Thiosugars. VIII. Preparation of new 4′-thio-L-lyxo pyrimidine nucleoside analogues

Article abstract of DOI:10.1081/NCN-100105900

Reaction of 1-O-acetyl-2,3,5-tri-O-benzyl-4-thio-L-lyxofuranose with silylated pyrimidine bases and subsequent deprotection with boron tribromide led to 4′-thio-L-lyxo pyrimidine nucleosides. The 5-bromo-6-methyl derivative was prepared from methyl 2,3,5-

Full text of DOI:10.1081/NCN-100105900

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THIOSUGARS. VIII.* PREPARATION OF NEW 4′-THIO-L-
LYXO PYRIMIDINE NUCLEOSIDE ANALOGUES
Jörn Wirsching a , Jürgen Voss b , Gunadi Adiwidjaja c , Jan Balzarini d & Erik De Clercq d
a Institut für Organische Chemie der Universität Hamburg , Martin-Luther-King-Platz 6,
Hamburg, 20146, Germany
b Institut für Organische Chemie der Universität Hamburg , Martin-Luther-King-Platz 6,
Hamburg, 20146, Germany
c Mineralogisch-Petrographisches Institut der Universität Hamburg , Grindelallee 48,
Hamburg, 20146, Germany
d Rega Institute for Medical Research, Catholic University of Leuven , Minderbroederstraat
10, Leuven, B-3000, Belgium
Published online: 21 Aug 2006.
To cite this article: Jörn Wirsching , Jürgen Voss , Gunadi Adiwidjaja , Jan Balzarini & Erik De Clercq (2001) THIOSUGARS.
VIII.* PREPARATION OF NEW 4′-THIO-L-LYXO PYRIMIDINE NUCLEOSIDE ANALOGUES, Nucleosides, Nucleotides and Nucleic Acids,
20:9, 1625-1645, DOI: 10.1081/NCN-100105900
To link to this article: http://dx.doi.org/10.1081/NCN-100105900
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NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS, 20(9), 1625À1645 (2001)
THIOSUGARS. VIII.* PREPARATION OF NEW
40-THIO-L-LYXO PYRIMIDINE NUCLEOSIDE
ANALOGUES
Jorn Wirsching,a Jurgen Voss,a,{ Gunadi Adiwidjaja,b Jan Balzarini,c
and Erik De Clercqc
aInstitut fur Organische Chemie der Universitat Hamburg,
Martin-Luther-King-Platz 6, 20146 Hamburg, Germany
bMineralogisch-Petrographisches Institut der Universitat
Hamburg, Grindelallee 48, 20146Hamburg, Germany
cRega Institute for Medical Research, Catholic University of
Leuven, Minderbroederstraat 10, B-3000 Leuven, Belgium
ABSTRACT
Reaction of 1-O-acetyl-2,3,5-tri-O-benzyl-4-thio-L-lyxofuranose with
silylated pyrimidine bases and subsequent deprotection with boron
tribromide led to 40-thio-L-lyxo pyrimidine nucleosides. The 5-bromo-6-
methyl derivative was prepared from methyl 2,3,5-tri-O-acetyl-4-thio-L-
lyxofuranoside. Deacetylation was performed with sodium methoxide.
The anomers were separated by HPLC and their configurations assigned
by NMR spectroscopy and X-ray structural analyses. The biological
activity of the nucleosides was tested.
*Part VII: Wirsching, J., Voss, J., Adiwidjaja, G., Giesler, A., Kopf, J. Eur. J. Org. Chem.
2001, in press.
{Corresponding author. Fax: þ49(0)40=42838-5592; E-mail: voss@chemie.uni-hamburg.de
1625
Copyright # 2001 by Marcel Dekker, Inc.
www.dekker.com

1626
WIRSCHING ET AL.
INTRODUCTION
Nucleoside analogues containing either modified nucleobases or unna-
tural carbohydrate moieties have found wide-spread interest in synthetic
chemistry1. In particular, their biological activity as compared with the
natural nucleosides has initiated intense research activities in the last decade.
Prominent examples, which have already found medicinal application as anti-
HIV2 (AZT, L-3TC) or anti-HSV (Penciclovir1) drugs, are 20,30-dideoxy- or
acyclocarba-nucleoside derivatives and can, therefore, act as chain
terminators. It seems, however, worthwhile to synthesise and test also 40-thio-
nucleoside analogues3 since the lipophilicity of a nucleoside and hence its
ability to penetrate into a cell should be increased by the replacement of
oxygen by sulfur in the furanose ring. We have, therefore, recently prepared
uracil analogues with the unnatural 4-thio-L-arabino-4a and 2-deoxy-4-thio-
L-threo-configuration4b of the carbohydrate.
RESULTS AND DISCUSSION
D-Ribose dibenzyldithioacetal 1 was prepared in three steps from D-
ribose according to literature procedures5À7 and transformed into benzyl 1,4-
dithio-L-lyxofuranoside 3 via the mesylate 2. The best result (82% yield) was
obtained by heating the crude mesylate 2 at 110 ꢀC in the presence of tet-
rabutylammonium iodide and barium carbonate in dry pyridine6À9. Heating
of 2 with sodium iodide and barium carbonate in dry acetone5,10 gave only
28% of 3. In both cases only one anomer was formed. It was not possible to
decide on the basis of NMR (NOE) spectra whether it was the a- or b-
anomer of 3. We have, however, proved the inversion of the configuration at
C-4, which leads from the D-ribo to the L-lyxo series for analogous com-
pounds7,11. Transformation of the dithiosugar 3 into the more suitable 1-O-
acetyl-2,3,5-tri-O-benzyl-4-thio-L-lyxofuranose (4) was achieved under the
Seebach conditions12À14 by using mercuric acetate in glacial acetic acid. We
obtained a 76% yield of 4 with an a:b ratio of 1:10 (Scheme 1). The anomeric
Scheme 1.

THIOSUGARS. VIII
1627
configurations of 4 could be assigned by NOE spectroscopy. The a-anomer
showed an NOE between H-1=H-5 and the b-anomer a significant NOE
between H-1=H-2.
Compound 4 was then transformed into protected 40-thionucleosides by
using various silylated nucleobases15,16 in the presence of trimethylsilyl tri-
fluoromethanesulfonate (TMSOTf) as coupling reagent6,17,18. The protected
40-thio-L-lyxouridine 5 was obtained with 88% yield as anomeric mixture
with an a:b ratio of 1:2. The protected 40-thio-L-lyxothymidine 6 (68% yield)
exhibited an a:b ratio of 2:1. In the case of the protected uridine nucleoside 5
the anomers could be separated by silica gel chromatography, whereas for 6 a
separation failed. The anomeric structures of 5 and 6 were assigned by
measurement of NOE spectra. The observed NOE interactions between H-6
and H-20, H-30 and H-40 doubtlessly indicated the a-anomer, whereas the
observed NOE between H-6and the two H-5 0 protons proved the b-structure
(Fig. 1).
The protected 6-methyl-40-thio-L-lyxouridine derivative 7 was isolated
with a yield of 80% (a-7:b-7 ¼ 10:1). The anomers were separated by column
chromatography. The configuration of b-7 could be assigned by the NOEs of
H-10 with H-20 and H-30 and of the methyl protons of the nucleobase with one
of the two protons at C-50 (Fig. 2). The a-anomer showed an intense NOE
between the methyl group of the nucleobase and the H-10 proton of the sugar
moiety.
The synthesis of the protected 5,6-dimethyl-40-thio-L-lyxouridine deri-
vative 8 yielded 70% of one pure anomer. It was not possible to assign its
structure by NOE measurements. Comparison of the one-dimensional NMR
spectra of 8 with those of 7 led us to the conclusion that the obtained anomer
exhibits a-configuration.
Figure 1. Observed NOE contacts for the a- and b-anomers of 5 and 6.

1628
WIRSCHING ET AL.
Figure 2. Observed NOE contacts for the b-anomer of 7.
Coupling of 4 with silylated 5-halo-6-methyluracil16 yielded protected 5-
iodo-6-methyl-40-thio-L-lyxouridine 9 with 53% and 5-bromo-6-methyl-40-
thio-L-lyxouridine 10 with 55%, respectively. Both 40-thio-L-lyxo nucleosides
were obtained as one pure anomer. Again the NOE measurements did not
allow configurational assignments, but the one-dimensional NMR spectra of
9 and 10 are very similar to that of a-7 (Scheme 2).
The final and crucial step was then the cleavage of the benzyl protecting
groups of the nucleosides 5À10. We achieved this by reaction of these
nucleosides with boron tribromide at À90 ꢀC6,13,19. In order to get satisfac-
tory results it was necessary that after quenching the excess boron tribromide
the resulting hydrobromic acid had to be neutralised. Without neutralisation
of the reaction mixture we were only able to isolate ill-defined hydrobromides
of the unprotected nucleosides. The best reagent for the neutralisation was
Scheme 2.

