Synthesis of 2-C-(4-aminocarbonyl-2-thiazoyl)-1,4-anhydro-L-xylitols and their fluoro derivatives

Article abstract of DOI:10.1016/S0957-4166(97)00615-0

3,5-O-Benzylidene-2-C-cyano-1,4-anhydro-L-xylitol 7 was synthesized stereoselectively from D-xylose in 7 steps, 2-C-(4-Aminocarbonyl-2-thiazoyl)- 1,4-anhydro-L-xylitols and their fluoro derivatives were synthesized from the cyanohydrin 7. Fluorination of compound 9 proceeded with retention of configuration using diethylaminosulfur trifluoride (DAST).

Full text of DOI:10.1016/S0957-4166(97)00615-0

Pergamon
Tetrahedron: Asymmetry 9 (1998) 141–149
Synthesis of 2-C-(4-aminocarbonyl-2-thiazoyl)-1,4-anhydro-L-
xylitols and their fluoro derivatives
H. Y. Zhang, H. W. Yu, L. T. Ma, J. M. Min and L. H. Zhang ∗
The National Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Beijing Medical
University, Beijing 100083, PR China
Received 4 November 1997; accepted 25 November 1997
Abstract
3,5-O-Benzylidene-2-C-cyano-1,4-anhydro-L-xylitol 7 was synthesized stereoselectively from D-xylose in 7
steps. 2-C-(4-Aminocarbonyl-2-thiazoyl)-1,4-anhydro-L-xylitols and their fluoro derivatives were synthesized
from the cyanohydrin 7. Fluorination of compound 9 proceeded with retention of configuration using diethy-
laminosulfur trifluoride (DAST). © 1998 Elsevier Science Ltd. All rights reserved.
1. Introduction
Considerable effort has been directed to the search for novel nucleoside analogues for use as antiviral
and antitumor agents. The biological activity of the naturally occurring C-nucleosides has stimulated
the research of this field in the last two decades. Among them, tiazofurin1 and its selenium analogue,
selenazofurin,2 with distinguished antitumor and antiviral activity, have gained significant attention.
Structural modifications of the ribofuranosyl moiety of tiazofurin have been reported including prepa-
ration of 50-, 30-, or 20-substituted derivatives,1,3,4 arabino- and xylofuranosyl,5,6 acyclic,7 pyranosyl,8
carbocyclic9 analogues. However, these substances were devoid of any significant biological activity.
Recently, a number of nucleosides with the unnatural L-configuration have been reported as
potent chemotherapeutic agents against HIV, HBV and certain forms of cancer. It is interesting
that these L-nucleosides have potent biological activities, while some of them show lower toxicity
∗
Corresponding author. E-mail: zdszlh@mail.bjmu.edu.cn
0957-4166/98/$19.00 © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(97)00615-0

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H. Y. Zhang et al. / Tetrahedron: Asymmetry 9 (1998) 141–149
profiles than their D-counterparts.10 We have reported the synthesis of 40-(R)-hydroxyl-50-(S)-
hydroxymethyl-tetrahydrofuranyl purines and pyridines from D-xylose11 and some derivatives of
4-deoxy-4-nucleobase-2,5-anhydro-L-mannitol from D-glucose.12 In this paper, we report the synthesis
of 2-C-(4-aminocarbonyl-2-thiazoyl)-1,4-anhydro-L-xylitols and their fluoro derivatives.
2. Results and discussion
1,2-O-Isopropylidene-α-D-xylose 1 was prepared from D-xylose according to the method of Morav-
cova et al.13 Tosylation of 1 was completed by the reaction of 1 with toluenesulfonyl chloride in
pyridine at 0°C to give compound 2.14 After treatment of 2 with 1% trifluoroacetic acid in methanol
at 80°C, followed by reaction with sodium borohydride, 1,4-anhydro-L-xylitol 4 was obtained and the
protection of 4 was completed in the presence of benzaldehyde and anhydrous zinc chloride in 34.7%
yield in one pot.11,12,14,15 The 2-OH in 5 was oxidized by using chromium trioxide/pyridine/acetic
anhydride in dichloromethane to give ketone 6. The key intermediate, cyanohydrin 7, was formed from a
stereoselective addition of potassium cyanide to 6 in ethyl acetate at room temperature. The cyano group
was introduced from the upper side on C-2 in 66.5% yield (Scheme 1). If the 2-hydroxy group is ‘up’ on
the ring, the cyanohydrin obtained may be less stable than 7 due to the stereoelectronic effect between
the neighboring oxygen atoms. The stereochemistry at C-2 of cyanohydrin 7 was determined by a single
crystal X-ray analysis (Fig. 1). It was shown that the cyano group on the cyanohydrin 7 was at the same
side of 3,5-O-benzylidene group.
