Thiosugars. X. Novel nucleoside analogues derived from 4-thio-L-lyxofuranose

Article abstract of DOI:10.1081/NCN-120025236

1-O-Acetyl-2,3,5-tri-O-benzyl-4-thio-L-lyxofuranose 1 was transformed into O-benzyl- and O-acetyl-protected 1-(4-thio-L-lyxofuranosyl) nucleoside derivatives by use of the TMSOTf method. Debenzylation with boron tribromide or deacetylation with sodium methoxide yielded the corresponding pyrimidine (7-11, 17, 18, 26 and 27) and purine (29 and 34) nucleoside analogues. The anomeric configurations were determined by NMR spectroscopy and, in the case of the 5-halo- (7-9) and nitrouridine derivative 11 and the 6-methylcytidine derivative 27, by X-ray structural analyses. - The unprotected nucleosides were not anti-virically inhibitory at 250 μM.

Full text of DOI:10.1081/NCN-120025236

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Thiosugars. X. Novel Nucleoside Analogues Derived
from 4-Thio-L-lyxofuranose
Jörn Wirsching a , Jürgen Voss a e , Anja Giesler b , Jürgen Kopf b , Gunadi Adiwidjaja c , Jan
Balzarini d & Erik De Clercq d
a Institut für Organische, Chemie der Universität Hamburg, Hamburg, Germany
b Institut für Anorganische und Angewandte, Chemie der Universität Hamburg, Hamburg,
Germany
c Mineralogisch-Petrographisches Institut der Universität Hamburg, Hamburg, Germany
d Rega Institute for Medical Research, Catholic University of Leuven, Leuven, Belgium
e Institut für Organische, Chemie der Universität Hamburg, Martin-Luther-King-Platz 6,
20146, Hamburg, Germany
Published online: 31 Aug 2006.
To cite this article: Jörn Wirsching , Jürgen Voss , Anja Giesler , Jürgen Kopf , Gunadi Adiwidjaja , Jan Balzarini & Erik De
Clercq (2003): Thiosugars. X. Novel Nucleoside Analogues Derived from 4-Thio-L-lyxofuranose, Nucleosides, Nucleotides and
Nucleic Acids, 22:10, 1867-1897
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NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS
Vol. 22, No. 10, pp. 1867–1897, 2003
Thiosugars. X. Novel Nucleoside Analogues Derived
from 4-Thio-L-lyxofuranose#
1
Jorn Wirsching, Jurgen Voss, Anja Giesler, Jurgen Kopf,
1,
2
2
*
¨
¨
¨
Gunadi Adiwidjaja,3 Jan Balzarini,4
and Erik De Clercq4
2
1Institut fur Organische and Institut fur Anorganische und
¨
¨
Angewandte, Chemie der Universita¨t Hamburg,
Hamburg, Germany
3Mineralogisch-Petrographisches Institut der Universita¨t Hamburg,
Hamburg, Germany
4Rega Institute for Medical Research, Catholic University of Leuven,
Leuven, Belgium
ABSTRACT
1-O-Acetyl-2,3,5-tri-O-benzyl-4-thio-l-lyxofuranose 1 was transformed into O-
benzyl- and O-acetyl-protected 1-(4-thio-l-lyxofuranosyl) nucleoside derivatives
by use of the TMSOTf method. Debenzylation with boron tribromide or deace-
tylation with sodium methoxide yielded the corresponding pyrimidine (7–11, 17,
18, 26 and 27) and purine (29 and 34) nucleoside analogues. The anomeric
configurations were determined by NMR spectroscopy and, in the case of the
5-halo- (7–9) and nitrouridine derivative 11 and the 6-methylcytidine derivative
27, by X-ray structural analyses. – The unprotected nucleosides were not anti-
virically inhibitory at 250 mM.
#Part IX: Wirsching, J.; Voss, J.; Adiwidjaja, G.; Balzarini, J.; De Clercq, E. Bioorg. Med.
Chem. Lett. 2001, 11, 1049–1051.
*Correspondence: Jurgen Voss, Institut fur Organische, Chemie der Universita¨t Hamburg,
¨
¨
Martin-Luther-King-Platz 6, 20146 Hamburg, Germany; Fax: 49-40-42838-5592; E-mail:
voss@chemie.uni-hamburg.de.
1867
DOI: 10.1081/NCN-120025236
Copyright # 2003 by Marcel Dekker, Inc.
1525-7770 (Print); 1532-2335 (Online)
www.dekker.com

1868
Wirsching et al.
Key Words: Thiosugars; Nucleosides; 4-Thio-L-lyxofuranose; Configurations;
Biological tests; X-ray structure.
INTRODUCTION
In 1992, the synthesis of 20,30-dideoxy-30-thia-l-cytidine (3TC) was described
and its anti-HIV activity was discovered.[1] Unfortunately, monotherapy with 3TC
resulted in the rapid appearance of a highly resistant virus strain. The activity
and, in particular, the long-time efficacy of the well-known anti-HIV drug
30-azido-20,30-dideoxythymidine (AZT) was, however, significantly improved when
a combination of 3TC and AZT was applied.[2] Further combinations of drugs that
reduce retrovirus replication more effectively and delay the onset of drug resistance
are nevertheless urgently required.[2] Because 3TC exhibits the l-configuration in the
pentofuranose moiety, a variety of l-nucleoside analogues have been synthesized
and tested for antiviral and other biological activities.[3] It has also been reported
that, in certain cases, replacement of oxygen by sulfur led to marked changes in
the biochemical properties of the corresponding nucleosides.[3–6] This effect may be
due to a higher lipophilicity of the thionucleoside and hence an increase of its ability
to penetrate a cell. Accordingly, the 40-thio-l-pentofuranosyl nucleosides became
interesting targets of synthetic efforts.[6–10] In continuation of our comprehensive
investigations of 4-thiofuranosyl nucleosides,[11–14] we were particularly interested in
the synthesis and biological activities of derivatives with l-lyxo-,[12] and 20-deoxy-l-
threo-(‘‘20-deoxy-l-lyxo’’)[13] configurations, because these compounds apparently
exhibit the same configuration at C-20 and C-30 as the natural d-ribo- and 20-deoxy-d-
ribo-nucleosides. The first examples of the 4-thio-l-lyxo series which we prepared
proved to be biologically inactive.[12] We therefore present here the synthesis and
structural assignment of novel 40-thio-l-lyxo-nucleoside analogues which, in addition
to the unnatural sugar moiety, contain modified nucleobases. Results on biological
tests are also reported.
RESULTS AND DISCUSSION
1-O-Acetyl-2,3,5-tri-O-benzyl-4-thio-l-lyxofuranose (1),[12] which is prepared in
six steps from d-ribose[15,16] with an overall yield of 39%, has proved to be a useful
starting material for the synthesis of 40-thionucleosides with l-lyxo configuration.[12]
Coupling of 1 with silylated 5-halo- and 5-nitrouracil derivatives in the presence of
trimethylsilyl trifluoromethanesulfonate (TMSOTf)[17–20] yielded the benzyl-pro-
tected nucleosides 2–6 (Sch. 1). According to our experiences with the 40-thio-l-lyxo-
uridine analogue and its methyl derivatives[12] and to the results which we have
recently obtained in the corresponding l-arabino[11] and in the 20-deoxy-40-thio-l-
threo-(‘‘20-deoxy-40-thio-l-lyxo’’)[13] series we achieved the best results for these
syntheses by using four equivalents of the silylated bases. The total yields varied
between 69% and 84%. The benzyl-protected nucleosides 2–6 were obtained as
anomeric mixtures (Sch. 1). The anomers of 5 and 6 could be separated by column
chromatography (see Experimental Part).

Thiosugars. X
1869
Scheme 1.
Cleavage of the benzyl groups was carried out with boron tribromide.[18,21–23]
It was absolutely necessary to neutralize the reaction mixture carefully with silver
carbonate[24] after the quenching with methanol. Otherwise, the large amounts
of hydrobromic acid which are formed would produce hydrobromides of the
nucleobases. These cannot be chromatographed or even isolated in a definitely pure
form. After column chromatography, the complete series of the four homologous
5-halouracil nucleoside analogues 7–10 were obtained as anomeric mixtures in the
unprotected form with total yields between 16% and 36% (Sch. 1). Separation by
reversed phase HPLC led to the pure anomers of 7–10. The two anomers of 11 (total
yield 8%) were separated by fractionated crystallization from water. First b-11
crystallized as colorless sheets. After complete crystallization of the b-anomer a-11
crystallized from the mother liquid as small needles.
Coupling of 1 with silylated 2-thiouracil in the presence of TMSOTf yielded 41%
of the benzyl-protected 2-thio-40-uridine nucleoside 12. Analogously, the 6-methyl-2-
thio-40-thiouridine nucleoside 13 was obtained from 1 and silylated 6-methyl-2-
thiouracil with a yield of 78%. Both uridine derivatives were formed as 2:1 mixtures
of anomers, the assignment of which was not possible. Subsequent cleavage of the
benzyl protecting groups with boron tribromide did, however, not lead to the desired
nucleosides 17 and 18. Only a large quantity of inseparable decomposition products
was obtained. Therefore, we prepared 17 and 18 by an alternative route via the
acetyl-protected methyl 4-thiofuranoside 14.[12] Coupling of 14 with silylated
2-thiouracil and silylated 6-methyl-2-thiouracil yielded anomeric mixtures of the
acetyl-protected uridine derivatives 15 (44%) and 16 (23%) with anomeric ratios of

1870
Wirsching et al.
Scheme 2.
5:2 (15) and 2:1 (16). The anomers could not be separated and assigned. The cleavage
of the O-acetyl groups was achieved by reaction of 15 and 16 with sodium methoxide
(Sch. 2). Due to significant losses during the purification of the crude products by
column chromatography and reversed-phase HPLC, only the b-anomer of the
2-thio-40-thiouridine derivative 17 could be isolated with 10% yield. Also, only the
b-anomer of the 6-methyl-2-thio-40-thiouridine 18 was obtained with 24% yield
after HPLC (Sch. 2).
Since 17 and 18 did not form suitable single crystals for X-ray structural analyses
and, in addition, no NOE contacts in their NMR spectra could be detected, the
assignment of the configurations was not straightforward. However, the comparison
of all NMR data enabled a reasonable assignment to be reached (see: Configurations
and Conformations).
When we tried to prepare the 40-thiocytidine nucleoside 24 from 1 and 2,4-bis-
N,O-(trimethylsilyl)cytosine,[25] we did not obtain the expected coupling product.
Instead, the bicyclic oxazoline 19 was formed with 75% yield. This can be explained
by nucleophilic attack of the solvent acetonitrile at the glycosyl donor (Sch. 3).
Replacement of acetonitrile by dichloromethane was not helpful, with 90% of the
starting material 1 being recovered in this solvent. Following a second strategy,[26]
we transformed 20 into the 4-(1,2,4-triazole-1-yl)uridine derivative 22 as described
by Uenishi et al.[27] We improved Uenishi0s moderate yield of 22% to 82% by apply-
ing a 60-fold molar excess of 1,2,4-triazole instead of only 10 equivalents as reported

Thiosugars. X
1871
Scheme 3.
by Uenishi et al. The anomers of 22 (a=b ¼ 1:2) were separable by column chroma-
tography. Replacement of the triazolyl substituent with 25% aqueous ammonia
solution led to a 82% yield of 24 as a separable mixture of anomers (a=b ¼ 1:2).
Cleavage of the benzyl protecting groups was achieved, again with great losses, by
reaction of 24 with boron tribromide at ꢀ90ꢁC.[24] After reversed-phase HPLC, only
the a-anomer of 40-thiocytidine 26 could be isolated with 3% yield (Sch. 3). The
b-anomer of 26 was not obtained. Analogously, the reaction of 21 with triazole[26,27]
gave 68% of 23, which was then treated with ammonia to yield 25 (85%). Cleavage of
the benzyl groups of 25 and subsequent reversed-phase HPLC finally led to a very
low quantity (3%) of the unprotected 6-methyl-40-thiocytidine nucleoside 27 with
a-configration (Sch. 3). We could not increase this poor yield, despite making every
effort.[28] Nevertheless, other O-benzyl-40-thio-l-lyxo-pyrimidine nucleoside analo-
gues could be deprotected significantly more successfully[11,12] and the result was also
better for 7–10. The nucleoside 27 was crystallized from water-ethanol as colorless
needles, which were suitable for an X- ray structural analysis (cf. Fig. 1).
Coupling of the thiosugar 1 with adenine in the presence of TMSOTf gave the
adenosine 28 with a yield of 65% as a 2:1 (a=b) mixture of anomers. The reaction

1872
Wirsching et al.
Figure 1. ORTEP views of the X-ray diffraction structures of the 5-nitrouridine derivative
b-11 (top) and the 6-methylcytidine derivative 27 (bottom; with one molecule of crystal water)
with atom numbering; thermal ellipsoids are drawn at the 50% probability level.
of 28 with boron tribromide led to a mixture of the completely unprotected adeno-
sine analogue 29 (6%, a=b ¼ 2:1) and its 20-O-benzyl derivative 30 (19%). HPLC
separation gave the pure anomers a-29 and b-29 and, in addition, 30 which also
exhibits a-configuration (Sch. 4).

Thiosugars. X
1873
Scheme 4.
The inosine derivative 31 was obtained from 1, hypoxanthine and TMSOTf as
a 5:4 mixture of anomers with 67% yield. Reaction of 31 with boron tribromide
failed to yield the unprotected inosine 34. Instead, the 20-O-benzyl derivative 32
was formed and after chromatographic work-up 7% of pure a-32 were isolated.
Therefore, we synthesized 34 via the alternative route from the thiosugar 14. The first
step led to 33% acetyl-protected inosine 33. The predominant formation of the a-
anomer is due to neighboring group participation. Treatment of 33 with sodium
methoxide and reversed phase HPLC gave the inosine derivative 34 with 16% yield
(Sch. 5).
Configurations and Conformations
The starting glycosyl donors 1, 14, 20 and 21 were used as anomeric mixtures
with a=b ratios of 1:10 for 1, 1:2 for 20 and 10:1 for 21. The anomers of 14 (1:2)
could not be assigned. These ratios are not preserved during the formation of the
N-glycosides under SN1-conditions. They are different for the products 2–6, 12,
13, 19, 28 and 31. Moreover, the reaction of the acetate 14 to form 15, 16 and 33
is controlled by the formation of an intermediate acetoxonium ion. In fact, in the
case of 33 only the expected a-anomer was isolated. The deprotection of the O-ben-
zyl derivatives with a large excess of the Lewis-acid boron tribromide also changed
the ratios considerably because anomerisation can take place under these conditions.
A consistent discussion of the stereochemistry is not well possible since the isolated
yields are low in many cases. The anomeric ratios found in the products are thus not
indicative of the stereochemical course of the reaction.
Irrespective of this, the configuration of the final products, the unprotected
nucleoside analogues, could be determined. The assignment of the anomers of 7,
8, 9, 11 and 27 was unequivocal, as X-ray structural analyses of one or both anomers
could be performed. For illustration, the ORTEP plots of a-7, b-7, b-11 and 27 are

1874
Wirsching et al.
Scheme 5.
shown in Fig. 1 and 2. The molecular structures of 8 and 9 resemble very closely
those of the corresponding anomers of 7. The sugar moieties of a-7 and b-7 have
twisted conformations (2T3), whereas both anomers of the chloro and bromo deriva-
2
tives exhibit envelope conformations (a-8 and a-9: E3; b-8 and b-9: E ).[29] Intra-
molecular hydrogen bridges between the hydroxyl groups at C-20 and the oxygen at
C-30 are observed for b-7 (254 pm), b-8 (248 pm), a-9 (254 pm) and b-9 (253 pm),
which might contribute to the stabilization of the respective twisted or envelope con-
formations in the crystal. An envelope conformation (2E ) of the thiofuranose moiety
with an intramolecular OHꢂ ꢂ ꢂO hydrogen bond of 237 pm length between 20-OH
(H 222) and O-30 (O 23) results from the X-ray structure of b-11 (cf. Fig. 2).[29]
The sugar moiety of 27 exhibits the envelope conformation E3, which was also
observed for the 6-methyluridine derivative a-21.[12] In contrast to a-21, no intramo-
lecular hydrogen bond was found in compound 27 (cf. Fig. 1).[29]
The configurations of the remaining 4-thio-l-lyxofuranosyl nucleosides were
1
assigned on the basis of their H NMR spectra. Although no NOE contacts could
be detected in spite of intensive efforts, the sequences of the chemical shifts and,
0
0
in particular, the coupling constants J1 ,2 allowed reliable and convincing assign-
ments in most cases. The relevant NMR data of the new compounds are compiled
in Table 1. For comparison, four related 4-thio-l-lyxofuranosyl nucleosides with
established configuration[12] are included in Table 1.
Two structural types of nucleosides must be distinguished. The majority of com-
pounds do not exhibit a substituent in the 6-position of the nucleobase. The purine
nucleosides 29, 30, 32, and 34 can be classed with this group. The compounds 18 and
27, on the other hand, are 6-methyl derivatives, in which steric hindrance might influ-
ence the NMR parameters. In the first class of nucleosides, the chemical shifts d
of H-10 are larger for the a-anomers ( > 6 ppm) than for the b-anomers ( < 6 ppm).

