Stereoselective synthesis of novel N-(α-l-arabinofuranos-1-yl)-l-amino acids

Article abstract of DOI:10.1016/j.tetasy.2009.01.014

In lead detoxification, the α-anomer of N-glycocyl-l-amino acid is more potent than its β-anomer. Here a six-step-reaction route for stereoselectively preparing N-(α-l-arabinose-1-yl)-l-amino acids is reported. Treating l-arabinose with acetic anhydride a

Full text of DOI:10.1016/j.tetasy.2009.01.014

Tetrahedron: Asymmetry 20 (2009) 247–258
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Stereoselective synthesis of novel N-(a-L-arabinofuranos-1-yl)-L-amino acids
*
Ming Zhao, Yuji Wang, Caixia Huo, Chunyu Li, Xiaoyi Zhang, Li Peng, Shiqi Peng
College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
In lead detoxification, the
a
-anomer of N-glycocyl-
L
-amino acid is more potent than its b-anomer. Here a
Received 15 December 2008
Accepted 13 January 2009
Available online 11 February 2009
six-step-reaction route for stereoselectively preparing N-(
Treating -arabinose with acetic anhydride and sodium acetate provided 1,2,3,5-tetra-O-acetyl-
ofuranose in 90% yield. After removing the 1-acetyl group, the thus formed 2,3,5-tri-O-acetyl- -arabinof-
uranose and N-(2-nitrophenylsulfonyl)- -amino acid t-butylesters were treated with triphenylphosphine
to perform Mitsunobu dehydration and form 2,3,5-tri-O-acetyl- -arabinofuranosyl- -[N-(2-nitrophenyl-
sulfonyl)]amino acid t-butylesters 2a–f, and the ratios of their - to b-anomer ranged from 8/1 to 9/1.
Chromatographic separation provided epimerically pure 2a–f- and 2a–f-b. In the presence of CF3CO2H,
2a–f- and 2a–f-b were converted to - and b-anomers of N-(2,3,5-tri-O-acetyl- -arabinofuranosyl)-N-
(2-nitrobenzenesulfonyl)- -amino acids, 3a–f- and 3a–f-b, in 87–92% yields. While in the presence of
NaOCH3, 3a–f- and 3a–f-b were converted to - and b-anomers of N-( -arabinofuranosyl)-N-(2-nitro-
benzenesulfonyl)- -amino acids, 4a–f- and 4a–f-b, in 90–96% yields. Treating 4a–f- and 4a–f-b with
N-ethyldiisopropylamine (DIPEA) and thiophenol, their 2-nitrophenylsulfonyl groups were removed,
and the - and b-anomers of N-( -arabinose-1-yl)- -amino acids were formed in 70–79% yields. The bio-
a-
L
-arabinose-1-yl)-
L
-amino acids is reported.
L
L
-arabin-
L
L
L
L
a
a
a
a
L
L
a
a
a
L
L
a
a
a
L
L
assay confirmed that the lead detoxification activity of the
a
-anomer was significantly higher than that of
the b-anomer.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
chain of drug carrier,19 and resulted in an increase in trans-mem-
brane permeability. In this context, the present paper reports a
Recently, the level of lead in air, water and soils has been
increasing both in urban centers of industrialized countries and
in developing countries.1–5 Lead is a widespread toxic metal and
accumulates inside human tissue, such as in bone, with a half-life
time between 6 and 10 years,4,6,7 and has been associated with
many adverse effects such as hypertension, cognitive deficits,
hyperthyroidism, osteoporosis, and skeletal diseases.3–5,8 Lead
exposure continues to be a major public health problem around
the world, and there is an urgent need to find novel compounds
for prevention of lead poisoning.9–13
stereoselective synthetic route of N-(
amino acids. To verify their use, the lead detoxification activities
of a pair of - and b-anomers were premiliminarily evaluated on
a-L-arabinofuranos-1-yl)-L-
a
a mouse lead intoxication model.
2. Results and discussion
2.1. Preparing N-(a-L-arabinofuranos-1-yl)-L-amino acids
A stereoselective route of preparing epimerically pure N-(
arabinofuranos-1-yl)- -amino acids includes six reactions
(Scheme 1). In the presence of acetic anhydride and sodium
acetate, the acetylation of -arabinose provided 1,2,3,5-tetra-O-
a-L-
In a previous investigation we pointed out that as the potential
in lead detoxificators glycosylamino acids were cell membrane
crossable and possess low toxicity,14–16 In the evaluation of che-
L
L
lates of N-(1-deoxy-
fication activity of N-(1-deoxy-
was significantly higher than that of its b-anomer. However, using
the reported procedure, the -anomer of N-(1-deoxy- -fructos-
1-yl)-
-amino acid was always obtained as a minor product.16
Therefore, a synthetic method capable of stereoselectively forming
the -anomers is needed. Compared to -glucose or -fructose,
recently
D-fructos-1-yl)-
L-amino acids, the lead detoxi-
acetyl-
L
-arabinofuranose in 90% yield. Treating 1,2,3,5-tetra-O-
a-
D
-fructos-1-yl)-
L
-phenyl alanine
acetyl-
L
-arabinofuranose with ethyldiamine and glacial acetic acid,
the 1-O-acetyl group was selectively removed and 2,3,5-tri-O-acet-
yl- -arabinofuranose was obtained in 90% yield.
The second reaction step involves Mitsunobu dehydration of
2,3,5-tri-O-acetyl- -arabinofuranose with N-(2-nitrophenylsulfonyl)-
-amino acid t-butylesters. In the presence of triphenylphosphine,
2,3,5-tri-O-acetyl- -arabinofuranose and N-(2-nitro-phenylsulfo-
nyl)- -amino acid t-butylesters smoothly underwent Mitsunobu
dehydration to form - and b-anomers of 2,3,5-tri-O-acetyl-
arabinofuranosyl- -[N-(2-nitrophenylsulfonyl)]amino acid t-buty-
lesters 2a–f in good yield. The ratio of - to b-anomers of
a
D
L
L
L
a
D
D
L
L
-arabinose was particularly used either as a pharmaco-
L
phore of new bioactive compounds17,18 or as a moiety of polymer
L
a
L-
L
* Corresponding author. Tel./fax: +86 1083911528.
E-mail address: sqpeng@bjmu.edu.cn (S. Peng).
a
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.01.014

248
M. Zhao et al. / Tetrahedron: Asymmetry 20 (2009) 247–258
O
O
O
i
ii
OH
OH
OAc
OAc
OH
OAc
OAc
HO
AcO
AcO
OH
OAc
1
OAc
ONs
iii
ONs
N
ONs
R
R
R
N
N
O
O
O
iv
t
v
AcO
CO2 Bu
OAc
CO2H
OH
CO2H
H
H
H
AcO
OAc
HO
OAc
OH
2(a-f)-
α
3(a-f)-
4(a-f)-
α
α
vi
H
R
N
OH
O
O
R
OH
CO2H
OH
OH
H
N
H
HO
CO2H
OH
5(a-f)-
5'(a-f)-
α
α
Scheme 1. Preparation of N-(
a
-
L
-arabinose-1-yl)-L-amino acids. (i) (CH3CO)2O, CH3CO2Na; (ii) ethylene diamine, glacial acetic acid; (iii) (C6H5)3P, DIAD, N-(2-
nitrophenylsulfonyl)-
L
-amino acid t-butylester, and chromatography; (iv) CF3CO2H; (v) NaOCH3/CH3OH; (vi) DIPEA, PhSH. In 2a R = CH2CO2tBu, 2b R = CH2StBu, 2c
R = CH2CH2CO2tBu, 2d R1 = CH2OtBu, 2e R = CH2C6H5, 2f R = CH(OtBu)CH3, 3–5a and 5a R = CH2CO2H, 3–5b and 5b R = CH2SH, (3–5)c and 5c R = CH2CH2CO2H, 3–5d and 5d
R1 = CH2OH, 3–5e and 5e R = CH2C6H5, 3–5f and 5f R = CH(OH)CH3.
2a–f depended on both the dehydration temperature and time.
Here the Mitsunobu dehydration was generally initiated at lower
temperature and continued for several hours, during which the
temperature was gradually raised to 20 °C. To get satisfactory yield
After chromatographic separation, the epimerically pure 2a–f-
and 2a–f-b resulting from the Mitsunobu dehydration were ob-
tained. Treating 2a–f- or 2a–f-b with CF3CO2H, the third reaction
step was carried out, their t-butylester groups were removed and
a
a
and higher ratios of
a
- to b-anomer, a series of procedures were
3a–f-
3a–f-
a
a
or 3a–f-b were obtained in 87–92% yields. In methanol
or 3a–f-b were treated with NaOCH3 and their acetyl
experienced, such as during 2 and 16 h the dehydration tempera-
ture was raised from ꢀ80 °C to 20 °C, during 8 h the dehydration
temperature was raised from ꢀ60 °C to 20 °C, during 10 h the
dehydration temperature was raised from ꢀ40 °C to 20 °C, and
the hydration was carried out at 20 °C for 8 h. It was found that a
groups were removed. The fourth reaction step was performed
and 4a–f- or 4a–f-b were obtained in 90–96% yields. In the fifth
reaction step, 4a–f- or 4a–f-b were treated with DIPEA and thio-
phenol, their 2-nitrophenylsulfonyl groups were removed, and the
final products N-( -arabinofuranos-1-yl)- -amino acids 5a–f- or
N-(b- -arabinofuranos-1-yl)- -amino acids 5a–f-b were formed in
70–79% yields.
a
a
suitable yield and higher ratio of
a- to b-anomer could be obtained
a
-L
L
a
when the dehydration temperature was raised from ꢀ80 °C to
L
L
20 °C, and the dehydration time was 8 h. Using this procedure,
the yields of 2a–f ranged from 87% to 90% and the ratios of 2
2b ranged from 8:1 to 9:1. The rather high stereoselectivity of
the Mitsunobu dehydration implies that N-(2-nitrophenylsulfo-
a
to
To assign the anomeric configurations of 5a–f, the chemical shifts
of H-1 of anomeric pair of 4a–f were compared. Based on the litera-
ture,20 theanomerhavingasmallerd valueof H-1wasassignedas4b.
On the contrary, the anomer having a larger d value of H-1 was as-
nyl)-
the upside of the ring of 2,3,5-tri-O-acetyl-
thus selectively forms the -anomer. It could be considered that
L-amino acid t-butylester approaches the C1 preferably from
L
-arabinofuranose and
signed as 4
of 5a–f. The d values of H-1 of 4a–f-
the d values of H-1 of 4a–f-b ranged from 4.53 to 5.00 with the indi-
vidual -anomer having larger d value for H-1 than the correspond-
a. These differences were also observed in the anomers
a
a
ranged from 4.69 to 5.09 and
a neighboring group participation of acetyl group at C-2 was in-
volved in the dehydration and was responsible for the stereoselec-
tivity. As postulated in Scheme 2, the neighboring participation of
the acetyl group in C-2 may lead to an intermediate having an
additional 1,3-dioxalane ring which blocks the pathway of N-(2-
a
ing b-anomer. Though the anomeric configurations of 5a–f were
deduced from 4a–f, similar differences were observed in the d values
of H-1 of 5a–f-
from 4.13 to 4.31 and the d values of H-1 of 5a–f-b ranged from
2.92 to 3.20 with the individual -anomer having larger d value for
a and 5a–f-b. The d values of H-1 of 5a–f-a ranged
nitrophenylsulfonyl)-L-amino acid t-butylester approaching the
C1 from the downside of the ring of 2,3,5-tri-O-acetyl-
L
-
a
arabinofuranose.
H-1 than the corresponding b-anomer.
ONs
R
N
H
t
CO2 Bu
O
O
OAc
OH
AcO
OAc
OH
AcO
OAc
O
OAc
1
O
CH3
O
ONs
R
N
O
H
t
OAc
CO2 Bu iii
2(a-f)-
H
AcO
O
AcO
α
O
OAc
CH3
Scheme 2. Supposed neighboring participation of acetyl group in C-2 for Mitsunobu dehydration.

M. Zhao et al. / Tetrahedron: Asymmetry 20 (2009) 247–258
249
2.2. Amadori rearrangement of N-(
a
-L
-arabinofuranos-1-yl)-
L
-
5a–f-a
and 50a–f-
a, respectively. The assignment of the signals
amino acids
was performed with 2D spectroscopy (H/H-COSY, H/C-COSY), and
the chemical shifts of the ring protons of 5(a–f)-
a
and 50(a–f)-b
The sixth reaction step is Amadori rearrangement of N-(
binofuranos-1-yl)- -amino acids 5(a–f)- . HPLC analysis, LC-MS,
and 1H NMR spectra indicated that in aqueous solution, all 5a–f-
underwent the Amadori rearrangement and N-(1-deoxy-b- -ara-
boketos-1-yl)- occurred in tautomeric
-amino acids 50a–f-
equilibrium.21–24 In the determination of the products of the Ama-
dori rearrangement of individual 5a–f- , HPLC analysis gave two
peaks and 1H NMR spectra exhibited two sets of signals corre-
sponding to 5a–f- , of which the integrations indi-
and 50a–f-
a
-
L
-ara-
are listed in Table 1. Based on the distinct chemical shifts of H-1
L
a
and H-2, their anomeric configuration could be simply assigned.
According to the integration of 1H signals, the ratios of 5 to 50a
a
a
L
ranged from 1.0:1.0 to 3.00:1.0. Similarly, the chemical shifts of
the ring protons of 5a–f-b and 50a–f-b were assigned, and are listed
in Table 2. According to integration of 1H signals, the ratios of 5b to
50b also ranged from 1.0:1.0 to 3.0:1.0.
L
a
a
a
a
2.4. Stereochemistry-dependent lead detoxification of N-(
arabinose-1-yl)- -amino acids
L-
cated that the ratios of 5a–f-
a
to 50a–f-
a
ranged from 1.0:2.0 to
L
1.0:3.0. Based on the facts that the 1H NMR spectrum of individual
anomers exhibited only two sets of signals, and the chemical shifts
To evaluate lead detoxification activity, themice loaded with lead
were treated with 5a–f- and 5a–f-b, the lead levels of kidney and
of the protons defined only 5a–f-
a
and 50a–f-
a
, a tautomeric equi-
a
librium involving ring opening, keto–enol tautomerism, and ring
closure is proposed (Scheme 3). A similar Amadori rearrangement
femur of the mice after chelating treatment were measured (see Ta-
ble 3). The data in Table 3 indicate that the kidney lead levels of the
was also observed for N-(b-
L
-arabinose-1-yl)-L-amino acids 5a–f-b,
mice receiving 0.4 mmol/kg of 5a–f-a and 5a–f-b ranged from
of which the tautomers were N-(1-deoxy-
a
-
L
-araboketos-1-yl)-
L
-
3.36 0.47 to 7.54 0.44 and from 4.04 0.50 to 9.13 1.03 mg/g
of kidney, respectively, all of them were significantly lower than that
of the mice receiving NS (11.03 1.72 mg/g of kidney, p < 0.001) and
mostof themwere significantlylowerthanthatof themicereceiving
0.4 mmol/kg of DL-penicillamine (9.46 0.63 mg/g of kidney,
p < 0.05–0.01). The femur lead levels of the mice receiving
amino acids 50a–f-b. In Scheme 3 the possible intramolecular
hydrogen bonds between 2-OH, 3-OH, and the oxygen of the car-
bonyl group of the keto-form were indicated. The formation of
these intramolecular hydrogen bonds led to five rings and six rings
that blocked the pathway of 4-OH approaching the carbonyl group
from the upside, and thus the rearrangement gave a single anomer.
0.4 mmol/kg of 5a–f-
a and 5a–f-b ranged from 37.43 1.68 to
40.43 1.29 and from 39.10 1.60 to 41.65 1.16 mg/g of femur,
respectively, all of them were significantly lower than that of the
mice receiving NS (45.43 2.89 mg/g of femur, p < 0.001) and most
of them were significantly lower than that of the mice receiving
0.4 mmol/kg of DL-penicillamine (40.74 1.19 mg/g of femur,
2.3. Chemical shifts of ring protons of the tautomers in D2O
The tautomerism of the anomers in D2O was investigated with
1H NMR. As mentioned above, individual
a- or b-anomer of N-(
L-
arabinose-1-yl)-L-amino acid simply gave two sets of spectra, one
p < 0.05–0.01). Thus both 5a–f-a and 5a–f-b effectively moved the
set of major peaks and another set of minor peaks for tautomers
lead accumulated in kidneys and femurs of the mice. Besides, the
H
R
O
H
OH
N
O
H
OH
CO2H
O
R
HO
HO
O
N
H
OH
Enol-form
CO2H
Keto-form
H
H
N
R
OH
O
O
R
OH
OH
OH
CO2H
N
H
H
CO2H
OH
5'(a-f)-α
5(a-f)-α
Scheme 3. Supposed Amadori rearrangement of 5a–f-a involving ring opening, keto–enol tautomerism, and ring closure.
Table 1
Chemical shifts (d) of ring protons of 5a–f-a and 5a–f-b in D2O
Ring proton
H-1
H-2
H-3
H-4
H-5a
H-5b
5a-
5b-
5c-
5d-
5e-
5f-
a
a
a
a
a
a
4.31
4.26
4.30
4.25
4.18
4.13
4.24
4.22
4.26
4.01
3.90
3.88
3.99
3.98
4.22
4.31
3.81
4.16
3.78
3.84
3.97
3.80
3.14
3.80
3.23
3.80
3.95
3.10
3.90
3.25
3.27
3.54
3.80
3.19
3.90
3.49
H
R
N
O
O
4
1
H
OH
3
CO2H
2
5
HO
HO
OH
5a-b
5b-b
5c-b
5d-b
5e-b
5f-b
2.98
2.92
3.16
3.20
3.15
3.12
2.92
2.90
3.09
3.10
3.00
3.02
3.83
3.81
3.55
4.06
3.09
3.00
3.75
3.81
3.62
3.90
3.99
4.15
3.31
3.44
3.61
3.70
3.93
3.37
3.25
3.37
3.52
3.60
3.86
3.33
H
1
N
4
CO2H
R
OH
3
2
5
OH
H

