Thiosugars, 2: Preparation of 2,3,5-tri-O-benzyl-4-thio-L-arabino- furanosides and the corresponding 4'-thionucleoside analogues

Article abstract of DOI:10.1002/(SICI)1099-0690(199903)1999:3<691::AID-EJOC691>3.0.CO;2-J

1-O-Acetyl-2,3,5-tri-O-benzyl-4-thio-L-arabino-furanose (9) has been prepared from D-xylose via the 1,4-dithio-L-arabino-furanoside 8. The crucial step of the reaction, i.e. the intramolecular cyclization of the open-chain dithioacetal 5, has been achieved in a yield of 90% by applying tetrabutylammonium iodide as promoter. Reaction of 9 with bis(trimethylsilyl)uracil or -thymine led to the benzyl derivatives 12 and 13 from which the deprotected 4'-thionucleoside analogues 14 and 15 have been prepared by debenzylation with boron tribromide.

Full text of DOI:10.1002/(SICI)1099-0690(199903)1999:3<691::AID-EJOC691>3.0.CO;2-J

FULL PAPER
Thiosugars, 2[°]
Preparation of 2,3,5-Tri-O-benzyl-4-thio--arabino-furanosides and the
Corresponding 4Ј-Thionucleoside Analogues
Jörn Wirsching[a] and Jürgen Voss*[a]
Keywords: Carbohydrates / 4-Thiofuranosides / Nucleosides / Reaction mechanisms / NOE measurements
1-O-Acetyl-2,3,5-tri-O-benzyl-4-thio-
has been prepared from -xylose via the 1,4-dithio-
arabino-furanoside 8. The crucial step of the reaction, i.e. the
L
-arabino-furanose (9)
tetrabutylammonium iodide as promoter. Reaction of 9 with
bis(trimethylsilyl)uracil or -thymine led to the benzyl
derivatives 12 and 13 from which the deprotected 4Ј-
D
L-
intramolecular cyclization of the open-chain dithioacetal 5, thionucleoside analogues 14 and 15 have been prepared by
has been achieved in yield of 90% by applying debenzylation with boron tribromide.
a
Carbohydrates with a sulfur atom in the 4-position of the tected -xylose derivative 3 with 85% yield following litera-
furanose ring have been of interest for a period of 30 years. ture procedures.[5,16] Both the α and the β anomer were ob-
The main target of all recent syntheses was and still is to tained in a ratio of 2:1 (α/β). It was possible to separate the
prepare such compounds with a minimum number of steps. anomers by column chromatography. In the next step sulfur
In 1964 Whistler et al.[1] reported the synthesis of methyl was introduced into the sugar moiety by using phen-
4-deoxy-4-thio--ribo-furanoside Ϫ one of the earliest pub- ylmethanethiol in the presence of concentrated hydrochloric
lications in this research area. Of course 4-thio--ribose[2,3] acid. This two-step process gave an 84% yield of the open-
and 2-deoxy-4-thio--ribose[4,5] derivatives are the most chain dithioacetal 4. This high yield demonstrates the pos-
popular compounds, because they are precursors for un- sibility to use the protected -xylose derivative 3 directly in
natural 4Ј-thionucleosides[6,7] and 2Ј-deoxy-4Ј-thionucleo- contrast to the analogous 2,3,5-tri-O-benzyl--lyxo-fu-
sides.[8,9] In 1995 Barascut and Imbach published the first ranose which requires deprotection in the 1-position.[7] Be-
results on the synthesis of 4Ј-thio-oligo-ribo-nucleotides;[10] sides 4 a 6% yield of the intermediate 1-S-benzyl -xylo-
the starting material for 4Ј-thio-RNA.
furanoside 6 was obtained as by-product in an anomeric
As a consequence of our studies on 2-(alkylthio)thiolanes ratio of 1:1.3 (Scheme 1).
Ϫ prototypes of 1,4-dithiofuranosides Ϫ we became inter-
ested in producing such 4-thiofuranosides, especially with 
configuration at C-4, and studying their structure and
chemistry. We describe here a novel synthesis of the 4-thio-
-arabino-furanose derivative 9 and its transformation into
the 4Ј-thionucleoside analogues 14 and 15, which might ex-
hibit interesting biochemical properties on account of their
 configuration. Ϫ The acetate 9 has very recently been pre-
pared by a different route by Yoshimura et al.[11] who also
obtained 15 and ist cytosine analogue. Ϫ The counterpart
of 9 with -xylo configuration has also been used as a key
intermediate for the synthesis of adenine nucleosides[12,13]
Scheme 1
as well as the enantiomer -9 which served as precursor for
several nucleosides.[14,15]
The free C-4 hydroxy group of 4 was mesylated at room
temperature in pyridine to obtain 5 which exhibits a good
leaving group for the following cyclisation step. Earlier[17,18]
and numerous recent publications[5,19] propose sodium iod-
ide and barium carbonate in dry acetone at reflux tempera-
ture for this cyclisation. We also tried this procedure but
were unable to obtain acceptable yields. In the best case we
achieved 20% of 8 and a large quantity of decomposition
products. The use of tetrabutylammonium iodide and bar-
ium carbonate in dry DMF at 120°C gave, however, 60%
of 8. The best cyclisation conditions turned out to be tetra-
Results and Discussion
Our synthesis started with commercially available and
cheap -xylose (1) which was transformed into the pro-
[°]
Part 1: Ref.[20]
[a]
Institut für Organische Chemie der Universität Hamburg,
Martin-Luther-King-Platz 6, D-20146 Hamburg, Germany
Fax: (internat.) ϩ 49(0)40/4123-5592
E-mail: voss@chemie.uni-hamburg.de
Eur. J. Org. Chem. 1999, 691Ϫ696
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
1434Ϫ193X/99/0303Ϫ0691 $ 17.50ϩ.50/0
691

J. Wirsching, J. Voss
FULL PAPER
butylammonium iodide and barium carbonate in dry pyri-
Sodium methoxide removed the acetyl group of 9 to yield
dine at reflux temperature.[7] This yielded 94% of 8 with an 79% of 2,3,5-tri-O-benzyl-4-thio--arabino-furanose (10).
anomeric ratio of 6.7:1. Compared with the other methods The anomers 10α and 10β were formed in a 1:1 ratio but
there are obvious advantages: 1) the better solubility of could not be separated. Also debenzylation of 9 was pos-
tetrabutylammonium iodide as compared with sodium iod- sible with boron tribromide. The product yield of 1-O-ace-
ide; 2) a higher reaction temperature and thus a shorter tyl-4-thio--arabino-furanose (11), again a mixture of the
reaction time as compared with acetone and, as a conse- two anomers, was, however, only moderate (29%) since
quence, the high yield of over 90% (Scheme 2).
quenching of boron tribromide caused losses and made the
work-up procedure difficult.