Thiosugars. X
1875
Figure 2. ORTEP views of the X-ray diffraction structures of the 5-fluorouridine derivatives
a-7 (top) and b-7 (bottom) with atom numbering; thermal ellipsoids are drawn at the 50%
probability level.
The same order is observed for H-30. For all a-anomers, d(H-40) is smaller than
d(H-50), whereas for the b-anomers d(H-40) is larger than d(H-50). Without exception,
the coupling constants of the anomeric protons are found significantly smaller in the
0
0
0
0
a-series (Jl ,2 ¼ 6.6–7.2 Hz) than in the b-series (J1 ,2 ¼ 8.4–9.1 Hz). In addition,
the carbon-13 data allow some conclusions on the configurations. In all cases studied
the signals of the anomeric carbon atom C-10 and of the neighboring center C-20 are
shifted downfield by ca. 2 ppm and by ca. 3 ppm, respectively, in the b-anomers as
compared with the a-anomers. – As mentioned above, there is some doubt about
the configuration of the 2-thio-nucleoside 17. However, the chemical shift data
0
0
and, in particular, the coupling constant (J1 ,2 ¼ 8.6 Hz) suggest its b-configuration.

1876
Wirsching et al.
0
0
Table 1. Proton chemical shifts d and coupling constants J1 ,2 (Hz) of (4-thio-l-lyxofurano-
syl)-pyrimidine and -purine nucleosides.
b
R-5a
H
R-6a
H
Nr.
H-10
H-20
H-30
H-40
H-5a0
H-5b0
0
J1 ,2
0
c
c
a
b
6.11
5.98
4.21
4.23
4.16
4.10
3.47
3.84
3.60
3.42
3.87
3.76
7.0
9.1
d
d
Me
F
H
H
H
H
H
H
ae
b
6.12
5.92
4.19
4.19
4.16
4.03
3.47
3.78
3.63
3.35
3.88
3.70
7.0
9.1
7
7
ae
be
6.08
5.97
4.24
4.29
4.14
4.09
3.47
3.86
3.59
3.42
3.87
3.76
7.2
8.9
Cl
Br
I
8
8
ae
be
6.08
5.97
4.23
4.31
4.15
4.09
3.49
3.91
3.60
3.42
3.88
3.76
7.2
8.9
9
9
ae
be
6.08
5.95
4.23
4.30
4.15
4.07
3.49
3.90
3.59
3.40
3.88
3.74
7.1
9.0
10
10
a
b
6.05
5.96
4.19
4.32
4.14
4.08
3.48
3.92
3.59
3.42
3.87
3.76
6.9
9.0
NO2
11
11
a
6.07
6.00
4.25
4.38
4.13
4.12
3.52
3.96
3.62
3.46
3.91
3.78
6.9
8.6
be
H
H
H
H
17
b
a
ae
b
5.05
6.26
4.00
4.13
4.13
4.18
3.55
3.45
3.40
3.63
3.73
3.84
8.6
6.6
H
26
f
Me
5.34
5.95
4.99
4.34
4.09
4.04
3.80
3.45
3.43
3.58
3.76
3.91
7.6
8.5
f
g
Me
H
Me
Me
Me
ae
5.29
5.01
5.56
5.04
4.12
5.1
4.1
3.8
3,43
3.41
3.41
3.8
7.5
18
27
b
ae
4.00
4.07
3.55
3.84
3.73
3.75
8.4
h
H
29
29
a
b
6.06
5.91
4.35
4.83
4.27
4.21
3.57
3.91
3.61
3.43
3.91
3.80
7.0
8.8
30
32
34
a
a
a
6.36
6.25
6.02
4.32
4.32
4.36
4.5
3.65
3.6
3.65
3.6
3.99
3.95
3.93
7.2
7.2
7.2
4.5
4.28
3.59
3.64
aSubstituent at C-5 or C-6 of the pyrimidine base.
bAnomer configuration.
c1-(4-Thio-l-lyxofuranosyl)uracil.[12]
d1-(4-Thio-l-lyxofuranosyl)thymine.[12]
eX-Ray structural analysis.
f
6-Methyl-1-(4-thio-l-lyxofuranosy)uracil; d(H-10) ¼ 5.51 and J1 2 ¼ 0.0 Hz given for the
0
0
a-anomer in Ref.[12] are erroneous.
g
5,6-Dimethyl-1-(4-thio-a-l-lyxofuranosyl)uracil; d(H-10) ¼ 5.50 and J1 2 ¼ 0.0 Hz given in
0
0
Ref.[12] are erroneous.
hNot detectable.

Thiosugars. X
1877
– Due to its X-ray structural analysis, the a-configuration of the 6-methylcytosine
derivative 27 is0 unmistakable. Interestingly, 27 exhibits chemical shifts d for H-40,
0
H-5a and H-5b which are typical of a b-configuration in the unsubstituted series.
They are, however, in good agreement with the data for the a-anomer of the corre-
sponding 6-methyluracil derivative. Again, the nature of the configuration of the 2-
thio-nucleoside 18 remains in doubt, but in our view, the coupling constant
0
0
J1 ,2 ¼ 8.4 Hz and the nearly identical proton chemical shifts in 18 and 17 argue
strongly in favor of the b-configuration.
Biological Activities
The unprotected nucleosides a- and b-7–11, 17, 18, 26, 27, a-29, b-29 and 34 were
biologically tested. The compounds 7–11, 26, 27 and 34 did not exhibit antiviral activ-
ity against HIV-1 (IIIB), HIV-2 (ROD), HCMV (Human Cytomegalovirus, strain
Davis) or VZV (Varicella Zoster virus, strain OKA) at the highest concentration tested
(250 mM). The compounds 11, 17, 18, 26, 27, 29 and 34 were also found to be inactive
against HSV-1 (KOS), HSV-2 (G), Vaccinia virus, Vesicular stomatitis virus, Cox-
sackie virus B4, Respiratory syncytial virus, Parainfluenza 3 virus, Reovirus-1, Sindbis
virus or Punta Toro virus. – None of the nucleoside analogues was cytotoxic at
250 mM. – The obvious lack of physiological activity might be due to the choice of
the nucleobases since their similarity with the natural nucleobases is low in most
cases, despite compounds 27, 29 and 34 being derived from the natural nucleobases
cytosine, adenine and hypoxanthine, respectively, which justified the testing of these
compounds.
EXPERIMENTAL SECTION
Melting points (corrected) were taken on an Electrothermal apparatus. IR spec-
tra (KBr pellets or films) were recorded on an ATI Mattson Genesis spectrometer.
NMR measurements were carried out with Bruker AMX 400 and DRX 500 spectro-
meters. Chemical shifts (ppm) are related to Me4Si (1H) and CDCl3 (13C, d ¼ 77.05 ).
Standard correlation techniques were used for assignments. Mass spectra were mea-
sured on Varian CH 7 (EI) and VG Analytical 70–250 S (FAB MS and FAB HRMS
with meta-nitrobenzyl alcohol as matrix). HPLC (Merck–Hitachi equipment): Semi-
preparative HPLC was carried out with a LiChroCART 250–10 column containing
LiChrosher 100 RP-18 (10 mm) and analytical HPLC was performed with an Eco-
CART 125-3 column containing LiChrosher 100 RP-18 end capped (5 mm). Solvents
for HPLC were obtained from Merck (MeCN, HPLC grade) and Riedel-de Hae¨n
(water, HPLC grade). A1 and A2 correspond to fast and slowly eluted fractions with-
out assignment of anomers. Optical rotations were measured with a Perkin Elmer
Polarimeter 341. Thin layer chromatography (TLC) was carried out on Merck
PF254 foils (detection: UV light, iodine vapour, or EtOH=H2SO4 spray=200ꢁC),
and column chromatography (CC) on Merck Kieselgel 60 (70–230 mesh). Solvents
(PE ¼ petroleum ether 60–70ꢁC) were purified and dried according to standard
laboratory procedures.[30]

1878
Wirsching et al.
X-Ray Structure Analyses
The crystal data and a summary of experimental details are given in Table 2,3,4.
The data collection for a-7, b-7, a-8, b-8, a-9, b-9 and b-11 was performed on a
Kappa-CCD Nonius diffractometer, with graphite-monochromated Mo-Ka radia-
˚
tion (l ¼ 0.71073 A) in the rotation F scan mode at 293 K. The X-ray data of 27 were
measured on an Enraf-Nonius CAD4 diffractometer, with graphite-monochromated
˚
Cu-Ka radiation (l ¼ 1.54178 A) in the 2y=o scan mode at 173 K. The
structures were solved by direct methods using the SIR-97[31] program, and refined
by full-matrix-block least-squares on F 2 using all data and the SHELXL-97[32]
program. Crystallographic data have been deposited with the Cambridge Crystallo-
graphic Data Centre as supplementary publications no. CCDC-144010 (a-7), CCDC-
144011 (b-7), CCDC-144012 (a-8), CCDC-144013 (b-8), CCDC-144014 (a-9),
CCDC-144015 (b-9), CCDC-144159 (b-11) and CCDC-148667 (27). Copies of the
Table 2. Crystal data and structure refinement for a-7, a-8, and a-9.
a-7
a-8
a-9
Crystal system
Space group
monoclinic
P21
orthorhombic
P212121
orthorhombic
P212121
˚
a [A]
4.8100 (10)
10.7500 (10)
10.7010 (10)
100.860 (10)
2
4.9120 (10)
11.3290 (10)
20.7010 (10)
4.9710 (10)
11.5180 (10)
20.5780 (10)
˚
b [A]
˚
c [A]
b [ꢁ]
Formula units per cell, Z
4
4
Crystal size [mm]
]
0.38 ꢃ 0.23 ꢃ 0.11
0.46 ꢃ 0.10 ꢃ 0.08
0.45 ꢃ 0.08 ꢃ 0.06
rcalcd. [g cmꢀ3
F000
1.701
288
0.330
1.699
608
0.529
1.912
680
3.682
m [mmꢀ1
]
h=k=l limits
y limits [ꢁ]
0,6=–13,12=ꢀ13,13
1.94=27.48
4996
0,6=0,14=ꢀ26,26
1.97=27.46
7232
0,6=0,14=ꢀ26,26
2.65=27.44
10494
Number of reflections
Independent reflections
Reflections with I ꢄ 2s(I )
Weighting scheme
2357
2196
2537
2351
2540
2328
w ¼ 1=[s2(F0 )
w ¼ 1=[s2(F0 )
w ¼ 1=[s2(F0 )
2
2
2
[Sw(F0 ꢀ Fc ) ]
þ (0.0350P)2
þ 0.0922P];
þ (0.0647P)2
þ 0.0352P];
þ (0.0276P)2
þ 0.4185P];
2
2 2
2
2
2
2
2
2
P ¼ (F0 þ 2Fc )=3
P ¼ (F0 þ 2Fc )=3
P ¼ (F0 þ 2Fc )=3
Number of parameters
Final R indices
[I ꢄ 2s(I )]
208
208
208
R1 ¼ 0.0276,
Rw ¼ 0.0649
R1 ¼ 0.0311,
Rw ¼ 0.0678
972
R1 ¼ 0.0298,
Rw ¼ 0.0779
R1 ¼ 0.0358,
Rw ¼ 0.0997
1.147
R1 ¼ 0.0265,
Rw ¼ 0.0548
R1 ¼ 0.0323,
Rw ¼ 0.0613
0.999
R indices (all data)
Goodness-of-fit on F2
Largest difference peak
0.168 and –0.165
0.408 and –0.341
0.269 and –0.340
ꢀ3
˚
and hole [e A
]
Refinement of H atoms
difmap=geom.
difmap=geom
difmap=geom

Thiosugars. X
1879
Table 3. Crystal data and structure refinement for b-7, b-8, and b-9.
b-7
b-8
b-9
Crystal system
Space group
monoclinic
P21
monoclinic
P21
monoclinic
P21
˚
a [A]
7.1750 (10)
6.6200 (10)
11.7830 (10)
100.040 (10)
2
7.1680 (10)
6.7180 (10)
12.3630 (10)
103.600 (10)
2
7.2020 (10)
6.7260 (10)
12.6030 (10)
104.800 (10)
2
˚
b [A]
˚
c [A]
b [ꢁ]
Formula units per cell, Z
Crystal size [mm]
]
0.45 ꢃ 0.32 ꢃ 0.12
0.40 ꢃ 0.34 ꢃ 0.06
0.18 ꢃ 0.17 ꢃ 0.06
rcalcd. [g cmꢀ3
F000
1.677
288
0.325
1.691
304
0.526
1.908
340
3.674
m[mmꢀ1
h=k=l limits
]
0,8=ꢀ7,7=ꢀ14,13
1.76=25.03
7924
0,9=ꢀ8,8=ꢀ16,15
1.69=27.48
5068
0,9=ꢀ8,8=ꢀ16,15
1.67=27.52
4872
y limits [ꢁ]
Number of reflections
Independent reflections
Reflections with I ꢄ 2s(I)
Weighting scheme
1934
1847
2503
2295
2613
2436
w ¼ 1=[s2(F0 )
w ¼ 1=[s2(F0 )
w ¼ 1=[s2(F0 )
2
2
2
[Sw(F0 ꢀ Fc ) ]
þ (0.0781P)2
þ 0.0514P];
þ (0.0397P)2
þ 0.1617P];
þ (0.0549P)2
þ 0.1712P];
2
2 2
2
2
2
2
2
2
P ¼ (F0 þ 2Fc )=3
P ¼ (F0 þ 2Fc )=3
P ¼ (F0 þ 2Fc )=3
Number of parameters
Final R indices [I ꢄ 2s(I )]
208
208
208
R1 ¼ 0.0306,
Rw ¼ 0.0926
R1 ¼ 0.0342,
Rw ¼ 0.1067
1.137
R1 ¼ 0.0281,
Rw ¼ 0.0678
R1 ¼ 0.0338,
Rw ¼ 0.0723
0.964
R1 ¼ 0.0331,
Rw ¼ 0.0804
R1 ¼ 0.0379,
Rw ¼ 0.0948
1.085
R indices (all data)
Goodness-of-fit on F2
Largest difference peak
0.306 and –0.308
0.209 and –0.209
0.416 and –0.424
ꢀ3
˚
and hole [e A
]
Refinement of H atoms
difmap=geom
difmap=geom
difmap=geom
data can be obtained free of charge on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK. [Tel. þ44-1223-336408, Fax þ44-1223-336033, E-mail
deposit@ccdc.cam.ac.uk.].
5-Nitro-2,4-bis-O-trimethylsilyluracil (viscous, yellowish liquid, 91% yield. B.p.
156ꢁC=0.5 Torr); 4-trimethylsilyloxy-2-trimethylsilylthiopyrimidine (yellow liquid, 86%
yield. B.p. 129ꢁC=0.5 Torr) and 6-methyl-4-trimethylsilyloxy-2-trimethylsilylthiopyrimidine
(colorless liquid, 93% yield. B.p. 134–136ꢁC=0.5 Torr) were obtained from the
corresponding pyrimidine bases (30 mmol) according to literature procedures.[25,33]
Glycosylation of Nucleobases. General Procedure (GP1) .[17] Millimolar amounts
of the glycosyl donor 1 (a=b ¼ 1:10)[12] or 14,[12] the respective silylated nucleobase
˚
(4.5 equivalents) and 4 A molecular sieves (40 mg) were dissolved in dry acetonitrile
(15 mL) at ꢀ18ꢁC. TMSOTf (3.3 equivalents) was added under rapid stirring.
Stirring was continued without further cooling until the reaction was complete

1880
Wirsching et al.
Table 4. Crystal data and structure refinement for b-11 and 27.
b-11
27
Crystal system
Space group
monoclinic
P21
tetragonal
P43
˚
a [A]
7.0470 (10)
6.7460 (10)
12.7560 (2)
104.00ꢁ (1)
0.42 ꢃ 0.35 ꢃ 0.08
2
1.723
316
0.316
8.8543 (6)
8.8543 (6)
16.282 (2)
˚
b [A]
˚
c [A]
b [ꢁ]
Crystal size [mm]
0.60 ꢃ 0.30 ꢃ 0.30
Formula units per cell, Z
]
4
1.516
rcalcd. [g cmꢀ3
F000
616
2.482
m [mmꢀ1
]
h=k=l limits
y limits [ꢁ]
0,9=ꢀ8,8=ꢀ16,16
1.65–27.49
4073
ꢀ3,11=ꢀ11,3=ꢀ20,3
4.99–76.43
1576
1386
Number of reflections
Independent reflections
Reflections with I ꢄ 2s(I )
Weighting scheme
2469
2405
1382
w ¼ 1=[s2(F0 )
w ¼ 1=[s2(F0 )
2
2
[Sw(F0 ꢀ Fc ) ]
þ (0.0611P)2
þ 0.1542P];
þ (0.0752P)2
þ 0.3532P];
2
2 2
2
2
2
2
P ¼ (F0 þ 2Fc )=3
P ¼ (F0 þ 2Fc )=3
Number of parameters
Final R indices [I ꢄ 2s(I )]
226
197
R1 ¼ 0.0323,
wR2 ¼ 0.0882
0.996
R1 ¼ 0.0335,
wR2 ¼ 0.0904
0.266 and ꢀ0.240
R1 ¼ 0.0352,
wR2 ¼ 0.0932
1.037
R1 ¼ 0.0353,
wR2 ¼ 0.0932
0.266 and ꢀ0.548
Goodness-of-fit on F2
R indices (all data)
Largest difference peak
ꢀ3
˚
and hole [e A
]
Refinement of H atoms
difmap=geom
geom
(ca. 1.5 h, TLC monitoring). The reaction mixture was quenched with satd. aq.
NaHCO3 solution (20 mL) and stirred for another 30 min. After filtration, the aq.
solution was extracted with CHCl3. The extract was dried with MgSO4 and evapo-
rated. The product was purified by CC.
Deprotection of O-Benzyl Derivatives. General Procedure (GP2).[24] Millimolar
amounts of the benzyl-protected nucleoside analogue were dissolved in dry CH2Cl2
(10 mL) and added dropwise under vigorous stirring at ꢀ80ꢁC to a cooled solution
(ꢀ80ꢁC) of BBr3 (5 equivalents) in dry CH2Cl2 under N2. Stirring was continued at
ꢀ90ꢁC for 1 h. The excess of BBr3 was quenched at ꢀ90ꢁC by dropwise addition of a
1:1 mixture of CH2Cl2=MeOH (10 mL). After warming to room temperature,
Ag2CO3 (30 mmol) was added to neutralize the HBr. After 30 min the inorganic salts
were filtered off, the solution was evaporated to dryness and the remaining product
was purified by CC. Further purification and separation steps followed when
required.

