Synthesis of Potentially Antiviral 2′,3′-Dideoxy-2′ -fluoro-3′-(hydroxyamino)nucleosides

Article abstract of DOI:10.1002/hlca.200490030

A series of novel 3′-(alkyl(hydroxy)amino)-2′-fluoronucleoside analogs were prepared via conjugate addition of N-methylhydroxylamine to various 2-fluorobutenolides. The adducts 13a and 16 were obtained as single isomers under absolute control of stereoche

Full text of DOI:10.1002/hlca.200490030

Helvetica Chimica Acta Vol. 87 (2004)
327
Synthesis of Potentially Antiviral 2',3'-Dideoxy-2'-fluoro-3'-
(hydroxyamino)nucleosides
by Songqing Wanga), Junbiao Changa), Shifeng Pan*a),b), and Kang Zhao*a)
a) College of Pharmaceuticals and Biotechnology, Tianjin University, 92 Weijin Road, Nankai District, 300072,
Tianjin, P.R. China (phone: ‡860222740-4031; fax: ‡860222789-0968;
e-mail: kz2@columbia.edu, zhaok1@hotvoice.com)
b) Department of Chemistry, New York University, New York, NY 10003, USA
A series of novel 3'-(alkyl(hydroxy)amino)-2'-fluoronucleoside analogs were prepared via conjugate
addition of N-methylhydroxylamine to various 2-fluorobutenolides. The adducts 13a and 16 were obtained as
single isomers under absolute control of stereochemistry. The crucial N-demethylation of 23 25 was readily
achieved by means of DDQ oxidation, followed by nitrone/oxime exchange reaction. By this procedure, a
variety of alkyl groups could be efficiently introduced at the 3'-N-atom of the nucleoside analogs, some of which
might display potentially interesting anti-HIV properties.
Introduction. Structural modifications of nucleoside analogs have been successful
in the search for effective antiviral agents against human immunodeficiency virus
(HIV) [1 3]. Of particular interest is the alteration of the 2'- and 3'-OH groups of
ribose rings, particularly the 2',3'-dideoxynucleoside analogs termed ddI, ddC, d4T,
DAPD, and lodenosine [4 7]. It has been established that the 3'-position of 2'-
deoxynucleoside analogs can tolerate various differently sized substituents, including
N-containing moieties, and still maintain their antiviral activities, e.g., AZT, 1a, and 1b
[8 11]. An interesting new class of nucleoside analogs of types 2 and 3 (R ˆ Me)
possess 3'-(hydroxyamino) substituents [12][13].
Compounds of type 3 differ from those of type 2 by an additional F-atom at the 2'b-
position and by different N-alkyl groups. It is known that the 2'-F-atom can stabilize
glycosyl bonds under both hydrolytic and enzymatic conditions [14]. As shown by

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structure/activity-relationship studies, 2'b-configured compounds typically exhibit
excellent antiviral activities [15] (in contrast to most 2'a-isomers), as exemplified by
2'-1-(2'-deoxy-2'-fluoro-b-l-arabinofuranosyl)uracil (L-FMAU) [16] and 1-(2',3'-di-
deoxy-2-fluoro-b-d-pentofuranosyl)cytosine (F-ddA, lodenosine) [17][18].
Although nucleosides 3 with N-Me groups (R ˆ Me) have been prepared by
hydroxylamine-concerted addition [19], a variety of compounds with other alkyl
substituents were required for antiviral studies [13]. Many synthetic approaches have
been made to introduce such N-alkyl groups into compounds of type 3, but without
much success. Here, we report a strategy for the stereoselective preparation of 2'-
fluoro-3'-(hydroxyamino)nucleosides of type 3. The main feature of the procedure
reported is that the different N-alkyl groups can be introduced via a common
intermediate at a late stage of the synthesis; moreover, our approach allows for
efficient preparation of many related derivatives required to study structure/activity
relationships.
Results and Discussion. To access the N-methylated nucleoside analogs 4 11, the
TBS-protected1) compound 12a was prepared and converted to 13a and 14a (Scheme 1)
[13]. Since the acetate derivative of 14a (X ˆ OAc) failed to give the coupling product
with nucleoside bases in the presence of catalytic amounts of TMSOTf, the
Scheme 1
1
)
For abbreviations, see the General section in the Exper. Part.

Helvetica Chimica Acta Vol. 87 (2004)
329
corresponding chloride 14b was selected as an alternative intermediate, which was
easily prepared from 14a with MsCl and 1 equiv. of Et3N(plus a catalytic amount of
Bu3N). Glycosyl chloride 14b was coupled with silylated uracil, thymine, 5-fluorouracil,
and cytosine by refluxing in CHCl3 to afford the protected nucleosides 4 7 (generally
as ca. 1:1 mixtures of a/b-anomers). Then, the two TBS groups were removed with
‡
Bu4N FÀ (TBAF) in anhydrous THF to afford 8 11 (83 99%), which, except for 8,
were separated into the corresponding 1'a- and 1'b-isomers by column chromatography
(SiO2).
The configuration at the anomeric center was derived from the chemical shift of
HÀC(4'). The b-configuration of the F-atom in 2'-position was confirmed by both 1H-
and 13C-NMR analyses. A long-range coupling between HÀC(6) and the F-atom, with
J(2'-F,HÀC(6)) ˆ 1 2 Hz was observed. Also, the coupling constants observed for
C(1') and the F-atom are known to be considerably larger for the a-isomer
(J(F,C(1')) ˆ 35 37 Hz) than for the b-isomer (J(F,C(1')) ˆ 16 18 Hz) [20].
We next developed a retrosynthetic strategy to access 2'-fluoro-3'-(hydroxyamino)
nucleosides of type 3 with N-alkyl substituents other than Me (Scheme 2). The addition
of various N-alkyl hydroxylamines to the 2-fluorobutenolactone 12a was not
investigated since the preparation of the corresponding starting materials would have
required great synthetic efforts. An efficient method would be to demethylate 15a to
15b as a key intermediate2). This compound could then be derivatized to access a large
series of products of type 3 by only a few chemical steps.
Scheme 2
The synthesis started from the TBDPS-protected1) butenolide 12b (Scheme 3).
Conjugate addition of N-methylhydroxylamine afforded the adduct 16 as a single
isomer in 65% yield. The latter was protected with TBSCl ( ! 17), reduced with
DIBAL ( ! 18), and chlorinated with MsCl to afford the intermediate 19, which was
then reacted with different silylated bases to the protected nucleosides 20 22 (as ca.
2
)
Direct addition of NH2OH to 12a afforded only low yields (<20%) of 15b.

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Helvetica Chimica Acta Vol. 87 (2004)
1:1 mixtures of a/b-anomers). The O-TBS group was selectively removed with 48%
HF in MeCNto yield the N-methyl derivatives 23 25.
The unique properties of hydroxylamines allow the potential replacement of N-Me
groups (which can be regarded as −unusual× N-protecting groups), by other alkyl
groups, i.e., by the sequential oxidation of the N-Me group, followed by alkyl exchange
and reduction. In a first attempt, 23 25 were subjected to HgO-promoted oxidation
[21] to the corresponding nitrone intermediates. However, these were contaminated
with Hg-containing compounds, even after column-chromatographic purification.
Finally, DDQ-mediated oxidation of 23 25 afforded the pure intermediate nitrones
(structures not shown), in which the N-Me group was selectively converted to an
NˆCH2 group, which was removed with NH2OH ¥ HCl by means of an exchange
reaction (MeOH, 508), affording the hydroxylamines 26 28.
In the next step, compounds 26 28 were reductively alkylated to 29 35 (65 93%)
by condensation with different aldehydes (butanal, 2-methylpropanal, cyclohexane-
carboxaldehyde), followed by in situ reduction with NaBH3CN( Scheme 4). Then,
TBDPS deprotection with TBAF finally afforded the desired nucleosides 36 42 in 70
96% yield.
Conclusions. We have developed a route towards the efficient synthesis of a
variety of new N-alkylated 2',3'-dideoxy-2'-fluoro-3'-(hydroxyamino)nucleoside ana-
logs by stereoselective addition to a,b-unsaturated lactones (furan-1-ones). The
compounds prepared were required to study their anti-HIVLAI and anti-HSV-1
activities. The two anomeric cytosine derivatives a-13 and b-13, indeed, showed
significant anti-HIVLAI activities in vitro; and a-13 displayed an acceptably low
cytotoxicity [19]. These compounds represent the first examples of nucleoside analogs
with vicinal fluoro and amino functionalities at the 2'- and 3'-positions, respectively, of
the dideoxyribose moiety and will certainly open up the way to further potentially
biorelevant compounds of this type.
Experimental Part
General. Abbreviations: DDQ, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone; DIBAL, (iBu)2AlH; Ms,
‡
MeSO2; TBAF, Bu4N FÀ; TBDPS, (tBu)Ph2Si; TBS, (tBu)Me2Si; Tf, F3CSO2; TMS, Me3Si. All reagents and
solvents were purchased from Aldrich, Fisher, or Acros Chimica, and were used without further purification
unless otherwise stated. Thin layer chromatography (TLC) was performed on Merck silica gel 60 F254 (0.25 mm;
glass plates). Column and flash chromatography (CC and FC, resp.) were performed on Mallinckrodt silica gel
60 (230 400 mesh). 1H- and 13C-NMR spectra were recorded on a Varian-200 spectrometer (200 and 50 MHz,
resp.) at ambient temp.; chemical shifts d in ppm rel. to SiMe4 (ˆ0 ppm), coupling constants J in Hz.
5-O-[(tert-Butyl)dimethylsilyl]-2,3-dideoxy-2-fluoro-3-[hydroxy(methyl)amino]-d-arabino-1,4-lactone
(13a). To a soln. of N-methylhydroxylamine hydrochloride (12.53 g, 150 mmol) in EtOH (300 ml) was added
EtONa (10.20 g, 150 mmol) portionwise. The resulting mixture was stirred at r.t. for 10 min, and 5-({[(tert-
butyl)dimethylsilyl]oxy}methyl)-3-fluorofuran-2(5H)one (12a; 7.38 g, 30 mmol) was added. The resulting soln.
was refluxed for 5 h and concentrated under reduced pressure. Then, H2O (100 ml) was added to the residue,
and the resulting soln. was extracted with CH2Cl2. The org. layer was washed with brine, dried (Na2SO4),
filtered, and concentrated. The residue was purified by FC (SiO2; AcOEt/petroleum ether 1:3): 6.08 g (69%) of
1
13a. Oil. H-NMR (CDCl3): 6.30 (br. s, OH); 5.53 (dd, J ˆ 7.2, 51.4, HÀC(2)); 4.51 (dt, J ˆ 7.2, 2.4, HÀC(4));
3.85 (m, HÀC(3), 2 HÀC(5)); 2.78 (s, MeN); 0.89 (s, t-Bu); 0.08 (s, Me2Si). 13C-NMR (CDCl3): 88.1, 84.3
(C(2)); 79.4, 79.3 (C(4)); 69.2, 68.8 (C(5)); 62.4 (C(3)); 47.5 (MeN); 26.3 (Me3C); À4.8, À4.9 (Me2Si). Anal.
calc. for C12H24FNO4Si: C 49.12, H 8.24, N4.77; found: C 49.23, H 8.30, N4.81.