1-O-Acetylfuranoses represent suitable starting com-
pounds for nucleoside syntheses.[9,19] Reaction of 9 with bi-
s(trimethylsilyl)uracil or -thymine in the presence of trime-
thysilyl triflate was indeed successful and the tri-O-benzyl-
4Ј-thionucleoside analogues 12 and 13 were obtained with
good yields. Their structures were assigned by NMR spec-
troscopy. In particular, the observed NOE (cf. Figure 1) un-
equivocally prove the configurations at C-1 and C-4. Inter-
actions between 6-H and 2Ј-H and 4Ј-H are only possible
in the -α-arabino stereoisomers 12α and 13α. Correspond-
ingly, interactions between 6-H and 3Ј-H and 5Ј-H and be-
tween 2Ј-H and 4Ј-H are observed in the β anomers 12β
and 13β.
Scheme 2
Obviously, the cyclisation is the key step for any synthesis
of a 4-thiofuranoside. Numerous reaction conditions for
this step have been reported in the past decade. Unani-
mously, iodide was used as a co-reagent and is in fact neces-
sary for the success of the reaction, which, according to our
own experience[20] does not at all take place in the absence
of iodide. This observation does, however, neither imply the
formation of an intermediate 4-iodopentose[18] nor a two-
step mechanism with two inversions of the configuration at
the 4-position. Rather the reaction is an intramolecular SN2
reaction with only a single inversion at C-4, which thus
leads from the  to the  series. We have undoubtedly pro-
ved this stereochemical course by NMR spectroscopy.[20]
The essential role which the iodide ions play is to remove
the S-benzyl group from the intermediate cyclic sulfonium
ion 7 by nucleophilic displacement. This cannot be brought
about by the mesylate anions present on account of their
poor nucleophilicity.[21]
Figure 1. Observed NOE (↔) as indicators for the α- and
β--arabino configuration of 12 and 13
The 1-O-acetyl-4-thio--arabino-furanose derivative 9
was obtained from 8 under the Seebach conditions.[17,22]
Using mercuric acetate in glacial acetic acid we achieved a
yield of 76% of 9α ϩ 9β as a 4:1 anomeric mixture (Scheme
3). Separation of the two anomers could not be achieved.
The assignment was, however, possible on the basis of the
optical rotation. Our 4:1 mixture exhibited [α]D20 ϭ Ϫ103.5
(c ϭ 1.3, CHCl3), whereas Yoshimura et al.[11] reported
[α]D25 ϭ ϩ29.8 (c ϭ 2.0, CHCl3) for their 1:2 mixture which
contained the β anomer as the main component. The sur-
prising difference of the anomeric ratios can be explained
by YoshimuraЈs different route of preparation (Pummerer
reaction of 1,4-anhydro-4-thio--arabitol).
In a final step deprotection of 12 and 13 was performed
with boron tribromide. In order to isolate the desired free
4Ј-thionucleoside analogues 14 and 15 it was necessary to
neutralize the strongly acidic solution with silver carbonate
after methanolic quenching of the excess boron tribromide
since otherwise no product could be recovered. Unexpec-
tedly, we obtained the partially deprotected 2-O-benzyl de-
rivative 16 from one reaction batch when we neutralized the
solution with an Amberlite ion exchanger (Scheme 4).
Scheme 3
692
Scheme 4
Eur. J. Org. Chem. 1999, 691Ϫ696

Thiosugars, 2
FULL PAPER
138.03, 138.17, 138.37, 138.44 (Cq). Ϫ C40H42O4S2 (650.9): calcd.
C 73.81, H 6.50, S 9.85; found C 73.92, H 6.64, S 9.57. Ϫ 6: IR
(film): ν˜ ϭ 3086, 3062, 3030, 2920, 2865, 1496, 1454, 1396, 1363,
1310, 1245, 1207, 1099, 1066, 1028, 913, 737, 698 cmϪ1. Ϫ Major
anomer: 1H NMR (400 MHz, CDCl3): δ ϭ 3.81Ϫ3.92 (m, 4 H, 5a-
H, 5b-H, SCH2Ph), 3.95Ϫ3.97 (m, 1 H, 4-H), 3.99 (dd, 1 H, 2-H),
4.31Ϫ4.63 (m, 7 H, 3-H, OCH2Ph), 4.98 (d, 1 H, 1-H), 7.18Ϫ7.37
(m, 20 H, ArH); J1,2 ϭ 2.2, J2,3 ϭ 4.7 Hz. Ϫ 13C NMR (101 MHz,
CDCl3): δ ϭ 35.55 (SCH2Ph), 68.75 (C-5), 71.79, 71.89, 73.46
(OCH2Ph), 81.02 (C-3), 82.01 (C-2), 86.38 (C-1), 87.04 (C-4), for
Experimental Section
General: IR: ATI Mattson Genesis spectrometer. Ϫ NMR: Bruker
AMX 400 and DRX 500. Chemical shifts (ppm) are related to
Me4Si (1H) and CDCl3 (13C, δ ϭ 77.05). Standard correlation tech-
niques were used for assignments. Ϫ Mass spectra: Varian CH 7
(EI) and VG Analytical 70-250 S (FAB, HRMS). Ϫ TLC was car-
ried out on Merck PF254 foils (detection: UV light, iodine vapour,
or EtOH/H2SO4 spray/200°C), and column chromatography on
Merck Kieselgel 60 (70Ϫ230 mesh). Solvents were purified and
dried according to standard laboratory procedures.[23]
1
signals of aromatic C atoms see note below. Ϫ Minor anomer: H
NMR (400 MHz, CDCl3): δ ϭ 3.70 (dd, 1 H, 5a-H), 3.79 (dd, 1
H, 5b-H), 3.81Ϫ3.92 (m, 2 H, SCH2Ph), 4.08Ϫ4.11 (m, 2 H, 2-H,
4-H), 4.31Ϫ4.63 (m, 7 H, 3-H, OCH2Ph), 5.44 (d, 1 H, 1-H),
7.18Ϫ7.37 (m, 20 H, ArH); J1,2 ϭ 5.0, J4,5a ϭ 6.2, J4,5b ϭ 5.5,
J5a,5b ϭ 10.3 Hz. Ϫ 13C NMR (101 MHz, CDCl3): δ ϭ 34.29
(SCH2Ph), 68.13 (C-5), 72.11, 72.75, 73.38 (OCH2Ph), 77.37 (C-3),
82.37 (C-2), 83.96 (C-4), 85.94 (C-1). Ϫ It was not possible to as-
sign the chemical shifts of the signals of aromatic C atoms for both
anomers; the observed chemical shifts are: δ ϭ 126.85, 126.98,
127.57, 127.61, 127.27, 127.737, 127.744, 127.78, 127.87, 127.88,
128.34, 128.38, 128.39, 128.42, 128.77, 129.10, 129.12 (CArH),
137.35, 137.40, 137.67, 137.85, 138.04, 138.27, 138.44 (Cq). Ϫ
C33H34O4S (526.7): calcd. C 75.25, H 6.51, S 6.09; found C 74.77,
H 6.58, S 6.72.
