Synthesis and biological evaluation of isonucleosides derived from methyl 3,5-anhydro-2-O-(2-fluorobenzyl)-D-xylofuranosides

Article abstract of DOI:10.1081/NCN-120003290

New isonucleosides [methyl 5-(1-pyrimidinyl)furanosides] are prepared by nucleophilic opening of the oxetane ring of methyl 3,5-anhydro-2-O-(2-fluorobenzyl)-D-xylofuranoside with silylated pyrimidine bases in the presence of trimethylsilyl triflate. Struc

Full text of DOI:10.1081/NCN-120003290

Nucleosides, Nucleotides and Nucleic Acids
ISSN: 1525-7770 (Print) 1532-2335 (Online) Journal homepage: http://www.tandfonline.com/loi/lncn20
SYNTHESIS AND BIOLOGICAL EVALUATION
OF ISONUCLEOSIDES DERIVED FROM METHYL
3,5-ANHYDRO-2-O-(2-FLUOROBENZYL)-d-
XYLOFURANOSIDES
Jörn Wirsching , Oliver Schulze , Jürgen Voss , Anja Giesler , Jürgen Kopf ,
Gunadi Adiwidjaja , Jan Balzarini & Erik De Clercq
To cite this article: Jörn Wirsching , Oliver Schulze , Jürgen Voss , Anja Giesler , Jürgen Kopf ,
Gunadi Adiwidjaja , Jan Balzarini & Erik De Clercq (2002) SYNTHESIS AND BIOLOGICAL
EVALUATION OF ISONUCLEOSIDES DERIVED FROM METHYL 3,5-ANHYDRO-2-O-(2-
FLUOROBENZYL)-d-XYLOFURANOSIDES, Nucleosides, Nucleotides and Nucleic Acids, 21:3,
257-274, DOI: 10.1081/NCN-120003290
To link to this article: http://dx.doi.org/10.1081/NCN-120003290
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Date: 11 October 2015, At: 04:15

NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS, 21(3), 257–274 (2002)
SYNTHESIS AND BIOLOGICAL EVALUATION OF
ISONUCLEOSIDES DERIVED FROM METHYL
3,5-ANHYDRO-2-O-(2-FLUOROBENZYL)-
D-XYLOFURANOSIDES
1
Jorn Wirsching,1 OliverSchulze, Jurgen Voss,1,* Anja Giesler,2
Jurgen Kopf,2 Gunadi Adiwidjaja,3 Jan Balzarini,4
and Erik De Clercq4
1Institut fur Organische Chemie der Universitat Hamburg,
Martin-Luther-King-Platz6, 20146 Hamburg, Germany
2Institut fur Anorganische und Angewandte Chemie der Universitat
Hamburg, Martin-Luther-King-Platz6, 20146 Hamburg, Germany
3Mineralogisch-Petrographisches Institut der Universitat Hamburg,
Grindelallee 48, 20146 Hamburg, Germany
4Rega Institute for Medical Research, Catholic University of
Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium
ABSTRACT
New isonucleosides [methyl 5-(1-pyrimidinyl)furanosides] are prepared
by nucleophilic opening of the oxetane ring of methyl 3,5-anhydro-2-O-
(2-fluorobenzyl)-D-xylofuranoside with silylated pyrimidine bases in the
presence of trimethylsilyl triflate. Structures, configurations and con-
formations were determined by NMR techniques and several X-ray dif-
fraction analyses. seven of the isonucleosides were tested for cytotoxicity
and activity against HIV, HSV and several other viruses.
*Corresponding author. Fax: +49(0)40=42838-5592; E-mail: voss@chemie.uni-hamburg.de
257
Copyright # 2002 by Marcel Dekker, Inc.
www.dekker.com

258
WIRSCHING ET AL.
INTRODUCTION
Since the mid-seventies the so-called isonucleosides in which the
nucleobase is linked to the primary carbon atom (C-5) of a pentofuranose
instead to the anomeric centre have found considerable scientific interest1.
Two general ways for the preparation of such compounds have been
described in the literature. One is to couple the sodium salt of a pyrimidine or
purine base with a sugar, which bears a good leaving group at C-5 (e.g., a
tosyl group). Using this method, Holy1 synthesised adenine and thymine
derivatives of type A. The second route to isonucleosides consists in the
reaction of a 3,5-anhydro-1-deoxypentofuranose with a nucleobase under
base-catalysis. In this way Ioannisyan et al.2 prepared 10-deoxy-isonucleo-
sides of type B. The synthesis of isonucleosides carrying an anomeric
hydroxy or methoxy group according to this method has, however, not been
reported in the literature. In our paper we describe the synthesis of pyr-
imidine isonucleosides of type C from 3,5-anhydro-D-xylofuranosides by use
of the well established triflate method3. Besides the question of the regios-
electivity of the oxetane ring opening reaction also the biological properties
of the products seemed to be interesting in our view.
RESULTS AND DISCUSSION
The preparation of the 2-O-(fluorobenzyl) substituted derivative 2 was
achieved by reaction of methyl 3,5-anhydro-a-D-xylofuranoside4 with 2-
fluorobenzyl bromide with a yield of 94%. The 2-O-(2-fluorobenzyl) sub-
stituent of 2 represents a substructure, which, in combination with the
nucleoside analogous structure of C, could induce interesting biological
activity5. Coupling of 2 with silylated uracil6 in the presence of trimethylsilyl
trifluoromethanesulfonate (TMSOTf)3 led to the 30-silylated isonucleoside 3
with a low yield of 8%. An isomer of 3 with the nucleobase linked to C-3 and a
trimethylsilyl group at O-5, which could have been formed by attack of the
base on C-3 under opening of the oxetane ring, was not detectable. Neither was
a regular uridine type nucleoside formed where the nucleobase is linked to the
anomeric centre C-1. The position of the nucleobase at the sugar moiety of 3
13
was proved by its C NMR-spectrum. The chemical shift of the C-50 atom
(49.6 ppm) is typical for a C-N bond, in contrast to the chemical shift of the C-
30 atom (75.0 ppm) which is in accordance with a C-O bond. We also measured
the HMBC spectrum of 3 in which we observed interactions between one of

NEW ISONUCLEOSIDES
259
the H-50 protons of the furanose with the C-2 atom and the C-6 atom of the
nucleobase. This is only possible if the base is linked to the C-5 atom of the
sugar moiety. Desilylation of the 30-position was achieved by stirring 3 in
chloroform, which, due to spontaneous hydrolysis and photooxidation, con-
tains traces of hydrochloric acid. Under these mild conditions it was possible
to obtain the uracil derivative 12 with a yield of 34%. The corresponding
silylated thymine isonucleoside 4 was obtained from 2 and 2,4-bis-O-tri-
methylsilylthymine6 with a low yield of 10%. Cleavage of the 30-O-silyl group
by hydrolysis led to the deprotected isothymine 13 with 64% yield. Analo-
gously we prepared the 30-silylated 5-halouracil isonucleosides 5^8 with yields
between 64% and 76%. Removal of the trimethylsilyl group led to the
unprotected target molecules 14^17 with high yields of 82%–90% (Sch. 1).
Scheme 1. (2-FBnBr ¼ 2-fluorobenzylbromide).

260
WIRSCHING ET AL.
Figure 1. ORTEP view of the X-ray diffraction structure of 15 with one molecule of crystal
water. Thermal ellipsoids are drawn at the 50% probability level.
The isonucleosides 15^17 were crystallised and investigated by X-ray
structural analyses. An ORTEP view of the 5-chloro derivative 15 is shown
as example in Fig. 1. The furanose ring of 15 exhibits the usual envelope
conformation (E1). In the case of 16 and 17 each two conformers occur in the
crystal. The furanose rings of 16 exhibit two different envelope conforma-
2
2
tions E1 and E whereas both the two different molecules of 17 exhibit E
envelopes. The orientation of the nucleobase, i.e., the torsion angle C14-C15-
N31-C32 is almost identical in 15^17. (cf. Table 1).
We obtained the silylated 6-methyluracil isonucleoside 9 and its 5,6-
dimethyl analogue 10 from silylated 6-methyluracil7 and 5,6-dimethyluracil7
Table 1. Selected Torsion Angles in 15^17 and 19
Torsion Angles [ꢀ]
Nucleoside
C14-C15-N31-C32
C12-O12-C21-C22
O12-C21-C22-C23
15
82
91
86
92
91
84
79
À 59
176
À 176
À 176
À 174
176
120
160
À 130
À 144
20
16, conformer 1
16, conformer 2
17, conformer 1
17, conformer 2
19, conformer 1
19, conformer 2
À 159
À 168
À 154

NEW ISONUCLEOSIDES
261
Figure 2. ORTEP view of one of the two conformers of 19. Thermal ellipsoids are drawn at
the 50% probability level.
with significantly higher yields (80% and 71%) as compared with 3 and 4.
Deprotection with acidic chloroform led to 65% of the 6-methyluracil deri-
vative 18 and 70% of the 5,6-dimethyluracil derivative 19 (Sch. 1). The 5,6-
dimethyluracil derivative 19 could be crystallised from water-acetonitrile.
A single crystal was suitable for an X-ray diffraction analysis. As in the case
of 16 and 17 two different conformers (0T1) were found for 19 (cf. Fig. 2 and
Table 1).
Coupling of 2 with silylated 5-nitrouracil8 in the presence of TMSOTf
and subsequent chromatography on silica gel directly led to 8% of the
unprotected 5-nitrouracil isonucleoside 20. The intermediate 30-O-silyl deri-
vative 11 could only be detected by TLC (PE=EA 1:3, 11: Rf ¼ 0.58; 20:
Rf ¼ 0.19).
The b-anomer 22 was prepared in a different way compared to the a-
anomer 2. Methyl 2-O-(2-fluorobenzyl)-b-D-xylofuranoside 21, which is
conveniently obtained from methyl b-D-xylofuranoside in three steps9, was
cyclised by an intramolecular Mitsunobu reaction to form the oxetane
22 with an acceptable yield of 69%. The reaction of 22 with silylated
pyrimidine bases in the presence of trimethylsilyl triflate led to the corre-
sponding isonucleosides 23^25 with b-configuration (Sch. 2). As in the case
of the nitrocompound 20, no silylated intermediates were isolated. Again,
no isomers, e.g., regular nucleosides, were obtained. Possibly due to steric
hindrance of the attack of the nucleobase on the b-anomer, the yields
were low.
The isonucleosides 12 and 14 ^19 were tested for antiviral activity
against HIV-1, HIV-2, HSV-1, HSV-2, Vaccinia virus, Vesicular stomatitis
virus, Parainfluenza-3 virus, Reovirus-1, Sindbis virus, Coxsackie virus B4,
Punta Toro virus and Respiratory syncytial virus cell cultures. With the
exception of 12, which reduced the virus-induced cytopathogenicity of