250
M. Zhao et al. / Tetrahedron: Asymmetry 20 (2009) 247–258
Table 2
Chemical shifts (d) of ring protons of 50a–f-
a
and 50a–f-b in D2O
Ring proton
H-1a
H-1b
H-3
H-4
H-5a
H-5b
50a-
50b-
50c-
50d-
50e-
50f-
a
a
a
a
a
a
3.35
3.08
3.25
3.34
3.25
3.32
3.15
3.28
3.15
3.06
2.98
3.57
4.14
4.17
4.14
4.18
4.08
4.12
4.37
4.32
4.37
4.32
4.25
4.22
4.07
4.05
4.06
4.05
3.98
3.97
3.82
3.82
3.83
3.88
3.67
3.69
OH
2
O
5
CO2H
R
OH
3
OH
N
H
1
4
50a-b
50b-b
50c-b
50d-b
50e-b
50f-b
3.30
3.03
3.16
3.37
3.16
3.23
3.12
2.92
3.09
3.17
3.15
3.48
3.70
3.81
3.65
4.17
4.04
4.11
3.85
3.81
3.65
4.25
4.22
4.19
3.64
3.60
3.55
3.90
3.86
3.85
3.39
3.41
3.40
3.79
3.65
3.67
H
N
R
1
O
5
2
OH
4
OH
3
CO2H
OH
Table 3
Kidney and femur lead levels of mice after chelating treatment
the mice receiving Le-
a
[N-(1-deoxy-
D
-
a
-fructos-1-yl)-
L
-phenylala-
nine, 4.12 0.483 mg/g of kidney, p < 0.01], the most potent com-
pound of the reported N-(1-deoxy- -fructos-1-yl)- -amino acids,
while the femur lead level of the mice receiving 5b- was
37.43 1.68 mg/g of femur and was similar to that of the mice
receiving Le-
(36.4 3.622 mg/g of femur, p > 0.05).16
Compounda
Kidney
Femur
D
L
a
NS
DL-PA
11.03 1.72
9.46 0.63d
10.33 2.54
10.68 2.02
10.00 2.69
10.88 2.87
11.18 2.27
11.20 1.98
10.98 1.95
4.12 0.48b
7.43 1.44c
9.13 1.03d
3.36 0.47g
4.04 0.50b
6.48 0.56c
7.02 0.52b
6.52 0.98c
7.44 0.81b
7.54 0.44c
8.10 0.40b
6.76 0.60c
7.77 0.51b
45.43 2.89
40.74 1.19f
43.22 2.08
45.66 2.76
43.59 3.55
44.02 2.97
45.28 3.11
43.95 3.16
44.88 3.21
36.4 3.62f
39.00 1.59e
40.87 1.64f
37.43 1.68e
39.10 1.60f
39.08 1.56e
40.78 1.34f
39.34 1.35e
41.07 1.21f
39.85 1.35e
41.22 1.31f
40.43 1.29f
41.65 1.16f
L
L
L
L
L
L
L
-Arab
-Asp
-Cys
-Glu
-Ser
a
3. Conclusion
-Phe
-Thr
Using the six reaction step procedure,
nose-1-yl)- -amino acids, the preferable anomers in lead detoxifi-
cation, could be exclusively formed, which makes it possible to
prepare individual N-( -arabinose-1-yl)- -amino acids as candi-
dates for developing lead detoxification drugs. In aqueous solution,
both - and b-anomers of N-( -arabinose-1-yl)- -amino acids were
in a tautomeric equilibrium with the - and b-anomers of N-(1-
deoxy- -araboketos-1-yl)- -amino acids. In this case the measured
a-anomers of N-(L-arabi-
L
Le-a16
5a
a
b
a
b
a
b
a
b
a
b
a
b
a
-L
L
5b
5c
5d
5e
5f
a
L
L
a
L
L
lead decorporation activity of each compound should be the contri-
bution of both its tautomers.
4. Experimental
4.1. General
OH
H
N
O
CH2C5H6
CO2H
HO
Le-α
=
OH
OH
All the reactions were carried out under nitrogen (1 bar). 1H
(300 and 500 MHz) and 13C (75 and 125 MHz) NMR spectra were
recorded on Bruker AMX-300 and AMX-500 spectrometers for
solution D2O, DMSO-d6, or CDCl3 with tetramethyl-silane as inter-
nal standard. FAB/MS was determined on VG-ZAB-MS. Melting
point was measured on an XT5 hot-stage microscope (Beijing keyi
electro-optic factory) and uncorrected. Optical rotations were
determined on a Schmidt and Haensch Polartronic D instrument
a
Data are represented with microgram lead per gram tissue (X SE), D
-Arab = -arabinose, NS = vehicle, n = 10, dose = 0.4 mmol/kg;
-Cys, -Glu, -Phe, and -Thr = reference compounds; kidney
L-PA =
DL-penicillamine,
-arabinose, -Asp,
L
L
L
L
L
L
L
L
lead levels of mice after reference compound treatment ranged from 10.00 2.69 to
11.20 1.98, compared to NS p > 0.05; Femur lead levels of mice after reference
compound treatment ranged from 43.22 2.08 to 45.66 2.76, compared to NS
p > 0.05.
b
Compared to NS and reference compounds p < 0.001, and to DL-penicillamine
at 20 °C. All L-amino acids and L-arabinose were purchased from
p < 0.01.
c
China Biochemical Corp. 2-Nitrophenylsulfonyl chloride (oNsCl),
Ph3P, DIAD, trifluoroacetic acid (TFA), DIPEA, PhSH, and 2-nitro-
phenylsulfenyl chloride (NpsCl) were purchased from Aldrich.
TLC was made with Qingdao silica gel GF254. Chromatography
was performed with Qingdao silica gel H60 or Sephadex-LH20. All
solvents were distilled and dried before use.
Compared to NS, reference compounds, and DL-penicillamine p < 0.001, and to
corresponding b-anomer p < 0.05.
d
Compared to NS and reference compounds p < 0.05.
Compared to NS and reference compounds p < 0.001, to DL-penicillamine and
e
corresponding b-anomer p < 0.05.
f
Compared to NS and reference compounds p < 0.001.
Compared to NS, reference compounds, and DL-penicillamine p < 0.001, to cor-
g
responding b-anomer p < 0.05 and to Le-a p < 0.01.
4.2. Chemical preparation
lead levels of the kidneys and femurs of the mice receiving 5a–f-
were significantly lower than that of the mice receiving 5a–f-b, thus
N-( -arabinofuranos-1-yl)- -amino acids obviously exhibited a ste-
reo-chemistry-dependent lead detoxification. On the other hand,
the kidney lead level of the mice receiving 5b- , the most potent
compound of N-( -arabinofuranos-1-yl)- -amino acids, was
3.36 0.47 mg/g of kidney and was significantly lower than that of
a
4.2.1. 2,3,5-Tri-O-acetyl–L-arabinose
The solution of 6.0 ml (90.0 mmol) of ethyldiamine, 5.3 ml
(90.0 mmol) of glacial acetic acid, and 150 ml of anhydrous THF
was stirred at room temperature for 0.5 h. To the solution, 15.9 g
L
L
a
(50.0 mmol) of 1,2,3,5-tetra-O-acetyl-
L-furanoarabinose was
L
L
added, which was prepared from -(+)-arabinose according to the
L