Methyl 2,3,5-Tri-O-benzyl--xylo-furanoside (3): Compound 3 was
prepared from methyl -xylo-furanoside (2) according to standard
procedures.[5,16] Compound 3 has been mentioned by Yoshimura et
al.[11] without data which are therefore dealt with here. Ϫ IR (film):
ν˜ ϭ 3062, 3030, 2910, 2870, 1496, 1454, 1365, 1311, 1250, 1205,
20
1122, 1100, 908, 820, 737, 698, 607 cmϪ1. Ϫ 3α: [α]D ϭ ϩ60.1
1
(c ϭ 1.0, CHCl3). Ϫ H NMR (400 MHz, CDCl3): δ ϭ 3.40 (s, 3
H, CH3), 3.59 (dd, 1 H, 5a-H), 3.71 (dd, 1 H, 5b-H), 4.02 (dd, 1 H,
2-H), 4.31 (dd, 1 H, 3-H), 4.39 (ddd, 1 H, 4-H), 4.49Ϫ4.69 (m, 6
H, CH2Ph), 4.81 (d, 1 H, 1-H), 7.23Ϫ7.37 (m, 15 H, ArH); J1,2
4.3, J2,3 ϭ 6.0, J3,4 ϭ 7.1, J4,5a ϭ 6.8, J4,5b ϭ 4.0, J5a,5b ϭ 10.6 Hz.
13C NMR (101 MHz, CDCl3): δ ϭ 54.85 (OCH3), 68.99 (C-5),
ϭ
Ϫ
72.18, 72.20, 73.04 (CH2Ph), 75.49 (C-4), 81.14 (C-3), 83.51 (C-2),
100.09 (C-1), 127.11, 127.15, 127.20, 127.34, 127.47, 127.70, 127.89,
20
127.92, 127.98 (CArH), 137.29, 137.69, 137.80 (Cq). Ϫ 3β: [α]D
ϭ
Benzyl 2,3,5-Tri-O-benzyl-1,4-dithio--arabino-furanoside (8):
A
1
Ϫ17.5 (c ϭ 1.0, CHCl3) Ϫ H NMR (400 MHz, CDCl3): δ ϭ 3.38
(s, 3 H, CH3), 3.72 (dd, 1 H, 5a-H), 3.78 (dd, 1 H, 5b-H), 3.97 (dd,
1 H, 2-H), 4.04 (dd, 1 H, 3-H), 4.43Ϫ4.64 (m, 7 H, CH2Ph, 4-H),
solution of mesyl chloride (4.3 mL, 6.3 g, 55 mmol) in dry pyridine
(60 mL) was added dropwise to an ice-cold solution of 4 (17.27 g,
26.53 mmol) in dry pyridine (130 mL). The mixture was allowed
to warm to room temp. and stirred for 24 h. When the reaction
was complete the pyridine was evaporated, the residue dissolved in
dichloromethane and extracted with 0.1  HCl, water and saturated
NaHCO3 solution to give the crude mesylate 5 (18.80 g). This was
dissolved in dry pyridine (200 mL), tetrabutylammonium iodide
(9.60 g, 25.79 mmol) and barium carbonate (5.30 g, 26.86 mmol)
were added and the mixture was refluxed for 2.5 h. Solid com-
pounds were filtered off and the pyridine was removed under re-
duced pressure. The residue was dissolved in dichloromethane and
4.91 (d, 1 H, 1-H), 7.25Ϫ7.37 (m, 15 H, ArH); J1,2 ϭ 1.6, J2,3
ϭ
2.6, J3,4 ϭ 5.9, J4,5a ϭ 7.2, J4,5b ϭ 4.9, J5a,5b ϭ 10.2 Hz. Ϫ 13C
NMR (101 MHz, CDCl3): δ ϭ 55.61 (OCH3), 69.73 (C-5), 71.98,
72.17, 73.40 (CH2Ph), 80.07 (C-4), 81.50 (C-3), 86.83 (C-2), 108.13
(C-1), 127.52, 127.59, 127.68, 127.74, 127.78, 127.82, 128.30,
128.37, 128.41 (CArH), 137.54, 137.76, 138.28 (Cq). Ϫ MS (70 eV);
m/z (%): 343 (0.05) [Mϩ Ϫ C7H7], 311 (0.66) [Mϩ Ϫ C7H7
Ϫ
CH3OH], 253 (16), 181 (7), 92 (15), 91 (100) [C7H7ϩ], 65 (5).
2,3,5-Tri-O-benzyl--xylose Dibenzyl Dithioacetal (4): Compound
3 (21.93 g, 50.5 mmol) was dissolved in phenylmethanethiol (33 extracted as described above. The crude product was chromatog-
mL, 34 g, 270 mmol) and concd. aq. HCl (30 mL) and stirred at
room temp. for 72 h. The mixture was diluted with water (200 mL)
raphed [petroleum ether/ethyl acetate, 4:1, Rf(8α,β) ϭ 0.43] to give
8 (13.55 g, 94%) as a 6.7:1 anomeric mixture (anomers were not
and dichloromethane (200 mL), the organic phase separated, separable); pale yellow syrup. Ϫ IR (film): ν˜ ϭ 3090, 3067, 3032,
washed twice with saturated NaHCO3 and water, dried with
MgSO4 and concentrated under reduced pressure. Column chroma-
tography of the residue (petroleum ether/ethyl acetate, 4:1, Rf ϭ
2923, 2865, 1498, 1454, 1400, 1365, 1313, 1244, 1210, 1180, 1103,
1
1076, 1027, 912, 737, 699 cmϪ1. Ϫ Major anomer: H NMR (400
MHz, CDCl3): δ ϭ 3.47 (ddd, 1 H, 4-H), 3.55 (dd, 1 H, 5a-H), 3.80
0.21) yielded 4 (27.47 g, 84%) as yellow syrup, [α]D20 ϭ Ϫ77.4 (c ϭ (dd, 1 H, 5b-H), 3.87 (s, 2 H, SCH2Ph), 4.19Ϫ4.21 (m, 2 H, 2-H,
1.0, CHCl3). The first fraction [Rf(6α,β) ϭ 0.39] was identified as
