Synthesis and reactions of anhydro-azido-thio-D-lyxofuranosides

Article abstract of DOI:10.1080/10426500500326545

2,5-anhydro-3-azido-2-thio-D-lyxofuranosides and 3,5-anhydro-2-azido-3- thio-D-lyxofuranosides were prepared from methyl D-xylofuranoside or methyl D-ribofuranoside via corresponding 2,3-epoxysugars or the 5-O-trityl derivative. The sulfur was introduced

Full text of DOI:10.1080/10426500500326545

Phosphorus, Sulfur, and Silicon, 181:1249–1270, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500500326545
Synthesis and Reactions of
Anhydro-Azido-thio-D-lyxofuranosides1
Dirk Otzen
¨
Jurgen Voss
Institut fu¨r Organische Chemie der Universita¨t Hamburg,
Hamburg, Germany
Gunadi Adiwidjaja
Mineralogisch-Petrographisches Institut der Universita¨t Hamburg,
Hamburg, Germany
2,5-anhydro-3-azido-2-thio-D-lyxofuranosides and 3,5-anhydro-2-azido-3-thio-D-
lyxofuranosides were prepared from methyl D-xylofuranoside or methyl D-
ribofuranoside via corresponding 2,3-epoxysugars or the 5-O-trityl derivative. The
sulfur was introduced into molecules by use of the thio-Mitsunobu reaction. Bicyclic
azido-thiosugars were transformed into nucleoside analogues, oxidized to sulfoxides
and sulfones, and reduced to bicyclic amino-thiosugars. Structures and configura-
tions of products were determined by NMR spectroscopy or X-ray structure analyses.
Keywords Azides; cyclization; oxidation; Thiosugars; X-ray diffraction
INTRODUCTION
The carbohydrates described in the following exhibit three particular
molecular features. They are thiosugars, they are bicyclic compounds
(anhydrosugar-type), and they are substituted with an azido group.
Each of these three peculiarities is known as a reason for special chemi-
cal and biochemical properties. Especially the thiosugars have recently
found widespread chemical and biochemical interest.2−4 Anhydrosug-
ars as well are interesting synthetic building blocks in carbohydrate
chemistry, and the corresponding nucleoside analogues represent pre-
cursors for the synthesis of locked nucleic acids.5 Finally, azidosugars
Received June 2, 2005; accepted June 16, 2005.
The University of Hamburg and the Fonds der Chemischen Industrie are gratefully
acknowledged for their financial support.
Address correspondence to Ju¨rgen Voss, Universita¨t Hamburg, Institut fu¨r Organ-
ische Chemie, Martin-Luther-King-Platz 6, Hamburg 20146, Germany. E-mail: voss@
chemie.uni-hamburg.de
1249

1250
D. Otzen et al.
are the most suitable starting compounds for the preparation of the
important aminosugars.6a Furthermore, the nucleoside analogue azi-
dothymine is known as the first chemotherapeutic drug with a signif-
icant activity against HIV.7,8 In continuation of our studies on mono-9
and bicyclic10,11 thiosugars, we present here our results on the synthe-
sis of monosaccharides with a corresponding combination of these three
structural moieties.
RESULTS AND DISCUSSION
Syntheses
Methyl 2,3-anhydro-α-D-ribofuranoside (1), which is available in large
amounts from inexpensive D-xylose,12 reacted with sodium azide and
ammonium chloride in refluxing aqueous ethanol to yield a mix-
ture of the 3-azido-3-deoxy-xylofuranoside 2 and the 2-azido-2-deoxy-
arabinofuranoside 3 by a nucleophilic ring opening of the epoxide. Two
isomers were formed with good overall yield in a ratio of 3:2 in favor
of 3. This slight regioselectivity is obviously due to steric hindrance of
the attack at C-3 by the hydroxymethyl substituent on C-4. Isomers
could be separated, by column chromatography, but also the mixture
was suitable as starting material for the thio-Mitsunobu reaction with
thioacetic acid in the next step. It resulted in an expected 2:3 mixture of
the 2-azido- and the 3-azido-5-S-thioacetates 4 and 5. The azido groups
of 2 and 3 were not reduced by thioacetic acid or triphenyl phosphine
under the conditions of the thio-Mitsunobu reaction as one could ex-
pect. Column chromatography led to pure isomers as yellowish syrups.
Structures and configurations of 2, 3, 4, and 5 follow from their 1H and
13C NMR spectra. In particular, chemical shifts δ(13C) of 66.5 ppm for
C-3 in 2 and 71.8 ppm for C-2 in 3 as compared with 76.9 ppm for C-2
in 2 and 75.4 ppm for C-3 in 3 are indicative of the respective positions
of the azido and the hydroxy substituents. The proton coupling con-
stants 3 J = 4.5 Hz and 3 J = 2.0 Hz, respectively, are characteristic
1,2
1,2
of the α-xylo configuration of 2 and the α-arabino configuration of 3.
Furthermore, X-ray structures of the follow-up products 27 and 29 (see
Reactions) corroborate the structural assignments.
The mesylation of 4 gave a 83% yield of the mesylate 6. Nucle-
ophilic thioester cleavage with sodium hydrogen carbonate and con-
comitant intramolecular displacement of the mesylate leaving group by
the 5-thiolate substituent under a ring closure finally resulted in the
bicyclic methyl 2,5-anhydro-3-azido-3-deoxy-2-thio-α-D-lyxofuranoside
(7) (Scheme 1). In spite of the presence of an azido substituent in the
syn-2,3-position, which might cause some steric hindrance, the yield

Anhydro-Azido-thio-D-lyxofuranosides
1251
SCHEME 1
of 7 was 75%. The azido group remained unaffected. The mesylate 8
obtained from the 3-azido-5-S-thioacetate 5, on the other hand, reacted
with sodium hydrogen carbonate to form the expected thietano-sugar
9 (Scheme 1).
In
a
related reaction sequence, methyl 2,3-anhydro-β-D-
ribofuranoside (10), which can be prepared in only two steps from
D-xylose,13 was transformed into methyl 2,5-anhydro-3-azido-3-deoxy-
2-thio-β-D-lyxofuranoside (14). In the first step, the reaction of 10 with
sodium azide, methyl 3-azido-3-deoxy-β-D-xylofuranoside (11) was
formed with a 74.5% yield as the only isomer. Steric hindrance as well
as the electronic repulsion by the β-glycosidic methoxy group in 10
and the known reduced reactivity for nucleophilic substitutions next
to anomeric centers6b,14−16 should be reasons for the regioselectivity in
this case as compared with the epoxide ring opening of the α-anomer
1. We have observed the same pronounced regioselectivities for the

1252
D. Otzen et al.
reactions of methyl 2,3-anhydro-α-D- and -α-L-lyxofuranoside with
sodium azide, which led to methyl 3-azido-3-deoxy-α-D- and -α-L-
arabinofuranoside as the only products with yields of over 90%.17,18
The thio-Mitsunobu reaction of 11 with thioacetic acid again selectively
led to the expected 3-azido-5-S-thioacetate 12 with a 79% yield. The
mesylation of 12 led to 13. The subsequent nucleophilic cleavage of the
thioester group with sodium hydrogen carbonate under concomitant
intramolecular displacement of the mesylate group and ring closure
gave 65% of the bicyclic azido-thietano-sugar 14 (Scheme 2). The total
yield for the six steps from D-xylose to 14 amounted to 11.4%.
SCHEME 2
We have also explored an alternative route to 14. First, methyl β-D-
ribofuranoside was tritylated.19 The 5-O-trityl-riboside 15 was mesy-
lated to form the dimesylate 16. Nucleophilic displacement with azide
expectedly (see preceeding paragraph) took place with complete re-
gioselectivity to yield the 3-azido-sugar 17 with β-D-xylo configuration.
The deprotection of 17 gave 18; the thio-Mitsunobu reaction also pro-
vided the precursor 13 for the preparation of the anhydrothio sugar 14
(Scheme 3). This sequence is however unfavorable as compared with
the aforementioned D-xylose-based route since it starts from D-ribose,
which is more expensive by a factor of five, and it includes seven steps
with an overall yield of only 7.6%. Also, methyl 2,3-di-O-sulfinyl-5-O-
trityl-β-D-ribofuranoside (19), which we have prepared from 15 by a