Thiosugars. X
1881
5-Fluoro-1-(2,3,5-tri-O-benzyl-4-thio-l-lyxofuranosyl)uracil (2). GP1; from 1[12]
(502 mg, 1.05 mmol) and 5-fluoro-2,4-bis-O-trimethylsilyluracil.[33] CC [PE=EtOAc
1:1, Rf (Al) 0.45, Rf (A2) 0.41] yielded the inseparable anomers (a=b ¼ 3:5) of 2
(484 mg, 84%) as a white solid. IR: n 3184 (NH), 1692 (C¼O), cmꢀ1. FAB MS;
m=z: 549 [M þ H]þ. FAB HRMS: calcd. 549.1859 [M þ H]þ; found 549.1903. a-2:
1H NMR (400 MHz, CDCl3): d 3.56–3.59 (m, 1H, H-40), 3.63 (dd, 1H, H-50a), 3.92
(dd, 1H, H-50b), 4.08 (dd, 1H, H-20), 4.20 (dd, 1H, H-30), 4.52–4.56 (m, 2H, CH2Ph),
4.66–4.69 (m, 2H, CH2Ph), 4.58, 4.79 (AB-system, 2H, CH2Ph, JAB ¼ 10.9 Hz), 6.39
(dd, 1H, H-10), 7.20–7.37 (m, 15H, ArH), 8.29 (d, 1H, H-6), 8.97 (d, 1H, NH).
0
0
0
0
0
0
0
0
0
0
0
0
0
J1 ,2 ¼ 7.0, J1 F ¼ 1.6, J2 ,3 ¼ 3.3, J3 ,4 ¼ 4.1, J4 ,5 a ¼ 6.7, J4 ,5 b ¼ 7.3, J5 a,5 b ¼ 9.0,
13
J6,F ¼ 7.2. JNH,F ¼ 4.7 Hz. C NMR (101 MHz, CDCl3): d 46.7 (C-40), 59.6 (C-10),
68.8 (C-50), 73.5 (CH2Ph), 73.6 (CH2Ph), 74.7 (CH2Ph), 79.2 (C-30), 82.9 (C-20),
127.85, 127.91, 127.95, 127.98, 128.17, 128.22, 128.27, 128.5, 128.6, 128.6 (C-6,
CArH), 137.6, 137.7, 138.0 (CAr), 139.1 (C-5), 150.2 (C-2), 156.9 (C-4). b-2: 1H
NMR (400 MHz, CDCl3): d 3.52–3.55 (m, 1H, H-50a), 3.80 (dd, 1H, H-20), 3.83–
3.88 (m, 2H, H-40, H-50b), 4.22–4.25, 4.66–4.69 (m, 2H, CH2Ph), 4.23–4.24 (m, 1H,
H-30), 4.50 (s. 2H, CH2Ph), 4.59, 4.78 (AB-system, 2H, CH2Ph, JAB ¼ 11.9 Hz),
6.26 (dd, 1H, H-10), 7.20–7.37 (m, 16H, H-6, ArH), 8.84 (d 1H, NH). J1 ,2 ¼ 8.1.
0
0
13
J1 ,F ¼ 1.5, J2 ,3 ¼ 3.0, JNH,F ¼ 4.7 Hz. C NMR (101 MHz, CDCl3) d 46.8 (C-40),
62.7 (C-10), 69.4 (C-50), 72.4 (CH2Ph), 73.5 (CH2Ph), 74.0 (CH2Ph), 75.7 (C-30),
84.8 (C-20), 123.6 (C-6), 127.5, 127.9, 128.1, 128.3, 128.4, 128.49, 128.53, 128.8
(CArH), 136.7, 137.0, 137.8 (CAr), 141.0 (C-5), 149.1 (C-2), 156.4 (C-4).
0
0
0
5-Chloro-1-(2,3,5-tri-O-benzyl-4-thio-l-lyxofuranosyl)uracil (3). GP1; from 1[12]
(500 mg, 1.04 mmol) and 5-chloro-2,4-bis-O-trimethylsilyluracil.[33] CC [PE=EtOAc
1:1, Rf (A1) 0.39, Rf (A2) 0.35] yielded the inseparable anomers (a=b ¼ 2:3) of
3 as a white solid (460 mg, 78%). IR: n 3185 (NH), 1691 (C¼O) cmꢀ1. FAB MS;
m=z: 565 [M þ H]þ. FAB HRMS: calcd. 565.1564 [M þ H]þ; found 565.1614. a-3:
1H NMR (500 MHz, CDCl3): d 3.59 (ddd, 1H, H-40), 3.65 (dd, 1H, H-50a), 3.95
(dd, 1H, H-50b). 4.08 (dd, 1H, H-20), 4.20 (dd, 1H, H-30), 4.53 (d, 2H, CH2Ph,
J ¼ 2.5 Hz), 4.58, 4.78 (AB-system, 2H, CH2Ph, JAB ¼ 11.0 Hz), 4.59, 4.67 (AB-sys-
tem, 2H, CH2Ph, JAB ¼ 12.1 Hz), 6.39 (d, 1H, H-10), 7.20–7.37 (m, 15H, ArH),
0
0
0
0
0
0
0
0
8.37 (s, 1H, H-6), 9.09 (bs, 1H, NH). J1 ,2 ¼ 6.9, J2 ,3 ¼ 3.6, J3 ,4 ¼ 4.1, J4 ,5 a ¼ 6.8,
J4 ,5 b ¼ 7.2, J5 a,5 b ¼ 9.0 Hz. 13C NMR (126 MHz, CDCl3): d 46.7 (C-40), 59.6 (C-10),
68.8 (C-50), 73.49 (CH2Ph), 73.53 (CH2Ph), 74.8 (CH2Ph), 79.4 (C-30), 82.9 (C-20),
107.4 (C-5), 127.90, 127.94, 127.96, 128.10, 128.14, 128.2, 128.56, 128.62, 128.7
0
0
0
0
1
(CArH), 137.0, 137.1, 137.6 (CAr), 141.4 (C-6), 150.7 (C-2), 158.9 (C-4). b-3: H
NMR (500 MHz, CDCl3): d 3.54 (dd, 1H, H-50a), 3.82–3.86 (m, 2H, H-20,
H-50b), 3.89 (ddd, 1H, H-40), 4.21–4.25 (m, 1H, H-30), 4.21–4.25, 4.66–4.70 (m, 2H,
CH2Ph), 4.50 (s, 2H, CH2Ph), 4.68, 4.87 (AB-system, 2H, CH2Ph, JAB ¼ 11.7 Hz),
6.26 (d, 1H, H-10), 7.23–7.37 (m, 15H, ArH), 7.39 (s, 1H, H-6), 8.97 (bs, 1H, NH).
Jl ,2 ¼ 8.1, J3 ,4 ¼ 3.7, J4 ,5 a ¼ 6.7, J4 ,5 b ¼ 6.8, J5 a,5 b ¼ 9.1 Hz. 13C NMR (126 MHz,
CDCl3): d 46.9 (C-40), 62.8 (C-10), 69.3 (C-50), 72.4 (CH2Ph), 73.5 (CH2Ph), 74.0
(CH2Ph), 75.7 (C-30), 84.9 (C-20), 109.3 (C-5), 127.5, 127.8, 128.1, 128.2. 128.4,
128.49, 128.52, 128.8 (CArH), 136.6, 137.0, 137.7 (CAr), 137.8 (C-6), 149.6 (C-2),
158.4 (C-4).
0
0
0
0
0
0
0
0
0
0

1882
Wirsching et al.
5-Bromo-1-(2,3,5-tri-O-benzyl-4-thio-l-lyxofuranosyl)uracil (4). GP1; from 1[12]
(505 mg, 1.06 mmol) and 5-bromo-2,4-bis-O-trimethylsilyluracil.[33] CC [PE=EtOAc
1:1, Rf (A1) 0.40, Rf (A2) 0.36] yielded the inseparable anomers (a=b ¼ 1:2) of 4 as
a white solid (498 mg, 77%). IR: n 3178 (NH), 1690 (C¼O) cmꢀ1. FAB MS; m=z:
611 [M þ H]þ for 81Br, 609 [M þ H]þ for 79Br. FAB HRMS: calcd. 611.1038
1
[M þ H]þ for 81Br, 609.1059 [M þ H]þ for 79Br; found 611.1080, 609.1088. a-4: H
NMR (400 MHz, CDCl3): d 3.59 (ddd, 1H, H-40), 3.66 (dd, 1H, H-50a), 3.95 (dd,
1H, H-50b), 4.07 (dd, 1H, H-20), 4.19–4.21 (m, 1H, H-30), 4.53 (s, 2H, CH2Ph),
4.58, 4.67 (AB-system, 2H, CH2Ph, JAB ¼ 12.0 Hz), 4.59, 4.78 (AB-system, 2H,
CH2Ph, JAB ¼ 11.1 Hz), 6.38 (d, 1H, H-10), 7.23–7.37 (m, 15H, ArH), 8.47 (s, 1H,
0
0
0
0
0
0
0
0
0
H-6), 8.87 (bs, 1H, NH). Jl ,2 ¼ 6.9, J2 ,3 ¼ 3.3, J3 ,4 ¼ 4.3, J4 ,5 a ¼ 6.8, J4 ,5b ¼ 7.1,
13
J5 a,5 b ¼ 9.1 Hz. C NMR (101 MHz, CDCl3): d 46.7 (C-40), 59.6 (C-10), 68.8
(C-50), 73.48 (CH2Ph), 73.53 (CH2Ph), 74.70 (CH2Ph), 79.4 (C-30), 82.9 (C-20),
90.0 (C-5), 127.91, 127.95, 127.96, 128.1, 128.2, 128.3, 128.5, 128.6, 128.7 (CArH),
137.0, 137.2, 137.6 (CAr), 144.0 (C-6), 150.8 (C-2), 158.9 (C-4). b-4: 1H NMR
(400 MHz, CDCl3): d 3.54 (dd, 1H, H-50a), 3.82 (dd, 1H, H-20), 3.83–3.87 (m, 1H,
H-50b), 3.89 (ddd, 1H, H-40), 4.22, 4.69 (AB-system, 2H, CH2Ph, JAB ¼ 11.9 Hz),
4.23–4.25 (m, 1H, H-30), 4.50 (s, 2H, CH2Ph), 4.69, 4.88 (AB-system, 2H, CH2Ph,
JAB ¼ 11.7 Hz), 6.26 (d, 1H, H-10), 7.23–7.37 (m, 15H, ArH), 7.50 (s, 1H, H-6),
0
0
0
0
0
0
0
0
0
0
0
0
8.77 (bs, 1H, NH). J1 ,2 ¼ 8.2, J2 ,3 ¼ 3.0, J3 ,4 ¼ 3.5, J4 ,5 a ¼ 6.5, J4 ,5 b ¼ 6.8,
13
J5 a,5 b ¼ 8.7 Hz. C NMR (101 MHz, CDCl3): d 46.7 (C-40), 62.7 (C-l0), 69.3
(C-50), 72.4 (CH2Ph), 73.5 (CH2Ph), 74.0 (CH2Ph), 75.6 (C-30), 85.0 (C-20), 97.1
(C-5), 127.5, 127.83, 127.84, 128.1, 128.2, 128.4, 128.5, 128.6, 128.8 (CArH), 136.5,
137.6, 137.7 (CAr), 139.6 (C-6), 149.8 (C-2), 158.4 (C-4).
0
0
5-Iodo-1-(2,3,5-tri-O-benzyl-4-thio-l-lyxofuranosyl)uracil (5). GP1; from 1[12]
(598 mg, 1.25 mmol) and 5-iodo-2,4-bis-O-trimethylsilyluracil.[33] CC [PE=EtOAc
1:1, Rf (a) 0.26, Rf (b) 0.33] yielded the separated anomers a-5 (231 mg, 28%) and
20
b-5 (364 mg, 44%) as white solids. a-5: [a]D þ 38.8 (c 1.0, CHCl3). M.p. 68–70ꢁC.
1
IR: n 3186 (NH), 1688 (C¼O) cmꢀ1. H NMR (400 MHz, CDCl3): d 3.59 (ddd,
1H, H-40), 3.67 (dd, 1H, H-50a), 3.95 (dd, 1H, H-50b), 4.16 (dd, 1H, H-20), 4.19
(dd, 1H, H-30), 4.53 (d, 2H, CH2Ph, J ¼ 1.1 Hz), 4.58, 4.65 (AB-system, 2H, CH2Ph,
JAB ¼ 12.0 Hz), 4.61, 4.77 (AB-system, 2H, CH2Ph, JAB ¼ 11.4 Hz), 6.36 (d, 1H,
0
0
0
H-1 ), 7.26–7.38 (m, 15H, ArH), 8.55 (s, 1H, H-6), 8.74 (bs, 1H, NH). Jl ,2 ¼ 6.9,
J2 ,3 ¼ 3.4, J3 ,4 ¼ 4.3, J4 ,5 a ¼ 6.8, J4 ,5 b ¼ 7.1, J5 a,5 b ¼ 9.2 Hz. 13C NMR
(101 MHz, CDCl3): d 46.8 (C-40), 59.4 (C-l0), 66.2 (C-5), 69.0 (C-50), 73.5 (CH2Ph),
73.5 (CH2Ph), 74.6 (CH2Ph), 79.4 (C-30), 82.9 (C-20), 127.6, 127.8, 128.0, 128.13,
128.14, 128.3, 128.5, 128.6 (CArH), 137.0, 137.3, 137.6 (CAr), 149.2 (C-6), 151.1
(C-2), 159.8 (C-4). FAB MS; m=z: 657 [M þ H]þ. FAB HRMS: calcd. 657.0920
0
0
0
0
0
0
0
0
0
0
[M þ H]þ; found 657.0930. b-5: [a]D ꢀ96.8 (c 1.0, CHCl3). M.p. 62–64ꢁC. IR: n
20
3187 (NH), 1689 (C¼O), 1610 (C¼O) cmꢀl. H NMR (400 MHz, CDCl3): d 3.54
1
(dd, 1H, H-50a), 3.82–3.86 (m, 2H, H-20, H-50b), 3.91 (ddd, 1H, H-40), 4.23–4.25
(m, 1H, H-30), 4.22, 4.68 (AB-system, 2H, CH2Ph, JAB ¼ 12.7 Hz), 4.50 (s, 2H,
CH2Ph), 4.68, 4.88 (AB-system, 2H, CH2Ph, JAB ¼ 11.7 Hz), 6.24 (d, 1H, H-10),
0
0
7.26–7.37 (m, 15H, ArH), 7.61 (s, 1H, H-6), 8.92 (bs, 1H, NH). Jl ,2 ¼ 8.1,
J3 ,4 ¼ 3.7, J4 ,5 a ¼ 6.8, J4 ,5 b ¼ 6.9, J5 a,5 b ¼ 8.9 Hz. 13C NMR (101 MHz, CDCl3):
0
0
0
0
0
0
0
0
d 47.0 (C-40), 62.8 (C-10), 69.0 (C-5), 69.3 (C-50), 72.4 (CH2Ph), 73.5 (CH2Ph), 73.9