THIOSUGARS. VIII
1629
silver carbonate7. It should be mentioned that obviously a tight silver com-
plex was formed when the silver carbonate got to long in contact with the
nucleoside, e.g. over night. As a consequence, it was no longer possible to
isolate the nucleoside from the solution without acidifying the silver residue
which inevitably led again to hydrohalides. The best compromise was a
neutralisation time of half an hour. We also tested sodium hydro-
gencarbonate13 or pyridine6 instead of silver carbonate. This led, however, to
the formation of large amounts of soluble salts, the separation of which from
the nucleoside, e.g. by Sephadex LH 20 column chromatography was lengthy
and expensive, whereas the silver salts could be easily filtered off.
Cleavage of the uridine derivative 5 with boron tribromide gave both
anomers of the unprotected nucleoside 11. The anomers could be separated
by crystallisation from water, which yielded 11% of pure b-11. Removal of
traces of b-11 from a-11 was achieved by reversed phase HPLC to give a-11 in
69% yield. The unprotected anomers of the analogous thymidine nucleoside
12 were only separable by HPLC. The yields were 23% a-12 and 15% b-12,
respectively. Cleavage of the benzyl groups of the 6-methyluridine derivative
7 gave the pure major anomer a-13 with a yield of 21% after HPLC
separation. The minor anomer b-13 was isolated with a yield of 13%. It was
possible to grow single crystals of a-12 and a-13 from water and determine
the structures by X-ray diffraction analyses which proved undoubtedly their
a-configuration (Fig. 3 and 4).
Removal of the benzyl groups of the 5,6-dimethyl-40-thio-L-lyxouridine
derivative 8 led to 7% of 14. Repetition of the NOE experiment with the
unprotected nucleoside 14 to assign its anomeric structure failed as men-
tioned before for 8. However, 14 crystallised from water-methanol and the
a-configuration was proved by X-ray diffraction analysis (Fig. 5). The thio-
furanose moieties of the three methyl-substituted nucleoside analogues a-12,
a-13 and 14 exhibit envelope conformations at C-30, whereas C-10, C-20, C-40
and S nearly form a plane with torsion angles of only 2.1ꢀ (a-12), 3.3ꢀ (a-13)
and À2.6ꢀ (14) at the bonds between sulfur and the anomeric centre (C10).
The torsion angles C2-N1-C10-S between the pyrimidine ring and the sugar
part are À135.3ꢀ (a-12), 63.2ꢀ (a-13) and 59.3ꢀ (14) (Fig. 3À5), i.e. a methyl
substituent at C-6causes steric hindrance with the sulfur atom.
Unprotected 5-iodo-6methyl-40-thio-L-lyxouridine 15 was obtained
after chromatography and recrystallisation from water with a yield of 9%.
The 5-bromo-6-methyl-40-thio-L-lyxouridine derivative 16 could not be iso-
lated after treatment of 10 with boron tribromide (Scheme 3).
However, we found an alternative pathway which made the desired
nucleoside 16 accessible. The acetate 4 was first treated with boron tri-
bromide followed by immediate acetylation to give the thiosugar 17 as a 2:1
mixture of anomers with a yield of 55%. The exchange of the anomeric acetyl
group by the methoxy group occurs during the work-up with methanol in the
presence of hydrobromic acid. Coupling of 17 with 5-bromo-6-methy

1630
WIRSCHING ET AL.
Figure 3. ORTEP view of the X-ray diffraction structure of a-12 with atom numbering.
Thermal ellipsoids are drawn at the 50% probability level.
l-2,4-bis-O-(trimethylsilyl)uracil16 in the presence of trimethylsilyl triflate
gave 30% nucleoside 18 (a-anomer). Cleavage of the acetyl groups with
sodium methoxide yielded the unprotected 5-bromo-6-methyl-40-thio-L-lyx-
ouridine 16 (7% after recrystallisation) (Scheme 4).
Biological tests were performed with the 40-thiouridine and 40-thiothy-
midine analogues a-11, b-11, b-12, a-12 as well as with the 6-methyl-40-thio-
nucleoside analogues a-13, b-13, a-14, a-15 and a-16. No significant inhibitor
activities against the following viruses were found for these L-lyxonucleoside
analogues at subtoxic concentrations: HIV-1 (IIIB), HIV-2 (ROD), HSV-1,
HSV-2, VZV (OKA), HCMV (Davis), Vaccinia V., Vesicular stomatitis
V., Parainfluenza-3 V., Reovirus-3, Sindbis V., Coxsackie V. B4, Punta Toro
V., Respiratory syncytial V.
EXPERIMENTAL
Melting points were taken on an Electrothermal apparatus (values are
corrected). NMR measurements were carried out with Bruker AMX 400
(400 MHz) and DRX 500 (500 MHz) spectrometers. Chemical shifts (ppm)
are related to Me4Si. Standard correlation techniques were used for assign-
ments. IR spectra were recorded on an ATI Mattson Genesis spectrometer.
Mass spectra were measured on Varian CH 7 (70 eV, EI) and VG Analytical

THIOSUGARS. VIII
1631
Figure 4. ORTEP view of the X-ray diffraction structure of a-13 with atom numbering.
Thermal ellipsoids are drawn at the 50% probability level.
70À250 S (FAB MS, FAB HRMS, HRMS). For FAB and FAB HRMS
meta-nitrobenzyl alcohol (mNBA) was used as matrix. HPLC (Merck-
Hitachi equipment): semipreparative HPLC was carried out with a LiChro-
CART 250-10 column containing LiChrosher 100 RP-18 (10 mm) and
analytical HPLC was performed with a EcoCART 125-3 column containing
Figure 5. ORTEP view of the X-ray diffraction structure of a-14 with atom numbering.
Thermal ellipsoids are drawn at the 50% probability level.

1632
WIRSCHING ET AL.
Scheme 3.
Scheme 4.
LiChrosher 100 RP-18 end capped (5 mm). Solvents for HPLC were obtained
from Merck (MeCN, HPLC grade) and Riedel-de Haen (water, HPLC
grade). Optical rotations were measured with Perkin Elmer Polarimeter 341.
TLC was carried out on Merck PF254 foils (detection: UV light, iodine
vapour, or EtOH-H2SO4 spray=200 ꢀC), and column chromatography on
Merck Kieselgel 60 (70À230 mesh). Solvents were purified and dried
according to standard laboratory procedures20.

THIOSUGARS. VIII
1633
X-ray structure analyses.—The crystal data and a summary of experi-
mental details for a-12, a-13 and 14 are given in Table 1. The data collection
was performed on a KappaCCD Nonius diffractometer, with graphite
monochromated Mo Ka radiation (0.71073 A) in the rotation F scan mode.
The structures were solved by direct methods using the SIR-9721 program,
and refined by full-matrix-block least-squares on F2 using all data and the
SHELXL-9722 program. 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 142899
(a-13), CCDC 142900 (14) and 142901 (a-12).
Benzyl 2,3,5-tri-O-benzyl-1,4-dithio-L-lyxofuranoside (3). Method A:
2,3,5-Tri-O-benzyl-D-ribose
dibenzyldithioacetal
(1)5À7
(29.72 g,
45.66 mmol) was dissolved in dry pyridine (200 mL) and cooled to 0 ꢀC.
A solution of mesyl chloride (7.0 mL, 10.29 g, 89.83 g) in dry pyridine
(50 mL) was added and the reaction mixture was stirred at room
temperature for 24 h. After the reaction was finished the excess of mesyl
chloride was quenched with water (300 mL) and the solution was
evaporated. The residue was dissolved in CHCl3, washed with dilute
hydrochloric acid, water and sat. NaHCO3 solution. The organic phase
was separated, dried with MgSO4 and evaporated to give the crude
mesylate 2 in quantitative yield (32.97 g). This was dissolved in dry
acetone (900 ml), sodium iodide (71.93 g, 0.48 mol) and barium carbonate
(141.3 g, 0.72 mol) were added and the mixture stirred for 24 h at 60 ꢀC.
After the reaction mixture was cooled to room temperature the solids were
filtered off and the acetone was removed. The residue was dissolved in
CHCl3, extracted with water, the organic phase separated, dried with
MgSO4 and evaporated. The resulting crude product was purified by
column chromatography (petroleum ether-EtOAc 4:1, Rf ¼ 0.42) to give
one pure anomer of 3 (6.93 g, 28%) as a pale yellow syrup. À Method B:
Mesylation of 1 was carried out as described for method A. The crude
mesylate 2 (33.27 g, 45.64 mmol) and tetrabutylammonium iodide (16.98 g,
45.97 mmol) were dissolved in dry pyridine (380 mL), barium carbonate
(9.19 g, 46.57 mmol) was added and the mixture was heated at 110 ꢀC for
2 h. After the reaction was completed the mixture was cooled to room
temperature and worked up as described for method A to yield 3 (20.31 g,
20
82%) as one pure anomer. ½aꢁ ¼ þ75.2 (c ¼ 1.0 in CHCl3); IR (film):
D
n ¼ 3086, 3063, 3030, 2920, 2826, 1492, 1455, 1361, 1311, 1241, 1208, 1124,
1090, 1028, 912, 736, 698 cmÀ1; 1H NMR (400 MHz, CDCl3):
d ¼ 7.20À7.36(m, 20H, CH arom), 4.71 (d, 1H, JA,B 11.7 Hz, OCH2Ph),
4.60 (d, 1H, JA,B 11.7 Hz, OCH2Ph), 4.47À4.54 (m, 4H, OCH2Ph), 4.45 (d,
1H, H-1), 4.27 (dd, 1H, H-3), 3.88 (dd, 1H, H-5b), 3.84 (dd, 1H, H-2),

