of 4 and 5. The same ratio of 4 and 5 was ob-
tained by the addition of pyridine, zinc chloride or sodium acetate
(data not shown). As shown in Table 2, the influence of the temper-
ature (120 vs 160 °C) or heating methods on the ratio of 4 and 5 is
not significant, except when long chain substitutions are present
such as j, k and l. For these long chain substituted products, the
4:5 ratio decreased under the higher temperature during micro-
wave synthesis. Because the ratio of 2 and 3 was roughly around
2:1 under the reaction conditions and a similar ratio of 4 and 5
Optimization of the microwave irradiation conditions to prepare 4b + 5b
Temp. (°C)
Time (h)
Yield (%)
120
130
140
150
160
170
180
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0
0
11
25
92
85
73
Table 2
Synthesis of 4 and 5 under microwave irradiation and classical heating
R
Oil bath heating
Microwave irradiation
Time (h)
Yielda (%)
Ratiob (4:5)
Time (h)
Yielda (%)
Ratiob (4:5)
a
b
c
d
e
f
g
h
i
CH3
12
12
12
24
24
24
24
24
24
48
48
48
81
51
58
51
50
54
55
48
51
47
40
45
70:30
65:35
66:34
65:35
64:36
63:37
64:36
62:38
65:35
74:26
77:23
87:13
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
94
92
90
89
91
88
85
86
87
83
84
80
67:33
66:34
68:32
65:35
60:40
66:34
67:33
66:34
62:38
69:31
71:39
72:38
n-C2H5
n-C3H7
n-C4H9
n-C5H11
n-C6H13
n-C7H15
n-C8H17
n-C9H19
n-C11H23
n-C15H31
n-C17H35
j
k
l
0.66
0.66
0.66
Oil bath heating at 120 °C for 12 h and microwave irradiation at 160 °C for 30 min.
a
Yield of 4 + 5.
b
The ratio was determined by column chromatography.

D. Han et al. / Tetrahedron: Asymmetry 20 (2009) 399–410
403
2.4. The cytotoxic activities of 4 and 5
O
O
N
O
O
The in vitro cytotoxic activities of the prepared compounds 4
and 5 against Hela, Hl-60, BGC-823, Bel-7402, and KP tumor cells
were evaluated by MTT and SRB assays. Assays were performed
using 96-well plates (Falcon, Becton Dickinson, Mountain View,
O
O
R
C
O
N
O
N
O
N
O
R'
O
R'
O
C
CA, USA) seeded with 105 cells per well in 200
lL RPMI 1640
R
without phenol red and supplemented with 10% FCS. After 24 h
incubation, the medium was replaced with fresh RPMI 1640 med-
ium containing the tested compounds 4 and 5. Cells were incu-
3 R'=H
2 R'=H
R= linear alkyl
6 R'=Ac
6 R'=Ac
bated for 48 h with molecules 4 and 5 (10 lM), followed by
Ac2O
Ac2O
MTT or SRB Cell Inhibition Assay (Promega, Madison, WI, USA)
(Table 3). The absorbance of each well was measured with a
microplate reader at 570 nm (MTT) and 540 nm (SRB). As shown
in Table 3, compounds 4 and 5 showed specific inhibiting activi-
ties toward Hela and HL-60 tumor cells, but showed no inhibiting
activities toward BGC-823, Bel-7402, and KP tumor cells. Com-
pounds 4i and 5k with long chain substitutions showed the best
inhibition activities for Hela cells. However, the activities were
generally not affected strongly by the length of the 5-alkyl substi-
tution for HL-60 cells. There was generally no difference in the
cytotoxic activity of the oxadiazoles with (R)- or (S)-configura-
tions, except when the substitutions were i, j, and k. Even for
those compounds showing a difference, no general trend can be
observed. As analogs of the anti-tumor compound 1, the in vitro
cytotoxic activities of 4 and 5 were not strong. Because the
anti-tumor mechanism of this type of compounds may depend
on their inhibition of tumor adhesion,16 studies on the activities
of compounds 4 and 5 on the adhesion of tumor cell and trans-
membrane water absorption mediated by aquaporin-1 (AQP1)
water channel are being investigated. Initially we carried out
docking studies to examine the binding affinity of a selected
few derivatives to AQP1. The docking energy of compounds 4a,
4h, and 4l, which were substituted with linear alkyl groups of
O
O
O
O
O
O
Ac
O
R
O
N
C
N
O
O
N
O
N
O
C
Ac
R
5
4
Scheme 4. The stereochemistry of heterocyclization.
was obtained, we propose that the formation of the (R/S)-configu-
rations of 4 and 5 might be determined by the E/Z configurations of
2 and 3 (Scheme 4). Different geometric configurations of hydra-
zone 2 and 3 might lead to different directions (below or above
the pyran ring) from where the carbonyl oxygen attacks the C-3
carbon during heterocyclization. The carbonyl oxygen of the major
isomer 2 with an E-configuration would attack from below the pyr-
an ring, and produce the major product 4 with an (R)-configura-
tion; the minor product 5 with an (S)-configuration is obtained
from the attacking of the carbonyl oxygen above the pyran ring
of the minor isomer 3 with Z configuration.
Based on the above hypothesis, the stereoselective synthesis of
4 and 5 could be achieved by enhancing the proportion of one iso-
mer under the heterocyclization conditions. For example, under
higher temperature, the percentage of the sterically hindered Z
configuration should increase and the formation of the minor prod-
uct 5 with an (S)-configuration should increase too, as we noticed
with the long chain substituted products. Moreover, compared
with these 5-linear alkyl oxadiazole derivatives, the 5-aryl oxadi-
azole 1 was obtained mainly as the (R)-isomer, which holds the
same configuration with the major isomer 4. Our previous work
indicated that the 5-aryl hydrazones were isolated only in the E
configuration. Therefore, only oxadiazoles with the (R)-configura-
tion were formed.
CH3, C8H17, and C15H31
,
is ꢀ6.88 kJ/mol, ꢀ8.78 kJ/mol, and
ꢀ7.81 kJ/mol, respectively, suggesting that 4h has the highest
binding affinity to AQP1. It seems the affinity to AQP1 revealed
by docking energies correlates with the cytotoxicity toward
HL60 cells, but not other cancer cells. More work is needed to
understand the mechanism of action of these compounds.
3. Conclusion
In summary, a series of carbohydrate hydrazones and oxadiaz-
oles were synthesized. The configurations of the hydrazones 2, 3
and oxadiazoles 4, 5 were confirmed by NMR and XRD data. Tauto-
merization of isomers 2 and 3 was observed in solution, which was
Table 3
Inhibition ratio (%) tumor cell proliferation by 1b, 4 and 5
Helaa
HL-60b
BGC-823a
Bel-7402a
KPa
4
5
4
5
4
5
4
5
4
5
a
b
c
d
e
f
g
h
i
4.01
3.75
3.88
2.29
2.64
3.21
3.26
4.03
26.85
11.35
7.20
7.55
4.81
6.28
2.64
4.34
3.87
1.93
3.13
4.40
3.09
3.48
34.52
4.76
7.32
10.78
5.62
5.79
4.01
11.81
19.84
9.89
15.54
18.96
11.58
16.41
15.02
9.58
11.27
0.78
ꢀ9.20
10.55
2.61
4.10
ꢀ9.27
13.21
ꢀ2.97
ꢀ6.54
9.74
ꢀ0.24
ꢀ2.65
ꢀ8.39
0.78
ꢀ8.76
ꢀ12.31
1.74
ꢀ8.39
ꢀ13.47
ꢀ3.62
ꢀ3.50
ꢀ4.40
1.96
ꢀ7.90
2.08
2.61
ꢀ7.20
ꢀ7.09
ꢀ5.37
ꢀ7.66
ꢀ11.60
ꢀ4.54
ꢀ5.26
ꢀ11.57
ꢀ3.61
ꢀ0.97
10.49
ꢀ1.71
ꢀ7.97
ꢀ3.99
ꢀ8.06
ꢀ11.19
ꢀ4.11
ꢀ6.83
ꢀ10.21
ꢀ4.38
ꢀ6.35
ꢀ6.61
2.01
12.31
15.68
17.85
13.16
18.87
12.70
12.81
17.24
7.99
ꢀ3.55
ꢀ8.91
ꢀ0.79
ꢀ4.55
ꢀ9.09
ꢀ4.70
ꢀ3.95
ꢀ11.67
ꢀ2.67
ꢀ2.83
7.79
9.79
8.26
ꢀ4.19
17.40
6.78
ꢀ7.79
j
k
l
9.09
ꢀ11.02
ꢀ3.29
ꢀ26.46
5.24
7.44
a
Detected by standard SRB method.
Detected by standard MTT method.
b

404
D. Han et al. / Tetrahedron: Asymmetry 20 (2009) 399–410
accelerated by heating or in the presence of acetic acid. The isola-
tion and identification of intermediate 6 provided evidence for the
reaction mechanism and the formation of by-products. Based on
these findings, an efficient method for the synthesis of 4 and 5
was developed with microwave irradiation. The stereochemistry
of the hydrazones and oxadiazoles was studied and we proposed
that the (R/S)-configurations of oxadiazoles were determined by
the E/Z configurations of hydrazones.
4.5. Separation of compound 6
A mixture of 2 and 3 (4.0 mmol) was dissolved in acetic anhy-
dride (5.0 ml) and boiled at 120 °C in an oil bath and stirred. After
5 h, TLC showed that a new spot appeared with an Rf value of about
0.6 (ethyl acetate/cyclohexane, 1:5, v/v). The solution was concen-
trated under reduced pressure. The residual solvent was removed
by toluene under reduced pressure three times. The residual syrup
was purified by chromatography (ethyl acetate/cyclohexane, 1:8,
v/v) to afford compound 6 as a colorless foam. Compounds 6a,
6d and 6k were isolated.
4. Experimental
4.1. General methods
4.6. Compounds 2–6
Unless specified otherwise, all reactants and reagents were
purchased commercially and used without further purification.