a 1:1.3 mixture of the α and β anomer of 1-S-benzyl 2,3,5-tri-O-
benzyl--xylo-furanoside (6) (1.53 g, 6%); yellow oil. Ϫ 4: IR (film):
3-H), 4.36 (d, 1 H, 1-H), 4.39, 4.56 (AB system, 2 H, JAB ϭ 11.7
Hz, OCH2Ph), 4.50, 4.54 (AB system, 2 H, JAB ϭ 11.9 Hz,
OCH2Ph), 4.60, 4.67 (AB system, 2 H, JAB ϭ 11.7 Hz, OCH2Ph),
ν˜ ϭ 3456, 3087, 3061, 3030, 2915, 2862, 1496, 1455, 1397, 1352, 7.21Ϫ7.36 (m, 20 H, ArH); J1,2 ϭ 4.6, J3,4 ϭ 5.0, J4,5a ϭ 7.2,
1239, 1209, 1104, 1072, 1028, 914, 878, 737, 700 cmϪ1. Ϫ 1H NMR J4,5b ϭ 7.3, J5a,5b ϭ 9.3 Hz. Ϫ 13C NMR (101 MHz, CDCl3): δ ϭ
(500 MHz, CDCl3): δ ϭ 2.25 (d, 1 H, 4-OH), 3.17 (dd, 1 H, 5a-H),
35.68 (SCH2Ph), 47.38 (C-4), 52.01 (C-1), 72.12, 72.66, 73.07
3.33 (dddd, 1 H, 4-H), 3.35 (dd, 1 H, 5b-H), 3.71 (d, 1 H, 1-H), (OCH2Ph), 73.59 (C-5), 84.96 (C-3), 86.62 (C-2), 127.79, 127.83,
3.76 (dd, 1 H, 3-H), 3.77, 3.81 (AB system, 4 H, JAB ϭ 13.6 Hz, 127.91, 128.31, 128.35, 128.53, 129.07 (CArH), 137.50, 137.70,
SCH2Ph), 4.12 (dd, 1 H, 2-H), 4.39, 4.44 (AB system, 2 H, JAB
ϭ
138.07, 138.15 (Cq). Ϫ Minor anomer: 1H NMR (400 MHz,
11.7 Hz, OCH2Ph), 4.47, 4.74 (AB system, 2 H, JAB ϭ 11.2 Hz, CDCl3): δ ϭ 3.53Ϫ3.59 (m, 1 H, 5a-H), 3.65Ϫ3.71 (m, 2 H, H-4,
OCH2Ph), 4.75, 4.91 (AB system, 2 H, JAB ϭ 11.0 Hz, OCH2Ph), 5b-H), 3.85 (s, 2 H, SCH2Ph), 3.97 (dd, 1 H, 2-H), 4.05 (dd, 1 H,
7.17Ϫ7.41 (m, 25 H, ArH); J1,2 ϭ 3.0, J2,3 ϭ 7.5, J3,4 ϭ 2.0, 3-H), 4.19Ϫ4.21 (m, 1 H, 1-H), 4.44Ϫ4.63 (m, 6 H, OCH2Ph),
J4,OH ϭ 6.5, J4,5a ϭ 4.9, J4,5b ϭ 6.9, J5a,5b ϭ 9.1 Hz. Ϫ 13C NMR 7.21Ϫ7.36 (m, 20 H, ArH); J1,2 ϭ 6.5, J2,3 ϭ 5.5, J3,4 ϭ 5.3 Hz. Ϫ
(101 MHz, CDCl3): δ ϭ 35.39, 36.16 (SCH2Ph), 51.34 (C-1), 69.52 13C NMR (101 MHz, CDCl3): δ ϭ 36.35 (SCH2Ph), 48.64 (C-4),
(C-4), 71.38 (C-5), 73.16, 75.05, 75.39 (OCH2Ph), 79.51 (C-3),
52.38 (C-1), 71.14 (C-5), 72.71, 72.92, 73.12 (OCH2Ph), 85.81 (C-
82.09 (C-2), 126.98, 127.08, 127.49, 127.68, 127.72, 127.83, 128.23, 2), 89.74 (C-3), 127.66, 127.69, 127.74, 127.84, 127.93, 128.38,
128.27, 128.31, 128.37, 128.45, 128.60, 129.07, 129.18 (CArH), 128.45, 128.58, 128.98, 129.08, 129.09 (CArH), 137.47, 137.63,
Eur. J. Org. Chem. 1999, 691Ϫ696
693

J. Wirsching, J. Voss
J1,2 ϭ 9.6, J2,3 ϭ 1.3, J3,4 ϭ 2.7, J4,5a ϭ 5.9, J4,5b ϭ 9.6, J5a,5b
FULL PAPER
137.89, 137.92 (Cq). Ϫ MS (70 eV); m/z (%): 542 (0.05) [Mϩ], 181
ϭ
(3), 107 (8), 106 (7), 92 (8), 91 (100) [C7H7ϩ], 79 (9), 77 (8), 65 (7). 9.6 Hz. Ϫ 13C NMR (125 MHz, CDCl3): δ ϭ 51.95 (C-4), 72.26
Ϫ C33H34O3S2 (542.8): calcd. C 73.03, H 6.31, S 11.81; found C
72.68, H 6.34, S 11.72.
(CH2Ph), 72.49 (C-5), 72.81, 73.44 (CH2Ph), 84.33 (C-3), 85.77 (C-
1), 89.00 (C-2). Ϫ It was not possible to assign the chemical shifts
of the signals of aromatic C atoms for both anomers; the observed
chemical shifts are as follows: δ ϭ 127.61, 127.68, 127.76, 127.88,
127.90, 127.94, 127.96, 127,98, 128.08, 128.38, 128.48, 128.51,
1-O-Acetyl-2,3,5-tri-O-benzyl-4-thio--arabino-furanose (9): 8 (993
mg, 1.83 mmol) and mercuric acetate (1.28 g, 3.71 mmol) were
dissolved in glacial acetic acid (25 mL) and stirred at room tem-
perature for 2.5 h. After the reaction was completed (TLC, petro-
leum ether/ethyl acetate, 4:1), the solvent was removed, the residue
diluted with dichloromethane, filtered through a Celite pad and
the crude product purified by column chromatography [petroleum
128.56 (CArH), 137.01, 137.36, 137.41, 137.53 (Cq,Ar).
Ϫ
C26H28O4S (436.6): calcd. C 71.50, H 6.46, S 7.34; found C 70.95,
H 6.53, S 7.45.
1-O-Acetyl-4-thio--arabino-furanose (11): Preparation as described
ether/ethyl acetate, 4:1, Rf(9α,β) ϭ 0.22] to yield the acetate 9 (668 for 14, using 9 (205 mg, 0.43 mmol) in dry dichloromethane (3.0
mg, 76%) as an unseparable 4:1 anomeric mixture; colourless oil.