M. Zhao et al. / Tetrahedron: Asymmetry 20 (2009) 247–258
251
method described in the literature.25 The reaction mixture was
stirred at room temperature for 18 h and TLC analysis (petroleum
ether:ethyl acetate, 2:1) indicated complete disappearance of
J = 8.5 Hz, J = 3.0 Hz, 1H), 3.61 (dd, J = 8.5 Hz, J = 3.0 Hz, 1H), 1.28
(s, 9H), 1.09 (s, 9H); FAB/MS (m/e) 403 [M+H]+. Anal. Calcd for
C17H26O7N2S: C, 50.74; H, 6.51; N, 6.96. Found: C, 51.01; H, 6.69;
N, 6.72.
1,2,3,5-tetra-O-acetyl-L-furanoarabinose. The reaction mixture
was evaporated under vacuum to remove the THF. The resulting
residue was dissolved in ethyl acetate (200 ml) and the solution
was washed successively with saturated NaCl solution, NaHCO3
solution (5%), hydrochloric acid (5%), and saturated NaCl solution.
The organic layer was dried over anhydrous MgSO4. After filtration,
the filtrate was evaporated under vacuum to give 12.4 g (90%) of
the title compound as pale yellow syrup. FAB/MS (m/e): 277
[M+H]+.
4.2.6. N-(2-Nitrobenzenesulfonyl)-
Using the same procedure as that used for the preparation of
N-(2-nitrobenzenesulfonyl)- -aspartic acid t-butylester with 2.6 g
(10 mmol) of -phenylalanine t-butylester hydrochloride instead
of -aspartic acid t-butylester, 3.7 g (92%) of title compound was
obtained as a colorless powder. Mp 92–93 °C; FAB/MS (m/e) 407
[M+H]+. Anal. Calcd for C19H22O6N2S: C, 56.15; H, 5.46; N, 6.89.
Found: C, 56.40; H, 5.69; N, 6.65.
L-phenylalanine t-butylester
L
L
L
4.2.2. N-(2-Nitrobenzenesulfonyl)-
di-t-butylester
L
-aspartic acid
-aspartic acid di-t-butylest-
4.2.7. N-(2-Nitrobenzenesulfonyl)-
t-butylester
L-O-t-butyl-theorine
The solution of 2.45 g (10 mmol) of
L
er, which was prepared according to the method published in the lit-
erature,26 2 ml (15 mmol) of triethylamine, and 0.33 g (2 mmol) of
4-dimethylaminopyridine (DMAP) in 100 ml of anhydrous CH2Cl2
was stirred at room temperature for 15 min. The reaction mixture
was cooled with ice bath to which 2.22 g (10 mmol) of oNsCl was
added proportionally. The reaction mixture was stirred at room tem-
perature for 3 h and TLC analysis (petroleum ether:ethyl acetate,
2:1) indicated complete disappearance of the starting materials.
The reaction mixture was evaporated under vacuum to remove the
CH2Cl2. The resulting residue was dissolved in 100 ml of ethyl ace-
tate and the solution was washed successively with saturated NaCl
solution, KHSO4 solution (5%), and saturated NaCl solution. The or-
ganic layer was finally dried over anhydrous MgSO4. After filtration,
the filtrate was evaporated under vacuum and 3.87 g (90%) of the ti-
tle compound was obtained as colorless solid. Mp 107–108 °C, FAB/
MS (m/e): 431[M+H]+. Anal. Calcd forC18H26O8N2S: C, 50.20; H, 6.09;
N, 6.51. Found: C, 50.40; H, 6.19; N, 6.38.
Using the same procedure as that used for the preparation of
N-(2-nitrobenzenesulfonyl)- -aspartic acid t-butylester with 2.2 g
(10 mmol) of -theorine t-butylester hydrochloride instead of
L
L
L
-aspartic acid t-butylester, 3.9 g (92 %) of title compound was ob-
tained as colorless powder. Mp 95 °C; FAB/MS (m/e): 417 [M+H]+.
Anal. Calcd for C18H28N2SO7: C, 51.92; H, 6.80; N, 6.75. Found: C,
52.05; H, 6.98; N, 6.93.
4.2.8. General procedure for preparing
N-[2,3,5-tri-O-acetyl- -arabinofuranos-1-yl]-N-(2-
nitrophenylsulfonyl)- -amino acid t-butyl-esters 2a–f
The solution of 0.6 g (2.0 mmol) of 2,3,5-tri-O-acetyl-
nose, 0.5 g (2.0 mmol) of Ph3P and 1.0 mmol of N-(2-nitrophenyl-
sulfonyl)- -amino acid t-butylester in 15 ml of anhydrous THF
a- and b-anomers of
L
L
L
-arabi-
L
was cooled to ꢀ80 °C under the protection of argon. To this cooled
solution, 0.4 ml (2.0 mmol) of DIAD was added immediately. The
reaction mixture was stirred initially at ꢀ60 °C and then gradually
warmed to 20 °C during 8 h, and TLC analysis (petroleum ether:-
ethyl acetate, 2:1) indicated complete disappearance of N-(2-nitro-
4.2.3. N-(2-Nitrobenzenesulfonyl)-S-t-butyl-
L-cysteine
t-butylester
phenylsulfonyl)-L-amino acid t-butylester. The reaction mixture
Using the same procedure as that used for the preparation of N-
(2-nitroben-zenesulfonyl)- -aspartic acid t-butylester with 0.7 g
(3 mmol) of S-t-butyl- -cysteine t-butylester instead of -aspartic
was evaporated under vacuum to remove the THF. The resulting
residue was purified and separated on chromatography (petroleum
ether:ethyl acetate, 2:1) to give a- and b-anomers of 2a–f.
L
L
L
acid t-butylester, 1.2 g (95%) of title compound was obtained as
yellow powder. Mp 97–100 °C, 1H NMR (500 MHz CDCl3):
d = 8.13 (d, J = 10.0 Hz, 1H), 7.58 (m, 1H), 7.30 (m, 1H), 6.32 (d,
J = 5.0 Hz, 1H), 4.32 (m, 1H), 3.56 (dd, J = 13.5 Hz, J = 5.5 Hz, 1H),
3.44 (dd, J = 13.5 Hz, J = 5.5 Hz, 1H), 1.3 (s, 18H); FAB/MS (m/e):
419 [M+H]+. Anal. Calcd for C17H26O6N2S2: C, 48.79; H, 6.26; N,
6.69. Found: C, 48.90; H, 6.40; N, 6.12.
4.2.8.1. Anomers of N-(2,3,5-tri-O-acetyl-
yl)-N-(2-nitrobenzenesulfonyl)- –aspartic acid di-t-butylester
(2a- and 2a-b). Using the general procedure for preparing
- and b-anomers of 2a–f from 431 mg (1.0 mmol) of N-(2-nitro-
phenylsulfonyl)- -aspartic acid di-t-butylester, 585 mg (85%) of
2a-
Compound 2a-
L-arabinofuranos-1-
L
a
a
L
a
and 69 mg (10%) of 2a-b were obtained as colorless powder.
a
: Mp 68–70 °C, ½a 2D5
ꢁ
¼ þ49:6 (c 1.1, CHCl3), 1H
4.2.4. N-(2-Nitrobenzenesulfonyl)-
L
-glutamic acid
NMR (500 MHz, CDCl3): d = 8.24 (d, J = 9.5 Hz, 1H), 7.69 (m,
J = 9.2 Hz, 2H), 7.59 (m, J = 9.0 Hz, 1H), 5.22 (t, J = 6.5 Hz, 1H),
5.03 (dd, J = 10.0 Hz, J = 3.5 Hz, 1H), 4.94 (q, J = 13.5 Hz, 1H), 4.04
(dd, J = 13.0 Hz, J = 3.0 Hz, 1H), 3.69 (d, J = 13.5 Hz, 1H), 3.03 (m,
J = 4.3 Hz, 1H), 2.75 (dd, J = 15.0 Hz, J = 4.5 Hz, 1H), 2.2 (s, 3H),
2.17 (s, 3H), 2.14 (m, J = 4.3 Hz, 2H), 2.00 (s, 3H), 1.45 (s, 9H),
1.32 (s, 9H). 13C NMR (500 MHz, CDCl3): d = 171.5, 169.9, 169.2,
168.6, 167.7, 147.8, 133.5, 132.3, 131.8, 123.9, 87.9, 81.7, 73.8,
73.7, 69.0, 68.5, 68.4, 65.3, 38.8, 27.5, 27.2, 21.0, 20.8, 20.6, 20.1.
FAB/MS (m/e): 689 [M+H]+. Anal. Calcd for C29H40O15N2S: C,
50.58; H, 5.85; N, 4.07. Found: C, 50.44; H, 5.69; N, 3.99.
di-t-butylester
Using the same procedure as that used for the preparation of N-
(2-nitrobenzenesulfonyl)- -aspartic acid t-butylester with 3.0 g
(10 mmol) of -glutamate di-t-butylester hydrochloride instead of
-aspartic acid t-butylester, 4.0 g (90%) of title compound was ob-
L
L
L
tained as colorless powder. Mp 101–103 °C, FAB/MS (m/e): 445
[M+H]+. Anal. Calcd for C19H28O8N2S: C, 51.34; H, 6.35; N, 6.30.
Found: C, 51.50; H, 6.60; N, 6.10.
4.2.5. N-(2-Nitrobenzenesulfonyl)-O-t-butyl-
L-serine
t-butylester
Compound 2a-b: Mp 76–79 °C, ½a D25
ꢁ
¼ þ8:0 (c 1.3, CHCl3), 1H
Using the same procedure as that used for the preparation of N-
(2-nitrobenzenesulfonyl)- -aspartic acid t-butylester with 2.5 g
(10 mmol) of O-t-butyl- -serine-t-butylester hydrochloride instead
of
NMR (500 MHz,CDCl3): d = 8.16 (dd, J = 5.8 Hz, J = 3.5 Hz, 1H),
7.58 (m, J = 6.2 Hz, 1H), 7.75 (m, J = 5.9 Hz, 2H), 5.51 (s, 1H), 5.29
(t, J = 5.5 Hz 1H), 5.21 (dd, J = 10.5 Hz, J = 2.5 Hz, 1H), 5.14 (m,
J = 4.9 Hz, 1H), 4.97 (m, J = 5.2 Hz, 1H), 4.81 (s, 1H), 3.89 (dd,
J = 10.5 Hz, J = 1.0 Hz, 1H), 3.93 (dd, J = 15.0 Hz, J = 5.5 Hz, 1H),
3.23 (dd, J = 17.0 Hz, J = 10.5 Hz, 1H), 2.22 (s, 9H), 1.46 (s, 9H),
1.32 (s, 9H). 13C NMR (500 MHz, CDCl3): d = 170.40, 169.90,
L
L
L
-aspartic acid t-butylester, 3.8 g (94%) of title compound was
obtained as colorless powder. Mp 103–104 °C; 1H NMR
(300 MHz, CDCl3) d = 8.09 (d, J = 10.0 Hz, 1H), 7.94 (m, 1H), 7.74–
7.77 (m, 2H), 6.37 (d, J = 5.0 Hz, 1H), 4.24 (m, 1H), 3.79 (dd,

252
M. Zhao et al. / Tetrahedron: Asymmetry 20 (2009) 247–258
169.50, 169.20, 167.90, 149.60, 134.70, 133.20, 132.60, 131.20,
123.80, 85.30, 83.90, 74.30, 74.00, 69.70, 67.50, 61.30, 55.90,
38.90, 27.90, 27.50, 20.60, 20.50, 20.49, 20.47. FAB/MS (m/e): 689
[M+H]+. Anal. Calcd for C29H40O15N2S: C, 50.58; H, 5.85; N, 4.07.
Found: C, 50.39; H, 5.73; N, 4.19.
4.2.8.4. Anomers of N-(2,3,5-tri-O-acetyl-
yl)-N-(2-nitrobenzenesulfonyl)- -O-t-butylserine-t-butylester
2d- and 2d-b. Using the general procedure for preparing - and b-
anomers of 2a–f from 402 mg (1.0 mmol) of N-(2-nitro-
benzenesulfonyl)-O-t-butyl- -serine t-butyl ester, 508 mg (77%) of
L-arabinofuranos-1-
L
a
a
L
2d-
a and 66 mg (10%) of 2d-b were obtained as colorless powder.
4.2.8.2. Anomers of N-(2,3,5-tri-O-acetyl-
yl)-N-(2-nitrobenzenesulfonyl)-S-t-butyl- -cysteine t-butylester
2b- and 2b-b. Using the general procedure for preparing - and
b-anomers of 2a–f from 418 mg (1.0 mmol) of N-(2-nitro-
benzenesulfonyl)-S-t-butyl- -cysteine t-butylester, 548 mg (81%)
L
-arabinofuranos-1-
Compound 2d-
a
: Mp 61–63 °C, ½a 2D5
ꢁ
¼ þ82:2 (c 1.1, CHCl3); 1H
L
NMR (500 MHz, CDCl3): d = 8.31 (d, J = 10 Hz, 1H), 7.64 (m,
J = 8.7 Hz, 2H), 7.51 (d, J = 9.0 Hz,1H), 5.95 (s, 1H), 5.25 (s, 1H),
5.20 (d, J = 5.0 Hz, 1H), 4.99 (dd, J = 9.5 Hz, J = 3.5 Hz, 1H), 4.50
(m, J = 8.8 Hz, 1H), 4.02 (dd, J = 10.5 Hz, J = 1.0 Hz, 1H), 3.76 (m,
J = 9.5 Hz, 2H), 3.64 (d, J = 14.5 Hz, 1H), 2.03 (s, 3H), 2.19 (s, 3H),
1.99 (s, 3H), 1.25 (s, 9H), 1.17 (s, 9H). 13C NMR (500 MHz, CDCl3):
d = 170.4, 170.1, 168.6, 167.7, 148.5, 133.5, 132.3, 131.1, 123.2,
81.7, 73.7, 86.6, 72.2, 68.5, 68.2, 67, 62.0, 60.6, 27.5, 27.2, 21.0,
20.8, 20.6. FAB/MS (m/e): 661 [M+H]+. Anal. Calcd for
C28H40O14N2S: C, 50.90; H, 6.10; N, 4.24. Found: C, 50.72; H,
6.21; N, 4.16.
a
a
L
of 2b-
a and 61 mg (9%) of 2b-b were obtained as colorless powder.
Compound 2b-
a
: Mp 66–67 °C, ½a 2D5
ꢁ
¼ þ50 (c 1.1, CHCl3). 1H
NMR (500 MHz, CDCl3): d = 8.26(d, J = 8.0 Hz, 1H), 7.69 (m,
J = 7.6 Hz, 2H), 7.55 (d, J = 7.5 Hz, 1H), 5.26 (s, 1H), 5.04 (dd,
J = 11.5 Hz, J = 3.5 Hz, 1H), 4.93 (m, J = 11.3 Hz, 2H), 4.43 (m,
J = 10.6 Hz, 1H), 4.01 (d, J = 15.0 Hz, 1H), 3.65 (d, J = 10.0 Hz, 1H),
3.10 (t, J = 10.0 Hz, 1H), 2.76 (s, 1H), 2.11 (s, 9H), 1.23 (s, 9H),
1.34 (s, 9H). 13C NMR (500 MHz,CDCl3): d = 170.3, 170.0, 168.6,
167.6, 148.8, 133.7, 132.9, 131.8, 131.0, 123.4, 85.3, 82.4, 72.2,
68.2, 67.8, 66.0, 60.0, 66.4, 42.9, 30.7, 27.4, 27.3, 21.8, 20.8, 20.7,
20.6, 20.5. FAB/MS (m/e): 677 [M+H]+. Anal. Calcd for
C28H40O13N2S2: C, 49.69; H, 5.96; N, 4.14. Found: C, 49.81; H,
5.83; N, 4.02.
Compound 2d-b: Mp 58–62 °C, ½a D25
ꢁ
¼ þ7:0 (c 1.2, CHCl3). 1H
NMR (500 MHz, CDCl3): d = 8.51 (d, J = 7.5 Hz, 1H), 7.70 (m,
J = 7.0 Hz, 2H), 7.65 (d, J = 6.8 Hz, 1H), 5.38 (m, (d, J = 5.2 Hz, 1H),
5.35 (s, 1H), 5.14 (m, J = 5.2 Hz, 1H), 4.98 (d, J = 4.0 Hz, 1H), 4.66
(m, J = 7.8 Hz, 1H), 4.04 (dd, J = 10.0 Hz, J = 5.0 Hz, 1H), 3.96 (dd,
J = 10.8 Hz, J = 5.5 Hz, 1H), 3.74 (m, J = 8.2 Hz, 2H), 1.99 (s, 9H),
1.15 (s, 9H), 1.45 (s, 9H). 13CNMR (500 MHz, CDCl3): d = 169.6,
168.9, 168.7, 168.6, 133.6, 131.8, 130.8, 124, 123.1, 81.3, 73.5,
83.3, 70.8, 66.4, 61.3, 64.0, 64.2, 61.4, 27.6, 27.4, 21.8, 21.1, 20.7,
20.6. FAB/MS (m/e): 661 [M+H]+. Anal. Calcd for C31H44O16N2S: C,
50.90; H, 6.10; N, 4.24. Found: C, 50.70; H, 6.19; N, 4.16.
Compound 2b-b: Mp 70–71 °C, ½a D25
ꢁ
¼ þ10 (c 1.1, CHCl3). 1H
NMR (500 MHz,CDCl3): d = 8.22 (m, J = 7.6 Hz, 1H), 7.74 (m,
J = 7.2 Hz, 1H), 7.58 (m, J = 7.3 Hz, 2H), 5.55 (s, 1H), 5.32 (t,
J = 7.0 Hz, 1H), 5.08 (m, J = 10.8 Hz, 1H), 4.83 (d, J = 3.5 Hz, 1H),
4.70 (dd, J = 8.8 Hz, J = 4.5 Hz, 1H), 3.94 (m, J = 3.8 Hz, 1H), 3.93
(d, J = 3.5 Hz, 1H), 3.45 (m, J = 9.2 Hz, 1H), 2.76 (dd, J = 15.0 Hz,
J = 4.5 Hz, 1H), 2.10 (s, 9H), 1.31 (s, 9H),1.47 (s, 9H). 13C NMR
(500 MHz, CDCl3): d = 169.7, 169.2, 168.8, 168.3, 148.8, 134.3,
132.3, 131.9, 131.4, 123.5, 80.7, 83.3, 70.7, 66.5, 63.9, 61.8, 66.4,
42.6, 30.7, 30.4, 27.6, 21, 20. FAB/MS (m/e): 677 [M+H]+. Anal. Calcd
for C28H40O13N2S2: C, 49.69; H, 5.96; N, 4.14. Found: C, 49.56; H,
6.01; N, 4.34.
4.2.8.5. Anomers of N-(2,3,5-tri-O-acetyl-
yl)-N-(2-nitrobenzenesulfonyl)- -phenylalanine t-butylester
2e- and 2e-b. Using the general procedure for preparing - and
b-anomers of 2a–f from 406 mg (1.0 mmol) of N-(2-nitro-
benzenesulfonyl)- -phenylalanine t-butylester, 574 mg (81%) of
2e-
Compound 2e-
a-L-arabinofuranos-1-
L
a
a
L
a
and 66 mg (9%) of 2e-b were obtained as colorless powder.
a
: Mp 75–77 °C, ½a 2D5
ꢁ
¼ þ14:8 (c 1.0, CHCl3), 1H
4.2.8.3. Anomers of N-(2,3,5-tri-O-acetyl-
yl)-N-(2-nitrobenzenesulfonyl)- -glutamic acid di-t-butylester
2c- and 2c-b. Using the general procedure for preparing and b
anomers of 2a–f from 70 mg (1.0 mmol) of N-(2-nitro-
benzenesulfonyl)- -glutamic acid di-t-butylester, 597 mg (85%) of
2c-
Compound 2c-
a
-L
-arabinofuranos-1-
NMR (500 MHz,CDCl3): d = 8.29 (dd, J = 4.2 Hz, J = 1.5 Hz, 1H),
7.55(d, J = 9.0 Hz, 1H), 7.67 (m, J = 8.7 Hz, 2H), 7.29 (t, J = 7.0 Hz,
1H), 7.28 (d, J = 7.2 Hz, 2H), 7.21 (t, J = 7.0 Hz, 2H), 6.01 (s, 1H),
5.30 (s, 1H), 5.11 (dd, J = 10.0 Hz, J = 3.5 Hz, 2H), 4.57 (m,
J = 7.2 Hz, 1H), 4.04 (dd, J = 10.0 Hz, J = 2.0 Hz, 1H), 3.70 (d,
J = 13.0 Hz, 1H), 3.23 (m, J = 7.8 Hz, 1H), 3.04 (m, J = 7.6 Hz, 1H),
2.10 (s, 9H), 1.26 (s, 9H). 13C NMR (500 MHz, CDCl3): d = 170.2,
169.9, 168.7, 167.9, 148,8, 133.8, 131.5, 131.3, 131.2, 129.4,
129.0, 128.2, 126.7, 123.3, 81.6, 85.2, 72.0, 68.1, 67.5, 60.7, 66.2,
38.5, 27.1, 26.9, 21.6, 20.7, 20.5, 20.4. FAB/MS (m/e): 665 [M+H]+.
Anal. Calcd for C30H36O13N2S: C, 54.21; H, 5.46; N, 4.21. Found: C,
54.18; H, 5.28; N, 4.33.
L
a
a
L
a
and 159 mg (10%) of 2c-b were obtained as colorless powder.
a
: Mp 73–75 °C, ½a 2D5
ꢁ
¼ þ45:0 (c 1.2, CHCl3), 1H
NMR (500 MHz,CDCl3): d = 8.24 (d, J = 8.0 Hz, 1H), 7.65 (m,
J = 7.5 Hz, 2H), 7.52 (d, J = 7.5 Hz, 1H), 6.03 (s, 1H), 5.23 (s, 1H),
5.00 (dd, J = 9.5 Hz, J = 3.5 Hz, 1H), 4.79 (s, 1H), 4.48 (t,
J = 15.0 Hz, 1H), 3.96 (dd, J = 13.5 Hz, J = 1.5 Hz, 1H), 3.59 (d,
J = 13.0 Hz, 1H), 2.35 (m, J = 9.5 Hz, 2H), 2.10 (m, J = 8.9 Hz, 2H),
2.01 (s, 9H),1.19 (s, 9H) ,1.44 (s, 9H). 13C NMR (500 MHz, CDCl3):
d = 171.4, 170.0, 169.6, 169.1, 168.1, 148.6, 133.8, 133.2, 132.0,
131.2, 123.5, 85.1, 82.3, 81.5, 74.0, 72.3, 69.7, 67.5, 60.3, 39.2,
28.0, 27.5, 20.7, 20.6, 20.5, 20.4. FAB/MS (m/e): 703 [M+H]+. Anal.
Calcd for C30H42O15N2S: C, 51.28; H, 6.02; N, 3.99. Found: C,
51.19; H, 5.98; N, 4.01.
Compound 2e-b: Mp 68–70 °C, ½a D25
ꢁ
¼ þ44:4 (c 1.1, CHCl3), 1H
NMR (500 MHz, CDCl3): d = 8.17 (d, J = 8.0 Hz, 1H), 7.67 (m,
J = 7.3 Hz, 2H), 7.59 (d, J = 7.5 Hz, 1H), 7.33 (t, J = 7.2 Hz, 1H), 7.32
(d, J = 7.0 Hz, 2H), 7.30 (t, J = 7.2 Hz, 2H), 5.63 (s, 1H), 5.35 (t,
J = 9.4 Hz, 1H), 5.20 (m, J = 8.6 Hz, 1H), 4.91 (m, J = 7.2 Hz, 2H),
3.97 (m, J = 7.1 Hz, 2H), 3.59 (dd, J = 13.5 Hz, J = 10.0 Hz, 1H), 3.13
(d, J = 13.5 Hz, 1H), 1.99 (s, 3H), 2.17 (s, 6H), 1.39 (s, 9H). 13C
NMR (500 MHz, CDCl3): d = 169.7, 169.2, 168.9, 168.3, 148.7,
139.3, 134.3, 132.3, 131.8, 131.2, 128.9, 128.1, 126.2, 123.4, 81.0,
82.7, 70.7, 66.4, 64.1, 64.0, 61.4, 39.2, 27.5, 20.5, 20.8. FAB/MS
(m/e): 665 [M+H]+. Anal. Calcd for C30H36O13N2S: C, 54.21; H,
5.46; N, 4.21. Found: C, 54.19; H, 5.38; N, 4.16.
Compound 2c-b: Mp 71–73 °C, ½a D25
ꢁ
¼ 15:0 (c 1.2, CHCl3), 1H
NMR (500 MHz,CDCl3): d = 8.08 (m, J = 7.8 Hz, 1H), 7.71 (m,
J = 7.7 Hz, 2H), 7.54 (m, J = 7.6 Hz, 1H), 5.5 (d, J = 1.5 Hz, 1H), 5.36
(s, 1H), 5.00 (m, J = 8.8 Hz, 1H), 4.92 (s, 1H), 4.62 (m, J = 9.0 Hz,
1H), 3.88 (m, J = 10.2 Hz, 2H), 2.45 (m, J = 8.7 Hz, 2H), 2.23 (m,
J = 8.6 Hz, 2H), 1.96 (s, 9H), 1.42 (s, 18H). 13C NMR (500 MHz,
CDCl3): d = 171.1, 170.2, 170.0, 169.0, 168.5, 148.7, 134.0, 132.6,
131.9, 131.7, 123.1, 84.3, 82.1, 80.5, 73.2, 70.1, 68.5, 67.1, 61.0,
31.4, 27.80, 27.3, 27.1, 20.5, 20.4, 20.3. FAB/MS (m/e): 703
[M+H]+. Anal. Calcd for C30H42O15N2S: C, 51.28; H, 6.02; N, 3.99.
Found: C, 51.19; H, 6.01; N, 4.01.
4.2.8.6. Anomers of N-(2,3,5-tri-O-acetyl-
yl)-N-(2-nitrobenzenesulfonyl)- -O-t-butyltheorine t-butylester
2f- and 2f-b. Using the general procedure for preparing - and
b-anomers of 2a–f from 416 mg (1.0 mmol) of N-(2-nitro-
a-L-arabinofuranos-1-
L
a
a