Helvetica Chimica Acta Vol. 87 (2004)
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Scheme 3
a) MeN(H)OH ¥ HCl, EtOH, EtONa; 65%. b) (tBu)Me2SiCl, imidazole, DMF; 89%. c) DIBAL, CH2Cl2, À788.
d) MeSO2Cl, Et3N , BuN(cat.), CH 2Cl2, À408 ! r.t. e) Me3Si-protected base, CHCl3; 65 70% (from 17).
3
f) 48% HF, MeCN; 97 99%. g) 1. DDQ/CH2Cl2; 2. H2NOH ¥ HCl, MeOH; 48 57% (2 steps).

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Helvetica Chimica Acta Vol. 87 (2004)
Scheme 4
5-O-[(tert-Butyl)dimethylsilyl]-2,3-dideoxy-2-fluoro-3-[hydroxy(methyl)amino]-a,b-d-arabino-1,4-lactol
(14a). A mixture of 13a (5.50 g, 18.7 mmol), TBSCl (3.10 g, 20.6 mmol), and imidazole (2.80 g, 41.2 mmol) in
anh. DMF (90 ml) was stirred under Ar gas at r.t. overnight. After addition of H2O, the resulting mixture was
extracted with CH2Cl2. The org. layer was washed with brine, dried (Na2SO4), filtered, and concentrated. The
residue was purified by FC (SiO2; AcOEt/petroleum ether 5 :95) to afford 5-O-[(tert-butyl)dimethylsilyl]-2,3-
dideoxy-2-fluoro-3-{[(tert-butyl)dimethylsilyl]oxy(methyl)amino}arabino-1,4-lactone (intermediate; not shown
in Scheme 1): 7.10 g (93%). Oil. 1H-NMR (CDCl3): 5.50 (br., HÀC(2)); 4.38 (br. s, HÀC(4)); 3.80 (m, HÀC(3),
2 HÀC(5)); 2.69 (s, MeN); 0.85 (s, 2 t-Bu); 0.08 (m, 2 Me2Si). 13C-NMR (CDCl3): 78.6, 78.5 (C(4)); 70.1, 69.7
(C(5)); 61.1 (C(3)); 47.7 (MeN); 26.4, 26.3 (2 Me3C); 18.8, 18.2 (2 Me3C); À3.9, À4.1, À4.8, À4.9 (2 Me2Si).
To a soln. of the above O-protected lactone (5.45 g, 13.5 mmol) in anh. CH2Cl2 (80 ml) was added DIBAL
(14.9 ml, 1.0m soln. in hexane) at À788 under Ar gas, and the mixture was stirred at this temp. for 1 h. Then, the
mixture was quenched with MeOH (10 ml) and sat. aq. NH4Cl soln. The mixture was filtered over Celite to
remove solid materials, and the filtrate was extracted with CH2Cl2. The org. layer was washed with brine, dried
(Na2SO4), filtered, and concentrated: 5.07 g (93%) of 14a. Colorless oil, which was directly used in the next step
without further purification.