1634
WIRSCHING ET AL.
3.80 (s, 2H, SCH2Ph), 3.69 (ddd, 1H, H-4), 3.58 (dd, 1H, H-5a) ppm.
J1,2 ¼ 6.6, J2,3 ¼ 3.1, J3,4 ¼ 5.0, J4,5a ¼ 7.1, J4,5b ¼ 6.8, J5a,5b ¼ 9.3 Hz;
13C NMR (101 MHz, CDCl3): d ¼ 138.2 (Carom), 138.1, 137.80, 137.78,
129.1 (CHarom), 128.6, 128.5, 128.43, 128.37, 127.9, 127.82, 127.81, 127.80,
127.74, 127.71, 127.2, 86.9 (C-2), 79.0 (C-3), 73.5 (OCH2Ph), 73.3, 73.0,
1
70.4 (C-5), 51.3 (C-1), 46.3 (C-4), 36.4 (2C, each SCH2Ph) ppm; H and
13C NMR data in agreement with the lower resolved spectra of ref6b. MS
(70 eVþ, EI): m=z (%): 542 (0.01) [Mþ], 181 (5), 108 (5), 92 (10), 91 (100)
[C7H7 ], 65 (8); C33H34O3S2 (542.77): calcd C 73.03, H 6.31, S 11.81;
found C 72.1123, H 6.33, S 11.53.
1-O-Acetyl-2,3,5-tri-O-benzyl-4-thio-L-lyxofuranose (4). A solution of
benzyl 1,4-dithio-L-lyxofuranoside 3 (8.94 g, 16.47 mmol) and mercuric
acetate (10.41 g, 32.67 mmol) in glacial acetic acid (220 mL) was stirred at
room temperature for 1.5 h. After removal of the acetic acid under reduced
pressure the residue was dissolved in EtOAc, diluted with petroleum ether
and kept overnight at À5 ꢀC. The precipitated mercuric salts were filtered off,
the solvents were removed and the crude product was purified by silica gel
column chromatography (petroleum ether-EtOAc 4:1; Rf,a,b ¼ 0.26) to give 4
(5.96g, 76%) as a pale yellow syrup with an anomeric ratio of 1:10 ( a:b).
The anomers were not separable. IR (film): n ¼ 3087, 3063, 3030, 2924, 2865,
1745 (C¼O), 1498, 1452, 1369, 1311, 1246, 1228, 1101, 1016, 912, 847, 794,
1
739, 700, 606 cmÀ1; H NMR (500 MHz, CDCl3): a-4: d ¼ 7.27À7.41 (m,
15H, CHarom), 6.25 (d, 1H, H-1), 4.46À4.70 (m, 6H, CH2Ph), 4.25 (dd, 1H,
H-3), 3.94À3.96(m, 1H, H-5 ), 3.91 (dd, 1H, H-2), 3.55 (dd, 1H, H-5a),
b
3.48À3.52 (m, 1H, H-4), 2.03 (s, 3H, CH3), ppm. J1,2 ¼ 4.9, J2,3 ¼ 3.2,
J3,4 ¼ 4.0, J4,5a ¼ 6.5, J5a,5b ¼ 9.0 Hz; b-4: d ¼ 7.27À7.41 (m, 15H, CHarom),
6.02 (d, 1H, H-1), 4.46À4.70 (m, 6H, CH2Ph), 4.25 (dd, 1H, H-3), 4.10 (dd,
1H, H-2), 3.98 (dd, 1H, H-5b), 3.78 (ddd, 1H, H-4), 3.69 (dd, 1H, H-5a), 2.04
(s, 3H, CH3), ppm. J1,2 ¼ 3.7, J2,3 ¼ 3.5, J3,4 ¼ 5.7, J4,5a ¼ 8.0, J4,5b ¼ 5.6,
J5a,5b ¼ 9.3Hz; 13C NMR (126MHz, CDCl 3): a-4: d ¼ 171.3 (CO), 139.5
(Carom), 138.5, 138.1, 129.0 (CHarom), 128.9, 128.6, 128.44, 128.41, 128.37,
128.2, 128.1, 128.0, 84.7 (C-2), 79.1 (C-3), 76.9 (C-1), 73.93 (CH2Ph), 73.87,
72.9, 70.2 (C-5), 46.7 (C-4), 21.8 (CH3), ppm; b-4: d ¼ 171.3 (CO), 138.1
(Carom), 137.9, 137.7, 128.40 (CHarom), 128.38, 128.36, 127.78, 127.77, 127.75,
127.7, 127.61, 127.57, 84.4 (C-2), 80.5 (C-1), 79.4 (C-3), 73.30 (CH2Ph),
73.26, 72.6, 71.0 (C-5), 46.4 (C-4), 21.0 (CH3), ppm; FAB MS: m=z: 479
[MþH]; C28H30O5S (478.61): calcd C 70.27, H 6.32, S 6.70; found C 68.6523,
H 6.26, S 6.68.
1-(2,3,5-Tri-O-benzyl-4-thio-L-lyxofuranosyl)uracil (5). A solution of 4
(414 mg, 0.87 mmol), 2,4-bis-O-(trimethylsilyl)uracil15 (850 mg, 3.31 mmol)
and molecular sieves A4 (50 mg) in dry MeCN (15 mL) was cooled to À18 ꢀC
and TMSOTf (0.50 mL, 615 mg, 2.77 mmol) was added. The reaction mixture

THIOSUGARS. VIII
1635
was stirred for 2 h and the temperature was allowed to rise to room
temperature. Then the mixture was quenched with an excess of sat.
NaHCO3 solution and stirred for another 0.5 h. The solids were filtered off
and the filtrate was extracted with CHCl3. The organic phase was separated,
dried with MgSO4 and evaporated. The resulting crude product was purified
by silica gel chromatography (petroleum ether-EtOAc 1:1, Rf,b ¼ 0.21,
Rf,a ¼ 0.15) to give separated anomers a-5 (132 mg, 29%) and b-5 (270 mg,
20
59%). Both anomers are white solids. a-5: M.p. 45À47 ꢀC; ½aꢁD ¼ À 62.1
20
D
(c ¼ 1.0 in CHCl3); b-5: M.p. 41À43 ꢀC; ½aꢁ ¼ þ89.0 (c ¼ 1.0 in CHCl3); IR
(KBr): a-5: n ¼ 3192 (NH), 3086, 3062, 3031, 2925, 2859, 1690 (C¼O), 1495,
1454, 1380, 1246, 1207, 1129, 1077, 1027, 808, 738, 699, 550, 515 cmÀ1; b-5:
n ¼ 3060, 3029, 2924, 2857, 1680 (C¼O), 1495, 1456, 1384, 1266, 1208, 1121,
1086, 1048, 1025, 806, 736, 697, 605, 551 cmÀ1; 1H NMR (400 MHz, CDCl3):
a-5: d ¼ 8.50 (ws, 1H, NH), 7.28À7.37 (m, 16H, H-6, CHarom), 6.26 (d, 1H,
H-10), 5.55 (dd, 1H, H-5), 4.85 (d, 1H, JA,B 11.7 Hz, CH2Ph), 4.67 (d, 1H,
J
A,B 11.7 Hz, CH2Ph), 4.65 (d, 1H, JA,B 12.5 Hz, CH2Ph) 4.50 (s, 2H, CH2Ph),
4.31 (d, 1H, JA,B 12.5 Hz, CH2Ph), 4.22 (dd, 1H, H-30), 3.91 (dd, 1H, H-20),
3.84À3.89 (m, 2H, H-40, H-5b0 ), 3.56(dd, 1H, H- 50a) ppm. J1 ,2 ¼ 7.8,
0
0
0
0
0
0
0
0
0
0
J2 ,3 ¼ 3.1, J3 ,4 ¼ 3.2, J4 ,5 a ¼ 9.3, J5 a,5 b ¼ 12.2, J5,6 ¼ 8.2, J5,NH ¼ 2.3 Hz;
b-5: d ¼ 8.82 (ws, 1H, NH), 8.06(d, 1H, H-6), 7.29 À7.37 (m, 15H, CHarom),
6.41 (d, 1H, H-10), 5.41 (dd, 1H, H-5), 4.75 (d, 1H, JA,B 10.9 Hz, CH2Ph),
4.66 (d, 1H, JA,B 12.0 Hz, CH2Ph), 4.58 (d, 1H, JA,B 12.0 Hz, CH2Ph), 4.57
(d, 1H, JA,B 10.9 Hz, CH2Ph), 4.56(d, 1H, JA,B 11.9 Hz, CH2Ph), 4.51 (d, 1H,
J
A,B 11.9 Hz, CH2Ph), 4.19 (dd, 1H, H-30), 4.09 (dd, 1H, H-20), 3.94 (dd, 1H,
H-50b), 3.65 (dd, 1H, H-50a), 3.60 (ddd, 1H, H-40), ppm. J1 ,2 ¼ 6.8, J2 ,3 ¼ 3.4,
0
0
0
0
0
0
0
0
0
0
0
0
J3 ,4 ¼ 4.4, J4 ,5 a ¼ 6.9, J4 ,5 b ¼ 6.7, J5 a,5 b ¼ 8.8, J5,6 ¼ 8.3, J5,NH ¼ 2.4 Hz;
13C NMR (101 MHz, CDCl3): a-5: d ¼ 162.1 (C-4), 149.9 (C-2), 139.9 (C-6),
137.4 (Carom), 137.3, 136.4, 128.3 (CHarom), 128.04, 127.98, 127.9, 127.59,
127.55, 127.49, 127.45, 127.42, 102.4 (C-5), 84.4 (C-20), 75.7 (C-30), 73.4
(CH2Ph), 73.1, 72.0, 69.0 (C-50), 62.3 (C-10), 46.4 (C-40) ppm. b-5: d ¼ 162.8
(C-4), 151.1 (C-2), 144.2 (C-6), 137.2 (Carom), 136.9, 136.7, 128.14 (CHarom),
128.06, 128.02, 127.8, 127.71, 127.65, 127.5, 127.2, 100.2 (C-5), 82.2 (C-20),
79.3 (C-30), 73.8 (CH2Ph), 73.1, 73.0, 68.6 (C-50), 58.4 (C-10), 46.3 (C-40) ppm;
FAB MS: a-5: m=z: 531 [MþH]; b-5: m=z: 531 [MþH]; C30H30N2O5S
(530.65): calcd C 67.90, H 5.70, N 5.28, S 6.04; a-5: found C 67.32, H
5.77, N 5.02, S 5.93; b-5: found C 67.48, H 5.45, N 5.12, S 6.28.
1-(2,3,5-Tri-O-benzyl-4-thio-L-lyxofuranosyl)thymine (6) was prepared
as described for 5 from 4 (580 mg, 1.21 mmol), 2,4-bis-O-(trimethylsilyl)
thymine15 (780 mg, 2.88 mmol), molecular sieves A4 (60 mg), TMSOTf
(0.70 mL, 861 mg, 3.87 mmol) and MeCN (20 mL). After chromatographic
work-up (petroleum ether-EtOAc 1:1, Rf ¼ 0.28) 6 was obtained as an
inseparable anomeric mixture (450 mg, 68%) with an a:b ratio of 2:1
(white solid). IR (KBr): n ¼ 3184, 3061, 3031, 2924, 2859, 1686, 1495, 1455,