Scheme 1.
Compound 8 was obtained by the reaction of 7 and hydrogen sulphide in the presence of a catalytic
amount of 4-methylaminopyridine. The thiazole 9 was synthesized by the reaction of thioamide 8 and
ethyl bromopyruvate in acetonitrile at room temperature in 73.5% yield (Scheme 2).
Ammonolysis of this ester afforded the amide 10 and 11 and deblocking of the benzylidene group
was completed using 0.5% aqueous trifluoroacetic acid solution at 75°C to give compounds 12 and 13 in
approximately quantitative yields (Scheme 3). The fluorinated analogue 14 was obtained by fluorination
of 9 with diethylaminosulfur trifluoride (DAST) in dichloromethane at room temperature in very good
yield. Usually, it was assumed that DAST fluorination of the hydroxyl group would proceed with
inversion of configuration.16 However, Jeong et al.17 reported that fluorination of hydroxyl groups at C20
and C30 of the 40-thioribofuranosyl ring with DAST proceeded with exclusive retention of configuration

H. Y. Zhang et al. / Tetrahedron: Asymmetry 9 (1998) 141–149
143
Fig. 1. Crystal X-ray structures of compounds 7 and 16
Scheme 2.
due to the participation of the 40-thiofuranose sulfur via a double inversion mechanism. The structure of
16 was determined by a single crystal X-ray analysis (Fig. 1). The X-ray derived structure of 16 shows
that fluorine was ‘down’ on the sugar ring. It appears, therefore, a double inversion mechanism during
the DAST reaction of compound 9 is responsible for the retention of the configuration.
Scheme 3.

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H. Y. Zhang et al. / Tetrahedron: Asymmetry 9 (1998) 141–149
3. Conclusion
Novel nucleosides 12, 13, 15 and 16 were synthesized stereoselectively by construction of a thiazole
moiety from cyanohydrin 7. The fluorination of compound 9 with DAST proceeded with the retention of
the configuration.
4. Experimental section
4.1. General procedures
Melting points were determined on a Kofler melting point apparatus and were uncorrected. Optical
rotations were determined with a Perkin–Elmer 243B polarimeter. IR spectra were recorded on a DE-
983G spectrophotometer in KBr pellets. UV spectra were recorded on a Pharmacia LKB Biochrom 4060
spectrophotometer. Mass spectra were obtained on either ZAB-HS or KYKY-ZHP-5 mass spectrometers.
NMR spectra were recorded on Varian-300, Varian-500 or Brucker DPX-400 spectrometers with TMS as
an internal standard. Exchangeable protons were detected by addition of D2O. Column chromatography
was performed on silica gel (200–300 mesh) and silica gel GF254 was used for TLC purchased from the
Qingdao Chemical Company, China.
4.2. 3,5-O-Benzylidene-1,4-anhydro-L-xylitol 5
Toluenesulfonyl chloride (50 g, 0.26 mol) was added to a stirred solution of 1 (46.0 g, 0.24 mol) in
pyridine (300 ml) at 0°C. The mixture was stirred at room temperature for 2 h. Some of the solvent was
evaporated and the residue was stirred with saturated NaHCO3 (100 ml) for 30 min. The mixture was
extracted with CHCl3, washed with 1 M H2SO4 and H2O, then dried over anhydrous Na2SO4 to yield
a yellow–white solid. The crude solid was allowed to react in 1% trifluoroacetic acid in methanol (600
ml) at 80°C for 24 h, followed by neutralization with solid NaHCO3. The solvents were evaporated and
the residue was extracted with acetone (300 ml). After the acetone solution was concentrated, a pale-
yellow syrup, in which compound 3 was contained, was dissolved in water (300 ml) containing 0.3%
trifluoroacetic acid. The solution was heated at 80°C for 6 h, then cooled to 0°C. After neutralization,
the mixture was treated with NaBH4 (13.0 g) at room temperature for 1.5 h, then cooled to 0°C and
neutralized again. The residue was evaporated and the mixture was applied to a silica gel column and
eluted with ethanol. The combined eluant was concentrated and evaporated with toluene (50 ml×2).