Solvents were purified by standard procedures. Melting points
were measured on an X4 melting point apparatus, which were
uncorrected. Optical rotations were measured at 25 °C using an
Optical Activity AA-10R automatic polarimeter. NMR spectra were
recorded on Jeol-300 instrument and Inova-500 instrument. Mass
spectra were measured on an IBI-MDS Sciex Q-star or an FAB-MS
mass spectrometer or a Bruker APEX IV FT_MS. Elemental analy-
ses were performed on a Perkin–Elmer 240 C instrument. TLC
was performed on Silica Gel GF254 plates (Hai Yang Chemical
Factory, Qingdao, Shandong, PR China) detected by UV fluores-
cence quenching and by spraying with 10% H2SO4. Column chro-
4.6.1. E-3-Acetylhydrazono-1,2:4,5-di-O-isopropylidene-b-
D-
erythro-2-hexulopyranose 2a
Colorless crystal; mp 107–109 °C; ½a D25
¼ ꢀ276:3 (c 0.97, MeOH);
ꢁ
1H NMR (500 MHz, CDCl3): d 10.23 (s, 1H, NH), 4.98 (d, 1H, J4,5 6 Hz,
H-4), 4.77 (d, 1H, J1a,1b 9.0 Hz, H-1a), 4.33, (m, 1H, H-5), 4.27 (dd, 1H,
J6a,6b 13.5 Hz, H-6a), 4.09 (d, 1H, J6a,6b 13.5 Hz, H-6b), 4.08 (d, 1H,
J1a,1b 9.0 Hz, H-1b), 2.22 (s, 3H, Ac), 1.53, 1.43, 1.41, 1.40 (4s, 12H,
C(CH3)2); 13C NMR (125 MHz, CDCl3): d 173.3 (C@O), 141.1 (C-3),
113.0, 110.7 (C(CH3)2), 103.9 (C-2), 74.2 (C-6), 71.6 (C-4), 71.5 (C-
1), 59.1 (C-5), 26.9, 26.6, 26.1, 26.0 (C(CH3)2), 19.8 (COCH3); FAB-
MS: m/z 315.1 [M+H]+; Anal. Calcd for C14H22N2O6: C, 53.49; H,
7.05; N, 8.91. Found: C, 53.32; H, 7.28; N, 8.87.
matography was performed on Silica Gel
H 60 (Hai Yang
Chemical Factory, Qingdao, Shandong, PR China). Microwave reac-
tion was conducted using a Biotage-Initiator EXP EO Microwave
Synthesizer.
4.6.2. Z-3-Acetylhydrazono-1,2:4,5-di-O-isopropylidene-b-
D-
erythro-2-hexulopyranose 3a
White solid; mp 93–94 °C; ½a D25
ꢁ
¼ ꢀ208:0 (c 1.00, MeOH); 1H
NMR (500 MHz, CDCl3): d 10.05 (s, 1H, NH), 4.76 (d, 1H, J4,5
7.5 Hz, H-4), 4.47 (dd, 1H, H-5), 4.14 (dd, 2H, J1a,1b 10.0 Hz, H-1),
3.78 (m, 2H, J6a,6b 13.0 Hz, H-6), 2.26 (s, 3H, Ac), 1.68, 1.55, 1.51,
1.38 (4s, 12H, C(CH3)2); 13C NMR (125 MHz, CDCl3): d 173.1
(C@O), 139.1 (C-3), 112.5, 110.6 (C(CH3)2), 103.2 (C-2), 76.1 (C-4),
74.4 (C-5), 74.0 (C-1), 64.7 (C-6), 26.7, 26.1, 25.8, 25.1 (C(CH3)2),
19.6 (COCH3); FAB-MS: m/z 315.1 [M+H]+; Anal. Calcd for
C14H22N2O6: C, 53.49; H, 7.05; N, 8.91. Found: C, 53.57; H, 7.17;
N, 8.87.
4.2. General procedures for the preparation of compounds 2
and 3
AcOH (0.5 ml) was added slowly to a stirred solution of 1,2:4,5-
di-O-isopropylidene-b-D-erythro-2,3-hexodiulo-2,6-pyranose
(2.0 g, 7.75 mmol) and hydrazide (7.75 mmol) in MeOH (40.0 ml)
at room temperature. The reaction was monitored by TLC (ethyl
acetate/n-hexane, 1:8, v/v) until the reaction was completed in
about 12 h, and the solvent was then removed. The residual foam
was separated by column chromatography to obtain E isomer 2
and Z isomer 3, respectively.
4.6.3. E-3-Propionylhydrazono-1,2:4,5-di-O-isopropylidene-b-
D
-erythro-2-hexulopyranose 2b
Colorless crystal; mp 106–107 °C; ½a D25
¼ ꢀ237:7 (c 1.06, MeOH);
ꢁ
1H NMR (300 MHz, CDCl3): d 10.2 (s, 1H, NH), 4.97 (d, 1H, J4,5 6.0 Hz,
H-4), 4.77 (d, 1H, J1a,1b 9.0 Hz, H-1a), 4.32 (d, 1H, H-5), 4.26 (d, 1H, H-
1b), 4.10 (dd, 2H, J6a,6b 9.0 Hz, H-6), 2.61 (m, 2H, CH2CO), 1.55, 1.43,
1.41, 1.39(4s, 12H, C(CH3)2), 1.17 (t, 3H, CH3CH2,); 13C NMR(75 MHz,
CDCl3): d 176.4 (C@O), 140.7 (C-3), 112.9, 110.6 (C(CH3)2), 103.9 (C-
2), 74.1 (C-5), 71.7 (C-1), 71.6 (C-4), 59.1 (C-6), 26.9, 26.6, 26.1, 26.0,
25.6 (C(CH3)2, COCH2), 8.5 (CH2CH3); FAB-MS: m/z 328.8 [M+H]+;
Anal. Calcd for C15H24N2O6: C, 54.87; H, 7.37; N, 8.53. Found: C,
54.77; H, 7.11; N, 8.39.
4.3. General procedures for the preparation of compounds 4
and 5 in oil bath heating
A mixture of 2 and 3 (4.0 mmol) was dissolved in acetic anhy-
dride (5.0 ml) and boiled at 120 °C in an oil bath and stirred until
TLC (ethyl acetate/cyclohexane, 1:5, v/v) showed that the reactant
had disappeared. The solution was concentrated under reduced
pressure. The residual solvent was removed by toluene under re-
duced pressure for three times. The residual syrup was purified
by chromatography (ethyl acetate/cyclohexane, 1:8, v/v) to afford
4 and 5, respectively.
4.6.4. Z-3-Propionylhydrazono-1,2:4,5-di-O-isopropylidene-b-
D
-erythro-2-hexulopyranose 3b
White solid; mp 98–100 °C; ½a D25
ꢁ
¼ ꢀ160:7 (c 1.17, MeOH); 1H
4.4. General procedure for the preparation of compounds 4 and
5 under microwave irradiation
NMR (300 MHz, CDCl3): d 10.2 (s, 1H, NH), 4.97 (d, 1H, J4,5 6.0 Hz,
H-4), 4.76 (d, 1H, H-5), 4.30 (m, 2H, H-1), 4.10 (dd, 2H, J6a,6b
9.0 Hz, H-6), 2.61 (m, 2H, CH2CO), 1.52, 1.42, 1.41, 1.39 (4s, 12H,
C(CH3)2), 1.17 (t, 3H, CH3CH2); 13C NMR (75 MHz, CDCl3): d 176.5
(C@O), 140.7 (C-3), 112.9, 110.6 (C(CH3)2), 103.9 (C-2), 74.1 (C-5),
71.7 (C-1), 71.6 (C-4), 59.1 (C-6), 27.0, 26.6, 26.1, 26.0, 25.6
(C(CH3)2, COCH2), 8.5 (CH2CH3); FAB-MS: m/z 329.2 [M+H]+; Anal.
Calcd for C15H24N2O6: C, 54.87; H, 7.37; N, 8.53. Found: C, 54.90;
H, 7.21; N, 8.46.
A mixture of 2 and 3 (2.0 mmol) was dissolved in acetic anhy-
dride (1.0 ml) and boiled at 160 °C under microwave heating con-
ditions for 30 min in the microwave initiator. The solution was
concentrated and the residual solvent was removed by adding tol-
uene under reduced pressure three times. The residual syrup was
purified by chromatography (ethyl acetate/cyclohexane, 1:8, v/v)
to afford 4 and 5, respectively.

D. Han et al. / Tetrahedron: Asymmetry 20 (2009) 399–410
405
4.6.5. E-3-Butyrylhydrazono-1,2:4,5-di-O-isopropylidene-b-
erythro-2-hexulopyranose 2c
D
-
4.6.10. Z-3-Caproylhydrazono-1,2:4,5-di-O-isopropylidene-b-
D-
erythro-2-hexulopyranose 3e
White foam; ½a 2D5
ꢁ
¼ ꢀ220:0 (c 1.00, MeOH); 1H NMR (300 MHz,
Yellowish foam;
½
a 2D5
ꢁ
¼ ꢀ178:6 (c 1.03, MeOH); 1H NMR
CDCl3): d 10.16 (s, 1H, NH), 4.97 (d, 1H, J4,5 5.7 Hz, H-4), 4.76 (d, 1H,
H-1a), 4.32 (d, 1H, H-5), 4.26 (s, 1H, H-1b), 4.10 (dd, 2H, J6a,6b
9.0 Hz, H-6), 2.60 (m, 2H, CH2CO), 1.68 (m, 2H, CH2CH3), 1.51,
1.42, 1.41, 1.39 (4s, 12H, C(CH3)2), 0.98 (t, 3H, CH3CH2); 13C NMR
(300 MHz, CDCl3): d 10.16 (s, 1H, NH), 4.97 (d, 1H, J4,5 5.7 Hz, H-
4), 4.75 (d, 1H, J1a,1b 9.0 Hz, H-1a), 4.32 (d, 1H, H-5), 4.26 (d, 1H,
H-1b), 4.10 (dd, 2H, J6a,6b 9.0 Hz, H-6), 2.58 (m, 2H, CH2CO),
1.56–0.87 (m, 21H, C(CH3)2, C4H9); 13C NMR (75 MHz, CDCl3): d
175.9 (C@O), 140.6 (C-3), 112.9, 110.6 (C(CH3)2), 103.9 (C-2), 74.1
(C-5), 71.5 (C-1), 71.4 (C-4), 59.1 (C-6), 32.2, 31.5, 26.9, 26.5,
26.1, 26.0, 24.4, 22.4, 13.9 (C(CH3)2, C5H11); FAB-MS: 371.1
[M+H]+; Anal. Calcd for C18H30N2O6: C, 58.36; H, 8.16; N, 7.56.
Found: C, 58.53; H, 7.97; N, 7.31.
(75 MHz, CDCl3):
d 175.7 (C@O), 140.6 (C-3), 112.9, 110.6
(C(CH3)2), 103.9 (C-2), 74.1 (C-5), 71.6 (C-1), 71.5 (C-4), 59.1 (C-
6), 34.1, 27.0, 26.6, 26.1, 26.0, 18.1, 13.9 (C(CH3)2, C3H7); FAB-
MS: m/z 343.2 [M+H]+; Anal. Calcd for C16H26N2O6: C, 56.13; H,
7.65; N, 8.18. Found: C, 56.00; H, 7.68; N, 7.93.
