Microwave-assisted efficient synthesis of glucose-based 3-acetyl-5-alkyl-2,3-dihydro-1,3,4-oxadiazole derivatives catalyzed by sodium acetate

Article abstract of DOI:10.1016/j.carres.2009.07.009

A novel approach to synthesize glucose-based 3-acetyl-5-alkyl-2,3-dihydro-1,3,4-oxadiazoles with the assistance of microwave irradiation was developed. The effects of different catalysts on the heterocyclization process were investigated, and the reaction conditions were optimized, with NaOAc emerging as the catalyst of choice. Under the optimized conditions, a series of novel 3-acetyl-5-alkyl-2,3-dihydro-1,3,4-oxadiazole derivatives 4 and 5 were successfully synthesized from hydrazones 2 and 3. The absolute configurations of hydrazones 2, 3 and oxadiazoles 4, 5 were confirmed by NMR spectroscopic data. The ratio of the isomers 4 and 5 was ～1:1.

Full text of DOI:10.1016/j.carres.2009.07.009

Carbohydrate Research 344 (2009) 2113–2119
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Microwave-assisted efficient synthesis of glucose-based 3-acetyl-5-alkyl-2,3-
dihydro-1,3,4-oxadiazole derivatives catalyzed by sodium acetate
*
Lin-Na Wang, Dong Han, Fei-Fei Xu, Xiang-Bao Meng, Zhong-Jun Li
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 14 May 2009
Received in revised form 15 July 2009
Accepted 23 July 2009
Available online 28 July 2009
A novel approach to synthesize glucose-based 3-acetyl-5-alkyl-2,3-dihydro-1,3,4-oxadiazoles with the
assistance of microwave irradiation was developed. The effects of different catalysts on the heterocycli-
zation process were investigated, and the reaction conditions were optimized, with NaOAc emerging as
the catalyst of choice. Under the optimized conditions, a series of novel 3-acetyl-5-alkyl-2,3-dihydro-
1,3,4-oxadiazole derivatives 4 and 5 were successfully synthesized from hydrazones 2 and 3. The abso-
lute configurations of hydrazones 2, 3 and oxadiazoles 4, 5 were confirmed by NMR spectroscopic data.
The ratio of the isomers 4 and 5 was ꢀ1:1.
Keywords:
Carbohydrate
1,3,4-Oxadiazole derivatives
Antitumor activity
Microwave irradiation
Cyclization
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
tempted to improve the conditions of the reaction by the addition
of catalysts such as a Lewis acid, a base, and an acetate.27
1,3,4-Oxadiazole compounds have shown a wide array of phar-
macological activities, including antibacterial, anti-fungal, analge-
sic, anti-inflammatory, anti-hypertension, and muscle-relaxing
activities. Consequently, they have attracted increasing attention
in the field of drug discovery.1–7 Various modifications of the struc-
ture of 1,3,4-oxadiazoles have been carried out,8–10 to increase
their hydrophobicity and bioavailability and transport across the
intestinal membrane and the blood–brain barrier.11–15 1,2:5,6-
2. Results and discussion
D
-Glucose reacted in anhydrous acetone with catalysis by zinc
chloride to obtain 1,2:5,6-di-O-isopropylidene- -glucofuranose,
which was then oxidized by PDC and acetic anhydride to afford
1,2:5,6-di-O-isopropylidene- -ribo-hexos-3-ulose (1) in 52.5%
a-D
a-D
yield.28 Catalyzed by acetic acid, compound 1 reacted with hydra-
zines in methanol over a range of 12–24 h to give a mixture of E/Z
hydrazones 2 and 3 (ꢀ1:1 ratio) in 70–90% yields (Table 1, Scheme
2). The Rf value of isomer 3 was smaller than that of isomer 2.
The configurations of the hydrazones 2 and 3 were confirmed
by their 1H and 13C NMR data. It was found in the 1H NMR spectra
that the chemical shifts of H-1, H-2, and H-4 of hydrazone 2 (d
5.88–5.94, 5.03–5.14, and 4.16–4.25, respectively) were smaller
than those of isomer 3 (d 5.95–6.02, 5.33–5.55, and 4.27–4.32,
respectively), and the chemical shift of H-4 of hydrazone 2 (d
4.99–5.11) was larger than that of isomer 3 (d 4.76–4.89). In the
13C NMR spectra, both the C-1 and the C-5 of isomer 2 showed
smaller chemical shifts than those of isomer 3, and the chemical
shifts of C-2, C-3, C-4, and C-6 of 2 were all larger than those of
3. Moreover, the NOESY spectrum of isomers 3d and 3e showed
a correlation between N–H and H-1 or H-2, and showed no corre-
lation between N–H and H-4, indicating a Z configuration. The
NOESY spectrum of isomers 2d and 2e showed a stronger correla-
tion signal between N–H and H-4 than between N–H and H-2;
therefore, 2 should be of the E configuration.
Di-O-isopropylidene-a-D-glucofuranose has been used in the
modification of various bioactive compounds, such as anticancer,
antibacterial, immune modulating,16 and photodynamic therapeutic
agents.17 Previously we have successfully synthesized a fructose-
based 3-acetyl-2,3-dihydro-1,3,4-oxadiazole (GLB) and its 5-linear
5-alkyl derivatives; these derivatives showed moderate cytotoxic
activities (Scheme 1).18 A combination of 1,2:5,6-di-O-isopropyli-
dene-a-D-glucofuranose and 3-acetyl-2,3-dihydro-1,3,4-oxadiaz-
oles might lead to novel compounds with better bioactivities.19–21
Therefore, we designed and synthesized a series of glucose-
based 1,3,4-oxadiazole derivatives using microwave irradiation.
Compared to the general microwave-assisted heterocyclic reac-
tions that last several minutes,22–26 the preparation of fructose-
based 1,3,4-oxadiazole derivatives can only be completed after
microwave irradiation for more than 30 min.18 Apparently, further
enhancement of the reaction rate is needed. Therefore, we at-
* Corresponding author. Tel.: +86 10 8280 1714; fax: +86 10 6236 7134.
E-mail address: zjli@bjmu.edu.cn (Z.-J. Li).
0008-6215/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2009.07.009

2114
L.-N. Wang et al. / Carbohydrate Research 344 (2009) 2113–2119
O
O
O
O
N
O
O
O
O
O
N
Ac
Ac
O
O
O
N
N
R
R=linear alkyl
Br
5-alkyl derivatives
GLB
Scheme 1. GLB and its derivatives that have antitumor activity.
Table 1
Synthesis of 4 and 5 under microwave irradiation and with classical heating
R
2+3
Microwave irradiation
Yielda (%)
Oil bath heating
Yielda (%)
Yielda (%)
Ratio (2:3)b
Time (min)
Ratio (4:5)b
Time (h)
Ratio (4:5)b
a
b
c
d
e
f
CH3
n-C3H7
92
80
86
83
87
84
79
1:1.1
1:1.2
1:1.1
1:1.5
1.4:1
1.2:1
1.7:1
10
10
10
10
10
10
10
92
88
91
87
90
91
89
1:1.4
1.5:1
1.3:1
1:1.2
1.3:1
1:1.3
1.4:1
24
48
24
38
12
12
12
77
50
61
53
73
70
77
1.5:1
1.3:1
1.3:1
1.3:1
1.7:1
1.2:1
1.2:1
n-C5H11
n-C7H15
C6H5
p-Br–C6H4
p-OMe–C6H4
g
a
Isolated yield.