Freshly dried zinc chloride (30 g) and 100 ml (0.98 mol) of benzaldehyde were added to the resulting
syrup and the suspension was stirred vigorously for 2 days at room temperature. The mixture was
poured into cold water and extracted with CHCl3. The combined organic layer was dried with anhydrous
Na2SO4. After filtration and removal of the solvent, the desired product 5 (10.2 g) was obtained as white
needles. An additional compound 5 (8.3 g) was obtained from the mother liquid. The total yield was
34.7% from 1. [α]2D2 +3.3 (c 0.060, MeOH). 1H NMR (CDCl3) δ ppm: 7.46 (2H, m, arom H), 7.36 (3H,
m, arom H), 5.44 (1H, s, PhCH<), 4.43 (1H, d, J5a,5b=13.3 Hz, H5a), 4.39 (1H, d, J1a,1b=11.1 Hz, H1a),
4.38 (1H, d, J3,4=6.0 Hz, H3), 4.31 (1H, d, J2,1b=2.4 Hz, H2), 4.12 (1H, dd, J5b,5a=13.3 Hz, J5b,4=1.8 Hz,
H5b), 3.99 (1H, m, H4), 3.82 (1H, dd, J1b,1a=11.1 Hz, J1b,2=2.4 Hz, H1b). Calcd for C12H14O4 (222.26):
C, 64.84; H, 6.36. Found: C, 64.45; H, 6.35.

H. Y. Zhang et al. / Tetrahedron: Asymmetry 9 (1998) 141–149
145
4.3. 3,5-O-Benzylidene-2-keto-1,4-anhydro-L-xylitol 6
To a stirred suspension of CrO3 (27 g, 0.27 mol) in CH2Cl2 (200 ml) under an ice–water external bath
were carefully added pyridine (44 ml, 0.54 mol), a solution of 5 (20 g, 0.090 mol) in CH2Cl2 (200 ml)
and Ac2O (25.5 ml, 0.27 mol). The mixture was stirred at room temperature for 3 h, then poured into
ethyl acetate (400 ml) and stirred for more than 30 min. After filtration through a short silica gel column
eluted with EtOAc, the combined eluant was concentrated and neutralized with concentrated NaOH
aqueous solution. The mixture was extracted with CHCl3, washed with 1 M H2SO4 and H2O, dried with
anhydrous Na2SO4 and evaporated to yield a brown solid which was recrystallized from ethanol to give
1
6 as a white solid (9.7 g, 49.0%). [α]2D2 −32.4 (c 0.074, MeOH). H NMR (CDCl3) δ ppm: 7.48 (2H,
m, arom H), 7.36 (3H, m, arom H), 5.55 (1H, s, PhCH<), 4.49 (1H, d, J5a,5b=12.6 Hz, H5a), 4.48 (1H,
d, J1a,1b=18.0 Hz, H1a), 4.29 (1H, d, J5b,5a=12.6 Hz, J5b,4=2.4 Hz, H5b), 4.28 (1H, d, J3,4=2.4 Hz, H3),
4.01 (1H, d, J1b,1a=18.0 Hz, H1b), 4.00 (1H, m, H4). 13C NMR (CDCl3) δ ppm: 206.4 (C2), 135.3, 127.7,
126.7 (×2), 124.5 (×2) (arom C), 97.9 (PhCH<), 72.2 (C3), 71.1 (C4), 69.4 (C1), 65.4 (C5). Calcd for
C12H12O4 (220.24): C, 65.43; H, 5.50. Found: C, 65.43; H, 5.39.
4.4. 3,5-O-Benzylidene-2-C-cyano-1,4-anhydro-L-xylitol 7
A mixture of 6 (8.7 g, 0.040 mmol), ethyl acetate (200 ml), water (100 ml), sodium hydrogen carbonate
(7.0 g) and potassium cyanide (3.0 g, 0.046 mmol) was stirred vigorously at room temperature overnight.