4.6.6. Z-3-Butyrylhydrazono-1,2:4,5-di-O-isopropylidene-b-D-
4.6.11. E-3-Heptanoylhydrazono-1,2:4,5-di-O-isopropylidene-b-
erythro-2-hexulopyranose 3c
D
-erythro-2-hexulopyranose 2f
White foam; ½a 2D5
ꢁ
¼ ꢀ192:2 (c 1.02, MeOH); 1H NMR (300 MHz,
Yellowish foam;
½
a 2D5
ꢁ
¼ ꢀ195:9 (c 0.98, MeOH); 1H NMR
CDCl3): d 10.17 (s, 1H, NH), 4.97 (d, 1H, J4,5 5.7 Hz, H-4), 4.76 (d, 1H,
H-1a), 4.32 (d, 1H, H-5), 4.26 (s, 1H, H-1b), 4.10 (dd, 2H, J6a,6b 9.0
Hz, H-6), 2.57 (m, 2H, CH2CO), 1.68 (m, 2H, CH2CH3), 1.53, 1.42,
1.41, 1.39 (4s, 12H, C(CH3)2), 0.98 (t, 3H, CH3CH2); 13C NMR
(300 MHz, CDCl3): d 10.18 (s, 1H, NH), 5.01 (d, 1H, J4,5 5.4 Hz, H-
4), 4.75 (d, 1H, J1a,1b 8.7 Hz, H-1a), 4.33 (d, 1H, H-5), 4.27 (d, 1H,
H-1b), 4.07 (dd, 2H, J6a,6b 9.0 Hz, H-6), 2.57 (m, 2H, CH2CO),
1.65–0.88 (m, 23H, C(CH3)2, C5H11); 13C NMR (75 MHz, CDCl3): d
175.4 (C@O), 140.4 (C-3), 112.5, 110.2 (C(CH3)2), 103.6 (C-2), 73.9
(C-5), 71.3 (C-1), 71.2 (C-4), 58.8 (C-6), 31.9, 31.2, 28.7, 26.6,
26.2, 25.8, 25.6, 24.4, 22.1, 13.6 (C(CH3)2, C6H13); FAB-MS: m/z
385.3 [M+H]+; Anal. Calcd for C19H32N2O6: C, 59.36; H, 8.39; N,
7.29. Found: C, 59.39; H, 7.31; N, 7.25.
(75 MHz, CDCl3):
d 175.7 (C@O), 140.6 (C-3), 112.9, 110.6
(C(CH3)2), 103.9 (C-2), 74.1 (C-5), 71.6 (C-1), 71.5 (C-4), 59.1 (C-
6), 34.1, 27.0, 26.6, 26.1, 26.0, 18.1, 13.9 (C(CH3)2, C3H7); FAB-
MS: m/z 343.3 [M+H]+; Anal. Calcd for C16H26N2O6: C, 56.13; H,
7.65; N, 8.18. Found: C, 56.22, H, 7.50; N, 7.91.
4.6.7. E-3-Valerylhydrazono-1,2:4,5-di-O-isopropylidene-b-
erythro-2-hexulopyranose 2d
D-
4.6.12. Z-3-Heptanoylhydrazono-1,2:4,5-di-O-isopropylidene-b-
Yellowish foam;
½ ꢁ
a 2D5
¼ ꢀ211:8 (c 1.02, MeOH); 1H NMR
D
-erythro-2-hexulopyranose 3f
Yellowish foam;
½
a 2D5
ꢁ
¼ ꢀ170:9 (c 1.03, MeOH); 1H NMR
(300 MHz, CDCl3): d 10.16 (s, 1H, NH), 4.97 (d, 1H, J4,5 5.7 Hz, H-
4), 4.76 (d, 1H, H-1a), 4.32 (d, 1H, H-5), 4.26 (d, 1H, H-1b),
4.11(dd, 2H, J6a,6b 9.0 Hz, H-6), 2.57 (m, 2H, CH2CO), 1.63 (m, 4H,
C2H4CH3), 1.53, 1.43, 1.41, 1.39 (4s, 12H, C(CH3)2), 0.94 (m, 3H,
CH3CH2); 13C NMR (75 MHz, CDCl3): d 175.9 (C@O), 140.7 (C-3),
112.9, 110.6 (C(CH3)2), 103.9 (C-2), 74.1 (C-5), 71.6 (C-1), 71.5 (C-
4), 59.1 (C-6), 32.0, 27.0, 26.9, 26.6, 26.1, 26.0, 22.5, 13.8
(C(CH3)2, C4H9); FAB-MS: m/z 357.1 [M+H]+; Anal. Calcd for
C17H28N2O6: C, 57.29; H, 7.92; N, 7.86. Found: C, 57.23; H, 7.82;
N, 7.95.
(300 MHz, CDCl3): d 10.16 (s, 1H, NH), 4.98 (d, 1H, J4,5 5.7 Hz, H-
4), 4.75 (d, 1H, J1a,1b 9.0 Hz, H-1a), 4.33 (d, 1H, H-5), 4.26 (d, 1H,
H-1b), 4.10 (dd, 2H, J6a,6b 9.0 Hz, H-6), 2.58 (m, 2H, CH2CO),
1.68–0.86 (m, 23H, C(CH3)2, C5H11); 13C NMR (75 MHz, CDCl3): d
175.7 (C@O), 140.6 (C-3), 112.8, 110.5 (C(CH3)2), 103.8 (C-2), 74.1
(C-5), 71.6 (C-1), 71.5 (C-4), 59.0 (C-6), 32.2, 31.4, 28.9, 26.9,
26.4, 26.0, 25.9, 24.6, 22.4, 13.9 (C(CH3)2, C6H13); FAB-MS: m/z
385.4 [M+H]+. Anal. Calcd for C19H32N2O6: C, 59.36; H, 8.39; N,
7.29. Found: C, 59.42; H, 7.28; N, 7.33.
4.6.8. Z-3-Valerylhydrazono-1,2:4,5-di-O-isopropylidene-b-
erythro-2-hexulopyranose 3d
D-
4.6.13. E-3-Oxtanoylhydrazono-1,2:4,5-di-O-isopropylidene-b-
D
-erythro-2-hexulopyranose 2g
Yellowish foam;
½
a 2D5
ꢁ
¼ ꢀ167:6 (c 1.05, MeOH); 1H NMR
Yellowish foam;
½
a 2D5
ꢁ
¼ ꢀ234:3 (c 0.99, MeOH); 1H NMR
(300 MHz, CDCl3): d 10.18 (s, 1H, NH), 5.00 (d, 1H, J4,5 5.7 Hz, H-
4), 4.76 (d, 1H, H-1a), 4.34 (d, 1H, H-5), 4.25 (d, 1H, H-1b), 4.10
(dd, 2H, J6a,6b 9.0 Hz, H-6), 2.60 (m, 2H, CH2CO), 1.63 (m, 4H,
C2H4CH3), 1.52, 1.42, 1.41, 1.39 (4s, 12H, C(CH3)2), 0.94 (m, 3H,
CH3CH2); 13C NMR (75 MHz, CDCl3): d 175.6 (C@O), 140.6 (C-3),
112.7, 110.4 (C(CH3)2), 103.7 (C-2), 74.0 (C-5), 71.4 (C-1), 71.3 (C-
4), 59.0 (C-6), 31.8, 26.7, 26.4, 26.3, 25.9, 25.8, 22.3, 13.6
(C(CH3)2, C4H9); FAB-MS: m/z 357.0 [M+H]+; Anal. Calcd for
C17H28N2O6: C, 57.29; H, 7.92; N, 7.86. Found: C, 57.02; H, 7.94;
N, 7.80.
(300 MHz, CDCl3): d 10.18 (s, 1H, NH), 4.98 (d, 1H, J4,5 6.0 Hz,
H-4), 4.75 (d, 1H, J1a,1b 9.0 Hz, H-1a), 4.32 (s, 1H, H-5), 4.25 (s,
1H, H-1b), 4.09 (d, 2H, H-6), 2.57 (m, 2H, CH2CO), 1.65ꢂ0.85
(m, 25H, C(CH3)2, C6H13); 13C NMR (75 MHz, DMSO): d 174.7
(C@O), 141.5 (C-3), 111.7, 109.4 (C(CH3)2), 103.5 (C-2), 73.2 (C-
5), 72.6 (C-1), 68.5 (C-4), 59.9 (C-6), 31.7, 31.1, 28.7, 28.4, 26.9,
26.2, 25.8, 25.4, 24.3, 22.0, 13.8 (C(CH3)2, C7H15); FAB-MS: m/z
399.0 [M+H]+; Anal. Calcd for C20H34N2O6: C, 60.28; H, 8.60; N,
7.03. Found: C, 60.14; H, 8.78; N, 6.98.
4.6.14. Z-3-Oxtanoylhydrazono-1,2:4,5-di-O-isopropylidene-b-
4.6.9. E-3-Caproylhydrazono-1,2:4,5-di-O-isopropylidene-b-
erythro-2-hexulopyranose 2e
D-
D
-erythro-2-hexulopyranose 3g
a 2D5
ꢁ
¼ ꢀ192:2 (c 1.02, MeOH); 1H NMR
Yellowish foam;
½ ꢁ
a 2D5
¼ ꢀ192:0 (c 1.00, MeOH); 1H NMR
Yellowish foam;
½
(300 MHz, CDCl3): d 10.15 (s, 1H, NH), 4.97 (d, 1H, J4,5 5.7 Hz,
H-4), 4.75(d, 1H, J1a,1b 8.7 Hz, H-1a), 4.32 (d, 1H, H-5), 4.26 (d,
1H, H-1b), 4.10 (dd, 2H, J6a,6b 9.0 Hz, H-6), 2.57 (m, 2H, CH2CO),
1.68–0.86 (m, 25H, C(CH3)2, C6H13); 13C NMR (75 MHz, CDCl3): d
175.9 (C@O), 140.6 (C-3), 112.9, 110.6 (C(CH3)2), 103.9 (C-2),
74.1 (C-5), 71.6 (C-1), 71.5 (C-4), 59.1 (C-6), 32.3, 31.6, 29.3,
29.0, 27.0, 26.5, 26.1, 26.0, 24.7, 22.5, 14.0 (C(CH3)2, C7H15);
FAB-MS: m/z 398.8 [M+H]+; Anal. Calcd for C20H34N2O6: C,
60.28; H, 8.60; N, 7.03. Found: C, 60.19; H, 8.68; N, 6.94.