Helvetica Chimica Acta Vol. 87 (2004)
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Synthesis of Nucleosides 4 7 (General Procedure A; GPA): MsCl (149 mg, 1.3 mmol) was added dropwise
at À408 under Ar gas to a soln. of crude 14a (409 mg, 1 mmol), Et3N(162 mg, 1.6 mmol), and Bu N(37 mg,
3
0.2 mmol) in anh. CH2Cl2 (1 ml). After stirring at r.t. for 1 h, the resulting mixture was diluted with CH2Cl2,
washed with H2O and brine, dried (Na2SO4), filtered, and concentrated to afford the crude chloro derivative 14b
(yellowish oil), which was refluxed overnight in the presence of a TMS-protected nucleoside base (3 mmol) in
EtOH-free CHCl3 (5 ml). Then, H2O was added, and the resulting mixture was extracted with CH2Cl2. The org.
layer was washed with brine, dried (Na2SO4), filtered, and concentrated. The residue was purified by FC (SiO2;
AcOEt/petroleum ether 1:3 ! 1 :1).
1-[5'-O-[(tert-Butyl)dimethylsilyl]-3'-({[(tert-butyl)dimethylsilyl]oxy}(methyl)amino)-2',3'-dideoxy-2'-fluoro-
a,b-d-arabinofuranosyl]thymine (a,b-4). GPA: 70% (anomeric mixture). White solid. 1H-NMR (CDCl3): 9.97
(m, NH); 7.38 (s, HÀC(6) (b)); 7.11 (s, HÀC(6) (a)); 6.17 (dd, J ˆ 4.4, 14.0, HÀC(1') (a)); 6.02 (dd, J ˆ 3.7, 19.7,
HÀC(1') (b)); 5.55 (br., HÀC(2')); 4.21 (br. s, HÀC(4') (a)); 3.75 (m, HÀC(3'), 2 HÀC(5'), HÀC(4') (b));
2.65 (s, MeN); 1.89 (s, MeÀC(5)); 0.89, 0.88 (2s, 2 t-Bu); 0.11 (m, 2 Me2Si). 13C-NMR (CDCl3): 164.8, 164.5
(C(4)); 150.9, 150.8 (C(2)); 137.5, 135.3 (C(6)); 111.8, 110.0 (C(5)); 89.1, 85.0 (C(2')); 88.7 (C(1')); 81.8, 81.7
(C(4')); 74.8, 74.3, 74.0, 73.6 (C(5')); 47.8 (MeN); 26.5, 26.4, 18.9, 19.2, 13.0 (2 t-Bu); À3.8, À4.0, À4.7, À4.8
(2 Me2Si).
1-[5'-O-[(tert-Butyl)dimethylsilyl]-3'-({[(tert-butyl)dimethylsilyl]oxy}(methyl)amino)-2',3'-dideoxy-2'-flu-
oro-a,b-d-arabinofuranosyl]uracil (a,b-5). GPA: 68% (anomeric mixture). White solid.
Data of b-5: 1H-NMR (CDCl3): 10.00 (br. s, NH); 7.63 (d, J ˆ 7.3, HÀC(6)); 6.09 (dd, J ˆ 3.7, 17.6,
HÀC(1')); 5.66 (d, J ˆ 8.1, HÀC(5)); 5.55 (br., HÀC(2')); 3.80 (m, HÀC(4'), 2 HÀC(5')); 3.50 (dd, J ˆ 5.1, 26.3,
HÀC(3')); 2.69 (s, MeN); 0.88 (s, 2 t-Bu); 0.15 (m, 2 Me2Si). 13C-NMR (CDCl3): 164.1 (C(4)); 150.7 (C(2));
141.8 (C(6)); 101.9 (C(5)); 85.1, 84.9 (C(2')); 74.5 (C(1')); 74.1 (C(4')); 62.8 (C(5')); 47.7 (MeN); 26.5, 26.4, 18.8,
18.2 (2 t-Bu); À3.8, À4.0, À4.8, À4.9 (2 Me2Si).
1
Data of a-5: H-NMR (CDCl3): 9.50 (s, NH); 7.35 (d, J ˆ 8.1, HÀC(6)); 6.17 (dd, J ˆ 3.9, 14.6, HÀC(1'));
5.75 (d, J ˆ 8.1, HÀC(5)); 5.55 (br., HÀC(2')); 4.23 (br. s, HÀC(4')); 3.88 (dd, J ˆ 2.6, 11.4, 1 HÀC(5')); 3.74
(dd, J ˆ 3.4, 11.4, 1 HÀC(5')); 3.62 (dt, J ˆ 5.4, 25.0, HÀC(3')); 2.68 (s, MeN); 0.90, 0.87 (2s, 2 t-Bu); 0.15
(m, 2 Me2Si). 13C-NMR (CDCl3): 163.8 (C(4)); 150.7 (C(2)); 139.8 (C(6)); 103.3 (C(5)); 90.2, 89.8 (C(2')); 82.5,
82.4 (C(1')); 74.4 (C(4')); 74.0 (C(5')); 47.9 (MeN); 26.5, 26.4, 18.9, 18.2 (2 t-Bu); À3.9, À4.0, À4.7, À4.8
(2 Me2Si).
1-[5'-O-[(tert-Butyl)dimethylsilyl]-3'-({[(tert-butyl)dimethylsilyl]oxy}(methyl)amino)-2',3'-dideoxy-2'-flu-
oro-a,b-d-arabinofuranosyl]-5-fluorouracil (a,b-6). GPA: 66% (anomeric mixture). White solid. 1H-NMR
(CDCl3): 9.62 (br. s, N H); 7.79 (d, J ˆ 6.2, HÀC(6) (b)); 7.41 (d, J ˆ 6.1, HÀC(6) (a)); 6.07 (dd, J ˆ 3.1, 17.3,
HÀC(1')); 5.55 (br., HÀC(2')); 3.90 (m, HÀC(4'), 2 HÀC(5')); 3.55 (dd, J ˆ 4.6, 25.3, HÀC(3')); 2.63
(s, MeN); 0.89, 0.88 (2s, 2 t-Bu); 0.11 (s, 2 Me2Si). 13C-NMR (CDCl3): 157.3, 157.0 (C(4)); 149.3, 142.7 (C(2));
138.0 (C(6)); 126.5, 125.8, 124.3, 123.6 (C(5)); 85.3, 82.6 (C(2')); 85.0, 82.5 (C(1')); 74.4 (C(4')); 74.0 (C(5')); 47.7
(MeN); 26.5, 26.4, 18.9, 18.3 (2 t-Bu); À3.8, À4.0, À4.8, À4.9 (2 Me2Si).
1-[5'-O-[(tert-Butyl)dimethylsilyl]-3'-({[(tert-butyl)dimethylsilyl]oxy}(methyl)amino)-2',3'-dideoxy-2'-fluoro-
1
a,b-d-arabinofuranosyl]cytosine (a,b-7). GPA: 65% (anomeric mixture). White solid. H-NMR (CDCl3): 7.65
(dd, J ˆ 1.4, 7.5, HÀC(6) (b)); 7.37 (d, J ˆ 7.4, HÀC(6) (a)); 6.10 (m, HÀC(1')); 5.78, 5.70 (2d, J ˆ 7.3 and 7.4,
HÀC(5)); 5.40 (br., HÀC(2')); 4.22 (br. s, HÀC(4') (a)); 3.81 (m, HÀC(4') (b), 2 HÀC(5')); 3.49
(m, HÀC(3')); 2.63 (m, MeN); 0.85 (m, 2 t-Bu); 0.05 (s, 2 Me2Si). 13C-NMR (CDCl3): 166.5, 166.3 (C(4));
156.2, 155.9 (C(2)); 142.8, 140.6 (C(6)); 95.2, 94.2, 92.0, 91.3 (C(5)); 86.1, 83.9 (C(2')); 85.6, 83.4 (C(1')); 75.4,
74.9 (C(4')); 60.3 (C(3')); 48.0 (MeN); 26.6, 26.5, 18.7, 18.2 (2 t-Bu); À3.8, À3.9, À4.6, À4.7 (2 Me2Si).
Synthesis of Nucleosides 8 11 (General Procedure B; GPB): Compounds 4 7 were treated with TBAF
(2.5 equiv.) in anh. THF for 2 h at r.t. The resulting mixture was directly (without evaporation of the solvent)
purified by CC (SiO2).
1-{2',3'-Dideoxy-2'-fluoro-3'-[hydroxy(methyl)amino]-a,b-d-arabinofuranosyl}thymine (a,b-8). GPB, with
1
a,b-4: 96% (anomeric mixture). White solid. H-NMR ((D6)DMSO): 11.46, 11.42 (2s, NH); 8.45 (dd, J ˆ 1.5,
4.7, NOH); 7.64 (s, HÀC(6) (b)); 7.46 (s, HÀC(6) (a)); 6.00 (m, HÀC(1')); 5.23 (m, HÀC(2')); 5.09
(m, C(5')ÀOH); 4.39 (m, HÀC(4') (a)); 4.02 (m, HÀC(4') (b)); 3.60 (m, HÀC(3'), 2 HÀC(5')); 2.63, 2.59
(2s, MeN); 1.79 (s, MeÀC(5)). Anal. calc. for C11H16FN3O5 ¥ 0.3 H2O: C 44.83, H 5.68, N14.26; found: C 45.08,
H 5.81, N14.30.
1-[2',3'-Dideoxy-2'-fluoro-3'-(hydroxy(methyl)amino)-a,b-d-arabinofuranosyl]uracil (a,b-9). GPB, with b-
5 and a-5: 99% of b-9 and 92% of a-9, resp. White solids.
Data of b-9: 1H-NMR ((D6)DMSO): 11.46 (s, NH); 8.49 (s, NOH); 7.76 (d, J ˆ 8.1, HÀC(6)); 5.95 (dd, J ˆ
4.0, 19.3, HÀC(1')); 5.66 (d, J ˆ 8.1, HÀC(5)); 5.40 (d, J ˆ 53.3, HÀC(2')); 5.08 (t, J ˆ 6.1, C(5')ÀOH); 4.06