The organic phase was separated and dried over anhydrous Na2SO4. After evaporation, the residue was
purified by silica gel chromatography and recrystallized from EtOH to give 7 as white crystals (6.5 g,
KBr
66.5%). m.p. >355°C. [α]2D2 −86.4 (c 0.044, MeOH). IR ν
(cm−1): 2245. EI-MS (m/z): 247[M+]. 1H
max
NMR (DMSO-d6) δ ppm: 7.42 (5H, m, arom H), 7.33 (1H, s, exchangeable, 2-OH), 5.66 (1H, s, PhCH<),
4.53 (1H, d, J3,4=2.4 Hz, H3), 4.26 (1H, d, J1a,1b=9.2 Hz, H1a), 4.20 (1H, d, J5a,5b=13.0 Hz, H5a), 4.15
(1H, d, J5b,5a=13.0 Hz, J5b,4=1.6 Hz, H5b), 4.02 (1H, d, J4,5b=1.6 Hz, H4), 3.98 (1H, d, J1b,1a=9.2 Hz, H1b).
13C NMR (CDCl3) δ ppm: 137.7, 128.9, 128.1 (×2), 126.0 (×2) (arom C), 118.0 (CN), 97.7 (PhCH<),
79.9 (C2), 76.5 (C3), 75.0 (C1), 72.5 (C4), 66.5 (C5). Calcd for C13H13O4N (247.27): C, 63.14; H, 5.31;
N, 5.67. Found: C, 63.17; H, 5.19; N, 5.65. Crystal data: empirical formula, C13H13O4N; formula weight,
247.25; crystal system, orthorhombic; space group, P212121; a=5.641(2), b=12.652(4), c=17.045(5) Å,
V=1216.5(7) Å3, Z=4, Dx=1.350 g/cm3.
4.5. 3,5-O-Benzylidene-2-C-aminothiocarbonyl-1,4-anhydro-L-xylitol 8
Hydrogen sulphide was introduced into the vigorously stirred reaction mixture of compound 7 (7.6
g, 0.031 mmol) and 4-dimethylaminopyridine (1.4 g) in ethanol (80 ml) and dioxane (80 ml) at room
temperature for 20 h. The reaction mixture was sealed and stirred for over 10 h. The solvent was
evaporated and the residue was purified by silica gel chromatography (2–20% ethyl acetate–petroleum
MeOH
max
ether) to yield compound 8 as a white solid (3.5 g, 40.5%). [α]2D2 −214.7 (c 0.034, MeOH). UV λ
(log ε): 207.6 (4.03), 268.9 (4.08). EI–MS (m/z): 281[M+]. 1H NMR (DMSO-d6) δ ppm: 9.83, 9.10 (each
1H, s, NH2), 7.38 (5H, m, arom H), 6.10 (1H, s, 2-OH), 5.48 (1H, s, PhCH<), 4.73 (1H, d, J1a,1b=9.2
Hz, H1a), 4.35 (1H, d, J5a,5b=12.0 Hz, H5a), 4.19 (1H, s, H3), 4.10 (1H, d, J5b,5a=12.0 Hz, H5b), 4.08 (1H,
s, H4), 3.80 (1H, d, J1b,1a=9.2 Hz, H1b). Calcd for C13H15O4NS (281.35): C, 55.49; H, 5.38; N, 4.98.
Found: C, 55.42; H, 5.37; N, 4.67.