262
WIRSCHING ET AL.
Scheme 2.
HSV-1 (KOS) in E6SM cell cultures by 50% at a concentration of 9.6 mg=mL,
none of the isonucleosides exhibited a significant antiviral activity against one
of the evaluated viruses. The 5-haloisonucleosides 15^17 and the methyl
derivative 18 were weakly cytotoxic (IC50: 100–250 mg=mL). Only 19 was
more inhibitory to human tumor cell proliferation (IC50: 12–30 mg=mL).
Selected details are given in Table 2.
Table 2. Inhibitory Effects of 15^19 on the Proliferation of Murine Leukemia Cells (L1210)
and Human T-lymphocyte Cells (Molt4/C8, CEM/0 and CEM/TKÀ
)
IC50 [mM]a
Compound
L1210
Molt4/C8
CEM/0
CEM/TK-
15
16
17
18
19
> 250
> 250
134 Æ 6
102 Æ 13
126 Æ 11
155 Æ 11
30 Æ 1
135 Æ 9
112 Æ 3
122 Æ 3
218 Æ 18
24 Æ 1
106 Æ 3
84 Æ 4
99 Æ 1
165 Æ 5
12 Æ 2
175 Æ 8
ꢁ250
104 Æ 3
a 50% inhibitory concentration or compound concentration required to inhibit tumor cell
proliferation by 50%.

NEW ISONUCLEOSIDES
263
EXPERIMENTAL SECTION
Melting points were determined by the use of an Electrothermal
apparatus (values are corrected). IR spectra (KBr pellets) were measured
with an ATI Mattson Genesis spectrometer. NMR spectra were recorded
with Bruker AMX 400 and DRX 500 spectrometers. Chemical shifts (ppm)
are related to Me4Si (1H and 13C), coupling constants are given in Hz.
Standard correlation techniques were used for assignments. Mass spectra
were measured on Varian CH 7 (EI, 70 eV) and VG Analytical 70–250 S
(HRMS, FAB) apparatus. Optical rotations were measured on a Perkin
Elmer Polarimeter 341. TLC was carried out on E. Merck PF254 foils
(detection: UV light, iodine vapour, EtOH-H2SO4 spray=200ꢀC), and column
chromatography on E. Merck Kieselgel 60 (70–230 mesh). Solvents
(EA ¼ ethyl acetate, PE ¼ petroleum ether) were purified and dried according
to standard laboratory procedures10.
X-ray Structure Analyses
The crystal data for 15 and 16 were collected on an Enraf-Nonius
CAD4 diffractometer in the 2y=o scan mode with graphite monochromated
Cu Ka radiation (1.54178 A) at a temperature of 173 K. For 17 data collec-
tion was performed on a Kappa CCD Nonius diffractometer with graphite
monochromated Mo Ka radiation (0.71073 A) in the Rotation F scan mode
at a temperature of 293 K. The X-ray diffraction of 19 was measured on a
Hilger & Watts Y290 diffractometer with graphite monochromated Mo Ka
radiation (0.71073 A) in the 2= scan mode at a temperature of 153 K. The
structures were solved by direct methods using the SIR-97 program11, and
refined by full-matrix-block least-squares on F2 using all data and the
SHELXL-97 program12. The full crystallographic details, excluding structure
features, have been deposited with the Cambridge Crystallographic Data
Centre. These data may be obtained, on request, from the CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK. Tel. þ44-1223-336408, Fax þ44-1223-
336033, E-mail deposit@ccdc.cam.ac.uk. Deposition number CCDC 144157
(15), 148803 (16), 148998 (17) and 145046 (19).
Methyl
3,5-Anhydro-2-O-(2-fluorobenzyl)-a-D-xylofuranoside
(2).
Sodium hydride (60% dispersion in mineral oil, 370 mg, 9.17 mmol) was
added to a solution of methyl 3,5-anhydro-a-D-xylofuranoside4 (1320 mg,
9.04 mmol), in dry THF (30 mL). After 5 min 2-fluorobenzyl bromide
(1.20 mL, 1870 mg, 9.89 mmol) was added. After 1 h the reaction mixture
was filtered, the solvent was evaporated and the crude product was
purified by column chromatography (PE=EA 2:1, Rf ¼ 0.35) to yield 2
20
1
(2170 mg, 94%) as colourless oil. ½aꢂD ¼ þ111:9 (c ¼ 1.0 in CHCl3). H

264
WIRSCHING ET AL.
NMR (CDCl3): d 3.47 (s, 3H, OCH3), 4.24 (dd, 1H, H-2), 4.28 (dd, 1H,
H-5endo), 4.68 (dd, 1H, H-5exo), 4.70 (s, 2H, CH2C6H4F), 4.92 (ddd, 1H,
H-4), 5.15 (dd, 1H, H-3), 5.26 (d, 1H, H-1), 7.02 (ddd, 1H, Har-3), 7.11
(ddd, 1H, Har-5), 7.23–7.30 (m, 1H, Har-4), 7.43 (ddd, 1H, Har-6).
J1,2 ¼ 3.9, J2,3 ¼ 1.8, J3,4 ¼ 4.6, J4,5endo ¼ 2.7, J4,5exo ¼ 4.6, J5endo,5exo
¼
7.7, J3ar,4ar ¼ 9.9, J3ar,5ar ¼ 0.9, J3ar,F ¼ 9.1, J4ar,5ar ¼ 7.5, J4ar,6ar ¼ 1.8,
J5ar,6ar ¼ 7.5, J6ar,F ¼ 7.5. 13C NMR (CDCl3): d 56.0 (OCH3), 66.1 (d,
CH2C6H4F), 75.4 (C-4), 76.4 (C-5), 84.7 (C-2), 88.6 (C-3), 105.2 (C-1),
115.0 (d, Car-3), 123.8 (d, Car-5), 124.2 (d, Car-1), 129.4 (d, Car-4), 130.2 (d,
Car-6), 160.8 (d, Car-2). JCH2,F ¼ 3.8, J1ar,F ¼ 14.6, J2ar,F ¼ 247.0,
J3ar,F ¼ 21.5, J4ar,F ¼ 8.2, J5ar,F ¼ 3.6, J6ar,F ¼ 4.1. EI MS m=z (%): 254 (0.1)
ꢃ
ꢃ
[Mþ ], 253 (0.2), 223 (0.8) [Mþ -OCH3], 195 (0.4), 194 (0.2), 193 (0.3), 192
ꢃ
(0.2), 163 (1), 135 (1), 123 (4), 115 (4), 110 (10), 109 (100) [C7H6Fþ ], 87
(5), 85 (10), 83 (8), 71 (3), 69 (9), 68 (4), 61 (4), 59 (4), 57 (3). Anal. Calcd.
for C13H15FO4: C, 61.41; H, 5.95. Found: C, 61.14; H, 6.03.
Reaction of 2 with silylated nucleobases (General procedure A).
A
solution of 2 (0.4–0.6 mmol), the corresponding silylated uracil derivative
(1.6–2.4 mmol), and molecular sieves A4 (40-60 mg) in dry MeCN (5–6 mL)
was cooled to À18ꢀC. Then, TMSOTf (0.2–0.3 mL, 1.1–1.7 mmol) was
added. the mixture was stirred for 90 min, whereat the temperature was
allowed to rise to 20 ꢀC. when the reaction was complete satd aq NaHCO3
solution (20 mL) was added and stirring was continued for 30 min. After
filtration the aq phase was extracted with CHCl3, the organic phase was
dried with MgSO4 and evaporated. The products were obtained as white
solids after purification by column chromatography. Appropriate eluents
are given with the melting points (M.p.).
Methyl 5-Deoxy-2-O-(2-fluorobenzyl)-3-O-trimethylsilyl-5-N-(uracil-1-
yl)-a-D-xylofuranoside (3). 21 mg (8%), from 2 (150 mg, 0.59 mmol) and
2,4-bis-O-trimethylsilyluracil6 (621 mg, 2.24 mmol). M.p. 122–125 ꢀC
20
(PE=EA 1:2, Rf ¼ 0.16, decomp.). ½aꢂD ¼ þ95.0 (c ¼ 1.0 in CHCl3). IR: n
3192 (NH), 1680 (C ¼ O) cmÀ 1
.
1H NMR (CDCl3): d 0.14 [s, 9H,
SI(CH3)3], 3.33 (s, 3H, OCH3), 3.41 (dd, 1H, H-50a), 3.81 (dd, 1H, H-20),
4.26 (dd, 1H, H-50b), 4.33 (ddd, 1H, H-40), 4.48 (dd, 1H, H-30), 4.65, 4.69
(AB-system, 2H, CH2C6H4f), 4.83 (d, 1H, H-10), 5.65 (dd, 1H, H-5), 7.05
(ddd, 1H, Har-3), 7.14 (ddd, 1H, Har-5), 7.26–7.32 (m, 1H, Har-4), 7.28 (d,
0
0
0
0
1H, H-6), 7.44 (ddd, 1H, Har-6), 8.97 (bs, 1H, NH). J1 ,2 ¼ 4.1, J2 ,3 ¼ 5.6,
0
0
0
0
0
0
0
0
J3 ,4 ¼ 6.7, J4 ,5 a ¼ 9.4, J4 ,5 b ¼ 2.8, J5 a,5 b ¼ 14.5, JAB ¼ 12.3, JAB,F ¼ 0.8,
J5,6 ¼ 7.9, J5,NH ¼ 2.2, J3ar,4ar ¼ 8.4, J3ar,5ar ¼ 1.1, J3ar,F ¼ 9.9, J4ar,5ar ¼ 7.5,
J4ar,6ar ¼ 1.8, J5ar,6ar ¼ 7.5, J6ar,F ¼ 7.5. 13C NMR (CDCl3): d À 0.1
[Si(CH3)3], 49.6 (C-50), 55.6 (OCH3), 66.2 (d, CH2C6H4F), 75.0 (C-30), 75.3
(C-40), 85.4 (C-20), 100.8 (C-10), 101.4 (C-5), 115.2 (d, Car-3), 124.2 (d, Car-5),
124.6 (d, Car-1), 129.8 (d, Car-4), 130.4 (d, Car-6), 145.9 (C-6), 150.7 (2-CO),