Isolated ratio.
b
O
OH
O
O
O
HO
HO
O
RCONHNH2
OH
OH
MeOH, AcOH
O
O
D-glucose
1
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
+
O
O
O
Ac2O
Ac
Ac
+
O
N
N
N
O
HN
N
O
O
A. AcONa,MW, 87-92%
B. heating, 50-77%
NH
N
N
ROC
ROC
(E isomer)
R
R
2a-g
3a-g (Z isomer)
4a-g (R isomer)
5a-g
(S isomer)
a
b
c
d
e
f
g
CH3
n-C3H7
n-C5H11
n-C7H15
R
Br
OMe
Scheme 2. Synthesis of oxadiazoles 4 and 5.
Equilibration (syn–anti) between the isomers 2 and 3 in solution
Hydrazones 2 and 3 reacted with acetic anhydride under micro-
wave irradiation above 160 °C to produce the target products 4 and
5, which were a pair of isomers on the C-3 of the furan ring. Given
the high temperature and acidic conditions, the pure isomer of
a hydrazone would isomerize (syn–anti) to reach equilibrium
was observed. Detailed investigation found that the equilibrium of
2b and 3b could be achieved in less than 5 min by heating (80 °C)
or in the presence of acetic acid (<0.1%), the ratio of the isomers
was round 1:1 after equilibrium (Scheme 3).

L.-N. Wang et al. / Carbohydrate Research 344 (2009) 2113–2119
2115
O
the optimal conditions of cyclization of hydrazones were at
150 °C for 10 min with NaOAc as the catalyst, giving products up
to 92%. Temperatures higher than 150 °C led to a decrease in the
yields of products.
O
O
O
O
acid or heating
O
O
O
O
Under the optimized conditions of 150 °C for 10 min with the
assistance of microwave irradiation, oxadiazoles 4a–g and 5a–g
were successfully synthesized in excellent yields (Table 1). The ra-
tios of the isomers 4a–g and 5a–g were always ꢀ1:1. All of these
oxadiazoles 4 and 5 were also synthesized under oil bath heating
(no microwave irradiation) to compare the effect of these two
methods. The results of the heterocyclization by oil bath heating
are summarized in Table 1. Compared with traditional oil bath
heating, heterocyclization of oxadiazoles 4 and 5 under microwave
irradiation required a much shorter reaction time and produced
higher yields of products.
N
O
NHCOR
RNOCH
N
~ 1 : 1 after equibrium
2
3
Scheme 3. syn–anti Equilibration between isomers 2 and 3.
between the isomers quickly. Therefore, a mixture of isomers 2 and
3 was used for the heterocyclization. Initially, the heterocyclization
of 2c and 3c was carried out under our previously optimized
microwave conditions at 160 °C for 30 min,18 and oxadiazoles 4c
and 5c were successfully obtained. In order to further optimize
the conditions of the heterocyclization and decrease the reaction
time under microwave irradiation, we investigated the effects of
different promoters on the rate and yields of the microwave reac-
tion. The results of the optimization are shown in Table 2.
First, we performed the reaction under microwave irradiation at
160 °C for a short time of 5 min to compare the effect of different
catalysts. When the heterocyclization of 2c and 3c was catalyzed
by Lewis acids such as SnCl4, ZnCl2, and FeCl3, the reaction solution
turned dark. Even though most of the reactants disappeared, the
product yields were very low and large amounts of byproducts
were generated. A yield of only 20% was obtained when 0.1 equiv
of FeCl3 was used. We presumed that the low yields of products
4c and 5c were caused by the Lewis acids, which could lead to
the degradation of the reactants, and they showed no positive ef-
fects on the heterocyclization of hydrazones 2c and 3c.
In the presence of a base like pyridine and DAMP, the yields of
heterocyclization increased to around 30% with 10–15% of the
reactants still remaining. These results indicated that pyridine
and DAMP could not accelerate the heterocyclization of 2c and
3c, but catalyzed the degradation of the reactants.
Among the several acetate salts examined as catalysts, the addi-
tion of NaOAc afforded the best results. Oxadiazoles 4c and 5c were
obtained in 45% yields, and 40% of the reactants still remained
when reacted at 160 °C for 5 min under microwave conditions.
We assumed that NaOAc buffered the acetic acid generated in
the reaction process and decreased the amount of acetic acid in
the reaction mixture, resulting promotion of the reaction. As a re-
sult, byproducts generated by acetic acid decreased, resulting in
higher yields of products. Therefore, NaOAc was selected to cata-
lyze the heterocyclization of hydrazones 2 and 3 with the assis-
tance of microwave irradiation.
As shown in Table 1, the ratio of the isomers of the heterocyc-
lization of glucose-based hydrazones was always ꢀ1:1 under both
heating and microwave irradiation; therefore, the cyclization
showed no stereoselectivity. The stereochemistry of the cyclization
should
be influenced by the steric hindrance of the two isopropyl-
idene groups. Because the isopropylidene group is far from the C-3
position of the furan ring, the chance for the oxygen atom to attack
the C-3 from the top or bottom of the furan rings is essentially the
same. Therefore, the ratio of the S:R configuration of the product is
ꢀ1:1. We have reported that the R and S configurations of the fruc-
tose-based 1,3,4-oxadiazoles are determined by the Z/E configura-
tions of the hydrazones.18 In this paper, the ratio of isomers of the
glucose-based 1,3,4-oxadiazoles 4 and 5 was about the same as
the ratio of the isomers of the hydrazones 2 and 3, which were
both ꢀ1:1. These results were in agreement with our previous
conclusions.18
The configurations of C-3 of compounds 4 and 5 were assigned
by their 1H NMR, 13C NMR, and NOESY spectra. It was found in the
1H NMR spectra that the chemical shifts of H-1 and H-2 of all oxa-
diazoles 4 (d 5.89–5.98 and 4.36–4.99, respectively) were smaller
than those of isomer 5 (d 5.95–6.22 and 4.72–5.33, respectively),
and the chemical shift of H-4 of the hydrazone 4 (d 5.45–5.68)
was larger than that of isomer 5 (d 4.09–4.76). In the 13C NMR
spectra, both the C-1 and the C-5 of isomer 4 showed smaller
chemical shifts than those of 5, and the chemical shifts of C-2, C-
3, and C-4 of 4 were all larger than those of 5. The 1D NOESY spec-
trum of 4b and 4g showed the strongest correlation between NAc
and H-4, indicating that the Ac group of the oxadiazole ring is be-
low the furan ring of the glucose; hence, the C-3 should be of the R
configuration. Moreover, the 1D NOESY spectrum of 5b and 5g
showed the strongest correlation between NAc and H-2, demon-
strating that the Ac group is above the furan ring of glucose; there-
fore 5 should be of the S configuration.