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H. Y. Zhang et al. / Tetrahedron: Asymmetry 9 (1998) 141–149
4.6. 3,5-O-Benzylidene-2-C-(4-ethoxycarbonyl-2-thiazoyl)-1,4-anhydro-L-xylitol 9
Compound 8 (3.0 g, 0.011 mol) in anhydrous acetonitrile (150 ml) was reacted with ethyl bromopy-
ruvate (5.3 ml, 0.042 mmol) for 48 h. The reaction mixture was concentrated and stirred with saturated
NaHCO3 solution (50 ml) for 20 min and then extracted with diethyl ether and dried. On removal of the
solvent, a brown syrup was obtained. After silica gel column chromatography (CHCl3:CH3OH, 200:1)
and recrystallization from ethanol, compound 9 was obtained as a white solid (2.96 g, 73.5%). [α]2D2
MeOH
1
−176.5 (c 0.034, MeOH). UV λ
(log ε): 205.1 (4.43), 233.6 (4.05). EI-MS (m/z): 377[M+]. H
max
0
NMR (DMSO-d6) δ ppm: 8.55 (1H, s, H5 ), 7.32 (5H, m, arom H), 6.92 (1H, s, 2-OH), 5.57 (1H,
s, PhCH<), 4.69 (1H, d, J1a,1b=9.5 Hz, H1a), 4.40 (1H, d, J3,4=2.0 Hz, H3), 4.31 (2H, q, J=7.5 Hz,
–OCH2CH3), 4.23 (1H, overlapped, H4), 4.21 (1H, d, J5a,5b=12.0 Hz, H5a), 4.17 (1H, dd, J5b,5a=12.0
Hz, J5b,4=1.5 Hz, H5b), 4.07 (1H, d, J1b,1a=9.5 Hz, H1b), 1.30 (3H, t, J=7.5 Hz, –OCH2CH3). 13C NMR
0
0
0
(DMSO-d6) δ ppm: 170.6 (C2 ), 160.8 (–COOEt), 145.4 (C4 ), 130.3 (C5 ), 138.1, 128.6, 127.9 (×2),
126.1 (×2) (arom C), 97.4 (PhCH<), 82.8 (C2), 81.2 (C3), 76.3 (C1), 73.2 (C4), 67.1 (–OCH2CH3), 60.7
(C5), 14.2 (–OCH2CH3). Calcd for C18H19O6NS (377.44): C, 57.24; H, 5.08; N, 3.71. Found: C, 57.11;
H, 4.93; N, 3.64.
4.7. 3,5-O-Benzylidene-2-C-(4-aminocarbonyl-2-thiazoyl)-1,4-anhydro-L-xylitol 10
The solution of ester 9 (0.20 g, 0.53 mmol) in ethanol (4 ml) was allowed to react with 25% ammonia
solution (4 ml) at room temperature until consumption of the starting material. The crude product was
purified by silica gel column chromatography (petroleum ether:ethyl acetate 1:3) and recrystallization
MeOH
from ethanol yielded amide 10 (150 mg, 81.2%). [α]2D2 −147.8 (c 0.046, MeOH). UV λ
(log ε):
max
+
1
0
206.0 (4.30), 234.7 (3.84). PFAB-MS (m/z): 349 [M+1] . H NMR (DMSO-d6) δ ppm: 8.26 (1H, s, H5 ),
7.66, 7.62 (each 1H, NH2), 7.32 (5H, m, arom H), 6.84 (1H, s, 2-OH), 5.54 (1H, s, PhCH<), 4.84 (1H,
d, J1a,1b=9.0 Hz, H1a), 4.34 (1H, d, J3,4=2.0 Hz, H3), 4.22 (1H, s, H4), 4.21 (1H, d, J5a,5b=12.0 Hz, H5a),
4.16 (1H, d, J5b,5a=12.0 Hz, H5b), 4.03 (1H, d, J1b,1a=9.0 Hz, H1b). Calcd for C16H16O5N2S (348.40): C,
55.15; H, 4.64; N, 8.04. Found: C, 54.93; H, 5.10; N, 7.83.
4.8. 3,5-O-Benzylidene-2-C-(4-methylaminocarbonyl-2-thiazoyl)-1,4-anhydro-L-xylitol 11
Compound 11 (160 mg, 83.3%) was obtained by the same procedure as 10, except using methylamine
MeOH
instead of ammonia. [α]2D2 −128.8 (c 0.052, MeOH). UV λ
(log ε): 205.7 (3.35), 232.7 (3.01).