Ϫ IR (film): ν˜ ϭ 3087, 3063, 3030, 2924, 2865, 1745, 1498, 1452,
1396, 1311, 1246, 1228, 1101, 1016, 960, 912, 794, 739, 700, 606
mL) and boron tribromide (0.19 mL, 500 mg, 2.00 mmol) in dry
dichloromethane (1.9 mL). Neutralization was performed with sil-
ver carbonate (1.68 g, 6.09 mmol). After chromatography [chloro-
cmϪ1. Ϫ 9α: 1H NMR (500 MHz, CDCl3): δ ϭ 2.10 (s, 3 H, CH3), form/methanol, 9:1, Rf(11α,β) ϭ 0.14], 11 (26 mg, 29%) was iso-
3.50 (dd, 1 H, 5a-H), 3.79 (dd, 1 H, 5b-H), 3.81 (ddd, 1 H, 4-H), lated with an anomeric ratio of 5:4; colourless oil. Ϫ Major an-
4.08 (dd, 1 H, 3-H), 4.31 (dd, 1 H, 2-H), 4.52 (s, 2 H, CH2Ph), omer: 1H NMR (400 MHz, CD3OD): δ ϭ 3.13 (ddd, 1 H, 4-H),
4.60, 4.69 (AB system, 2 H, JAB ϭ 11.7 Hz, CH2Ph), 4.58Ϫ4.72 3.32 (s, 3 H, CH3), 3.50 (m, 1 H, 5a-H), 3.85Ϫ3.89 (m, 2 H, 3-H,
(m, 2 H, CH2Ph), 6.03 (d, 1 H, 1-H), 7.28Ϫ7.39 (m, 15 H, ArH);
J1,2 ϭ 3.0, J2,3 ϭ 5.3, J3,4 ϭ 6.4, J4,5a ϭ 6.8, J4,5b ϭ 6.1, J5a,5b
5b-H), 3 97 (dd, 1 H, 2-H), 4.68 (d, 1 H, 1-H); J1,2 ϭ 4.3, J2,3
ϭ
ϭ
7.6, J3,4 ϭ 4.6, J4,5a ϭ 7.8, J4,5b ϭ 7.7, J5a,5b ϭ 11.0 Hz. Ϫ 13C
9.6 Hz. Ϫ 13C NMR (125 MHz, CDCl3): δ ϭ 21.10 (CH3), 49.35 NMR (125 MHz, CD3OD): δ ϭ 50.67 (C-4), 56.81 (CH3), 67.24
(C-4), 70.88 (C-5), 72.59, 72.68, 73.13 (CH2Ph), 81.93 (C-1), 84.60 (C-5), 78.25 (C-3), 81.12 (C-2), 88.06 (C-1), 169.56 (Cq,OAc). Ϫ
1
(C-3), 88.83 (C-2), 127.67, 127.79, 127.84, 127.91, 128.35, 128.37, Minor anomer: H NMR (400 MHz, CD3OD): δ ϭ 3.35 (s, 3 H,
128.45 (CArH), 137.44, 137.85, 137.87 (Cq,Ar), 170.20 (Cq,OAc). Ϫ
9β: 1H NMR (500 MHz, CDCl3): δ ϭ 2.10 (s, 3 H, CH3), H), 3.90 (dd, 1 H, 5b-H), 3.99 (dd, 1 H, 2-H), 4.84 (d, 1 H, 1-H);
3.41Ϫ3.47 (m, 1 H, 4-H), 3.55 (dd, 1 H, 5a-H), 3.72 (dd, 1 H, 5b- J1,2 ϭ 4.5, J2,3 ϭ 6.6, J3,4 ϭ 5.9, J4,5a ϭ 7.2, J4,5b ϭ 7.7, J5a,5b
H), 4.17 (dd, 1 H, 3-H), 4.22 (dd, 1 H, 2-H), 4.56 (s, 2 H, CH2Ph), 10.6 Hz. Ϫ 13C NMR (125 MHz, CD3OD): δ ϭ 53.17 (C-4), 57.82
4.58Ϫ4.72 (m, 2 H, CH2Ph), 4.70, 4.86 (AB system, 2 H, JAB (CH3), 65.01 (C-5), 79.05 (C-3), 84.55 (C-2), 92.77 (C-1), 170.12
11.5 Hz, CH2Ph), 6.12 (d, 1 H, H-1), 7.28Ϫ7.39 (m, 15 H, ArH); (Cq,OAc). Ϫ MS (70 eV); m/z (%): 208 (0.1) [Mϩ], 180 (5), 163 (8),
CH3), 3.40 (ddd, 1 H, 4-H), 3.58 (dd, 1 H, 5a-H), 3.75 (dd, 1 H, 3-
ϭ
ϭ
J1,2 ϭ 4.1, J2,3 ϭ 8.5, J3,4 ϭ 7.0, J4,5a ϭ 7.0, J4,5b ϭ 5.8, J5a,5b
ϭ
162 (42), 145 (7), 103 (20), 89 (30), 87 (26), 77 (100), 74 (90), 73
9.7 Hz. Ϫ 13C NMR (125 MHz, CDCl3): δ ϭ 21.29 (CH3), 45.27 (51), 62 (35), 60 (44), 58 (49), 48 (24), 46 (63).
(C-4), 72.77, 73.12, 73.14 (CH2Ph), 73.39 (C-5), 74.65 (C-1), 83.78
1-(2,3,5-Tri-O-benzyl-4-thio--arabino-furanosyl)uracil (12): A solu-
(C-3), 85.99 (C-2), 127.65, 127.66, 127.68, 127.80, 127.90, 127.97,
128.34, 128.37, 128.45 (CArH), 137.44, 137.92, 138.26 (Cq,Ar),
170.15 (Cq,OAc). Ϫ MS (70 eV); m/z (%): 122 (5), 108 (8), 107 (7),
105 (12), 92 (7), 91 (100) [C7H7ϩ], 79 (8), 77 (14), 66 (7), 60 (6), 52
(7). Ϫ C28H30O5S (478.6): calcd. C 70.27, H 6.32, S 6.70; found C
69.72, H 6.32, S 7.07.
tion of 9 (488 mg, 1.02 mmol), 2,4-bis-O-(trimethylsilyl)uracil (988
mg, 3.85 mmol) and molecular sieves (20 mg) in dry acetonitrile
(10 mL) was cooled to Ϫ18°C. Under stirring TMSOTf (0.45 mL,
554 mg, 2.49 mmol) was added and stirring was continued for 2 h.