Thiosugars. X
1883
(CH2Ph), 75.7 (C-30), 85.0 (C-20), 127.8, 127.88, 127.92, 128.05, 128.14, 128.4, 128.5,
128.7, 128.8 (CArH), 136.6, 137.65, 137.67 (CAr), 144.9 (C-6), 150.1 (C-2), 159.5
(C-4). FAB MS; m=z: 657 [M þ H]þ. FAB HRMS: calcd. 657.0920 [M þ H]þ; found
657.0887.
5-Nitro-1-(2,3,5-tri-O-benzyl-4-thio-l-lyxofuranosyl)uracil (6). GP1; from 1[12]
(603 mg, 1.26 mmol) and 5-nitro-2,4-bis-O-trimethylsilyluracil. CC [PE=EtOAc 1:2,
Rf (b) 0.37, Rf (a) 0.28] yielded a-6 (173 mg, 24%) and b-6 (326 mg, 45%) as white
20
solids. a-6: M.p. 66–68ꢁC. [a]D þ 56.4 (c 0.9, CHCl3). IR: n 3201 (NH), 1712
1
(C¼O), 1617 (C¼O), 1517 (NO2), 1346 (NO2) cmꢀ1. H NMR (500 MHz, CDCl3):
d 3.62 (ddd, 1H, H-40), 3.69 (dd, 1H, H-50a), 3.96 (dd, 1H, H-50b), 4.08 (dd, 1H,
H-20), 4.22 (dd, 1H, H-30), 4.55, 4.67 (AB system, 2H, CH2Ph, JAB ¼ 10.6 Hz),
4.56 (s, 2H, CH2Ph), 4.59, 4.70 (AB system, 2H, CH2Ph, JAB ¼ 11.9 Hz), 6.33 (d,
1H, H-10), 7.13–7.38 (m, 15H, ArH), 8.62 (s, 1H, H-6), 9.57 (bs, 1H, NH).
J1 ,2 ¼ 6.5, J2 ,3 ¼ 3.4, J3 ,4 ¼ 4.1, J4 ,5 a ¼ 6.7, J4 ,5 b ¼ 7.5, J5 a,5 b ¼ 9.2 Hz. 13C
NMR (126 MHz, CDCl3): d 47.0 (C-40), 61.6 (C-10), 68.7 (C-50), 73.7 (CH2Ph),
73.8 (CH2Ph), 75.0 (CH2Ph), 78.9 (C-30), 83.2 (C-20), 123.9 (C-5), 127.7, 127.9,
128.1, 128.4, 128.52, 128.54, 128.6, 128.7 (CArH), 136.4, 136.8, 137.4 (CAr), 149.46
(C-6), 149.48 (C-2), 153.8 (C-4). FAB MS; m=z: 576 [M þ H]þ. C30H29N3O7S
(575.65): calcd. C 62.60, H 5.08, N 7.30, S 5.57; found C 62.51, H 5.09, N 7.09, S
0
0
0
0
0
0
0
0
0
0
0
20
5.38. b-6: M.p. 79–80ꢁC. [a]D ꢀ171.6 (c ¼ 1.0, CHCl3). IR: n 3207 (NH), 1712
1
(C¼O), 1621 (C¼O), 1517 (NO2), 1346 (NO2) cmꢀ1. H NMR (500 MHz, CDCl3):
d 3.56 (dd, 1H, H-50a), 3.87 (dd, 1H, H-50b), 3.89 (dd, 1H, H-20), 4.01 (ddd, 1H,
H-40), 4.15, 4.71 (AB system, 2H, CH2Ph, JAB ¼ 12.5 Hz), 4.30 (dd, 1H, H-30),
4.52 (s, 2H, CH2Ph), 4.72, 4.89 (AB system, 2H, CH2Ph, JAB ¼ 11.6 Hz), 6.27 (d,
1H, H-10), 7.17–7.36 (m, 15H, ArH), 8.60 (s, 1H, H-6), 8.61 (bs, 1H, NH).
J1 ,2 ¼ 8.4, J2 ,3 ¼ 3.1, J3 ,4 ¼ 3.4, J4 ,5 a ¼ 7.0, J4 ,5 b ¼ 7.3, J5 a,5 b ¼ 9.3 Hz. 13C
NMR (126 MHz, CDCl3): d 47.2 (C40), 63.5 (C-10), 69.1 (C-50), 72.6 (CH2Ph), 73.5
(CH2Ph), 74.1 (CH2Ph), 75.5 (C-30), 85.5 (C-20), 125.5 (C-5), 127.8, 128.0, 128.05,
128.09, 128.46, 128.51, 128.6, 128.8, 129.0 (CArH), 136.4, 137.6, 137.6 (CAr), 144.6
(C-6), 148.3 (C-2), 153.2 (C-4). FAB MS; m=z: 576 [M þ H]þ. FAB HRMS: calcd.
576.1804 [M þ H]þ; found 576.1827. C30H29N3O7S (575.65): calcd. C 62.60, H
5.08, N 7.30, S 5.57; found C 62.50, H 5.08, N 7.04, S 5.62.
0
0
0
0
0
0
0
0
0
0
0
0
5-Fluoro-1-(4-thio-l-lyxofuranosyl)uracil (7). GP2; from 2 (770 mg, 1.40 mmol,
a=b ¼ 3:5). CC [CHCl3=MeOH 4:1, Rf (a) 0.23, Rf (b) 0.14] yielded a-7 (68 mg, 19%)
and b-7 (53 mg, 15%). Further purification by reversed phase HPLC (MeCN=H2O
8:92) gave a-7 (59 mg, 16%) and b-7 (44 mg, 12%) as white solids. a-7 was crystallized
from water (thin, colorless needles) and b-7 from MeOH (colorless needles). In both
cases the crystals were suitable for an X-ray structural analysis. a-7: M.p. 236ꢁC
20
(decomp.). [a]D ꢀ16.2 (c 1.0, MeOH). IR: n 3402 (OH), 3153 (NH), 1697
(C¼O), 1659 (C¼O) cmꢀ1
.
1H NMR (500 MHz, [D6]DMSO): d 3.47 (ddd, 1H,
H-40), 3.59 (ddd, 1H, H-50a), 3.87 (ddd, 1H, H-50b), 4.14 (ddd, 1H, H-30), 4.24
(ddd, 1H, H-20), 4.94 (dd, 1H, 50-OH), 5.62 (d, 1H, 20-OH), 5.65 (d, 1H, 30-OH),
6.08 (dd, IH, H-10), 8.54 (d, 1H, H-6), 11.74 (bs, 1H, NH). J1 ,2 ¼ 7.2, J1 ,F ¼ 1.8,
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
J2 ,3 ¼ 3.8, J2 ,OH ¼ 5.4, J3 ,4 ¼ 7.0, J3 ,OH ¼ 4.2, J4 ,5 a ¼ 7.8, J4 ,5 b ¼ 5.6, J5 a,5 b ¼ 10.7,
J5 a,OH ¼ 5.8, J5 b,OH ¼ 5.1, J6,F ¼ 8.2 Hz. 13C NMR (126 MHz, [D6]DMSO): d 51.3
0
0

1884
Wirsching et al.
(C-40), 61.0 (C-10), 61.2 (C-50), 72.7 (C-30), 75.4 (C-20), 129.7 (d, C-6), 138.6 (d, C-5),
150.4 (C-2), 157.3 (d, C-4). J4,F ¼ 26.4, J5,F ¼ 226.5, J6,F ¼ 35.1 Hz. 19F NMR
0
(471 MHz, [D6]DMSO):
d
ꢀ169.4 (ddd, 1F, F-5). J1 ,F ¼ 1.9, JNH,F ¼ 5.5,
J6,F ¼ 7.4 Hz. MS (70 eV); m=z: 278 (1.1) [Mþꢅ], 260 (20) [M ꢀ H2O]þꢅ, 230 (6),
212 (11), 131 (99) [C5H7O2Sþ], 130 (64), 101 (38), 87 (51), 86 (10), 85 (28), 57
(100), 44 (71). FAB HRMS: calcd. 260.0267 [M ꢀ H2O]þꢅ; found 260.0295. b-7:
20
M.p. 229–230ꢁC (decomp.). [a]D –103.0 (c 1.0, MeOH). IR: n 3417 (OH), 1680
(C¼O), 1658 (C¼O) cmꢀ1
.
1H NMR (500 MHz, [D6]DMSO) d 3.42 (ddd, 1H,
H-50a), 3.76 (ddd, 1H, H-50b), 3.86 (ddd, 1H, H-40), 4.09 (ddd, 1H, H-30), 4.25
(ddd, 1H, H-20), 4.79 (dd, 1H, 50-OH), 5.20 (d, 1H, 30-OH), 5.51 (d, 1H, 20-OH),
5.97 (dd, 1H, H-10), 8.40 (d, 1H, H-6), 11.82 (bs, 1H, NH). J1 ,2 ¼ 8.9, J1 ,F ¼ 2.0,
0
0
0
0
0
0
0
0
0
0
0
0
0
J2 ,3 ¼ 3.4, J2 ,OH ¼ 6.0, J3 ,4 ¼ 3.3, J3 ,OH ¼ 4.1, J4 ,5 a ¼ 7.6, J4 ,5 b ¼ 6.4,
J5 a,5 b ¼ 10.7, J5 a,OH ¼ 5.4, J5 b,OH ¼ 4.9, J6,F ¼ 7.4 Hz. 13C NMR (126 MHz,
[D6]DMSO): d 50.4 (C-40), 61.7 (C-50), 63.2 (C-10), 72.4 (C-30), 78.6 (C-20), 126.7
(d, C-6), 140.7 (d, C-5), 150.6 (C-4), 157.5 (d, C-4). J4,F ¼ 25.4, J5,F ¼ 230.8,
J6,F ¼ 34.2 Hz. 19F NMR (471 MHz, [D6]DMSO): d ¼ –166.4 (bd, 1F, F-5).
J ¼ 6.5 Hz. MS (70 eV); m=z: 278 (0.1) [M]þꢅ, 260 (16) [M ꢀ H2O]þꢅ, 212 (13), 131
(88) [C5H7O2Sþ], 101 (35), 87 (31), 57 (100), 45 (34). FAB HRMS: calcd. 260.0267
[M ꢀ H2O]þꢅ found 260.0270.
0
0
0
0
5-Chloro-1-(4-thio-l-lyxofuranosyl)uracil (8). GP2; from 3 (920 mg, 1.63 mmol,
a=b ¼ 2:3). CC [CHCl3=MeOH 4:1, Rf (a) 0.29, Rf (b) 0.17] yielded a-8 (92 mg, 19%)
and b-8 (55 mg, 11%). Further purification by reversed phase HPLC (MeCN=H2O
11:89) gave a-8 (79 mg, 16%) and b-8 (49 mg, 10%) as white solids. a-8 was crystal-
lized from water (colorless sheets) and b-8 was crystallized from water=MeOH (thin,
colorless, needles). The crystals were suitable for X-ray structural analyses. a-8: M.p.
20
243ꢁC (decomp.). [a]D –8.9 (c 1.0, MeOH). IR: n 3436 (OH), 3177 (NH), 1692
1
(C¼O), 1632 (C¼O) cmꢀ1. H NMR (500 MHz, [D6]DMSO): d 3.49 (ddd, 1H,
H-40), 3.60 (ddd, 1H, H-50a), 3.88 (ddd, 1H, H-50b), 4.15 (ddd, 1H, H-30), 4.23
(ddd, 1H, H-20), 4.95 (dd, 1H, 50-OH), 5.647 (d, 1H, 30-OH), 5.650 (d, 1H, 20-
OH), 6.08 (d, 1H, H-10), 8.61 (s, 1H, H-6), 11.73 (bs, 1H, NH). J1 ,2 ¼ 7.2,
0
0
0
0
0
0
0
0
0
0
0
0
0
0
J2 ,3 ¼ 3.8, J2 ,OH ¼ 6.9, J3 ,4 ¼ 4.2, J3 ,OH ¼ 4.2, J4 ,5 a ¼ 5.8, J4 ,5 b ¼ 7.9, J5 a,5 b ¼ 10.7,
13
J5 a,OH ¼ 5.8, J5 b,OH ¼ 5.1 Hz. C NMR (126 MHz, [D6]DMSO): d 51.4 (C-40), 61.1
(C-10), 61.2 (C-50), 72.8 (C-30), 75.4 (C-20), 105.3 (C-5), 142.7 (C-6), 150.9 (C-2), 159.3
(C-4). MS (70 eV); m=z: 276 (4) [M ꢀ H2O]þꢅ, 131 (100) [C5H7O2Sþ], 103 (18), 85
(15), 57 (49), 40 (17). FAB HRMS: calcd. 275.9972 [M ꢀ H2O]þꢅ, found 275.9967.
0
0
20
b-8: M.p. 223–227ꢁC (decomp.). [a]D –126.6 (c 1.0, MeOH). IR: n 3465 (OH),
3188 (NH), 1694 (C¼O), 1628 (C¼O) cmꢀ1. H NMR (500 MHz, [D6]DMSO):
1
d 3.42 (ddd, 1H, H-50a), 3.76 (ddd, 1H, H-50b), 3.91 (ddd, 1H, H-40), 4.09 (ddd,
1H, H-30), 4.31 (ddd, 1H, H-20), 4.79 (dd, 1H, 50-OH), 5.20 (d, 1H, 30-OH), 5.52
(d, 1H, 20-OH), 5.97 (d, 1H, H-10), 8.43 (s, 1H, H-6), 11.84 (bs, 1H, NH).
0
0
0
0
0
0
0
0
0
0
0
0
J1 ,2 ¼ 8.9, J2 ,3 ¼ 3.2, J2 ,OH ¼ 5.9, J3 ,4 ¼ 3.1, J3 ,OH ¼ 4.0, J4 ,5 a ¼ 7.8, J4 ,5 b ¼ 6.3,
J5 a,5 b ¼ 10.7, J5 a,OH ¼ 5.7, J5 b,OH ¼ 4.8 Hz. 13C NMR (126 MHz, [D6]DMSO): d
50.4 (C-40), 61.5 (C-50), 62.9 (C-10), 72.2 (C-30), 78.5 (C-20), 108.1 (C-5), 139.5 (C-6),
150.8 (C-2), 159.2 (C-4). MS (70 eV); m=z: 276 (6) [M ꢀ H2O]þꢅ, 131 (53)
[C5H7O2Sþ], 103 (46), 76 (22), 57 (100), 40 (45). FAB HRMS: calcd. 275.9972
[M ꢀ H2O]þꢅ, found 275.9979.
0
0
0
0