max
PFAB-MS (m/z): 363 [M+1]+. H NMR (DMSO-d6) δ ppm: 8.28 (1H, q, J=5.0 Hz, –NHCH3), 8.23
(1H, s, H5 ), 7.31 (5H, m, arom H), 6.84 (1H, s, 2-OH), 5.54 (1H, s, PhCH<), 4.88 (1H, d, J1a,1b=9.5
1
0
Hz, H1a), 4.34 (1H, d, J3,4=2.0 Hz, H3), 4.22 (1H, s, H4), 4.21 (1H, d, J5a,5b=11.0 Hz, H5a), 4.16 (1H,
d, J5b,5a=11.0 Hz, H5b), 4.04 (1H, d, J1b,1a=9.5 Hz, H1b), 2.81 (3H, d, J=5.0 Hz, –NHCH3). Calcd for
C17H18O5N2S (362.43): C, 56.33; H, 5.02; N, 7.73. Found: C, 56.62; H, 4.91; N, 7.64.
4.9. 2-C-(4-Aminocarbonyl-2-thiazoyl)-1,4-anhydro-L-xylitol 12
Compound 10 (0.10 g, 0.29 mmol) was heated in 10 ml of 0.5% aqueous trifluoroacetic acid at 75°C
to remove the benzylidene group to yield compound 12 (93.8%), [α]2D2 −52.8 (c 0.036, MeOH). UV
MeOH
λ
(log ε): 204.5 (4.15), 231.2 (3.79). PFAB-MS (m/z): 261 [M+1]+. 1H NMR (DMSO-d6) δ ppm:
max
0
8.24 (1H, s, H5 ), 7.72, 7.56 (each 1H, –NH2), 6.53 (1H, s, 2-OH), 5.16 (1H, d, J3-OH, H3=6.0 Hz, 3-
OH), 4.58 (1H, t, J5-OH, H5=5.5 Hz, 5-OH), 4.49 (1H, d, J1a,1b=9.0 Hz, H1a), 4.22 (1H, m, J4,5=5.5 Hz,

H. Y. Zhang et al. / Tetrahedron: Asymmetry 9 (1998) 141–149
147
J4,3=3.0 Hz, H4), 3.92 (1H, dd, JH3,3-OH=6.0 Hz, J3,4=3.0 Hz, H3), 3.83 (1H, d, J1a,1b=9.0 Hz, H1b), 3.64
(1H, m, J5a,5-OH=5.5 Hz, J5a,4=5.5 Hz, J5a,5b=10.5 Hz, H5a), 3.52 (1H, m, J5b,5-OH=5.5 Hz, J5b,4=5.5 Hz,
13
0
0
J
5b,5a=10.5 Hz, H5b). C NMR (DMSO-d6) δ ppm: 172.1 (C2 ), 162.4 (–CONH2), 149.4 (C4 ), 125.0
0
(C5 ), 83.4 (C2), 82.9 (C4), 77.9 (C3), 75.0 (C1), 59.6 (C5). Calcd for C9H12O5N2S (260.29): C, 41.52;
H, 4.61; N, 10.76. Found: C, 41.25; H, 4.58; N, 10.58.
4.10. 2-C-(4-Methylaminocarbonyl-2-thiazoyl)-1,4-anhydro-L-xylitol 13
After removal of the benzylidene group as above, compound 11 (0.10 g, 0.28 mmol) was converted to
MeOH
yield 13 (95.1%), [α]2D2 −36.8 (c 0.068, MeOH). UV λ
(log ε): 203.5 (4.04), 233.4 (3.81). PFAB-
max
MS (m/z): 275 [M+1]+. H NMR (DMSO-d6) δ ppm: 8.29 (1H, q, J=5.0 Hz, –NHCH3), 8.20 (1H, s,
H5 ), 6.54 (1H, s, 2-OH), 5.12 (1H, d, J3-OH, H3=5.5 Hz, 3-OH), 4.57 (1H, t, J5-OH, H5=5.5 Hz, 5-OH),
1
0
4.50 (1H, d, J1a,1b=9.0 Hz, H1a), 4.20 (1H, m, H4), 3.91 (1H, dd, JH3,3-OH=5.5 Hz, J3,4=3.5 Hz, H3), 3.82
(1H, d, J1a,1b=9.0 Hz, H1b), 3.63 (1H, m, H5a), 3.50 (1H, m, H5b), 2.77 (3H, d, J=5.0 Hz, –NHCH3).
Calcd for C10H14O5N2S (274.32): C, 43.78; H, 5.15; N, 10.21. Found: C, 43.37; H, 5.26; N, 9.98.