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(m, HÀC(4')); 3.60 (m, HÀC(3'), 2 HÀC(5')); 2.65 (s, MeN). 13C-NMR ((D6)DMSO): 163.2 (C(4)); 150.3
(CÀ(2)); 141.8, 141.7 (C(6)); 101.1 (C(5)); 93.9, 90.2 (C(2')); 84.2, 83.9 (CÀ(1')); 79.8 (C(4')); 73.0, 72.5 (C(5'));
61.5 (C(3')); 46.7 (MeN). Anal. calc. for C10H14FN3O5 ¥ 0.5 H2O: C 42.26, H 5.32, N14.78; found: C 42.53, H 5.05,
N14.37.
Data of a-9: 1H-NMR ((D6)DMSO): 11.41 (s, NH); 8.42 (s, NOH); 7.58 (d, J ˆ 8.1, HÀC(6)); 6.05 (dd, J ˆ
2.8, 16.2, HÀC(1')); 5.65 (dd, J ˆ 1.3, 8.0, HÀC(5)); 5.42 (dt, J ˆ 51.6, 2.8, HÀC(2')); 5.09 (t, J ˆ 5.8,
C(5')ÀOH); 4.39 (m, HÀC(4')); 3.60 (m, HÀC(3'), HÀC(5')); 2.68 (s, MeN). 13C-NMR ((D6)DMSO): 163.4
(C(4)); 150.7 (C(2)); 140.6 (C(6)); 101.9 (C(5)); 98.9, 95.2 (C(2')); 89.9, 89.2 (C(1')); 83.6, 83.5 (C(4')); 73.9, 73.4
(C(5')); 62.5 (C(3')); 46.9 (MeN). Anal. calc. for C10H14FN3O5 ¥ 0.2 H2O: C 43.08, H 5.21, N15.07; found: C
43.41, H 5.26, N14.79.
1-{2',3'-Dideoxy-2'-fluoro-3'-[hydroxy(methyl)amino]-a,b-d-arabinofuranosyl}-5-fluorouracil (a,b-10).
GPB, with a,b-6: 99% (anomeric mixture). White solid. The two anomers were partially separated by FC
(SiO2).
1
Data of b-10: H-NMR (CD3OD): 8.08 (dd, J ˆ 1.8, 6.9, HÀC(6)); 6.04 (ddd, J ˆ 1.6, 3.9, 18.0, HÀC(1'));
5.45 (dt, J ˆ 1.8, 52.8, HÀC(2')); 4.15 (m, HÀC(4')); 3.92 (dd, J ˆ 2.8, 12.4, HÀC(5')); 3.76 (dd, J ˆ 4.4, 12.4,
HÀC(5')); 3.48 (ddd, J ˆ 1.7, 6.2, 27.1, HÀC(3')); 2.72 (s, MeN). 13C-NMR (CD3OD): 150.7 (C(4)); 143.8
(C(2)); 139.2 (C(6)); 128.1, 127.4 (C(5)); 95.1, 91.4 (C(2')); 86.5, 86.2 (C(1')); 81.5 (C(4')); 74.6, 74.1 (C(5')); 63.1
(C(3')); 47.4 (MeN). Anal. calc. for C10H13F2N3O5 ¥ 0.6 H2O: C 39.50, H 4.71, N13.82; found: C 39.23, H 4.70, N
13.99.
Data of a-10: 1H-NMR (CD3OD): 7.87 (d, J ˆ 6.6, HÀC(6)); 6.10 (dt, J ˆ 1.6, 15.8, HÀC(1')); 5.46 (dt, J ˆ
2.3, 50.9, HÀC(2')); 4.51 (m, HÀC(4')); 3.80 (dd, J ˆ 4.0, 11.8, HÀC(5')); 3.70 (dd, J ˆ 5.3, 12.1, HÀC(5')); 3.43
(ddd, J ˆ 2.6, 5.1, 24.5, HÀC(3')); 2.70 (s, MeN). 13C-NMR (CD3OD): 163.6 (C(4)); 151.0 (C(2)); 144.2 (C(6));
126.9, 126.2 (C(5)); 100.2, 96.5 (C(2')); 92.8, 92.0 (C(1')); 86.0 (C(4')); 75.7, 75.3 (C(5')); 64.2 (C(3')); 47.6
(MeN). Anal. calc. for C10H13F2N3O5 ¥ 0.2 H2O: C 40.46, H 4.55, N14.16; found: C 40.61, H 4.37, N14.43.
1-{2',3'-Dideoxy-2'-fluoro-3'-[hydroxy(methyl)amino]-a,b-d-arabinofuranosyl}cytosine (a,b-11). GPB,
with a,b-7; followed by separation by FC (SiO2): 47% of b-11 and 36% of a-11. White solids.
Data of b-11: 1H-NMR ((D6)DMSO): 8.47 (s, NOH); 7.69 (d, J ˆ 6.3, HÀC(6)); 7.22 (m, N H); 5.93
2
(dd, J ˆ 3.4, 20.2, HÀC(1')); 5.75 (d, J ˆ 7.5, H ÀC(5)); 5.33 (md, J ˆ 53.0, HÀC(2')); 5.02 (t, J ˆ 5.9,
C(5')ÀOH); 4.01 (m, HÀC(4')); 3.65 (m, 2 HÀC(5')); 3.35 (m, HÀ(3')); 2.63 (s, MeN ). 13C-NMR
((D6)DMSO): 165.9 (C(4)); 153.8 (C(2)); 142.3 (C(6)); 93.9, 93.8 (C(5)); 89.9, 85.2 (C(2')); 84.9 (C(1')); 79.5
(C(4')); 73.6, 73.2 (C(5')); 61.8 (C(3')); 46.7 (MeN). Anal. calc. for C10H15FN4O4 ¥ 0.8 H2O: C 41.61, H 5.80, N
19.41; found: C 41.78, H 5.62, N19.57.
Data of a-11: 1H-NMR ((D6)DMSO): 8.37 (s, NOH); 7.54 (d, J ˆ 7.5, HÀC(6)); 7.19 (m, N H); 6.01
2
(dd, J ˆ 2.4, 16.6, HÀC(1')); 5.74 (d, J ˆ 7.5, HÀC(5)); 5.33 (d, J ˆ 51.7, HÀC(2')); 5.06 (t, J ˆ 5.5, C(5')ÀOH);
4.34 (m, HÀC(4')); 3.49 (m, HÀC(3'), 2 HÀC(5')); 2.54 (s, MeN). 13C-NMR ((D6)DMSO): 166.0 (C(4)); 155.4
(C(2)); 141.2 (C(6)); 99.3, 95.6 (C(2')); 94.3 (C(5)); 90.6, 89.9 (C(1')); 83.3 (C(4')); 74.1, 73.6 (C(5')); 62.5
(C(3')); 47.0 (MeN). Anal. calc. for C10H15FN4O4 ¥ 0.2 H2O: C 43.23, H 5.59, N20.16; found: C 43.43, H 5.57, N
19.97.
5-O-[(tert-Butyl)diphenylsilyl]-2,3-dideoxy-2-fluoro-3-[hydroxy(methyl)amino]-d-arabino-1,4-lactone
(16). Prepared from 12b in analogy to 13a: Yield: 65% of 16. Oil. 1H-NMR (CDCl3): 7.69 (m, 4 arom. H); 7.42
(m, 6 arom. H); 5.92 (br. s, OH); 5.57 (dd, J ˆ 7.3, 50.9, HÀC(2)); 4.51 (m, HÀC(4)); 3.95 (m, HÀC(3),
2 HÀC(5)); 2.78 (s, MeN); 1.08 (s, t-Bu). 13C-NMR (CDCl3): 170.4; 170.0; 136.2; 136.0; 133.3; 132.9; 130.4;
128.3; 88.1; 84.2; 79.3; 79.1; 69.4; 69.1; 63.3; 47.5; 27.3; 19.9.
5-O-[(tert-Butyl)diphenylsilyl]-3-({[(tert-butyl)dimethylsilyl]oxy}(methyl)amino)-2,3-dideoxy-2-fluoro-d-
arabino-1,4-lactone (17). From 16 by standard silylation methodology (TBSCl, imidiazole, DMF): 89% of 17.
Oil. 1H-NMR (CDCl3): 7.71 (m, 4 arom. H); 7.45 (m, 6 arom. H); 4.47 (br. s, HÀC(4)); 3.95 (m, HÀC(3),
2 HÀC(5)); 2.72 (s, MeN); 1.09 (s, t-Bu); 0.90 (s, t-Bu); 0.12 (m, 2 MeSi). 13C-NMR (CDCl3): 170.4, 170.0
(C(1)); 136.2, 136.0, 133.3, 132.9, 130.4, 128.3 (2 Ph); 78.7, 78.6 (CÀ(4)); 70.4, 70.0 (C(5)); 62.5 (C(3)); 47.8
(MeN); 27.3, 26.5, 19.9, 18.3 (2 t-Bu); À3.9, À4.0 (Me2Si).
1-[5'-O-[(tert-Butyl)diphenylsilyl]-3'-({[(tert-butyl)dimethylsilyl]oxy}(methyl)amino)-2',3'-dideoxy-2'-fluoro-
a,b-d-arabinofuranosyl]thymine (a,b-20). Prepared, in analogy to a,b-4, from 17 in three steps: 70% (anomeric
mixture). White solid. 1H-NMR (CDCl3): 9.60 (m, NH); 7.76 7.33 (m, 10 arom. H, HÀC(6)); 6.28 (dd, J ˆ 4.2,
14.2, HÀC(1') (a)); 6.10 (dd, J ˆ 3.7, 20.1, HÀC(1') (b)); 4.32 (br. s, HÀC(4') (a)); 3.85 (m, HÀC(3'),
2 HÀC(5'), HÀC(4') (b)); 2.67 (s, MeN); 1.95, 1.79 (2s, MeÀC(5)); 1.12 (s, t-Bu); 0.90 (m, t-Bu); 0.14
(m, Me2Si). 13C-NMR (CDCl3): 164.6, 164.4 (C(4)); 150.8 (C(2)); 137.6 (C(6)); 136.1, 135.9, 133.6, 133.4, 130.4,