(300 MHz, CDCl3): d 10.16 (s, 1H, NH), 4.98 (d, 1H, J4,5 5.7 Hz, H-
4), 4.75 (d, 1H, J1a,1b 9.0 Hz, H-1a), 4.32(d, 1H, H-5), 4.27 (d, 1H,
H-1b), 4.10 (dd, 2H, J6a,6b 9.0 Hz, H-6), 2.58 (m, 2H, CH2CO),
1.68–0.87 (m, 21H, C(CH3)2, C4H9); 13C NMR (75 MHz, CDCl3): d
175.9 (C@O), 140.6 (C-3), 112.9, 110.6 (C(CH3)2), 103.9 (C-2),
74.1 (C-5), 71.6 (C-1), 71.5 (C-4), 59.1 (C-6), 32.2, 31.5, 26.9, 26.5,
26.1, 26.0, 24.4, 22.4, 13.9 (C(CH3)2, C5H11); FAB-MS: m/z 370.8
[M+H]+; Anal. Calcd for C18H30N2O6: C, 58.36; H, 8.16; N, 7.56.
Found: C, 58.14; H, 8.09; N, 7.29.

406
D. Han et al. / Tetrahedron: Asymmetry 20 (2009) 399–410
4.6.15. E-3-Nonanoylhydrazono-1,2:4,5-di-O-isopropylidene-b-
4.6.20. Z-3-Lauroylhydrazono-1,2:4,5-di-O-isopropylidene-b-
D-
D
-erythro-2-hexulopyranose 2h
erythro-2-hexulopyranose 3j
Yellowish foam;
½
a 2D5
ꢁ
¼ ꢀ210:1 (c 0.99, MeOH); 1H NMR
White wax; ½a 2D5
ꢁ
¼ ꢀ154:8 (c 0.93, MeOH); 1H NMR (300 MHz,
(300 MHz, CDCl3): d 10.16 (s, 1H, NH), 4.97 (d, 1H, J4,5 6.0 Hz, H-
4), 4.76 (d, 1H, J1a,1b 9.0 Hz, H-1a), 4.32 (d, 1H, H-5), 4.26 (d, 1H,
H-1b), 4.10 (dd, 2H, J6a,6b 9.0 Hz, H-6), 2.57 (m, 2H, CH2CO),
1.68–0.85 (m, 27H, C(CH3)2, C7H15); 13C NMR (75 MHz, CDCl3): d
175.9 (C@O), 140.7 (C-3), 112.9, 110.6 (C(CH3)2), 103.9 (C-2), 74.1
(C-5), 71.6 (C-1), 71.5 (C-4), 59.1 (C-6), 32.3, 31.8, 29.4, 29.3,
29.1, 27.0, 26.6, 26.1, 26.0, 24.8, 22.6, 14.0 (C(CH3)2, C8H17); FAB-
MS: m/z 413.1 [M+H]+; Anal. Calcd for C21H36N2O6: C, 61.14; H,
8.80; N, 6.79. Found: C, 61.38; H, 8.67; N, 6.68.
CDCl3): d 10.15 (s, 1H, NH), 4.97 (d, 1H, J4,5 5.7 Hz, H-4), 4.76 (d,
1H, J1a,1b 9.0 Hz, H-1a), 4.30 (s, 1H, H-5), 4.26 (s, 1H, H-1b), 4.10
(dd, 2H, J6a,6b 9.0 Hz, H-6), 2.57 (m, 2H, CH2CO), 1.68–0.86 (m,
33H, C(CH3)2, C10H21); 13C NMR (75 MHz, CDCl3): d 175.9 (C@O),
140.6 (C-3), 112.9, 110.6 (C(CH3)2), 103.9 (C-2), 74.1 (C-5), 71.6
(C-1), 71.5 (C-4), 59.1 (C-6), 32.3, 31.9, 29.6, 29.4, 29.3, 27.0,
26.6, 26.1, 26.0, 24.8, 22.7, 14.1 (C(CH3)2, C11H23); FAB-MS: m/z
455.0 [M+H]+; Anal. Calcd for C24H42N2O6 C, 63.41; H, 9.31; N,
6.16. Found: C, 63.32; H, 9.51; N, 6.00.
4.6.21. E-3-Palmitoylhydrazono-1,2:4,5-di-O-isopropylidene-b-
4.6.16. Z-3-Nonanoylhydrazono-1,2:4,5-di-O-isopropylidene-b-
D
-erythro-2-hexulopyranose 2k
D
-erythro-2-hexulopyranose 3h
White wax; ½a 2D5
ꢁ
¼ ꢀ193:9 (c 0.99, MeOH); 1H NMR (300 MHz,
Yellowish foam; ½a D25
ꢁ
¼ ꢀ193:9 (c 0.99, MeOH); 1H NMR
CDCl3): d 10.16 (s, 1H, NH), 4.98 (d, 1H, J4,5 5.4 Hz, H-4), 4.76 (d,
1H, J1a,1b 8.7 Hz, H-1a), 4.32 (m, 1H, H-5), 4.25 (s, 1H, H-1b), 4.07
(m, 2H, J6a,6b 8.7 Hz, H-6), 2.56 (m, 2H, CH2CO), 1.67–0.88 (m,
41H, C(CH3)2, C14H29); 13C NMR (75 MHz, CDCl3): d 175.9 (C@O),
140.6 (C-3), 112.9, 110.7 (C(CH3)2), 103.9 (C-2), 74.1 (C-5), 71.6
(C-1), 71.5 (C-4), 59.1 (C-6), 32.3, 31.9, 29.7, 29.5, 29.4, 29.3,
27.0, 26.6, 26.1, 26.0, 24.8, 22.7, 14.1 (C(CH3)2, C15H31); FAB-MS:
m/z 511.3 [M+H]+; Anal. Calcd for C28H50N2O6: C, 65.85; H, 9.87;
N, 5.49. Found: C, 65.80; H, 9.65; N, 5.53.
(300 MHz, CDCl3): d 10.16 (s, 1H, NH), 4.98 (d, 1H, J4,5 5.7 Hz,
H-4), 4.76 (d, 1H, J1a,1b 9.0 Hz, H-1a), 4.32 (d, 1H, H-5), 4.2 (d,
1H, H-1b), 4.10 (dd, 2H, J6a,6b 8.7 Hz, H-6), 2.57 (m, 2H, CH2CO),
1.68–0.85 (m, 27H, C(CH3)2, C7H15); 13C NMR (75 MHz, CDCl3): d
175.7 (C@O), 140.6 (C-3), 112.8, 110.5 (C(CH3)2), 103.8 (C-2),
74.1 (C-5), 71.5 (C-1), 71.4 (C-4), 59.0 (C-6), 32.2, 31.7, 29.3,
29.2, 29.0, 26.9, 26.5, 26.0, 25.9, 24.7, 22.5, 13.9 (C(CH3)2,
C8H17); FAB-MS: m/z 413.0 [M+H]+; Anal. Calcd for C21H36N2O6:
C, 61.14; H, 8.80; N, 6.79. Found: C, 61.20; H, 8.79; N, 6.66.
4.6.22. Z-3-Palmitoylhydrazono-1,2:4,5-di-O-isopropylidene-b-
4.6.17. E-3-Decanoylhydrazono-1,2:4,5-di-O-isopropylidene-b-
D
-erythro-2-hexulopyranose 3k
D
-erythro-2-hexulopyranose 2i
White wax; ½a 2D5
ꢁ
¼ ꢀ134:7 (c 1.01, MeOH); 1H NMR (300 MHz,
Yellowish foam;
½
a 2D5
ꢁ
¼ ꢀ196:6 (c 1.03, MeOH); 1H NMR
CDCl3): d 10.15 (s, 1H, NH), 4.97 (d, 1H, J4,5 5.4 Hz, H-4), 4.76 (d,
1H, J1a,1b 8.7 Hz, H-1a), 4.30 (d, 1H, H-5), 4.25 (s, 1H, H-1b), 4.10
(dd, 2H, J6a,6b 8.7 Hz, H-6), 2.57 (m, 2H, CH2CO), 1.68–0.86 (m,
41H, C(CH3)2, C14H29); 13C NMR (75 MHz, CDCl3): d 175.9 (C@O),
140.6 (C-3), 112.9, 110.7 (C(CH3)2), 103.9 (C-2), 74.2 (C-5), 71.6
(C-1), 71.5 (C-4), 59.1 (C-6), 32.3, 31.9, 29.7, 29.5, 29.4, 29.3,
27.0, 26.6, 26.1, 26.0, 24.8, 22.7, 14.1 (C(CH3)2, C15H31); ESI-TOF-
MS: m/z 511.5448 [M+H]+, 533.5283 (M+Na+); Anal. Calcd for
C28H50N2O6: C, 65.85; H, 9.87; N, 5.49. Found: C, 66.00; H, 9.72;
N, 5.49.
(300 MHz, CDCl3): d 10.16 (s, 1H, NH), 4.97 (d, 1H, J4,5 6.0 Hz, H-
4), 4.76 (d, 1H, J1a,1b 8.7 Hz, H-1a), 4.32 (d, 1H, H-5), 4.25 (s, 1H,
H-1b), 4.10 (dd, 2H, J6a,6b 8.7 Hz, H-6), 2.58 (m, 2H, CH2CO),
1.68–0.85 (m, 29H, C(CH3)2, C8H17); 13C NMR (75 MHz, CDCl3): d
175.8 (C@O), 140.6 (C-3), 112.9, 110.6 (C(CH3)2), 103.9 (C-2), 74.1
(C-5), 71.6 (C-1), 71.5 (C-4), 59.1 (C-6), 32.3, 31.8, 29.4, 29.2,
26.9, 26.5, 26.1, 26.0, 24.7, 22.6, 14.0 (C(CH3)2, C9H19); FAB-MS:
m/z 426.7 [M+H]+; Anal. Calcd for C22H38N2O6: C, 61.95; H, 8.98;
N, 6.57. Found: C, 61.68; H, 8.76; N, 6.33.
4.6.18. Z-3-Decanoylhydrazono-1,2:4,5-di-O-isopropylidene-b-
4.6.23. E-3-Stearoylhydrazono-1,2:4,5-di-O-isopropylidene-b-
D-
D
-erythro-2-hexulopyranose 3i
erythro-2-hexulopyranose 2l
a 2D5
ꢁ
¼ ꢀ157:2 (c 0.97, MeOH); 1H NMR
White wax; ½a 2D5
ꢁ
¼ ꢀ148:6 (c 1.05, MeOH); 1H NMR (300 MHz,
Yellowish foam;
½
(300 MHz, CDCl3): d 10.15 (s, 1H, NH), 4.97 (d, 1H, J4,5 5.7 Hz,
H-4), 4.76 (d, 1H, J1a,1b 9.0 Hz, H-1a), 4.32 (d, 1H, H-5), 4.25 (s,
1H, H-1b), 4.10 (dd, 2H, J6a,6b 8.7 Hz, H-6), 2.58 (m, 2H, CH2CO),
1.68–0.85 (m, 29H, C(CH3)2, C8H17); 13C NMR (75 MHz, CDCl3): d
175.9 (C@O), 140.6 (C-3), 112.9, 110.6 (C(CH3)2), 103.9 (C-2),
74.1 (C-5), 71.6 (C-1), 71.5 (C-4), 59.1 (C-6), 32.3, 31.8, 29.4,
29.2, 27.0, 26.7, 26.6, 26.1, 26.0, 24.8, 22.6, 14.1 (C(CH3)2,
C9H19); FAB-MS: m/z 427.1 [M+H]+; Anal. Calcd for C22H38N2O6:
C, 61.95; H, 8.98; N, 6.57. Found: C, 61.79; H, 8.79; N, 6.41.