Anhydro-Azido-thio-D-lyxofuranosides
1253
SCHEME 3
reaction with thionyl chloride and triethyl amine, does not offer advan-
tages as an intermediate. The nucleophilic displacement with sodium
azide once more occurred in the 3-position under the formation of the
β-D-xylo derivative 20 with a moderate yield of 50% (Scheme 3). Sub-
stitution at the 2-position to form a compound with the desired β-D-
arabino configuration was not achieved. Furthermore, 20 could not be
successfully transformed into 14.20,21
Reactions
In continuation of our investigations on sulfur-containing nucleoside
analogues,22 we have used 7 as a glycosyl donor. Its reaction with bis-
trimethylsilylthymine under the Vorbru¨ggen conditions23 led to 21 with
a 54% yield (Scheme 4).
The α-configuration of 21 was proved by NOESY measurements. The
proton H-6 of the base moiety exhibits through-space interactions with
the three carbohydrate protons H-2ꢀ, H-3ꢀ, and H-4ꢀ, which is only pos-
sible if all of these four protons are located below the furanose ring, i.e.,
if the molecule exhibits the α-D-lyxo configuration. The correct connec-
tion of the anomeric center with the 1-position of the nucleobase was
demonstrated by the characteristic UV spectrum of 21.

1254
D. Otzen et al.
SCHEME 4
Since we were also interested in sulfoxides and sulfones derived from
azido-thiosugars,24 we have studied the oxidation of 7, 14, 9, and 21
with various oxidizing reagents. First, the relatively mild oxidant hy-
drogen peroxide was used. The oxidation of the thietane 9 gave a 53%
yield of the exo-sulfoxide 23 as the only product (Scheme 5). Presum-
ably, steric hindrance by the azido substituent in the 2-position had
prevented the formation of the diastereoisomeric endo-sulfoxide and of
SCHEME 5

Anhydro-Azido-thio-D-lyxofuranosides
1255
the corresponding sulfone. The assignment of the exo-configuration to
1
23 was possible on account of its H NMR spectrum. The aniosotropic
effect of the sulfoxide group upon the syn-proton H-4 caused a down-
field shift to 5.23 ppm as compared with 4.42 ppm for the anti-proton
H-2. This observation agrees with results which we have obtained with
several related compounds (see the following paragraph).
Next, we applied potassium permanganate in the presence of ben-
zoic acid under phase transfer catalysis with benzyltriethylammonium
chloride, which mixture reacts similarly but not identically as compared
with perbenzoic acid.25 A mixture of the two possible sulfoxides (24/25)
with yields of 75% and 4%, respectively, together with 7% of the sulfone
26 was formed on reaction with 14 (Scheme 5).
The structural assignment of the two diastereoisomeric sulfoxides
was not unequivocal since no discriminating anisotropic effect of the
sulfoxide oxygen on neighboring protons was observed. In fact, chemical
shifts of H-1 are not significantly different in 24 and 25, and also the
chemical shifts of the two geminal protons H-5 and H-5ꢀ are nearly
the same in each of the two compounds. Our presumptive assignment
(Scheme 5) rests on the much higher yield of the exo-sulfoxide 25, the
formation of which should be favored on stereochemical reasons. The
structure and configuration of the sulfone 26, and as a consequence, also
of its precursors 14, 13, 12, and 11, were proved by an X-ray structure
analysis (Figure 1).
Finally, furanosides 7 and 14 and the nucleoside analogue 21 were
oxidized with meta-chloroperbenzoic acid. Again, a mixture of the two
possible diastereoisomeric sulfoxides 28 (40%) and 27 (8%) and the sul-
fone 29 (34%) was produced from 7, whereas the β-anomer 14, not un-
expectedly, gave only the exo-sulfoxide 25 with a 51% yield (Scheme 5).
Since a large amount of the sulfone 29 was produced from 7, one cannot
FIGURE 1 ORTEP view of the X-ray diffraction structure of the sulfone 26;
thermal ellipsoids are drawn at the 50% probability level.

1256
D. Otzen et al.
FIGURE 2 ORTEP view of the X-ray diffraction structure of the sulfoxide 27;
thermal ellipsoids are drawn at the 50% probability level.
take the observed relative yields of 28 and 27 as indicative of a corre-
sponding diastereoselectivity of the oxidation reaction. The sulfoxide 27
could be well formed at a higher rate but also could be further oxidized
to the sulfone 29 in a fast follow-up reaction.
In this case, X-ray diffraction analyses of 27 (Figure 2) and 29
(Figure 3) left no doubt on the structures of the stereoisomers, although
the NMR spectra were no more conclusive than for 24 und 25. The
unequivocal structures of 27 and 29 also corroborate the structural
FIGURE 3 ORTEP view of the X-ray diffraction structure of the sulfone 29;
thermal ellipsoids are drawn at the 50% probability level.

Anhydro-Azido-thio-D-lyxofuranosides
1257
assignments of their precursors 7, 6, 4, and 2, and in addition, of 5
and 3.
The thymidine derivative 21 gave a 74% yield of the endo-sulfoxide
22 (Scheme 4) as the only product. This diastereoselectivity seems to
be due to steric repulsion of the azido substituent. It may, in addition,
result from the formation of a hydrogen bridge between N-1 of the base
in the substrate 21 and the oxidant meta-chloroperbenzoic acid, which
would direct the transfer of the oxygen to the endo-position in 22. The
configuration of 22 was evident from a significant downfield shift to
6.40 ppm for H-1 as compared with 5.80 ppm for H-1 in 21.
Reduction of the azido group should lead to aminosugars, which are
very interesting compounds from a biochemical point of view.6a We have,
therefore, studied the exemplary reduction of 7, 9, and 23. In particular,
we were interested to find out whether the functional groups present in
these compounds, i.e., the sulfide and the sulfoxide functions, remain
uneffected during the reduction of the azide substituent. We chose triph-
enylphosphine as a reducing agent, which is known for its good chemos-
electivity and yields in azide reductions.26,27 In fact, all three starting
compounds were cleanly transformed into the corresponding aminogars
30, 31, and 32, with yields of 64–69% (Scheme 6).
SCHEME 6
The products exhibited the expected spectroscopic data. The missing
azido band and the appearance of an amino band in the IR spectra

1258
D. Otzen et al.
revealed the success of the reduction. The NMR spectra are indicative
of intact structures of bicyclo-thiosugars. In particular, the unchanged
sulfoxide function of 32, which is, of course, anyhow clearly distinct
from compound 31, is evident from 13C chemical shifts of 75.8 ppm for
C-3 and 53.2 ppm for C-5 (31: 57.7 ppm and 33.9 ppm, respectively).
Conclusion
We have shown that methyl azido-deoxypentofuranosides can be se-
lectively transformed into the corresponding 5-S-acetyl-azido-5-thio
derivatives by a thio-Mitsunobu reaction with thioacetic acid. Base-
promoted tandem thioacetate splitting/intramolecular cyclization of the
2-O-mesyl- and 3-O-mesyl-thioacetates yields 3-azido-2,5-thioanhydro-
(“thiolano”-) or 2-azido-3,5-thioanhydro- (“thietano”-) pentofuranosides.
These can be transformed easily into nucleoside analogues and
aminosugars. Oxidation of sulfur leads to sulfoxides and/or sulfones
with pronounced chemo- and diastereoselectivity depending on the
structure and configuration of the substrate and the nature of the ap-
plied oxidant.
EXPERIMENTAL
General Procedure
IR spectra were measured on an ATI Mattson Genesis spectrometer
(films or KBr pellets). UV spectra were recorded on a Varian Cary 1 E
spectrometer. NMR spectra were measured on a Bruker AMX 400 spec-
trometer (1H: 400 MHz, 13C: 100.6 MHz) in CDCl3 if not stated oth-
erwise. Chemical shifts (ppm) are relative to Me4Si (1H) and CDCl3
1
(13C, δ = 77.05). In order to enhance the resolution of the H signals,
the spectra were recalculated from the FID by use of the WinNMR
1
1
software (Bruker). H-1H-COSY-, H-13C-Cosy-, NOESY-, and DEPT-
experiments were performed to assign the signals. Mass spectra were
measured on a Finnegan MAT 311 A (EI, 70 eV) spectrometer. Cor-
rected melting points were taken with an Electrothermal apparatus.
Optical rotations were measured on a Perkin-Elmer polarimeter 341.
TLC was performed on Merck PF254 foils. The spots were detected by
(a) spraying with 20% H2SO4 in EtOH and heating, (b) spraying with
4-methoxybenzaldehyde in 2.5% H2SO4 and 0.4% AcOH in EtOH, (c)
by UV absorption. Column chromatography (CC) was performed with
Merck Kieselgel 60 (70–230 mesh), PE = redistilled petroleum ether.
X-Ray Structure Analyses
The crystal data and a summary of experimental details are given
in Table I. Data collection was performed with a Kappa-CCD