Helvetica Chimica Acta Vol. 87 (2004)
335
130.3, 128.3, 128.2 (2 Ph); 111.8, 110.2 (C(5)); 85.1, 84.8 (C(2')); 81.9, 81.8 (C(1')); 74.9, 74.5 (C(4')); 74.2, 73.8
(C(5')); 47.9 (MeN); 27.4, 26.6, 26.5, 20.0, 18.3 (2 t-Bu); 12.8 (MeÀC(5)); À3.7, À3.9 (Me2Si).
1-[5'-O-[(tert-Butyl)diphenylsilyl]-3'-({[(tert-butyl)dimethylsilyl]oxy}(methyl)amino)-2',3'-dideoxy-2'-flu-
oro-a,b-d-arabinofuranosyl]uracil (a,b-21). Prepared, in analogy to 5, from 17 in three steps: 68% (anomeric
mixture). The mixture was separated by FC (SiO2).
Data of b-21: 1H-NMR (CDCl3): 10.12 (br. s, NH); 7.70 (m, 4 arom. H); 7.45 (m, 6 arom. H, HÀC(6)); 6.12
(dd, J ˆ 4.0, 18.7, HÀC(1')); 5.58 (d, J ˆ 8.4, HÀC(5)); 3.95 (m, HÀC(4'), 2 HÀC(5')); 3.63 (dd, J ˆ 5.6, 26.3,
HÀC(3')); 2.69 (s, MeN); 1.11, 0.93 (2s, 2 t-Bu); 0.18 (m, Me2Si). 13C-NMR (CDCl3): 164.2 (C(4)); 150.9 (C(2));
141.8, 136.1 (C(5)); 136.0, 133.5, 133.3, 130.4, 128.3 (2 Ph); 102.0 (C(6)); 85.2, 84.9 (C(1')); 74.8 (C(4')); 74.3
(C(5')); 47.8 (MeN); 27.4, 26.6, 19.9, 19.3 (2 t-Bu); À3.7, À4.0 (Me2Si).
Data of a-21: 1H-NMR (CDCl3): 9.88 (s, NH); 7.71 (m, 4 arom. H); 7.42 (m, 6 arom. H, HÀC(6)); 6.25
(dd, J ˆ 3.7, 14.6, HÀC(1')); 5.78 (d, J ˆ 8.0, HÀC(5)); 4.32 (br. s, HÀC(4')); 3.89 (m, 2 HÀC(5')); 3.68 (dd, J ˆ
4.3, 6.4, HÀC(3')); 2.65 (s, MeN); 1.12, 0.88 (2s, 2 t-Bu); 0.12 (m, Me2Si). 13C-NMR (CDCl3): 163.9 (C(4));
150.8 (C(2)); 139.9 (C(5)); 136.1, 136.0, 133.5, 133.3, 130.3, 128.3 (2 Ph); 103.3 (C(6)); 90.3, 89.6 (C(2')); 82.6,
82.4 (C(1')); 74.6 (C(4')); 74.2 (C(5')); 64.8 (C(3')); 47.9 (MeN); 27.4, 26.6, 26.5, 19.9, 18.3 (2 t-Bu); À3.9
(Me2Si).
1-[5'-O-[(tert-Butyl)diphenylsilyl]-3'-({[(tert-butyl)dimethylsilyl]oxy}(methyl)amino)-2',3'-dideoxy-2'-fluoro-
a,b-d-arabinofuranosyl]-5-fluorouracil (a,b-22). Prepared, in analogy to a,b-6, from 17 in three steps: 65%
(anomeric mixture). White solid. 1H-NMR (CDCl3): 7.80 7.35 (m, 10 arom. H, HÀC(6)); 6.22 (m, HÀC(1'));
1
4.41 (br. s, 1³2 HÀC(4')); 4.16 3.52 (m, HÀC(3'), ³2 HÀC(4'), 2 HÀC(5')); 2.69 (s, MeN); 1.15, 0.95 (2s, 2 t-
Bu); 0.21 (m, Me2Si). 13C-NMR (CDCl3): 157.9, 157.8, 157.4, 157.3 (C(4)); 149.6 (C(2)); 143.7, 142.9 (C(5));
138.9, 138.2 (C(6)); 136.1, 136.0, 133.5, 133.3, 130.5, 130.4, 128.4, 128.3 (2 Ph); 85.4, 85.1 (C(2')); 82.8, 82.7
(C(1')); 74.8 (C(4')); 74.3 (C(5')); 48.0 (MeN); 27.5, 26.6, 19.9, 18.3 (2 t-Bu); À3.7, À3.9 (Me2Si).
Synthesis of Nucleosides 23 25 (General Procedure C; GPC). To a soln. of 20 22 (1 mmol) in MeCN
(10 ml) was added 48% HF in H2O (36 ml), and the resulting mixture was stirred at r.t. for 1 h. Then, H2O
(10 ml) was added, and the mixture was extracted with CH2Cl2. The org. layer was washed with sat. aq. NaHCO3
soln. and brine, dried (Na2SO4), filtered, and concentrated. The crude products 23 25, resp., were purified by
FC (SiO2).
1-{5'-O-[(tert-Butyl)diphenylsilyl]-2',3'-dideoxy-2'-fluoro-3'-[hydroxy(methyl)amino]-a,b-d-arabinofura-
nosyl}thymine (a,b-23). GPC, with a,b-20: 99% (anomeric mixture). White solid. 1H-NMR (CDCl3): 10.85,
10.70 (2 br. s, NH); 7.71 (m, 4 arom. H); 7.41 (m, 6 arom. H, HÀC(6)); 6.12 (m, HÀC(1')); 5.50 (m, HÀC(2'));
4.52 (m, HÀC(4') (a)); 4.24 (m, HÀC(4') (b)); 3.82 (m, HÀC(3'), 2 HÀC(5')); 2.78 (s, MeN); 1.91, 1.75
(2s, MeÀC(5)); 1.11 (s, t-Bu). 13C-NMR (CDCl3): 165.2, 165.1 (C(4)); 151.5, 151.2 (C(2)), 138.2, 136.9 (C(6));
136.1, 135.9, 133.6, 133.5, 133.3, 130.5, 130.3, 128.3, 128.2 (2 Ph); 111.3, 110.3 (C(5)); 100.6, 96.2, 94.7, 90.3
(C(2')); 85.2, 84.9, 83.3, 83.2 (C(1')); 79.5, 77.8 (C(4')); 73.9, 73.4 (C(5')); 65.8, 63.9 (C(3')); 47.0 (MeN); 27.5,
20.0, 19.9 (t-Bu); 12.9, 12.7 (C(5)ÀMe).
1-{5'-O-[(tert-Butyl)diphenylsilyl]-2',3'-dideoxy-2'-fluoro-3'-[hydroxy(methyl)amino]-a,b-d-arabinofura-
nosyl}uracil (a,b-24). GPC, with b-21 and a-21: 99% of b-24 and 98% of a-24, resp. White solids.
Data of b-24: 1H-NMR (CDCl3): 10.68 (br. s, NH); 7.68 (m, 4 arom. H, HÀC(6)); 7.42 (m, 6 arom. H); 6.21
(dd, J ˆ 3.6, 19.0, HÀC(1')); 5.57 (d, J ˆ 8.1, HÀC(5)); 5.50 (dd, J ˆ 3.0, 52.0, HÀC(2')); 4.29 (m, HÀC(4'));
4.07 (dd, J ˆ 3.4, 11.4, HÀC(5')); 3.92 (dd, J ˆ 6.0, 11.7, HÀC(5')); 3.69 (dd, J ˆ 4.9, 25.6, HÀC(3')); 2.76
(s, MeN); 1.11 (s, t-Bu). 13C-NMR (CDCl3): 164.5 (C(4)); 151.0 (C(2)); 142.2 (C(6)); 136.1, 136.0, 133.6, 133.3,
130.4, 128.4 (2 Ph); 102.0 (C(5)); 94.5, 90.8 (C(2')); 85.4, 85.0 (C(1')); 79.6 (C(4')); 73.8, 73.4 (C(5')); 64.3
(C(3')); 46.9 (MeN); 27.5, 19.9 (t-Bu).
Data of a-24: 1H-NMR (CDCl3): 11.11 (br. s, NH); 7.72 (m, 4 arom. H); 7.40 (m, 6 arom. H, HÀC(6)); 6.05
(dd, J ˆ 1.7, 14.7, H ÀC(1')); 5.71 (d, J ˆ 8.1, HÀC(5)); 5.59 (m, HÀC(2')); 4.60 (m, HÀC(4')); 3.87
(m, HÀC(3'), 2 HÀC(5')); 2.76 (s, MeN); 1.12 (s, t-Bu). 13C-NMR (CDCl3): 165.1 (C(4)); 151.3 (C(2)); 141.5
(C(6)); 136.1, 136.0, 133.5, 130.4, 128.3 (2 Ph); 102.2 (C(5)); 99.5, 95.7 (C(2')); 92.5, 91.7 (C(1')); 83.8 (C(4'));
74.2, 73.7 (C(5')); 65.5 (C(3')); 47.0 (MeN); 27.5, 19.9 (t-Bu).
{5'-O-[(tert-Butyl)diphenylsilyl]-2',3'-dideoxy-2'-fluoro-3'-[hydroxy(methyl)amino]-a,b-d-arabinofurano-
syl}-5-fluorouracil (a,b-25). GPC, with a,b-22: 97% (anomeric mixture). White solid. The anomers were
separated by FC (SiO2).
Data of b-25: 1H-NMR (CDCl3): 7.72 (m, 4 arom. H); 7.40 (m, 6 arom. H, HÀC(6)); 6.14 (d, J ˆ 17.7,
HÀC(1')); 5.49 (dd, J ˆ 1.7, 52.9, HÀC(2')); 4.30 (m, HÀC(4')); 3.98 (m, 2 HÀC(5')); 3.65 (dd, J ˆ 5.0, 26.6,
HÀC(3')); 2.71 (s, MeN); 1.11 (s, t-Bu). 13C-NMR (CDCl3): 158.3, 157.7 (C(4)); 149.7 (C(2)); 142.9, 138.2