4.11. 3,5-O-Benzylidene-2-C-(4-ethoxycarbonyl-2-thiazoyl)-2-deoxy-2-fluoro-1,4-anhydro-L-xylitol 14
A solution of 9 (0.40 mg, 1.1 mmol) in anhydrous CH2Cl2 (20 ml) was treated with diethylaminosulfur
trifluoride for 6 h at room temperature. The mixture was evaporated and purified by column chromatog-
MeOH
raphy to yield compound 14 (0.39 g, 97.0%). [α]3D4 −78.8 (c 0.035, MeOH). UV λ
(log ε): 207.0
max
+
1
0
(4.63), 236.0 (3.91). PFAB-MS (m/z): 380 [M+1] . H NMR (DMSO-d6) δ ppm: 8.71 (1H, s, H5 ),
7.32 (5H, m, arom H), 5.67 (1H, s, PhCH<), 4.94 (1H, dd, J3,4=2.5 Hz, J3,F=8.0 Hz, H3), 4.74 (1H,
dd, J1a,1b=11.0 Hz, J1a,F=41.0 Hz, H1a), 4.44 (1H, dd, J1b,1a=11.0 Hz, J1b,F=26.0 Hz, H1b), 4.32 (2H,
q, J=7.5 Hz, –OCH2CH3), 4.29 (1H, d, J5a,5b=12.5 Hz, H5a), 4.26 (1H, overlapped, H4), 4.24 (1H, dd,
J
5b,5a=12.5 Hz, J5b.4=1.5 Hz, H5b), 1.30 (3H, t, J=7.5 Hz, –OCH2CH3). 13C NMR (DMSO-d6) δ ppm:
0
0
0
162.1 (d, J=24.9 Hz, C2 ), 160.4 (–COOEt), 146.0 (C4 ), 131.7 (C5 ), 137.6, 128.9, 128.0 (×2), 126.0
(×2) (arom C), 102.2 (d, J=177.1 Hz, C2), 97.8 (PhCH<), 78.7 (d, J=34.5 Hz, C3), 74.1 (d, J=22.0 Hz,
C1), 73.3 (C4), 66.6 (–OCH2CH3), 61.0 (C5), 14.2 (–OCH2CH3). 19F NMR (DMSO-d6, CF3COOH as
an external strandard) δ ppm: −12.58 (dddd, J1a,F=41.0 Hz, J1b,F=26.0 Hz, J3,F=8.0 Hz, J4,F=3.8 Hz).
Calcd for C18H18O5NSF (379.43): C, 56.97; H, 4.79; N, 3.69. Found: C, 56.69; H, 4.71; N, 3.35.
4.12. 2-C-(4-Aminocarbonyl-2-thiazoyl)-2-deoxy-2-fluoro-1,4-anhydro-L-xylitol 15
After ammonolysis and removal of the benzylidene group as above, compound 14 (90 mg, 0.24 mmol)
was converted to yield 15 (50 mg, 80.4%). [α]3D4 −8.3 (c 0.040, MeOH). UV λmMaexOH (log ε): 203.4 (4.37),
+
1
0
232.3 (3.93, sh). PFAB-MS (m/z): 263 [M+1] . H NMR (DMSO-d6) δ ppm: 8.42 (1H, s, H5 ), 7.80,
7.65 (each 1H, s, –NH2), 5.78 (1H, d, J3-OH, H3=6.0 Hz, 3-OH), 4.73 (1H, t, J5-OH, H5=6.0 Hz, 5-OH), 4.64
(1H, d, J1a,1b=11.5 Hz, J1a,F=42.0 Hz, H1a), 4.30 (1H, m, JH3,3-OH=6.0 Hz, J3,4=3.5 Hz, J3,F=9.5 Hz, H4),
4.18 (1H, dd, J1b,1a=11.5 Hz, J1b, F=26.0 Hz, H1b), 4.17 (1H, overlapped, H4), 3.68 (1H, m, J5a,5b=11.5
Hz, J5a,5-OH=6.0 Hz, J5a,4=5.5 Hz, H5a), 3.56 (1H, m, J5b,5a=11.5 Hz, J5b,5-OH=6.0 Hz, J5b.4=5.5 Hz, H5b).