Anhydro-Azido-thio-D-lyxofuranosides
1259
TABLE I Crystal Data and Structure Refinement for 27, 29, and 26
Compound
27
29
26
Empirical formula
Formula weight
Crystal system
Space group
C6H9N3O3S
203.22
Orthorhombic
P212121
5.494(1)
6.706(1)
14.265(1)
C6H9N3O4S
219.22
Monoclinic
P21
8.760(1)
10.944(1)
8.385(1)
110.69(1)
2
C6H9N3O4S
219.22
Orthorhombic
P212121
8.522(1)
10.209(1)
10.345(1)
˚
a [A]
˚
b [A]
˚
c [A]
β [◦]
Z
4
0.33 × 0.25 × 0.16
1.574
0.356
424
2.35/27.48
0, 7/0, 14/0, 18
9348
4
0.33 × 0.28 × 0.15
1.574
0.344
456
2.80/30.02
0, 12/0, 14/0, 14
9913
Crystal size [mm]
0.37 × 0.27 × 0.23
ρcalcd. [g cm−1
]
1.624
µ [mm−1
F(000)
]
0.355
228
θ limits [◦]
2.60/30.02
0, 9/0, 11/-11, 11
3565
h/k/l limits
Reflections collected
Unique reflections
Number of parameters
R indices (all data)
1169 [R (int) = 0.047] 1376 [R (int) = 0.026] 1565 [R (int) = 0.033]
143
152
152
R = 0.0318
R = 0.0497
R = 0.0457
1
1
1
wR = 0.0770
wR = 0.1100
wR = 0.0837
2
2
2
Final R indices
[I > 2σ(I)]
R = 0.0268
R = 0.0432
R = 0.0324
1
1
1
wR = 0.0739
wR = 0.1051
wR = 0.0769
2
2
2
Goodness of fit on F 2
Abs. struct. parameter
Extinction coefficient
Largest difference
peak and hole [e A−3
1.036
0.39(10)
1.016
−0.06(13)
1.003
0.20(10)
0.015(5)
0.43(3)
0.037(4)
0.156 and −0.198
0.582 and −0.631
0.166 and −0.211
]
Nonius diffractometer with graphite-monochromated Mo-Kα radiation
˚
(0.71073 A) in the rotation ꢀ scan mode at 293 K. Structures were
solved by direct methods using the SIR-97 program28 and refined by
full-matrix block least squares on F 2 using all data and the SHELX-
97 program.29 Crystallographic data reported in this article have been
deposited with the Cambridge Crystallographic Data Centre as supple-
mentary publications no. CCDC-272968 (27), CCDC-272967 (29), and
CCDC-272969 (26). Copies of data can be obtained free of charge on
application to CCDC, 12 Union Road, Cambridge CB2 IEZ, UK [Fax:
(international) + 44-1223/336-033; E-mail: deposit@ccdc.cam.uk].
Methyl 3-Azido-3-deoxy-α-D-xylofuranoside (2) and Methyl
2-azido-2-deoxy-α-D-arabinofuranoside (3)
A solution of methyl 2,3-anhydro-α-D-ribofuranoside12 (1, 5.60 g,
38.2 mmol), NaN3 (8.47 g, 130.3 mmol), and NH4Cl (6.56 g, 122.6 mmol)
in H2O (196 mL)/EtOH (46 mL) was heated to 80◦C for 72 h. The

1260
D. Otzen et al.
solvents were distilled off, and the residue was worked up with H2O
as usual. Purification and separation by CC (EtOAc/PE 3:2) yielded
2.32 g 2 (12.3 mmol, 32.0%) and 3.49 g 3 (18.5 mmol, 48.1%) as color-
less syrups. 2 : Rf = 0.23. IR: ν = 3399 (OH), 2111 (N3) cm−1. 1H NMR:
δ = 2.83 (bs, 1H, OH), 3.36 (bs, 1H, OH), 3.48 (s, 3H, OMe), 3.72 (d, 2H,
H-5, H-5ꢀ), 4.13 (m, 1H, H-3), 4.25 (m, 1H, H-2), 4.27 (m, 1H, H-4), 4.91
(d, 1H, H-1). J = 4.5, J = 7.0, J = 4.0, J = 4.0 Hz. 13C NMR:
ꢀ
1,2
3,4
4,5
δ = 55.5 (OMe), 61.7 (C-5), 66.5 (C-3), 76.9 (C-42,5), 77.0 (C-4), 101.3 (C-
1). 3 : Rf = 0.29. IR: ν = 3391 (OH), 2113 (N3) cm−1. 1H NMR: δ = 3.13
(bs, 1H, OH), 3.43 (s, 3H, OMe), 3.75 (dd, 1H, H-5), 3.84 (dd, 1H, H-
5ꢀ), 3.92 (dd, 1H, H-2), 3.95 (bs, 1H, OH), 4.02 (m, 1H, H-4), 4.08 (m,
ꢀ
1H, H-3), 4.87 (d, 1H, H-1). J = 2.0, J = 4.0, J = 4.2, J = 3.5,
1,2
2,3
4,5
4,5
J
= 12.2 Hz. 13C NMR: δ = 55.4 (OMe), 61.5 (C-5), 71.8 (C-2), 75.4
ꢀ
5,5
(C-3), 83.9 (C-4), 106.6 (C-1).
Methyl 5-S-Acetyl-3-azido-3-deoxy-5-thio-α-D-
xylofuranoside (4) and Methyl 5-S-Acetyl-2-azido-2-deoxy-5-
thio-α-D-arabinofuranoside (5)
A solution of PPh3 (9.62 g, 36.7 mmol) in dry THF (100 mL) was
stirred at 0◦C under an Ar atmosphere. Diisopropyl azodicarboxylate
(DIAD, 7.26 g, 6.93 mL, 35.9 mmol) was added. The resulting white
suspension was stirred at 0◦C for 30 min. Then a solution of a 2:3
mixture of 2 and 3 (5.81 g, 30.7 mmol) and thioacetic acid (vacuum-
distilled three times at low temp., 2.93 g, 2.74 mL, 38.5 mmol) in dry
THF (100 mL) was slowly added. The resulting yellow solution, which
slowly turned green and finally formed a greenish yellow suspension,
was stirred at r.t. for 16 h. The THF was distilled off, and the residue
was worked up with H2O as usual. Purification and separation by CC
(EtOAc/PE, gradient of 1:4 to 1:2) yielded 2.01 g 4 (8.13 mmol, 26.5%)
and 3.32 g 5 (13.4 mmol, 43.7%) as light yellow syrups. 4: Rf = 0.26. IR:
ν = 3459 (OH), 2110 (N3), 1692 (C O) cm−1. 1H NMR: δ = 2.36 (s, 3H,
MeCO), 2.88 (bs, 1H, OH), 3.07 (dd, 1H, H-5), 3.13 (dd, 1H, H-5ꢀ), 3.49
(s, 3H, OMe), 3.99 (dd, 1H, H-3), 4.24 (m, 1H, H-2), 4.28 (m, 1H, H-4),
ꢀ
4.94 (d, 1H, H-1). J = 4.5, J = 4.5, J = 5.8, J = 6.3, J = 7.0,
1,2
2,3
3,4
4,5
4,5
ꢀ
J
= 13.8 Hz. 13C NMR: δ = 29.3 (C-5), 30.5 (CH3CO), 55.9 (OMe),
658,.50 (C-3), 76.4 (C-4), 77.0 (C-2), 101.3 (C-1), 194.9 (C O). 5: Rf = 0.33.
IR: ν = 3448 (OH), 2107 (N3), 1694 (C O) cm−1. H NMR: δ = 2.40 (s,
1
3H, CH3CO), 3.06 (bs, 1H, OH), 3.16 (dd, 1H, H-5), 3.25 (dd, 1H, H-
5ꢀ), 3.40 (s, 3H, OMe), 3.79 (dd, 1H, H-3), 3.91 (dd, 1H, H-2), 4.10 (m,
1H, H-4), 4.83 (d, 1H, H-1). J = 2.1, J = 4.4, J = 5.5, J = 5.3,
1,2
2,3
3,4
4,5
ꢀ
ꢀ
J
= 5.2, J = 14.3 Hz. 13C NMR: δ = 30.6 (CH3CO), 30.8 (C-5), 55.5
(OMe), 71.1 5(,C5 -2), 77.7 (C-3), 82.0 (C-4), 106.5 (C-1), 196.7 (C O).
4,5