CDCl3): d 10.15 (s, 1H, NH), 4.97 (d, 1H, J4,5 5.4 Hz, H-4), 4.76 (d,
1H, J1a,1b 8.7 Hz, H-1a), 4.30 (d, 1H, H-5), 4.26 (s, 1H, H-1b), 4.10
(dd, 2H, J6a,6b 9.0 Hz, H-6), 2.56 (m, 2H, CH2CO), 1.68–0.86 (m,
45H, C(CH3)2, C16H33); 13C NMR (75 MHz, CDCl3): d 175.9 (C@O),
140.6 (C-3), 112.9, 110.6 (C(CH3)2), 103.9 (C-2), 74.2 (C-5), 71.6
(C-1), 71.5 (C-4), 59.1 (C-6), 32.3, 31.9, 29.7, 29.5, 29.4, 29.3,
27.0, 26.6, 26.1, 26.0, 24.8, 22.7, 14.1 (C(CH3)2, C17H35); FAB-MS:
m/z 539.4 [M+H]+; Anal. Calcd for C30H54N2O6): C, 66.88; H,
10.10; N, 5.20. Found: C, 67.09; H, 9.96; N, 5.04.
4.6.19. E-3-Lauroylhydrazono-1,2:4,5-di-O-isopropylidene-b-
D-
4.6.24. Z-3-Stearoylhydrazono-1,2:4,5-di-O-isopropylidene-b-
D-
erythro-2-hexulopyranose 2j
erythro-2-hexulopyranose 3l
White wax; ½a 2D5
ꢁ
¼ ꢀ192:0 (c 1.00, MeOH); 1H NMR (300 MHz,
White wax; ½a 2D5
ꢁ
¼ ꢀ114:9 (c 1.01, MeOH); 1H NMR (300 MHz,
CDCl3): d 10.16 (s, 1H, NH), 4.97 (d, 1H, J4,5 5.7 Hz, H-4), 4.76 (d,
1H, J1a,1b 9.0 Hz, H-1a), 4.30 (m, 1H, H-5), 4.26 (s, 1H, H-1b), 4.10
(dd, 2H, J6a,6b 9.0 Hz, H-6), 2.57 (m, 2H, CH2CO), 1.55–0.86 (m,
33H, C(CH3)2, C10H21); 13C NMR (75 MHz, CDCl3): d 175.9 (C@O),
140.6 (C-3), 112.9, 110.6 (C(CH3)2), 103.9 (C-2), 74.1 (C-5), 71.6
(C-1), 71.5 (C-4), 59.1 (C-6), 32.3, 31.9, 29.6, 29.5, 29.4, 29.3,
27.0, 26.6, 26.1, 26.0, 24.8, 22.6, 14.1 (C(CH3)2, C11H23); FAB-MS:
m/z 454.9 [M+H]+; Anal. Calcd for C24H42N2O6: C, 63.41; H, 9.31;
N, 6.16. Found: C, 63.31; H, 9.45; N, 6.08.
CDCl3): d 10.15 (s, 1H, NH), 4.97 (d, 1H, J4,5 5.4 Hz, H-4), 4.76 (d,
1H, J1a,1b 8.7 Hz, H-1a), 4.30 (d, 1H, H-5), 4.25 (s, 1H, H-1b), 4.10
(dd, 2H, J6a,6b 9.3 Hz, H-6), 2.57 (m, 2H, CH2CO), 1.68–0.86 (m,
45H, C(CH3)2, C16H33); 13C NMR (75 MHz, CDCl3): d 175.9 (C@O),
140.6 (C-3), 112.9, 110.7 (C(CH3)2), 103.9 (C-2), 74.2 (C-5), 71.6
(C-1), 71.5 (C-4), 59.1 (C-6), 32.3, 31.9, 29.7, 29.6, 29.5, 29.4,
29.4, 29.3, 27.0, 26.6, 26.1, 26.0, 24.8, 22.7, 14.1 (C(CH3)2,
C17H35); FAB-MS: m/z 539.1 [M+H]+; Anal. Calcd for C30H54N2O6:
C, 66.88; H, 10.10; N, 5.20. Found: C, 67.01; H, 9.89; N, 4.92.

D. Han et al. / Tetrahedron: Asymmetry 20 (2009) 399–410
407
4.6.25. (2R,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
methyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dioxo-
lano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 4a
25.8, 25.6, 23.9, 19.0, 13.6 (C(CH3)2, COCH3, C3H7); FAB-MS: m/z
384.8 [M+H]+; Anal. Calcd for C18H28N2O7: C, 56.24; H, 7.34; N,
7.29. Found: C, 56.21; H, 7.30; N, 7.27.
Colorless crystal. mp 126–128 °C; ½a D25
¼ ꢀ11:2 (c 1.07, MeOH);
ꢁ
1H NMR (300 MHz, CDCl3): d 5.96 (d, 1H, J4,5 6.0 Hz, H-4), 4.38 (d,
1H, H-5), 4.26 (dd, 2H, J6a,6b 13.5 Hz, H-6), 4.01 (dd, 2H, J1a,1b
9.0 Hz, H-1), 2.07 (s, 3H, CH3C@N), 2.27 (s, 3H, Ac), 1.55, 1.51,
1.36 (4s, 12H, C(CH3)2); 13C NMR (75 MHz, CDCl3): d 168.1
(C@O), 153.9 (C@N), 114.1, 109.6 (C(CH3)2), 105.1 (C-2), 96.9 (C-
3), 72.5 (C-5), 71.0 (C-1), 68.2 (C-4), 59.6 (C-6), 26.3, 25.8, 25.6
(C(CH3)2), 23.8 (COCH3), 11.3 (CH3C@N); FAB-MS: m/z 356.5
[M+H]+; Anal. Calcd for C16H24N2O7: C, 53.92; H, 6.79; N, 7.86.
Found: C, 53.80; H, 6.75; N, 7.71.
4.6.30. (2S,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
propyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dioxo-
lano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 5c
Colorless foam.
½
a 2D5
ꢁ
¼ ꢀ33:0 (c 1.08, MeOH); 1H NMR
(300 MHz, CDCl3): d 5.97 (d, 1H, J4,5 6.0 Hz, H-4), 4.37 (dd, 1H, H-
5), 4.26 (dd, 2H, J6a,6b 13.5 Hz, H-6),3.99 (dd, 2H, J1a,1b 9.0 Hz, H-
1), 2.58 (m, 2H, CH2C@N), 2.07 (s, 3H, Ac), 1.65 (m, 2H, CH2CH3),
1.55, 1.50, 1.36, 1.35 (4s, 12H, C(CH3)2), 0.99, 0.97, 0.94 (t, 3H,
CH3CH2); 13C NMR (75 MHz, CDCl3): d 170.6 (C@O), 153.6 (C@N),
113.8, 109.5 (C(CH3)2), 105.1 (C-2), 96.8 (C-3), 72.4 (C-5), 71.2 (C-
1), 68.2 (C-4), 59.5 (C-6), 37.5, 26.3, 26.2, 25.8, 25.6, 17.9, 13.6,
11.2 (C(CH3)2, COCH3, C3H7); FAB-MS: m/z 384.8 [M+H]+; Anal.
Calcd for C18H28N2O7: C, 56.24; H, 7.34; N, 7.29. Found: C, 56.23;
H, 7.33; N, 7.25.
4.6.26. (2S,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
methyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dioxo-
lano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) (5a)
Colorless foam.
½
a 2D5
ꢁ
¼ ꢀ18:5 (c 0.96, MeOH); 1H NMR
(300 MHz, CDCl3): d 5.91 (d, 1H, J4,5 6.0 Hz, H-4), 4.33 (dd, 1H, H-
5), 4.21 (dd, 2H, J6a,6b 13.5 Hz, H-6), 3.96 (dd, 2H, J1a,1b 9.0 Hz, H-
1), 2.22 (s, 3H, CH3C@N), 2.03 (s, 3H, Ac), 1.51, 1.47, 1.33, 1.32
(4s, 12H, C(CH3)2); 13C NMR (75 MHz, CDCl3): d 168.1 (C@O),
153.9 (C@N), 114.0, 109.7 (C(CH3)2), 105.1 (C-2), 96.9 (C-3), 72.5
(C-5), 71.1 (C-1), 68.2 (C-4), 59.6 (C-6), 26.3, 25.8, 25.5 (C(CH3)2),
23.8 (COCH3), 11.3 (CH3C@N); FAB-MS: m/z 356.5 [M+H]+; Anal.
Calcd for C16H24N2O7: C, 53.92; H, 6.79; N, 7.86. Found: C, 53.73;
H, 6.74; N, 7.89.
4.6.31. (2R,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
butyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dioxo-
lano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 4d
Colorless foam.
½
a 2D5
ꢁ
¼ ꢀ29:8 (c 0.94, MeOH); 1H NMR
(300 MHz, CDCl3): d 5.97 (d, 1H, J4,5 6.0 Hz, H-4), 4.37 (dd, 1H, H-
5), 4.25 (m, 2H, J6a,6b 13.5 Hz, H-6), 3.99 (dd, 2H, J1a,1b 9.0 Hz, H-
1), 2.36 (m, 2H, CH2C@N), 2.27 (s, 3H, Ac), 1.75–0.91 (m, 19H,
C(CH3)2, C3H7); 13C NMR (75 MHz, CDCl3): d 168.1 (C@O), 157.0
(C@N), 113.9, 109.5 (C(CH3)2), 105.1 (C-2), 96.4 (C-3), 72.3 (C-5),
70.9 (C-1), 68.1 (C-4), 59.4 (C-6), 27.4, 26.3, 25.7, 25.4, 25.2, 23.8,
22.0, 13.4 (C(CH3)2, COCH3, C4H9); FAB-MS: m/z 398.9 [M+H]+;
Anal. Calcd for C19H30N2O7: C, 57.27; H, 7.59; N, 7.03. Found: C,
57.11; H, 7.50; N, 6.95.