We then optimized the temperature and time of the heterocyc-
lization with sodium acetate as the catalyst. As shown in Table 2,
Table 2
Microwave-assisted cyclization of 2c and 3c with different promoters
Entry
T (°C)
Promotera
Time (min)
Reactant remainingb (%)
Yield (%) and ratio (4:5)c
1
2
3
4
5
6
7
8
9
160
160
160
160
160
160
160
160
160
170
150
140
SnCl4
ZnCl2
FeCl3
5
5
5
5
5
5
5
5
10
10
10
10
—
—
—
10
15
40
45
—
—
—
—
40
—
—
20(1.1:1)
34(1.2:1)
30(1.1:1)
45(1.3:1)
40(1.2:1)
—
80(1.1:1)
68(1.2:1)
92(1.3:1)
44(1.1:1)
Pyridine
DMAP
NaOAc
KOAc
Cu(OAc)2
NaOAc
NaOAc
NaOAc
NaOAc
10
11
12
a
The amount of SnCl4, ZnCl2, FeCl3, and DMAP is 0.1 equiv; the amount of NaOAc, KOAc, and Cu(OAc)2 is 2.25 equiv; pyridine is used as a solvent with the same volume
(0.5 mL) as Ac2O.
b
All reactions were performed with 2c and 3c (100 mg) and promoters in 1 mL of solvent under microwave irradiation.
Isolated yield.
c

2116
L.-N. Wang et al. / Carbohydrate Research 344 (2009) 2113–2119
H-6b), 2.08 (s, 3H, CH3CO), 1.41–1.24 (m, 12H, CH3 ꢂ 4); 13C
3. Conclusions
NMR (75 MHz, DMSO-d6): dC 172.3 (C@O), 151.2 (C-3), 112.8,
109.8 (CMe2), 103.3 (C-1), 79.5 (C-2), 76.9 (C-5), 75.4 (C-4), 66.3
(C-6), 27.5, 26.0, 25.1, 21.6 20.0 (C(CH3)2, COCH3); HRESIMS: Calcd
for C14H22N2O6: 315.1551 [M+H]+. Found: 315.1546 [M+H]+.
In summary, a novel approach to synthesize 3-acetyl-1,3,4-oxa-
diazole derivatives was developed with NaOAc as the catalyst un-
der the assistance of microwave irradiation. Under the optimized
conditions, a series of glucose-based 3-acetyl-1,3,4-oxadiazole
derivatives 4 and 5 were synthesized from hydrazones 2 and 3 in
good yields, and the ratio of the isomers 4 and 5 is ꢀ1:1. The abso-
lute configurations of hydrazones 2, 3 and oxadiazoles 4, 5 were
confirmed by NMR data.
4.4.2. (Z)-1,2:5,6-Di-O-isopropylidene-a-D-ribo-hexofuranos-3-
ulose acetylhydrazone (3a)
Colorless foam; ½a D26
ꢁ
+237.8 (c 0.74, MeOH); 1H NMR (300 MHz,
DMSO-d6): dH 10.60 (s, 1H, NH), 5.96 (d, 1H, J1,2 4.2 Hz, H-1), 5.35
(d, 1H, H-2), 4.79 (d, 1H, H-4), 4.29 (m, 1H, H-5), 4.02 (m, 1H, H-
6a), 3.98 (m, 1H, H-6b), 2.05 (s, 3H, CH3CO), 1.46–1.04 (m, 12H,
CH3 ꢂ 4); 13C NMR (75 MHz, DMSO-d6): dC 172.4 (C@O), 152.9
(C-3), 112.7, 108.8 (CMe2), 104.5 (C-1), 78.1 (C-2), 77.1 (C-5),
74.0 (C-4), 63.5 (C-6), 27.2, 26.1, 25.1, 21.5, 20.2 (C(CH3)2, COCH3);
HRESIMS: Calcd for C14H22N2O6: 315.1551 [M+H]+. Found:
315.1545 [M+H]+.
4. Experimental
4.1. General methods
Unless specified otherwise, all reactants and reagents were pur-
chased commercially and used without further purification. Sol-
vents were purified by standard procedures. Melting points were
measured with an X4 melting-point apparatus and are uncor-
rected. Optical rotations were measured at 25 °C using an Optical
Activity AA-10R automatic polarimeter. NMR spectra were re-
corded on a Jeol-300 instrument and a Varian Inova-500 instru-
ment. Mass spectra were measured on an IBI-MDS Sciexciex Q-
star or an FAB-MS mass spectrometer. Elemental analyses were
determined on a Perkin–Elmer 240 C instrument. TLC was per-
formed on Silica Gel GF254 plates (Hai Yang Chemical Factory,
Qingdao, Shandong, PR China) with detection by UV fluorescence
quenching and by spraying with 10% H2SO4. Column chromatogra-
phy was performed on Silica Gel H60 (Hai Yang Chemical Factory,
Qingdao, Shandong, PR China). Microwave reactions were con-
ducted using a Biotage-Initiator EXP EO Microwave Synthesizer.
4.4.3. (E)-1,2:5,6-Di-O-isopropylidene-a-D-ribo-hexofuranos-3-
ulose butyrylhydrazone (2b)
Colorless foam; ½a D25
ꢁ
ꢃ85.7 (c 0.98, MeOH); 1H NMR (300 MHz,
DMSO-d6): dH 5.88 (d, 1H, J1,2 3.3 Hz, H-1), 5.04 (d, 1H, H-2), 4.99
(d, 1H, H-4), 4.16 (m, 1H, H-5), 4.01 (m, 1H, H-6a), 3.84 (m, 1H,
H-6b), 2.15 (t, 2H, CH2CO), 1.56–0.84 (m, 17H, CH3 ꢂ 4, C2H5);
13C NMR (75 MHz, DMSO-d6): dC 174.6 (C@O), 153.8 (C-3), 112.7,
109.8 (CMe2), 103.3 (C-1), 79.5 (C-2), 76.9 (C-5), 75.0 (C-4), 66.3
(C-6), 33.5, 27.3, 26.6, 26.0, 25.2, 17.5, 13.7 (C(CH3)2), C3H7); HRE-
SIMS: Calcd for C16H26N2O6: 343.1864 [M+H]+. Found: 343.1863
[M+H]+.
4.4.4. (Z)-1,2:5,6-Di-O-isopropylidene-a-D-ribo-hexofuranos-3-
ulose butyrylhydrazone (3b)
Colorless foam, ½a D25
ꢁ
ꢃ125.7 (c 1.40, MeOH); 1H NMR (300 MHz,
4.2. General procedures for the preparation of compounds 2a–g
and 3a–g
DMSO-d6): dH 5.98 (d, 1H, J1,2 4.5 Hz, H-1), 5.34 (d, 1H, H-2), 4.78
(d, 1H, H-4), 4.28 (m, 1H, H-5), 4.02 (m, 1H, H-6a), 3.97 (m, 1H,
H-6b), 2.24 (t, 2H, CH2CO), 1.58–0.86 (m, 17H, CH3 ꢂ 4, C2H5);
13C NMR (75 MHz, DMSO-d6): dC 174.6 (C@O), 153.0 (C-3), 112.7,
108.9 (CMe2), 104.5 (C-1), 78.4 (C-2), 77.2 (C-5), 74.0 (C-4), 63.7
(C-6), 33.8, 27.2, 27.0, 26.0, 25.3, 18.5, 13.8 (C(CH3)2, C3H7); HRE-
SIMS: Calcd for C16H26N2O6: 343.1864 [M+H]+. Found: 343.1867
[M+H]+.