Anhydro-Azido-thio-D-lyxofuranosides
1261
Methyl 5-S-Acetyl-3-azido-3-deoxy-2-O-mesyl-5-thio-α-D-
xylofuranoside (6)
Mesyl chloride (1.37 g, 0.93 mL, 12.0 mmol) was added to a stirred
solution of 4 (2.32 g, 9.38 mmol) in dry pyridine (60 mL) at −10◦C.
After 1 h, the solution was warmed up to r.t. and stirred for 16 h.
CHCl3 was added, and the solution was washed subsequently with a 3M
Na2SO4 solution (3×), satd. NaHCO3 solution (2×), and H2O (1×). The
organic layer was dried with MgSO4 and evaporated. CC of the residue
(EtOAc/PE 1:3, Rf = 0.20) yielded 2.54 g 6 (7.82 mmol, 83.4%) as a
light yellow syrup. IR: ν = 2106 (N3), 1696 (C O), 1346 (MeSO3), 1170
1
(MeSO3) cm−1. H NMR: δ = 2.37 (s, 3H, MeCO), 3.06 (dd, 1H, H-5),
3.13 (s, 3H, MeSO3), 3.21 (dd, 1H, H-5ꢀ), 3.45 (s, 3H, OMe), 4.37 (m, 1H,
H-4), 4.39 (m, 1H, H-3), 4.82 (dd, 1H, H-2), 5.03 (d, 1H, H-1). J = 4.2,
1,2
= 6.0, J = 6.1, J = 5.5, J = 13.9 Hz. 13C NMR: δ = 29.5 (C-
ꢀ
ꢀ
J
2,3
4,5
5,5
5), 30.5 (CH3CO), 38.74(,M5 eSO3), 55.7 (OMe), 64.3 (C-3), 75.0 (C-4), 81.3
(C-2), 99.9 (C-1), 194.7 (C O).
Methyl 2,5-Anhydro-3-azido-3-deoxy-2-thio-α-D-
lyxofuranoside (7)
Compound 6 (7.63 g, 23.5 mmol) was dissolved in dry MeOH (an-
alytical grade, 600 mL) under an Ar atmosphere in a carefully dried
apparatus. Ar was bubbled through the solution for 2 h, and then dry
NaHCO3 (4.20 g, 50.0 mmol) was added. After another 30 min, the Ar
current was stopped, and the solution was refluxed until 6 was con-
sumed (tlc control, ca. 3 h). The solvent was evaporated. The residue
was dissolved in CH2Cl2. The excess of NaHCO3 was filtered, and the
CH2Cl2 was evaporated. CC (EtOAc/PE 1:3, Rf = 0.58) gave 7 (3.30 g,
17.6 mmol, 75.1%) as a colorless syrup. [α]2D0 = +47 (c 0.90, CHCl3). IR:
1
ν = 2109 (N3) cm−1. H NMR: δ = 2.75 (dd, 1H, H-5), 2.91 (dd, 1H, H-
5ꢀ), 3.30 (s, 3H, OMe), 3.30 (m, 1H, H-2), 4.43 (m, 1H, H-4), 4.44 (s, 1H,
H-3), 4.86 (s, 1H, H-1). J = 1.0, J = 1.2, J = 10.4 Hz. 13C NMR:
ꢀ
ꢀ
4,5
4,5
5,5
δ = 33.6 (C-5), 48.4 (C-2), 54.0 (OMe), 63.1 (C-3), 75.9 (C-4), 108.5 (C-1).
MS; m/z : 187 [M+·].
Methyl 5-S-Acetyl-2-azido-2-deoxy-2-O-mesyl-5-thio-α-D-
arabinofuranoside (8)
Compound 8 was prepared as described for 6 from 5 (2.97 g,
12.0 mmol) and mesyl chloride (1.76 g, 1.20 mL, 15.4 mmol) in pyridine
(65 mL). Reaction time: 17 h. CC (EtOAc/PE 1:3, Rf = 0.25) gave 3.30 g
8 (10.1 mmol, 84.5%) as a light yellow syrup. IR: ν = 2113 (N3), 1694
1
(C O), 1361 (MeSO3), 1178 (MeSO3) cm−1. H NMR: δ = 2.40 (s, 3H,
MeCO), 3.17 (s, 3H, MeSO3), 3.27 (dd, 1H, H-5), 3.32 (dd, 1H, H-5ꢀ),