NEW ISONUCLEOSIDES
265
160.7 (d, Car-2), 163.7 (4-CO). J1ar,F ¼ 14.8, J2ar,F ¼ 247.0, J3ar,F ¼ 21.6,
J4ar,F ¼ 8.1, J5ar,F ¼ 3.6, J6ar,F ¼ 4.1, JCH2,F ¼ 3.7.
Methyl 5-Deoxy-2-O-(2-fluorobenzyl)-5-N-(thymine-1-yl)-3-O-trimethylsilyl-
a-D-xylofuranoside (4). 26 mg (10%), from 2 (100 mg, 0.39 mmol) and 2,4-
bis-O-trimethylsilylthymine6 (454 mg, 1.68 mmol). M.p. 98–100 ꢀC (PE=EA
20
1:1, Rf ¼ 0.20, decomp.). ½aꢂD ¼þ66.3 (c ¼ 1.0 in CHCl3). IR: n 3180 (NH),
1
1690 (C¼O) cmÀ 1. H NMR (CDCl3): d 0.02 [s, 9H, Si(CH3)3], 1.83 (d,
3H, CH3), 3.33 (s, 3H, OCH3), 3.44 (dd, 1H, H-50a), 3.78 (dd, 1H, H-20),
4.24 (ddd, 1H, H-40), 4.28 (dd, 1H, H-50b), 4.38 (dd, 1H, H-30), 4.74 (s, 2H,
CH2C6H4F), 4.83 (d, 1H, H-10), 6.93 (ddd, 1H, Har-3), 7.05 (q, 1H, H-6),
7.08 (ddd, 1H, Har-5), 7.21–7.23 (m, 1H, Har-4), 7.39 (ddd, 1H, Har-6),
0
0
0
0
0
0
0
0
0
0
9.65 (bs, 1H, NH). J1 ,2 ¼ 4.0, J2 ,3 ¼ 5.0, J3 ,4 ¼ 5.5, J4 ,5 a ¼ 6.1, J4 ,5 b ¼ 5.5,
0
0
J5 a,5 b ¼ 14.2, J6,Me ¼ 1.2, J3ar,4ar ¼ 8.3, J3ar,5ar ¼ 1.2, J3ar,F ¼ 9.8, J4ar,5ar
¼
7.3, J4ar,6ar ¼ 2.0, J5ar,6ar ¼ 7.5, J6ar,F ¼ 7.5. 13C NMR (CDCl3): d À 0.1
[Si(CH3)3], 10.6 (CH3), 46.2 (C-50), 53.9 (OCH3), 64.4 (d, CH2C6H4F), 72.4
(C-30), 74.2 (C-40), 82.8 (C-20), 99.7 (C-10), 109.0 (C-5), 114.1 (d, Car-3),
122.3 (d, Car-5), 122.7 (d, Car-1), 128.0 (d, Car-4), 128.6 (d, Car-6), 139.5
(C-6), 149.8 (2-CO), 158.9 (d, Car-2), 162.2 (4-CO). J1ar,F ¼ 14.4,
J2ar,F ¼ 245.7, J3ar,F ¼ 21.4, J4ar,F ¼ 8.5, J5ar,F ¼ 3.5, J6ar,F ¼ 4.1, JCH2,F ¼ 3.6.
Methyl 5-Deoxy-2-O-(2-fluorobenzyl)-5-N-(5-fluorouracil-1-yl)-3-O-tri-
methylsilyl-a-D-xylofuranoside (5). 179 mg (64%), from
2
(156 mg,
0.61 mmol) and 5-fluoro-2,4-bis-O-trimethylsilyluracil13 (678 mg, 2.47 mmol).
20
M.p. 133ꢀC (PE/EA 1:3, Rf ¼ 0.52). ½aꢂD ¼ þ138:1 (c ¼ 1.0 in CHCl3). IR: n
1
3179 (NH), 1691 (C¼O) cmÀ 1. H NMR (CDCl3): d 0.15 [s, 9H, Si(CH3)3],
3.33 (s, 3H, OCH3), 3.51 (dd, 1H, H-50a), 3.88 (dd, 1H, H-20), 4.30 (ddd, 1H,
H-40), 4.37 (dd, 1H, H-50b), 4.56 (dd, 1H, H-30), 4.75 (s, 2H, CH2C6H4F), 4.81
(d, 1H, H-10), 7.03 (ddd, 1H, Har-3), 7.14 (ddd, 1H, Har-5), 7.27–7.30 (m, 1H,
0
0
Har-4), 7.42 (d, 1H, H-6), 7.46 (ddd, 1H, Har-6), 9.52 (d, 1H, NH). J1 ,2 ¼ 4.1,
0
0
0
0
0
0
0
0
0
0
J2 ,3 ¼ 5.5, J3 ,4 ¼ 6.5, J4 ,5 a ¼ 7.4, J4 ,5 b ¼ 3.7, J5 a,5 b ¼ 14.0, J6,F ¼ 5.6,
JNH,F ¼ 4.7, J3ar,4ar ¼ 8.5, J3ar,5ar ¼ 1.2, J3ar,F ¼ 9.8, J4ar,5ar ¼ 7.7, J4ar,6ar
¼
1.5, J5ar,6ar ¼ 7.5, J6ar,F ¼ 7.5. 13C NMR (CDCl3): d À 0.2 [Si(CH3)3], 49.1
(C-50), 55.6 (OCH3), 66.2 (d, CH2C6H4F), 74.4 (C-30), 75.6 (C-40), 85.0 (C-
20), 101.1 (C-10), 115.3 (d, Car-3), 124.3 (d, Car-5), 124.7 (d, Car-1), 129.8
(d, Car-4), 130.3 (d, C-6), 130.6 (d, Car-6), 140.2 (d, C-5), 150.1 (2-CO),
157.3 (d, 4-CO), 160.4 (d, Car-2). J4,F ¼ 26.2, J5,F ¼ 237.5, J6,F ¼ 33.0,
J1ar,F ¼ 14.7,
JCH2,F ¼ 3.5.
J2ar,F ¼ 246.8,
J3ar,F ¼ 21.5,
J5ar,F ¼ 3.7,
J6ar,F ¼ 4.2,
Methyl 5-N-(5-Chlorouracil-1-yl)-5-deoxy-2-O-(2-fluorobenzyl)-3-O-tri-
methylsilyl-a-D-xylofuranoside (6). 183 mg (68%), from
2
(145 mg,
0.57 mmol) and 5-chloro-2,4-bis-O-trimethylsilyluracil13 (712 mg, 2.45 mmol).
20
M.p. 115ꢀC (PE/EA 1:3, Rf ¼ 0.50, decomp.). ½aꢂD ¼ þ122:0 (c ¼ 1.0 in