M. Zhao et al. / Tetrahedron: Asymmetry 20 (2009) 247–258
253
benzenesulfonyl)-
of 2f-
Compound 2f-
L
-O-t-butyl-theorine t-butylester, 519 mg (77%)
d = 8.59 (s, 2H,), 8.18 (d, J = 9.2 Hz, 1H), 7.48 (m, J = 8.2 Hz, 2H),
7.31 (m, J = 8.4 Hz, 1H), 5.20 (t, J = 6.3 Hz, 1H), 5.00 (dd,
J = 10.0 Hz, J = 3.3 Hz, 1H), 4.86 (q, J = 13.2 Hz, 1H), 3.97 (dd,
J = 13.0 Hz, J = 3.2 Hz, 1H), 3.70 (d, J = 13.2 Hz, 1H), 3.12 (m,
J = 4.9 Hz, 1H), 2.72 (dd, J = 15.0 Hz, J = 4.3 Hz, 1H), 2.22 (s, 3H),
2.19 (s, 3H), 2.12 (m, J = 5.7 Hz, 2H), 2.02 (s, 3H). FAB/MS (m/e):
577 [M+H]+. Anal. Calcd for C21H24O15N2S: C, 43.75; H, 4.20; N,
4.86. Found: C, 43.82; H, 4.30; N, 4.99.
a
and 68 mg (10%) of 2f-b were obtained as colorless powder.
a
: Mp 77–79 °C, ½a 2D5
ꢁ
¼ þ6:0 (c 1.0, CHCl3), 1H
NMR (500 MHz, CDCl3): d = 8.38 (m, J = 8.0 Hz, 1H), 7.64 (m,
J = 7.6 Hz, 2H), 7.54 (m, J = 7.3 Hz, 1H), 5.23 (d, J = 2.7 Hz, 1H),
4.92 (dd, J = 10.2 Hz, J = 3.3 Hz, 1H), 4.50 (d, J = 3.0 Hz, 1H), 4.33
(m, J = 8.2 Hz, 1H), 3.84 (d, J = 13.2 Hz, 2H), 3.62 (m, J = 9.6 Hz,
1H), 3.59 (m, J = 13.5 Hz, 1H), 2.21 (s, 9H), 2.09 (s, 9H), 1.74 (d,
J = 6.0 Hz, 3H), 1.30 (s, 9H). 13C NMR (500 MHz, CDCl3): d = 170.4,
170.1, 168.6, 167.3, 148.6, 134.6, 133.4, 132.8, 131.1, 123.4, 81.7,
74.1, 87.4, 73.2, 69.4, 65.2, 68.9, 67.1, 68.7, 31.6, 28.7, 27.8, 21.1,
21.0, 20.6, 19.4. FAB/MS (m/e): 675 [M+H]+. Anal. Calcd for
C30H36O13N2S: C, 51.62; H, 6.27; N, 4.15. Found: C, 51.59; H,
6.15; N, 4.21.
4.2.9.3. N-(2,3,5-Tri-O-acetyl-
nitrobenzenesulfonyl)-S-t-butyl-
eral procedure for preparing - and b-anomers of 3a–f from
676 mg (1.0 mmol) of N-(2,3,5-tri-O-acetyl- -arabinofuranos-1-
yl)-N-(2-nitrobenzenesulfonyl)-S-t-butyl- -cysteine t-butylester
a
-L
-arabinofuranos-1-yl)-N-(2-
L
-cysteine 3b- . Using the gen-
a
a
a-L
L
Compound 2f-b: Mp 73–75 °C, ½a D25
ꢁ
¼ þ64:0 (c 1.0, CHCl3), 1H
2b-
a, 539 mg (87%) of 3b-a was obtained as colorless powder.
NMR (300 MHz,CDCl3): d = 8.28 (m, J = 7.1 Hz, 1H), 7.72 (m,
J = 6.9 Hz, 2H), 7.56 (m, J = 6.7 Hz, 1H), 5.27 (dd, J = 14.4 Hz,
J = 5.0 Hz, 1H), 5.14 (d, J = 3.0 Hz, 1H), 4.50 (t, J = 16.2 Hz, 1H),
4.28 (m, J = 7.8 Hz, 1H), 3.97 (d, J = 8.1 Hz, 2H), 3.66 (m,
J = 9.4 Hz, 1H), 3.61 (m, J = 12.5 Hz, 1H), 1.80 (d, J = 6.6 Hz, 3H),
2.13 (s, 9H), 2.02 (s, 9H), 1.37 (s, 9H). 13C NMR (300 MHz, CDCl3):
d = 169.7, 169.5, 168.8, 168.1, 148.0, 134.6, 133.4, 132.8, 131.0,
123.4, 81.7, 83.6, 74.4, 71.7, 70.1, 68.5, 67.0, 63.9, 64.6, 34.4,
29.1, 27.8, 21.6, 21.1, 21.0, 19.4. FAB/MS (m/e): 675 [M+H]+. Anal.
Calcd for C30H36O13N2S: C, 51.62; H, 6.27; N, 4.15. Found: C,
51.65; H, 6.33; N, 4.21.
Mp 117–120 °C,
½
a 2D5
ꢁ
¼ þ101:0 (c 1.2, CHCl3). 1H NMR
(500 MHz,CDCl3): d = 8.79 (s, 1H), 8.26 (d, J = 8.0 Hz, 1H), 7.70 (m,
J = 7.5 Hz, 2H), 7.55 (d, J = 7.5 Hz, 1H), 5.26 (s , 1H), 5.00 (dd,
J = 11.5 Hz, J = 3.5 Hz, 1H), 4.93 (m, J = 11.0 Hz, 2H), 4.43 (m,
J = 10.2 Hz, 1H), 4.01 (d, J = 15.0 Hz, 1H), 3.65 (d, J = 10.0 Hz, 1H),
3.10 (t, J = 10.0 Hz, 1H), 2.76 (s, 1H), 2.12 (s, 9H), 1.34 (s, 9H);
FAB/MS (m/e): 621 [M+H]+. Anal. Calcd for C24H32O13N2S2: C,
46.45; H, 5.20; N, 4.51. Found: C, 46.51; H, 5.07; N, 4.39.
4.2.9.4. N-(2,3,5-Tri-O-acetyl-b-
nitrobenzenesulfonyl]-S-t-butyl-
eral procedure for preparing - and b-anomers of 3a–f from
676 mg (1.0 mmol) of N-(2,3,5-tri-O-acetyl-b- -arabinofuranos-1-
yl)-N-(2-nitrobenzenesulfonyl)-S-t-butyl- -cysteine t-butylester
L-arabinofuranos-1-yl)-N-[2-
L
-cysteine 3b-b. Using the gen-
a
4.2.9. General procedure for preparing
N-(2,3,5-tri-O-acetyl- -arabinofuranos-1-yl)-N-(2-nitro-
benzenesulfonyl)- -amino acid (3a–f)
The solution of 1.0 mmol of epimerically pure N-(2,3,5-tri-O-
acetyl- -arabino-furanos-1-yl)-N-(2-nitrophenylsulfonyl)- -amino
acid t-butyl ester 2a–f- or 2a–f-b and 5.5 ml of CF3CO2H was vig-
a- and b-anomers of
L
L
L
L
2b-b, 558 mg (90%) of 3b-b was obtained as colorless powder.
Mp 102–104 °C,
½
a 2D5
ꢁ
¼ þ48:0 (c 1.3, CHCl3). 1H NMR
L
L
(500 MHz,CDCl3): d = 8.60 (s, 1H), 8.20 (d, J = 8.1 Hz, 1H), 7.55 (m,
J = 7.3 Hz, 2H), 7.42 (d, J = 7.3 Hz, 1H), 5.17 (s , 1H), 4.89 (dd,
J = 11.2 Hz, J = 3.3 Hz, 1H), 4.78 (m, J = 11.2 Hz, 2H), 4.36 (m,
J = 10.0 Hz, 1H), 3.92 (d, J = 15.1 Hz, 1H), 3.90 (d, J = 10.2 Hz, 1H),
3.01 (t, J = 10.2 Hz, 1H), 2.70 (s, 1H), 2.10 (s, 9H), 1.32 (s, 9H);
FAB/MS (m/e): 621 [M+H]+. Anal. Calcd for C24H32O13N2S2: C,
46.45; H, 5.20; N, 4.51. Found: C, 46.34; H, 5.31; N, 4.42.
a
orously stirred at room temperature for 3 h, and TLC analysis
(petroleum ether:ethyl acetate:glacial acetic acid, 2:1:0.2) indi-
cated complete disappearance of 2a–f-
mixture was evaporated under vacuum to remove the CF3CO2H.
The residue was dissolved in acetone and evaporated under vac-
uum, which was repeated three times to remove the trace
CF3CO2H. The residue was purified by chromatography (petroleum
ether:ethyl acetate:glacial acetic acid, 1:1:0.2) to provide the cor-
a or 2a–f-b. The reaction
4.2.9.5. N-(2,3,5-Tri-O-acetyl-
nitrobenzenesulfonyl)- -glutamic acid 3c-
procedure for preparing - and b-anomers of 3a–f from 702 mg
(1.0 mmol) of N-(2,3,5-tri-O-acetyl- -arabinofuranos-1-yl)-N-
(2-nitrobenzenesulfonyl)- -glutamic acid di-t-butylester 2c-
531 mg (90%) of 3c-
a
-L
-arabinofuranos-1-yl)-N-(2-
L
a. Using the general
responding 3a–f-
a
or 3a–f-b.
a
a
-L
4.2.9.1. N-(2,3,5-Tri-O-acetyl-
nitrophenylsulfonyl)- -aspartic acid 3a-
procedure for preparing - and b-anomers of 3a–f from 688 mg
(1.0 mmol) of N-(2,3,5-tri-O-acetyl- -arabinofuranos-1-yl)-N-
(2-nitrobenzenesulfonyl)- -aspartic acid di-t-butylester 2a-
a-L
-arabinofuranos-1-yl)-N-(2-
L
a,
L
a. Using the general
a was obtained as colorless powder. Mp
a
117–119 °C,
½
a 2D5
ꢁ
¼ þ94:0 (c 1.1, CHCl3). 1H NMR (500 MHz,
a-
D
CDCl3): d = 8.97 (s, 2H), 8.24 (d, J = 8.0 Hz, 1H), 7.65 (m, J = 7.5 Hz,
2H), 7.51 (d, J = 7.5 Hz, 1H), 5.97 (s, 1H), 5.13 (s, 1H), 5.00 (dd,
J = 9.5 Hz, J = 3.5 Hz, 1H), 4.70 (s, 1H), 4.41 (t, J = 15.0 Hz, 1H),
3.96 (dd, J = 13.5 Hz, J = 1.5 Hz, 1H), 3.59 (d, J = 13.0 Hz, 1H), 2.55
(m, J = 9.5 Hz, 2H), 2.10 (m, J = 8.9 Hz, 2H), 2.11 (s, 9H). FAB/MS
(m/e): 591 [M+H]+. Anal Calcd for C22H26O15N2S: C, 44.75; H,
4.44; N, 4.74. Found: C, 44.68; H, 4.51; N, 4.79.
L
a,
0.489 g (90%) of 3a-a was obtained as colorless powder. Mp 110–
113 °C, ½a 2D5
ꢁ
¼ þ25:3 (c 1.0, CHCl3). 1H NMR (500 MHz, CDCl3):
d = 8.72(s, 2H), 8.24 (d, J = 9.5 Hz, 1H), 7.69 (m, J = 8.6 Hz, 2H),
7.59 (m, J = 8.7 Hz, 1H), 5.23 (t, J = 6.5 Hz, 1H), 5.03 (dd,
J = 10.0 Hz, J = 3.5 Hz, 1H), 4.94 (q, J = 13.5 Hz, 1H), 4.04 (dd,
J = 13.0 Hz, J = 3.0 Hz, 1H), 3.69(d, J = 13.5 Hz, 1H), 3.03 (m,
J = 4.9 Hz, 1H), 2.75 (dd, J = 15.0 Hz, J = 4.5 Hz, 1H), 2.20 (s, 3H),
2.17 (s, 3H), 2.14 (m, J = 5.9 Hz, 2H), 2.00 (s, 3H). FAB/MS (m/e):
577 [M+H]+. Anal. Calcd for C21H24O15N2S: C, 43.75; H, 4.20; N,
4.86. Found: C, 43.68; H, 4.15 N, 4.69.
4.2.9.6. N-(2,3,5-Tri-O-acetyl-b-
nitrobenzenesulfonyl)- -glutamic acid 3c-b. Using the general
procedure for preparing - and b-anomers of 3a–f from 702 mg
(1.0 mmol) of N-(2,3,5-tri-O-acetyl-b- -arabinofuranos-1-yl)-N-(2-
nitrobenzenesulfonyl)- -glutamic acid di-t-butylester 2c-b,
L-arabinofuranos-1-yl)-N-(2-
L
a
L
L
4.2.9.2. N-(2,3,5-Tri-O-acetyl-b-
L
-arabinofuranos-1-yl)-N-(2-
-aspartic acid 3a-b. Using the general pro-
- and b-anomers of 3a–f from 688 mg
-arabinofuranos-1-yl)-N-
-aspartic acid di-t-butylester 2a-b,
507 mg (86%) of 3c-b was obtained as colorless powder. Mp 128–
nitrophenylsulfonyl)-
L
130 °C, ½a 2D5
ꢁ
¼ þ45:5 (c 1.1, CHCl3), 1H NMR (500 MHz, CDCl3):
cedure for preparing
a
d = 8.69 (s, 2H), 8.06 (d, J = 8.2 Hz, 1H), 7.51 (m, J = 7.3 Hz, 2H),
7.39 (d, J = 7.3 Hz, 1H), 5.88 (s, 1H), 5.02 (s, 1H), 4.87 (dd,
J = 9.2 Hz, J = 3.4 Hz, 1H), 4.66 (s, 1H), 4.22 (t, J = 15.1 Hz, 1H),
3.81(dd, J = 13.2 Hz, J = 1.8 Hz, 1H), 3.46 (d, J = 13.2 Hz, 1H), 2.42
(m, J = 9.3 Hz, 2H), 2.13 (m, J = 8.7 Hz, 2H), 2.14 (s, 9H). FAB/MS
(1.0 mmol) of N-(2,3,5-tri-O-acetyl-b-
D
(2-nitrobenzenesulfonyl)-
L
0.465 g (85%) of 3a-b was obtained as colorless powder. Mp 125–
128 °C, ½a 2D5
ꢁ
¼ þ5:8 (c 1.1, CHCl3). 1H NMR (500 MHz, CDCl3):