1262
D. Otzen et al.
3.39 (s, 3H, OMe), 4.16 (dd, 1H, H-2), 4.30 (m, 1H, H-4), 4.61 (dd,
1H, H-3), 4.89 (d, 1H, H-1). J = 1.2, J = 2.7, J = 5.7, J = 5.4,
1,2
2,3
3,4
4,5
= 5.1, J = 14.4 Hz. 13C NMR: δ = 30.2 (C-5), 30.5 (CH3CO), 38.5
ꢀ
ꢀ
J
4,5
5,5
(MeSO3), 55.2 (OMe), 70.4 (C-2), 79.6 (C-4), 83.4 (C-3), 106.7 (C-1), 195.0
(C O).
Methyl 3,5-Anhydro-2-azido-2-deoxy-3-thio-α-D-
lyxofuranoside (9)
Compound 9 was prepared as described for 7 from 8 (3.06 g,
9.40 mmol) and NaHCO3 (1.14 g, 16.8 mmol) in MeOH (analytical grade,
340 mL). Reaction time: 3 h. CC (EtOAc/PE 1:2, Rf = 0.71) gave 1.00 g 9
(5.34 mmol, 56.8%) as a colorless syrup. [α]2D0 = +26 (c1.40, CHCl3). IR:
ν = 2107 (N3) cm−1. 1H NMR: δ = 3.08 (dd, 1H, H-5), 3.46 (s, 3H, OMe),
3.47 (dd, 1H, H-5ꢀ), 3.93 (dd, 1H, H-2), 4.20 (dd, 1H, H-3), 5.13 (ddd,
1H, H-4), 5.32 (d, 1H, H-1). J = 3.1, J = 6.9, J = 6.3, J = 3.0,
1,2
2,3
3,4
4,5
= 6.3, J = 10.6 Hz. 13C NMR: δ = 31.9 (C-5), 45.8 (C-3), 56.3
ꢀ
ꢀ
J
4,5
(OMe), 67.2 5(C,5-2), 79.5 (C-4), 108.0 (C-1). MS; m/z: 156 [M − OMe].+
C6H9O2N3S (187.2): calcd.: C, 38.49; H, 4.85; N, 22.44; S, 17.13; found:
C, 38.46; H 4.89: N, 21.30; S, 17.45.
Methyl 3-Azido-3-deoxy-β-D-xylofuranoside (11)
Compound 11 was prepared as described for 2 from methyl 2,3-
anhydro-β-D-ribofuranoside13 (10, 2.56 g, 15.5 mmol), NaN3 (4.02 g,
61.8 mmol), and NH4Cl (3.04 g, 56.8 mmol) in EtOH (90 mL)/H2O
(20 mL). Reaction time: 12 d. CC (EtOAc/PE, Rf = 0.27) gave 2.47 g
11 (13.1 mmol, 74.5%) as a colorless syrup. 1H NMR: δ = 2.80 (bs, 2H,
OH), 3.45 (s, 3H, OMe), 3.73 (dd, 1H, H-5), 3.78 (dd, 1H, H-5’), 4.11
(dd, 1H, H-3), 4.36 (dd, 1H, H-2), 4.39 (m, 1H, H-4), 4.86 (d, 1H, H-1).
ꢀ
ꢀ
J
= 2.3, J = 4.9, J = 7.1, J = 4.5, J = 4.2, J = 12.3 Hz.
1,2
2,3
3,4
4,5
4,5
5,5
13C NMR: δ = 56.2 (OMe), 62.1 (C-5), 66.7 (C-3), 80.1 (C-2), 80.5 (C-4),
109.3 (C-1).
Methyl 5-S-Acetyl-3-azido-3-deoxy-5-thio-β-D-xylofuranoside
(12)
Compound 12 was prepared as described for 4 from 11 (1.46 g,
7.72 mmol), DIAD (1.74 mL, 9.02 mmol), PPh3 (2.42 g, 9.22 mmol) and
thioacetic acid (0.69 mL, 9.69 mmol) in THF (50 mL). Reaction time:
20 h. CC (EtOAc/PE 1:1, Rf = 0.36) gave 1.50 g 12 (6.07 mmol, 78.6%)
1
as a colorless syrup. H NMR: δ = 2.36 (s, 3H, CH3CO), 2.88 (bs, 1H,
OH), 3.07 (dd, 1H, H-5), 3.13 (dd, 1H, H-5ꢀ), 3.49 (s, 3H, OMe), 3.99
(dd, 1H, H-3), 4.24 (d, 1H, H-2), 4.28 (m, 1H, H-4), 4.94 (s, 1H, H-1).
ꢀ
ꢀ
J
1,2
= 4.5, J = 4.5, J = 5.8, J = 6.3, J = 7.0, J = 13.8 Hz.
2,3
3,4
4,5
4,5
5,5

Anhydro-Azido-thio-D-lyxofuranosides
1263
13C NMR: δ = 30.3 (C-5), 30.5 (CH3CO), 55.8 (OMe), 67.5 (C-3), 79.6
(C-4), 80.2 (C-2), 109.4 (C-1).
Methyl 5-S-Acetyl-3-azido-3-deoxy-2-O-mesyl-5-thio-β-D-
xylofuranoside (13)
Compound 13 was prepared as described for 6 from 12 (1.76 g,
7.10 mmol) and mesyl chloride (0.68 mL, 8.80 mmol) in pyridine
(50 mL). Reaction time: 16 h. CC (EtOAc/petroleum ether 1:2, Rf =
1
0.65) gave 1.87 g 13 (5.75 mmol, 81.0%) as a light yellow syrup. H
NMR: δ = 2.38 (s, 3H, MeCO), 3.12 (s, 3H, MeSO3), 3.17 (d, 1H, H-5),
3.19 (d, 1H, H-5ꢀ), 3.43 (s, 3H, OMe), 4.31 (dd, 1H, H-3), 4.39 (m, 1H, H-
4), 4.98 (dd, 1H, H-2), 5.01 (d, 1H, H-1). J = 1.0, J = 2.4, J = 5.9,
1,2
2,3
3,4
= 6.3, J = 1.3 Hz. 13C NMR: δ = 30.0 (C-5), 30.5 (CH3CO), 38.5
ꢀ
J
4,5
4,5
(MeSO3), 56.0 (OMe), 65.6 (C-3), 79.7 (C-4), 85.5 (C-2), 106.7 (C-1), 194.9
(C O).
Methyl 2,5-Anhydro-3-azido-3-deoxy-2-thio-β-D-
lyxofuranoside (14)
Compound 14 was prepared as described for 7 from 13 (1.50 g,
4.61 mmol) and NaHCO3 (0.77 g, 9.22 mmol) in MeOH (analytical grade,
120 mL). Reaction time: 2 h. CC (EtOAc/PE 1:3, Rf = 0.40) gave 0.69 g
1
14 (3.68 mmol, 79.8%) as a colorless syrup. H NMR: δ = 2.90 (m, 2H,
H-5, H-5ꢀ), 3.40 (s, 3H, OMe), 3.50 (m, 1H, H-2), 4.30 (m, 1H, H-3), 4.50
(m, 1H, H-4), 5.20 (m, 1H, H-1). 13C NMR: δ = 34.8 (C-5), 51.2 (C-2),
56.7 (OMe), 64.9 (C-3), 78.8 (C-4), 106.7 (C-1).
Methyl 2,3-di-O-mesyl-5-O-trityl-β-D-ribofuranoside (16)
Compound 16 was prepared as described for 6 from methyl 5-O-
trityl-β-D-ribofuranoside19 (15, 0.25 g, 0.62 mmol) and mesyl chloride
(0.05 mL, 0.65 mmol) in pyridine (5 mL). Reaction time: 66 h. Recrys-
tallisation from EtOAc/PE gave 0.29 g, 16 (0.52 mmol, 84.6%) as a
light yellow solid. Rf = 0.56 (EtOAc/PE 1:1). 1H NMR: δ = 2.86 (s, 3H,
MeSO3), 3.13 (s, 3H, MeSO3), 3.14 (dd, 1H, H-5), 3.49 (s, 3H, OMe),
3.54 (dd, 1H, H-5ꢀ), 4.31 (m, 1H, H-4), 5.09 (dd, 1H, H-2), 5.15 (d, 1H,
H-1), 5.28 (dd, 1H, H-3), 7.23–7.34 (m, 9H, Har), 7.44–7.48 (m, 6H, Har).
ꢀ
ꢀ
J
1,2
= 1.7, J = 4.6, J = 6.5, J = 3.2, J = 3.5, J = 10.7 Hz.
2,3
3,4
4,5
4,5
5,5
13C NMR: δ = 37.8 (MeSO3), 38.4 (MeSO3), 56.1 (OMe), 62.0 (C-5), 76.7
(C-3), 79.6 (C-4), 80.0 (C-2), 87.0 (Cq), 105.8 (C-1), 127.26, 127.30, 128.0,
143.3 (each 1 Car).