AcOH (0.5 mL) was added slowly to a stirred solution of 1,2:4,5-
di-O-isopropylidene-
a-
D-ribo-hexofuranos-3-ulose
(1)
(2.0 g,
7.75 mmol) and the appropriate hydrazine (7.75 mmol) in MeOH
(40.0 mL) at room temperature (reflux at 60 °C for aromatic substi-
tuted compounds). The reaction was monitored by TLC (1:3 petro-
leum ether–EtOAc) until the reactant disappeared after ꢀ12–24 h;
the solvent was then evaporated. The residual foam was separated
by column chromatography to obtain hydrazone isomers 2 and 3,
respectively. See Section 4.4 for characterization and physicochem-
ical and spectral data.
4.4.5. (E)-1,2:5,6-Di-O-isopropylidene-a-D-ribo-hexofuranos-3-
ulose hexanoylhydrazone (2c)
Colorless foam; ½a D25
ꢁ
+166.0 (c 1.03, MeOH); 1H NMR (300 MHz,
DMSO-d6): dH 10.29 (s, 1H, NH), 5.88 (d, 1H, J1,2 4.2 Hz, H-1), 5.04
(d, 1H, H-2), 5.00 (d, 1H, H-4), 4.18 (m, 1H, H-5), 4.04 (m, 1H, H-
6a), 3.79 (m, 1H, H-6b), 2.16 (t, 2H, CH2CO), 1.53–0.83 (m, 21H,
CH3 ꢂ 4, C4H9); 13C NMR (75 MHz, DMSO-d6): dC 153.8 (C-3),
112.7, 109.8 (CMe2), 103.3 (C-1), 79.5 (C-2), 76.9 (C-5), 75.0 (C-
4), 66.2 (C-6), 31.5, 30.9, 27.5, 27.3, 26.0, 25.2, 23.8, 22.0, 13.9
(C(CH3)2, C5H11); HRESIMS: Calcd for C18H30N2O6: 371.2177
[M+H]+. Found: 371.2171 [M+H]+.
4.3. General procedures for the preparation of compounds 4a–g
and 5a–g under microwave irradiation
A mixture of 2 and 3 (2.0 mmol) was dissolved in Ac2O (1.0 mL)
and boiled at 150 °C under microwave heating for 10 min in the
microwave initiator. The solution was concentrated, and the resid-
ual solvent was removed by adding toluene and evaporating under
reduced pressure three times. The residual foam was purified by
chromatography (1:8 EtOAc–cyclohexane) to afford oxadiazoles 4
and 5, respectively. See Section 4.4 for characterization and physi-
cochemical and spectral data.
4.4.6. (Z)-1,2:5,6-Di-O-isopropylidene-a-D-ribo-hexofuranos-3-
ulose hexanoylhydrazone (3c)
Colorless foam; ½a D25
ꢁ
+212.0 (c 1.17, MeOH); 1H NMR (300 MHz,
DMSO-d6): dH 10.51 (s, 1H, NH), 5.96 (d, 1H, J1,2 4.8 Hz, H-1), 5.34
(d, 1H, H-2), 4.78 (d, 1H, H-4), 4.28 (m, 1H, H-5), 3.96–3.82 (m,
2H, H-6a, H-6b), 2.25 (t, 2H, CH2CO), 1.55–0.82 (m, 21H, CH3 ꢂ 4,
C4H9); 13C NMR (75 MHz, DMSO-d6): dC 150.1 (C-3), 112.7, 108.9
(CMe2), 104.5 (C-1), 78.4 (C-2), 77.2 (C-5), 74.0 (C-4), 63.7 (C-6),
31.8, 31.0, 27.3, 27.1, 26.1, 25.1, 24.0, 22.0, 13.9 (C(CH3)2, C5H11);
HRESIMS: Calcd for C18H30N2O6: 371.2177 [M+H]+. Found:
371.2175 [M+H]+.
4.4. Compounds 2–5
4.4.1. (E)-1,2:5,6-Di-O-isopropylidene-a-D-ribo-hexofuranos-3-
ulose acetylhydrazone (2a)
Colorless foam; ½a D25
ꢁ
+106.7 (c 1.50, MeOH); 1H NMR (300 MHz,
DMSO-d6): dH 5.89 (d, 1H, J1,2 4.5 Hz, H-1), 5.03 (d, 1H, H-2), 5.00
(d, 1H, H-4), 4.17 (m, 1H, H-5), 4.04 (m, 1H, H-6a), 3.80 (m, 1H,

L.-N. Wang et al. / Carbohydrate Research 344 (2009) 2113–2119
2117
4.4.7. (E)-1,2:5,6-Di-O-isopropylidene-
ulose octanoylhydrazone (2d)
a
-
D
-ribo-hexofuranos-3-
H-6), 1.26–1.38 (m, 12H, CH3 ꢂ 4); 13C NMR (75 MHz, DMSO-d6):
dC 162.8 (C@O), 157.0 (C-3), 132.4 (C-10), 131.5 (C-30, C-50), 130.0
(C-20, C-60), 125.7 (C-40), 112.8, 109.0 (CMe2), 104.5 (C-1), 78.8
(C-2), 77.3 (C-4), 74.9 (C-5), 63.6 (C-6), 27.4, 27.0, 26.1, 25.1
(C(CH3)2); HRESIMS: Calcd for C19H23BrN2O6: 455.0812 [M+H]+.
Found: 455.0805 [M+H]+.
Colorless foam; ½a D25
ꢁ
+137.3 (c 1.02, MeOH); 1H NMR (300 MHz,
DMSO-d6): dH 10.29 (s, 1H, NH), 5.88 (d, 1H, J1,2 4.2 Hz, H-1), 5.04
(d, 1H, H-2), 5.02 (d, 1H, H-4, J 3.6 Hz), 4.16 (m, 1H, H-5), 4.04
(m, 1H, H-6a), 3.77 (m, 1H, H-6b), 2.17 (t, 2H, CH2CO), 1.53–0.82
(m, 25H, CH3 ꢂ 4, C6H13). HRESIMS: Calcd for C20H34N2O6:
399.2490 [M+H]+. Found: 399.2490 [M+H]+.
4.4.13. (E)-1,2:5,6-Di-O-isopropylidene-a-D-ribo-hexofuranos-
3-ulose p-methoxylbenzoylhydrazone (2g)
4.4.8. (Z)-1,2:5,6-Di-O-isopropylidene-
a
-
D
-ribo-hexofuranos-3-
White amorphous solid; mp 162–163 °C; ½a D25
ꢃ102.4 (c 1.25,
ꢁ
ulose octanoylhydrazone (3d)
MeOH); 1H NMR (300 MHz, DMSO-d6): dH 10.81 (s, 1H, NH), 7.78
(d, 2H, H-20, H-60), 7.05 (d, 2H, H-30, H-50), 5.91 (d, 1H, J1,2 3.9 Hz,
H-1), 5.11 (d, 1H, H-2), 5.05 (d, 1H, J 8.1 Hz, H-4), 4.23 (m, 1H, H-
5), 4.10 (m, 1H, H-6a), 3.90 (m, 1H, H-6b), 3.88 (s, 3H, OCH3),
1.38–1.25 (m, 12H, CH3 ꢂ 4); 13C NMR (75 MHz, DMSO-d6): dC
162.4 (C@O), 155.0 (C-3), 129.6 (C-10), 125.0 (C-30, C-50), 113.9
(C-20, C-60), 112.8 (C-40), 110.3 (CMe2), 103.2 (C-1), 100.2, 80.0 (C-
2), 77.5 (C-4), 74.9 (C-5), 66.9 (C-6), 55.6 (OCH3), 27.6, 27.3, 26.2,
25.5 (C(CH3)2); HRESIMS: Calcd for C20H26N2O7: 407.1813
[M+H]+. Found: 407.1811 [M+H]+.