254
M. Zhao et al. / Tetrahedron: Asymmetry 20 (2009) 247–258
(m/e): 591 [M+H]+. Anal Calcd for C22H26O15N2S: C, 44.75; H, 4.44;
N, 4.74. Found: C, 44.83; H, 4.56; N, 4.60.
4.2.9.11. N-(2,3,5-Tri-O-acetyl-
nitrobenzenesulfonyl)- -threonine 3f-
cedure for preparing - and b-anomers of 3a–f from 674 mg
(1.0 mmol) of N-(2,3,5-tri-O-acetyl- -arabinofuranos-1-yl)-N-
(2-nitrobenzenesulfonyl)- -O-t-butyl-theonine t-butylester 2f-a,
a
-
L
-arabinofuranos-1-yl)-N-(2-
L
a. Using the general pro-
a
4.2.9.7. N-(2,3,5-Tri-O-acetyl-
nitrobenzenesulfonyl)- -serine 3d-
dure for preparing - and b-anomers of 3a–f from 660 mg
(1.0 mmol) of N-(2,3,5-tri-O-acetyl- -arabinofuranos-1-yl)-N-
(2-nitrobenzenesulfonyl)- -O-t-butyl-serine t-butylester 2d-
503 mg (88%) of 3d-
a-L
-arabinofuranos-1-yl)-N-(2-
a-L
L
a. Using the general proce-
L
a
556 mg (95%) of 3f-a was obtained as colorless powder. Mp 103–
a-L
105 °C, ½a 2D5
ꢁ
¼ þ67:0 (c 1.2, CHCl3). 1H NMR (300 MHz, CDCl3):
L
a,
d = 8.65 (s, 1H), 8.38 (m, J = 8.0 Hz, 1H), 7.64 (m, J = 7.6 Hz, 2H),
7.54 (m, J = 7.3 Hz, 1H), 6.18 (t, J = 19.5 Hz, 1H), 5.41 (d,
J = 12.0 Hz, 1H), 5.34 (d, J = 2.7 Hz, 1H), 4.92 (dd, J = 10.2 Hz,
J = 3.3 Hz, 1H), 4.50 (d, J = 3.0 Hz, 1H), 4.33 (m, J = 8.2 Hz, 1H),
3.84 (d, J = 13.2 Hz, 1H), 3.59 (d, J = 13.5 Hz, 1H), 2.01 (s, 3H),
2.09 (s, 3H), 2.21 (s, 3H), 1.34 (d, J = 6.0 Hz, 3H). FAB/MS (m/e):
549[M+H]+. Anal. Calcd for C21H26O14N2S: C, 56.93; H, 4.78; N,
5.11. Found: C, 56.78; H, 4.58; N, 5.23.
a
was obtained as colorless powder. Mp
106–109 °C,
½
a 2D5
ꢁ
¼ þ83:2 (c 1.2, CHCl3). 1H NMR (500 MHz,
CDCl3): d = 8.89 (s, 1H), 8.31 (d, J = 10.0 Hz, 1H), 7.64 (m,
J = 8.7 Hz, 2H), 7.51 (d, J = 9.0 Hz,1H), 5.95 (s, 1H), 5.25 (s, 1H),
5.20 (d, J = 5.0 Hz, 1H), 4.99 (dd, J = 3.5 Hz, J = 9.5 Hz, 1H), 4.50
(m, J = 8.8 Hz, 1H), 4.01 (dd, J = 10.5 Hz, J = 1.0 Hz, 1H), 3.76 (m,
J = 9.5 Hz, 2H), 3.64 (d, J = 14.5 Hz, 1H), 1.99 (s, 3H), 2.03 (s, 3H),
2.19 (s, 3H). FAB/MS (m/e): 549 [M+H]+. Anal Calcd for
C20H24O14N2S: C, 43.80; H, 4.41; N, 5.11. Found: C, 43.67; H,
4.19; N, 4.89.
4.2.9.12. N-(2,3,5-Tri-O-acetyl-b-
nitrobenzenesulfonyl)- -threonine 3f-b. Using the general pro-
cedure for preparing - and b-anomers of 3a–f from 674 mg
(1.0 mmol) of N-(2,3,5-tri-O-acetyl-b- -arabinofuranos-1-yl)-N-(2-
nitrobenzenesulfonyl)- -O-t-butyl-threonine t-butylester 2f-b,
L-arabinofuranos-1-yl)-N-(2-
L
a
L
4.2.9.8. N-(2,3,5-Tri-O-acetyl-b-
nitrobenzenesulfonyl)- -serine 3d-b. Using the general proce-
dure for preparing - and b-anomers of 3a–f from 660 mg
(1.0 mmol) of N-(2,3,5-tri-O-acetyl-b- -arabinofuranos-1-yl)-N-(2-
nitrobenzenesulfonyl)- -O-t-butyl-serine t-butylester 2d-b, 466 mg
L-arabinofuranos-1-yl)-N-(2-
L
L
482 mg (88%) of 3f-b was obtained as colorless powder. Mp 115–
a
117 °C, ½a 2D5
ꢁ
¼ þ40:3 (c 1.1, CHCl3). 1H NMR (300 MHz, CDCl3):
L
d = 8.47 (s, 1H), 8.20 (m, J = 8.1 Hz, 1H), 7.52 (m, J = 7.4 Hz, 2H),
7.43 (m, J = 7.2 Hz, 1H), 6.04 (t, J = 19.2 Hz, 1H), 5.25 (d,
J = 12.2 Hz, 1H), 5.17 (d, J = 2.9 Hz, 1H), 4.77 (dd, J = 10.0 Hz,
J = 3.5 Hz, 1H), 4.38 (d, J = 3.2 Hz, 1H), 4.27 (m, J = 8.4 Hz, 1H),
3.96 (d, J = 13.0 Hz, 1H), 3.68 (d, J = 13.0 Hz, 1H), 2.24 (s, 3H),
2.04 (s, 3H), 2.12 (s, 3H), 1.32 (d, J = 6.2 Hz, 3H). FAB/MS (m/e):
549 [M+H]+. Anal. Calcd for C21H26O14N2S: C, 56.93; H, 4.78; N,
5.11. Found: C, 56.80; H, 4.89; N, 5.00.
L
(85%) of 3d-b was obtained as colorless powder. Mp 112–114 °C,
½
a 2D5
ꢁ
¼ þ40:9 (c 1.1, CHCl3). 1H NMR (500 MHz, CDCl3): d = 8.66
(s, 1H), 8.20 (d, J = 10.1 Hz, 1H), 7.52 (m, J = 8.5 Hz, 2H), 7.38 (d,
J = 8.8 Hz,1H), 5.85 (s, 1H), 5.11 (s, 1H), 5.00 (d, J = 5.2 Hz, 1H),
4.76 (dd, J = 3.6 Hz, J = 9.5 Hz, 1H), 4.34 (m, J = 8.6 Hz, 1H), 4.24
(dd, J = 10.2 Hz, J = 1.0 Hz, 1H), 3.62 (m, J = 9.4 Hz, 2H), 3.53 (d,
J = 14.0 Hz, 1H), 2.18 (s, 3H), 2.08 (s, 3H), 2.01 (s, 3H). FAB/MS
(m/e): 549 [M+H]+. Anal. Calcd for C20H24O14N2S: C. 43.80; H.
4.41; N. 5.11. Found: C, 43.93; H, 4.58; N, 5.25.
4.2.10. General procedure for preparing
N-( -arabinofuranos-1-yl)-N-(2-nitrophenylsulfonyl)-
acids 4a–f
The solution of 1.0 mmol of
acetyl- -arabinofuranos-1-yl)-N-(2-nitrophenylsulfonyl)-
a
- and b-anomers of
L
L
-amino
4.2.9.9. N-(2,3,5-Tri-O-acetyl-
nitrobenzenesulfonyl)- -phenylalanine 3e-
procedure for preparing - and b-anomers of 3a–f from 664 mg
(1.0 mmol) of N-(2,3,5-tri-O-acetyl- -arabinofuranos-1-yl)-N-
(2-nitrobenzenesulfonyl)- -phenylalanine t-butylester 2e-
565 mg (93%) of 3e-
a-L
-arabinofurano-1-syl)-N-(2-
a
- and b-anomers of N-(2,3,5-tri-O-
-amino
L
a
. Using the general
L
L
a
acid 3a–f in 20 ml of anhydrous MeOH was treated at 0 °C with
CH3ONa (1.2 equiv, pH 9.5). The reaction mixture was stirred and
gradually warmed to room temperature in 5 h and then TLC anal-
ysis (chloroform:methanol:water:glacial acetic acid, 3:1:0.15:0.1)
indicated complete disappearance of 3a–f. The reaction mixture
was neutralized with Amberlite IRC 50 (H+ form) and filtered.
The filtrate was evaporated under vacuum to produce the corre-
a-L
L
a,
a
was obtained as colorless powder. Mp
117–119 °C,
½
a 2D5
ꢁ
¼ þ85:2 (c 1.1, CHCl3). 1H NMR (500 MHz,
CDCl3): d = 8.69 (s, 1H), 8.29 (dd, J = 1.5 Hz, J = 4.2 Hz, 1H), 7.70
(m, J = 7.2 Hz, 2H), 7.55 (d, J = 7.6 Hz, 1H), 7.31 (t, J = 7.0 Hz, 1H),
7.29 (d, J = 7.2 Hz, 2H), 7.22 (t, J = 7.0 Hz, 2H), 5.99 (s, 1H), 5.29
(s, 1H), 5.11 (dd, J = 10.0 Hz, J = 3.5 Hz, 2H), 4.54 (m, J = 7.0 Hz,
1H), 4.04 (dd, J = 10.0 Hz, J = 2.0 Hz, 1H), 3.70 (d, J = 13.0 Hz, 1H),
3.23 (m, J = 7.8 Hz, 1H), 3.04 (m, J = 7.6 Hz, 1H), 2.10 (m, 9H).
FAB/MS (m/e): 609 [M+H]+. Anal. Calcd for C26H28O13N2S: C,
51.31; H, 4.64; N, 4.60. Found: C, 51.19; H, 4.51; N, 4.38.
sponding a- and b-anomers of 4a–f.
4.2.10.1. N-(
nyl)- -aspartic acid 4a-
ing - and b-anomers of 4a–f from 576 mg (1.0 mmol) of N-(2,3,5-
tri-O-acetyl- -arabinofuranos-1-yl)-N-(2-nitrophenylsulfonyl)-
a
-
L
-Arabinofuranos-1-yl)-N-(2-nitrobenzenesulfo-
L
a. Using the general procedure for prepar-
a
a-
L
L-
aspartic acid (3a-a), 432 mg (96%) of 4a-a was obtained as pale
yellow solid. Mp 128–130 °C, ½a D25
ꢁ
¼ þ97:0 (c 1.1, CH3OH). 1H
4.2.9.10. N-(2,3,5-Tri-O-acetyl-b-
nitrobenzenesulfonyl)- -phenylalanine 3e-b. Using the general
procedure for preparing - and b-anomers of 3a–f from 664 mg
(1.0 mmol) of N-(2,3,5-tri-O-acetyl-b- -arabinofuranos-1-yl)-N-(2-
nitrobenzenesulfonyl)- -phenylalanine t-butylester 2e-b, 523 mg
L-arabinofuranos-1-yl)-N-(2-
L
NMR (300 MHz, DMSO-d6): d = 10.31 (s, 2H), 8.20 (d, J = 7.20 Hz,
1H), 7.86 (m, J = 7.7 Hz, 2H), 7.78 (m, J = 7.9 Hz, 1H), 4.74 (d,
J = 8.7 Hz, 1H), 4.52 (m, J = 8.3 Hz, 1H), 4.21 (m, J = 8.5 Hz, 1H),
4.04 (t, J = 6.4 Hz, 1H), 3.92 (dd, J = 6.3 Hz, J = 3.2 Hz, 1H), 3.55 (d,
J = 12.9 Hz, 1H), 3.52 (m, J = 5.9 Hz, 1H), 2.85 (s, 1H), 2.83 (s, 1H),
2.81 (s, 1H) 2.13 (d, J = 5.7 Hz, 2H). FAB/MS (m/e): 451 [M+H]+.
Anal. Calcd for C15H18O12N2S: C, 40.00; H, 4.03; N, 6.22. Found: C,
39.91; H, 3.92; N, 6.19.
a
L
L
(86%) of 3e-b was obtained as colorless powder. Mp 130–132 °C,
½
a 2D5
ꢁ
¼ þ50:8 (c 1.1, CHCl3). 1H NMR (500 MHz, CDCl3): d = 8.51
(s, 1H), 8.12 (dd, J = 1.7 Hz, J = 4.4 Hz, 1H), 7.51 (m, J = 7.0 Hz,
2H), 7.40 (d, J = 7.2 Hz, 1H), 7.24 (t, J = 7.2 Hz, 1H), 7.14 (d,
J = 7.0 Hz, 2H), 7.03 (t, J = 7.2 Hz, 2H), 5.80 (s, 1H), 5.12 (s, 1H),
4.97 (dd, J = 10.1 Hz, J = 3.6 Hz, 2H), 4.39 (m, J = 7.2 Hz, 1H), 4.15
(dd, J = 10.2 Hz, J = 2.0 Hz, 1H), 3.55 (d, J = 13.0 Hz, 1H), 3.14 (m,
J = 7.7 Hz, 1H), 2.94 (m, J = 7.2 Hz, 1H), 2.12 (m, 9H). FAB/MS (m/
e): 609 [M+H]+. Anal. Calcd for C26H28O13N2S: C, 51.31; H, 4.64;
N, 4.60. Found: C, 51.47; H, 4.59; N, 4.73.
4.2.10.2. N-(b-
nyl)- -aspartic acid 4a-b. Using the general procedure for prepar-
ing - and b-anomers of 4a–f from 576 mg (1.0 mmol) of N-(2,3,5-
tri-O-acetyl-b- -arabinofuranos-1-yl)-N-(2-nitrophenylsulfonyl)-
aspartic acid 3a-b, 405 mg (90%) of 4a-b was obtained as pale
L-Arabinofuranos-1-yl)-N-(2-nitrobenzenesulfo-
L
a
L
L-