1264
D. Otzen et al.
Methyl 3-Azido-3-deoxy-2-O-mesyl-5-O-triphenylmethyl-β-D-
xylofuranoside (17)
Compound 17 was prepared as described for 2 from 16 (22.73 g,
40.40 mmol) and NaN3 (12.93 g, 198.9 mmol) in dry DMF (120 mL).
The reaction time was 43 h at 110◦C. CC (EtOAc/PE 1:2, Rf = 0.27)
1
gave 17 (6.93 g, 13.6 mmol, 34.0%) as a light yellow syrup. H NMR:
δ = 3.06 (s, 3H, MeSO3), 3.33 (dd, 1H, H-5), 3.37 (s, 3H, OMe), 3.40 (dd,
1H, H-5ꢀ), 4.28 (dd, 1H, H-3), 4.45 (ddd, 1H, H-4), 4.99 (dd, 1H, H-2), 5.01
(d, 1H, H-1), 7.20–7.49 (m, 15H, ArH). J = 1.6, J = 2.8, J = 5.9,
1,2
2,3
3,4
= 5.6, J = 5.9, J = 10.0 Hz. 13C NMR: δ = 38.4 (MeSO3), 56.0
ꢀ
ꢀ
J
4,5
4,5
5,5
(OMe), 62.8 (C-5), 64.7 (C-3), 79.9 (C-4), 85.1 (C-2), 87.3 (Cq), 106.6
(C-1), 127.0, 127.9, 128.7, 143.6 (Car).
Methyl 3-Azido-3-deoxy-2-O-mesyl-β-D-xylofuranoside (18)
A solution of BF3-MeOH complex (20%, 17.8 mmol) in MeOH (10 mL)
was added to a solution of 17 (6.93 g, 13.6 mmol) in CH2Cl2 (50 mL).
The mixture was stirred r.t. for 40 h. Solvents were distilled off, and the
residue was purified by CC (EtOAc/PE 1:1, Rf = 0.37) to yield 9.93 g 18
(1.96 g, 7.33 mmol, 54.0%) as a light yellow syrup. Rf = 0.56 (EtOAc/Pe
2:1). 1H NMR: δ = 2.45 (bs, 1H, OH), 3.14 (s, 3H, MeSO3), 3.48 (s, 3H,
OMe), 3.76 (dd, 1H, H-5), 3.81 (dd, 1H, H-5’), 4.36 (dd, 1H, H-3), 4.43
(m, 1H, H-4), 5.07 (d, 1H, H-1), 5.08 (dd, 1H, H-2). J = 2.1, J
=
1,2
2,3
4.6, J = 7.2, J = 4.1, J = 4.0, J = 12.5 Hz. 13C NMR: δ = 38.4
ꢀ
ꢀ
3,4
4,5
(MeSO3), 56.4 (OMe), 61.84(,C5 -5), 64.8 5(C,5-3), 80.9 (C-4), 86.1 (C-2), 106.7
(C-1).
Methyl 5-S-Acetyl-3-azido-3-deoxy-2-O-mesyl-5-thio-β-D-
xylofuranoside (13)
Compound 13 was prepared as described for 4 from 18 (0.18 g,
0.67 mmol), DIAD (0.15 mL, 0.79 mmol), PPh3 (0.21 g, 0.80 mmol),
and thioacetic acid (0.06 mL, 0.80 mmol) in dry THF (14 mL). Reaction
time: 16 h. CC (EtOAc/PE 1:1) gave 0.18 g 13 (0.55 mmol, 81.6%) with
spectroscopic data, which agreed with the ones previously described.
Methyl 2,3-O-Sulfinyl-5-O-triphenylmethyl-β-D-ribofuranoside
(19)
A solution of 15 (3.30 g, 8.13 mmol) and triethyl amine (4.60 mL,
33.2 mmol) in dry THF (40 mL) was cooled to −17◦C. Thionyl chloride
(1.20 mL, 16.6 mmol) was dropped in under stirring to maintain the
temperature between −15◦C and −10◦C. Stirring was continued for 1 h.
Then EtOAc was added and the solution was washed twice with satd.
NaCl solution. The organic solvents were evaporated in a vacuum. CC

Anhydro-Azido-thio-D-lyxofuranosides
1265
of the residue (EtOAc/PE 1:1, Rf = 0.57) gave 19 (3.47 g, 7.67 mmol,
1
94.3%) as a light yellow syrup. H NMR: δ = 3.51 (s, 3H, OMe), 3.73
(dd, 1H, H-5), 3.76 (dd, 1H, H-5ꢀ), 4.79 (dd, 1H, H-4), 5.10 (d, 1H, H-3),
5.31 (s, 1H, H-2), 5.35 (s, 1H, H-1), 7.25–7.33 (m, 15H, ArH). J = 2.6,
4,5
= 2.4, J = 12.8 Hz. 13C NMR: δ = 56.1 (OMe), 63.6 (C-5), 85.5
ꢀ
ꢀ
J
4,5
5,5
(C-2), 87.2 (C-4), 88.0 (C-3), 108.6 (C-1), 127.3, 127.7, 127.9, 146.9 (Car).
Methyl 3-Azido-3-deoxy-5-O-triphenylmethyl-β-D-
xylofuranoside (20)
A solution of 19 (1.12 g, 2.47 mmol) and NaN3 (0.66 g, 10.2 mmol)
in dry DMSO (15 mL) was heated to 130◦C for 40 h. The solvent was
distilled off in a vacuum. CC of the residue (EtOAc/PE 1:2) gave 20
(0.53 g, 1.23 mmol, 49.8%) as a light yellow syrup. Rf = 0.45 (EtOAc/PE
1:1). IR: ν = 3421 (OH), 2105 (N3). 1H NMR: δ = 2.46 (d, 1H, OH), 3.29
(dd, 1H, H-5), 3.43 (s, 3H, OMe), 3.39 (dd, 1H, H-5’), 3.95 (d, 1H, H-
3), 4.23 (m, 1H, H-2), 4.49 (ddd, 1H, H-4), 4.81 (d, 1H, H-1), 7.20–7.50
(m, 15H, ArH). J = 1.1, J
= 3.6, J = 2.5, J = 5.6, J = 5.7,
1,2
2,OH
2,3
3,4
4,5
= 6.3, J = 9.8 Hz. 13C NMR: δ = 56.2 (OMe), 62.1 (C-5), 66.8
ꢀ
ꢀ
J
4,5
5,5
(C-3), 80.4 (C-2), 80.6 (C-4), 87.1 (Cq), 109.3 (C-1), 127.3, 127.7, 127.9,
146.9 (Car).
1-(2,5-Anhydro-3-azido-3-deoxy-2-thio-α-D-
lyxofuranosyl)thymine (21)
A solution of thymine (0.100 g, 0.793 mmol) and a catalytic amount
of (NH4)2SO4 in hexamethyldisilazane (HMDS, 2 mL) was refluxed un-
der the exclusion of moisture for 2 h. Excess HMDS was distilled off
under Ar and then codistilled with xylene (3×). Compound 7 (0.100 g,
0.534 mmol) in dry acetonitrile (4 mL) was added to the residue un-
der a dry Ar atmosphere. The resulting solution was cooled to −40◦C.
Trimethylsilyl triflate (0.13 mL, 0.694 mmol) was added under vigor-
ous stirring. Stirring was continued for 2 h at −40◦C and finally over
night at r.t. The reaction mixture was diluted with CH2Cl2 and washed
with NaHCO3 solution. The organic layer was dried over Na2SO4
and evaporated. CC (EtOAc, Rf = 0.45) gave 0.082 g 21 (0.29 mmol,
54.3%) as colorless crystals, m.p. 108◦C. [α]D20 = −38 (c1.0, CHCl3). UV:
λmax(lg ε) = 209 nm (1.23), 267 nm (1.37); λmin(log ε) = 234 nm (0.24). 1H
NMR: δ = 1.95 (d, 3H, CH3), 3.03 (dd, 1H, H-5ꢀa), 3.11 (dd, 1H, 5ꢀb), 3.92
(d, 1H, H-2ꢀ), 4.15 (dd, 1H, H-3ꢀ), 4.76 (ddd, 1H, H-4ꢀ), 5.80 (s, 1H, H-1ꢀ),
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ ꢀ
7.28 (q, 1H, H-6), 9.30 (bs, 1H, NH). J
= 2.2, J
= 2.8, J
= 1.3,
2 ,3
3 ,4
4 ,5 a
= 1.2 Hz. 13C NMR: δ = 12.8 (CH3),
ꢀ
ꢀ
ꢀ
ꢀ
J
= 1.8, J
= 11.0, J
4 ,5 b
5 a,5b
6,Me
34.6 (C-5ꢀ), 50.0 (C-2ꢀ), 62.3 (C-3ꢀ), 79.0 (C-4ꢀ), 92.5 (C-1ꢀ), 110.3 (C-5),
133.9 (C-6), 150.0 (C2 O), 163.8 (C4 O).