266
WIRSCHING ET AL.
1
CHCl3). IR: n 3187 (NH), 1671 (C¼O) cmÀ 1. H NMR (CDCl3): d 0.06 [s,
9H, Si(CH3)3], 3.32 (s, 3H, OCH3), 3.54 (dd, 1H, H-50a), 3.95 (dd, 1H, H-20),
4.31 (ddd, 1H, H-40), 4.44 (dd, 1H, H-50b), 4.46 (dd, 1H, H-30), 4.75 (s, 2H,
CH2C6H4F), 4.87 (d, 1H, H-10), 7.03 (ddd, 1H, Har-3), 7.11 (ddd, 1H, Har-
5), 7.25–7.29 (m, 1H, Har-4), 7.45 (ddd, 1H, Har-6), 7.56 (s, 1H, H-6), 8.76
0
0
0
0
0
0
0
0
0
0
(bs, 1H, NH). J1 ,2 ¼ 4.1, J2 ,3 ¼ 5.7, J3 ,4 ¼ 6.5, J4 ,5 a ¼ 8.3, J4 ,5 b ¼ 3.5,
0
0
J5 a,5 b ¼ 14.5, J3ar,4ar ¼ 8.5, J3ar,5ar ¼ 1.2, J3ar,F ¼ 9.9, J4ar,5ar ¼ 7.5, J4ar,6ar
¼
1.8, J5ar,6ar ¼ 7.5, J6ar,F ¼ 7.5. 13C NMR (CDCl3): d; À 0.1 [Si(CH3)3], 49.6
(C-50), 55.6 (OCH3), 66.2 (d, CH2C6H4F), 74.6 (C-30), 75.3 (C-40), 84.7 (C-
20), 101.0 (C-10), 108.6 (C-5), 115.2 (d, Car-3), 124.2 (d, Car-5), 124.6 (d,
Car-1), 129.9 (d, Car-4), 130.5 (d, Car-6), 142.6 (C-6), 150.6 (2-CO), 159.5
(4-CO), 160.6 (d, Car-2). J1ar,F ¼ 14.6, J2ar,F ¼ 247.2, J3ar,F ¼ 21.4,
J4ar,F ¼ 8.3, J5ar,F ¼ 3.6, J6ar,F ¼ 4.2, JCH2,F ¼ 3.6.
Methyl 5-N-(5-Bromouracil-1-yl)-5-deoxy-2-O-(2-fluorobenzyl)-3-O-tri-
methylsilyl-a-D-xylofuranoside (7). 211 mg (73%), from
2
(142 mg,
0.56 mmol) and 5-bromo-2,4-bis-O-trimethylsilyluracil13 (792 mg, 2.07 mmol).
20
M.p. 129ꢀC (PE=EA 1:3, Rf ¼ 0.54). ½aꢂD ¼ þ109:0 (c ¼ 1.0 in CHCl3). IR: n;
1
3208 (NH), 1695 (C¼O) cmÀ 1. H NMR (CDCl3): d 0.01 [s, 9H, Si(CH3)3],
3.32 (s, 3H, OCH3), 3.60 (dd, 1H, H-50a), 3.94 (dd, 1H, H-20), 4.22 (ddd, 1H,
H-40), 4.35 (dd, 1H, H-50b), 4.54 (dd, 1H, H-30), 4.77 (s, 2H, CH2C6H4F), 4.89
(d, 1H, H-10), 7.02 (ddd, 1H, Har-3), 7.12 (ddd, 1H, Har-5), 7.26–7.29 (m, 1H,
Har-4), 7.46 (ddd, 1H, Har-6), 7.65 (s, 1H, H-6), 9.66 (bs, 1H, NH).
0
0
0
0
0
0
0
0
0
0
J1 ,2 ¼ 4.2, J2 ,3 ¼ 6.0, J3 ,4 ¼ 6.0, J4 ,5 a ¼ 9.2, J5 a,5 b ¼ 14.3, J3ar,4ar ¼ 8.3,
J3ar,5ar ¼ 1.1, J3ar,F ¼ 9.9, J4ar,5ar ¼ 7.5, J4ar,6ar ¼ 1.8, J5ar,6ar ¼ 7.5, J6ar,F ¼ 7.5.
13C NMR (CDCl3): d À 0.1 [Si(CH3)3], 48.1 (C-50), 55.8 (OCH3), 66.3 (d,
CH2C6H4F), 74.3 (C-30), 74.9 (C-40), 84.8 (C-20), 96.3 (C-5), 101.0 (C-10),
115.3 (d, Car-3), 124.2 (d, Car-5), 124.5 (d, Car-1), 129.9 (d, Car-4), 130.5 (d,
Car-6), 145.2 (C-6), 150.7 (2-CO), 160.8 (d, Car-2), 164.1 (4-CO).
J1ar,F ¼ 14.5, J2ar,F ¼ 247.4, J3ar,F ¼ 21.4, J4ar,F ¼ 8.1, J5ar,F ¼ 3.6, J6ar,F ¼ 4.2,
JCH2,F ¼ 3.7.
Methyl 5-Deoxy-2-O-(2-fluorobenzyl)-5-N-(5-iodouracil-1-yl)-3-O-trimethyl-
silyl-a-D-xylofuranoside (8). 269 mg (76%), from 2 (160 mg, 0.63 mmol)
and 5-iodo-2,4-bis-O-trimethylsilyluracil13 (920 mg, 2.41 mmol). M.p. 156–
20
158ꢀC (PE/EA 1:3, Rf ¼ 0.50, decomp.). ½aꢂD ¼ þ90:0 (c ¼ 1.0 in CHCl3).
1
IR: n 3205 (NH), 1679 (C¼O) cmÀ 1. H NMR (CDCl3): d 0.10 [s, 9H,
Si(CH3)3], 3.37 (s, 3H, OCH3), 3.61 (dd, 1H, H-50a), 3.84 (dd, 1H, H-20),
4.14–4.21 (m, 2H, H-40, H-50b), 4.40 (dd, 1H, H-30), 4.66 (s, 2H,
CH2C6H4F), 4.90 (d, 1H, H-10), 7.03 (ddd, 1H, Har-3), 7.11 (ddd, 1H, Har-
5), 7.25–7.29 (m, 1H, Har-4), 7.45 (ddd, 1H, Har-6), 7.73 (s, 1H, H-6), 8.75
0
0
0
0
0
0
0
0
0
0
(bs, 1H, NH). J1 2 ¼ 4.1, J2 ,3 ¼ 5.7, J3 4 ¼ 6.0, J4 ,5 a ¼ 9.2, J5 a,5 b ¼ 14.6,
J3ar,4ar ¼ 8.5, J3ar,5ar ¼ 1.1, J3ar,F ¼ 9.9, J4ar,5ar ¼ 7.5, J4ar,6ar ¼ 1.8, J5ar,6ar
¼
13
7.5, J6ar,F ¼ 7.5. C NMR (CDCl3): d À 0.1 [Si(CH3)3], 48.3 (C-50), 55.6

NEW ISONUCLEOSIDES
267
(OCH3), 66.2 (d, CH2C6H4F), 67.2 (C-5), 73.0 (C-30), 74.9 (C-40), 85.1 (C-20),
101.0 (C-10), 115.2 (d, Car-3), 124.2 (d, Car-5), 124.6 (d, Car-1), 129.8 (d, Car-
4), 130.4 (d, Car-6), 150.4 (C-6), 151.1 (2-CO), 160.9 (d, Car-2), 162.1 (4-CO).
J1ar,F ¼ 14.5, J2ar,F ¼ 246.8, J3ar,F ¼ 21.5, J4ar,F ¼ 8.3, J5ar,F ¼ 3.7, J6ar,F ¼ 4.4,
JCH2,F ¼ 3.6.
Methyl 5-Deoxy-2-O-(2-fluorobenzyl)-5-N-(6-methyluracil-1-yl)-3-O-tri-
methylsilyl-a-D-xylofuranoside (9). 153 mg (80%), from
2
(107 mg,
0.42 mmol) and 6-methyl-2,4-bis-O-trimethylsilyluracil7 (430 mg, 1.59 mmol).
20
M.p. 153–156ꢀC (EA, Rf ¼ 0.36, decomp.). ½aꢂD ¼ þ129:4 (c ¼ 1.0 in CHCl3).
1
IR: n 3192 (NH), 1688 (C¼O) cmÀ 1. H NMR (CDCl3): d 0.14 [s, 9H,
Si(CH3)3], 2.26 (s, 3H, CH3), 3.37 (s, 3H, OCH3), 3.67 (dd, 1H, H-50a),
3.82 (dd, 1H, H-20), 4.12 (dd, 1H, H-50b), 4.41 (ddd, 1H, H-40), 4.48 (dd,
1H, H-30), 4.64, 4.68 (AB-system, 2H, CH2C6H4F), 4.82 (d, 1H, H-10), 5.52
(s, 1H, H-5), 7.02 (ddd, 1H, Har-3), 7.12 (ddd, 1H, Har-5), 7.27 (dddd, 1H,
0
0
0 0
Har-4), 7.44 (ddd, 1H, Har-6), 9.65 (bs, 1H, NH). J1 ,2 ¼ 4.1, J2 3 ¼ 5.5,
0
0
0
0
0
0
0
0
J3 ,4 ¼ 6.7, J4 ,5 a ¼ 9.9, J4 ,5 b ¼ 2.4, J5 a, b ¼ 14.9, JAB ¼ 12.4, JA,B,F ¼ 0.8,
J3ar,4ar ¼ 8.4, J3ar,5ar ¼ 1.2, J3ar,F ¼ 9.9, J4ar,5ar ¼ 7.6, J4ar,6ar ¼ 1.8, J5ar,6ar
¼
7.5, J6ar,F ¼ 7.5. 13C NMR (CDCl3): d À 0.2 [Si(CH3)3], 22.8 (CH3), 45.7
(C-50), 55.5 (OCH3), 66.1 (d, CH2C6H4F), 74.8 (C-40), 75.3 (C-30), 85.5 (C-
20), 100.6 (C-10), 101.8 (C-5), 115.1 (d, Car-3), 124.1 (d, Car-5), 124.7 (d,
Car-1), 129.6 (d, Car-4), 130.3 (d, Car-6), 151.5, 155.1 (2-CO, C-6), 163.2 (d,
Car-2), 163.8 (4-CO). J1ar,F ¼ 14.5, J2ar,F ¼ 246.8, J3ar,F ¼ 21.4, J4ar,F ¼ 8.2,
J5ar,F ¼ 3.6, J6ar,F ¼ 4.2, JCH2,F ¼ 3.8.
Methyl 5-Deoxy-5-N-(5,6-dimethyluracil-1-yl)-2-O-(2-fluorobenzyl)-3-O-
tri-methylsilyl-a-D-xylofuranoside (10). 129 mg (71%), from 2 (104 mg,
0.41 mmol) and 5,6-dimethyl-2,4-bis-O-trimethylsilyluracil7 (448 mg,
20
1.57 mmol). M.p. 169ꢀC (PE/EA 1:6, Rf ¼ 0.57). ½aꢂD ¼ þ145:9 (c ¼ 1.0 in
1
CHCl3). IR: n 3178 (NH), 1674 (C¼O) cmÀ 1. H NMR (CDCl3): d 0.14
[s, 9H, Si(CH3)3], 1.95 (s, 3H, CH3), 2.27 (s, 3H, CH3), 3.31 (s, 3H,
OCH3), 3.75 (dd, 1H, H-50a), 3.83 (dd, 1H, H-20), 4.15 (dd, 1H, H-50b),
4.42 (ddd, 1H, H-40), 4.49 (dd, 1H, H-30), 4.65, 4.69 (AB-system, 2H,
CH2C6H4F), 4.82 (d, 1H, H-10), 7.03 (ddd, 1H, Har-3), 7.13 (ddd, 1H, Har-
5), 7.27 (dddd, 1H, Har-4), 7.44 (ddd, 1H, Har-6), 9.64 (bs, 1H, NH).
0
0
0
0
0
0
0
0
0
0
0
0
J1 ,2 ¼ 4.1, J2 ,3 ¼ 5.5, J3 ,4 ¼ 6.8, J4 ,5 a ¼ 9.7, J4 ,5 b ¼ 2.4, J5 a,5 b ¼ 15.1,
JAB ¼ 12.3, J3ar,4ar ¼ 8.5, J3ar,5ar ¼ 0.9, J3ar,F ¼ 9.8, J4ar,5ar ¼ 7.6, J4ar,6ar ¼ 1.8,
J5ar,6ar ¼ 7.5, J6ar,F ¼ 7.5. 13C NMR (CDCl3): d À 0.2 [Si(CH3)3], 11.2
(CH3), 17.0 (CH3), 45.9 (C-50), 55.4 (OCH3), 66.1 (d, CH2C6H4F), 75.0
(C-40), 75.3 (C-30), 85.5 (C-20), 100.5 (C-10), 107.5 (C-5), 115. (1, Car-3),
124.1 (d, Car-5), 124.7 (d, Car-1), 129.6 (d, Car-4), 130.3 (d, Car-6), 149.9,
151.0 (2-CO, C-6), 160.6 (d, Car-2), 163.8 (4-CO). J1ar,F ¼ 14.6,
J2ar,F ¼ 246.8, J3ar,F ¼ 21.5, J4ar,F ¼ 8.1, J5ar,F ¼ 3.7, J6ar,F ¼ 4.2, JCH2,F ¼ 3.8.