Colorless foam; ½a D25
ꢁ
ꢃ140.9 (c 1.02, MeOH); 1H NMR (300 MHz,
DMSO-d6): dH 10.50 (s, 1H, NH), 5.95 (d, 1H, J1,2 5.4 Hz, H-1), 5.33
(d, 1H, H-2), 4.76 (d, 1H, H-4), 4.27 (d, 1H, H-5), 3.92–3.81 (m,
2H, H-6), 2.24 (m, 2H, CH2CO), 1.51–0.83 (m, 25H, CH3 ꢂ 4,
C6H13); 13C NMR (75 MHz, DMSO-d6): dC 150.1 (C-3), 112.7, 108.9
(CMe2), 104.5 (C-1), 78.4 (C-2), 77.2 (C-5), 74.0 (C-4), 63.8 (C-6),
33.7, 31.8, 31.2, 28.5, 27.3, 27.0, 26.1, 25.3, 24.3, 22.1, 14.0
(C(CH3)2, C7H15); HRESIMS: Calcd for C20H34N2O6: 399.2490
[M+H]+. Found: 399.2492 [M+H]+.
4.4.9. (E)-1,2:5,6-Di-O-isopropylidene-
a-
D-ribo-hexofuranos-3-
4.4.14. (Z)-1,2:5,6-Di-O-isopropylidene-a-D-ribo-hexofuranos-
ulose benzoylhydrazone (2e)
3-ulose p-methoxylbenzoylhydrazone (3g)
White amorphous solid; mp 188–190 °C; ½a D25
ꢁ
+130.0 (c 0.77,
White amorphous solid; mp 161–162 °C; ½a D25
ꢃ230.3 (c 0.66,
ꢁ
MeOH); 1H NMR (300 MHz, DMSO-d6): dH 10.93 (s, 1H, NH), 7.82
(d, 2H, H-20, H-60), 7.62 (dd, 1H, H-40), 7.55 (d, 2H, H-30, H-50),
5.94 (d, 1H, J1,2 3.9 Hz, 1H), 5.14 (d, 1H, H-2), 5.10 (m, 1H, H-4),
4.22 (m, 1H, H-5), 4.12 (t, 1H, H-6a), 3.89 (t, 1H, H-6b), 1.24–1.39
(m, 12H, CH3 ꢂ 4); 13C NMR (75 MHz, DMSO-d6): dC 163.4 (C@O),
155.8 (C-3), 133.2 (C-10), 132.2 (C-40), 128.6 (C-30, C-50), 127.5 (C-
20, C-60), 112.8, 110.2 (CMe2), 103.2 (C-1), 79.9 (C-2), 77.4 (C-4),
74.8 (C-5), 66.8 (C-6), 27.5, 27.2, 26.0, 25.3 (C(CH3)2). HRESIMS:
Calcd for C19H24N2O6: 377.1707 [M+H]+. Found: 377.1702 [M+H]+.
MeOH); 1H NMR (300 MHz, DMSO-d6): dH 10.89 (s, 1H, NH), 7.81
(d, 2H, H-20, H-60), 7.06 (d, 2H, H-30, H-50), 6.01 (d, 1H, J1,2 4.5 Hz,
H-1), 5.55 (d, 1H, H-2), 4.86 (s, 1H, H-4), 4.30 (m, 1H, H-5), 3.98,
3.96 (m, 2H, H-6a, H-6b), 3.88 (s, 3H, OCH3), 1.38–1.27 (m, 12H,
CH3 ꢂ 4); 13C NMR (75 MHz, DMSO-d6): dC 130.1, 125.3 (C-40),
113.7, 112.7 (CMe2), 108.9 (C-1), 104.4, 94.6, 78.7 (C-2), 77.3 (C-
4), 74.8 (C-5), 63.6 (C-6), 55.4 (OCH3), 27.4, 26.9, 26.1, 25.1
(C(CH3)2); HRESIMS: Calcd for C20H26N2O7: 407.1813 [M+H]+.
Found: 407.1811 [M+H]+.
4.4.10. (Z)-1,2:5,6-Di-O-isopropylidene-
a
-
D
-ribo-hexofuranos-
4.4.15. (3R)-40-N-Acetyl-1,2:4,5-di-O-isopropylidene-20-methyl-
3-ulose benzoylhydrazone (3e)
spiro-[3-deoxy-a-D
-ribo-hexofuranos-3-C-3-yl-3,50-[1,3,4]-
White amorphous solid; mp 165–166 °C; ½a D25
ꢁ
+177.1 (c 0.70,
oxadiazoline] (4a)
MeOH); 1H NMR (300 MHz, DMSO-d6): dH 11.05 (s, 1H, NH), 7.78
(d, 2H, H-20, H-60), 7.57–7.52 (m, 3H, H-30, H-40, H-50), 5.99 (s, 1H,
J1,2 4.5 Hz, H-1), 5.53 (s, 1H, H-2), 4.86 (s, 1H, H-4), 4.30 (m, 1H,
H-5), 3.96 (m, 1H, H-6a), 3.87 (m, 1H, H-6b), 1.37–1.25 (m, 12H,
CH3 ꢂ 4); 13C NMR (75 MHz, DMSO-d6): dC 156.6 (C-3), 133.3 (C-
10), 132.0 (C-40), 128.5 (C-30, C-50), 128.0 (C-20, C-60), 112.8, 109.0
(CMe2), 104.6 (C-1), 78.8 (C-2), 77.4 (C-4), 75.0 (C-5), 63.6 (C-6),
27.4, 27.0, 26.1, 25.1 (C(CH3)2); HRESIMS: Calcd for C19H24N2O6:
377.1707 [M+H]+. Found: 377.1705 [M+H]+.
Colorless foam; ½a D25
ꢁ
ꢃ55.4 (c 0.65, MeOH); 1H NMR (300 MHz,
CDCl3): dH 5.89 (d, 1H, J1,2 3.9 Hz, H-1), 5.57 (d, 1H, H-2), 4.39 (d,
1H, H-4), 4.18–4.01 (m, 3H, H-5, H-6), 2.21 (s, 3H, CH3C@N), 2.05
(s, 3H, CH3CO), 1.64–1.24 (m, 12H, CH3 ꢂ 4); 13C NMR (75 MHz,
CDCl3): dC 168.4 (C@O), 153.0 (C@N), 114.1, 109.6 (CMe2), 103.8
(C-1), 103.1 (C-3), 83.2 (C-2), 72.9 (C-4), 72.5 (C-5), 67.4 (C-6),
26.9, 26.2, 26.0, 25.2, 23.4, 11.1 (C(CH3)2, COCH3); HRESIMS: Calcd
for C16H24N2O7: 357.1656 [M+H]+. Found: 357.1657 [M+H]+.