1266
D. Otzen et al.
1-(2,5-Anhydro-3-azido-3-deoxy-2-thio-α-D-
lyxofuranosyl)thymine (S)-S-oxide (22)
A solution of meta-chloroperbenzoic acid (MCPBA, 70%, 0.049 g,
0.20 mmol) in CH2Cl2 (5 mL) was dropped into a solution of 21
(0.032 g, 0.12 mmol) in CH2Cl2 (5 mL). After 30 min, (TLC control) satd.
NaHCO3-solution and Na2S2O3-solution were added. The mixture was
extracted with CH2Cl2 (3×). The extract was dried with Na2SO4 and
evaporated. CC (EtOAc/PE 3:1, Rf = 0.51) gave 0.025 g 22 (0.080 mmol,
73.8%) as colorless crystals. UV: λmax (lg ε) = 211 nm (0.67), 266 nm
(0.76); λmin (log ε) = 235 nm (0.20). IR: ν = 3269 (NH), 2121 (N3), 1697
1
(C O), 1676 (C O), 1058 (S O) cm−1. H NMR (CD3OD): δ = 1.93 (d,
3H, Me), 2.54 (dd, 1H, H-5ꢀa), 3.63 (dd, 1H, 5ꢀb), 4.45 (d, 1H, H-2ꢀ),
4.89 (dd, 1H, H-3ꢀ), 5.07 (dd, 1H, H-4ꢀ), 6.40 (s, 1H, H-1ꢀ), 7.63 (q,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
1H, H-6), J
J
6,Me
= 2.2, J
= 5.6, J
= 2.1, J
= 2.3, J
= 14.0,
2 ,3
3 ,4
4 ,5 a
4 ,5 b
5 a,5b
= 1.2 Hz. 13C NMR (CD3OD): δ = 11.2 (CH3), 55.3 (C-5ꢀ), 61.9
(C-2ꢀ), 64.1 (C-3ꢀ), 79.4 (C-4ꢀ), 80.3 (C-1ꢀ), 111.7 (C-5), 136.1 (C-6), 151.2
(C2 O), 164.4 (C4 O).
Methyl 3,5-Anhydro-2-azido-2-deoxy-3-thio-α-D-
lyxofuranoside (R)-S-oxide (23)
H2O2 (30%, 5.0 mL, 90 mmol) was slowly added to a solution of 9
(0.660 g, 3.53 mmol) in MeOH (50 mL). After 72 h of stirring at r.t., the
reaction mixture was poured into satd. NaCl-solution and extracted
with CH2Cl2. The extract was dried with MgSO4 and evaporated. CC
(EtOAc/PE 2:1, Rf = 0.22) of the residue gave 0.38 g of 23 (1.87 mmol,
1
53.0%) as colorless crystals, m.p. 163◦C. H NMR: δ = 3.17 (ddd, 1H,
H-5), 3.36 (s, 3H, OMe), 3.66 (ddd, 1H, H-5ꢀ), 3.95 (dddd, 1H, H-3), 4.42
(dd, 1H, H-2), 5.05 (d, 1H, H-1), 5.23 (ddd, 1H, H-4). J = 1.0, J = 7.5,
1,2
4,5ꢀ
5,5ꢀ
3,5ꢀ
4,5
J
= 5.9, J = 0.9, J = 1.1, J = 5.7, J = 1.1, J = 21,33.0 Hz.
3,4
3,5
13C NMR: δ = 53.1 (C-5), 55.7 (OMe), 68.9 (C-2), 71.9 (C-3), 74.5 (C-4),
110.9 (C-1).
Methyl 2,5-Anhydro-3-azido-3-deoxy-2-thio-β-D-
lyxofuranoside (R)-S-oxide (24), Methyl 2,5-Anhydro-3-azido-
3-deoxy-2-thio-β-D-lyxofuranoside (S)-S-oxide (25),
and Methyl 2,5-Anhydro-3-azido-3-deoxy-2-thio-β-D-
lyxofuranoside S,S-dioxide (26)
Compound 14 (200 mg, 1.07 mmol) was dissolved in CH2Cl2 (10 mL).
Benzoic acid (131 mg, 1.07 mmol) and benzyltriethylammonium chlo-
ride (24 mg, 0.11 mmol) were added, and the mixture was stirred
for 10 min. Then, a solution of KMnO4 (338 mg, 2.14 mmol) in H2O
(20 mL) was added, and the two-phase mixture was stirred vigorously

Anhydro-Azido-thio-D-lyxofuranosides
1267
for 12 h. After quenching with Na2S2O5, the solution turned colorless
and was filtered through celite and extracted with CH2Cl2 (2×). The
combined organic layers were dried with Na2SO4 and evaporated. Pu-
rification and separation of the residue by CC (EtOAc/PE 1:1) gave
8 mg 24 (0.04 mmol, 3.7%), 163 mg 25 (0.80 mmol, 75.0%), and 16 mg
26 (0.07 mmol, 6.9%). 24: colorless syrup. Rf = 0.22 (EtOAc/PE 2:1). IR:
ν = 3446 (OH), 2129 (N3), 1057 (S O) cm−1. 1H NMR: δ = 3.43 (m, 1H,
H-5), 3.44 (m, 1H, H-5ꢀ), 3.54 (s, 3H, OMe), 3.70 (m, 1H, H-2), 4.70 (m,
1H, H-4), 4.71 (m, 1H, H-3), 5.30 (d, 1H, H-1). J = 2.4 Hz. 13C NMR:
1,2
δ = 58.4 (OMe), 59.6 (C-5), 62.1 (C-2), 63.3 (C-3), 77.2 (C-4), 103.6 (C-1).
MS; m/z = 218 [M+·]. 25: slightly yellow syrup: Rf = 0.23 (EtOAc/PE
1
2:1). IR: ν = 2131 (N3), 1053 (S O) cm−1. H NMR: δ = 3.18 (ddd, 1H,
H-5), 3.28 (m, 1H, H-5ꢀ), 3.44 (s, 3H, OMe), 3.67 (m, 1H, H-2), 4.76 (m,
ꢀ
1H, H-4), 4.99 (m, 1H, H-3), 5.36 (s, 1H, H-1). J = 1.4, J = 0.7,
2,5
2,5
ꢀ
ꢀ
J
4,5
= 1.5, J = 2.1, J = 12.7 Hz. 13C NMR: δ = 56.3 (OMe), 56.7
(C-5), 63.4 (4C,5-3), 64.8 (C-2), 77.2 (C-4), 102.3 (C-1). 26: colorless crys-
tals, m.p. 157◦C Rf = 0.32 (EtOAc/PE 2:1). [α]D20 = +40 (c1.0, CHCl3).
IR: ν = 2121 (N3), 1319 (SO2), 1153 (SO2) cm−1. 1H NMR: δ = 3.25 (dd,
1H, H-5), 3.42 (dd, 1H, H-5ꢀ), 3.46 (s, 3H, OMe), 4.38 (dd, 1H, H-3), 4.88
(ddd, 1H, H-4), 5.01 (d, 1H, H-2), 5.07 (d, 1H, H-1). J = 1.1, J = 2.2,
5,5
1,2
2,3
ꢀ
ꢀ
J
3,4
= 5.7, J = 3.3, J = 8.9, J = 14.9 Hz. 13C NMR: δ = 53.6
4,5
4,5
5,5
(C-5), 57.0 (OMe), 65.8 (C-3), 75.7 (C-4), 84.5 (C-2), 107.4 (C-1).
C6H9O4N3S (219.2): calcd: C, 32.87; H, 4.14; N, 19.17; S, 14.63; found:
C, 32.78; H, 4.09; N, 19.22; S, 14.59.
Methyl 2,5-Anhydro-3-azido-3-deoxy-2-thio-α-D-
lyxofuranoside (S)-S-oxide (27), Methyl
2,5-Anhydro-3-azido-3-deoxy-2-thio-α-D-lyxofuranoside (R)-S-
oxide (28), and methyl 2,5-Anhydro-3-azido-3-deoxy-2-thio-α-
D-lyxofuranoside S,S-dioxide (29)
Compound 7 (1.00 g, 5.34 mmol) was oxidized with MCPBA (70%,
2.70 g, 11.0 mmol) in CH2Cl2 (150 mL) as described for the prepara-
tion of 22. Reaction time: 30 min. Purification and separation by CC
(EtOAc/PE, gradient 1:1 to 2:1) gave 0.090 g 27 (0.44 mmol, 8.2%),
0.430 g 28 (2.12 mmol, 39.7%), and 0.40 g 29 (1.82 mmol, 34.1%). 27:
colorless crystals, m.p. 119◦C. Rf = 0.63 (EtOAc). IR: ν = 3371 (OH),
2121 (N3), 976 (S O) cm−1. 1H NMR: δ = 2.54 (d, 1H, H-5), 3.46 (s, 3H,
OMe), 3.61 (dd, 1H, H-5ꢀ), 4.04 (d, 1H, H-3), 4.79 (m, 1H, H-2), 4.84
ꢀ
(m, 1H, H-4), 5.41 (s, 1H, H-1). J = 2.1, J = 2.2, J = 13.4 Hz.
3,4
4,5
5,5
13C NMR: δ = 55.1 (C-5), 56.4 (OMe), 58.8 (C-2), 64.8 (C-3), 80.2 (C-4),
1
99.8 (C-1). 28: colorless syrup. Rf = 0.37 (EtOAc). H NMR: δ = 2.49
(d, 1H, H-5), 3.35 (dd, 1H, H-5ꢀ), 3.46 (s, 3H, OMe), 3.99 (s, 1H, H-3),