268
WIRSCHING ET AL.
Desilylation of 3–10 (General procedure B). A solution of the 3-O-
trimethylsilyl-isonucleoside (5–50 mmol) in CHCl3 (10–100 mL) containing
traces of HCl due to spontaneous hydrolysis was stirred at 20ꢀC for
24–100 h. When the reaction was complete (TLC control) the CHCl3 was
removed in vacuo. The products were obtained as colourless crystals by
recrystallisation from H2O=MeCN (20:1) or as white solids (13, 18, and
20) by column chromatography. In the latter cases, appropriate eluents are
given with the melting points (M.p.).
Methyl 5-Deoxy-2-O-(2-fluorobenzyl)-5-N-(uracil-1-yl)-a-D-xylofurano-
side (12). 6 mg (34%), from 3 (21 mg, 0.05 mmol, 100 h). M.p. 127ꢀC.
20
1
½aꢂD ¼ þ73:2 (c ¼ 0.6 in CHCl3). IR: n 3443 (OH), 1691 (C¼O) cmÀ 1. H
NMR (CDCl3): d 3.36 (s, 3H, OCH3), 3.56 (dd, 1H, H-50a), 3.89 (dd, 1H,
H-20), 4.30 (ddd, 1H, H-40), 4.36 (dd, 1H, H-50b), 4.49 (dd, 1H, H-30), 4.74
(s, 2H, CH2C6H4F), 4.87 (d, 1H, H-10), 5.69 (d, 1H, H-5), 7.03 (ddd, 1H,
Har-3), 7.13 (ddd, 1H, Har-5), 7.25–7.31 (m, 1H, Har-4), 7.29 (d, 1H, H-6),
0
0
0
0
0
0
7.45 (ddd, 1H, Har-6), 9.54 (bs, 1H, NH). J1 ,2 ¼ 4.2, J2 ,3 ¼ 5.5, J3 ,4 ¼ 5.7,
0
0
0
0
0
0
J4 ,5 a ¼ 7.1, J4 ,5 b ¼ 4.4, J5 a,5 b ¼ 14.1, J5,6 ¼ 7.9, J3ar,4ar ¼ 8.4, J3ar,5ar ¼ 1.2,
J3ar,F ¼ 9.9, J4ar,5ar ¼ 7.5, J4ar,6ar ¼ 1.8, J5ar,6ar ¼ 7.5, J6ar,F ¼ 7.5. 13C NMR
(CDCl3): d 48.7 (C-50), 55.7 (OCH3), 66.2 (d, CH2C6H4F), 74.3 (C-30), 75.8
(C-40), 84.8 (C-20), 101.2 (C-10), 102.2 (C-5), 115.3 (d, Car-3), 124.2 (d, Car-
5), 124.6 (d, Car-1), 129.8 (d, Car-4), 130.5 (d, Car-6), 145.7 (C-6), 151.4 (2-
CO), 160.8 (d, Car-2), 163.7 (4-CO). J1ar,F ¼ 14.6, J2ar,F ¼ 247.0, J3ar,F
¼
21.5, J4ar,F ¼ 8.4, J5ar,F ¼ 3.7, J6ar,F ¼ 4.2, JCH2,F ¼ 3.7. FAB MS (mNBA)
m=z: 367 [M þ H]. FAB HRMS (mNBA) calcd 367.1305 (C17H20FN2O6);
found 367.1348.
Methyl 5-Deoxy-2-O-(2-fluorobenzyl)-5-N-(thymine-1-yl)-a-D-xylofurano-
side (13). 14 mg (64%), from 4 (25mg, 0.06mmol, 48h). M.p. 118ꢀC
20
(PE=EA 1:3, Rf ¼ 0.17). ½aꢂD ¼ þ84:4 (c ¼ 1.0 in CHCl3). IR: n 3441 (OH),
1
1678 (C¼O) cmÀ 1. H NMR (CDCl3): d 1.85 (d, 3H, CH3), 3.32 (s, 3H,
OCH3), 3.46 (dd, 1H, H-50a), 3.80 (dd, 1H, H-20), 4.24 (ddd, 1H, H-40), 4.29
(dd, 1H, H-50b), 4.38 (dd, 1H, H-30), 4.68 (s, 2H, CH2C6H4F), 4.84 (d, 1H, H-
10), 6.97 (ddd, 1H, Har-3), 7.03 (q, 1H, H-6), 7.07 (ddd, 1H, Har-5), 7.22 (dddd,
0
0
0
0
1H, Har-4), 7.40 (ddd, 1H, Har-6), 9.24 (bs, 1H, NH). J1 ,2 ¼ 4.1, J2 ,3 ¼ 5.0,
0
0
0
0
0
0
0
0
J3 ,4 ¼ 5.5, J4 ,5 a ¼ 6.0, J4 ,5 b ¼ 5.4, J5 a,5 b ¼ 14.0, J6,Me ¼ 1.2, J3ar,4ar ¼ 8.4,
J3ar,5ar ¼ 1.2, J3ar,F ¼ 9.9, J4ar,5ar ¼ 7.5, J4ar,6ar ¼ 1.8, J4ar,F ¼ 5.6, J5ar,6ar ¼ 7.5,
13
J6ar,F ¼ 7.5. C NMR (CDCl3): d 10.4 (CH3), 46.3 (C-50), 53.9 (OCH3), 64.4
(d, CH2C6H4F), 72.4 (C-30), 74.3 (C-40), 82.7 (C-20), 99.7 (C-10), 109.1 (C-5),
113.3 (d, Car-3), 122.3 (d, Car-5), 122.8 (d, Car-1), 127.8 (d, Car-4), 128.6 (d,
Car-6), 139.5 (C-6), 149.7 (2-CO), 158.9 (d, Car-2), 162.1 (4-CO). J1ar,F ¼ 14.5,
J2ar,F ¼ 246.9, J3ar,F ¼ 21.4, J4ar,F ¼ 8.3, J5ar,F ¼ 3.6, J6ar,F ¼ 4.1, JCH2,F ¼ 3.8.
FAB MS (mNBA) m=z 381 [M þ H]. FAB HRMS (mNBA) calcd 381.1462
(C18H22FN2O6); found 381.1485.