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Helvetica Chimica Acta Vol. 87 (2004)
(C(5)); 136.1, 136.0, 133.3, 133.2, 130.5, 128.4 (2 Ph); 126.8, 126.1 (C(6)); 94.7, 90.9 (C(2')); 85.6, 85.2 (C(1'));
79.7 (C(4')); 73.7, 73.3 (C(5')); 64.2 (C(3')); 46.8 (MeN); 27.4, 19.9 (t-Bu).
Data of a-25: 1H-NMR (CDCl3): 7.78 7.33 (m, 10 arom. H, HÀC(6), OH); 5.90 (d, J ˆ 14.3, HÀC(1'));
5.59 (d, J ˆ 50.7, HÀC(2')); 4.61 (m, HÀC(4')); 3.81 (m, HÀC(3'), HÀC(5')); 2.71 (s, MeN); 1.12 (s, t-Bu).
13C-NMR (CDCl3): 158.7, 158.1 (C(4)); 149.8 (C(2)); 142.9, 138.2 (C(5)); 136.1, 133.4, 130.4, 126.4, 125.7 (2 Ph);
128.3 (C(6)); 99.3, 95.6 (C(2')); 93.0, 92.3 (C(1')); 83.3 (C(4')); 74.0, 73.5 (C(5')); 65.3 (C(3')); 46.9 (MeN); 27.5,
19.9 (t-Bu).
Synthesis of Nucleosides 26 28 (General Procedure D; GPD). To a soln. of 23 25 (1 mmol) in CH2Cl2
(10 ml) was added a soln. of DDQ (272 mg, 1.2 mmol) in CH2Cl2 (10 ml) in small portions, and the resulting
mixture was stirred at r.t. for 30 min. Then, the mixture was diluted with CH2Cl2 (10 ml), washed successively
with sat. aq. NaHCO3 soln., brine, and H2O, dried (Na2SO4), filtered, and concentrated. The resulting crude
nitrone intermediate was purified by FC (short column of SiO2; MeOH/CH2Cl2 1 :9). To this nitrone in MeOH
(10 ml) was added NH2OH ¥ HCl (104 mg, 1.5 mmol), the resulting mixture was warmed to 508 and stirred for
1 h at this temp. The solvent was evaporated, the residue, dissolved in CH2Cl2 (20 ml), was washed with brine,
dried (Na2SO4), filtered, and concentrated to give the crude products 26 28, resp., which were purified by FC
(SiO2).
1-{5'-O-[(tert-Butyl)diphenylsilyl]-2',3'-dideoxy-2'-fluoro-3'-(hydroxyamino)-a,b-d-arabinofuranosyl}thy-
mine (a,b-26): GPD, with a,b-23: 51% (two steps; anomeric mixture). White solid. 1H-NMR (CDCl3): 10.38
(br. s, NH); 7.75 7.30 (m, 10 arom. H, HÀC(6)); 6.20 (m, HÀC(1') (b)); 5.82 (m, HÀC(1') (a)); 5.39
(m, HÀC(2')); 4.48 (m, HÀC(4') (a)); 4.00 (m, HÀC(4') (b), HÀC(3'), 2 HÀC(5')); 1.85 (s, MeÀC(5) (a));
1.69 (s, MeÀC(5) (b)); 1.10 (s, t-Bu).
1-{5'-O-[(tert-Butyl)diphenylsilyl]-2',3'-dideoxy-2'-fluoro-3'-(hydroxyamino)-b-d-arabinofuranosyl}uracil
(b-27). GPD, with b-24: 57% (two steps). White solid. 1H-NMR (CDCl3): 10.05 (br. s, NH); 7.70 7.30
(m, 10 arom. H, HÀC(6)); 6.20 (d, J ˆ 19.5, HÀC(1')); 5.56 (d, J ˆ 8.1, HÀC(5)); 5.40 (m, HÀC(2')); 4.01
(m, HÀC(3'), HÀC(4'), 2 HÀC(5')); 1.08 (s, t-Bu). 13C-NMR (CDCl3): 164.5 (C(4)); 151.0 (C(2)); 142.2
(C(6)); 136.1, 136.0, 133.4, 133.2, 130.5, 128.3 (2 Ph); 102.1 (C(5)); 95.2, 91.4 (C(2')); 85.7, 85.5 (C(1')); 80.1
(C(4')); 67.9, 67.5 (C(5')); 64.1 (C(3')); 27.4, 19.9 (t-Bu).
1-{5'-O-[(tert-Butyl)diphenylsilyl]-2',3'-dideoxy-2'-fluoro-3'-(hydroxyamino)-b-d-arabinofuranosyl}-5-flu-
orouracil (b-28). GPD, with b-25: 53% (2 steps). White solid. 1H-NMR (CDCl3): 7.72 7.31 (m, 10 arom. H,
HÀC(6), OH); 6.17 (d, J ˆ 18.7, HÀC(1')); 5.35 (d, J ˆ 53.0, HÀC(2')); 3.95 (m, HÀC(3'), HÀC(4'),
2 HÀC(5')); 1.11 (s, t-Bu). 13C-NMR (CDCl3): 158.2, 157.7 (C(4)); 149.7 (C(2)); 143.0, 138.3 (C(5)); 136.1,
136.0, 133.2, 130.5, 128.4, 126.7 (2 Ph); 125.9 (C(6)); 95.5, 91.7 (C(2')); 85.7, 85.5 (C(1')); 80.6 (C(4')); 68.1, 67.6
(C(5')); 64.0 (C(3')); 27.4, 19.8 (t-Bu).
1-{5'-O-[(tert-Butyl)diphenylsilyl]-2',3'-dideoxy-2'-fluoro-3'-(hydroxyamino)-a-d-arabinofuranosyl}-5-fluoro-
uracil (a-28). GPD, with a-25: 48% (2 steps). White solid. 1H-NMR (CDCl3): 7.72 7.31 (m, 10 arom. H,
HÀC(6)); 5.92 (d, J ˆ 15.4, HÀC(1')); 5.44 (d, J ˆ 48.8, HÀC(2')); 4.37 (m, HÀC(4')); 3.90 (m, HÀC(3'),
2 HÀC(5')); 1.11 (s, t-Bu). 13C-NMR (CDCl3): 158.8, 158.3 (C(4)); 149.5 (C(2)); 142.7, 138.0 (C(5)); 136.1,
133.5, 133.4, 130.4, 126.8, 126.0 (2 Ph); 128.3 (C(6)); 99.6, 96.0 (C(2')); 93.5, 92.7 (C(1')), 77.8 (C(4')); 68.2
(C(5')); 68.0 (C(5')); 64.7 (C(3')); 27.4, 19.8 (t-Bu).
Synthesis of Nucleosides 29 35 (General Procedure E; GPE). To a soln. of 26 28 (1 equiv.) in MeOH was
added the aldehyde (1.2 equiv.; see Scheme 4), and the resulting mixture was stirred at r.t. for 10 min. Then,
NaBH3CN(2 equiv.) was added in small portions, and the mixture was stirred at r.t. for another 10 min. After
evaporation to dryness, the residue was dissolved in CH2Cl2, and the resulting soln. was washed with brine, dried
(Na2SO4), filtered, and concentrated. The crude products were purified by FC (SiO2).
{5'-O-[(tert-Butyl)diphenylsilyl]-3'-[butyl(hydroxy)amino]-2',3'-dideoxy-2'-fluoro-a,b-d-arabinofurano-
syl}thymine (a,b-29): GPE, with a,b-26 and butanal: 84% (two steps; anomeric mixture). White solid. 1H-NMR
(CDCl3): 10.48 (m, N H); 7.50 (m, 10 arom. H, HÀC(6)); 6.20 (m, HÀC(1')); 5.50 (m, HÀC(2')); 4.48
(m, HÀC(4') (a)); 4.00 (m, HÀC(4') (b), HÀC(3'), 2 HÀC(5')); 2.82 (m, CH2N); 0.90 0.79 (m, MeÀC(5),
t-Bu, Me, 2 CH2). 13C-NMR (CDCl3): 164.8 (C(4)); 151.3, 151.0 (C(2)); 138.0, 136.9 (C(6)); 136.1, 136.0, 133.6,
133.3, 130.4, 130.3, 128.3, 128.2 (2 Ph); 111.2, 110.3 (C(5)); 94.6, 90.8 (C(2')); 85.1, 84.8, 82.9, 82.8 (C(1')); 79.2
(C(4')); 72.5, 72.1 (C(5')); 65.7, 63.8 (C(3')), 61.0, 59.0 (NCH2); 29.4, 27.4 (2 CH2); 20.9, 19.9 (t-Bu); 14.5, 12.7
(2 Me).
1-{5'-O-[(tert-Butyl)diphenylsilyl]-2',3'-dideoxy-2'-fluoro-3'-[hydroxy(2-methylpropyl)amino]-a,b-d-ara-
binofuranosyl}thymine (a,b-30): GPE, with a,b-26 and 2-methylpropanal: 87% (two steps; anomeric mixture).
White solid. 1H-NMR (CDCl3): 10.01 (br. s, NH); 7.75 7.29 (m, 10 arom. HÀC(6)); 6.94, 6.40 (2 br. s, OH);
6.12 (m, HÀC(1')); 5.42 (m, HÀC(2')); 4.49 (m, HÀC(4') (a)); 4.23 (m, HÀC(4') (b)); 3.78 (m, HÀC(3'),