Then a saturated aq. NaHCO3 solution (20 mL) was added, fol-
lowed by filtration and extraction with dichloromethane. The or-
ganic phase was dried with MgSO4 and the resulting crude product
was purified by column chromatography [petroleum ether/ethyl
acetate, 1:1, Rf(12β) ϭ 0.37, Rf(12α) ϭ 0.30] to yield 12α ϩ 12β
(2:1) (488 mg, 88%), colourless amorphous solid. Ϫ IR (KBr): ν˜ ϭ
3191, 3088, 3058, 3032, 2922, 2861, 1689, 1496, 1454, 1380, 1251,
1209, 1178, 1092, 1028, 909, 810, 738, 699, 605, 515 cmϪ1. Ϫ 12α:
2,3,5-Tri-O-benzyl-4-thio--arabino-furanose (10): A solution of 9
(200 mg, 0.42 mmol) in dry methanol (2 mL) was added dropwise
to a sodium methoxide solution from 1 mg (0.04 mmol) of sodium
and dry methanol (4 mL) and stirred at room temp. for 2 h. After
the reaction was complete, water (10 mL) was added, the solution
was neutralized and concentrated. The residue was dissolved in di-
chloromethane, extracted with water, dried with MgSO4 and con- 1H NMR (400 MHz, CDCl3): δ ϭ 3.53 (dd, 1 H, 5Јa-H), 3.76 (dd,
centrated. The crude product was purified by column chromatogra- 1 H, 5Јb-H), 3.91 (ddd, 1 H, 4Ј-H), 4.11 (dd, 1 H, 2Ј-H), 4.13Ϫ4.22
phy [petroleum ether/ethyl acetate, 4:1, Rf(10α,β) ϭ 0.14] to yield a (m, 1 H, 3Ј-H), 4.33Ϫ4.67 (m, 4 H, CH2Ph), 4.63, 4.88 (AB system,
1:1 anomeric mixture of 10 (145 mg, 79%), pale yellow syrup. Ϫ
IR (film): ν˜ ϭ 3406, 3088, 3063, 3030, 2923, 2863, 1498, 1454, 1402,
2 H, JAB ϭ 12.2 Hz, CH2Ph), 5.50 (d, 1 H, 5-H), 6.29 (d, 1 H, 1Ј-
H), 7.24Ϫ7.39 (m, 15 H, ArH), 7.88 (d, 1 H, 6-H), 9.29 (br. s, 1 H,
1362, 1253, 1207, 1106, 1029, 883, 740, 699, 600, 437 cmϪ1. Ϫ NH); J1Ј,2Ј ϭ 2.0, J2Ј,3Ј ϭ 1.9, J3Ј,4Ј ϭ 2.0, J4Ј,5Јa ϭ 6.7, J4Ј,5Јb
ϭ
Anomer 1: 1H NMR (500 MHz, CDCl3): δ ϭ 3.29 (br. s, 1 H, OH),
8.6, J5Јa,5Јb ϭ 9.5, J5,6 ϭ 8.3 Hz. Ϫ 13C NMR (101 MHz, CDCl3):
4.22 (ddd, 1 H, 4-H), 3.52 (dd, 1 H, 5a-H), 3.57 (dd, 1 H, 5b-H), δ ϭ 53.45 (C-4Ј), 66.53 (C-1Ј), 71.41 (C-5Ј), 71.72, 71.83, 72.82
4.08 (dd, 1 H, 2-H), 4.20Ϫ4.23 (m, 1 H, 3-H), 4.42Ϫ4.72 (m, 6 H,
CH2Ph), 5.18 (br. d, 1 H, 1-H), 7.21Ϫ7.35 (m, 15 H, ArH); J1,2
(CH2Ph), 84.49 (C-3Ј), 88.87 (C-2Ј), 100.78 (C-5), 127.27, 127.31,
127.37, 127.58, 127.62, 128.01, 128.06, 128.08, 128.12 (CArH),
ϭ
3.8, J2,3 ϭ 7.2, J3,4 ϭ 4.9, J4,5a ϭ 4.8, J4,5b ϭ 5.1, J5a,5b ϭ 9.5 Hz. 136.29, 136.88, 137.40 (Cq), 142.26 (C-6), 150.37 (2-CO), 162.92 (4-
13C NMR (125 MHz, CDCl3): δ ϭ 47.30 (C-4), 71.86, 71.94 CO). Ϫ 12β: 1H NMR (400 MHz, CDCl3): δ ϭ 3.42 (ddd, 1 H, 4Ј-
(CH2Ph), 72.14 (C-5), 73.04 (CH2Ph), 76.46 (C-1), 83.87 (C-3), H), 3.63 (dd, 1 H, 5Јa-H), 3.70 (dd, 1 H, 5Јb-H), 4.13Ϫ4.22 (m, 2
Ϫ
88.15 (C-2), for signals of aromatic C atoms see note below. Ϫ
H, 2Ј-H, 3Ј-H), 4.33Ϫ4.74 (m, 6 H, CH2Ph), 5.22 (d, 1 H, 5-H),
6.35 (d, 1 H, 1Ј-H), 7.24Ϫ7.39 (m, 15 H, ArH), 8.19 (d, 1 H, 6-H),
Anomer 2: 1H NMR (500 MHz, CDCl3): δ ϭ 3.27 (br. s, 1 H, OH),
3.45 (dd, 1 H, 5a-H), 3.65 (dd, 1 H, 5b-H), 3.93Ϫ3.96 (m, 1 H, 4- 9.16 (br. s, 1 H, NH); J1Ј,2Ј ϭ 5.7, J3Ј,4Ј ϭ 2.0, J4Ј,5Јa ϭ 3.8, J4Ј,5Јb ϭ
H), 4.20Ϫ4.23 (m, 1 H, 2-H), 4.28 (dd, 1 H, 3-H), 4.42Ϫ4.72 (m, 3.8, J5Јa,5Јb ϭ 10.3, J5,6 ϭ 8.2 Hz. Ϫ 13C NMR (101 MHz, CDCl3):
6 H, CH2Ph), 5.39 (br. d, 1 H, 1-H), 7.21Ϫ7.35 (m, 15 H, ArH); δ ϭ 45.96 (C-4Ј), 57.90 (C-1Ј), 68.10 (C-5Ј), 72.64, 73.06, 73.26
694
Eur. J. Org. Chem. 1999, 691Ϫ696

Thiosugars, 2
FULL PAPER
(CH2Ph), 79.69 (C-3Ј), 84.82 (C-2Ј), 101.11 (C-5), 127.37, 127.51,
(dd, 2 H, 2Ј-H), 5.69 (d, 1 H, 5-H), 6.28 (d, 1 H, 1Ј-H), 8.31 (d, 1
127.61, 127.62, 127.65, 127.74, 127.77, 127.78, 128.15 (CArH), H,6-H); J1Ј,2Ј ϭ 5.8, J3Ј,4Ј ϭ 6.4, J5,6 ϭ 8.1 Hz. Ϫ 13C NMR (101
136.51, 136.95, 137.29 (Cq), 142.68 (C-6), 150.79 (2-CO), 162.83 (4-
MHz, CD3OD): δ ϭ 54.18 (C-4Ј), 62.20 (C-1Ј), 63.11 (C-5Ј), 77.56
CO). Ϫ FAB MS (mNBA); m/z: 531 [M ϩ H]. Ϫ C30H30N2O5S (C-3Ј), 79.21 (C-2Ј), 101.48 (C-5), 145.51 (C-6), 154.23 (2-CO),
(530.7): calcd. C 67.90, H 5.70, N 5.28, S 6.04; found[25] C 66.80,
H 5.73, N 5.08, S 6.39.
169.67 (4-CO). Ϫ MS (70 eV); m/z (%): 260 (0.35) [Mϩ], 131 (29),
113 (45), 112 (100), 101 (20), 85 (18), 70 (32), 69 (82), 58 (42), 45
(50). Ϫ HR MS [Mϩ]: calcd. 260.0467; found 260.0464.