4.4.16. (3S)-40-N-Acetyl-1,2:4,5-di-O-isopropylidene-20-methyl-
4.4.11. (E)-1,2:5,6-Di-O-isopropylidene-
3-ulose p-bromobenzoylhydrazone (2f)
a-
D-ribo-hexofuranos-
spiro-[3-deoxy-a-D
-ribo-hexofuranos-3-C-3-yl-3,50-[1,3,4]-
oxadiazoline] (5a)
White amorphous solid; mp 220–221 °C; ½a D25
ꢁ
+133.3 (c 0.48,
Colorless foam; ½a D25
ꢁ
ꢃ11.6 (c 1.03, MeOH); 1H NMR (300 MHz,
MeOH); 1H NMR (300 MHz, DMSO-d6): dH 10.92 (s, 1H, NH), 7.78
(s, 4H, H-20, H-30, H-50, H-60), 5.94 (d, 1H, J1,2 4.2 Hz, H-1), 5.14
(1H, H-2), 5.11 (1H, H-4), 4.25 (m, 1H, H-5), 4.11 (dd, 1H, H-6a),
3.87 (dd, 1H, H-6b), 1.25–1.39 (m, 12H, CH3 ꢂ 4); 13C NMR
(75 MHz, DMSO-d6): dC 162.5 (C@O), 156.5 (C-3), 132.2 (C-10),
131.7 (C-30, C-50), 129.6 (C-20, C-60), 125.9 (C-40), 112.8, 110.2
(CMe2), 103.2 (C-1), 79.8 (C-2), 77.4 (C-4), 74.8 (C-5), 66.7 (C-6),
27.5, 27.3, 26.1, 25.3 (C(CH3)2); HRESIMS: Calcd for C19H23BrN2O6:
455.0812 [M+H]+. Found: 455.0806 [M+H]+.
CDCl3): dH 6.18 (d, 1H, J1,2 3.6 Hz, H-1), 4.80 (d, 1H, H-2), 4.10 (d,
1H, H-4), 4.09–3.99 (m, 3H, H-5, H-6), 2.27 (s, 3H, CH3C@N), 2.02
(s, 3H, CH3CO), 1.62–1.24 (m, 12H, CH3 ꢂ 4); 13C NMR (75 MHz,
CDCl3): dC 167.4 (C@O), 155.2 (C@N), 113.3, 109.5 (CMe2), 106.1
(C-1), 103.8 (C-3), 82.7 (C-2), 81.7 (C-4), 73.8 (C-5), 67.4 (C-6),
27.0, 26.6, 25.1, 22.0, 11.3 (C(CH3)2, COCH3); HRESIMS: Calcd for
C16H24N2O7: 357.1656 [M+H]+. Found: 357.1658 [M+H]+.
4.4.17. (3R)-40-N-Acetyl-1,2:4,5-di-O-isopropylidene-20-propyl-
spiro-[3-deoxy-a-D
-ribo-hexofuranos-3-C-3-yl-3,50-[1,3,4]-
4.4.12. (Z)-1,2:5,6-Di-O-isopropylidene-
3-ulose p-bromobenzoylhydrazone (3f)
a
-
D
-ribo-hexofuranos-
oxadiazoline] (4b)
Colorless foam; ½a D25
ꢁ
ꢃ57.1 (c 0.63, MeOH); 1H NMR (300 MHz,
White amorphous solid; mp 141–142 °C; ½a D25
ꢁ
+196.9 (c 0.65,
CDCl3): dH 5.89 (d, 1H, J1,2 3.9 Hz, H-1), 5.58 (d, 1H, H-4), 4.38 (d,
1H, H-2), 4.37–4.01 (m, 3H, H-5, H-6), 2.36 (m, 2H, CH2C@N),
2.24 (s, 3H, CH3CO), 1.67–0.94 (m, 17H, CH3 ꢂ 4, C2H5); 13C NMR
(75 MHz, CDCl3): dC 168.6 (C@O), 155.8 (C@N), 114.0, 109.6
MeOH); 1H NMR (300 MHz, DMSO-d6): dH 11.18 (s, 1H, NH), 7.76
(s, 4H, H-20, H-30, H-50,H-60), 6.02 (d, 1H, J1,2 4.5 Hz, H-1), 5.52 (s,
1H, H-2), 4.89 (s, 1H, H-4), 4.32 (m, 1H, H-5), 3.98, 3.88 (m, 2H,

2118
L.-N. Wang et al. / Carbohydrate Research 344 (2009) 2113–2119
(CMe2), 103.9 (C-1), 103.1 (C-3), 83.1 (C-2), 72.8 (C-4), 72.6 (C-5),
67.4 (C-6), 27.2, 26.6, 26.3, 26.0, 25.2, 23.5, 13.3 (C(CH3)2, COC3H7);
HRESIMS: Calcd for C18H28N2O7: 385.1969 [M+H]+. Found:
385.1968 [M+H]+.
14.0 (C(CH3)2, COC7H15); HRESIMS: Calcd for C22H36N2O7:
441.2595 [M+H]+. Found: 441.2599 [M+H]+.
4.4.23. (3R)-40-N-Acetyl-1,2:4,5-di-O-isopropylidene-20-phenyl-
spiro-[3-deoxy-a-D
-ribo-hexofuranos-3-C-3-yl-3,50-[1,3,4]-
4.4.18. (3S)-40-N-Acetyl-1,2:4,5-di-O-isopropylidene-20-propyl-
oxadiazoline] (4e)
spiro-[3-deoxy-
a
-D
-ribo-hexofuranos-3-C-3-yl-3,50-[1,3,4]-
Colorless foam; ½a D25
ꢁ
ꢃ58.3 (c 0.96, MeOH); 1H NMR (300 MHz,
oxadiazoline] (5b)
CDCl3): dH 7.82 (dd, 2H, H-20, H-60), 7.52 (m, 3H, H-30, H-40, H-50),
5.98 (d, J1,2 4.2 Hz, 1H, H-1), 5.68 (d, 1H, H-4), 4.49 (d, 1H, H-2),
4.26 (m, 1H, H-5), 4.13 (m, 2H, H-6), 2.35 (s, 3H, CH3CO), 1.67–
1.21 (m, 12H, CH3 ꢂ 4); 13C NMR (75 MHz, CDCl3): dC 168.7
(C@O), 152.8 (C@N), 131.6 (C-40), 128.7 (C-10), 126.7 (C-20, C-60),
124.3 (C-30, C-50), 114.2, 109.7 (CMe2), 103.8 (C-1), 103.6 (C-3),
83.1 (C-2), 76.5 (C-4), 72.9 (C-5), 67.2 (C-6), 27.0, 26.1, 25.2, 22.7
(C(CH3)2); HRESIMS: Calcd for C21H26N2O7: 419.1813 [M+H]+.
Found: 419.1804 [M+H]+.
Colorless foam; ½a D25
ꢁ
ꢃ33.8 (c 1.30, MeOH); 1H NMR (300 MHz,
CDCl3): dH 6.10 (d, 1H, J1,2 3.9 Hz, H-1), 4.72 (d, 1H, H-2), 4.03ꢀ3.94
(m, 4H, H-4, H-5, H-6), 2.26 (m, 2H, J 7.5 Hz, CH2C@N), 2.20 (s, 3H,
CH3CO), 1.65–0.93 (m, 17H, CH3 ꢂ 4, C2H5); 13C NMR (100 MHz,
CDCl3): dC 167.5 (C@O), 158.1 (C@N), 113.3, 109.6 (CMe2), 106.1
(C-1), 103.6 (C-3), 82.8 (C-2), 82.0 (C-4), 73.7 (C-5), 67.5 (C-6),
27.4, 27.0, 26.9, 26.7, 25.2, 22.1, 18.8, 13.7 (C(CH3)2, COC3H7); HRE-
SIMS: Calcd for C18H28N2O7: 385.1969 [M+H]+. Found: 385.1965
[M+H]+.