4.6.27. (2R,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
ethyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dioxo-
lano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 4b
Colorless crystal. mp 99–102 °C; ½a D25
¼ ꢀ35:0 (c 1.03, MeOH);
ꢁ
1H NMR (300 MHz, CDCl3): d 5.98 (d, 1H, J4,5 6.0 Hz, H-4), 4.37
(dd, 1H, H-5), 4.26 (dd, 2H, J6a,6b 13.5 Hz, H-6), 3.99 (dd, 2H, J1a,1b
9.0 Hz, H-1), 2.38 (m, 2H, CH2C@N), 2.28 (s, 3H, Ac), 1.55, 1.51,
1.36 (4s, 12H, C(CH3)2), 1.26, 1.23, 1.21 (t, 3H, CH3CH2). 13C NMR
4.6.32. (2S,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
butyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dioxo-
lano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 5d
(75 MHz, CDCl3):
d
168.3 (C@O), 158.1 (C@N), 114.1, 109.7
Colorless foam. ½a D25
ꢁ
¼ ꢀ11:0 (c 1.09, MeOH); 1H NMR (300
(C(CH3)2), 105.2 (C-2), 96.7 (C-3), 72.4 (C-5), 71.0 (C-1), 68.3 (C-
4), 59.5 (C-6), 26.4, 25.8, 25.5 (C(CH3)2), 23.9 (COCH3), 19.2, 9.9
(C2H5); FAB-MS: m/z 370.7 [M+H]+; Anal. Calcd for C17H26N2O7:
C, 55.13; H, 7.08; N, 7.56. Found: C, 55.05; H, 6.92; N, 7.51.
MHz, CDCl3): d 5.97(d, 1H, J4,5 6.0 Hz, H-4), 4.37 (dd, 1H, H-5),
4.25 (dd, 2H, J6a,6b 13.5 Hz, H-6), 4.00 (dd, 2H, J1a,1b 9.0 Hz, H-1),
2.60 (m, 2H, CH2C@N), 2.07 (s, 3H, Ac), 1.73–0.89 (m, 19H,
C(CH3)2, C3H7); 13C NMR (75 MHz, CDCl3): d 168.1 (C@O), 157.1
(C@N), 113.9, 109.5 (C(CH3)2), 105.1 (C-2), 96.5 (C-3), 72.3 (C-5),
70.9 (C-1), 68.1 (C-4), 59.4 (C-6), 27.4, 26.3, 25.7, 25.4, 25.2, 23.7,
22.0, 13.4 (C(CH3)2, COCH3, C4H9); FAB-MS: m/z 399.0 [M+H]+;
Anal. Calcd for C19H30N2O7: C, 57.27; H, 7.59; N, 7.03. Found: C,
57.06; H, 7.46; N, 6.94.
4.6.28. (2S,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
ethyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dioxo-
lano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 5b
Colorless foam.
½
a 2D5
ꢁ
¼ ꢀ34:3 (c 1.04, MeOH); 1H NMR
(300 MHz, CDCl3): d 5.98 (d, 1H, J4,5 6.0 Hz, H-4), 4.37 (dd, 1H, H-
5), 4.26 (dd, 2H, J6a,6b 13.5 Hz, H-6), 3.99 (dd, 2H, J1a,1b 9.0 Hz, H-
1), 2.62 (m, 2H, CH2C@N), 2.07 (s, 3H, Ac), 1.55, 1.50, 1.37, 1.35
(4s, 12H, C(CH3)2), 1.14, 1.12, 1.09 (t, 3H, CH3CH2); 13C NMR
4.6.33. (2R,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
pentyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dioxo-
lano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 4e
(75 MHz, CDCl3):
d
171.5 (C@O), 153.8 (C@N), 114.0, 109.6
Colorless foam.
½
a 2D5
ꢁ
¼ ꢀ24:0 (c 1.00, MeOH); 1H NMR
(C(CH3)2), 105.2 (C-2), 96.8 (C-3), 72.5 (C-5), 71.1 (C-1), 68.3 (C-
4), 59.6 (C-6), 29.0, 26.3, 25.8, 25.5 (C(CH3)2, COCH3), 11.3, 8.7
(C2H5); FAB-MS: m/z 371.2 [M+H]+; Anal. Calcd for C17H26N2O7:
C, 55.13; H, 7.08; N, 7.56. Found: C, 55.20; H, 6.98; N, 7.47.
(300 MHz, CDCl3): d 5.97 (d, 1H, J4,5 6.0 Hz, H-4), 4.37 (dd, 1H, H-
5), 4.25 (m, 2H, J6a,6b 13.2 Hz, H-6), 3.99 (dd, 2H, J1a,1b 9.0 Hz, H-
1), 2.36 (m, 2H, CH2C@N), 2.27 (s, 3H, Ac), 1.67–0.89 (m, 21H,
C(CH3)2, C4H9); 13C NMR (75 MHz, CDCl3): d 168.1 (C@O), 157.0
(C@N), 113.9, 109.4 (C(CH3)2), 105.1 (C-2), 96.4 (C-3), 72.3 (C-5),
71.0 (C-1), 68.1 (C-4), 59.4 (C-6), 31.0, 26.3, 25.7, 25.4, 25.0, 23.7,
22.0, 13.7 (C(CH3)2, COCH3, C5H11); FAB-MS: m/z [M+H]+; Anal.
Calcd for C20H32N2O7: C, 58.24; H, 7.82; N, 6.79. Found: C, 58.19;
H, 7.80; N, 6.75.
4.6.29. (2R,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
propyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dioxo-
lano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 4c
Colorless foam. ½a D25
ꢁ
¼ ꢀ16:7 (c 1.05, MeOH); 1H NMR (300 MHz,
CDCl3): d 5.97 (d, 1H, J4,5 6.0 Hz, H-4), 4.36 (d, 1H, H-5), 4.25 (dd, 2H,
J6a,6b 13.2 Hz, H-6), 3.99(dd, 2H, J1a,1b 9.0 Hz, H-1), 2.32 (m, 2H,
CH2C@N), 2.28 (s, 3H, Ac), 1.68 (dd, 2H, CH3CH2,), 1.54, 1.51, 1.36
(4s, 12H, C(CH3)2), 1.01 (t, 3H, CH3CH2); 13C NMR (75 MHz, CDCl3):
d 168.3 (C@O), 157.0 (C@N), 114.1, 109.6 (C(CH3)2), 105.2 (C-2),
96.6 (C-3), 72.4 (C-5), 71.1 (C-1), 68.2 (C-4), 59.5 (C-6), 27.5, 26.4,
4.6.34. (2S,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
pentyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dioxo-
lano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 5e
Colorless foam.
½
a 2D5
ꢁ
¼ ꢀ43:5 (c 0.92, MeOH); 1H NMR
(300 MHz, CDCl3): d 5.97 (d, 1H, J4,5 6.0 Hz, H-4), 4.37 (dd, 1H, H-

408
D. Han et al. / Tetrahedron: Asymmetry 20 (2009) 399–410
5), 4.25 (dd, 2H, J6a,6b 13.2 Hz, H-6), 3.99 (dd, 2H, J1a,1b 9.0 Hz, H-1),
2.58 (m, 2H, CH2C@N), 2.07 (s, 3H, Ac), 1.59–0.86 (m, 21H, C(CH3)2,
C4H9); 13C NMR (75 MHz, CDCl3): d 171.0 (C@O), 153.7 (C@N),
114.0, 109.6 (C(CH3)2), 105.2 (C-2), 96.9 (C-3), 72.5 (C-5), 71.1 (C-
1), 68.3 (C-4), 59.6 (C-6), 35.6, 31.4, 26.3, 25.8, 25.6, 25.5, 24.2,
22.4, 13.9, 11.3 (C(CH3)2, COCH3, C5H11); FAB-MS: m/z 412.3
[M+H]+; Anal. Calcd for C20H32N2O7: C, 58.24; H, 7.82; N, 6.79.
Found: C, 58.22; H, 7.86; N, 6.71.
4.6.39. (2R,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
octyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dioxo-
lano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 4h
Colorless foam.
½
a 2D5
ꢁ
¼ ꢀ11:5 (c 1.04, MeOH); 1H NMR
(300 MHz, CDCl3): d 5.97 (d, 1H, J4,5 6.0 Hz, H-4), 4.37 (dd, 1H, H-
5), 4.25 (dd, 2H, J6a,6b 13.2 Hz, H-6), 3.99 (dd, 2H, J1a,1b 9.0 Hz, H-
1), 2.35 (m, 2H, CH2C@N), 2.27 (s, 3H, Ac), 1.71–0.86 (m, 27H,
C(CH3)2, C7H15); 13C NMR (75 MHz, CDCl3): d 168.2 (C@O), 157.2
(C@N), 114.0, 109.6 (C(CH3)2), 105.2 (C-2), 96.5 (C-3), 72.4 (C-5),
71.0 (C-1), 68.2 (C-4), 59.5 (C-6), 31.7, 29.6, 29.0, 26.4, 25.8, 25.5,
23.8, 22.5, 14.0, (C(CH3)2, COCH3, C8H17); FAB-MS: m/z 455.2
[M+H]+; Anal. Calcd for C23H38N2O7: C, 60.77; H, 8.43; N, 6.16.
Found: C, 60.74; H, 8.38; N, 6.05.
4.6.35. (2R,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
hexyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dioxo-
lano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 4f
Colorless foam. ½a D25
ꢁ
¼ ꢀ8:4 (c 0.95, MeOH); 1H NMR (300 MHz,
CDCl3): d 5.97 (d, 1H, J4,5 6.0 Hz, H-4), 4.37 (d, 1H, H-5), 4.25 (dd,
2H, J6a,6b 13.5 Hz, H-6), 3.98 (dd, 2H, J1a,1b 9.0 Hz, H-1), 2.35 (m,
2H, CH2C@N), 2.27 (s, 3H, Ac), 1.69–0.87 (m, 23H, C(CH3)2,
C5H11); 13C NMR (75 MHz, CDCl3): d 168.1 (C@O), 157.1 (C@N),
113.8, 109.4 (C(CH3)2), 105.0 (C-2), 96.4 (C-3), 72.2 (C-5), 70.9 (C-
1), 68.0 (C-4), 59.3 (C-6), 31.0, 28.5, 26.2, 25.7, 25.4, 25.3, 23.6,
22.2, 13.8 (C(CH3)2, COCH3, C6H13); FAB-MS: m/z 427.0 [M+H]+;
Anal. Calcd for C21H34N2O7: C, 59.14; H, 8.04; N, 6.57. Found: C,
59.06; H, 7.92; N, 6.55.
4.6.40. (2S,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
octyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dioxo-
lano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 5h
Colorless foam.