Thiosugars. X
1885
5-Bromo-1-(4-thio-l-lyxofuranosyl)uracil (9). GP2; from 4 (960 mg, 1.57 mmol,
a=b ¼ 1:2). CC [CHCl3=MeOH 4:1, Rf (a) 0.26, Rf (b) 0.17] yielded a-9 (102 mg, 19%)
and b-9 (89 mg, 17%). Further purification by reversed phase HPLC (MeCN=H2O
10:90) gave a-9 (87 mg, 16%) and b-9 (79 mg, 15%) as white solids. a-9 and b-9 were
crystallized from water to give colorless sheets and thin, colorless needles, respec-
tively. The crystals were suitable for X-ray structural analyses. a-9: M.p. 227ꢁC
20
(decomp.). [a]D þ5.0 (c 1.0, MeOH). IR: n 3438 (OH), 3187 (NH), 1693 (C¼O),
1
1626 (C¼O) cmꢀ1. H NMR (500 MHz, [D6]DMSO): d 3.49 (ddd, 1H, H-40), 3.59
(ddd, 1H, H-50a), 3.88 (ddd, 1H, H-50b), 4.15 (ddd, 1H, H-30), 4.23 (ddd, 1H, H-20),
4.95 (dd, 1H, 50-OH), 5.64 (d, 1H, 30-OH), 5.65 (d, 1H, 20-OH), 6.08 (d, 1H, H-10),
0
0
0
0
0
8.69 (s, 1H, H-6), 11.70 (bs, 1H, NH). J1 ,2 ¼ 7.1, J2 ,3 ¼ 3.8, J2 ,OH ¼ 6.9,
0
0
0
0
0
0
0
0
0
0
0
J3 ,4 ¼ 4.3, J3 ,OH ¼ 4.6, J4 ,5 a ¼ 7.9, J4 ,5 b ¼ 5.5, J5 a,5 b ¼ 10.7, J5 a,OH ¼ 5.8, J5 b,OH
¼
13
5.1 Hz. C NMR (126 MHz, [D6]DMSO): d 51.4 (C-40), 61.0 (C-10), 61.3 (C-50),
72.8 (C-30), 75.4 (C-20), 93.8 (C-5), 145.2 (C-6), 151.2 (C-2), 159.5 (C-4). MS
(70 eV); m=z: 340 (1) [Mþꢅ] (for 81Br), 338 (1) [Mþꢅ] (for 79Br), 322 (4)
[M ꢀ H2O]þꢅ (for 81Br), 320 (4) [M ꢀ H2O]þꢅ (for 79Br), 258 (10), 192 (20)
[C4H3BrN2O2þꢅ] (for 81Br), 190 (19) [C4H3BrN2O2þꢅ] (for 79Br), 153 (14), 131
(74) [C5H7O2S]þ, 101 (31), 85 (29), 57 (100), 44 (100). FAB HRMS: calcd.
339.9552 [Mþꢅ] (for 81Br), 337.9572 [Mþꢅ] (for 79Br), 321.9446 [M ꢀ H2O]þꢅ (for
81Br), 319.9466 [M ꢀ H2O]þꢅ (for 79Br); found 339.9548, 337.9579, 321.9445,
20
319.9474. b-9: M.p. 243ꢁC (decomp.). [a]D –35.4 (c 0.7, MeOH). IR: n 3352
(OH), 1682 (C¼O), 1623 (C¼O) cmꢀ1
.
1H NMR (500 MHz, [D6]DMSO):
d ¼ 3.40 (ddd, 1H, H-50a), 3.74 (ddd, 1H, H-50b), 3.90 (ddd, 1H, H-40), 4.07
(ddd, 1H, H-30), 4.30 (ddd, 1H, H-20), 4.77 (dd, 1H, 50-OH), 5.17 (d, 1H, 30-OH),
5.50 (d, 1H, 20-OH), 5.95 (d, 1H, H-10), 8.45 (s, 1H, H-6), 11.82 (bs, 1H, NH)
0
0
0
0
0
0
0
0
0
0
ppm. J1 ,2 ¼ 9.0, J2 ,3 ¼ 3.1, J2 ,OH ¼ 6.0, J3 ,4 ¼ 3.0, J3 ,OH ¼ 3.9, J4 ,5 a ¼ 7.8,
J4 ,5 b ¼ 6.3, J5 a,5 b ¼ 10.8, J5 a,OH ¼ 5.8, J5 b,OH ¼ 4.8 Hz. 13C NMR (126 MHz,
[D6]DMSO): d 49.9 (C-40), 61.0 (C-50), 62.4 (C-10), 71.8 (C-30), 78.1 (C-20), 96.2
(C-5), 141.4 (C-6), 150.5 (C-2), 158.8 (C-4). MS (70 eV); m=z: 322 (5) [M ꢀ H2O]þꢅ
(for 81Br), 320 (5) [M ꢀ H2O]þꢅ (for 79Br), 192 (16) [C4H3BrN2O2þꢅ] (for 81Br),
190 (17) [C4H3BrN2O2þꢅ] (for 79Br), 131 (71) [C5H7O2Sþ], 101 (19), 85 (36), 57
(100), 45 (32). FAB HRMS: calcd. 321.9446 [M ꢀ H2O]þꢅ (for 81Br), 319.9466
[M ꢀ H2O]þꢅ (for 79Br); found 321.9453, 319.9459.
0
0
0
0
0
0
5-Iodo-1-(4-thio-l-lyxofuranosyl)uracil (10). GP2; from 5 (538 mg, 0.82 mmol,
a=b ¼ 5:8). CC [CHCl3=MeOH 4:1, Rf (a) 0.26, Rf (b) 0.19] yielded a-10 (22 mg,
7%) and b-10 (29 mg, 9%). Further purification by reversed phase HPLC
(MeCN=H2O 12:88) gave a-10 (16 mg, 5%) and b-10 (26 mg, 8%) as white solids.
20
a-10: M.p. 186–189ꢁC, (decomp.). [a]D þ6.9 (c 0.6, MeOH). IR: n 3424 (OH),
1
1689 (C¼O), 1607 (C¼O) cmꢀ1. H NMR (500 MHz, [D6]DMSO): d 3.48 (ddd,
1H, H-40), 3.59 (ddd, 1H, H-50a), 3.87 (ddd, 1H, H-50b), 4.14 (ddd, 1H, H-30), 4.19
(ddd, 1H, H-20), 4.95 (dd, 1H, 50-OH), 5.59 (d, 1H, 30-OH), 5.63 (d, 1H, 20-OH),
6.05 (d, 1H, H-10), 8.70 (s, 1H, H-6), 11.56 (bs, 1H, NH). J1 ,2 ¼ 6.9, J2 ,3 ¼ 3.8,
0
0
0
0
0
0
0
0
0
0
0
0
0
0
J2 ,OH ¼ 6.6, J3 ,4 ¼ 4.4, J3 ,OH ¼ 4.4, J4 ,5 a ¼ 7.9, J4 ,5 b ¼ 5.4, J5 a,5 b ¼ 10.7,
13
J5 a,OH ¼ 5.5, J5 b,OH ¼ 5.2 Hz. C NMR (126 MHz, [D6]DMSO): d 49.1 (C-40),
58.6 (C-10), 59.1 (C-50), 64.9 (C-5), 70.6 (C-30), 73.1 (C-20), 147.8 (C-6), 149.3 (C-2),
158.6 (C-4). MS (70 eV); m=z: 386 (17) [Mþꢅ], 368 (22) [M ꢀ H2O]þꢅ, 320 (8), 253
0
0

1886
Wirsching et al.
(66), 238 (100) [C4H3IN2O2þꢅ], 195 (34), 168 (15), 131 (41) [C5H7O2Sþ], 101 (11), 85
(7), 57 (24), 40 (30). FAB HRMS: calcd. 385.9433 [Mþꢅ], 367.9328 [M ꢀ H2O]þꢅ
20
,
237.9239 [C4H3IN2O2þꢅ]; found 385.9446, 367.9341, 237.9239. b-10: Decomp. at
209–212ꢁC without melting. [a]D –88.3 (c 1.0, MeOH). IR: n 3421 (OH), 1691
1
(C¼O), 1608 (C¼O) cmꢀ1. H NMR (500 MHz, [D6]DMSO): d 3.42 (ddd, 1H,
H-50a), 3.76 (ddd, 1H, H-50b), 3.92 (ddd, 1H, H-40), 4.08 (ddd, 1H,
H-30), 4.32 (ddd, 1H, H-20), 4.79 (dd, 1H, 50-OH), 5.18 (d, 1H, 30-OH), 5.51 (d,
1H, 20-OH), 5.96 (d, 1H, H-10), 8.43 (s, 1H, H-6), 11.67 (bs, 1H, NH). J1 ,2 ¼ 9.0,
0
0
0
0
0
0
0
0
0
0
0
0
0
0
J2 ,3 ¼ 3.1, J2 ,OH ¼ 6.1, J3 ,4 ¼ 3.0, J3 ,OH ¼ 4.0, J4 ,5 a ¼ 7.9, J4 ,5 b ¼ 6.2, J5 a,5 b ¼ 10.8,
13
J5 a,OH ¼ 5.8, J5 b,OH ¼ 4.8 Hz. C NMR (126 MHz, [D6]DMSO): d 49.8 (C-40), 61.0
(C-50), 62.1 (C-10), 70.0 (C-5), 71.7 (C-30), 77.9 (C-20), 145.8 (C-6), 150.8 (C-2), 160.1
(C-4). MS (70 eV); m=z: 386 (7) [Mþꢅ], 368 (21) [M ꢀ H2O]þꢅ, 320 (5), 253 (55), 238
(16) [C4H3IN2O2þꢅ], 205 (6), 179 (6), 151 (10), 131 (38) [C5H7O2Sþ], 109 (15), 97
0
0
(24), 57 (34), 40 (100). FAB HRMS: calcd. 385.9433 [Mþꢅ], 367.9328 [M ꢀ H2O]þꢅ
,
237.9239 [C4H3IN2O2þꢅ]; found 385.9465, 367.9343, 237.9232.
5-Nitro-1-(4-thio-l-lyxofuranosyl)uracil (11). GP2; from 6 (467 mg, 0.81 mmol).
CC [CHCl3=MeOH 4:1, Rf (Al) 0.16, Rf (A2) 0.11] followed by fractionated crystal-
lization from water gave first b-11 (11 mg, 5%) as colorless sheets and then a-11 as
20
white needles (9 mg, 4%). a-11: M.p. 154ꢁC (decomp.). [a]D ꢀ11.2 (c 1.0, MeOH).
IR: n 3382 (OH), 1709 (C¼O), 1610 (C¼O), 1518 (NO2), 1344 (NO2) cmꢀ1. 1H NMR
(500 MHz, [D6]DMSO): d 3.52 (ddd, 1H, H-40), 3.62 (ddd, 1H, H-50a), 3.91 (ddd, 1H,
H-50b), 4.13 (ddd, 1H, H-30), 4.25 (ddd, 1H, H-20), 4.97 (dd, 1H,
50-OH), 5.65 (d, 1H, 30-OH), 5.68 (d, 1H, 20-OH), 6.07 (d, 1H, H-10), 9.77 (s, 1H,
0
0
0
0
0
0
0
0
H-6), 11.93 (bs, 1H, NH). J1 ,2 ¼ 6.9, J2 ,3 ¼ 3.7, J2 ,OH ¼ 7.4, J3 ,4 ¼ 4.2, J3 ,OH ¼ 4.3,
J4 ,5 a ¼ 8.1, J4 ,5 b ¼ 5.5, J5 a,5 b ¼ 10.5, J5 a,OH ¼ 5.3, J5 b,OH ¼ 5.2 Hz. 13C NMR
(126 MHz, [D6]DMSO): d ¼ 51.5 (C-40), 61.4 (C-50), 62.7 (C-10), 73.0 (C-30), 75.8
(C-20), 124.3 (C-5), 150.0 (C-6), 150.8 (C-2), 155.0 (C-4). b-11: M.p. ¼ 188ꢁC
0
0
0
0
0
0
0
0
20
(decomp.). [a]D ꢀ49.4 (c 0.9, MeOH). IR: n 3447 (OH), 1709 (C¼O), 1613
(C¼O), 1509 (NO2), 1343 (NO2) cmꢀ1. H NMR (500 MHz, [D6]DMSO): d 3.46
1
(ddd, 1H, H-50a), 3.78 (ddd, 1H, H-50b), 3.96 (ddd, 1H, H-40), 4.12 (ddd, 1H, H-30),
4.38 (ddd, 1H, H-20), 4.83 (dd, 1H, 50-OH), 5.27 (d, 1H, 30-OH), 5.60 (d, 1H, 20-
OH), 6.00, (d, 1H, H-10), 9.31 (s, 1H, H-6), 12.10 (bs, 1H, NH). J1 ,2 ¼ 8.6,
0
0
0
0
0
0
0
0
0
0
0
0
0
0
J2 ,3 ¼ 3.1, J2 ,OH ¼ 5.7, J3 ,4 ¼ 3.2, J3 ,OH ¼ 4.2, J4 ,5 a ¼ 8.1, J4 ,5 b ¼ 5.9, J5 a,5 b ¼ 10.7,
13
J5 a,OH ¼ 5.8, J5 b,OH ¼ 4.8 Hz. C NMR (126 MHz, [D6]DMSO): d 50.6 (C-40),
61.3 (C-50), 63.9 (C-10), 72.7 (C-30), 79.4 (C-20), 126.6 (C-5), 146.6 (C-6), 149.7
(C-2), 154.6 (C-4).
0
0
1-(2,3,5-Tri-O-benzyl-4-thio-l-lyxofuranosyl)-2-thiouracil (12). GP1; from 112
(600 mg, 1.25 mmol) and 4-trimethylsilyloxy-2-trimethylsilylthiopyrimidine. CC
[PE=EtOAc 1:2, Rf (a,b) 0.21] yielded the inseparable anomers of 12 (283 mg, 41%,
A1=A2 ¼ 2:1) as a white solid. IR: n 3195 (NH), 1664 (C¼O), 1565 (thioamide-B)
cmꢀ1. C30H30N2O4S2 (546.71): calcd. C 65.91, H 5.53, N 5.12, S 11.73; found C
1
65.25, H 5.81, N 4.90, S 11.14. Major anomer: H NMR (500 MHz, CDCl3): d
3.74–3.79 (m, 2H, H-40, H-50a), 4.01 (dd, 1H, H-50b), 4.18 (dd, 1H, H-20), 4.35 (dd,
1H, H-30), 4.41–5.00 (m, 6H, 3 CH2Ph), 5.31 (d, 1H, H-10), 6.22 (d, 1H, H-5),

Thiosugars. X
1887
0
0
0
0
0
0
7.23–7.40 (m, 15H, ArH), 7.82 (d, 1H, H-6). J1 ,2 ¼ 4.1, J2 ,3 ¼ 3.3, J3 ,4 ¼ 5.4,
13
J4 ,5 b ¼ 4.2, J5 a,5 b ¼ 9.0, J5,6 ¼ 6.6 Hz. C NMR (126 MHz, CDCl3): d 47.0 (C-40),
50.6 (C-10), 71.4 (C-50), 72.5 (CH2Ph), 73.27 (CH2Ph), 73.33 (CH2Ph), 79.4 (C-30),
85.9 (C-20), 111.6 (C-5), 127.6, 127.68, 127.71, 127.8, 128.1, 128.4, 128.4, 128.5
(CArH), 137.8, 137.8, 138.2 (CAr), 154.6 (C-6), 161.0, 164.1 (C-2, C-4). Minor
0
0
0
0
1
anomer: H NMR (500 MHz, CDCl3): d 3.52 (dd, 1H, H-50a), 3.58–3.62 (m, 1H,
H-40), 3.86–3.90 (m, 1H, H-50b), 4.27–4.29 (m, 2H, H-20, H-30), 4.41–5.00 (m, 6H,
3 CH2Ph), 5.94 (d, 1H, H-10), 6.15 (d, 1H, H-5), 7.23–7.40 (m, 15H, ArH),
7.82 (d, 1H, H-6). J1 ,2 ¼ 6.2, J4 ,5 a ¼ 6.4, J5 a,5 b ¼ 9.1, J5,6 ¼ 6.6 Hz. 13C NMR
(126 MHz, CDCl3): d 46.0 (C-40), 52.1 (C-10), 69.7 (C-50), 72.4 (CH2Ph), 73.4
(CH2Ph), 73.5 (CH2Ph), 79.6 (C-30), 83.7 (C-20), 110.9 (C-5), 127.59, 127.63,
127.82, 127.83, 127.96, 127.98, 128.4, 128.5, 128.7 (CArH), 136.9, 137.2, 137.9
(CAr), 154.3 (C-6), 162.7, 163.7 (C-2, C-4).
0
0
0
0
0
0
6-Methyl-1-(2,3,5-tri-O-benzyl-4-thio-l-lyxofuranosyl)-2-thiouracil (13). GP1;
from 112 (600 mg, 1.25 mmol) and 6-methyl-4-trimethylsilyloxy-2-trimethylsilylthio-
pyrimidine. CC [PE=EtOAc 1:2, Rf (a,b) 0.34] yielded the inseparable anomers of
13 as a white solid (548 mg, 78%, A1=A2 ¼ 2:1). IR: n 3199 (NH), 1659 (C¼O),
1580 (thioamide-B) cmꢀ1. FAB MS: m=z: 561 [M þ H]þ. C31H32N2O4S2 (560.74):
calcd. C 66.40, H 5.75, N 5.00, S 11.44; found C 65.70, H 5.74, N 5.05, S 11.11.
1
Major anomer: H NMR (500 MHz, CDCl3): d 2.24 (d, 3H, CH3), 3.51 (dd, 1H,
H-50a), 3.57 (ddd, 1H, H-40), 3.88 (dd, 1H, H-50b), 4.26–4.28 (m, 2H, H-20, H-30),
4.42, 4.45 (AB system, 2H, CH2Ph, JAB ¼ 11.8 Hz), 4.53, 4.73 (AB system, 2H,
CH2Ph, JAB ¼ 11.9 Hz), 4.67, 5.01 (AB system, 2H, CH2Ph, JAB ¼ 11.7 Hz), 5.96
(d, 1H, H-10), 5.99 (q, 1H, H-5), 7.24–7.40 (m, 15H, ArH). J1 ,2 ¼ 5.7, J3 ,4 ¼ 4.1,
0
0
0
0
J4 ,5 a ¼ 6.7, J4 ,5 b ¼ 7.7, J5 a,5 b ¼ 8.9, J5,Me ¼ 0.9 Hz. 13C NMR (126 MHz, CDCl3):
d 24.1 (CH3), 45.9 (C-40), 51.9 (C-10), 69.7 (C-50), 72.4 (CH2Ph), 73.4 (CH2Ph),
74.0 (CH2Ph), 79.5 (C-30), 83.7 (C-20), 108.2 (C-5), 127.68, 127.69, 127.74, 127.8,
128.1, 128.3, 128.38, 128.39, 128.5 (CArH), 137.6, 138.0, 138.2 (CAr), 161.0 (C-6),
0
0
0
0
0
0
1
164.1, 165.1 (C-2, C-4). Minor anomer: H NMR (500 MHz, CDCl3): d 2.25 (d,
3H, CH3), 3.75–3.81 (m, 2H, H-40, H-50a), 4.02 (dd, 1H, H-50b), 4.21 (dd, 1H, H-20),
4.37 (dd, 1H, H-30), 4.48, 4.53 (AB system, 2H, CH2Ph, JAB ¼ 12.0 Hz), 4.58, 4.61
(AB system, 2H, CH2Ph, JAB ¼ 11.7 Hz), 4.70, 4.88 (AB system, 2H, CH2Ph,
JAB ¼ 12.2 Hz), 5.33 (d, 1H, H-10), 6.05 (q, 1H, H-5), 7.24–7.40 (m, 15H, ArH).
Jl ,2 ¼ 3.3, J2 ,3 ¼ 3.3, J3 ,4 ¼ 6.2, J4 ,5 b ¼ 4.0, J5 a,5 b ¼ 8.8, J5,Me ¼ 0.9 Hz. 13C
NMR (126 MHz, CDCl3): d 24.0 (CH3), 47.0 (C-40), 50.3 (C-10), 71.46 (C-50),
72.48 (CH2Ph), 73.2 (CH2Ph), 73.3 (CH2Ph), 79.8 (C-30), 86.4 (C-20), 108.9 (C-5),
127.3, 127.6, 127.7, 127.8, 127.9, 127.95, 128.00, 128.4, 128.5 (CArH), 137.8, 138.0,
138.3 (CAr), 159.5 (C-6), 164.6, 165.5 (C-2, C-4).
0
0
0
0
0
0
0
0
0
0
1-(2,3,5-Tri-O-acetyl-4-thio-l-lyxofuranosyl)-2-thiouracil (15). GP1; from 1412
(100 mg, 0.33 mmol) and 4-trimethylsilyloxy-2-trimethylsilylthiopyrimidine. CC
[PE=EtOAc 1:2, Rf (a,b) 0.11] yielded the inseparable anomers of 15 as a white
solid (58 mg, 44%, A1=A2 ¼ 5:2). IR: n 3436 (NH), 1753 (C¼O), 1667 (C¼O), 1528
(thioamide-B) cmꢀ1. FAB MS; m=z: 403 [M þ H]þ. Major anomer: 1H NMR
(500 MHz, CDCl3): d 2.04 (s, 3H, COCH3), 2.09 (s, 3H, COCH3), 2.11 (s, 3H,
COCH3), 4.00 (ddd, 1H, H-40), 4.14 (dd, 1H, H-50a), 4.40 (dd, 1H, H-50b), 5.38