M. Zhao et al. / Tetrahedron: Asymmetry 20 (2009) 247–258
255
yellow solid. Mp 120–122 °C, ½a D25
ꢁ
¼ þ51:0 (c 1.2, CH3OH). 1H NMR
J = 4.9 Hz, 2H). FAB/MS (m/e): 465 [M+H]+. Anal. Calcd for
C16H20O12N2S: C, 41.38; H, 4.34; N, 6.03. Found: C, 41.25; H,
4.47; N, 6.16.
(300 MHz, DMSO-d6): d = 10.16 (s, 2H), 8.09 (d, J = 7.0 Hz, 1H), 7.71
(m, J = 7.5 Hz, 2H), 7.63 (m, J = 7.5 Hz, 1H), 4.61 (d, J = 8.5 Hz, 1H),
4.41 (m, J = 8.2 Hz, 1H), 4.18 (m, J = 8.3 Hz, 1H), 4.12 (t, J = 6.6 Hz,
1H), 3.80 (dd, J = 6.5 Hz, J = 3.2 Hz, 1H), 3.41 (d, J = 12.2 Hz, 1H),
3.37 (m, J = 5.8 Hz, 1H), 2.80 (s, 1H), 2.77 (s, 1H), 2.70 (s, 1H)
2.12 (d, J = 5.5 Hz, 2H). FAB/MS (m/e): 451 [M+H]+. Anal. Calcd for
C15H18O12N2S: C, 40.00; H, 4.03; N, 6.22. Found: C, 39.89; H,
4.20; N, 6.39.
4.2.10.7. N-(
nyl)- -serine 4d-
- and b-anomers of 4a–f from 548 mg (1.0 mmol) of N-(2,3,5-
tri-O-acetyl- -arabinofuranos-1-yl)-N-(2-nitrobenzenesulfonyl)-
a
-
L
-Arabinofuranos-1-yl)-N-(2-nitrobenzenesulfo-
L
a. Using the general procedure for preparing
a
a-L
L
-serine 3d-a, 388 mg (92%) of 4d-a was obtained as colorless
powder. Mp 105–108 °C, ½a D25
ꢁ
¼ þ39:0 (c 1.2, CH3OH). 1H NMR
4.2.10.3. N-(
nyl)-S-t-butyl-
preparing - and b-anomers of 4a–f from 620 mg (1.0 mmol) of
N-(2,3,5-tri-O-acetyl- -arabinofuranos-1-yl)-N-(2-nitrobenzene-
a
-
L
L
-Arabinofuranos-1-yl)-N-(2-nitrobenzenesulfo-
(300 MHz, DMSO-d6): d = 10.52 (s, 1H), 8.23 (d, J = 7.5 Hz, 1H),
7.92 (m, J = 7.6 Hz, 2H), 7.78 (d, J = 7.4 Hz, 1H), 4.71 (d, J = 9.0 Hz,
1H), 4.51 (m, J = 5.8 Hz, 1H), 4.48 (m, J = 6.3 Hz, 1H), 4.15 (m,
J = 8.0 Hz, 1H), 3.99 (m, J = 10.5 Hz, 2H), 3.72 (d, J = 6.3 Hz, 2H),
3.69 (m, J = 6.3 Hz, 1H), 2.88 (s, 1H), 2.85 (s, 1H), 2.83 (s, 1H),
2.79 (s, 1H). FAB/MS (m/e): 423 [M+H]+. Anal. Calcd for
C14H18O11N2S: C, 39.81; H, 4.30; N, 6.63. Found: C, 39.61; H,
4.18; N, 6.41.
-cysteine 4b- . Using the general procedure for
a
a
a-L
sulfonyl)-S-t-butyl-
L
-cysteine (3b-
a
), 459 mg (93%) of 4b-
a
was
obtained as colorless powder. Mp 127–129 °C, ½a D25
ꢁ
¼ þ90:0 (c
1.2, CH3OH). 1H NMR (300 MHz, DMSO-d6): d = 10.01 (s, 1H),
8.26 (d, J = 7.2 Hz, 1H), 7.78 (m, J = 7.3 Hz, 2H), 7.65 (m,
J = 7.3 Hz, 1H), 4.69 (d, J = 9.0 Hz, 1H), 4.56 (m, J = 6.7 Hz, 1H),
4.29 (m, J = 5.6 Hz, 1H), 4.11 (m, J = 7.6 Hz, 1H), 3.68 (d,
J = 5.8 Hz, 2H), 3.41 (d, J = 11.2 Hz, 2H), 3.36 (m, J = 5.7 Hz, 1H),
2.86 (s, 1H), 2.84 (s, 1H), 2.82 (s, 1H), 1.69 (s, 9H). FAB/MS (m/e):
495 [M+H] +. Anal. Calcd for C18H26O10N2S2: C, 43.72; H, 5.30; N,
5.66. Found: C, 43.61; H, 5.19; N, 5.78.
4.2.10.8. N-(b-
nyl)- -serine 4d-b. Using the general procedure for preparing
- and b-anomers of 4a–f from 548 mg (1.0 mmol) of N-(2,3,5-
tri-O-acetyl-b- -arabinofuranos-1-yl)-N-(2-nitrobenzenesulfonyl)-
L-Arabinofuranos-1-yl)-N-(2-nitrobenzenesulfo-
L
a
L
L
-serine 3d-b, 359 mg (85%) of 4d-b was obtained as colorless pow-
der. Mp 121–123 °C,
½
a 2D5
ꢁ
¼ þ25:2 (c 1.2, CH3OH). 1H NMR
4.2.10.4. N-(b-
nyl)-S-t-butyl-
L
-Arabinofuranos-1-yl)-N-(2-nitrobenzenesulfo-
-cysteine 4b-b. Using the general procedure for
(300 MHz, DMSO-d6): d = 10.33 (s, 1H), 8.09 (d, J = 7.2 Hz, 1H),
7.74 (m, J = 7.3 Hz, 2H), 7.62 (d, J = 7.2 Hz, 1H), 4.55 (d, J = 9.2 Hz,
1H), 4.37 (m, J = 5.9 Hz, 1H), 4.29 (m, J = 6.5 Hz, 1H), 4.22 (m,
J = 8.41 Hz, 1H), 3.72 (m, J = 10.2 Hz, 2H), 3.61 (d, J = 6.5 Hz, 2H),
3.41 (m, J = 6.5 Hz, 1H), 2.80 (s, 1H), 2.78 (s, 1H), 2.77 (s, 1H),
2.75 (s, 1H). FAB/MS (m/e): 423 [M+H]+. Anal. Calcd for
C14H18O11N2S: C, 39.81; H, 4.30; N, 6.63. Found: C, 39.94; H,
4.44; N, 6.50.
L
preparing
N-(2,3,5-tri-O-acetyl-b-
a
- and b-anomers of 4a–f from 620 mg (1.0 mmol) of
-arabinofuranos-1-yl)-N-(2-nitrobenzene-
L
sulfonyl)-S-t-butyl-L-cysteine (3b-b), 435 mg (88%) of 4b-b was ob-
tained as colorless powder. Mp 120–122 °C, ½a D25
¼ þ44:6 (c 1.1,
ꢁ
CH3OH). 1H NMR (300 MHz, DMSO-d6): d = 9.95 (s, 1H), 8.12 (d,
J = 7.4 Hz, 1H), 7.64 (m, J = 7.2 Hz, 2H), 7.42 (m, J = 7.2 Hz, 1H),
4.53 (d, J = 9.2 Hz, 1H), 4.38 (m, J = 6.5 Hz, 1H), 4.22 (m,
J = 5.8 Hz, 1H), 4.18 (m, J = 7.6 Hz, 1H), 3.52 (d, J = 5.9 Hz, 2H),
3.38 (d, J = 11.0 Hz, 2H), 3.28 (m, J = 5.7 Hz, 1H), 2.80 (s, 1H), 2.77
(s, 1H), 2.70 (s, 1H), 1.66 (s, 9H). FAB/MS (m/e): 495 [M+H]+. Anal.
Calcd for C18H26O10N2S2: C, 43.72; H, 5.30; N, 5.66. Found: C, 41.84;
H, 5.21; N, 5.53.
4.2.10.9. N-(
phenylalanine 4e-
- and b-anomers of 4a–f from 608 mg (1.0 mmol) of N-(2,3,5-
tri-O- -acetyl- -arabinofuranos-1-yl)-N-(2-nitrophenylsulfonyl)-
a
-
L
-Arabinofuranos-1-yl)-N-(2-nitrophenylsulfonyl)-
L-
a. Using the general procedure for preparing
a
a
L
L-
phenylalanine 3e-a, 459 mg (93%) of 4e-a was obtained as col-
orless powder. Mp 127–129 °C, ½a D25
ꢁ
¼ þ90:0 (c 1.1, CH3OH). 1H
4.2.10.5. N-(
nyl)- -glutamic acid 4c-
paring - and b-anomers of 4a–f from 590 mg (1.0 mmol) of N-
(2,3,5-tri-O-acetyl- -arabinofuranos-1-yl)-N-(2-nitrobenzene-
a
-
L
-Arabinofuranos-1-yl)-N-(2-nitrobenzenesulfo-
NMR (500 MHz, DMSO-d6): d = 10.41 (s, 1H), 8.03 (d,
J = 7.01 Hz, 1H), 7.65 (d, J = 7.6 Hz, 2H), 7.47 (t, J = 7.7 Hz,
2H), 7.29 (m, J = 8.1 Hz, 1H), 7.21 (m, J = 8.2 Hz, 1H), 7.18 (t,
J = 7.6 Hz, 1H), 7.15 (m, J = 7.6 Hz, 1H), 5.09 (d, J = 9.0 Hz, 1H),
4.60 (dd, J = 5.7 Hz, J = 3.4 Hz, 1H), 4.14 (d, J = 8.7 Hz, 1H),
4.02 (t, J = 6.5 Hz, 1H), 3.79 (d, J = 12.9 Hz, 2H), 3.71 (m,
J = 5.9 Hz, 1H), 2.97 (d, J = 6.1 Hz, 2H), 2.89 (s, 1H), 2.87 (s,
1H), 2.80 (s, 1H). FAB/MS (m/e): 495 [M+H]+. Anal. Calcd for
C18H26O10N2S2: C, 49.79; H, 4.60; N, 5.81. Found: C, 49.81; H,
4.62; N, 5.79.
L
a. Using the general procedure for pre-
a
a
-L
sulfonyl)-
L
-glutamic acid 3c-
a
, 418 mg (90%) of 4c-
a
was obtained
as colorless powder. Mp 117–119 °C, ½a D25
ꢁ
¼ þ105:0 (c 1.2, CH3OH).
1H NMR (300 MHz, DMSO-d6): d = 9.98 (s, 1H), 8.31 (d, J = 8.0 Hz,
1H), 7.48 (m, J = 7.6 Hz, 2H), 7.38 (d, J = 7.5 Hz, 1H), 4.93 (d,
J = 9.0 Hz, 1H), 4.60 (m, J = 6.1 Hz, 1H), 4.71 (m, J = 5.8 Hz, 1H),
4.11 (d, J = 3.5 Hz, 1H), 3.79 (t, J = 10.1 Hz, 2H), 3.01 (m, 2H), 2.88
(s, 1H), 2.85 (s, 1H), 2.83 (s, 1H), 2.54 (t, J = 5.2 Hz, 2H), 1.69 (d,
J = 4.9 Hz, 2H). FAB/MS (m/e): 465 [M+H]+. Anal. Calcd for
C16H20O12N2S: C, 41.38; H, 4.34; N, 6.03. Found: C, 41.55; H,
4.25; N, 5.89.
4.2.10.10. N-(b-
fonyl)- -phenyl-alanine 4e-b. Using the general procedure for
preparing - and b-anomers of 4a–f from 608 mg (1.0 mmol) of
N -(2,3,5-tri-O-b-acetyl- -arabinofuranos-1-yl)-N-(2-nitrophenyl-
L-Arabinofuranos-1-yl)-N-(2-nitrophenylsul-
L
a
L
4.2.10.6. N-(b-
nyl)- -glutamic acid 4c-b. Using the general procedure for pre-
paring - and b-anomers of 4a–f from 590 mg (1.0 mmol) of N-
(2,3,5-tri-O-acetyl-b- -arabinofuranos-1-yl)-N-(2-nitrobenzene-
L
-Arabinofuranos-1-yl)-N-(2-nitrobenzenesulfo-
sulfonyl)-L-phenylalanine 3e-b, 395 mg (80%) of 4e-b was obtained
L
as colorless powder. Mp 121–123 °C, ½a D25
¼ þ50:1 (c 1.2, CH3OH).
ꢁ
a
1H NMR (500 MHz, DMSO-d6): d = 10.02 (s, 1H), 7.95 (d, J = 7.0 Hz,
1H), 7.48 (d, J = 7.4 Hz, 2H), 7.24 (t, J = 7.5 Hz, 2H), 7.17 (m,
J = 8.0 Hz, 1H), 7.08 (m, J = 8.0 Hz, 1H), 7.04 (t, J = 7.4 Hz, 1H),
7.00 (m, J = 7.4 Hz, 1H), 5.00 (d, J = 9.1 Hz, 1H), 4.55 (dd, J =
5.5 Hz, J = 3.4 Hz, 1H), 4.09 (d, J = 8.5 Hz, 1H), 4.07 (t, J = 6.6 Hz,
1H), 3.65 (d, J = 12.6 Hz, 2H), 3.53 (m, J = 5.7 Hz, 1H), 2.84 (d,
J = 6.0 Hz, 2H), 2.80 (s, 1H), 2.76 (s, 1H), 2.72 (s, 1H). FAB/MS (m/
e): 495 [M+H]+. Anal. Calcd for C18H26O10N2S2: C, 49.79; H, 4.60;
N, 5.81. Found: C, 49.66; H, 4.71; N, 5.95.
L
sulfonyl)-L-glutamic acid 3c-b, 394 mg (85%) of 4c-b was obtained
as colorless powder. Mp 122–124 °C, ½a D25
¼ þ60:1 (c 1.2, CH3OH).
ꢁ
1H NMR (300 MHz, DMSO-d6): d = 9.90 (s, 1H), 8.20 (d, J = 8.1 Hz,
1H), 7.35 (m, J = 7.4 Hz, 2H), 7.24 (d, J = 7.2 Hz, 1H), 4.83 (d,
J = 9.1 Hz, 1H), 4.48 (m, J = 6.2 Hz, 1H), 4.66 (m, J = 5.6 Hz, 1H),
4.20 (d, J = 3.6 Hz, 1H), 3.60 (t, J = 10.0 Hz, 2H), 2.96 (m, 2H), 2.84
(s, 1H), 2.77 (s, 1H), 2.70 (s, 1H), 2.52 (t, J = 5.2 Hz, 2H), 1.67 (d,