1636
WIRSCHING ET AL.
1367, 1308, 1265, 1208, 1133, 1085, 1026, 909, 818, 739, 699, 544, 475 cmÀ1;
1H NMR (400 MHz, CDCl3): a-6: d ¼ 8.66 (ws, 1H, NH), 7.27À7.38 (m,
15H, CHarom), 7.00 (q, 1H, H-6), 6.30 (d, 1H, H-10), 4.88, (d, 1H, JA,B
11.7 Hz, CH2Ph) 4.68 (d, 1H, JAB 11.7 Hz, CH2Ph), 4.50 (s, 2H, CH2Ph), 4.66
(d, 1H, JA,B 12.6Hz, CH2Ph), 4.26(d, 1H, JAB ¼ 12.6Hz, CH2Ph), 4.24À4.25
(m, 1H, H-30), 3.83À3.89 (m, 3H, H-20, H-40, H-50b), 3.51À3.57 (m, 1H, H-
5a0 ), 1.75 (d, 3H, CH3) ppm. J1 ,2 ¼ 8.2, J6,Me ¼ 1.2 Hz; b-6: d ¼ 8.72 (ws, 1H,
NH), 7.90 (q, 1H, H-6), 7.27À7.38 (m, 15H, CHarom), 6.45 (d, 1H, H-10), 4.77
(d, 1H, JA,B 10.7 Hz, CH2Ph), 4.57 (d, 1H, JAB ¼ 10.7 Hz, CH2Ph),
4.55À4.67 (m, 4H, CH2Ph), 4.21 (dd, 1H, H-30), 4.10 (dd, 1H, H-20), 4.01
(dd, 1H, H-50b), 3.69 (dd, 1H, H-50a), 3.62 (ddd, 1H, H-40), 1.50 (d, 3H, CH3),
0
0
0
0
0
0
0
0
0
0
0
0
ppm.
J1 ,2 ¼ 7.0, J2 ,3 ¼ 3.5, J3 ,4 ¼ 4.5, J4 ,5 a ¼ 6.8, J4 ,5 b ¼ 7.1,
J5 a,5 b ¼ 9.1, J6,Me ¼ 1.2 Hz; 13C NMR (101 MHz, CDCl3): a-6: d ¼ 163.3
(C-4), 150.6(C-2), 137.9 (C arom), 137.7, 136.9, 135.9 (C-6), 128.6 (CHarom),
128.51, 128.46, 128.4, 128.1, 128.0, 127.9, 127.8, 127.6, 111.3 (C-5), 84.7 (C-
20), 75.8 (C-30), 73.9 (CH2Ph), 73.5, 72.2, 69.4 (C-50), 62.1 (C-10), 46.7 (C40),
12.5 (CH3) ppm; b-6: d ¼ 163.8 (C-4), 151.6 (C-2), 140.3 (C-6), 137.7 (Carom),
137.5, 137.3, 128.5 (CHarom), 128.46, 128.34, 128.26, 128.13, 128.05, 128.0,
127.9, 127.8, 109.0 (C-5), 82.9 (C-20), 79.7 (C-30), 74.5 (CH2Ph), 73.5, 73.4,
69.0 (C-50), 58.5 (C-10), 46.5 (C-40), 12.1 (CH3) ppm; FAB MS: m=z: 545
[MþH]; C31H32N2O5S (544.68): calcd C 68.36, H 5.92, N 5. 14, S 5.89; found
C 67.4423, H 5.91, N 4.87, S 5.79.
0
0
6-Methyl-1-(2,3,5-tri-O-benzyl-4-thio-L-lyxofuranosyl)uracil
(7) was
prepared as described for 5 from 4 (600 mg, 1.25 mmol), 6-methyl-2,4-bis-
O-(trimethylsilyl)uracil16 (1.36g, 5.03 mmol), molecular sieves A4 (75 mg),
TMSOTf (0.71 mL, 873 mg, 3.93 mmol) and MeCN (15 mL).
After chromatographic work-up (petroleum ether-EtOAc 1:1, Rf, b ¼ 0.37,
Rf,a ¼ 0.29) the separated anomers a-7 (497 mg, 73%) and b-7 (51 mg, 7%)
20
were obtained as white solids. a-7: M.p. 90À92 ꢀC; ½aꢁ ¼ À 106.9 (c ¼ 1.0 in
D
20
CHCl3); b-7: M.p. 82À84 ꢀC; ½aꢁD ¼ À 89.7 (c ¼ 1.0 in CHCl3); IR (KBr): a-
7: n ¼ 3192 (N-H), 3087, 3061, 3030, 2922, 2860, 1693 (C¼O), 1496, 1454,
1370, 1237, 1205, 1126, 1072, 1027, 821, 738, 699, 600, 536, 495, 416 cmÀ1; b-
7: n ¼ 3190 (N-H), 3087, 3061, 3031, 2925, 2859, 1679 (C¼O), 1496, 1455,
1394, 1353, 1207, 1153, 1101, 1047, 1026, 911, 822, 737, 699, 650, 616, 541,
1
513, 428 cmÀ1; H NMR (500 MHz, CDCl3): a-7: d ¼ 8.64 (ws, 1H, NH),
7.26À7.38 (m, 15H, CHarom), 5.72 (s, 1H, H-10), 5.48 (ws, 1H, H-5), 5.05 (d,
1H, H-20), 4.87 (d, 1H, JA,B 11.8 Hz, CH2Ph), 4.70 (d, 1H, JA,B 11.8 Hz,
CH2Ph), 4.58 (d, 1H, JA,B 12.2 Hz, CH2Ph), 4.48 (s, 2H, CH2Ph), 4.30 (dd,
1H, H-30), 4.23 (d, 1H, JA,B 12.2 Hz, CH2Ph), 4.12À4.15 (m, 1H, H-40), 3.79
(dd, 1H, H-50b), 3.50 (dd, 1H, H-5a0 ), 2.22 (ws, 3H, CH3) ppm. J1 ,2 ¼ 0,
0
0
0
0
0
0
0
0
0
0
0
0
J2 ,3 ¼ 2.9, J3 ,4 ¼ 2.9, J4 ,5 a ¼ 6.2, J4 ,5 b ¼ 8.8, J5 a,5 b ¼ 9.1 Hz; b-7: d ¼ 9.01
(ws, 1H, NH), 7.26À7.39 (m, 15H, CHarom), 6.73 (d, 1H, H-10), 5.43 (ws, 1H,

THIOSUGARS. VIII
1637
H-5), 4.75 (d, 1H, JA,B 11.5 Hz CH2Ph), 4.67 (d, 1H, JA,B 11.8 Hz, CH2Ph),
4.60 (d, 1H, JA,B 11.8 Hz, CH2Ph), 4.57 (d, 1H, JA,B 12.0 Hz, CH2Ph) 4.48 (d,
1H, JA,B 12.0 Hz, CH2Ph), 4.43 (d, 1H, JA,B 11.5 Hz, CH2Ph), 4.27 (dd, 1H,
H-20), 4.20 (dd, 1H, H-30), 4.01À4.05 (m, 2H, H-5a0 , H-50b), 3.81 (ddd, 1H, H-
40), 2.58 (d, 3H, CH3) ppm. J1 ,2 ¼ 5.5, J2 ,3 ¼ 3.6, J3 ,4 ¼ 7.0, J4 ,5 a ¼ 6.0,
0
0
0
0
0
0
0
0
J4 ,5 b ¼ 7.2, J5,Me ¼ 0.6 ¼ Hz; 13C NMR (126 ¼ MHz, CDCl3): a-7: d ¼ 162.3
(C-4), 154.0 (C-6), 149.7 (C-2), 138.3 (Carom), 137.8, 137.4, 128.6(CH arom),
128.43, 128.35, 128.24, 128.20, 128.1, 127.84, 127.81, 127.80, 103.1 (C-5), 83.1
(C-20), 77.2 (C-30), 74.2 (CH2Ph), 73.3, 73.1, 68.3 (C-50), 64.5 (C-10), 48.3
(C40), 21.0 (CH3) ppm; b-7: d ¼ 161.9 (C-4), 157.7 (C-6), 152.4 (C-2), 138.0
(Carom), 137.3, 137.0, 128.6(CH arom), 128.5, 128.4, 128.3, 128.2, 128.1, 127.9,
127.7, 127.5, 104.0 (C-5), 81.4 (C-20), 79.4 (C-30), 74.9 (CH2Ph), 73.3, 72.7,
69.6 (C-50), 58.0 (C-10), 49.4 (C-40), 23.8 (CH3) ppm; FAB MS: a-7: m=z: 545
[MþH]; b-7: m=z: 545 [MþH]; FAB HRMS: C31H33N2O5S: calcd 545.2110;
a-7: found 545.2103; b-7: found 545.2114.
0
0
5,6-Dimethyl-(2,3,5-tri-O-benzyl-4-thio-a,L-lyxofuranosyl)uracil
(8)
was prepared as described for 5 from 4 (600 mg, 1.25 mmol), 5,6-dimethyl-
2,4-bis-O-(trimethylsilyl)uracil16 (1.42 g, 4.99 mmol), molecular sieves A4
(70 mg), TMSOTf (0.71 mL, 873 mg, 3.93 mmol) and MeCN (15 mL). After
chromatographic work-up (petroleum ether-EtOAc 1:1, Rf ¼ 0.36) only the
a-anomer of 8 could be isolated (488 mg, 70%) as a white solid. M.p. 64 ꢀC;
20
½aꢁD ¼ À70.8 (c ¼ 1.0 in CHCl3); IR (KBr): n ¼ 3188 (N-H), 3086, 3060, 3030,
2926, 2865, 1676 (C¼O), 1496, 1455, 1343, 1307, 1125, 1073, 1027, 911, 819,
739, 699, 608, 504, 469 cmÀ 1; 1H NMR (500 MHz, CDCl3): d ¼ 8.57 (ws, 1H,
NH), 7.24À7.37 (m, 15H, CHarom), 5.80 (s, 1H, H-10), 5.12 (d, 1H, H-20), 4.88
(d, 1H, JA,B 11.8 Hz, CH2Ph), 4.70 (d, 1H, JA,B 11.8 Hz, CH2Ph), 4.59 (d, 1H,
J
A,B 12.3 Hz, CH2Ph), 4.48 (s, 2H, CH2Ph), 4.31 (dd, 1H, H-30), 4.25 (d, 1H,
JA,B 12.3 Hz, CH2Ph), 4.15 (ddd, 1H, H-40), 3.79 (dd, 1H, H-5b0 ), 3.49 (dd,
1H, H-50a), 2.20 (d, 3H, CH3), 1.92 (d, 3H, CH3) ppm. J1 ,2 ¼ 0, J2 ,3 ¼ 3.3,
0
0
0
0
J3 ,4 ¼ 2.9, J4 ,5 a ¼ 6.1, J4 ,5 b ¼ 8.4, J5 a,5 b ¼ 9.3 Hz; 13C NMR (126MHz,
CDCl3): d ¼ 163.0 (C-4), 149.4 (C-6), 148.8 (C-2), 138.4 (Carom), 137.9,
137.6, 128.5 (CHarom), 128.4, 128.3, 128.09, 128.08, 127.83, 127.77, 127.74,
108.9 (C-5), 83.6(C-2 0), 77.5 (C-30), 74.2 (CH2Ph), 73.2, 68.3 (C-50), 64.9 (C-
10), 48.2 (C-40), 17.1 (CH3), 11.5 ppm; FAB MS: m=z: 559 [MþH]; FAB
HRMS: C32H35N2O5S: calcd 559.2267; found 559.2375.
0
0
0
0
0
0
0
0
5-Iodo-6-methyl-1-(2,3,5-tri-O-benzyl-4-thio-a,L-lyxofuranosyl)uracil (9)
was prepared as described for 5 from 4 (591 mg, 1.23 mmol), 5-iodo-6-
methyl-2,4-bis-O-(trimethylsilyl)uracil16 (1.92 g, 4.83 mmol), TMSOTf
(0.71 mL, 873 mg, 3.93 mmol) and molecular sieves A4 (80 mg) in dry
MeCN (15 mL). The resulting crude product was recrystallised from
EtOAc to yield the pure a-anomer of 9 (437 mg, 53%) as colourless
20
needles. M.p. 162 ꢀC; ½aꢁ ¼ À79:8 (c ¼ 1.0 in CHCl3); IR (KBr): n ¼ 3207
D