Helvetica Chimica Acta Vol. 87 (2004)
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2 HÀC(5')); 2.55 (d, J ˆ 7.0, CH2N); 1.90 (m, 2.2 H, MeÀC(5), CH); 1.75 (s, 1.8 H; MeÀC(5)); 1.10 (s, t-Bu);
0.94 (d, J ˆ 6.6, 2 Me). 13C-NMR (CDCl3): 164.8, 164.6 (C(4)); 151.0 (C(2)); 137.9, 136.9 (C(6)); 136.1, 135.9,
133.6, 133.4, 130.4, 130.3, 128.3 (2 Ph); 110.7, 110.4 (C(5)); 98.9, 95.2, 95.0, 91.4 (C(2')); 91.3, 90.7, 85.3, 84.9
(C(1')); 83.8, 79.2 (C(4')); 73.5, 73.3, 73.0, 72.8 (C(5')); 67.5, 66.9 (C(3')); 65.4, 64.0 (NCH2); 27.4, 26.7, 26.5, 19.9
(3 Me); 21.4, 21.3, 13.0, 12.8 (t-Bu).
1-{5'-O-[(tert-Butyl)diphenylsilyl]-3'-[(cyclohexylmethyl)(hydroxy)amino]-2',3'-dideoxy-2'-fluoro-a,b-d-
arabinofuranosyl}thymine (a,b-31): GPE, with a,b-26 and cyclohexanecarboxaldehyde: 68% (two steps;
anomeric mixture). White solid. 1H-NMR (CDCl3): 10.00 (m, NH); 7.53 (m, 10 arom. H, HÀC(6)); 6.93
(br. s, OH (a)); 6.41 (br. s, OH (b)); 6.14 (m, HÀC(1')); 5.49 (m, HÀC(2')); 4.48 (m, HÀC(4') (a)); 4.26
(m, HÀC(4') (b)); 3.81 (m, HÀC(3'), 2 HÀC(5')); 2.58 (d, J ˆ 6.6, NCH2); 1.92 0.78 (m, MeÀC(5), 5 CH2,
CH); 1.11 (s, t-Bu). 13C-NMR (CDCl3): 164.9, 164.7 (C(4)); 151.3 (C(2)); 137.9, 137.3 (C(6)); 136.0, 135.9, 133.7,
133.5, 130.2, 130.1, 128.1 (2 Ph); 110.6, 110.3 (C(5)); 98.9, 95.4, 95.3, 91.5 (C(2')); 90.5, 85.2, 84.9 (C(1')); 84.0,
79.1 (C(4')); 73.8, 73.6, 72.8 (C(5')); 66.2, 65.9 (C(3')); 65.7, 64.1 (NCH2); 36.1, 32.2, 27.6, 26.4 (5 CH2); 19.9, 12.8
(t-Bu).
1-{5'-O-[(tert-Butyl)diphenylsilyl]-3'-[butyl(hydroxy)amino]-2',3'-dideoxy-2'-fluoro-b-d-arabinofuranosyl}-
uracil (b-32). GPE, with b-27 and butanal: 93% (two steps). White solid. 1H-NMR (CDCl3): 10.58 (br. s, N H);
7.69 (m, 4 arom. H, HÀC(6)); 7.40 (m, 6 arom. H); 7.11 (br. s, OH); 6.20 (dd, J ˆ 3.4, 18.5, HÀC(1')); 5.56
(d, J ˆ 8.2, HÀC(5)); 5.50 (dd, J ˆ 3.2, 52.7, HÀC(2')); 4.28 (m, HÀC(4')); 3.92 (m, HÀC(3'), 2 HÀC(5')); 2.81
(m, N CH); 1.67 0.88 (m, t-Bu, Me, 2 CH2). 13C-NMR (CDCl3): 164.4 (C(4)); 150.9 (C(2)); 142.3 (C(6)); 136.1,
2
136.0, 133.6, 133.3, 130.4, 128.3 (2 Ph); 101.9 (C(5)); 94.6, 90.9 (C(2')); 85.4, 85.0 (C(1')); 79.4 (C(4')); 72.5
(C(5')); 72.0 (C(5')); 64.2 (C(3')); 58.9 (CH2N); 29.6 (2 CH2); 20.9, 14.6 (t-Bu); 19.9 (Me).
1-{5'-O-[(tert-Butyl)diphenylsilyl]-2',3'-dideoxy-2'-fluoro-3'-[hydroxy(2-methylpropyl)amino]-b-d-arabi-
nofuranosyl}uracil (b-33): GPE, with b-27 and 2-methylpropanal: 92% (two steps). White solid. 1H-NMR
(CDCl3): 10.16 (br. s, NH); 7.69 (m, 4 arom. H, HÀC(6)); 7.41 (m, 6 arom. H); 6.51 (br. s, OH); 6.19 (dd, J ˆ
3.2, 18.7, HÀC(1')); 5.58 (d, J ˆ 8.1, HÀC(5)); 5.45 (m, HÀC(2')); 4.27 (m, HÀC(4')); 4.04 (dd, J ˆ 3.0, 11.6,
1 HÀC(5')); 3.88 (dd, J ˆ 3.0, 11.0, 1 HÀC(5')); 3.69 (dd, J ˆ 5.0, 26.4, HÀC(3')); 2.55 (d, J ˆ 7.0, CH2N); 1.91
(m, CH); 1.11 (s, t-Bu); 0.94 (dd, J ˆ 1.8, 6.6, 2 Me). 13C-NMR (CDCl3): 164.2 (C(4)); 150.8 (C(2)); 142.1
(C(6)); 136.1, 136.0, 133.5, 133.3, 130.5, 130.4, 128.3 (2 Ph); 102.0 (C(5)); 94.9, 91.2 (C(2')); 85.5, 85.1 (C(1'));
79.3 (C(4')); 73.2, 72.7 (C(5')); 66.9 (C(3')); 64.3 (NCH); 27.5, 26.7 (2 Me); 21.3, 19.9 (t-Bu).
1-{5'-O-[(tert-Butyl)diphenylsilyl]-3'-[(cyclohexylmethyl)(hydroxy)amino]-2',3'-dideoxy-2'-fluoro-b-d-
arabinofuranosyl}uracil (b-34): GPE, with b-27 and cyclohexanecarboxaldehyde: 88% (two steps). White solid.
1H-NMR (CDCl3): 9.89 (br. s, NH); 7.53 (m, 10 arom. H, HÀC(6)); 6.25 (br. s, OH); 6.17 (dd, J ˆ 3.7, 18.8,
HÀC(1')); 5.56 (d, J ˆ 8.3, HÀC(5)); 5.42 (m, HÀC(2')); 4.22 (m, HÀC(4')); 4.02 (dd, J ˆ 3.0, 11.1, 1 HÀC(5'));
3.87 (dd, J ˆ 3.3, 11.3, 1 HÀC(5')); 3.69 (dd, J ˆ 4.4, 27.1, HÀC(3')); 2.59 (d, J ˆ 6.7, CH2N); 1.85 0.79 (m, CH,
5 CH2); 1.09 (s, t-Bu). 13C-NMR (CDCl3): 164.1 (C(4)); 150.9 (C(2)); 142.1 (C(6)); 136.1, 136.0, 133.5, 133.3,
130.4, 128.3 (2 Ph); 102.0 (C(5)); 94.8, 91.0 (C(2')); 85.4, 85.1 (C(1')); 79.3 (C(4')); 73.0, 72.5 (C(5')); 65.8
(C(3')); 64.2 (CH2N); 36.1 (CH); 32.2, 27.5 (5 CH2), 27.3, 26.6, 19.9 (t-Bu).
1-{5'-O-[(tert-Butyl)diphenylsilyl]-2',3'-dideoxy-2'-fluoro-3'-[hydroxy(2-methylpropyl)amino]-b-d-arabi-
nofuranosyl}-5-fluorouracil (b-35). GPE, with b-28 and 2-methylpropanal: 65% (2 steps). White solid.
1H-NMR (CDCl3): 10.34 (br. s, NH); 7.71 (m, 4 arom. H, HÀC(6)); 7.43 (m, 6 arom. H); 6.30 (br. s, OH); 6.13
(d, J ˆ 18.0, HÀC(1')); 5.45 (dd, J ˆ 2.4, 52.1, HÀC(2')); 4.28 (m, HÀC(4')); 4.02 (dd, J ˆ 3.6, 11.4, 1 HÀC(5'));
3.84 (dd, J ˆ 3.3, 11.4, 1 HÀC(5')); 3.64 (dd, J ˆ 5.0, 27.0, HÀC(3')); 2.50 (d, J ˆ 6.7, CH2N); 1.89 (m, CH); 1.11
(s, t-Bu); 0.92 (dd, J ˆ 2.5, 6.6, 2 Me). 13C-NMR (CDCl3): 157.9, 157.4 (C(4)); 149.5 (C(2)); 142.9, 138.2 (C(5));
136.1, 136.0, 133.3, 130.5, 128.3, 126.6 (2 Ph); 126.0 (C(6)); 95.1, 91.4 (C(2')); 85.7, 85.4 (C(1')); 79.4 (C(4')); 73.2,
72.7 (C(5')); 66.7 (C(3')); 64.2 (CH2N); 27.4 (CH); 26.6, 19.8 (t-Bu); 21.2 (2 Me).
1-{5'-O-[(tert-Butyl)diphenylsilyl]-2',3'-dideoxy-2'-fluoro-3'-[hydroxy(2-methylpropyl)amino]-a-d-arabi-
nofuranosyl}-5-fluorouracil (a-35). GPE, with a-28 and 2-methylpropanal: 83% (2 steps). White solid.
1H-NMR (CDCl3): 10.46 (br. s, NH); 7.55 (m, 10 arom. H, HÀC(6)); 6.62 (br. s, OH); 6.00 (d, J ˆ 14.6,
HÀC(1')); 5.62 (d, J ˆ 49.1, HÀC(2')); 4.49 (m, HÀC(4')); 3.84 (m, 2 HÀC(5')); 3.64 (m, HÀC(3')); 2.51
(d, J ˆ 6.4, CH2N); 1.95 (m, CH); 1.10 (s, t-Bu); 0.90 (dd, J ˆ 2.3, 6.6, 2 Me). 13C-NMR (CDCl3): 158.5, 158.1
(C(4)); 149.2 (C(2)); 142.5, 137.8 (C(5)); 136.1, 133.4, 130.4, 128.3, 126.5 (2 Ph); 125.8 (C(6)); 99.5, 95.9 (C(2'));
92.6, 91.8 (C(1')); 84.9 (C(4')); 74.1, 73.6 (C(5')); 67.5 (C(3')); 65.1 (CH2N); 27.4 (CH), 26.4, 19.8 (t-Bu); 21.3
(2 Me).
Synthesis of Nucleosides 36 42 (General Procedure F; GPF). To a soln. of compounds 29 35, resp., in anh.
THF was added a soln of TBAF (1.2 equiv.) in THF. The mixture was stirred for 1 h at r.t., then directly (without
evaporation) subjected to FC (SiO2).