256
M. Zhao et al. / Tetrahedron: Asymmetry 20 (2009) 247–258
4.2.10.11. N-(
benzenesulfonyl)-
for preparing
a
-
L
-Arabinofuranos-1-yl)-N-(2-nitro-
-theonine 4f- . Using the general procedure
- and b-anomers of 4a–f from 548 mg (1.0 mmol)
of N-(2,3,5-tri-O-acetyl- -arabinofuranos-1-yl)-N-(2-nitrobenzene
2.76 (m, J = 4.6 Hz, 2H). 13C NMR (500 MHz, D2O): d = 175.0,
173.0, 96, 77, 72.0, 71.1, 61.0, 50.0, 35.7. FAB/MS (m/e): 266
[M+H]+. Anal. Calcd for C9H15O8N: C, 40.76; H, 5.70; N, 5.28. Found:
C, 40.88; H, 5.84; N, 5.40.
L
a
a
a-L
sulfonyl)-
L
-threonine 3f-
a
, 414 mg (95%) of 4f-
a
was obtained as
colorless powder. Mp 119–120 °C, ½a D25
ꢁ
¼ þ87:0 (c 1.2, CH3OH).
4.2.11.3. N-(
argon the solution of 91 mg (0.27 mmol) of N-(
anos-1-yl)-S-t-butyl- -cysteine and 75 mg (0.4 mmol) of 2-nitro-
a
-L
-Arabinofuranos-1-yl)-
L
-cysteine 5b-a. Under
1H NMR (300 MHz, DMSO-d6): d = 10.33 (s, 1H), 8.30 (d,
J = 7.2 Hz, 1H), 7.81 (m, J = 7.4 Hz, 2H), 7.77 (d, J = 7.5 Hz, 1H),
4.98 (d, J = 9.0 Hz, 1H), 4.82 (dd, J = 6.5 Hz, J = 4.5 Hz, 1H), 4.44
(m, J = 5.2 Hz, 1H), 4.28 (m, J = 6.2 Hz, 1H), 3.72 (m, J = 105 Hz,
2H), 3.68 (m, J = 5.7 Hz, 1H), 3.62 (d, J = 6.5 Hz, 1H), 2.87 (s, 1H),
2.86 (s, 1H), 2.84 (s, 1H), 2.80 (s, 1H), 1.84 (d, J = 4.6 Hz, 3H).
FAB/MS (m/e): 437 [M+H]+. Anal. Calcd for C15H20O11N2S: C,
41.29; H, 4.62; N, 6.42. Found: C, 41.16; H, 4.38; N, 6.28.
a-L-arabinofur-
L
phenylsulfenyl chloride in 2 ml of glacial acetic acid was stirred
at room temperature for 2 h, and TLC analysis (chloroform:metha-
nol:water:glacial acetic acid, 1:1:0.2:0.1) indicated complete dis-
appearance of N-(a-L-arabinofuranos-1-yl)-S-t-butyl-L-cysteine.
The reaction mixture was evaporated under vacuum and the resi-
due was dissolved in 3 ml of CH3OH. The formed solution was
cooled with ice bath and treated with 20 mg (0.54 mmol) of so-
dium borohydride. The reaction mixture was stirred at room tem-
perature for 2 h and then evaporated under vacuum to remove the
solvent. The residue was dissolved in water, washed with ethyl
acetate, and the water phase was evaporated under vacuum. The
residue was purified by Sephadex LH-20 and eluted with ethanol
(10%). The collected fractions were combined, frozen, and lyophi-
lized to provide 11 mg (43%) of the title compound as colorless
4.2.10.12. N-(b-
nyl)- -threonine 4f-b. Using the general procedure for preparing
- and b-anomers of 4a–f from 548 mg (1.0 mmol) of N-(2,3,5-
tri-O-acetyl-b- -arabinofuranos-1-yl)-N-(2-nitrobenzenesulfo-
L-Arabinofuranos-1-yl)-N-(2-nitrobenzenesulfo-
L
a
L
nyl)-L-threonine 3f-b, 392 mg (90%) of 4f-b was obtained as color-
less powder. Mp 111–113 °C, ½a D25
ꢁ
¼ þ50:7 (c 1.2, CH3OH). 1H NMR
(300 MHz, DMSO-d6): d = 10.00 (s, 1H), 8.21 (d, J = 7.4 Hz, 1H), 7.77
(m, J = 7.2 Hz, 2H), 7.62 (d, J = 7.3 Hz, 1H), 4.77 (d, J = 9.2 Hz, 1H),
4.64 (dd, J = 6.7 Hz, J = 4.5 Hz, 1H), 4.30 (m, J = 5.4 Hz, 1H), 4.15
(m, J = 6.4 Hz, 1H), 3.84 (m, J = 10.2 Hz, 2H), 3.60 (m, J = 5.5 Hz,
1H), 3.53 (d, J = 6.6 Hz, 1H), 2.83 (s, 1H), 2.80 (s, 1H), 2.77 (s, 1H),
2.75 (s, 1H), 1.82 (d, J = 4.8 Hz, 3H). FAB/MS (m/e): 437 [M+H]+.
Anal. Calcd for C15H20O11N2S: C, 41.29; H, 4.62; N, 6.42. Found: C,
41.35; H, 4.46; N, 6.63.
powder. Mp 243 °C (decomp.), ½a D25
ꢁ
¼ þ38:1 (c 1.1, H2O). 1H NMR
(500 MHz, D2O): d = 4.32 (m, J = 5.4 Hz, 1H), 4.17 (d, J = 4.0 Hz,
1H), 4.05 (dd, J = 12.0 Hz, J = 4.0 Hz, 1H), 3.82 (dd, J = 12.5 Hz,
J = 3.0 Hz, 1H), 3.81 (m, J = 4.7 Hz, 1H), 3.28 (d, J = 10.0 Hz, 1H),
3.08 (d, J = 10.0 Hz, 1H), 2.89 (m, J = 5.0 Hz, 2H). FAB/MS (m/e):
254 [M+H]+. Anal. Calcd for C9H17O7NS: C, 37.94; H, 5.70; N, 5.53.
Found: C, 37.86; H, 5.89; N, 5.67.
4.2.11. General procedure for preparing
-arabinofuranos-1-yl)- -amino acid 5a–f
Under argon, the solution of 0.1 mmol of N-(
1-yl)-N-(2-nitrophenylsulfonyl)- -amino acid
a- and b-anomers of N-
4.2.11.4. N-(b-
argon, the solution of 91 mg (0.27 mmol) of N-(b-
anos-1-yl)-S-t-butyl- -cysteine and 75 mg (0.4 mmol) of 2-nitro-
phenylsulfenyl chloride in 2 ml of glacial acetic acid was stirred
at room temperature for 2 h, and TLC analysis (chloroform:meth-
anol:water: glacial acetic acid, 1:1:0.2:0.1) indicated complete
L
-Arabinofuranos-1-yl)-
L
-cysteine
5b-b. Under
(a-
L
L
L
-arabofur-
L
-arabinofuranos-
4a–f, 0.7 ml
L
L
(4.0 mmol) of DIPEA, and 0.71 ml (7 mmol) of PhSH in 2 ml of
anhydrous DMF was stirred at room temperature for 4–6 h, and
TLC analysis (chloroform:methanol:water:glacial acetic acid,
1:1:0.2:0.1) indicated complete disappearance of 4a–f. The reac-
tion mixture was evaporated under vacuum to remove the DMF.
The residue was extracted with water and the water layer was
washed with ethyl acetate. The separated water layer was evapo-
rated under vacuum. The resulting residue was purified by Sepha-
dex LH-20 and eluted with ethanol (10%) to give the corresponding
epimerically pure 5a–f.
disappearance of N-(b-L-arabofuranos-1-yl)-S-t-butyl-L-cysteine.
The reaction mixture was evaporated under vacuum and the res-
idue was dissolved in 3 ml of CH3OH. The formed solution was
cooled with ice bath and treated with 20 mg (0.54 mmol) of so-
dium borohydride. The reaction mixture was stirred at room tem-
perature for 2 h and then evaporated under vacuum to remove
the solvent. The residue was dissolved in water, washed with
ethyl acetate, and the water phase was evaporated under vacuum.
The residue was purified by Sephadex LH-20 and eluted with eth-
anol (10%). The collected fractions were combined, frozen, and
lyophilized to provide 13 mg (50%) of the title compound as col-
4.2.11.1. N-(
the general procedure for preparing
45 mg (0.1 mmol) of N-( -arabinofuranos-1-yl)-N-(2-nitrophen-
a
-
L
-Arabinofuranos-1-yl)-
L-aspartic acid 5a-a. Using
a- and b-anomers of 5a–f from
a-L
orless powder. Mp 252 °C (decomp.), ½a D25
ꢁ
¼ ꢀ16:0 (c 1.1, H2O). 1
H
ylsulfonyl)-
L
-aspartic acid 4a-
a
, 18.6 mg (70%) of 5a-
a
was ob-
NMR (500 MHz, D2O): d = 4.25 (m, J = 5.6 Hz, 1H), 4.11 (d,
J = 4.2 Hz, 1H), 3.97 (dd, J = 12.1 Hz, J = 4.2 Hz, 1H), 3.89 (dd,
J = 12.5 Hz, J = 3.0 Hz, 1H), 3.66 (m, J = 4.9 Hz, 1H), 3.20 (d,
J = 10.0 Hz, 1H), 3.01(d, J = 10.0 Hz, 1H), 2.80 (m, J = 5.0 Hz, 2H).
FAB/MS (m/e): 254 [M+H]+. Anal. Calcd for C9H17O7NS: C, 37.94;
H, 5.70; N, 5.53. Found: C, 37.81; H, 5.56; N, 5.37.
tained as colorless powder. Mp 127–129 °C, ½a D25
ꢁ
¼ þ7:6 (c 1.1,
H2O). 1H NMR (500 MHz, D2O): d = 4.37 (m, J = 5.2 Hz, 1H), 4.14
(d, J = 5.0 Hz, 1H), 4.07 (dd, J = 12.5 Hz, J = 4.5 Hz, 1H), 3.35 (d,
J = 12.5 Hz, 1H), 3.15 (d, J = 12.5 Hz, 1H), 3.82 (m, J = 4.9 Hz, 2H),
2.78 (m, J = 4.6 Hz, 2H). 13CNMR (500 MHz, D2O): d = 177.0,
176.0, 97, 78, 71.8, 72.2, 61.4, 50.3, 36.1. FAB/MS (m/e): 266
[M+H]+. Anal. Calcd for C9H15O8N: C, 40.76; H, 5.70; N, 5.28. Found:
C, 40.67; H, 5.62; N, 5.11.
4.2.11.5. N-(
the general procedure for preparing
46.3 mg (0.1 mmol) of N-( -arabinofuranos-1-yl)-N-(2-nitro-
a-L-Arabinofuranos-1-yl)-L-glutamic acid 5c-a. Using
a- and b-anomers of 5a–f from
a-L
4.2.11.2. N-(
the general procedure for preparing
45 mg (0.1 mmol) of N-(b- -arabinofuranos-1-yl)-N-(2-nitrophen-
a-L
-Arabinofuranos-1-yl)-
L-aspartic acid 5a-b. Using
benzenesulfonyl)-L-glutamic acid (4c-a), 20.9 mg (75%) of 5c-a
a- and b-anomers of 5a–f from
was obtained as colorless powder. ½a D25
ꢁ
¼ þ10:0 (c 1.2, H2O). 1H
L
NMR (500 MHz, D2O): d = 4.31(dd, J = 8.7 Hz, J = 2.3 Hz, 1H), 4.25
(m, J = 2.2 Hz, 1H), 4.14 (d, J = 4.5 Hz, 1H), 3.97 (dd, J = 8.8 Hz,
J = 2.6 Hz, 1H), 3.83 (dd, J = 9.8 Hz, J = 2.7 Hz, 1H), 3.80 (dd,
J = 8.0 Hz, J = 2.4 Hz, 1H), 3.25 (d, J = 11.0 Hz, 1H), 3.15 (d,
J = 10.5 Hz, 1H), 2.06 (m, J = 4.1 Hz, 2H), 1.74 (m, J = 4.0 Hz, 2H).
ylsulfonyl)-L-aspartic acid (4a-b), 19.3 mg (73%) of 5a-b was ob-
tained as a colorless powder. Mp 102–104 °C, ½a D25
¼ ꢀ20:9 (c 1.1,
ꢁ
H2O). 1H NMR (500 MHz, D2O): d = 4.30 (m, J = 5.2 Hz, 1H), 4.09
(d, J = 5.0 Hz, 1H), 4.00 (dd, J = 12.5 Hz, J = 4.5 Hz, 1H), 3.65 (d,
J = 12.5 Hz, 1H), 3.62 (d, J = 12.5 Hz, 1H), 3.55 (m, J = 4.9 Hz, 2H),