1638
WIRSCHING ET AL.
(N-H), 3064, 3031, 2926, 2879, 2847, 2795, 1681 (C¼O), 1587, 1496, 1453,
1433, 1402, 1357, 1342, 1288, 1210, 1128, 1073, 1027, 1005, 909, 797, 747,
701, 652, 600, 568, 497, 411 cmÀ1; 1H NMR (500 MHz, CDCl3): d ¼ 8.39 (ws,
1H, NH), 7.13À7.38 (m, 15H, CHarom), 5.85 (s, 1H, H-10), 5.00 (bs, 1H, H-
20), 4.88 (d, 1H, JA,B 11.8 Hz, CH2Ph), 4.71 (d, 1H, JAB ¼ 11.8 Hz, CH2Ph),
4.61 (d, 1H, JA,B 11.8 Hz, CH2Ph), 4.48 (s, 2H, CH2Ph), 4.30 (dd, 1H, H-30),
4.17 (d, 1H, JAB ¼ 12.3 Hz, CH2Ph), 4.11À4.15 (m, 1H, H-40), 3.78 (dd, 1H,
H-50b), 3.49 (dd, 1H, H-5a0 ), 2.62 (s, 3H, CH3) ppm. J1 ,2 ¼ 0, J2 ,3 ¼ 3.2,
0
0
0
0
J3 ,4 ¼ 3.2, J4 ,5 a ¼ 6.2, J4 ,5 a ¼ 8.4, J5 a,5 b ¼ 9.2 Hz; 13C NMR (126MHz,
CDCl3): d ¼ 159.3 (C-4), 154.4, (C-2), 148.8 (C-6), 138.2 (Carom), 137.8,
137.4, 128.6(CH arom), 128.44, 128.39, 128.37, 128.2, 128.1, 127.9, 127.8,
83.5 (C-20), 76.8À77.3 (C-30, C-5; the peaks of both carbon atoms were
covered by the solvent. Their position could be determined by an HMBC
measurement.), 74.3 (CH2Ph), 73.28, 73.27, 68.2 (C-50), 67.8 (C-10), 48.5 (C-
40), 26.5 (CH3) ppm; FAB MS: m=z: 671 [MþH]; FAB HRMS: calcd
671.1077; found 671.1343; C31H31IN2O5S (670.57): calcd C 55.53, H 4.66, I
18.92, N 4.18, S 4.78; found C 55.52, H 4.61, I 19.26, N 4.10, S 4.96.
0
0
0
0
0
0
0
0
5-Bromo-6-methyl-1-(2,3,5-tri-O-benzyl-4-thio-a,L-lyxofuranosyl)uracil
(10) was prepared as described for 5 from 4 (600 mg, 1.25 mmol), 5-bromo-
6-methyl-2,4-bis-O-(trimethylsilyl)uracil16 (1.74 g, 4.98 mmol), molecular
sieves A4 (60 mg) and TMSOTf (0.71 mL, 873 mg, 3.93 mmol) in dry
MeCN (15 ml). After recrystallisation of the crude product from EtOAc
the a-anomer of nucleoside 10 was obtained as colourless needles (430 mg,
20
55%). M.p. 175 ꢀC; ½aꢁD ¼ À97:6 (c ¼ 1.0 in CHCl3); IR (KBr): n ¼ 3203 (N-
H), 3064, 3030, 2947, 2929, 2866, 2797, 1692 (C¼O), 1598, 1496, 1454, 1439,
1402, 1356, 1341, 1290, 1256, 1209, 1162, 1129, 1074, 1026, 1006, 910, 795,
1
748, 700, 656, 600, 576, 497, 463, 412 cmÀ1. H NMR (500 MHz, CDCl3):
d ¼ 8.61 (ws, 1H, NH), 7.13À7.37 (m, 15H, CHarom), 5.80 (s, 1H, H-10), 5.01
(ws, 1H, H-20), 4.88 (d, 1H, JA,B 11.8 Hz, CH2Ph), 4.70 (d, 1H, JAB ¼ 11.8 Hz,
CH2Ph), 4.61 (d, 1H, JA,B 12.3 Hz, CH2Ph), 4.48 (s, 2H, CH2Ph), 4.30 (dd,
1H, H-30), 4.18 (d, 1H, JAB ¼ 12.3 Hz, CH2Ph), 4.11À4.16(m, 1H, H-4 0), 3.79
(dd, 1H, H-50b), 3.50 (dd, 1H, H-5a0 ), 2.49 (s, 3H, CH3) ppm. J1 ,2 ¼ 0,
0
0
J2 ,3 ¼ 3.1, J3 ,4 ¼ 3.1, J4 ,5 a ¼ 6.3, J4 ,5 b ¼ 8.3, J5 a,5 b ¼ 9.3 Hz. 13C NMR
(126MHz, CDCl 3): d ¼ 158.2 (C-4), 151.7 (C-2), 148.5 (C-6), 138.2 (Carom),
137.8, 137.4, 128.6(CH arom), 128.43, 128.37, 128.14, 128.08, 127.84, 127.80,
100.3 (C-5), 83.4 (C-20), 77.3 (C-30), 74.3 (CH2Ph), 73.28, 73.26, 68.2 (C-50),
66.5 (C-10), 48.5 (C-40), 21.2 (CH3) ppm. FAB MS: m=z: 625 [MþH, for 81Br],
623 [MþH, for 79Br]. C31H31BrN2O5S (623.58): calcd C 59.71, H 5.01, Br
12.81, N 4.49, S 5.14; found C 59.34, H 4.98, Br 12.61, N 4.39, S 5.19.
0
0
0
0
0
0
0
0
0
0
1-(4-Thio-L-lyxofuranosyl)uracil (11). Boron tribromide (0.21 mL,
554 mg, 2.21 mmol) was added into dry CH2Cl2 (2.10 mL) and cooled to
À90 ꢀC. A solution of 5 (250 mg, 0.47 mmol, a:b ¼ 1:2) in CH2Cl2 (3.20 mL)