1888
Wirsching et al.
(d, 1H, H-10), 5.51 (dd, 1H, H-20), 5.73 (dd, 1H, H-30), 6.25 (d, 1H, H-5), 7.89
0
0
0
0
0
0
0
0
0
0
0
0
(d, 1H, H-6). Jl ,2 ¼ 6.9, J2 ,3 ¼ 3.5, J3 ,4 ¼ 5.3, J4 ,5 a ¼ 7.4, J4 ,5 b ¼ 7.3, J5 a,5 b ¼ 11.1,
J5,6 ¼ 6.6 Hz. 13C NMR (126 MHz, CDCl3): d 21.0 (COCH3), 21.05 (COCH3), 21.08
(COCH3), 44.6 (C-40), 50.9 (C-10), 64.6 (C-50), 72.3 (C-30), 77.5 (C-20), 112.0 (C-5),
155.2 (C-6), 160.6 (C-2, C-4), 169.8 (COCH3), 170.1 (COCH3), 170.8 (COCH3).
1
Minor anomer: H NMR (500 MHz, CDCl3): d 2.03 (s, 3H, COCH3), 2.06 (s, 3H,
COCH3), 2.20 (s, 3H, COCH3), 3.86 (ddd, 1H, H-40), 4.15 (dd, 1H, H-50a), 4.42
(dd, 1H, H-50b), 5.60 (dd, 1H, H-20), 5.72 (dd, 1H, H-30), 5.88 (d, 1H, H-10), 6.22
0
0
0
0
0
0
0
0
(d, 1H, H-5), 7.85 (d, 1H, H-6). Jl ,2 ¼ 6.3, J2 ,3 ¼ 3.4, J3 ,4 ¼ 5.2, J4 ,5 a ¼ 7.3,
J4 ,5 b ¼ 7.7, J5 a,5 b ¼ 11.1, J5,6 ¼ 6.6 Hz. 13C NMR (126 MHz, CDCl3): d 21.0
(COCH3), 21.07 (COCH3), 21.08 (COCH3), 44.6 (C-40), 51.6 (C-10), 63.5 (C-50),
72.3 (C-30), 74.6 (C-20), 111.6 (C-5), 155.2 (C-6), 161.5, 164.8 (C-2, C-4), 169.8
(COCH3), 169.9 (COCH3), 170.8 (COCH3).
0
0
0
0
6-Methyl-1-(2,3,5-tri-O-acetyl-4-thio-l-lyxofuranosyl)-2-thiouracil (16). GP1;
from 1412 (100 mg, 0.33 mmol) and 6-methyl-4-trimethylsilyloxy-2-trimethylsilylthio-
pyrimidine. CC [PE=EtOAc 1:2, Rf (a,b) 0.13] gave the inseparable anomers of 16 as
a white solid (31 mg, 23%, A1=A2 ¼ 2:1). IR: n 3451 (NH), 1753 (C¼O), 1659 (C¼O),
1
1581 (thioamide-B) cmꢀ1. FAB MS; m=z: 417 [M þ H]þ. Major anomer: H NMR
(500 MHz, CDCl3): d 2.05 (s, 3H, COCH3), 2.11 (s, 3H, COCH3), 2.12 (s, 3H,
COCH3), 2.26 (s, 3H, CH3), 3.98 (ddd, 1H, H-40), 4.17 (dd, 1H, H-50a), 4.41
(dd, 1H, H-50b), 5.31 (d, 1H, H-10), 5.61 (dd, 1H, H-20), 5.70 (dd, 1H, H-30), 6.08
0
0
0
0
0
0
0
0
0
0
0
0
(q, 1H, H-5). J1 ,2 ¼ 5.3, J2 ,3 ¼ 3.7, J3 ,4 ¼ 6.0, J4 ,5 a ¼ 7.5, J4 ,5 b ¼ 7.2, J5 a,5 b ¼ 11.2,
J5,Me ¼ 0.8 Hz. 13C NMR (126 MHz, CDCl3): d 21.0 (COCH3), 21.08 (COCH3),
21.10 (COCH3), 24.4 (CH3), 44.7 (C-40), 50.9 (C-10), 64.2 (C-50), 72.6 (C-30), 78.0
(C-20), 109.2 (C-5), 159.0 (C-6), 165.5, 166.4 (C-2, C-4), 169.6 (COCH3), 170.0
1
(COCH3), 170.8 (COCH3). Minor anomer: H NMR (500 MHz, CDCl3): d 2.03
(s, 3H, COCH3), 2.04 (s, 3H, COCH3), 2.20 (s, 3H, COCH3), 2.25–2.26 (m, 3H,
CH3), 3.85 (ddd, 1H, H-40), 4.12 (dd, 1H, H-50a), 4.14 (dd, 1H, H-50b), 5.60–5.63
(m, 1H, H-20), 5.72 (dd, 1H, H-30), 5.89 (d, 1H, H-10), 6.05 (q, 1H, H-5).
0
0
0
0
0
0
0
0
0
0
0
0
J1 ,2 ¼ 6.3, J2 ,3 ¼ 3.4, J3 ,4 ¼ 5.1, J4 ,5 a ¼ 7.3, J4 ,5 b ¼ 7.3, J5 a,5 b ¼ 11.1, J5,Me
¼
0.9 Hz. 13C NMR (126 MHz, CDCl3): d 20.95 (COCH3), 21.05 (COCH3), 21.13
(COCH3), 24.4 (CH3), 44.4 (C-40), 51.7 (C-10), 63.5 (C-50), 73.1 (C-30), 74.5 (C-20),
108.8 (C-5), 160.0 (C-6), 165.4, 166.2 (C-2, C-4), 169.7 (COCH3), 170.0 (COCH3),
170.8 (COCH3).
1-(4-Thio-b-l-lyxofuranosyl)-2-thiouracil (17).
A solution of 15 (56 mg,
0.14 mmol) in dry MeOH (1.0 mL) was added to a solution of sodium (1 mg,
0.04 mmol) in dry MeOH (6.0 mL). The reaction mixture was stirred at room tem-
perature for 24 h. Water was added. The solvent was evaporated and the residue
was purified by CC (CHCl3=MeOH 4:1, Rf 0.21) and reversed phase HPLC
(MeCN=H2O 7:93) to yield 17 (4 mg, 10%) as a white solid. M.p. 169–172ꢁC
(decomp.). [a]D20 ꢀ89.7 (c 0.4, MeOH). IR: n 3433 (OH), 1662 (C¼O), 1531 thioa-
1
mide-B) cmꢀ1. H NMR (500 MHz, [D6]DMSO): d 3.40 (dd, 1H, H-50a), 3.55 (ddd,
1H, H-40), 3.73 (dd, 1H, H-50b), 4.00 (dd, 1H, H-20), 4.13 (dd, 1H, H-30), 4.75 (bs, 1H,
50-OH), 5.05 (d, 1H, H-10), 5.11 (bs, 2H, 20-OH, 30-OH), 6.08 (d, 1H, H-5), 7.84 (d,
0
0
0
0
0
0
0
0
0
0
0
0
1H, H-6). J1 ,2 ¼ 8.6, J2 ,3 ¼ 3.4, J3 ,4 ¼ 3.8, J4 ,5 a ¼ 7.3, J4 ,5 b ¼ 6.2, J5 ,a,5 b ¼ 10.7,

Thiosugars. X
1889
J5,6 ¼ 6.4 Hz. 13C NMR (126 MHz, [D6]DMSO): d 50.2 (C-40), 52.6 (C-l0), 61.1 (C-50),
72.6 (C-30), 79.7 (C-20), 109.6 (C-5), 154.1 (C-6), 164.0 (C-4), 172.3 (C-2). FAB MS;
m=z: 277 [M þ H]þ. FAB HRMS: calcd. 277.0317 [M þ H]þ; found 277.0319.
6-Methyl-1-(4-thio-b-l-lyxofuranosyl)-2-thiouracil (18). Compound 18 was
prepared as described for 17 from 16 (30 mg, 0.07 mmol). CC (CHCl3=MeOH 4:1,
Rf ¼ 0.25) and reversed phase HPLC (MeCN=H2O 9:91) gave 18 as a white solid
20
(5 mg, 24%). M.p. 162–164ꢁC (decomp.). [a]D ꢀ46.0 (c 0.5, MeOH). IR: n 3434
1
(OH), 1655 (C¼O), 1565 (thioamide-B) cmꢀ1. H NMR (500 MHz, [D6]DMSO): d
2.12 (d, 3H, CH3), 3.41 (dd, 1H, H-50a), 3.55 (ddd, 1H, H-40), 3.73 (dd, 1H,
H-50b), 4.00 (dd, 1H, H-30), 4.12 (dd, 1H, H-20), 4.75 (bs, 1H, 50-OH), 5.01 (d, 1H,
H-10), 5.10 (bs, 2H, 20-OH, 30-OH), 5.90 (bs, 1H, H-5). J1 ,2 ¼ 8.4, J2 ,3 ¼ 3.4,
0
0
0
0
J3 ,4 ¼ 3.7, J4 ,5 a ¼ 7.4, J4 ,5 b ¼ 6.2, J5 a,5 b ¼ 10.7, J5,Me ¼ 0.6 Hz. 13C NMR
(126 MHz, [D6]DMSO): d 23.3 (CH3), 50.4 (C-40), 52.5 (C-10), 61.0 (C-50), 72.9
(C-30), 80.4 (C-20), 106.6 (C-5), 151.7 (C-6), 163.8 (C-4), 171.9 (C-2). FAB MS;
m=z: 291 [M þ H]þ. – FAB HRMS: calcd. 291.0473 [M þ H]þ; found 291.0492.
0
0
0
0
0
0
0
0
2-Methyl-4,5-dihydro-(3,5-di-O-benzyl-1,2-dideoxy-4-thio-b-l-lyxofuranoso)-[1,2-
d]-1,3-oxazole (19). GP1; from 1 (100 mg, 0.21 mmol) and 2,4-bis-N,O-trimethyl-
silylcytosine.[25] CC (CHCl3=MeOH 10:1, Rf 0.70) gave 19 as a pale yellow oil
(58 mg, 75%). [a]D þ20.5 (c 1.0, CHCl3). IR (film): n 1741 (C¼N) cmꢀ1
.
1H
20
NMR (400 MHz, CDCl3): d 1.82 (d, 3H, CH3), 3.36 (dd, 1H, H-5a), 3.61 (ddd,
1H, H-4), 3.87 (dd, 1H, H-5b), 4.23 (dd, 1H, H-3), 4.53, 4.58 (AB system, 2H,
CH2Ph, JAB ¼ 12.3 Hz), 4.64, 4.75 (AB system, 2H, CH2Ph, JAB ¼ 12.1 Hz), 4.96
(dd, 1H, H-2), 5.35 (dq, 1H, H-1), 7.27–7.38 (m, 10H, ArH). J1,2 ¼ 7.6, J1,Me ¼ 0.8,
J2,3 ¼ 5.0, J3,4 ¼ 6.5, J4,5a ¼ 8.9, J4,5b ¼ 4.4, J5a,5b ¼ 9.9 Hz. 13C NMR (101 MHz,
CDCl3): d 12.5 (CH3), 46.4 (C-4), 68.3 (C-5), 70.8 (CH2Ph), 71.5 (CH2Ph), 71.6
(C-1), 81.2 (C-3), 82.3 (C-2), 125.8, 126.0, 126.2, 126.4, 126.6, 126.8 (CArH), 135.3,
136.2 (CAr), 165.9 (CCH3).
4-(1,2,4-Triazol-1-yl)-1-(2,3,5-tri-O-benzyl-4-thio-l-lyxofuranosyl)-2(1H)-pyrimi-
dinone (22). POCl3 (0.93 mL, 1.56 g, 10.19 mmol) was added at 0ꢁC to a suspension
of 1,2,4-triazole (3.23 g, 46.75 mmol) in dry MeCN (10 mL). After stirring for 0.5 h,
Et3N (6.20 mL, 4.53 g, 44.73 mmol) was added and the suspension was warmed to
room temperature. A solution of 20[12] (416 mg, 0.78 mmol; a=b ¼ 1:2) in dry MeCN
(5 mL) was added and stirring was continued for 2.5 h. When the reaction was
completed Et3N (4.28 mL, 3.12 g, 30.88 mmol) and water (1.13 mL, 62.71 mmol) were
added. The suspension was stirred for another 0.5 h. The resulting suspension was
diluted with water (100 mL) and extracted with CHCl3. The extract was dried with
MgSO4 and evaporated. The residue was purified by CC [PE=EtOAc 1:2, Rf (a)
0.19, Rf (b) 0.27] to yield a-22 (130 mg, 29%) and b-22 (239 mg, 53%) as white
20
resinous solids. a-22: [a]D ꢀ71.2 (c 1.0, CHCl3). IR: n 3112 (NH), 1674 (C¼O),
1
1630 (C¼N) cmꢀ1. H NMR (400 MHz, CDCl3): d 3.72 (dd, 1H, H-50a), 3.96–3.98
(m, 1H, H-40), 3.97 (dd, 1H, H-50b), 4.11–4.13 (m, 2H, H-20, H-30), 4.52, 4.55 (AB
system, 2H, CH2Ph, JAB ¼ 11.7 Hz), 4.54, 4.74 (AB system, 2H, CH2Ph,
JAB ¼ 12.4 Hz), 4.57, 4.69 (AB system, 2H, CH2Ph, JAB ¼ 11.6 Hz), 6.31 (d, 1H, H-10),