½
a 2D5
ꢁ
¼ ꢀ30:5 (c 1.05, MeOH); 1H NMR
(300 MHz, CDCl3): d 5.97 (d, 1H, J4,5 6.0 Hz, H-4), 4.37 (dd, 1H,
H-5), 4.25 (dd, 2H, J6a,6b 13.2 Hz, H-6), 3.99 (dd, 2H, J1a,1b
9.0 Hz, H-1), 2.57 (m, 2H, CH2C@N), 2.07 (s, 3H, Ac), 1.64–0.85
(m, 27H, C(CH3)2, C7H15); 13C NMR (75 MHz, CDCl3): d 170.9
(C@O), 153.7 (C@N), 113.9, 109.6 (C(CH3)2), 105.1 (C-2), 96.9
(C-3), 72.5 (C-5), 71.0 (C-1), 68.2 (C-4), 59.5 (C-6), 35.6, 31.7,
29.2, 29.1, 29.0, 26.3, 25.9, 25.8, 25.6, 25.5, 24.5, 22.5, 14.0,
11.2 (C(CH3)2, COCH3, C8H17); FAB-MS: m/z 455.0 [M+H]+; Anal.
Calcd for C23H38N2O7: C, 60.77; H, 8.43; N, 6.16. Found: C,
60.65; H, 8.37; N, 6.11.
4.6.36. (2S,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
hexyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dioxo-
lano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 5f
Colorless foam.
½
a 2D5
ꢁ
¼ ꢀ25:0 (c 1.12, MeOH); 1H NMR
(300 MHz, CDCl3): d 5.95 (d, 1H, J4,5 6.0 Hz, H-4), 4.37 (d, 1H, H-
5), 4.25 (dd, 2H, J6a,6b 13.5 Hz, H-6), 3.99 (dd, 2H, J1a,1b 9.0 Hz, H-
1), 2.65 (m, 2H, CH2C@N), 2.07 (s, 3H, Ac), 1.63–0.86 (m, 23H,
C(CH3)2, C5H11); 13C NMR (75 MHz, CDCl3): d 170.8 (C@O), 153.6
(C@N), 113.7, 109.4 (C(CH3)2), 105.0 (C-2), 96.7 (C-3), 72.3 (C-5),
70.9 (C-1), 68.1 (C-4), 59.4 (C-6), 35.5, 31.4, 28.7, 26.1, 25.6, 25.5,
25.4, 24.3, 22.3, 13.8, 11.1 (C(CH3)2, COCH3, C6H13); FAB-MS: m/z
427.0 [M+H]+; Anal. Calcd for C21H34N2O7: C, 59.14; H, 8.04; N,
6.57. Found: C, 58.99; H, 7.97; N, 6.51.
4.6.41. (2R,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
nonyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dioxo-
lano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 4i
Colorless foam.
½
a 2D5
ꢁ
¼ ꢀ33:0 (c 0.97, MeOH); 1H NMR
(300 MHz, CDCl3): d 5.98 (d, 1H, J4,5 6.0 Hz, H-4), 4.37 (dd, 1H, H-
5), 4.25 (dd, 2H, J6a,6b 13.2 Hz, H-6), 3.99 (dd, 2H, J1a,1b 9.0 Hz, H-
1), 2.34 (m, 2H, CH2C@N), 2.27 (s, 3H, Ac), 1.69–0.86 (m, 29H,
C(CH3)2, C8H17); 13C NMR (75 MHz, CDCl3): d 171.0 (C@O), 153.7
(C@N), 114.0, 109.6 (C(CH3)2), 105.2 (C-2), 96.9 (C-3), 72.5 (C-5),
71.1 (C-1), 68.3 (C-4), 59.6 (C-6), 35.7, 31.8, 29.4, 29.3, 29.2, 26.3,
25.8, 25.6, 25.5, 24.5, 22.6, 14.1, 11.3 (C(CH3)2, COCH3, C9H19);
FAB-MS: m/z 469.0 [M+H]+; Anal. Calcd for C24H40N2O7: C, 61.52;
H, 8.60; N, 5.98. Found: C, 61.48; H, 8.51; N, 5.92.
4.6.37. (2R,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
heptyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dioxo-
lano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 4g
Colorless foam.
½
a 2D5
ꢁ
¼ ꢀ46:3 (c 0.95, MeOH); 1H NMR
(300 MHz, CDCl3): d 5.97 (d, 1H, J4,5 6.0 Hz, H-4), 4.37 (dd, 1H,
H-5), 4.25 (m, 2H, J6a,6b 13.5 Hz, H-6), 3.99 (dd, 2H, J1a,1b 9.0 Hz,
H-1), 2.34 (m, 2H, CH2C@N), 2.27 (s, 3H, Ac), 1.68–0.86 (m, 25H,
C(CH3)2, C6H13); 13C NMR (75 MHz, CDCl3): d 168.3 (C@O), 157.2
(C@N), 114.1, 109.7 (C(CH3)2), 105.2 (C-2), 96.6 (C-3), 72.5 (C-5),
71.1 (C-1), 68.2 (C-4), 59.5 (C-6), 31.9, 29.5, 29.4, 29.3, 29.1,
29.0, 26.5, 25.9 25.6, 23.9, 22.6, 14.1 (C(CH3)2, COCH3, C7H15);
FAB-MS: m/z 442.0 [M+H]+; Anal. Calcd for C22H36N2O7: C,
59.98; H, 8.24; N, 6.36. Found: C, 59.96; H, 8.20; N, 6.33.
4.6.42. (2S,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
nonyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dioxo-
lano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 5i
Colorless foam.
½
a 2D5
ꢁ
¼ ꢀ53:6 (c 0.97, MeOH); 1H NMR
(300 MHz, CDCl3): d 5.97 (d, 1H, J4,5 6.0 Hz, H-4), 4.37 (dd, 1H,
H-5), 4.25 (dd, 2H, J6a,6b 13.2 Hz, H-6), 3.99 (dd, 2H, J1a,1b 9.0
Hz, H-1), 2.59 (m, 2H, CH2C@N), 2.07 (s, 3H, Ac), 1.63–0.85 (m,
29H, C(CH3)2, C8H17); 13C NMR (75 MHz, CDCl3):
d 171.0
(C@O), 153.7 (C@N), 114.0, 109.6 (C(CH3)2), 105.2 (C-2), 96.9
(C-3), 72.5 (C-5), 71.1 (C-1), 68.3 (C-4), 59.6 (C-6), 35.7, 31.8,
29.4, 29.3, 29.2, 26.3, 25.8, 25.6, 25.5, 24.5, 22.6, 14.1, 11.3
(C(CH3)2, COCH3, C9H19); FAB-MS: m/z 469.1 [M+H]+; Anal. Calcd
for C24H40N2O7: C, 61.52; H, 8.60; N, 5.98. Found: C, 61.50; H,
8.59; N, 5.93.
4.6.38. (2S,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
heptyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dioxo-
lano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 5g
Colorless foam.
½
a 2D5
ꢁ
¼ ꢀ47:3 (c 1.10, MeOH); 1H NMR
(300 MHz, CDCl3): d 5.96 (d, 1H, J4,5 6.0 Hz, H-4), 4.36 (dd, 1H, H-
5), 4.25 (dd, 2H, J6a,6b 13.2 Hz, H-6), 3.98 (dd, 2H, J1a,1b 9.0 Hz, H-
1), 58 (m, 2H, CH2C@N), 2.06 (s, 3H, Ac), 1.65–0.84 (m, 25H,
C(CH3)2, C6H13); 13C NMR (75 MHz, CDCl3): d 168.3 (C@O), 157.2
(C@N), 114.1, 109.7 (C(CH3)2), 105.2 (C-2), 96.6 (C-3), 72.5 (C-5),
71.1 (C-1), 68.2 (C-4), 59.6 (C-6), 31.5, 29.0, 28.7, 26.5, 25.9, 25.6,
23.9, 22.5, 14.0 (C(CH3)2, COCH3, C7H15); FAB-MS: m/z 441.9
[M+H]+; Anal. Calcd for C22H36N2O7: C, 59.98; H, 8.24; N, 6.36.
Found: C, 59.94; H, 8.23; N, 6.35.
4.6.43. (2R,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
undecyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dioxo-
lano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 4j
Yellowish foam.
½
a 2D5
ꢁ
¼ ꢀ23:5 (c 1.36, MeOH); 1H NMR
(300 MHz, CDCl3): d 5.97 (d, 1H, J4,5 6.0 Hz, H-4), 4.36 (dd, 1H,
H-5), 4.24 (dd, 2H, J6a,6b 13.2 Hz, H-6), 3.98 (dd, 2H, J1a,1b
9.0 Hz, H-1), 2.32 (m, 2H, CH2C@N), 2.26 (s, 3H, Ac), 1.67–0.86
(m, 33H, C(CH3)2, C10H21); 13C NMR (75 MHz, CDCl3): d 168.2

D. Han et al. / Tetrahedron: Asymmetry 20 (2009) 399–410
409
(C@O), 157.1 (C@N), 114.0, 109.6 (C(CH3)2), 105.2 (C-2), 96.5 (C-
4.6.48. (2S,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
3), 72.4 (C-5), 71.0 (C-1), 68.2 (C-4), 59.5 (C-6), 31.8, 29.5, 29.3,
29.2, 29.0, 28.9, 27.3, 26.4, 25.8, 25.5, 25.4, 23.8, 22.6, 14.0
(C(CH3)2, COCH3, C11H23); FAB-MS: m/z 496.6 [M+H]+; Anal. Calcd
for C26H44N2O7: C, 62.88; H, 8.93; N, 5.64. Found: C, 62.69; H,
8.80; N, 5.53.
heptadecyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dio-
xolano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 5l
White wax. ½a 2D5
ꢁ
¼ ꢀ24:0 (c 0.5, MeOH); 1H NMR (300 MHz,
CDCl3): d 5.97 (d, 1H, J4,5 6.0 Hz, H-4), 4.36 (dd, 1H, H-5), 4.24
(dd, 2H, J6a,6b 13.2 Hz, H-6), 3.98 (dd, 2H, J1a,1b 9.0 Hz, H-1), 2.62
(m, 2H, CH2C@N), 2.07 (s, 3H, Ac), 1.65–0.86 (m, 45H, C(CH3)2,
C16H33); 13C NMR (75 MHz, CDCl3): d 168.2 (C@O), 157.1 (C@N),
114.1, 109.6 (C(CH3)2), 105.2 (C-2), 96.5 (C-3), 72.5 (C-5), 71.0
(C-1), 68.2 (C-4), 59.5 (C-6), 31.8, 29.5, 29.3, 29.2, 29.0, 28.9,
27.3, 26.4, 25.8, 25.5, 25.4, 23.8, 22.6, 14.0, 11.2, 11.1 (C(CH3)2,
COCH3, C17H35); FAB-MS: m/z 581.3 [M+H]+; Anal. Calcd for
C32H56N2O7: C, 66.18; H, 9.72; N, 4.82. Found: C, 66.33; H, 9.91;
N, 4.65.