NEW ISONUCLEOSIDES
269
Methyl 5-Deoxy-2-O-(2-fluorobenzyl)-5-N-(5-fluorouracil-1-yl)-a-D-xylo-
furanoside (14). 129 mg (88%), from 5 (175 mg, 0.38 mmol, 48 h). M.p.
20
151–152ꢀC. ½aꢂD ¼ þ124:8 (c ¼ 1.0 in CHCl3). IR: n 3439 (OH), 3203 (NH),
1
1693 (C¼O) cmÀ 1. H NMR (CDCl3): d 3.36 (s, 3H, OCH3), 3.51 (dd, 1H,
H-50a), 3.89 (dd, 1H, H-20), 4.32 (ddd, 1H, H-40), 4.37 (dd, 1H, H-50b), 4.54
(dd, 1H, H-30), 4.74 (s, 2H, CH2C6H4F), 4.87 (d, 1H, H-10), 7.04 (ddd, 1H,
Har-3), 7.14 (ddd, 1H, Har-5), 7.29 (dddd, 1H, Har-4), 7.42 (d, 1H, H-6), 7.45
0
0
0
0
0
0
(ddd, 1H, Har-6), 9.68 (d, 1H, NH). J1 ,2 ¼ 4.2, J2 ,3 ¼ 5.8, J3 ,4 ¼ 6.5,
0
0
0
0
0
0
J4 ,5 a ¼ 7.4, J4 ,5 b ¼ 3.8, J5 a,5 b ¼ 14.1, J6,F ¼ 5.6, JNH,F ¼ 4.8, J3ar,4ar ¼ 8.4,
J3ar,5ar ¼ 1.2, J3ar,F ¼ 9.9, J4ar,5ar ¼ 7.6, J4ar,6ar ¼ 1.9, J4ar,F ¼ 5.5, J5ar,6ar ¼ 7.5,
13
J6ar,F ¼ 7.5. C NMR (CDCl3): d 49.1 (C-50), 55.7 (OCH3), 66.2 (d,
CH2C6H4F), 74.4 (C-30), 75.5 (C-40), 84.9 (C-20), 101.1 (C-10), 115.3 (d, Car-
3), 124.2 (d, Car-5), 124.5 (d, Car-1), 129.9 (d, Car-4), 130.1 (d, C-6), 130.6 (d,
Car-6), 140.2 (d, C-5), 150.0 (2-CO), 157.3 (d, 4-CO), 160.8 (d, Car-2).
J4,F ¼ 26.2, J5,F ¼ 237.1, J6,F ¼ 32.9, J1ar,F ¼ 14.7, J2ar,F ¼ 247.1, J3ar,F ¼ 21.5,
J4ar,F ¼ 8.2, J5ar,F ¼ 3.6, J6ar,F ¼ 4.1, JCH2,F ¼ 3.6. 19F NMR (CDCl3): d
À 166.58 (dd, 1F, F-5, J ¼ 5.3, 5.3 Hz), À 119.11 (m, 1F, CH2C6H4F). FAB
MS (mNBA) m=z 385 [M þ H]. FAB HRMS (mNBA) calcd 385.1211
(C17H19F2N2O6); found 385.1104.
Methyl 5-N-(5-Chlorouracil-1-yl)-5-deoxy-2-O-(2-fluorobenzyl)-a-D-xylo-
furanoside (15). 138 mg (90%), from 6 (181mg, 0.38 mmol, 48h). M.p.
20
166ꢀC. ½aꢂD ¼ þ115:2 (c¼ 1.0 in CHCl3). IR: n 3421 (OH), 3192 (NH), 1680
(C¼O), 1623 (C¼O) cm-1. 1H NMR (CDCl3): d 3.35 (s, 3H, OCH3), 3.54 (dd,
1H, H-50a), 3.92 (dd, 1H, H-20), 4.32 (ddd, 1H, H-40), 4.39 (dd, 1H, H-50b),
4.57 (dd, 1H, H-30), 4.74 (s, 2H, CH2C6H4F), 4.86 (d, 1H, H-10), 7.03 (ddd,
1H, Har-3), 7.12 (ddd, 1H, Har-5), 7.28 (dddd, 1H, Har-4), 7.45 (ddd, 1H, Har-
0
0
0
0
0
0
6), 7.54 (s, 1H, H-6), 10.00 (bs, 1H, NH). J1 ,2 ¼ 4.2, J2 ,3 ¼ 6.0, J3 ,4 ¼ 6.5,
0
0
0
0
0
0
J4 ,5 a ¼ 8.2, J4 5 b ¼ 3.5, J5 a,5 b ¼ 14.4, J3ar,4ar ¼ 8.5, J3ar,5ar ¼ 1.1, J3ar,F ¼ 9.8,
J4ar,5ar ¼ 7.6, J4ar,6ar ¼ 1.9, J4ar,F ¼ 5.7, J5ar,6ar ¼ 7.5, J6ar,F ¼ 7.5. 13C NMR
(CDCl3): d 49.5 (C-50), 55.7 (OCH3), 66.2 (d, CH2C6H4F), 74.3 (C-30), 75.3 (C-
40), 84.7 (C-20), 100.9 (C-10), 108.6 (C-5), 115.3 (d, Car-3), 124.2 (d, Car-5),
124.5 (d, Car-1), 129.8 (d, Car-4), 130.5 (d, Car-6), 142.7 (C-6), 150.6 (2-CO),
159.6 (4-CO), 160.8 (d, Car-2). J1ar,F ¼ 14.5, J2ar,F ¼ 236.1, J3ar,F ¼ 21.4,
J4ar,F ¼ 8.3, J5ar,F ¼ 3.7, J6ar,F ¼ 5.0, JCH2,F ¼ 3.6. FAB MS (mNBA) m=z: 401
[Mþ H]. FAB HRMS (mNBA) calcd 401.0916 (C17H19ClFN2O6); found
401.0840.
Methyl 5-N-(5-Bromouracil-1-yl)-5-deoxy-2-O-(2-fluorobenzyl)-a-D-xylo-
furanoside (16). 146 mg (82%), from 7 (206mg, 0.40 mmol, 72h). M.p.
20
169ꢀC. ½aꢂD ¼ þ100:5 (c¼ 1.0 in CHCl3). IR: n 3442 (OH), 3196 (NH), 1690
1
(C¼O) cmÀ 1. H NMR (CDCl3): d 3.37 (s, 3H, OCH3), 3.59 (dd, 1H, H-
50a), 3.90 (dd, 1H, H-20), 4.37–4.37 (m, 2H, H-40, H-50b), 4.54 (dd, 1H, H-30),
4.74 (s, 2H, CH2C6H4F), 4.88 (d, 1H, H-10), 7.04 (ddd, 1H, Har-3), 7.14

270
WIRSCHING ET AL.
(ddd, 1H, Har-5), 7.29 (dddd, 1H, Har-4), 7.45 (ddd, 1H, Har-6), 7.65 (s, 1H, H-
0
0
0
0
0
0
0
0
6), 9.43 (bs, 1H, NH). J1 ,2 ¼ 4.2, J2 ,3 ¼ 5.8, J3 ,4 ¼ 6.0, J4 ,5 a ¼ 9.1,
0
0
J5 a,5 b ¼ 14.5,
J3ar,4ar ¼ 8.3,
J3ar,5ar ¼ 1.2,
J3ar,F ¼ 9.9,
J4ar,5ar ¼ 7.5,
J4ar,6ar ¼ 1.9, J4ar,F ¼ 5.4, J5ar,6ar ¼ 7.5, J6ar,F ¼ 7.5. 13C NMR (CDCl3): d 49.3
(C-50), 55.7 (OCH3), 66.3 (d, CH2C6H4F), 74.4 (C-30), 75.3 (C-40), 84.8 (C-
20), 96.3 (C-5), 101.0 (C-10), 115.3 (d, Car-3), 124.2 (d, Car-5), 124.5 (d, Car-
1), 129.9 (d, Car-4), 130.6 (d, Car-6), 145.1 (C-6), 150.6 (2-CO), 160.8 (d, Car-
2), 164.2 (4-CO). J1ar,F ¼ 14.6, J2ar,F ¼ 247.2, J3ar,F ¼ 21.5, J4ar,F ¼ 8.1,
J5ar,F ¼ 3.6, J6ar,F ¼ 4.2, JCH2,F ¼ 3.8. FAB MS (mNBA) m=z: 445 [M þ H
for 79Br], 447 [M þ H for 81Br]. FAB HRMS (mNBA) calcd 445.0411
(C17H1979BrFN2O6), 447.0390 (C17H1981BrFN2O6); found 445.0398, 447.0451.
Methyl 5-Deoxy-2-O-(2-fluorobenzyl)-5-N-(5-iodouracil-1-yl)-a-D-xylo-
furanoside (17). 205 mg (88%), from 8 (266 mg, 0.47 mmol, 24 h). M.p.
20
203ꢀC. ½aꢂD ¼ þ82:0 (c ¼ 1.0 in CHCl3). IR: n 3446 (OH), 3188 (NH), 1690
1
(C¼O), 1614 (C¼O) cmÀ 1. H NMR (CDCl3): d 3.32 (s, 3H, OCH3), 3.53
(dd, 1H, H-50a), 3.84 (dd, 1H, H-20), 4.14–4.21 (m, 2H, H-40, H-50b), 4.41
(dd, 1H, H-30), 4.67, 4.71 (AB-system, 2H, CH2C6H4F), 4.84 (d, 1H, H-10),
7.01 (ddd, 1H, Har-3), 7.10 (ddd, 1H, Har-5), 7.26 (dddd, 1H, Har-4), 7.41
0
0
(ddd, 1H, Har-6), 7.74 (s, 1H, H-6), 9.78 (bs, 1H, NH). J1 ,2 ¼ 4.2,
0
0
0
0
0
0
0
0
J2 ,3 ¼ 5.7, J3 ,4 ¼ 5.9, J4 ,5 a ¼ 9.1, J5 a,5 b ¼ 15.3, JAB ¼ 12.3, JAB,F ¼ 1.0,
J3ar,4ar ¼ 8.4, J3ar,5ar ¼ 1.2, J3ar,F ¼ 9.9, J4ar,5ar ¼ 7.5, J4ar,6ar ¼ 1.9, J4ar,F ¼ 5.6,
13
J5ar,6ar ¼ 7.5, J6ar,F ¼ 7.5. C NMR (CDCl3): d 49.2 (C-50), 55.6 (OCH3),
66.2 (d, CH2C6H4F), 67.4 (C-5), 72.8 (C-30), 75.8 (C-40), 84.9 (C-20), 101.0
(C-10), 115.2 (d, Car-3), 124.1 (d, Car-5), 124.4 (d, Car-1), 129.8 (d, Car-4),
130.4 (d, Car-6), 150.2 (C-6), 151.0 (2-CO), 160.7 (d, Car-2), 161.5 (4-CO).
J1ar,F ¼ 14.6, J2ar,F ¼ 247.2, J3ar,F ¼ 21.5. J4ar,F
¼
8.3, J5ar,F ¼ 3.7,
J6ar,F ¼ 4.2, JCH2,F ¼ 3.8. FAB MS (mNBA) m=z: 493 [M þ H]. FAB
HRMS (mNBA) calcd 493.0272 (C17H19FIN2O6); found 493.0295.
Methyl
5-Deoxy-2-O-(2-fluorobenzyl)-5-N-(6-methyluracil-1-yl)-a-D-
xylo-furanoside (18). 82 mg (65%), from 9 (149 mg, 0.33 mmol, 24 h). M.p.
20
169ꢀC (EtOAc, Rf ¼ 0.10). ½aꢂD ¼ þ101:5 (c ¼ 1.0 in CHCl3). IR: n 3424
1
(OH), 3218 (NH), 1679 (C¼O) cmÀ 1. H NMR (CDCl3): d 2.31 (s, 3H,
CH3), 3.36 (s, 3H, OCH3), 3.74 (dd, 1H, H-50a), 3.96 (dd, 1H, H-20), 4.33
(ddd, 1H, H-40), 4.39 (dd, 1H, H-50b), 4.44 (dd, 1H, H-30), 4.75 (s, 2H,
CH2C6H4F), 4.90 (d, 1H, H-10), 5.59 (s, 1H, H-5), 7.02 (ddd, 1H, Har-3),
7.12 (ddd, 1H, Har-5), 7.26 (dddd, 1H, Har-4), 7.47 (ddd, 1H, Har-6), 10.02
0
0
0
0
0
0
0
0
0
0
(bs, 1H, NH). J1 ,2 ¼ 4.2, J2 ,3 ¼ 4.9, J3 ,4 ¼ 5.3, J4 ,5 a ¼ 6.9, J4 ,5 b ¼ 4.6,
0
0
J5 a,5 b ¼ 14.6, J3ar,4ar ¼ 8.5, J3ar,5ar ¼ 1.2, J3ar,F ¼ 9.9, J4ar,5ar ¼ 7.5,
J4ar,6ar ¼ 1.9, J5ar,6ar ¼ 7.5, J6ar,F ¼ 7.8. 13C NMR (CDCl3): d 20.6 (CH3),
44.6 (C-50), 55.8 (OCH3), 66.2 (d, CH2C6H4F), 74.3 (C-30), 76.4 (C-40),
84.8 (C-20), 101.4 (C-10), 102.6 (C-5), 115.2 (d, Car-3), 124.1 (d, Car-5), 124.8