1268
D. Otzen et al.
4.74 (s, 2H, H-2, H-4), 5.41 (s, 1H, H-1). J = 1.5, J = 13.3 Hz. 13
C
ꢀ
4,5
5,5
NMR: δ = 55.2 (C-5), 56.4 (OMe), 63.2 (C-3), 65.9 (C-2), 77.9 (C-4), 98.7
1
(C-1). 29: colorless crystals, m.p. 142◦C. Rf = 0.56 (EtOAc). H NMR:
δ = 3.47 (s, 3H, OMe), 4.18 (dd, 1H, H-5), 4.30 (dd, 1H, H-2), 4.31 (ddd,
1H, H-5ꢀ), 4.89 (ddd, 1H, H-3), 5.04 (dd, 1H, H-4), 5.35 (d, 1H, H-1).
ꢀ
ꢀ
J
1,2
= 3.2, J = 7.9, J = 6.1, J = 2.0, J = 6.1, J = 14.1 Hz.
2,3
3,4
4,5
4,5
5,5
13C NMR: δ = 57.0 (OMe), 64.8 (C-3), 67.4 (C-2), 72.1 (C-5), 83.4 (C-4),
110.7 (C-1). C6H9O4N3S (219.2): calcd.: C, 32.87; H, 4.14; N, 19.17; S,
14.63; found: C, 32.62; H, 4.09; N, 18.77; S, 14.60.
Methyl 2,5-Anhydro-3-azido-3-deoxy-2-thio-β-D-
lyxofuranoside (R)-S-Oxide (25)
Compound 25 was also obtained by the oxidation of 14 (22 mg,
0.12 mmol) with MCPBA (69 mg, 0.40 mmol) in CH2Cl2 (15 mL) as
described for 28. Reaction time: 2 h. Yield: 13 mg (0.060 mmol, 50.5%).
The spectroscopic data agreed with the ones previously described.
Methyl 3-Amino-2,5-anhydro-3-deoxy-2-thio-α-D-
lyxofuranoside (30)
PPh3 (0.168 g, 0.64 mmol) was added to a solution of 7 (0.100 g,
0.53 mmol) in THF (5 mL). The solution was stirred at r.t. until 7 was
consumed (TLC control, ca. 16 h). H2O (40 µL, 2.0 mmol) was added,
and the solution was heated at 60◦C for 5 h and then stirred at r.t.
for 60 h. The solvent was distilled off in a vacuum. Purification of the
residue by CC (EtOAc/PE 3:1 with a trace of NH3, Rf = 0.39) gave
0.055 g 30 (0.34 mmol, 64.2%) as a colorless syrup. IR: ν = 3371 (NH2),
3324 (NH2), 3289 (NH2), 3225 (NH2) cm−1. 1H NMR: δ = 1.68 (bs, 2H,
NH2), 2.95 (dd, 1H, H-5), 3.33 (dd, 1H, H-2), 3.46 (s, 3H, OMe), 3.50
(dd, 1H, H-5ꢀ), 4.18 (ddd, 1H, H-3), 5.05 (dd, 1H, H-1), 5.10 (ddd, 1H,
ꢀ
H-4). J = 3.8, J = 0.4, J = 7.2, J = 6.3, J = 2.7, J = 6.4,
1,2
1,3
2,3
3,4
4,5
4,5
ꢀ
J
= 10.7 Hz. 13C NMR: δ = 31.4 (C-5), 48.9 (C-3), 56.5 (OMe), 58.4
5,5
(C-2), 79.3 (C-4), 111.0 (C-1).
Methyl 2-Amino-3,5-anhydro-2-deoxy-3-thio-α-D-
lyxofuranoside (31)
Compound 31 was prepared as described for 30 from 9 (20 mg,
0.107 mmol), PPh3 (34 mg, 0.128 mmol) in THF (2 mL), and H2O (4 µL,
0.21 mmol). Reaction times: 16 h/6 h. CC (EtOAc/PE 3:1 with a trace
of NH3, Rf = 0.46) gave 11 mg 31 (0.07 mmol, 63.8%) as a colorless
syrup. 1H NMR: δ = 1.48 (bs, 2H, NH2), 2.76 (dd, 1H, H-5), 2.88 (dd, 1H,
H-5ꢀ), 3.10 (d, 1H, H-2), 3.36 (s, 3H, OMe), 3.92 (m, 1H, H-3), 4.27 (ddd,
ꢀ
1H, H-4), 4.89 (a, 1H, H-1). J = 2.0, J = 2.9, J = 1.4, J = 1.8,
2,3
3,4
4,5
4,5

Anhydro-Azido-thio-D-lyxofuranosides
1269
= 10.7 Hz. 13C NMR: δ = 33.9 (C-5), 52.7 (C-2), 54.9 (OMe), 56.7
ꢀ
J
5,5
(C-3), 78.3 (C-4), 109.6 (C-1).
Methyl 2-Amino-3,5-anhydro-2-deoxy-3-thio-α-D-
lyxofuranoside (R)-S-Oxide (32)
Compound 32 was prepared as described for 30 from 23 (22 mg,
0.108 mmol), and PPh3 (33 mg, 0.124 mmol) in THF (2 mL), and H2O
(4 µL, 0.21 mmol). Reaction times: 16 h/5 h. CC (EtOAc/PE 3:1 with
a trace of NH3, Rf = 0.24) gave 13.3 mg 32 (0.075 mmol, 69.4%) as a
1
colorless syrup. H NMR: δ = 2.02 (bs, 2H, NH2), 3.18 (dd, 1H, H-5),
3.30 (s, 3H, OMe), 3.67 (dd, 1H, H-5ꢀ), 3.85 (dd, 1H, H-2), 3.91 (dd,
1H, H-3), 4.79 (d, 1H, H-1), 5.22 (ddd, 1H, H-4). J = 1.4, J = 7.3,
1,2
2,3
= 5.7, J = 5.8, J = 0.8, J = 12.9 Hz. 13C NMR: δ = 53.2 (C-
ꢀ
ꢀ
J
3,4
4,5
4,5
5), 55.8 (OMe), 61.0 (C-2), 74.4 (C5-,45), 75.8 (C-3), 114.3 (C-1).
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D. Otzen et al.
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