4.4.24. (3S)-40-N-Acetyl-1,2:4,5-di-O-isopropylidene-20-phenyl-
4.4.19. (3R)-40-N-Acetyl-1,2:4,5-di-O-isopropylidene-20-pentyl-
spiro-[3-deoxy-a-D
-ribo-hexofuranos-3-C-3-yl-3,50-[1,3,4]-
spiro-[3-deoxy-
a
-D
-ribo-hexofuranos-3-C-3-yl-3,50-[1,3,4]-
oxadiazoline] (5e)
oxadiazoline] (4c)
Colorless foam; ½a D25
ꢁ
ꢃ59.1 (c 1.10, MeOH); 1H NMR (300 MHz,
Colorless foam; ½a D25
ꢁ
ꢃ32.8 (c 1.34, MeOH); 1H NMR (300 MHz,
CDCl3): dH 7.86 (dd, 2H, H-20, H-60), 7.47 (m, 3H, H-30, H-40, H-50),
6.22 (d, 1H, J1,2 3.9 Hz, H-1), 4.87 (d, 1H, H-2), 4.24–4.03 (m, 3H,
H-4, H-5, H-6), 2.36 (s, 3H, CH3CO), 1.67–1.22 (m, 2H, CH3 ꢂ 4);
13C NMR (75 MHz, CDCl3): dC 167.0 (C@O), 153.3 (C@N), 131.9
(C-40), 129.0 (C-10), 126.4 (C-20, C-60), 123.7 (C-30, C-50), 112.6,
108.8 (CMe2), 105.5 (C-1), 104.0 (C-3), 81.9 (C-2), 81.4 (C-4) 73.4
(C-5), 66.6 (C-6), 26.9, 26.1, 25.1, 21.9 (C(CH3)2); HRESIMS: Calcd
for C21H26N2O7: 419.1813 [M+H]+. Found: 419.1803 [M+H]+.
CDCl3): dH 5.97 (d, 1H, J1,2 4.2 Hz, H-1), 5.45 (d, 1H, H-4), 4.47 (d,
1H, H-2), 4.12 (m, 1H, H-5), 4.08 (m, 1H, H-6a), 4.03 (m, 1H, H-
6b), 2.36 (t, 2H, CH2C@N), 2.05 (s, 3H, CH3CO), 1.58–0.85 (m,
21H, CH3 ꢂ 4, C4H9); 13C NMR (75 MHz, CDCl3): dC 167.2 (C@O),
156.1 (C@N), 112.6, 108.7 (CMe2), 103.4 (C-1), 102.1 (C-3), 82.1
(C-2), 82.8 (C-4), 72.1 (C-5), 66.2 (C-6), 30.2, 26.6, 25.9, 25.8,
24.8, 24.5, 23.2, 21.7, 13.8 (C(CH3)2, COC5H11); HRESIMS: Calcd
for C20H32N2O7: 413.2282 [M+H]+. Found: 413.2278 [M+H].
4.4.25. (3R)-40-N-Acetyl-1,2:4,5-di-O-isopropylidene-20-p-
4.4.20. (3S)-40-N-Acetyl-1,2:4,5-di-O-isopropylidene-20-pentyl-
bromophenyl-spiro-[3-deoxy-a-D-ribo-hexofuranos-3-C-3-yl-
spiro-[3-deoxy-
a
-D
-ribo-hexofuranos-3-C-3-yl-3,50-[1,3,4]-
3,50-[1,3,4]-oxadiazoline] (4f)
oxadiazoline] (5c)
White amorphous solid; mp 220–221 °C; ½a D25
ꢁ
+118.9 (c 0.74,
Colorless foam; ½a D25
ꢁ
ꢃ18.2 (c 1.10, MeOH); 1H NMR (300 MHz,
MeOH); 1H NMR (300 MHz, CDCl3): dH 7.69 (dd, 2H, H-20, H-60),
7.58 (dd, 2H, H-30, H-50), 5.98 (d, 1H, J1,2 4.2 Hz, H-1), 5.64 (d, 1H,
H-4), 4.48 (d, 1H, H-2), 4.22 (m, 1H, H-5), 4.10 (m, 2H, H-6), 2.32
(s, 3H, CH3CO), 1.67, 1.33, 1.20 (m, 12H, CH3 ꢂ 4); 13C NMR
(75 MHz, CDCl3): dC 168.7 (C@O), 152.0 (C@N), 132.0 (C-30, C-50),
128.1 (C-20, C-60), 126.1 (C-10), 123.2 (C-40), 114.2, 109.7 (CMe2),
103.9 (C-1), 103.8 (C-3), 83.1 (C-2), 76.5 (C-4), 72.8 (C-5), 67.3
(C-6), 26.9, 26.2, 25.2, 23.5 (C(CH3)2); HRESIMS: Calcd for
C21H25BrN2O7: 497.0918 [M+H]+. Found: 497.0928 [M+H]+.
CDCl3): dH 6.16 (d, 1H, J1,2 3.6 Hz, H-1), 4.78 (d, 1H, H-2), 4.09–4.01
(m, 4H, H-4, H-5, H-6), 2.36 (t, 2H, CH2C@N), 2.30 (s, 3H, CH3CO),
1.68–0.90 (m, 21H, CH3 ꢂ 4, C4H9; 13C NMR (75 MHz, CDCl3): dC
158.4 (C@N), 113.3, 109.6 (CMe2), 106.0 (C-1), 103.6 (C-3), 82.7
(C-2), 81.9 (C-4), 73.7 (C-5), 67.4 (C-6), 31.2, 27.0, 26.7, 25.5,
25.2, 25.0, 22.2, 22.1, 13.9 (C(CH3)2, COC5H11); HRESIMS: Calcd
for C20H32N2O7: 413.2282 [M+H]+. Found: 413.2278 [M+H]+.
4.4.21. (3R)-40-N-Acetyl-1,2:4,5-di-O-isopropylidene-20-heptyl-
spiro-[3-deoxy-
a
-D
-ribo-hexofuranos-3-C-3-yl-3,50-[1,3,4]-
4.4.26. (3S)-40-N-acetyl-1,2:4,5-di-O-isopropylidene-20-p-
oxadiazoline] (4d)
bromophenyl-spiro-[3-deoxy-a-D-ribo-hexofuranos-3-C-3-yl-
Colorless foam; ½a D25
ꢁ
+7.62 (c 1.05, MeOH); 1H NMR (300 MHz,
3,50-[1,3,4]-oxadiazoline] (5f)
CDCl3): dH 5.89 (d, 1H, J1,2 3.6 Hz, H-1), 5.59 (d, 1H, H-4), 4.36 (d,
1H, H-2), 4.13–4.02 (m, 3H, H-5, H-6), 2.36 (t, 2H, CH2C@N), 2.20
(s, 3H, CH3CO), 1.64–0.88 (m, 27H, CH3 ꢂ 4, C6H13); 13C NMR
(75 MHz, CDCl3): dC 168.6 (C@O), 156.0 (C@N), 114.1, 109.6
(CMe2), 103.7 (C-1), 102.9 (C-3), 83.2 (C-2), 72.9 (C-4), 72.6 (C-5),
67.5 (C-6), 31.6, 29.0, 28.7, 27.0, 26.3, 26.1, 25.3, 25.2, 24.3, 22.5,
14.0 (C(CH3)2, COC7H15); HRESIMS: Calcd for C22H36N2O7:
441.2595 [M+H]+. Found: 441.2592 [M+H]+.