NEW ISONUCLEOSIDES
271
(d, Car-1), 129.6 (d, Car-4), 130.4 (d, Car-6), 152.3, 155.0 (2-CO, C-6), 160.7 (d,
Car-2), 163.0 (4-CO). J1ar,F ¼ 14.6, J2ar,F ¼ 247.0, J3ar,F ¼ 21.4, J4ar,F ¼ 8.1,
J5ar,F ¼ 3.6, J6ar,F ¼ 4.2, JCH2,F ¼ 3.7. FAB MS (mNBA) m=z 381 [MþH].
FAB HRMS (mNBA) calcd 381.1462 (C18H22FN2O6); found 381.1411.
Methyl 5-Deoxy-5-N-(5,6-dimethyluracil-1-yl)-2-O-(2-fluorobenzyl)-a-D-
xylofuranoside (19). 73 mg (70%), from 10 (123 mg, 0.26 mmol, 100 h).
20
M.p. 188ꢀC. ½aꢂD ¼ þ110:7 (c ¼ 1.0 in CHCl3). IR: n 3426 (OH), 3218
1
(NH), 1679 (C¼O) cmÀ 1. H NMR (CDCl3): d 1.96 (s, 3H, CH3), 2.31 (s,
3H, CH3), 3.38 (s, 3H, OCH3), 3.78 (dd, 1H, H-50a), 3.98 (dd, 1H, H-20),
4.31 (ddd, 1H, H-40), 4.38 (dd, 1H, H-30), 4.45 (dd, 1H, H-50b), 4.75 (s, 2H,
CH2C6H4F), 4.93 (d, 1H, H-10), 7.01 (ddd, 1H, Har-3), 7.11 (ddd, 1H,
Har-5), 7.26 (dddd, 1H, Har-4), 7.47 (ddd, 1H, Har-6), 10.00 (bs, 1H, NH).
0
0
0
0
0
0
0
0
0
0
0
0
J1 ,2 ¼ 4.1, J2 ,3 ¼ 4.5, J3 ,4 ¼ 5.3, J4 ,5 a ¼ 6.5, J4 ,5 b ¼ 5.5, J5 a,5 b ¼ 15.1,
J3ar,4ar ¼ 8.5,
J3ar,5ar ¼ 1.0,
J3ar,F ¼ 9.8,
J4ar,5ar ¼ 7.6,
J4ar,6ar ¼ 1.8,
J5ar,6ar ¼ 7.5, J6ar,F ¼ 7.5. 13C NMR (CDCl3): d 11.3 (CH3), 16.8 (CH3),
44.4 (C-50), 55.9 (OCH3), 66.3 (d, CH2C6H4F), 74.3 (C-30), 76.9 (C-40), 84.6
(C-20), 101.8 (C-10), 108.8 (C-5), 115.2 (d, Car-3), 124.1 (d, Car-5), 124.8 (d,
Car-1), 129.5 (d, Car-4), 130.4 (d, Car-6), 149.5, 151.9 (2-CO, C-6), 160.7 (d,
Car-2), 163.5 (4-CO). J1ar,F ¼ 14.6, J2ar,F ¼ 246.8, J3ar,F ¼ 21.5, J4ar,F ¼ 8.1,
J5ar,F ¼ 3.6, J6ar,F ¼ 4.2, JCH2,F ¼ 3.8. FAB MS (mNBA) m=z 395 [M þ H].
FAB HRMS (mNBA) calcd 395.1618 (C19H24FN2O6); found 395.1584.
Methyl 5-Deoxy-2-O-(2-fluorobenzyl)-5-N-(5-nitrouracil-1-yl)-a-D-xylo-
furanoside (20). The nitro derivative 20 was obtained directly according
to the General procedure A from 2 (96 mg, 0.38 mmol) and 5-nitro-2,4-bis-O-
trimethylsilyluracil8 (460 mg, 1.53 mmol). Yield: 13 mg (8%). M.p. 164–
20
166ꢀC (PE/EA 1:3, Rf ¼ 0.19, decomp.). ½aꢂD ¼ þ73:7 (c ¼ 1.0 in MeOH).
IR: n 3476 (OH), 1706 (C¼O), 1614 (C¼O), 1513 (NO2), 1370 (NO2)
1
cmÀ 1. H NMR (CDCl3): d 3.31 (s, 3H, OCH3), 3.80 (dd, 1H, H-50a), 3.93
(dd, 1H, H-20), 4.30–4.36 (m, 2H, H-40, H-50b), 4.41 (dd, 1H, H-30), 4.67,
4.71 (AB-system, 2H, CH2C6H4F), 4.90 (d, 1H, H-10), 7.02 (ddd, 1H, Har-
3), 7.12 (ddd, 1H, Har-5), 7.28–7.31 (m, 1H, Har-4), 7.45 (ddd, 1H, Har-6),
0
0
0
0
0
0
0
0
9.06 (s, 1H, H-6). J1 ,2 ¼ 4.2, J2 ,3 ¼ 5.6, J3 ,4 ¼ 6.2, J4 ,5 a ¼ 9.7,
0
0
J5 a,5 b ¼ 15.1, JAB ¼ 12.0, J3ar,4ar ¼ 8.6, J3ar,5ar ¼ 1.1, J3ar,F ¼ 9.9, J4ar,5ar
¼
7.5, J4ar,6ar ¼ 1.6, J5ar,6ar ¼ 7.5, J6ar,F ¼ 7.5. 13C NMR (CDCl3): d 51.4 (C-
50), 56.2 (OCH3), 67.4 (d, CH2C6H4F), 75.0 (C-30), 75.7 (C-40), 86.3 (C-20),
102.6 (C-10), 116.2 (d, Car-3), 125.3 (d, Car-5), 126.0 (d, Car-1), 126.2 (C-5),
131.0 (d, Car-4), 131.8 (d, Car-6), 152.3 (C-6), 150.8 (2-CO), 157.2 (4-CO),
162.2 (d, Car-2). J1ar,F ¼ 14.5, J2ar,F ¼ 246.5, J3ar,F ¼ 21.6, J4ar,F ¼ 8.3,
J5ar,F ¼ 3.6, J6ar,F ¼ 4.2, JCH2,F ¼ 3.9. FAB MS (mNBA) m=z: 412 [M þ H].
Methyl
3,5-Anhydro-2-O-(2-fluorobenzyl)-b-D-xylofuranoside
(22).
Diisopropyl azodicarboxylate (730 mg, 3.61 mmol) and, shortly after that, a