1890
Wirsching et al.
6.89 (d, 1H, H-5), 7.21–7.38 (m, 15H, ArH), 8.14 (s, 1H, CHtriazole), 8.15 (d, 1H,
0
0
0
0
0
0
0
0
H-6), 9.28 (s, 1H, CHtriazole). J1 ,2 ¼ 5.1, J4 ,5 a ¼ 10.0, J4 ,5 b ¼ 6.1, J5 a,5 b ¼ 11.5, J5,6
¼
7.4 Hz. 13CNMR (101MHz, CDCl3): d 47.6 (C-40), 65.9 (C-10), 70.3 (C-50), 72.3 (CH2Ph),
73.5 (2C, CH2Ph), 77.2 (C-30), 86.7 (C-20), 95.1 (C-5), 127.81, 127.83, 127.9, 128.06,
128.14, 128.4, 128.46, 128.51 (CArH), 137.1, 137.5, 137.9 (CAr), 143.2 (CHtriazole),
147.7 (C-6), 154.1 (CHtriazole), 154.8, 158.9 (C-2, C-4). FAB MS; m=z: 582
[M þ H]þ. b-22: [a]D þ54.2 (c 0.9, CHCl3). IR: n 3134 (NH), 1682 (C¼O), 1631
20
(C¼N) cmꢀ1. 1H NMR (400 MHz, CDCl3): d 3.69–3.75 (m, 1H, H-40), 3.95–3.99 (m,
1H, H-50a), 4.09–4.15 (m, 1H, H-50b), 4.22–4.25 (m, 2H, H-20, H-30), 4.52–4.76 (m,
6H, 3CH2Ph), 6.64–6.66 (m, 2H, H-10, H-5), 7.20–7.37 (m, 15H, ArH), 8.12 (s, 1H,
CHtriazole), 8.65 (d, 1H, H-6), 9.27 (s, 1H, CHtriazole). J5,6 ¼ 7.4 Hz. 13C NMR
(101 MHz, CDCl3): d 47.0 (C-40), 61.0 (C-10), 69.0 (C-50), 73.4 (CH2Ph), 74.0 (CH2Ph),
74.1 (CH2Ph), 80.3 (C-30), 82.4 (C-20), 93.5 (C-5), 127.78, 127.84, 127.92, 127.94,
128.17, 128.22, 128.40, 128.41, 128.5 (CArH), 137.1, 137.3, 137.7 (CAr), 152.0 (C-6),
153.8, 154.8 (CHtriazole), 155.9, 158.6 (C-2, C-4). FAB MS; m=z: 582 [M þ H]þ.
1-(2,3,5-Tri-O-benzyl-4-thio-l-lyxofuranosyl)cytosine (24). A 25% aq. NH3
solution (17.2 mL) was added to a solution of 22 (330 mg, 0.57 mmol, a=b ¼ 1:2) in
1,4-dioxane (7.0 mL). The mixture was stirred at room temperature for 24 h. The sol-
vents were evaporated, the residue was dissolved in CHCl3 and washed with water.
The organic phase was dried with MgSO4 and evaporated. The crude 24 was purified
by CC [CHCl3=MeOH 9:1, Rf (a) 0.35, Rf (b) 0.19] to yield a-24 (80 mg, 27%) and
20
b-24 (167 mg, 56%) as white solids. a-24: M.p. 80–83ꢁC. [a]D ꢀ33.6 (c 1.0, CHCl3).
1
IR: n 3192 (NH), 1690 (C¼O) cmꢀ1. H NMR (400 MHz, CDCl3): d 3.63 (dd, 1H,
H-50a), 3.85–3.93 (m, 2H, H-40, H-50b), 4.06–4.10 (m, 2H, H-20, H-30), 4.47, 4.50
(AB system, 2H, CH2Ph, JAB ¼ 11.8 Hz), 4.55, 4.61 (AB system, 2H, CH2Ph,
JAB ¼ 12.4 Hz), 4.55, 4.69 (AB system, 2H, CH2Ph, JAB ¼ 11.7 Hz), 5.78 (d, 1H,
H-5), 6.27 (d, 1H, H-10), 7.20–7.34 (m, 15H, ArH), 7.45 (d, 1H, H-6), 8.18 (bs,
2H, NH2). J1 ,2 ¼ 5.8, J4 ,5 a ¼ 6.5, J5 a,5 b ¼ 8.2, J5,6 ¼ 7.5 Hz. 13C NMR (101 MHz,
CDCl3): d 47.0 (C-40), 64.2 (C-10), 70.4 (C-50), 72.3 (CH2Ph), 73.4 (CH2Ph), 73.5
(CH2Ph), 77.7 (C-30), 85.0 (C-20), 95.7 (C-5), 127.7, 127.75, 127.76, 127.78, 127.79,
127.80, 128.35, 128.41, 128.5 (CArH), 137.5, 137.9, 138.0 (CAr), 141.8 (C-6), 156.2,
0
0
0
0
0
0
165.5 (C-2, C-4). FAB MS; m=z: 530 [M þ H]þ. b-24: M.p. 51–53ꢁC. [a]D þ26.0
20
1
(c 1.0, CHCl3). IR: n 3180 (NH), 1678 (C¼O) cmꢀ1. H NMR (400 MHz, CDCl3):
d 3.59–3.63 (m, 1H, H-40), 3.71 (dd, 1H, H-50a), 3.97 (dd, 1H, H-50b), 4.14–4.17
(m, 2H, H-20, H-30), 4.48, 4.53 (AB system, 2H, CH2Ph, JAB ¼ 11.9 Hz), 4.51, 4.57
(AB system, 2H, CH2Ph, JAB ¼ 11.8 Hz), 4.55, 4.68 (AB system, 2H, CH2Ph,
JAB ¼ 11.3 Hz), 5.54 (d, 1H, H-5), 6.60 (d, 1H, H-10), 7.17–7.34 (m, 15H, ArH),
0
0
0
0
0
0
8.07 (d, 1H, H-6), 8.36 (bs, 2H, NH2). J1 ,2 ¼ 6.3, J4 ,5 a ¼ 7.6, J4 ,5 b ¼ 6.2,
13
J5 a,5 b ¼ 9.5, J5,6 ¼ 7.6 Hz. C NMR (101 MHz, CDCl3): d ¼ 47.0 (C-40), 59.2
(C-10), 69.8 (C-50), 73.3 (CH2Ph), 73.5 (CH2Ph), 73.6 (CH2Ph), 80.6 (C-30), 81.6
(C-20), 93.7 (C-5), 127.74, 127.75, 127.9, 128.0, 128.35, 128.36, 128.4 (CArH),
137.55, 137.63, 137.9 (CAr), 145.9 (C-6), 156.8, 165.3 (C-2, C-4). FAB MS; m=z:
530 [M þ H]þ.
0
0
1-(4-Thio-a-l-lyxofuranosyl)cytosine (26). GP2; from 26 (780 mg, 1.47 mmol,
a=b ¼ 1:2). CC (CHCl3=MeOH 2:1, Rf 0.10) and reversed phase HPLC (MeCN=H2O

Thiosugars. X
1891
20
O 9:91) gave 26 as a white solid (13 mg, 3%). M.p. 188–191ꢁC. [a]D ꢀ48.5 (c 1.0,
1
MeOH). IR: n 3352 (OH), 3210 (NH), 1645 (C¼O), 1603 (C¼N) cmꢀ1. H NMR
(500 MHz, [D6]DMSO): d 3.45 (ddd, 1H, H-40), 3.63 (ddd, 1H, H-50a), 3.84 (ddd,
1H, H-50b), 4.13 (ddd, 1H, H-20), 4.18 (ddd, 1H, H-30), 4.94 (dd, 1H, 50-OH), 5.35
(d, 1H, 30-OH), 5.49 (d, 1H, 20-OH), 5.68 (d, 1H, H-5), 6.26 (d, 1H, H-10), 6.97
0
0
0
0
(bs, 1H, NHH), 7.07 (bs, 1H, NHH), 8.20 (d, 1H, H-6). J1 ,2 ¼ 6.6, J2 ,3 ¼ 3.7,
0
0
0
0
0
0
0
0
0
0
J2 ,OH ¼ 6.0, J3 ,4 ¼ 5.1, J3 ,OH ¼ 4.6, J4 ,5 a ¼ 7.3, J4 ,5 b ¼ 5.2, J5 a,5 b ¼ 10.9,
J5 a,OH ¼ 5.5, J5 b,OH ¼ 5.2, J5,6 ¼ 7.5 Hz. 13C NMR (126 MHz, [D6]DMSO): d 50.4
(C-40), 59.2 (C-10), 60.3 (C-50), 72.6 (C-30), 73.5 (C-20), 91.8 (C-5), 144.9 (C-6),
155.4, 164.5 (C-2, C-4). FAB MS; m=z: 260 [M þ H]þ. FAB HRMS: calcd.
260.0705 [M þ H]þ; found 260.0707.
0
0
6-Methyl-4-(1,2,4-triazol-1-yl)-1-(2,3,5-tri-O-benzyl-4-thio-a-l-lyxofuranosyl)-2(1H)-
pyrimidinone (23). Compound 23 was prepared as described for 22 from 1,2,4-tri-
azole (12.86 g, 186 mmol) and 21[12] (1.69 g, 3.10 mmol, a=b ¼ 10:1). CC (PE=EtOAc
20
EtOAc 1:2, Rf 0.21) gave 23 as a white solid (1.25g, 68%). M.p. 54–56ꢁC. [a]D
ꢀ128.5 (c 1.0, CHCl3). IR: n 1680 (C¼O), 1644 (C¼N) cmꢀ1. H NMR (400 MHz,
1
CDCl3): d 2.47 (s, 3H, CH3), 3.55 (dd, 1H, H-50a), 3.83 (dd, 1H, H-50b), 4.25, 4.52
(AB system, 2H, CH2Ph, JAB ¼ 12.1 Hz), 4.34 (ddd, 1H, H-40), 4.38 (dd, 1H,
H-30), 4.50 (s, 2H, CH2Ph), 4.72, 4.88 (AB system, 2H, CH2Ph, JAB ¼ 11.7 Hz),
5.30 (dd, 1H, H-20), 5.96 (d, 1H, H-10), 6.76 (s, 1H, H-5), 7.17–7.38 (m, 15H,
0
0
0
ArH), 8.11 (s, 1H, CHtriazole), 9.21 (s, 1H, CHtriazole). J1 ,2 ¼ 7.5, J2 ,3 ¼ 3.4,
J3 ,4 ¼ 3.0, J4 ,5 a ¼ 6.1, J4 ,5 b ¼ 8.5, J5 a,5 b ¼ 9.3 Hz. 13C NMR (101 MHz, CDCl3):
d 21.9 (CH3), 49.0 (C-40), 65.8 (C-10), 68.1 (C-50), 73.2 (CH2Ph), 73.4 (CH2Ph),
74.3 (CH2Ph), 77.8 (C-30), 83.2 (C-20), 96.3 (C-5), 127.7, 127.78, 127.80, 127.82,
128.0, 128.1, 128.36, 128.44, 128.5 (CArH), 137.5, 137.8, 138.3 (CAr), 143.9
(CHtriazole), 153.9 (CHtriazole), 154.3 (C-6), 157.8, 161.7 (C-2, C-4). FAB MS;
m=z: 596 [M þ H]þ.
0
0
0
0
0
0
0
0
6-Methyl-1-(2,3,5-tri-O-benzyl-4-thio-a-l-lyxofuranosyl)cytosine (25). Compound
25 was prepared as described for 24 from 23 (1.24 g, 2.08 ) and 25% aq. NH3 solution
(16.8 mL). CC (PE=EtOAc 1:2, Rf 0.29) gave 25 as a white solid (959 mg, 68%).
M.p. 82–83ꢁC. [a]D ꢀ107.7 (c 1.1, CHCl3). IR: n 3191 (NH), 1665 (C¼O) cmꢀ1
.
20
1H NMR (400 MHz, CDCl3): d ¼ 2.12 (s, 3H, CH3), 3.53 (dd, 1H, H-50a), 3.80
(dd, 1H, H-50b), 4.24 (ddd, 1H, H-40), 4.29 (dd, 1H, H-30), 4.39, 4.50 (AB system,
2H, CH2Ph, JAB ¼ 11.9 Hz), 4.43, 4.47 (AB system, 2H, CH2Ph, JAB ¼ 11.7 Hz),
4.65, 4.87 (AB system, 2H, CH2Ph, JAB ¼ 11.8 Hz), 5.36 (dd, 1H, H-20), 5.40 (s,
1H, H-5), 5.81 (d, 1H, H-10), 7.17–7.34 (m, 15H, ArH). J1 ,2 ¼ 7.3, J2 ,3 ¼ 3.4,
0
0
0
0
J3 ,4 ¼ 3.0, J4 ,5 a ¼ 7.0, J4 ,5 a ¼ 7.3, J5 a,5 b ¼ 9.3 Hz. 13C NMR (101 MHz, CDCl3):
d 28.8 (CH3), 49.7 (C-40), 64.6 (C-10), 69.1 (C-50), 73.3 (CH2Ph), 73.4 (CH2Ph),
74.0 (CH2Ph), 78.4 (C-30), 84.4 (C-20), 94.4 (C-5), 127.4, 127.7, 127.76, 127.80,
128.04, 128.3, 128.4, 128.5 (CArH), 137.9, 138.0, 138.5 (CAr), 154.3, 156.3, 165.0
(C-4, C-2, C-6). FAB MS; m=z: 544 [M þ H]þ. FAB HRMS: calcd. 544.2270
[M þ H]þ; found 544.2209.
0
0
0
0
0
0
0
0
6-Methyl-1-(4-thio-a-l-lyxofuranosyl)cytosine (27). GP2; from 25 (940 mg,
1.73 mmol). CC (CHCl3=MeOH 2:1, Rf 0.10) and reversed phase HPLC