THIOSUGARS. VIII
1639
was added dropwise under vigorous stirring. The temperature was kept below
À 80 ꢀC. After complete addition stirring was continued at À 90 ꢀC for 1 h.
Then the excess of boron tribromide was quenched at À 90 ꢀC by dropwise
adding a 1:1 mixture of CH2Cl2-MeOH (8 mL). After the solution had
warmed to room temperature silver carbonate (2.18 g, 7.91 mmol) was
added to neutralise the hydrobromic acid. After 0.5 h the inorganic salts
were filtered off, the solution was evaporated to dryness and the remaining
crude product was purified by silica gel chromatography (CHCl3-MeOH 4:1,
Rf,a ¼ 0.12, Rf,b ¼ 0.23), to yield a-11 (34 mg, 84%) and b-11 (14 mg, 17%) as
white solids. For further work up of the a-anomer it was purified by reversed
phase HPLC (MeCN-H2O 8:92) to yield a-11 as white solid (28 mg, 69%). b-
11 was recrystallised from water to yield colourless needles (11 mg, 13%). a-
20
11: M.p. 234 ꢀC; ½aꢁ ¼ À107:5 (c ¼ 1.0 in MeOH); b-11: M.p. 235À238 ꢀC;
D
20
½aꢁD ¼ À19:6 (c ¼ 1.0 in MeOH); IR (KBr): a-11: n ¼ 3449 (O-H), 3178 (N-
H), 3064, 2977, 2940, 2866, 2824, 1710 (C¼O), 1689 (C¼O), 1458, 1420,
1390, 1271, 1201, 1147, 1099, 1016, 980, 815, 757, 679, 630, 556, 538, 510,
407 cmÀ1; b-11: n ¼ 3416(O-H), 3055, 2930, 2883, 2824, 1688 (C ¼O), 1466,
1389, 1249, 1179, 1123, 1043, 808, 628, 556, 518, 420 cmÀ1; 1H NMR
(500 MHz, [D6]Me2SO): a-11: d ¼ 11.18 (ws, 1H, NH), 8.26(d, 1H, H-6),
6.11 (d, 1H, H-10), 5.58À5.60 (m, 2H, 20-OH, H-5), 5.47 (d, 1H, 30-OH), 4.92
0
(dd, 1H, 50-OH), 4.21 (ddd, 1H, H-20), 4.16(ddd, 1H, H-3 ), 3.87 (ddd, 1H,
H-50b), 3.60 (ddd, 1H, H-50a), 3.47 (ddd, 1H, H-40) ppm. J1 ,2 ¼ 7.0, J2 ,3 ¼ 3.7,
0
0
0
0
0
0
0
0
0
0
0
0
0
0
J2 ,OH ¼ 6.8, J3 ,4 ¼ 4.6, J3 ,OH ¼ 4.5, J4 ,5 a ¼ 7.7, J4 ,5 b ¼ 5.4, J5 a,5 b ¼ 10.8,
0
0
J5 a,OH ¼ 5.4, J5 b,OH ¼ 5.3, J5,6 ¼ 8.2 Hz; b-11: d ¼ 11.29 (ws, 1H, NH), 8.00
(d, 1H, H-6), 5.98 (d, 1H, H-10), 5.72 (d, 1H, H-5), 5.50 (d, 1H, 20-OH), 5.20
(d, 1H, 30-OH), 4.79 (dd, 1H, 50-OH), 4.23 (ddd, 1H, H-20), 4.10 (ddd, 1H, H-
30), 3.84 (ddd, 1H, H-40), 3.76(ddd, 1H, H- 5b0 ), 3.42 (ddd, 1H, H-50a) ppm.
0
0
0
0
0
0
0
0
0
0
J1 ,2 ¼ 9.1, J2 ,3 ¼ 3.4, J2 ,OH ¼ 6.3, J3 ,4 ¼ 3.4, J3 ,OH ¼ 3.9, J4 ,5 a ¼ 7.6,
J4 ,5 b ¼ 6.3, J5 a,5 b ¼ 10.7, J5 a,OH ¼ 5.8, J5 b,OH ¼ 4.8, J5,6 ¼ 8.1 Hz; 13C
NMR (126MHz, [D 6]Me2SO): a-11: d ¼ 163.6 (C-4), 151.8 (C-2), 145.3 (C-
6), 100.2 (C-5), 75.2 (C-20), 73.0 (C-30), 61.3 (C-50), 60.2 (C-10), 51.4 (C-40)
ppm; b-11: d ¼ 163.3 (C-4), 151.6 (C-2), 142.2 (C-6), 102.7 (C-5), 78.5 (C-20),
72.2 (C-30), 62.3 (C-10), 61.5 (C-50), 50.2 (C-40) ppm; MS (70 eV, EI): a-11:
m=z (%): 242 (56) [Mþ À H2O], 224 (19) [Mþ À 2H2O], 194 (67), 181 (9),
0
0
0
0
0
0
þ
151 (28), 131 (34) [C5H7O2Sþ], 113 (78), 112 (100) [C4H4N2O2 ], 85 (18), 57
(43), 42 (25); b-11: m=z (%): 242 (93) [Mþ À H2O], 211 (8), 194 (100), 183
þ
(16), 151 (39), 131 (45) [C5H7O2Sþ], 113 (67), 112 (77) [C4H4N2O2 ], 87 (21),
57 (48), 55 (22); HRMS: calcd 261.0545 (MþþH), 242.0361 (Mþ À H2O),
244.0256(M þ À 2H2O); a-11: found 261.0551, 242.0279, 224.0225; b-11:
found 261.0592, 224.0258.
1-(4-Thio-L-lyxofuranosyl)thymine (12) was prepared as described for
11 from 6 (500 mg, 0.92 mmol, a:b ¼ 2:1) in CH2Cl2 (6.33 mL), boron
tribromide (0.42 mL, 1.11g, 4.43 mmol) in CH2Cl2 (4.20 mL) and silver

1640
WIRSCHING ET AL.
carbonate (4.27 g, 15.49 mmol) to yield the separated anomers a-12 (45 mg,
26%) and b-12 (16mg, 19%) after chromatographic work-up (CHCl 3-MeOH
4:1, Rf,a ¼ 0.23, Rf,b ¼ 0.32). Further purification of the anomers was carried
out by reversed phase HPLC (MeCN-H2O 8:92) to give a-12 (38 mg, 23%)
and b-12 (13 mg, 15%) as white solids. The anomer a-12 could be crystallised
20
from water. a-12: M.p. 228 ꢀC, under decomposition; ½aꢁD ¼ À20:0 (c ¼ 1.0
20
in MeOH); b-12: M.p. 213 ꢀC; ½aꢁD ¼ À28:2 (c ¼ 0.5 in MeOH); IR (KBr): a-
12: n ¼ 3435 (O-H), 2926, 2856, 1750 (C¼O), 1688 (C¼O), 1473, 1384,
1233, 1121, 1040, 977, 901, 838, 779, 671, 601, 464 cmÀ1; b-12: n ¼ 3476(O-
H), 3227 (N-H), 2993, 2934, 2905, 2881, 2821, 1695 (C¼O), 1465, 1423, 1377,
1
1334, 1252, 1226, 1200, 1116, 1044, 1020, 896, 772, 654, 541, 425 cmÀ1; H
NMR (500 MHz, [D6]Me2SO): a-12: d ¼ 11.17 (ws, 1H, NH), 8.14 (q, 1H, H-
6), 6.12 (d, 1H, H-10), 5.57 (d, 1H, 20-OH), 5.45 (d, 1H, 30-OH), 4.95 (dd, 1H,
50-OH), 4.19 (ddd, 1H, H-20), 4.16(ddd, 1H, H-3 0), 3.88 (ddd, 1H, H-50b), 3.63
(ddd, 1H, H-50a), 3.47 (ddd, 1H, H-40), 1.77 (d, 3H, CH3) ppm. J1 ,2 ¼ 7.0,
0
0
0
0
0
0
0
0
0
0
0
0
J2 ,3 ¼ 3.6, J2 ,OH ¼ 6.4, J3 ,4 ¼ 4.8, J3 ,OH ¼ 4.3, J4 ,5 a ¼ 7.6, J4 ,5 b ¼ 5.4,
0
0
0
0
J5 a,5 b ¼ 10.9, J5 a,OH ¼ 5.8, J5 b,OH ¼ 5.2, J6,Me ¼ 1.2 Hz; b-12: d ¼ 11.20 (ws,
1H, NH), 7.80 (q, 1H, H-6), 5.92 (d, 1H, H-10), 5.38 (d, 1H, 20-OH), 5.11 (d,
1H, 30-OH), 4.71 (dd, 1H, 50-OH), 4.19 (ddd, 1H, H-20), 4.03 (ddd, 1H, H-30),
3.78 (ddd, 1H, H-40), 3.70 (ddd, 1H, H-5b0 ), 3.35 (ddd, 1H, H-50a), 1.76(d, 3H,
0
0
0
0
0
0
0
0
CH3) ppm. J1 ,2 ¼ 9.1, J2 ,3 ¼ 3.4, J2 ,OH ¼ 6.4, J3 ,4 ¼ 3.2, J3 ,OH ¼ 3.9,
0
0
0
0
0
0
0
0
J4 ,5 a ¼ 7.6, J4 ,5 b ¼ 6.2, J5 a,5 b ¼ 10.7, J5 a,OH ¼ 5.8, J5 b,OH ¼ 4.8, J6,Me
¼
1.2 Hz; 13C NMR (126MHz, [D 6]Me2SO): a-12: d ¼ 163.2 (C-4), 150.9 (C-
2), 140.2 (C-6), 106.3 (C-5), 74.2 (C-20), 72.1 (C-30), 60.3 (C-50), 59.0 (C-10),
50.5 (C-40), 11.9 (CH3) ppm; b-12: d ¼ 163.3 (C-4), 151.0 (C-2), 136.9 (C-6),
109.8 (C-5), 77.7 (C-20), 71.6(C-3 ), 61.5 (C-50), 60.9 (C-10), 49.6(C-4 ), 11.9
(CH3), ppm; MS (70 eV, EI): a-12: m=z (%): 274 (7) [Mþ], 256(100)
[Mþ À H2O], 208 (42), 205 (7), 171 (12), 165 (11), 131 (88) [C5H7O2Sþ], 126
0
0
þ
(94) [C5H6N2O2 ], 101 (31), 83 (26), 57 (70), 40 (100); b-12: m=z (%): 274 (1)
[Mþ], 256(85) [M þ À H2O], 238 (20) [Mþ À 2H2O], 208 (47), 205 (7), 171 (14),
165 (10), 131 (100) [C5H7O2Sþ], 126(53) [C H6N2O2 ], 101 (38), 85 (26), 57
þ
5
(68), 55 (26); HRMS: calcd 274.0623 (Mþ), 256.0518 (Mþ À H2O), 238.0412
(Mþ À 2H2O); a-12: found 274.0605, 256.0515; b-12: found 256.0527,
238.0413.
6-Methyl-1-(4-thio-L-lyxofuranosyl)uracil (13) was prepared as
described for 11 from 7 (518 mg, 0.95 mmol, a:b ¼ 10:1) in CH2Cl2
(6.20 mL), boron tribromide (0.46 mL, 1.21 g, 4.85 mmol) in CH2Cl2
(4.60 mL) and silver carbonate (4.95 g, 17.95 mmol) to yield after
chromatographic work-up (CHCl3-MeOH 4:1, Rf,a,b ¼ 0.21) the
unseparated anomers of 13 (74 mg, 28%). Separation of these was carried
out by reversed phase HPLC (MeCN-H2O 7:93) to yield a-13 (49 mg, 21%)
and b-13 (3 mg, 13%) as white solids, whereas a-13 could be crystallised from
water to give colourless needles. a-13: M.p. 244 ꢀC, under decomposition;