Colorless foam; ½a D25
ꢁ
+32.0 (c 1.00, MeOH); 1H NMR (300 MHz,
CDCl3): dH 7.74 (d, 2H, H-20, H-60), 7.58 (dd, 2H, H-30, H-50), 6.20
(d, 1H, J1,2 3.9 Hz, H-1), 4.86 (d, 1H, H-2), 4.20 (m, 1H, H-4), 4.11
(m, 1H, H-5), 4.06, 4.04 (m, 2H, H-6), 2.37 (s, 3H, CH3CO), 1.66,
1.38, 1.17, 1.11 (m, 12H, CH3 ꢂ 4); 13C NMR (75 MHz, CDCl3): dC
167.9 (C@O), 153.9 (C@N), 131.9 (C-30, C-50), 128.3 (C-20, C-60),
126.1 (C-10), 123.2 (C-40), 113.4, 109.6 (CMe2), 106.1 (C-1), 104.7
(C-3), 82.7 (C-2), 81.9 (C-4), 73.9 (C-5), 67.3 (C-6), 27.0, 26.8,
25.1, 22.1 (C(CH3)2); HRESIMS: Calcd for C21H25BrN2O7: 497.0918
[M+H]+. Found: 497.0920 [M+H]+.
4.4.22. (3S)-40-N-Acetyl-1,2:4,5-di-O-isopropylidene-20-heptyl-
spiro-[3-deoxy-a-D
-ribo-hexofuranos-3-C-3-yl-3,50-[1,3,4]-
oxadiazoline] (5d)
4.4.27. (3R)-40-N-Acetyl-1,2:4,5-di-O-isopropylidene-20-p-
Colorless foam; ½a D25
ꢁ
ꢃ7.62 (c 1.05, MeOH); 1H NMR (300 MHz,
methoxylphenyl-spiro-[3-deoxy-a-D-ribo-hexofuranos-3-C-3-
CDCl3): dH 5.90 (d, 1H, J1,2 3.6 Hz, H-1), 5.60 (d, 1H, H-2), 4.37 (d,
1H, H-4), 4.16–4.00 (m, 3H, H-5, H-6), 2.35 (t, 2H, CH2C@N), 2.21
(s, 3H, CH3CO), 1.65–0.85 (m, 27H, CH3 ꢂ 4, C6H13); 13C NMR
(75 MHz, CDCl3): dC 167.5 (C@O), 158.4 (C@N), 113.3, 109.6
(CMe2), 106.0 (C-1), 103.6 (C-3), 82.7 (C-2), 82.0 (C-4), 73.7 (C-5),
67.5 (C-6), 31.7, 29.1, 28.7, 26.9, 26.3, 26.2, 25.4, 25.3, 24.4, 22.5,
yl-3,50-[1,3,4]-oxadiazoline] (4g)
White amorphous solid; mp 153–154 °C; ½a D25
ꢃ52.7 (c 0.91,
ꢁ
MeOH); 1H NMR (300 MHz, CDCl3): dH 7.76 (dd, 2H, H-20, H-60),
6.94 (dd, 2H, H-30, H-50), 5.98 (d, 1H, J1,2 4.2 Hz, H-1), 5.68 (d, 1H,
H-4), 4.48 (d, 1H, H-2), 4.25 (m, 1H, H-5), 4.09 (dd, 2H, H-6), 3.87
(s, 3H, OCH3), 2.32 (s, 3H, CH3CO), 1.67–1.22 (m, 12H, CH3 ꢂ 4);

L.-N. Wang et al. / Carbohydrate Research 344 (2009) 2113–2119
2119
13C NMR (75 MHz, CDCl3): dC 168.6 (C@O), 162.3 (C-40), 152.8
(C@N), 128.5 (C-30, C-50), 116.5 (C-20, C-60), 114.1, 109.6 (CMe2),
103.9 (C-1), 103.3 (C-3), 83.1 (C-2), 77.4 (C-4), 72.9 (C-5), 67.1
(C-6), 55.4 (OCH3), 27.0, 26.3, 25.2, 23.4 (C(CH3)2); HRESIMS: Calcd
for C22H28N2O8: 449.1918 [M+H]+. Found: 449.1919 [M+H]+.
2. Morton, H. M.; Heuser, D. J.; Joyner, C. T.; Batchelor, J. F.; White, H. L. J. Med.
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4.4.28. (3S)-40-N-acetyl-1,2:4,5-di-O-isopropylidene-20-p-
methoxylphenyl-spiro-[3-deoxy-
a
-
D
-ribo-hexofuranos-3-C-3-
yl-3,50-[1,3,4]-oxadiazoline] (5g)
White solid; mp 152–153 °C; ½a D25
ꢁ
ꢃ50.8 (c 0.63, MeOH); 1H
NMR (300 MHz, CDCl3): dH 7.80 (dd, 2H, H-20, H-60), 6.94 (dd, 2H,
H-30, H-50), 6.21 (d, 1H, J1,2 3.9 Hz, H-1), 4.87 (d, 1H, H-2), 4.21
(d, 1H, H-4), 4.13–4.00 (m, 3H, H-5, H-6), 3.84 (s, 3H, OCH3), 2.38
(s, 3H, CH3CO), 1.66–1.14 (m, 12H, CH3 ꢂ 4); 13C NMR (75 MHz,
CDCl3): dC 167.7 (C@O), 162.1 (C-40), 154.7 (C@N), 128.7 (C-30, C-
50), 116.5 (C-20, C-60), 114.0, 109.6 (CMe2), 106.1 (C-1), 104.1 (C-
3), 82.8 (C-2), 81.8 (C-4), 73.9 (C-5), 67.3 (C-6), 55.3 (OCH3), 27.0,
26.8, 25.1, 22.1 (C(CH3)2); HRESIMS: Calcd for C22H28N2O8:
449.1918 [M+H]+. Found: 449.1916 [M+H]+.
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Acknowledgment
18. Han, D.; Meng, X. B.; Wang, L. N.; Liu, H.; Yao, Y.; Wang, Z.; Yang, Z. J.; Liu, Z. M.;
Li, Z. J. Tetrahedron: Asymmetry 2009, 20, 399–410.
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Bioorg. Med. Chem. Lett. 2006, 16, 5036–5040.
This work was supported by the National Natural Science Foun-
dation of China (20732001, 30672525).
22. Molteni, V.; Ellis, D. A. Curr. Org. Synth. 2005, 2, 333–375.
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Supplementary data
24. Martins Alho, M. A.; D0Accorso, N. B. J. Heterocycl. Chem. 2007, 44, 901–907.
25. Yu, J. X.; Zhang, S. N.; Li, Z. J.; Lu, W. J.; Zhang, L. J.; Zhou, R.; Liu, Y. T.; Cai, M. S. J.
Carbohydr. Chem. 2001, 20, 877–884.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2009.07.009.
26. Li, Z. J.; Zhang, S. N.; Cui, J. R.; Yu, J. X.; Cai, M. S. ZL 03119612.8, 2004.
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