1892
Wirsching et al.
(MeCN=H2O 6:94) gave 27 as a white solid (15 mg, 3%), which was crystallized from
20
H2O=EtOH 1:2 (colorless needles). M.p. 157ꢁC (decomp.). [a]D ꢀ50.8 (c 0.5,
1
MeOH). IR: n 3408 (OH), 3217 (NH), 1649 (C¼O) cmꢀ1. H NMR (500 MHz,
[D6]DMSO): d 2.22 (s, 3H, CH3), 3.41 (ddd, 1H, H-50a), 3.75 (ddd, 1H, H-50b),
3.84 (ddd, 1H, H-40), 4.07 (ddd, 1H, H-30), 4.71 (dd, 1H, 50-OH), 4.98 (d, 1H,
30-OH), 5.10–5.14 (m, 2H, H-20, 20-OH), 5.53 (s, 1H, H-5), 5.56 (bs, 1H, H-10),
0
0
0
0
0
0
0
0
0
6.92 (bs, 2H, NH2). J2 ,3 ¼ 3.3, J3 ,4 ¼ 3.0, J3 ,OH ¼ 4.4, J4 ,5 a ¼ 7.2, J4 ,5 b ¼ 6.8,
J5 a,5 b ¼ 10.6, J5 a,OH ¼ 5.7, J5 b,OH ¼ 5.3 Hz. 13C NMR (126 MHz, [D6]DMSO): d
22.7 (CH3), 54.5 (C-40), 60.6 (C-10), 62.8 (C-50), 75.1 (C-30), 78.1 (C-20), 97.1 (C-5),
156.8, 157.7, 166.8 (C-6, C-2, C-4). FAB MS; m=z: 274 [M þ H]þ. FAB HRMS:
calcd. 274.0862 [M þ H]þ; found 274.0869.
0
0
0
0
9-(2,3,5-Tri-O-benzyl-4-thio-l-lyxofuranosyl)adenine (28). GP1; from 112 (500 mg,
1.04 mmol) and adenine. CC (CHCl3=MeOH 19:1, Rf 0.41) gave 28 as a white amor-
phous solid (377 mg, 65%, a=b ¼ 2:1). IR: n 3184 (NH), (C¼N) cmꢀ1. FAB MS; m=z:
1
544 [M þ H]þ. FAB HRMS: calcd. 554.2226 [M þ H]þ; found 554.2218. a-28: H
NMR (400 MHz, CDCl3): d 3.70–3.76 (m, 2H, H-40, H-50a), 4.03 (dd, 1H, H-50b),
4.21 (dd, 1H, H-20), 4.32 (dd, 1H, H-30), 4.47–4.56 (m, 4H, 2 CH2Ph), 4.61, 4.76
(AB system, 2H, CH2Ph, JAB ¼ 11.5 Hz), 6.16 (bs, 2H, NH2), 6.39 (d, 1H, H-10),
0
0
7.24–7.37 (m, 15H, ArH), 8.31 (s, 1H, Hadenine), 8.47 (s, 1H, Hadenine). J1 ,2 ¼ 6.5,
J2 ,3 ¼ 3.3, J3 ,4 ¼ 4.0, J4 ,5 b ¼ 9.7, J5 a,5 b ¼ 12.0 Hz. – 13C NMR (101 MHz, CDCl3):
d 46.8 (C-40), 56.2 (C-10), 69.4 (C-50), 73.0 (CH2Ph), 73.5 (CH2Ph), 74.1 (CH2Ph),
79.9 (C-30), 82.8 (C-20), 118.9 (Cadenine), 127.5, 127.6, 127.8, 127.99, 128.03, 128.2,
128.4, 128.47, 128.48 (CArH), 137.0, 137.5, 137.8 (CAr), 143.1 (CHadenine), 150.7
0
0
0
0
0
0
0
0
1
(Cadenine), 152.4 (CHadenine), 155.3 (Cadenine). b-28: H NMR (400 MHz, CDCl3): d
3.58 (dd, 1H, H-50a), 3.91 (dd, 1H, H-50b), 4.14 (ddd, 1H, H-40), 4.36 (dd, 1H, H-
30), 4.47–4.56 (m, 4H, 2 CH2Ph), 4.70, 4.87 (AB system, 2H, CH2Ph, JAB ¼ 11.7 Hz),
4.74–4.77 (m, 1H, H-20), 6.09 (bs, 2H, NH2), 6.12 (d, 1H, H-10), 7.24–7.37 (m, 15H,
0
0
0
0
0
0
ArH), 7.82 (s, 1H, Hadenine), 8.27 (s, 1H, Hadenine). J1 ,2 ¼ 7.8, J2 ,3 ¼ 3.5, J3 ,4 ¼ 3.8,
J4 ,5 a ¼ 6.6, J4 ,5 b ¼ 7.7, J5 a,5 b ¼ 9.3 Hz. 13C NMR (101 MHz, CDCl3): d 47.0 (C-40),
61.7 (C-10), 69.2 (C-50), 72.6 (CH2Ph), 73.4 (CH2Ph), 74.0 (CH2Ph), 76.9 (C-30), 84.6
(C-20), 120.4 (Cadenine), 127.80, 127.81, 127.86, 127.89, 128.2, 128.38, 128.42, 128.45,
128.46 (CArH), 136.77, 137.81, 138.0 (CAr), 140.2 (CHadenine), 149.9 (Cadenine), 152.7
(CHadenine), 155.5 (Cadenine).
0
0
0
0
0
0
9-(4-Thio-l-lyxofuranosyl)adenine (29) and 9-(2-O-Benzyl-4-thio-a-l-lyxofurano-
syl)adenine (30). GP2; from 28 (370 mg, 0.67 mmol, a=b ¼ 2:1). CC (CHCl3=MeOH
2:1, Rf 0.15) and reversed phase HPLC (MeCN=H2O 8:92) gave a-29 (7 mg, 4 %),
b-29 (4 mg, 2%) and 30 (47 mg, 19%) as white solids. a-29: M.p. 148ꢁC (decomp.).
[a]D þ16.3 (c 0.7, MeOH). IR: n 3429 (OH), 1645 (C¼N) cmꢀ1
.
1H NMR
20
(500 MHz, [D6]DMSO): d 3.57 (ddd, 1H, H-40), 3.61 (dd, 1H, H-50a), 3.91 (dd,
1H, H-50b), 4.27 (dd, 1H, H-30), 4.35 (dd, 1H, H-20), 5.01 (bs, 1H, 50-OH), 5.68
(bs, 1H, 30-OH), 5.86 (bs, 1H, 20-OH), 6.06 (d, 1H, H-10), 7.14 (bs, 2H, NH2), 8.10
0
0
0
0
0
0
0
0
(s, 1H, Hadenine), 8.51 (s, 1H, Hadenine). – J1 ,2 ¼ 7.0, J2 ,3 ¼ 3.7, J3 ,4 ¼ 4.1, J4 ,5 a ¼ 7.5,
13
J4 ,5 b ¼ 5.4, J5 a,5 b ¼ 10.3 Hz. – C NMR (126 MHz, [D6]DMSO): d ¼ 51.2 (C-40),
58.0 (C-10), 61.2 (C-50), 72.9 (C-30), 75.6 (C-20), 118.2 (Cadenine), 142.7 (CHadenine),
150.3 (Cadenine), 152.3 (CHadenine), 156.0 (Cadenine). FAB MS; m=z: 284 [M þ H]þ.
0
0
0
0

Thiosugars. X
1893
FAB HRMS: calcd. 284.0817 [M þ H]þ; found 284.0813. b-29: M.p. 196–198ꢁC
(decomp.). [a]D ꢀ5.0 (c 0.4, MeOH). IR: n 3411 (OH), 1650 (C¼N) cmꢀ1. H
NMR (500 MHz, [D6]DMSO): d 3.43 (dd, 1H, H-50a), 3.80 (dd, 1H, H-50b), 3.91
(ddd, 1H, H-40), 4.21 (dd, 1H, H-30), 4.83 (dd, 1H, H-20), 4.88 (bs, 1H, 50-OH),
5.60 (bs, 2H, 20-OH, 30-OH), 5.91 (d, 1H, H-10), 7.21 (bs, 2H, NH2), 8.12 (s, 1H,
20
1
0
0
0
0
0
0
0
0
Hadenine), 8.42 (s, 1H, Hadenine). J1 ,2 ¼ 8.8, J2 ,3 ¼ 3.1, J3 ,4 ¼ 3.2, J4 ,5 a ¼ 7.5,
13
J4 ,5 b ¼ 6.5, J5 a,5 b ¼ 10.7 Hz. C NMR (500 MHz, [D6]DMSO): d 50.6 (C-40), 61.2
(C-50), 61.3 (C-10), 72.2 (C-30), 78.9 (C-20), 119.2 (Cadenine), 140.1 (CHadenine), 150.1
(Cadenine), 152.6 (CHadenine), 156.1 (Cadenine). FAB MS; m=z: 284 [M þ H]þ. FAB
HRMS: calcd. 284.0817 [M þ H]þ; found 284.0809. 30: M.p. 128–131ꢁC (decomp.).
0
0
0
0
– [a]D þ34.1 (c 1.0 in MeOH). IR: n 3426 (OH), 1655 (C¼N) cmꢀ1. H NMR
(500 MHz, [D6]DMSO): d 3.64–3.67 (m, 2H, H-40, H-50a), 3.99 (dd, 1H, H-50b),
4.32 (dd, 1H, H-20), 4.46, 4.54 (AB system, 2H, CH2Ph, JAB ¼ 11.7 Hz), 4.49–4.51
(m, 1H, H-30), 4.95 (bs, 1H, 50-OH), 5.84 (d, 1H, 30-OH), 6.36 (d, 1H, H-10), 7.02
(bs, 2H, NH2), 7.18–7.25 (m, 5H, ArH), 8.17 (s, 1H, Hadenine), 8.62 (s, 1H, Hadenine).
20
1
J1 ,2 ¼ 7.2, J2 ,3 ¼ 3.4, J4 5 b ¼ 5.4, J5 a,5 b ¼ 9.9 Hz. 13C NMR (126 MHz, [D6]DMSO):
d 51.0 (C-40), 56.3 (C-10), 61.2 (C-50), 71.2 (C-31), 83.1 (C-20), 118.3 (Cadenine), 127.6,
127.8, 128.4 (CArH), 138.0 (CAr), 142.9 (CHadenine), 150.4 (Cadenine), 152.6 (CHadenine),
156.2 (Cadenine).
0
0
0
0
0
0
0
0
9-(2,3,5-Tri-O-benzyl-4-thio-l-lyxofuranosyl)inosine (31). GP1; from 112 (600 mg,
1.25 mmol) and hypoxanthine. CC (CHCl3=MeOH 9:1, Rf 0.51) yielded 31 as a
white amorphous solid (464 mg, 67%, A1=A2 ¼ 5:4). IR: n 3437 (NH), 1627 (C¼O)
cmꢀ1. FAB MS; m=z: 555 [M þ H]þ. FAB HRMS: calcd. 555.2066 [M þ H]þ; found
1
555.2075. Major anomer: H NMR (400 MHz, CDCl3): d 3.70–3.79 (m, 2H, H-40,
H-50a), 3.98–4.02 (m, 1H, H-50b), 4.26–4.29 (m, 2H, H-20, H-30), 4.43–4.76 (m, 6H,
3 CH2Ph), 6.32 (d, 1H, H-10), 7.18–7.38 (m, 15H, ArH), 8.20 (s, 1H, Hinosine), 8.51 (s,
13
1H, Hinosine). J1 ,2 ¼ 6.5 Hz. C NMR (101 MHz, CDCl3): d 47.5 (C-40), 56.7 (C-10),
69.4 (C-50), 73.5 (CH2Ph), 73.6 (CH2Ph), 74.0 (CH2Ph), 79.8 (C-30), 82.2 (C-20),
123.7 (Cinosine), 127.4, 127.5, 127.85, 127.91, 128.2, 128.4, 128.5 (CArH), 136.6, 137.2,
137.7 (CAr), 141.2 (CHinosine), 144.9 (Cinosine), 149.0 (CHinosine), 159.0 (Cinosine).
0
0
1
Minor anomer: H NMR (400 MHz, CDCl3): d 3.70–3.79 (m, 2H, H-40, H-50a),
3.98–4.02 (m, 1H, H-50b), 4.20 (dd, 1H, H-20), 4.32 (dd, 1H, H-30), 4.43–4.76
(m, 6H, 3 CH2Ph), 6.64–6.65 (m, 1H, H-10), 7.18–7.38 (m, 15H, ArH), 8.06 (s, 1H,
Hinosine), 9.16 (s, 1H, Hinosine). J1 ,2 ¼ 6.5, J2 ,3 ¼ 3.4 Hz. – 13C NMR (101 MHz,
CDCl3): d 47.0 (C-40), 61.3 (C-10), 73.0 (C-50), 73.5 (CH2Ph), 73.6 (CH2Ph), 74.2
(CH2Ph), 79.6 (C-30), 82.9 (C-20), 114.4 (Cinosine), 127.5, 127.89, 127.94, 128.01,
128.02, 128.1, 128.3, 128.4, 128.6 (CArH), 136.9, 137.4, 137.7 (CAr), 138.3 (CHinosine),
142.9 (Cinosine), 149.9 (CHinosine), 159.0 (Cinosine).
0
0
0
0
9-(2-O-Benzyl-4-thio-a-l-lyxofuranosyl)inosine (32). GP2; from 31 (676 mg,
1.22 mmol, A1=A2 ¼ 5:4). CC (CHCl3=MeOH 2:1, Rf 0.17) yielded 32 (34 mg, 7%)
20
as a pale pink colored solid. M.p. 152ꢁC. [a]D ꢀ16.3 (c 1.0, CHCl3). IR: n 3420
1
(OH), 1687 (C¼O) cmꢀ1. H NMR (400 MHz, [D6]DMSO): d 3.56–3.65 (m, 2H,
H-40, H-50a), 3.95 (ddd, 1H, H-50b), 4.32 (dd, 1H, H-20), 4.46, 4.55 (AB system,
2H, CH2Ph, JAB ¼ 11.8 Hz), 4.47–4.50 (m, 1H, H-30), 4.93 (dd, 1H, 50-OH), 5.73
(d, 1H, 30-OH), 6.25 (d, 1H, H-10), 7.18–7.29 (m, 5H, ArH), 8.04 (d, 1H, H-8),

1894
Wirsching et al.
0
0
0
0
0
0
0
0
0
8.53 (s, 1H, H-2). J1 ,2 ¼ 7.1, J2 ,3 ¼ 3.3, J3 ,OH ¼ 4.4, J4 ,5 b ¼ 9.3, J5 a,5 b ¼ 9.3,
J5 a,OH ¼ 5.6, J5 b,OH ¼ 4.9, J8,NH ¼ 2.6 Hz. 13C NMR (101 MHz, [D6]DMSO): d
51.1 (C-40), 56.8 (C-10), 61.2 (C-50), 71.1 (C-30), 71.8, (CH2Ph), 83.2 (C-20), 123.4
(Cinosine), 127.5, 127.8, 128.4 (CArH), 138.1 (CAr), 142.4 (C-2), 145.8 (C-8), 149.2
(Cinosine), 156.9 (Cinosine). FAB MS; m=z: 375 [M þ H]þ. FAB HRMS: calcd.
375.1127 [M þ H]þ; found 375.1130.
0
0
9-(2,3,5-Tri-O-acetyl-4-thio-a-l-lyxofuranosyl)inosine (33). GP1; from 14
(118 mg, 0.39 mmol) and hypoxanthine. CC (CHCl3=MeOH 9:1, Rf 0.28) yielded
20
33 as a white solid (52 mg, 33%). M.p. 210–212ꢁC. [a]D ꢀ19.2 (c 1.0 CHCl3). IR:
n 3113 (NH), 1744 (C¼O), 1690 (C¼O) cmꢀ1
.
1H NMR (500 MHz, CDCl3): d
1.80 (s, 3H, COCH3), 2.05 (s, 3H, COCH3), 2.09 (s, 3H, COCH3), 4.06 (ddd, 1H,
H-40), 4.37 (dd, 1H, H-50a), 4.59 (dd, 1H, H-50b), 5.66 (dd, 1H, H-20), 5.80 (dd,
1H, H-30), 6.34 (d, 1H, H-10), 8.22 (s, 1H, Hinosine), 8.47 (s, 1H, Hinosine), 13.16
0
0
0
0
0
0
0
0
0
0
(bs, 1H, NH). J1 ,2 ¼ 6.4, J2 ,3 ¼ 3.8, J3 ,4 ¼ 4.8, J4 ,5 a ¼ 7.2, J4 ,5 b ¼ 7.5,
J5 a,5 b ¼ 11.2 Hz. 13C NMR (126 MHz, CDCl3): d 20.3 (COCH3), 20.6 (COCH3),
20.7 (COCH3), 45.1 (C-40), 57.9 (C-10), 62.3 (C-50), 72.1 (C-30), 73.9 (C-20), 124.2
(Cinosine), 140.3 (Cinosine), 141.1 (CHinosine), 145.3, (CHinosine), 158.9 (Cinosine), 168.8
(COCH3), 169.1 (COCH3), 170.4 (COCH3).
0
0
9-(4-Thio-a-l-lyxofuranosyl)inosine (34). Compound 34 was prepared as
described for 17 from 33 (45 mg, 0.11 mmol). CC (Sephadex LH20, MeOH, Rf
0.13 in CHCl3=MeOH 2:1) and reversed phase HPLC (MeCN=H2O 8:92) gave 34
20
as a white solid (5 mg, 16%). M.p. 145ꢁC (decomp.). [a]D þ11.0 (c 0.5 MeOH).
1
IR: n 3393 (OH), 3170 (NH), 1699 (C¼O) cmꢀ1. H NMR (500 MHz, [D6]DMSO):
d 3.59 (ddd, 1H, H-40), 3.64 (dd, 1H, H-50a), 3.93 (dd, 1H, H-50b), 4.28 (dd, 1H, H-30),
4.36 (dd, 1H, H-20), 4.96 (bs, 1H, 50-OH), 5.65 (bs, 2H, 20-OH, 30-OH), 6.02 (d, 1H,
H-10), 8.00 (s, 1H, Hinosine), 8.42 (s, 1H, Hinosine). J1 ,2 ¼ 7.0, J2 ,3 ¼ 3.8, J3 ,4 ¼ 4.1,
0
0
0
0
0
0
J4 ,5 a ¼ 7.7, J4 ,5 b ¼ 5.4, J5 a,5 b ¼ 10.5 Hz. – 13C NMR (126 MHz, [D6]DMSO):
d ¼ 51.5 (C-40), 58.6 (C-10), 61.4 (C-50), 73.1 (C-30), 75.9 (C-20), 123.4 (Cinosine),
142.0 (CHinosine), 146.3 (CHinosine), 149.4 (Cinosine), 157.9 (Cinosine). FAB MS; m=z:
285 [M þ H]þ. FAB HRMS: calcd. 285.0658 [M þ H]þ; found 285.0639.
0
0
0
0
0
0
ACKNOWLEDGMENTS
The Deutsche Forschungsgemeinschaft, the European Commission, and the
Fonds der Chemischen Industrie are gratefully acknowledged for their financial
support. We thank the Degussa-Huls AG for supplying silver carbonate. We also
¨
thank Prof. Dr. Chris Meier and Dipl.-Chem. Andreas Lomb for making their
HPLC equipment available to us as well as Mrs. Ann Absillis, Mrs. Anita Camps,
Mrs. Anita Van Lierde, Mrs. Frieda De Meyer and Miss Lies Vandenheurck for
technical assistance.

Thiosugars. X
1895
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