272
WIRSCHING ET AL.
solution of methyl 2-O-(2-fluorobenzyl)-b-D-xylofuranoside9 (21) (450 mg,
1.65 mmol) in dry pyridine (1 mL) were added to a solution of
triphenylphosphine (880 mg, 3.35 mmol) in dry pyridine (10 mL) under N2.
The reaction mixture was heated to 80ꢀC for 16 h. The solvent was
removed under vacuum. The residue was dissolved in EA and filtered over
silica gel (50 g). Repeated column chromatography over silica gel (50 g; 1.:
PE/EA 1:1, 2.: EA) gave 22 (290 mg, 69%) as a colourless syrup
containing traces of diisopropyl hydrazodicarboxylate. Rf(EA) ¼ 0.73,
1
Rf(EA=PE) ¼ 0.56. H NMR (CDCl3): d 3.52 (s, 3H, CH3), 4.13 (s, 1H, H-
2), 4.44 (dd, 1H, H-5endo), 4.62 (d, 1H, CH2Ar), 4.65 (d, 1H, CH2Ar), 4.79
(dd, 1H, H-5exo), 5.12 (ddd, 1H, H-4), 5.23 (d, 1H, H-3), 5.33 (d, 1H, H-
1), 7.04 (ddd, 1H, H-3ar), 7.12 (ddd, 1H, H-5ar), 7.28 (dddd, 1H, H-4ar),
7.36 (ddd, 1H, H-6ar). J1,2 ¼ 0.6, J3,4 ¼ 4.6, J4,5endo ¼ 2.8, J4,5exo ¼ 4.9,
J5endo,5exo ¼ 7.5, JCH2Ar ¼ 12.3. 13C NMR (CDCl3): d 55.8 (CH3), 65.8
(CH2Ar), 78.9 (C-4), 79.6 (C-5), 85.6 (C-2), 88.9 (C-3), 111.6 (C-1), 115.4
(d, Car-3), 124.2 (d, Car-5), 124.4 (d, Car-1), 129.9 (d, Car-4), 130.2 (d, Car-
6), 160.8 (d, Car-2). JCH2,F ¼ 3.1, J3ar,F ¼ 21.4, J5ar,F ¼ 4.1, J1ar,F ¼ 15.1,
ꢃ
J4ar,F ¼ 8.1, J6ar,F ¼ 4.1, J2ar,F ¼ 247.2. EI MS m=z (%): 254 (0.1) [Mþ ],
ꢃ
253 (0.2), 223 (0.2) [Mþ -OCH3], 195 (0.5), 194 (0.4), 193 (0.3), 192
(0.1), 165 (0.5), 164 (2), 163 (3), 153 (1), 136 (1), 135 (2.5), 134 (1), 129
(2), 126 ꢃ(1), 125 (3), 124 (1), 123 (8.5), 115 (10), 110 (15), 109 (100)
[C7H6Fþ ], 87 (7), 85 (16), 83 (10), 71 (5), 69 (18), 68 (5), 61 (5), 59 (4.5),
57 (4), 45 (8).
Methyl
5-Deoxy-2-O-(2-fluorobenzyl)-5-N-(5-fluorouracil-1-yl)-b-D-xylo-
furanoside (23). Compound 23 was obtained directly according to the
General procedure A from 22 (50 mg, 0.20 mmol) and 5-fluoro-2,4-bis-O-
trimethylsilyluracil13 (168 mg, 0.61 mmol). Yield: 10 mg (13%). M.p. 182ꢀC
20
(PE/EA 1:3, Rf ¼ 0.12). ½aꢂD ¼ À40:0 (c¼ 1.0, CHCl3). IR: n 3443 (OH),
1
3188 (NH), 1696 (C¼O) cmÀ 1. H NMR (CDCl3): d 3.42 (s, 3H, CH3),
0
0
0
0
3.76 (dd, 1H, H-5a ), 3.97 (d, 1H, H-2 ), 4.20–4.22 (m, 2H, H-3 , H-5b ), 4.42
(ddd, 1H, H-40), 4.63, 4.66 (AB-system, 2H, CH2C6H4F), 4.94 (s, 1H, H-10),
7.03 (ddd, 1H, Har-3), 7.12 (ddd, 1H, Har-5), 7.29 (dddd, 1H, Har-4), 7.42
0
0
0
0
(ddd, 1H, Har-6), 7.46 (d, 1H, H-6), 8.86 (bs, 1H, NH). J1 ,2 ¼ 0, J2 ,3 ¼ 1.1,
0
0
0
0
0
0
0
0
J3 ,4 ¼ 4.1, J4 ,5a ¼ 8.2, J4 ,5b ¼ 4.1, J5a ,5b ¼ 14.3, JAB ¼ 11.7, J6,F ¼ 5.6,
J3ar,4ar ¼ 8.4, J3ar,5ar ¼ 1.1, J3ar,F ¼ 9.9, J4ar,5ar ¼ 7.5, J4ar,6ar ¼ 1.9, J4ar,F ¼ 5.7,
13
J5ar,6ar ¼ 7.5, J6ar,F ¼ 7.5. C NMR (CDCl3): d 49.17 (C-50), 55.8 (CH3),
65.8 (d, CH2C6H4F), 73.5 (C-30), 80.5 (C-40), 86.3 (C-20), 107.3 (C-10), 115.4
(d, Car-3), 124.3 (d, Car-5), 124.7 (d, Car-1), 130.0 (d, Car-4), 130.1 (d, Car-
6), 130.3 (d, C-6), 140.4 (d, C-5), 149.4 (2-CO), 157.0 (4-CO), 160.6 (d, Car-
2). J5,F ¼ 236.8, J6,F ¼ 32.8, J1ar,F ¼ 14.8, J2ar,F ¼ 245.7, J3ar,F ¼ 21.2,
J4ar,F ¼ 8.0, J5ar,F ¼ 3.5, J6ar,F ¼ 4.2, JCH2F ¼ 3.9.

NEW ISONUCLEOSIDES
273
Methyl
5-N-(5-Chlorouracil-1-yl)-5-deoxy-2-O-(2-fluorobenzyl)-b-D-
xylo-furanoside (24). Compound 24 was obtained directly according to
the General procedure A from 22 (50 mg, 0.20 mmol) and 5-chloro-2,4-bis-
trimethylsilyluracil13 (148 mg, 0.67 mmol). Yield: 9 mg (11%). M.p. 186ꢀC
20
(PE/EA 1:4, Rf ¼ 0.09). ½aꢂD ¼ À31:4 (c ¼ 0.9, CHCl3). IR: n 3434 (OH),
1
3206 (NH), 1688 (C¼O) cmÀ 1. H NMR (CDCl3): 3.43 (s, 3H, CH3), 3.81
0
0
0
(dd, 1H, H-5a ), 3.98 (d, 1H, H-2 ), 4.22 (dd, 1H, H-3 ), 4.25 (dd, 1H, H-
0
0
5b ), 4.43 (ddd, 1H, H-4 ), 4.63–4.66 (AB system, 2H, CH2C6H4F), 4.94 (s,
1H, H-10), 7.04 (ddd, 1H, Har-3), 7.12 (ddd, 1H, Har-5), 7.29 (dddd, 1H,
H-4ar), 7.34 (ddd, 1H, Har-6), 7.58 (s, 1H, H-6), 8.70 (bs, 1H, NH).
0
0
0
0
0
0
0
0
0
0
0
0
J1 ,2 ¼ 0, J2 ,3 ¼ 1.5, J3 ,4 ¼ 4.2, J4 ,5a ¼ 8.2, J4 ,5b ¼ 4.4, J5a ,5b ¼ 14.5,
JAB ¼ 12.3, JAB,F ¼ 1.3, J3ar,4ar ¼ 8.5, J3ar,5ar ¼ 1.3, J3ar,F ¼ 9.9, J4ar,5ar ¼ 7.5,
13
J4ar,6ar ¼ 1.8, J4ar,F ¼ 5.7, J5ar,6ar ¼ 7.5, J6ar,F ¼ 7.4 . C NMR: d 49.3 (C-50),
55.9 (CH3), 65.8 (d, CH2C6H4F, 73.6 (C-30), 80.3 (C-40), 86.4 (C-20), 107.3
(C-10), 108.5 (C-5), 115.3 (d, Car-3), 124.1 (d, Car-1), 124.3 (d, Car-5), 130.0
(d, Car-4), 130.1 (d, Car-6), 142.2 (C-6), 149.9 (2-CO), 160.6 (d, C-2ar),
162.8 (4-CO). J1ar,F ¼ 14.5, J2ar,F ¼ 238.0, J3ar,F ¼ 21.5, J4ar,F ¼ 8.3,
J5ar,F ¼ 3.7, J6ar,F ¼ 4.9, JCH2,F ¼ 3.8.
Methyl 5-Deoxy-2-O-(2-fluorobenzyl)-5-N-(5-iodouracil-1-yl)-b-D-xylo-
furanoside (25). Compound 25 was obtained directly according to the
General procedure A. from 22 (50 mg, 0.20 mmol) and 5-iodo-2,4-bis-
trifluorouracil13 (230 mg, 0.60 mmol). Yield: 7 mg (7%). M.p. 167–170ꢀC
20
(PE/EA 1:5, Rf ¼ 0.13, decomp.). ½aꢂD ¼ À16:1 (c ¼ 0.7, CHCl3). IR: n
1
3435 (OH), 3192 (NH), 1689 (C¼O) cmÀ 1. H NMR (CDCl3): d 3.45 (s,
0
0
0
3H, CH3), 3.83 (dd, 1H, H-5a ), 3.97 (d, 1H, H-2 ), 4.22 (dd, 1H, H-3 ),
0
0
4.24 (dd, 1H, H-5b ), 4.44 (ddd, 1H, H-4 ), 4.63, 4.67 (AB system, 2H,
CH2C6H4F), 4.95 (s, 1H, H-10), 7.04 (ddd, 1H, Har-3), 7.12 (ddd, 1H, Har-
5), 7.25–7.28 (m, 1H, Har-4), 7.39 (ddd, 1H, Har-6), 7.69 (s, 1H, H-6), 8.53
0
0
0
0
0
0
0
0
0
0
(bs, 1H, NH). J1 ,2 ¼ 0, J2 ,3 ¼ 1.3, J3 ,4 ¼ 4.1, J4 ,5a ¼ 8.4, J4 ,5b ¼ 4.2,
0
0
J5a ,5b ¼ 14.3, JAB ¼ 12.1, J3ar,4ar ¼ 8.4, J3ar,5ar ¼ 1.1, J3ar,F ¼ 9.9, J4ar,5ar
¼
7.4, J4ar,6ar ¼ 1.8, J5ar,6ar ¼ 7.5, J6ar,F ¼ 7.5. 13C NMR (CDCl3): d 49.3 (C-
50), 55.9 (CH3), 65.6 (d, CH2C6H4F), 67.5 (C-5), 73.4 (C-3), 80.2 (C-40),
86.3 (C-20), 107.3 (C-10), 115.2 (d, Car-3), 124.1 (d, Car-1), 124.4 (d, Car-5),
130.1 (d, Car-4), 130.2 (d, Car-6), 149.8 (C-6), 150.7 (2-CO), 160.6 (d, Car-
2), 161.6 (4-CO). J1ar,F ¼ 14.5, J2ar,F ¼ 237.3, J3ar,F ¼ 21.4, J4ar,F ¼ 8.3,
J5ar,F ¼ 3.8, J6ar,F ¼ 4.8, JCH2,F ¼ 3.7.
ACKNOWLEDGMENTS
We thank the Deutsche Forschungsgemeinschaft, the Fonds der Che-
mischen Industrie and the European Commission for their financial support.

274
WIRSCHING ET AL.
We also thank Mrs. AnnAbsillis, Mrs. AnitaCamps and Mrs.LiesVandenheurck
for technical assistance. The BAYER AG, Leverkusen, provided valuable
chemicals.
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Received November 15, 2001
Accepted January 10, 2002