THIOSUGARS. VIII
1641
20
½aꢁD ¼ À56:0 (c ¼ 1.0 in MeOH); b-13: M.p. 206 ꢀC, under decomposition;
20
D
½aꢁ ¼ À1:4 (c ¼ 0.3 in MeOH); IR (KBr): a-13: n ¼ 3456(O-H), 3225 (N-H),
3029, 2935, 2872, 2797, 1697 (C¼O), 1664 (C¼O), 1474, 1407, 1388, 1237,
1193, 1131, 1096, 1049, 1018, 888, 857, 816, 765, 681, 540, 503 cmÀ1; b-13:
n ¼ 3454 (O-H), 3223 (N-H), 3083, 2934, 2872, 2796, 1697 (C¼O), 1665
(C¼O), 1474, 1406, 1387, 1336, 1191, 1132, 1096, 1049, 1018, 937, 888, 816,
1
764, 681, 540, 503 cmÀ1; H NMR (500 MHz, [D6]Me2SO): a-13: d ¼ 11.20
(ws, 1H, NH), 5.54 (s, 1H, H-5), 5.51 (ws, 1H, H-10), 5.34 (d, 1H, 20-OH),
5.09 (d, 1H, 30-OH), 4.99 (ws, 1H, H-20), 4.74 (dd, 1H, 50-OH), 4.09 (ddd, 1H,
H-30), 3.80 (ddd, 1H, H-40), 3.76(ddd, 1H, H- 5b0 ), 3.43 (ddd, 1H, H-50a), 2.22
0
0
0
0
0
0
0
0
(ws, 3H, CH3) ppm. J1 ,2 ¼ 0, J2 ,3 ¼ 3.9, J2 ,OH ¼ 7.6, J3 ,4 ¼ 2.8, J3 ,OH ¼ 4.2,
0
0
0
0
0
0
0
0
J4 ,5 a ¼ 6.9, J4 ,5 b ¼ 6.5, J5 a,5 b ¼ 10.3, J5 a,OH ¼ 5.8, J5 b,OH ¼ 4.9 Hz; b-13:
d ¼ 11.35 (ws, 1H, NH), 5.95 (d, 1H, H-10), 5.61À5.64 (m, 2H, H-5, 30-
OH), 5.45 (d, 1H, 20-OH), 4.81 (dd, 1H, 50-OH), 4.34 (ddd, 1H, H-20), 4.04
(ddd, 1H, H-30), 3.91 (ddd, 1H, H-5b0 ), 3.58 (ddd, 1H, H-50a), 3.45 (ddd, 1H,
H-40), 2.34 (s, 3H, CH3) ppm. J1 ,2 ¼ 8.5, J2 ,3 ¼ 4.7, J2 ,OH ¼ 5.4, J3 ,4 ¼ 2.8,
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
J3 ,OH ¼ 4.7, J4 ,5 a ¼ 7.7, J4 ,5 b ¼ 5.8, J5 a,5 b ¼ 10.6, J5 a,OH ¼ 5.4, J5 b,OH
¼
4.9 Hz; 13C NMR (126MHz, [D 6]Me2SO): a-13: d ¼ 162.7 (C-4), 154.7 (C-
6), 149.2 (C-2), 105.7 (C-5), 76.2 (C-20), 72.8 (C-30), 66.2 (C-10), 61.0 (C-50),
52.4 (C-40), 20.6(CH ) ppm; b-13: d ¼ 164.3 (C-4), 157.5 (C-6), 154.3 (C-2),
3
105.3 (C-5), 77.7 (C-20), 74.8 (C-30), 63.3 (C-10), 62.9 (C-50), 54.0 (C-40), 23.4
(CH3) ppm; MS (70 eV, EI): a-13: m=z (%): 274 (0.3) [Mþ], 256(1) [M þ À
H2O], 238 (10) [Mþ À 2H2O], 208 (8), 165 (5), 131 (19) [C5H7O2Sþ], 126(70)
þ
[C5H6N2O2 ], 101 (16), 83 (36), 68 (44), 57 (50), 42 (100); b-13: m=z (%): 274
(3) [Mþ], 256(6) [M þ À H2O], 238 (38) [Mþ À 2H2O], 208 (18), 182 (5), 165
þ
(8), 131 (35) [C5H7O2Sþ], 126(100) [C H6N2O2 ], 100 (24), 83 (42), 57 (37),
5
42 (57); HRMS: calcd 275.0702 (MþþH), 274.0623 (Mþ), 256.0518
(Mþ À H2O), 238.0412 (Mþ À 2H2O); a-13: found 256.0503, 238.0408; b-13:
found 275.0671, 274.0665, 256.0480, 238.0407.
5,6-Dimethyl-1-(4-thio-a,L-lyxofuranosyl)uracil (14) was prepared as
described for 11 from 8 (478 mg, 0.86mmol) in CH 2Cl2 (6.0 mL), boron
tribromide (0.41 mL, 1.08 g, 4.32 mmol) in CH2Cl2 (4.10 mL) and silver
carbonate (4.48 g, 16.25 mmol) to yield after chromatographic work-up
(CHCl3-MeOH 4:1, Rf ¼ 0.23) and crystallisation from H2O-MeOH
nucleoside 14 (17 mg, 7%) as colourless needles, which decomposed at
20
241 ꢀC without melting. ½aꢁD ¼ À62:2 (c ¼ 1.0, MeOH); IR (KBr): n ¼ 3422
(O-H), 3172 (N-H), 2928, 2822, 1713 (C¼O), 1661 (C¼O), 1479, 1419, 1350,
1309, 1276, 1178, 1120, 1075, 1046, 1019, 936, 860, 789, 717, 608, 506,
1
473 cmÀ1; H NMR (500 MHz, [D6]Me2SO): d ¼ 11.22 (ws, 1H, NH), 5.50
(ws, 1H, H-10), 5.29 (d, 1H, 20-OH), 5.06(d, 1H, 3 0-OH), 5.04 (ws, 1H, H-20),
4.72 (dd, 1H, 50-OH), 4.08À4.10 (m, 1H, H-30), 3.74À3.82 (m, 2H, H-40,
H-50b), 3.43 (ddd, 1H, H-5a0 ), 2.23 (s, 3H, CH3), 1.83 (s, 3H, CH3) ppm.
0
0
0
0
0
0
0
0
0
J1 ,2 ¼ 0, J2 ,OH ¼ 7.5, J3 ,OH ¼ 3.2, J4 ,5 a ¼ 7.0, J5 a,5 b ¼ 10.8, J5 a,OH ¼ 5.7,

1642
WIRSCHING ET AL.
J5 b,OH ¼ 5.3 Hz; 13C NMR (126MHz, [D 6]Me2SO): d ¼ 162.9 (C-4), 150.2
0
(C-2), 149.8 (C-6), 107.9 (C-5), 76.6 (C-20), 73.1 (C-30), 61.3 (C-50), 59.3 (C-
0
10), 52.6(C-4 ), 17.6(CH ), 11.7 (CH3) ppm; MS (70 eV, EI): m=z (%): 288
(1) [Mþ], 270 (12) [Mþ À3H2O], 252 (6) [Mþ À 2H2O], 222 (15), 196(7), 140
(100), 113 (10), 101 (23), 85 (20), 57 (88), 42 (35); HRMS: calcd 270.0674
(Mþ À H2O), 252.0569 (Mþ À 2H2O); found 270.0675, 252.0562.
5-Iodo-6-methyl-1-(4-thio-a,L-lyxofuranosyl)uracil (15) was prepared
as described for 11 from 9 (369 mg, 0.55 mmol) in dry CH2Cl2 (3.51 mL)
and boron tribromide (0.27 mL, 713 mg, 2.85 mmol) in dry CH2Cl2
(2.70 mL). After neutralisation with Ag2CO3 (2.93 g, 10.63 mmol) and
chromatographic work-up (CHCl3-MeOH 4:1, Rf ¼ 0.26) 15 was obtained
as pale brown solid (19 mg, 9%). Recrystallisation from MeOH yielded pure
15 (12 mg, 5%) as white solid, which decomposes at 211 ꢀC without
20
melting; ½aꢁ ¼ À16:8 (c ¼ 0.5 in MeOH); IR (KBr): n ¼ 3458, 3172, 2924,
D
2853, 1712, 1667, 1584, 1448, 1411, 1305, 1165, 1117, 1072, 1049, 1018, 935,
864, 751, 656, 573, 501 cmÀ1; 1H NMR (400 MHz, [D6]Me2SO): d ¼ 11.88 (bs,
1H, NH), 5.85 (bs, 1H, H-10), 5.60 (d, 1H, 20-OH), 5.33 (d, 1H, 30-OH), 5.14
(bs, 1H, H-20), 4.98 (dd, 1H, 50-OH), 4.28 (ddd, 1H, H-30), 3.92À4.01 (m, 2H,
H-40, H-5b0 ), 3.61À3.64 (m, 1H, H-5a0 ; covered by H2O), 2.84 (s, 3H, CH3)
0
0
0
0
0
0
0
0
ppm. J1 ,2 ¼ 0, J2 ,3 ¼ 3.3 or 4.3, J2 ,OH ¼ 7.2, J3 ,4 ¼ 3.3 or 4.3, J3 ,OH ¼ 3.8,
J5 a,OH ¼ 5.0, J5 b,OH ¼ 5.0 Hz; 13C NMR (101 MHz, [D6]Me2SO): d ¼ 160.5
(C-4), 155.2 (C-2), 149.6 (C-6), 77.8 (C-5), 76.5 (C-20), 72.7 (C-30), 61.0 (2C,
C-10, C-50), 52.5 (C-40), 26.6 (CH3) ppm; MS (70 eV, EI): m=z (%): 252 (7)
0
0
þ
[C5H5IN2O2 ], 131 (16) [C5H7O2Sþ], 97 (33), 69 (60), 44 (100).
5-Bromo-6-methyl-1-(4-thio-a,L-lyxofuranosyl)uracil (16). A solution
of sodium (1 mg, 0.04 mmol) in dry MeOH (3.0 mL) and a solution of 18
(77 mg, 0.16mmol) in dry MeOH (3.0 mL) were mixed and stirred for 24 h at
room temperature. After addition of water (1.0 mL), the solution was
evaporated to dryness and the residue was purified by column
chromatography (Sephadex LH 20, MeOH). The resulting pale red solid
was recrystallised from MeOH to give the unprotected nucleoside 16 (4 mg,
7%) as white solid, which decomposes at 186 ꢀC without melting;
20
D
½aꢁ ¼ À9:6 (c ¼ 0.2 in MeOH); IR (KBr): n ¼ 3448 (O-H), 3258, 3173 (N-
H), 2925, 2855, 2822, 1716(C ¼O), 1674 (C¼O), 1594, 1454, 1417, 1344,
1
1304, 1243, 1167, 1117, 1074, 1052, 938, 867, 733, 659, 582, 501 cmÀ1; H
NMR (500 MHz, [D6]Me2SO): d ¼ 8.61 (ws, 1H, NH), 5.63 (s, 1H, H-10), 5.38
(ws, 1H, 20-OH), 5.11 (ws, 1H, 30-OH), 4.95 (ws, 1H, H-20), 4.75 (dd, 1H, 50-
OH), 4.10 (ddd, 1H, H-30), 3.75À3.82 (m, 2H, H-40, H-50b), 3.44 (ddd, 1H,
H-50a), 2.42 (s, 3H, CH3) ppm. J1 ,2 ¼ 0, J2 ,3 ¼ 3.0, J3 ,4 ¼ 3.0, J3 ,OH ¼ 3.0,
0
0
0
0
0
0
0
J4 ,5 a ¼ 6.7, J5 a,5 b ¼ 10.4, J5 a,OH ¼ 5.3, J5 b,OH ¼ 5.1 Hz; 13C NMR
(126MHz, [D 6]Me2SO): d ¼ 160.3 (C-4), 154.1, (C-2), 144.9 (C-6), 100.8
(C-5), 77.7 (C-20), 74.0 (C-30), 53.8 (C-40), 22.7 (CH3) ppm. Because of
0
0
0
0
0
0