13
0
0
0
C NMR (DMSO-d6) δ ppm:163.3 (d, J=26.9 Hz, C2 ), 162.0 (–COONH2), 149.9 (C4 ), 126.5 (C5 ),
103.8 (d, J=177.1 Hz, C2), 82.9 (C4), 75.5 (d, J=29.8 Hz, C3), 72.4 (d, J=22.0 Hz, C1), 59.1 (C5). 19F
NMR (DMSO-d6, CF3COOH as an external standard) δ ppm: −7.37 (dddd, JH1a,F=42.0 Hz, JH1b,F=26.0
Hz, JH3,F=9.5 Hz, JH4,F=4.7 Hz). Calcd for C9H11O4N2SF (262.28): C, 41.21; H, 4.24; N, 10.68. Found:
C, 41.40; H, 4.37; N, 10.29.

148
H. Y. Zhang et al. / Tetrahedron: Asymmetry 9 (1998) 141–149
4.13. 2-C-(4-Methylaminocarbonyl-2-thiazoyl)-2-deoxy-2-fluoro-1,4-anhydro-L-xylitol 16
Compound 14 (0.25 g, 0.66 mmol) was converted as above to yield 16 (0.15 g, 82.4%). m.p.
MeOH
152–153°C. [α]3D4 −2.3 (c 0.068, MeOH). UV λ
(log ε): 206.1 (4.16), 231.3 (3.84). PFAB-MS
max
+
1
0
(m/z): 277 [M+1] . H NMR (DMSO-d6) δ ppm: 8.40 (1H, s, H5 ), 8.38 (1H, q, J =5.0 Hz, –NHCH3),
5.78 (1H, d, J3-OH, H3=6.0 Hz, 3-OH), 4.73 (1H, t, J5-OH, H5=6.0 Hz, 5-OH), 4.65 (1H, dd, J1a,1b=11.5
Hz, J1a,F=42.0 Hz, H1a), 4.30 (1H, m, JH3,3OH=6.0 Hz, J3,4=3.5 Hz, J3,F=9.5 Hz, H3),4.18 (1H, dd,
J1b,1a=11.5 Hz, J1b,F=26.0 Hz, H1b), 4.17 (1H, overlapped, H4), 3.68 (1H, m, J5a,5b=11.0 Hz, J5a,5-OH=6.0
Hz, J5a,4=5.5 Hz, H5a), 3.57 (1H, m, J5b,5a=11.0 Hz, J5b,5-OH=6.0 Hz, J5b.4=5.5 Hz, H5b), 2.79 (3H, d,
J=5.0 Hz, –NHCH3). 13C NMR (DMSO-d6) δ ppm: 163.4 (d, J=26.8 Hz, C2 ), 160.7 (–COONHCH3),
0
0
0
149.7 (C4 ), 125.8 (C5 ), 103.8 (d, J=177.1 Hz, C2), 82.9 (C4), 75.5 (d, J=30.6 Hz, C3), 72.4 (d, J=21.0
Hz, C1), 59.1 (C5), 25.8 (–NHCH3). 19F NMR (DMSO-d6, CF3COOH as external standard) δ ppm:
−7.76 (dddd, JH1a,F=42.0 Hz, JH1b,F=26.0 Hz, JH3,F=9.5 Hz, JH4,F=5.2 Hz). Calcd for C10H13O4N2SF
(276.28): C, 43.47; H, 4.74; N, 10.14. Found: C, 43.57; H, 4.76; N, 10.32. Crystal data: empirical
formula, C13H13O4N; formula weight, 276.26; crystal system, monoclinic; space group, P21; a=6.889(1),
b=9.677(2), c=8.982(1) Å, β=96.96(3)°, V=594.4(8) Å3, Z=2, Dc=1.54 g/cm3, F (000)=286.
Acknowledgements
This project was supported by the National Natural Science Foundation of China and we thank Mrs.
Yang Lu, Mr. Wenjun Kang and Prof. Qitai Zheng (Chinese Academy of Medicine Science) and Mrs.
Xiuyun Lin and Prof. Yicheng Dong (Institute of Biophysics, Chinese Academy of Sciences) for single-
crystal X-ray analyses.
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