4.6.44. (2S,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
undecyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dioxo-
lano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 5j
Yellowish foam.
½
a 2D5
ꢁ
¼ ꢀ39:3 (c 1.12, MeOH); 1H NMR
(300 MHz, CDCl3): d 5.97 (d, 1H, J4,5 6.0 Hz, H-4), 4.37 (dd, 1H, H-
5), 4.25 (dd, 2H, J6a,6b 13.2 Hz, H-6), 3.99 (dd, 2H, J1a,1b 9.0 Hz, H-
1), 2.58 (m, 2H, CH2C@N), 2.07 (s, 3H, Ac), 1.64–0.86 (m, 33H,
C(CH3)2, C10H21); 13C NMR (75 MHz, CDCl3): d 170.9 (C@O), 153.7
(C@N), 113.9, 109.5 (C(CH3)2), 105.2 (C-2), 96.9 (C-3), 72.5 (C-5),
71.0 (C-1), 68.2 (C-4), 59.5 (C-6), 35.6, 31.8, 29.5, 29.4, 29.3, 29.2,
29.1, 26.4, 26.3, 26.2, 25.9, 25.8, 25.7, 25.6, 25.5, 24.5, 22.6, 14.0,
11.3, 11.2 (C(CH3)2, COCH3, C11H23); FAB-MS: m/z 496.9 [M+H]+;
Anal. Calcd for C26H44N2O7: C, 62.88; H, 8.93; N, 5.64. Found: C,
62.65; H, 8.81; N, 5.50.
4.6.49. N-Acetyl-3-acetylhydrazono-1,2:4,5-di-O-isopropy-
lidene-b-D-erythro-2-hexulopyranose 6a
Colorless foam; 1H NMR (300 MHz, CDCl3): d 4.72 (d, 1H, J4,5
6.3 Hz, H-4), 4.65 (d, 1H, J1a,1b 9.3 Hz, H-1a), 4.38 (dd, 1H, H-5),
4.22 (dd, 1H, J6a,6b 13.2 Hz, H-6a), 4.03 (d, 1H, H-1b), 3.99 (d, 1H,
H-6b), 2.42 (s, 6H, Ac), 1.53, 1.45, 1.37, 1.32 (4s, 12H, C(CH3)2);
13C NMR (75 MHz, CDCl3): d 169.6 (C@O), 166.8 (C-3), 112.7,
110.3 (C(CH3)2), 104.3 (C-2), 75.4 (C-5), 72.4 (C-4), 72.1 (C-1),
61.9 (C-6), 26.5, 26.4, 26.0, 26.0 (C(CH3)2), 25.8 (COCH3); HR-ESI-
MS: Calcd for C16H25N2O7: 357.1662 [M+H]+. Found:
357.1667[M+H]+.
4.6.45. (2R,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
pentadecyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-diox-
olano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 4k
White wax. ½a 2D5
ꢁ
¼ ꢀ3:6 (c 1.11, MeOH); 1H NMR (300 MHz,
CDCl3): d 5.97 (d, 1H, J4,5 6.0 Hz, H-4), 4.37 (dd, 1H, H-5), 4.25
(dd, 2H, J6a,6b 13.2 Hz, H-6), 3.99 (dd, 2H, H-1, J1a,1b 9.0 Hz, H-
1), 2.34 (m, 2H, CH2C@N), 2.27 (s, 3H, Ac), 1.67–0.86 (m, 41H,
C(CH3)2, C14H29); 13C NMR (75 MHz, CDCl3): d 168.3 (C@O),
157.2 (C@N), 114.1, 109.6 (C(CH3)2), 105.2 (C-2), 96.6 (C-3),
72.4 (C-5), 71.1 (C-1), 68.2 (C-4), 59.5 (C-6), 31.9, 29.6, 29.5,
29.4, 29.1, 27.3, 26.4, 25.9, 25.5, 23.9, 22.6, 14.1 (C(CH3)2, COCH3,
C15H31); FAB-MS: m/z 552.9 [M+H]+; Anal. Calcd for C30H52N2O7:
C, 65.19; H, 9.48; N, 5.07. Found: C, 64.98; H, 9.22; N, 5.17.
4.6.50. N-Acetyl-3-valerylhydrazono-1,2:4,5-di-O-isopropy-
lidene-b-D-erythro-2-hexulopyranose 6d
Colorless foam; 1H NMR (300 MHz, CDCl3): d 4.72 (d, 1H, J4,5 6.3
Hz, H-4), 4.64 (d, 1H, J1a,1b 9.3 Hz, H-1a), 4.38 (dd, 1H, H-5), 4.22
(dd, 1H, J6a,6b 13.2 Hz, H-6a), 4.08 (d, 1H, H-1b), 3.98 (d, 1H, H-
6b), 2.57 (m, 2H, CH2CO), 2.43 (s, 6H, Ac), 1.65 (m, 4H, C2H4CH3),
1.55, 1.44, 1.42, 1.39 (4s, 12H, C(CH3)2), 0.90 (m, 3H, CH3CH2);
13C NMR (75 MHz, CDCl3): d 170.8 (COC15H31), 169.9 (C@O),
166.9 (C-3), 112.8, 110.6 (C(CH3)2), 104.2 (C-2), 74.7 (C-6), 72.0
(C-4), 71.8 (C-1), 62.0 (C-5), 37.5, 32.1, 31.6, 26.9, 26.5, 26.1,
26.0, 24.4, 22.4, 13.9 (C(CH3)2, C5H11); HR-ESI-MS: Calcd for
C19H31N2O7: 399.2131 [M+H]+. Found: 399.2124 [M+H]+.
4.6.46. (2S,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
pentadecyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-dio-
xolano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 5k
White wax. ½a 2D5
ꢁ
¼ ꢀ11:3 (c 1.06, MeOH); 1H NMR (300 MHz,
4.6.51. N-Acetyl-3-palmitoylhydrazono-1,2:4,5-di-O-isopropy-
lidene-b-D-erythro-2-hexulopyranose 6k
CDCl3): d 5.97 (d, 1H, J4,5 6.0 Hz, H-4), 4.36 (m, 1H, H-5), 4.25
(dd, 2H, J6a,6b 13.2 Hz, H-6), 3.99 (dd, 2H, J1a,1b 9.0 Hz, H-1), 2.59
(m, 2H, CH2C@N), 2.07 (s, 3H, Ac), 1.63–0.86 (m, 41H, C(CH3)2,
C14H29); 13C NMR (75 MHz, CDCl3): d 170.9 (C@O), 153.7 (C@N),
113.9, 109.5 (C(CH3)2), 105.2 (C-2), 96.9 (C-3), 72.5 (C-5), 71.0 (C-
1), 68.2 (C-4), 59.5 (C-6), 35.6, 31.8, 29.5, 29.4, 29.3, 29.2, 29.1,
26.4, 26.3, 26.2, 25.9, 25.8, 25.7, 25.6, 25.5, 24.5, 22.6, 14.0, 11.3,
11.2 (C(CH3)2, COCH3, C15H31); FAB-MS: m/z 553.3 [M+H]+; Anal.
Calcd for C30H52N2O7: C, 65.19; H, 9.48; N, 5.07. Found: C, 65.37;
H, 9.50; N, 5.02.
Colorless foam; 1H NMR (300 MHz, CDCl3): d 4.70 (d, 1H, J4,5
6.3 Hz, H-4), 4.61 (d, 1H, J1a,1b 9.3 Hz, H-1a), 4.39 (dd, 1H, H-5),
4.20 (dd, 1H, J6a,6b 13.2 Hz, H-6a), 4.15 (d, 1H, H-1b), 3.97 (d, 1H,
H-6b), 2.57 (m, 2H, CH2CO), 2.43 (s, 3H, Ac), 1.65–0.86 (m, 41H,
C(CH3)2, C14H29); 13C NMR (75 MHz, CDCl3): d 172.9 (COC15H31),
169.6 (COCH3), 166.8 (C-3), 112.7, 110.3 (C(CH3)2), 104.3 (C-2),
75.4 (C-6), 72.4 (C-4), 72.1 (C-1), 61.9 (C-5), 26.5, 26.4, 26.0, 26.0
(C(CH3)2), 25.8 (COCH3); 167.0 (C-3), 112.7, 110.4 (CMe2), 104.4
(C-2), 75.6 (C-5), 72.7 (C-4), 71.8 (C-1), 62.2 (C-6), 37.6, 31.9,
29.7, 29.5, 29.4, 29.3, 29.2, 26.6, 26.4, 26.2, 26.0, 25.8, 24.3, 22.7,
14.1(C(CH3)2, C15H31); HR-ESI-MS: Calcd for C30H53N2O7:
553.3853 [M+H]+. Found: 553.3857 [M+H]+.
4.6.47. (2R,3a0R,60S,7a0R)-3-Acetyl-20,20,200,200-tetramethyl-5-
heptadecyl-2,3-dihydro-1,3,4-oxadiazole-2-spiro-70-{10,30-diox-
olano[4,5-c]pyrano}-60-spiro-400-(100,300-diaoxolane) 4l
White wax. ½a 2D5
ꢁ
¼ ꢀ12:6 (c 0.95, MeOH); 1H NMR (300 MHz,
Acknowledgment
CDCl3): d 5.97 (d, 1H, J4,5 6.0 Hz, H-4), 4.35 (dd, 1H, H-5), 4.24
(dd, 2H, J6a,6b 13.2 Hz, H-6), 3.98 (dd, 2H, J1a,1b 9.0 Hz, H-1),
2.34 (m, 2H, CH2C@N), 2.27 (s, 3H, Ac), 1.67–0.86 (m, 45H,
C(CH3)2, C16H33); 13C NMR (75 MHz, CDCl3): d 168.2 (C@O),
157.1 (C@N), 114.0, 109.6 (C(CH3)2), 105.2 (C-2), 96.5 (C-3),
72.4 (C-5), 71.0 (C-1), 68.2 (C-4), 59.5 (C-6), 31.8, 29.5, 29.3,
29.2, 29.0, 28.9, 27.3, 26.4, 25.8, 25.5, 25.4, 23.8, 22.6, 14.0
(C(CH3)2, COCH3, C17H35). FAB-MS: m/z 580.7 [M+H]+; Anal. Calcd
for C32H56N2O7: C, 66.18; H, 9.72; N, 4.82. Found: C, 65.99; H,
9.70; N, 4.77.
This work was supported by the National Natural Science Foun-
dation of China (20732001, 30672525).
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