THIOSUGARS. VIII
1643
dynamic effects it was not possible to detect the signal of C-10; MS (70 eV,
EI): m=z (%): 354 (0.2) [Mþ, for 81Br], 352 (0.2) [Mþ, for 79Br], 336(4)
[Mþ À H2O, for 81Br], 334 (4) [Mþ À H2O, for 79Br], 288 (6), 286 (6), 206 (97)
þ
þ
[C5H581BrN2O2 ], 204 (100) [C5H579BrN2O2 ], 163 (56), 161 (55), 131 (45)
[C5H7O2Sþ], 12þ0 (34), 83 (13), 57 (38), 42 (78); HRMS: calcd 205.9514
(C5H581BrN2O2 ), 203.9534 (C5H579BrN2O2 ); found 205.9508, 203.9529.
þ
Methyl 2,3,5-tri-O-acetyl-4-thio-L-lyxofuranoside(17) was prepared in
the same way as 11 from 4 (869 mg, 1.82 mmol) in dry CH2Cl2 (9.0 mL)
and boron tribromide (0.89 mL, 2.35 g, 9.38 mmol) in dry CH2Cl2
(8.90 mL). After quenching the reaction with CH2Cl2=MeOH 1:1,
neutralisation with barium carbonate (6.52 g, 33.04 mmol) and filtration
the residue was dissolved in dry pyridine (15.0 mL). Then acetic anhydride
(2.85 mL, 3.08 g, 30.17 mmol) was added and the solution was stirred at
room temperature for 24 h. After the reaction was completed sat. NaHCO3
solution was added and stirring was continued for another 0.5 h. Then the
solution was diluted with water and extracted with CHCl3. The organic
phase was separated, dried with Na2SO4, concentrated and the resulting
crude product was purified by silica gel chromatography (petroleum ether-
EtOAc 1:1, Rf,a ¼ 0.38, Rf,b ¼ 0.27) to give the minor anomer (99 mg, 18%)
and the major anomer (207 mg, 37%) of 17. Both anomers are colourless
20
syrups. Minor anomer: ½aꢁ ¼ À166:9 (c ¼ 1.0 in CHCl3); Major anomer:
D
20
½aꢁD ¼ þ143:3 (c ¼ 1.0 in CHCl3); IR (film): Minor anomer: n ¼ 2992, 2934,
2830, 1730 (C¼O), 1496, 1454, 1371, 1315, 1260, 1112, 1030, 893, 843, 812,
778, 702, 610 cmÀ1; Major anomer: n ¼ 2993, 2938, 2830, 1747 (C¼O), 1445,
1371, 1229, 1097, 878, 840, 787, 720, 661, 636, 603 cmÀ1; 1H NMR
(500 MHz, CDCl3): Minor anomer: d ¼ 5.60 (dd, 1H, H-3), 5.39 (dd, 2H,
H-2), 5.05 (d, 1H, H-1), 4.36(dd, 1H, H-5 ), 4.17 (dd, 1H, H-5a), 3.96(ddd,
b
1H, H-4), 3.36(s, 3H, OCH ), 2.12, 2.11, 2.05 (s, each 3H, COCH3), ppm.
3
J1,2 ¼ 3.7, J2,3 ¼ 3.7, J3,4 ¼ 6.3, J4,5a ¼ 7.3, J4,5b ¼ 7.2, J5a,5b ¼ 11.2 Hz; Major
anomer: d ¼ 5.79 (dd, 1H, H-3), 5.14À5.17 (m, 2H, H-1, H-2), 4.36(dd, 1H,
H-5b), 4.17 (dd, 1H, H-5a), 3.82 (ddd, 1H, H-4), 3.35 (s, 3H, OCH3), 2.12,
2.11, 2.03 (s, each 3H, COCH3) ppm. J2,3 ¼ 4.3, J3,4 ¼ 5.7, J4,5a ¼ 6.6,
J4,5b ¼ 8.6, J5a,5b ¼ 11.0 Hz; 13C NMR (126MHz, CDCl 3): Minor anomer:
d ¼ 170.93 (COCH3), 170.17, 170.07, 88.83 (C-1), 78.33 (C-2), 72.80 (C-3),
64.58 (C-5), 57.38 (OCH3), 43.11 (C-4), 20.82 (COCH3), 20.74, 20.62 ppm;
Major anomer: d ¼ 170.41 (COCH3), 170.10, 170.01, 87.35 (C-1), 75.27 (C-
2), 71.28 (C-3), 63.54 (C-5), 57.28 (OCH3), 43.12 (C-4), 20.75 (COCH3),
20.69 ppm; MS (70 eV, EI): Minor anomer: m=z (%): 246(7), 217 (6), 186
(48), 172 (49), 144 (56), 127 (76), 115 (33), 85 (27), 74 (33), 69 (26), 43 (100)
[C2H3Oþ]; Major anomer: m=z (%): 246(18), 186(34), 172 (68), 144 (63),
127 (49), 113 (32), 103 (19), 85 (21), 69 (28), 43 (100) [C2H3Oþ]; C12H18O7S
(306.34): calcd C 47.05, H 5.92, S 10.47; Major anomer: found C 46.87, H
6.03, S 9.46.

1644
WIRSCHING ET AL.
5-Bromo-6-methyl-1-(2,3,5-tri-O-acetyl-4-thio-a,L-lyxofuranosyl)uracil
(18) was prepared as described for 5 from 17 (176mg, 0.57 mmol), 5-
(780 mg, 2.23 mmol),
bromo-6-methyl-2,4-bis-O-(trimethylsilyl)uracil16
TMSOTf (0.38 mL, 467 mg, 2.10 mmol) and molecular sieves A4 (35 mg) in
dry MeCN (10 mL). After chromatographic work-up (petroleum ether-
EtOAc 1:2, Rf ¼ 0.22) the a-anomer of 18 could be isolated as a white
20
solid (82 mg, 30%). M.p. 75 ꢀC; ½aꢁD ¼ À51:3 (c ¼ 1.0 in CHCl3); IR (KBr):
n ¼ 3205 (N-H), 3044, 2936, 2816, 1748 (C¼O), 1703 (C¼O), 1596, 1443,
1
1402, 1373, 1231, 1046, 901, 769, 667, 593, 497 cmÀ1; H NMR (500 MHz,
0
CDCl3): d ¼ 9.14 (bs, 1H, NH), 6.28 (bs, 1H, H-20), 5.86(s, 1H, H-1 ), 5.84
(dd, 1H, H-30), 4.45À4.50 (m, 1H, H-40), 4.37 (dd, 1H, H-50b), 4.10 (dd, 1H,
H-50a), 2.57 (s, 3H, CH3), 2.18, 2.05, 2.04 (s, each 3H, COCH3) ppm. J1 ,2 ¼ 0,
0
0
J2 ,3 ¼ 3.7, J3 ,4 ¼ 3.7, J4 ,5 a ¼ 7.1, J4 ,5 b ¼ 7.6, J5 a,5 b ¼ 11.1 Hz; 13C NMR
(126MHz, CDCl 3): d ¼ 170.4 (COCH3), 169.8, 169.5, 158.2 (C-4), 150.4 (C-
2), 148.9 (C-6), 101.6 (C-5), 79.5 (C-20), 76.2 (C-30), 66.1 (C-10), 61.7 (C-50),
47.3 (C-40), 21.1 (COCH3), 20.8 (CH3), 20.7 (COCH3), 20.5 ppm; FAB MS:
m=z: 481 [MþH, for 81Br], 479 [MþH, for 79Br].
0
0
0
0
0
0
0
0
0
0
ACKNOWLEDGMENTS
The Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industrie and
the European Commission are gratefully acknowledged for their financial support.
We like to thank the Degussa-Hˇls AG for support of this work by supplying silver
carbonate. We also thank Prof. Dr. Chris Meier and Dipl.-Chem. Andreas Lomp,
University of Hamburg, for making their HPLC equipment available to us. We also
thank Mrs. Ann Absillis, Mrs. Anita Camps and Miss LiesVandenheurck for technical
assistance.
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Received November 2, 2000
Accepted February 26, 2001