M. Zhao et al. / Tetrahedron: Asymmetry 20 (2009) 247–258
257
FAB/MS (m/e): 280 [M+H]+. Anal. Calcd for C10H17O8N: C, 43.01; H,
6.14; N, 5.02. Found: C, 42.88; H, 6.05; N, 5.13.
J = 4.6 Hz, 2H). FAB/MS (m/e): 298 [M+H]+. Anal. Calcd for
C14H19O6N: C, 56.56; H, 6.44; N, 4.71. Found: C, 56.72; H, 6.32;
N, 4.83.
4.2.11.6. N-(b-
the general procedure for preparing
46.3 mg (0.1 mmol) of N-(b- -arabinofuranos-1-yl)-N-(2-nitro-
L
-Arabinofuranos-1-yl)-
L-glutamic acid 5c-b. Using
a- and b-anomers of 5a–f from
4.2.11.11. N-(
the general procedure for preparing
43.5 mg (0.1 mmol) of N-( -arabinofuranos-1-yl)-N-(2-nitro-
a
-
L
-Arabinofuranos-1-yl)-
L-threonine 5f-a. Using
L
a- and b-anomers of 5a–f from
benzenesulfonyl)-
L
-glutamic acid 4c-b, 19.5 mg (70%) of 5c-b was
a-L
obtained as colorless powder. ½a D25
ꢁ
¼ ꢀ9:2 (c 1.1, H2O). 1H NMR
benzenesulfonyl)-L-theorine 4f-a, 19.0 mg (75%) of 5f-a was ob-
(500 MHz, D2O): d = 4.23 (dd, J = 8.5 Hz, J = 2.3 Hz, 1H), 4.18 (m,
J = 2.5 Hz, 1H), 4.06 (d, J = 4.6 Hz, 1H), 4.00 (dd, J = 8.6 Hz,
J = 2.6 Hz, 1H), 3.71 (dd, J = 9.6 Hz, J = 2.7 Hz, 1H), 3.64 (dd,
J = 8.1 Hz, J = 2.4 Hz, 1H), 3.17 (d, J = 10.7 Hz, 1H), 3.10 (d,
J = 10.6 Hz, 1H), 2.00 (m, J = 4.3 Hz, 2H), 1.70 (m, J = 4.1 Hz, 2H).
FAB/MS (m/e): 280 [M+H]+. Anal. Calcd for C10H17O8N: C, 43.01;
H, 6.14; N, 5.02. Found: C, 43.13; H, 6.00; N, 4.98.
tained as colorless powder. ½a D25
ꢁ
¼ þ8:0 (c 1.2, H2O). 1H NMR
(500 MHz, D2O): d = 4.22 (m, J = 3.9 Hz, 1H), 4.12 (d, J = 6.5 Hz,
1H), 4.08 (d, J = 4.5 Hz, 1H), 3.97 (dd, J = 11.0 Hz, J = 3.0 Hz, 1H),
3.82 (m, J = 5.2 Hz, 1H), 3.66 (m, J = 6.4 Hz, 1H), 3.27 (d,
J = 10.0 Hz, 1H), 3.20 (d, J = 10.0 Hz, 1H), 2.54 (m, J = 5.0 Hz, 1H),
1.23 (d, J = 6.7 Hz, 3H). FAB/MS (m/e): 252 [M+H]+. Anal. Calcd for
C14H19O6N: C, 43.03; H, 6.82; N, 5.58. Found: C, 42.88; H, 6.59;
N, 5.46.
4.2.11.7. N-(
general procedure for preparing
44.4 mg (0.1 mmol) of N-(
a
-
L
-Arabinofuranos-1-yl)-
- and b-anomers of 5a–f from
-arabinofuranos-1-yl)-N-(2-nitro-
L-serine 5d-a. Using the
a
4.2.11.12. N-(b-
the general procedure for preparing
43.5 mg (0.1 mmol) of N-(b- -arabinofuranos-1-yl)-N-(2-nitro-
L
-Arabinofuranos-1-yl)-
L-theorine 5f-b. Using
a-L
a- and b-anomers of 5a–f from
benzenesulfonyl)-
L
-serine (4d-
a
ꢁ
), 18.0 mg (76%) of 5d-
a
was ob-
L
tained as colorless powder. ½a D25
¼ þ20:0 (c 1.1, H2O), 1H NMR
benzenesulfonyl)-L-threonine (4f-b), 18.1 mg (72%) of 5f-b was ob-
(500 MHz, D2O): d = 4.30(m, J = 3.2 Hz, 1H), 4.18 (d, J = 4.6 Hz,
1H), 4.05 (dd, J = 10.2 Hz, J = 4.7 Hz, 1H), 3.87 (dd, J = 10.2 Hz,
J = 5.7 Hz, 1H), 3.83 (m, J = 3.8 Hz, 1H), 3.34 (d, J = 10.2 Hz, 1H),
3.06 (d, J = 10.2 Hz, 1H), 2.56 (m, J = 3.9 Hz, 2H), 1.71 (m,
J = 4.3 Hz, 2H). FAB/MS (m/e): 238 [M+H]+. Anal. Calcd for
C8H15O7N: C, 40.51; H, 6.37; N, 5.91. Found: C, 40.39; H, 6.19; N,
5.86.
tained as colorless powder. ½a D25
ꢁ
¼ ꢀ9:0 (c 1.1, H2O). 1H NMR
(500 MHz, D2O): d = 4.18 (m, J = 3.8 Hz, 1H), 4.16 (d, J = 6.6 Hz,
1H), 4.12 (d, J = 4.7 Hz, 1H), 3.85(dd, J = 11.1 Hz, J = 3.0 Hz, 1H),
3.78 (m, J = 5.0 Hz, 1H), 3.57 (m, J = 6.5 Hz, 1H), 3.19 (d,
J = 10.1 Hz, 1H), 3.08 (d, J = 10.1 Hz, 1H), 2.51 (m, J = 5.0 Hz, 1H),
1.20 (d, J = 6.7 Hz, 3H). FAB/MS (m/e): 252 [M+H]+. Anal. Calcd for
C14H19O6N: C, 43.03; H, 6.82; N, 5.58. Found: C, 43.15; H, 6.94;
N, 5.70.
4.2.11.8. N-(b-
general procedure for preparing
44.4 mg (0.1 mmol) of N-(b-
L
-Arabinofuranos-1-yl)-
- and b-anomers of 5a–f from
-arabinofuranos-1-yl)-N-(2-nitro-
L-serine 5d-b. Using the
a
4.3. Animals
L
benzenesulfonyl)-
L
-serine 4d-b, 18.9 mg (80%) of 5d-b was ob-
Male ICR mice (weighting 23 2 g) were purchased from the
Experimental Animal Center of Peking University. All the chemicals
used in the animal experiments were purchased from Sigma
Chemical Co. The study described herein was performed according
to a protocol reviewed and approved by the ethics committee of
Peking University. The committee assures that the welfare of the
animals was maintained in accordance to the requirements of
the animal welfare act and according to the guide for care and
use of laboratory animals.
tained as colorless powder. ½a D25
ꢁ
¼ ꢀ19:0 (c 1.1, H2O). 1H NMR
(500 MHz, D2O): d = 4.22 (m, J = 3.4 Hz, 1H), 4.10 (d, J = 4.5 Hz,
1H), 3.98 (dd, J = 10.0 Hz, J = 4.7 Hz, 1H), 3.92 (dd, J = 10.0 Hz,
J = 5.7 Hz, 1H), 3.75 (m, J = 3.9 Hz, 1H), 3.26 (d, J = 10.0 Hz, 1H),
3.00 (d, J = 10.0 Hz, 1H), 2.50 (m, J = 3.9 Hz, 2H), 1.69 (m,
J = 4.3 Hz, 2H). FAB/MS (m/e): 238 [M+H]+. Anal. Calcd for
C8H15O7N: C, 40.51; H, 6.37; N, 5.91. Found: C, 40.64; H, 6.50; N,
5.83.
4.2.11.9. N-(
the general procedure for preparing
49.4 mg (0.1 mmol) of N-( -arabinofuranos-1-yl)-N-(2-nitro-
a
-
L
-Arabinofuranos-1-yl)-
L
-phenylalanine 5e-
a
. Using
4.4. Lead decorporation assay13
a- and b-anomers of 5a–f from
a-L
Twenty groups (each 10) of mice were loaded with lead via ip
injection of 8.2 mg/kg of Pb(C2H3O2)2ꢂ3H2O in 0.5 ml of 0.9% sal-
ine (NS) per day for seven consecutive days. After a 2-day inter-
val, one group served as the control and were given a daily
injection of 0.5 ml of NS instead of 5a–f; another seven groups
served as the positive controls and was given a daily ip injection
phenylsulfonyl)-L-phenyl-alanine 4e-a, 24.0 mg (79%) of 5e-a
was obtained as colorless powder. ½a D25
ꢁ
¼ þ6:7 (c 1.2, H2O), 1H
NMR (500 MHz, D2O): d = 7.30 (d, J = 7.2 Hz, 2H), 7.22 (t,
J = 7.0 Hz, 1H), 7.19 (t, J = 7.3 Hz, 1H), 4.32 (m, J = 3.9 Hz, 1H),
4.25 (m, J = 3.8 Hz, 1H), 4.08 (d, J = 4.4 Hz, 1H), 3.98 (dd,
J = 10.2 Hz, J = 2.7 Hz, 1H), 3.86 (m, J = 4.0 Hz, 1H), 3.25 (d,
J = 10.5 Hz, 1H), 3.19 (m, J = 10.5 Hz, 1H), 2.68 (m, J = 4.5 Hz, 2H),
1.71 (m, J = 4.6 Hz, 2H). FAB/MS (m/e): 298 [M+H]+. Anal. Calcd
for C14H19O6N: C, 56.56; H, 6.44; N, 4.71. Found: C, 56.35; H,
6.65; N, 4.46.
of 0.4 mmol/kg of
-Glu, -Ser, -Phe, and
groups were given a daily ip injection (0.4 mmol/kg in 0.2 ml of
NS) of 5a–f- and 5a–f-b for five consecutive days. On each
DL
-penicillamine,
L-arabinose, L-Asp, L-Cys
L
L
L
L-Thr in 0.2 ml of NS. The remaining twelve
a
day, 2 h after the administration of the agents, the urine samples
of each group were continually collected for 5 h. After administra-
tion of the agents, the fecal samples of each group were continu-
ally collected for 24 h. Twenty-four hours after the last
administration of the agents, all the mice were sacrificed by
diethyl ether anesthesia and dissected to immediately obtain kid-
ney and left femur.
All the bio-samples were digested in HClO4:HNO3 (1:3) on a
heating block, dried at 80 °C, redissolved in 1% nitric acid to deter-
mine lead content using a Varian Spectr AA-40 atomic absorption
spectrometer in the graphite furnace. The variety of trace metals
was determined by synchrotron X-ray fluorescence. All data are
4.2.11.10. N-(b-
the general procedure for preparing
49.4 mg (0.1 mmol) of N-(b- -arabinofuranos-1-yl)-N-(2-nitro-
L
-Arabinofuranos-1-yl)-
L-phenylalanine 5e-b. Using
a- and b-anomers of 5a–f from
L
phenylsulfonyl)-L-phenyl-alanine 4e-b, 20.7 mg (70%) of 5e-b was
obtained as colorless powder. ½a D25
ꢁ
¼ ꢀ11:0 (c 1.2, H2O). 1H NMR
(500 MHz, D2O): d = 7.21 (d, J = 7.0 Hz, 2H), 7.13 (t, J = 7.1 Hz,
1H), 7.04 (t, J = 7.0 Hz, 1H), 4.24 (m, J = 3.8 Hz, 1H), 4.19 (m,
J = 3.9 Hz, 1H), 4.14 (d, J = 4.2 Hz, 1H), 3.78 (dd, J = 10.0 Hz,
J = 2.7 Hz, 1H), 3.62 (m, J = 4.2 Hz, 1H), 3.17 (d, J = 10.1 Hz, 1H),
3.08 (m, J = 10.2 Hz, 1H), 2.64 (m, J = 4.5 Hz, 2H), 1.70 (m,

258
M. Zhao et al. / Tetrahedron: Asymmetry 20 (2009) 247–258
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carried out by using ANOVA test, p < 0.05 is considered significant.
Acknowledgments
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This work was completed in the Beijing area major laboratory of
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National Natural Scientific Foundation of China (30672513,
30801426), and the Beijing Municipal Commission of Education
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