1-(2,3,5-Tri-O-benzyl-4-thio--arabino-furanosyl)thymine
(13):
Preparation was performed following the same procedure as de-
scribed for 12, using 9 (602 mg, 1.26 mmol), 2,4-bis-O-(trimethyl-
1-(4-Thio--arabino-furanosyl)thymine (15): Preparation analogous
to the procedure described for 14 from 13 (238 mg, 0.44 mmol) in
silyl)thymine (1.10 g, 4.07 mmol), TMSOTf (0.55 mL, 677 mg, 3.05 dry dichloromethane (3.1 mL) and boron tribromide (0.20 mL, 528
mmol) and molecular sieves (20 mg) in dry acetonitrile (20 mL). mg, 2.11 mmol) in dry dichloromethane (2 mL). Neutralization
After chromatography [petroleum ether/ethyl acetate, 1:1,
Rf(13α,β) ϭ 0.39], 13 (537 mg, 78%) was isolated with an anomeric chromatography [chloroform/methanol, 4:1, Rf(15α,β) ϭ 0.10], the
ratio of 2:1 (α/β), white solid. Ϫ IR (KBr): ν˜ ϭ 3185, 3062, 3030, unprotected nucleoside (56 mg, 47%) was isolated with an anomeric
was performed with silver carbonate (2.06 g, 7.47 mmol). After
2924, 2856, 1688, 1497, 1454, 1387, 1364, 1253, 1206, 1095, 1075, ratio of 5:1 (α/β), white solid. Ϫ IR (KBr): ν˜ ϭ 3389, 2925, 2854,
1027, 820, 737, 699, 605, 573, 481 cmϪ1. Ϫ 13α: 1H NMR (400 1687, 1469, 1387, 1257, 1227, 1096, 1045, 900, 826, 780, 723, 659,
MHz, CDCl3): δ ϭ 1.66 (d, 3 H, CH3), 3.55 (dd, 1 H, 5Јa-H), 3.77
(dd, 1 H, 5Јb-H), 3.92 (ddd, 1 H, 4Ј-H), 4.12 (dd, 1 H, 2Ј-H),
567, 478 cmϪ1. Ϫ 15α: 1H NMR (400 MHz, CD3OD): δ ϭ 1.92
(d, 3 H, CH3), 3.60Ϫ3.67 (m, 2 H, 4Ј-H, 5Јa-H), 3.84Ϫ3.97 (m, 2
4.16Ϫ4.20 (m, 1 H, 3Ј-H), 4.44Ϫ4.56 (m, 4 H, CH2Ph), 4.64, 4.79 H, 3Ј-H, 5Јb-H), 4.11 (dd, 1 H, 2Ј-H), 5.98 (d, 1 H, 1Ј-H), 7.82 (q,
(AB system, 2 H, JAB ϭ 12.2 Hz, CH2Ph), 6.24 (d, 1 H, 1Ј-H), 1 H, 6-H); J1Ј,2Ј ϭ 7.5, J2Ј,3Ј ϭ 7.6, J6,Me ϭ 1.1 Hz (in agreement
7.25Ϫ7.37 (m, 15 H, ArH), 7.59 (q, 1 H, 6-H), 9.05 (br. s, 1 H, with ref.[11]). Ϫ 13C NMR (101 MHz, CD3OD): δ ϭ 11.70 (CH3),
NH); J1Ј,2Ј ϭ 2.5, J2Ј,3Ј ϭ 2.5, J3Ј,4Ј ϭ 2.6, J4Ј,5Јa ϭ 7.2, J4Ј,5Јb
ϭ
51.77 (C-4Ј), 61.94 (C-1Ј), 63.69 (C-5Ј), 76.28 (C-3Ј), 81.13 (C-2Ј),
111.31 (C-5), 137.89 (C-6), 153.19 (2-CO), 166.62 (4-CO). Ϫ 15β:
7.9, J5Јa,5Јb ϭ 9.5, J6,Me ϭ 1.2 Hz. Ϫ 13C NMR (101 MHz, CDCl3):
δ ϭ 11.89 (CH3), 52.68 (C-4Ј), 65.27 (C-1Ј), 71.41 (C-5Ј), 71.91, 1H NMR (400 MHz, CD3OD): δ ϭ 1.89 (d, 1 H, CH3), 3.27Ϫ3.31
71.98, 72.85 (CH2Ph), 84.82 (C-3Ј), 88.80 (C-2Ј), 109.56 (C-5), (m, 1 H, 4Ј-H), 3.84Ϫ3.97 (m, 2 H, 5Јa-H, 5Јb-H), 4.09Ϫ4.13 (m,
127.28, 127.42, 127.50, 127.52, 127.66, 128.02, 128.05, 128.12 1 H, 3Ј-H), 4.18 (dd, 1 H, 2Ј-H), 6.24 (d, 1 H, 1Ј-H), 8.21 (d, 1 H,
(CArH), 136.44, 136.89, 137.41 (Cq), 137.68 (C-6), 150.39 (2-CO), 6-H); J1Ј,2Ј ϭ 5.9, J2Ј,3Ј ϭ 7.0, J6,Me ϭ 1.1 Hz (in agreement with
1
163.32 (4-CO). Ϫ 13β: H NMR (400 MHz, CDCl3): δ ϭ 1.65 (d, ref.[11]). Ϫ 13C NMR (101 MHz, CD3OD): δ ϭ 11.68 (CH3), 52.46
3 H, CH3), 3.42Ϫ3.45 (m, 1 H, 4Ј-H), 3.63 (dd, 1 H, 5Јa-H), 3.70 (C-4Ј), 60.69 (C-1Ј), 61.52 (C-5Ј), 76.01 (C-3Ј), 78.36 (C-2Ј), 109.74
(dd, 1 H, 5Јb-H), 4.16Ϫ4.20 (m, 2 H, 2Ј-H, 3Ј-H), 4.44Ϫ4.73 (m, 6 (C-5), 140.13 (C-6), 153.06 (2-CO), 166.41 (4-CO). Ϫ MS (70 eV);
H, CH2Ph), 6.39 (d, 1 H, 1Ј-H), 7.25Ϫ7.37 (m, 15 H, ArH), 7.99 m/z (%): 274 (0.16) [Mϩ], 256 (37) [Mϩ Ϫ H2O], 238 (5), 209 (10),
(q, 1 H, 6-H), 8.97 (br. s, 1 H, NH); J1Ј,2Ј ϭ 5.2, J4Ј,5Јa ϭ 4.4,
149 (18), 132 (5), 131 (78), 126 (82), 113 (16), 101 (34), 96 (18), 91
J4Ј,5Јb ϭ 4.0, J5Јa,5Јb ϭ 10.2, J6,Me ϭ 1.2 Hz. Ϫ 13C NMR (101 (40), 85 (24), 74 (17), 73 (24), 59 (21), 57 (67), 56 (100), 54 (32), 47
MHz, CDCl3): δ ϭ 11.78 (CH3), 46.12 (C-4Ј), 57.70 (C-1Ј), 68.11 (20), 45 (59). Ϫ HR MS [Mϩ]: calcd. 274.0623; found 274.0669.
(C-5Ј), 72.60, 72.92, 73.22 (CH2Ph), 79.94 (C-3Ј), 84.75 (C-2Ј),
1-(2-O-Benzyl-4-thio--arabino-furanosyl)uracil (16): Preparation as
109.68 (C-5), 127.37, 127.50, 127.56, 127.57, 127.67, 127.71, 128.03,
described for 14, using 12 (458 mg, 0.86 mmol) in dry dichloro-
128.06, 128.16 (CArH), 136.51, 137.03, 137.26 (Cq), 138.31 (C-6),
methane (6.1 mL) and boron tribromide (0.38 mL, 1.00 g, 3.99
150.86 (2-CO), 163.31 (4-CO). Ϫ FAB MS (mNBA); m/z: 545 [M
mmol) in dry dichloromethane (3.8 mL). Neutralization was per-
formed with ion exchanger Amberlite IRA-420. After chromatog-
raphy [chloroform/methanol, 4:1, Rf(16α,β) ϭ 0.53], nucleoside 16
ϩ H]. Ϫ C31H32N2O5S (544.68): calcd. C 68.36, H 5.92, N 5.14, S
5.89; found C 68.12, H 6.18, N 4.66, S 5.90.
1-(4-Thio--arabino-furanosyl)uracil (14): A solution of boron trib-
(48 mg, 47%) was isolated with an anomeric ratio of 5:2 (α/β), white
romide (0.28 mL, 739 mg, 2.95 mmol) in dry dichloromethane (2.8 solid. Ϫ IR (KBr): ν˜ ϭ 3430, 3088, 3030, 2925, 2853, 1702, 1656,
mL) was cooled to Ϫ90°C. Into this solution was added dropwise
a solution of 12 (331 mg, 0.62 mmol) in dichloromethane (4.4 mL)
under vigorous stirring. It is necessary that the reaction temp. does
not rise above Ϫ80°C. Stirring was continued for 2 h at this temp.
followed by quenching of the reaction solution with a 1:1 mixture
1458, 1391, 1254, 1197, 1089, 1055, 813, 757, 728, 699, 601, 562
cmϪ1. Ϫ 16α: 1H NMR (500 MHz, [D6]DMSO): δ ϭ 3.37Ϫ3.43
(m, 1 H, 5Јa-H), 3.55 (ddd, 1 H, 4Ј-H), 4.13Ϫ4.22 (m, 1 H, 3Ј-H),
3.77Ϫ3.86 (m, 1 H, 5Јb-H), 4.00Ϫ4.05 (m, 1 H, 2Ј-H), 4.95 (br. s,
1 H, OH-5Ј), 4.98 (s, 2 H, CH2Ph), 5.56 (br. s, 1 H, OH-3Ј), 5.78
of methanol/dichloromethane (8 mL). After the solution had (br. s, 1 H, NH), 5.81 (d, 1 H, 1Ј-H), 5.88 (d, 1 H, 5Ј-H), 7.23Ϫ7.32
warmed to room temp., the hydrobromic acid was neutralized with
silver carbonate (2.58 g, 9.34 mmol), followed by filtration and con-
centration. The crude nucleoside was purified by column chroma-
tography [chloroform/methanol, 4:1, Rf(14α,β) ϭ 0.11] to yield 14
(50 mg, 31%) as an anomeric mixture with an α/β ratio of 4:1,
(m, 5 H, ArH), 8.11 (d, 1 H, 6-H); J1Ј,2Ј ϭ 6.7, J3Ј,4Ј ϭ 4.1, J4Ј,5Јa ϭ
7.8, J4Ј,5Јb ϭ 7.8, J5,6 ϭ 8.2 Hz. Ϫ 13C NMR (125 MHz,
[D6]DMSO): δ ϭ 44.07 (CH2Ph), 53.07 (C-4Ј), 63.69 (C-5Ј), 63.75
(C-1Ј), 76.07 (C-3Ј), 80.76 (C-2Ј), 101.62 (C-5), 127.54, 128.04,
128.67 (CArH), 137.38 (Cq), 141.55 (C-6), 151.66 (2-CO), 162.13 (4-
1
white solid. Ϫ IR (KBr): ν˜ ϭ 3430, 1687, 1486, 1401, 1304, 1258,
CO). Ϫ 16β: H NMR (500 MHz, [D6]DMSO): δ ϭ 3.18 (ddd, 1
1
1178, 1103, 1046, 980, 931, 820, 558 cmϪ1. Ϫ 14α: H NMR (400 H, 4Ј-H), 3.63Ϫ3.72 (m, 1 H, 5Јa-H), 3.77Ϫ3.86 (m, 1 H, 5Јb-H),
MHz, CD3OD): δ ϭ 3.63Ϫ3.66 (m, 2 H, 4Ј-H, 5Јa-H), 3.85Ϫ3.97 3.92Ϫ3.96 (m, 1 H, 3Ј-H), 4.00Ϫ4.05 (m, 1 H, 2Ј-H), 4.97Ϫ5.00
(m, 2 H, 3Ј-H, 5Јb-H), 4.10 (dd, 1 H, 2Ј-H), 5.79 (d, 1 H, 5-H),
(m, 2 H, CH2Ph), 5.17 (br. s, 1 H, OH-5Ј), 5.46 (br. s, 1 H, OH-
5.96 (d, 1 H, 1Ј-H), 8.07 (d, 1 H, 6-H); J1Ј,2Ј ϭ 6.8, J2Ј,3Ј ϭ 7.2, 3Ј), 5.78 (br. s, 1 H, NH), 5.80 (d, 1 H, 5-H), 6.20 (d, 1 H, 1Ј-H),
J5,6 ϭ 8.1 Hz. Ϫ 13C NMR (101 MHz, CD3OD): δ ϭ 53.61 (C-
7.23Ϫ7.32 (m, 5 H, ArH), 8.14 (d, 1 H, 6-H); J1Ј,2Ј ϭ 5.8, J3Ј,4Ј ϭ
4Ј), 64.00 (C-1Ј), 64.64 (C-5Ј), 77.62 (C-3Ј), 82.58 (C-2Ј), 103.29 5.4, J4Ј,5Јa ϭ 5.8, J4Ј,5Јb ϭ 5.8, J5,6 ϭ 8.2 Hz. Ϫ 13C NMR (125
(C-5), 143.71 (C-6), 153.41 (2-CO), 166.69 (4-CO). Ϫ 14β: 1H MHz, [D6]DMSO): δ ϭ 44.00 (CH2Ph), 53.86 (C-4Ј), 61.74 (C-1Ј),
NMR (400 MHz, CD3OD): δ ϭ 3.30Ϫ3.32 (m, 1 H, 4Ј-H), 62.31 (C-5Ј), 76.15 (C-3Ј), 77.73 (C-2Ј), 99.97 (C-5), 127.45, 127.92,
3.85Ϫ3.97 (m, 2 H, 5Јa-H, 5Јb-H), 4.07Ϫ4.09 (m, 1 H, 3Ј-H), 4.19
128.64 (CArH), 137.43 (Cq), 142.60 (C-6), 151.89 (2-CO), 162.23 (4-
Eur. J. Org. Chem. 1999, 691Ϫ696
695

J. Wirsching, J. Voss
FULL PAPER
thank Prof. Yoshimura for a reprint of his brand-new publi-
cation.
CO). Ϫ FAB MS (mNBA); m/z: 351 [M ϩ H]. Ϫ C16H18N2O5S
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H 5.51, N 7.30, S 8.42.
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