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1-{3'-[Butyl(hydroxy)amino]-2',3'-dideoxy-2'-fluoro-a,b-d-arabinofuranosyl}thymine (a,b-36): GPF, with
a,b-29: 82% (anomeric mixture). White solid. 1H-NMR (CD3OD): 7.71 (s, HÀC(6) (b)); 7.54 (s, HÀC(6) (a));
6.12 (dd, J ˆ 2.8, 16.1, HÀC(1') (a)); 6.05 (dd, J ˆ 3.9, 18.7, HÀC(1') (b)); 5.56 (dt, J ˆ 2.9, 51.6, HÀC(2') (a));
5.45 (ddd, J ˆ 1.7, 3.7, 53.0, HÀC(2') (b)); 4.56 (m, HÀC(4') (a)); 4.19 (m, HÀC(4') (b)); 3.75 (m, HÀC(3'),
2 HÀC(5')); 2.89 (m, CH2N); 1.87 (s, MeÀC(5)); 1.45 (m, 2 CH2); 0.96 (t, J ˆ 7.2, Me). 13C-NMR (CD3OD):
166.5, 166.4 (C(4)); 152.7, 152.6 (C(2)); 139.5, 138.5 (C(6)); 111.9, 110.8 (C(5)); 95.9, 95.1, 92.4 (C(2')); 91.7, 91.4,
86.3, 86.0 (C(1')); 84.9, 80.8 (C(4')); 74.6, 74.2, 73.7, 73.2 (C(5')); 64.2, 63.1 ((C(3')); 59.7 (CH2N), 30.6, 30.2, 21.6
(2 CH2); 14.7, 12.9, 12.7 (2 Me). Anal. calc. for C14H22FN3O5 ¥ 0.3 H2O: C 49.93, H 6.77, N12.48; found: C 50.16,
H 6.75, N12.65.
1-{2',3'-Dideoxy-2'-fluoro-3'-[hydroxy(2-methylpropyl)amino]-a,b-d-arabinofuranosyl}thymine (a,b-37):
GPF, with a,b-30: 95% (anomeric mixture). White solid. 1H-NMR (CD3OD): 7.72 (s, HÀC(6) (b)); 7.54
(s, HÀC(6) (a)); 6.13 (dd, J ˆ 2.3, 13.7, HÀC(1') (a)); 6.04 (dd, J ˆ 3.9, 18.7, HÀC(1') (b)); 5.45 (dt, J ˆ 2.5, 51.3,
HÀC(2') (a)); 5.32 (ddd, J ˆ 1.8, 3.8, 53.4, HÀC(2') (b)); 4.52 (m, HÀC(4') (a)); 4.17 (m, HÀC(4') (b)); 3.97
3.29 (m, HÀC(3'), 2 HÀC(5')); 2.72 2.38 (m, CH2N); 1.89 (m, MeÀC(5), CH); 0.92 (m, 2 Me). 13C-NMR
(CD3OD): 166.7, 166.5 (C(4)); 152.6, 152.3 (C(2)); 139.5, 138.3 (C(6)); 111.5, 110.7 (C(5)); 100.2, 96.6, 95.4, 92.3
(C(2')); 91.6, 86.3, 86.0, 85.7 (C(1')); 81.2, 81.1 (C(4')); 75.1, 74.7, 74.2, 73.8 (C(5')); 68.2, 68.0 (C(3')); 64.3, 63.2
(CH2N); 27.7, 27.6 (CH); 21.5 (Me); 21.4 (Me2CH). Anal. calc. for C14H22FN3O5 ¥ 0.8 H2O: C 48.63, H 6.88, N
12.15; found: C 48.58, H 6.62, N12.37.
1-{3'-[(Cyclohexylmethyl)(hydroxy)amino]-2',3'-dideoxy-2'-fluoro-a,b-d-arabinofuranosyl}thymine (a,b-
1
38): GPF, with a,b-31: 96% (anomeric mixture). White solid. H-NMR (CD3OD): 7.72 (s, HÀC(6) (b)); 7.54
(s, HÀC(6) (a)); 6.09 (m, HÀC(1')); 5.42 (m, HÀC(2')); 4.51 (m, HÀC(4') (a)); 4.14 (m, HÀC(4') (b)); 3.97
3.29 (m, HÀC(3'), 2 HÀC(5')); 2.73 2.40 (m, CH2N); 2.00 0.78 (m, MeÀC(5)), CH, 5 CH2). 13C-NMR
(CD3OD): 166.5, 164.7 (C(4)); 152.3 (C(2)); 139.5, 138.3 (C(6)); 111.4, 110.7 (C(5)); 100.4, 96.4, 95.4, 92.4
(C(2')); 91.6, 86.3, 86.0 (C(1')); 81.1 (C(4')); 74.2, 73.8 (C(5')); 66.8, 64.4 (C(3')); 63.2 (CH2N); 37.2, 37.1 (CH);
33.0, 32.9, 28.3, 27.6 (5 CH2); 13.0, 12.8 (Me). Anal. calc. for C17H26FN3O5 ¥ 0.1 H2O: C 54.71, H 7.08, N11.26;
found: C 54.97, H 7.13, N11.19.
1-{3'-[Butyl(hydroxy)amino]-2',3'-dideoxy-2'-fluoro-b-d-arabinofuranosyl}uracil (b-39). GPF, with b-32:
93%. White solid. 1H-NMR (CD3OD): 7.86 (dd, J ˆ 2.0, 8.1, HÀC(6)); 6.06 (dd, J ˆ 3.7, 18.7, HÀC(1')); 5.69
(d, J ˆ 8.1, HÀC(5)); 5.43 (ddd, J ˆ 1.5, 3.7, 53.1, HÀC(2')); 4.19 (m, HÀC(4')); 3.90 (dd, J ˆ 2.9, 12.4,
1 HÀC(5')); 3.75 (dd, J ˆ 4.72, 12.4, 1 HÀC(5')); 3.52 (ddd, J ˆ 1.5, 6.1, 27.5, HÀC(3')); 2.79 (m, CH2N); 1.48
(m, 2 CH2); 0.95 (t, J ˆ 7.1, Me ) . 13C-NMR (CD3OD): 166.3 (C(4)); 152.2 (C(2)); 143.9, 143.8 (C(6)); 102.1
(C(5)); 95.4, 91.6 (C(2')); 86.6, 86.3 (C(1')); 81.3, 81.2 (C(4')); 74.0, 73.5 (C(5')); 63.3 (C(3')); 59.6 (CH2N); 31.1,
21.7 (2 CH2); 14.8 (Me). Anal. calc. for C13H20FN3O5 ¥ 0.5 H2O: C 47.85, H 6.49, N12.88; found: C 48.00, H 6.62,
N12.97.
1-{2',3'-Dideoxy-2'-fluoro-3'-[hydroxy(2-methylpropyl)amino]-b-d-arabinofuranosyl}uracil (b-40): GPF,
with b-33: 94%. White solid. 1H-NMR (CD3OD): 7.86 (dd, J ˆ 2.0, 8.1, HÀC(6)); 6.06 (dd, J ˆ 3.7, 18.6,
HÀC(1')); 5.69 (d, J ˆ 8.1, HÀC(5)); 5.43 (ddd, J ˆ 1.6, 3.8, 53.2, HÀC(2')); 4.18 (m, HÀC(4')); 3.83 (ddd, J ˆ
2.8, 12.2, 29.4, 2 HÀC(5')); 3.48 (ddd, J ˆ 1.5, 6.1, 27.4, HÀC(3')); 2.67 (dd, J ˆ 6.2, 12.1, 1 H of CH2N); 2.46
(dd, J ˆ 7.6, 12.2, 1 H of CH2N); 1.90 (m, CH); 0.95 (m, 2 Me). 13C-NMR (CD3OD): 166.3 (C(4)); 152.2 (C(2));
143.8 (C(6)); 102.1 (C(5)); 95.4, 91.7 (C(2')); 86.6, 86.3 (C(1')); 81.3 (C(4')); 74.3, 73.9 (C(5')); 67.9 (C(3')); 63.4
(CH2N); 27.7 (CH); 21.5, 21.4 (2 Me). Anal. calc. for C13H20FN3O5 ¥ 0.2 H2O: C 48.65, H 6.41, N13.09; found: C
48.61, H 6.65, N12.93.
1-{3'-[(Cyclohexylmethyl)(hydroxy)amino]-2',3'-dideoxy-2'-fluoro-b-d-arabinofuranosyl}uracil (b-41):
1
GPF, with b-34: 85%. White solid. H-NMR (CD3OD): 7.86 (dd, J ˆ 2.0, 8.1, HÀC(6)); 6.05 (dd, J ˆ 3.8, 18.6,
HÀC(1')); 5.68 (d, J ˆ 8.1, HÀC(5)); 5.41 (ddd, J ˆ 1.6, 3.8, 53.2, HÀC(2')); 4.17 (m, HÀC(4')); 3.90 (dd, J ˆ
3.2, 12.4, HÀC(5')); 3.74 (dd, J ˆ 4.6, 12.2, 1 HÀC(5')); 3.46 (ddd, J ˆ 1.7, 6.3, 27.4, HÀC(3')); 2.68 (dd, J ˆ 5.6,
12.1, 1 H of CH2N); 2.51 (dd, J ˆ 7.4, 12.5, 1 H of CH2N); 1.98 0.81 (m, CH, 5 CH2). 13C-NMR (CD3OD): 166.3
(C(4)); 152.2 (C(2)); 143.8 (C(6)); 102.0 (C(5)); 95.4, 91.7 (C(2')); 86.6, 86.3 (C(1')); 81.4, 81.3 (C(4')); 74.4, 73.9
(C(5')); 66.7 (C(3')); 63.4 (CH2N); 37.2 (CH); 33.0, 28.3, 27.6 (5 CH2). Anal. calc. for C16H24FN3O5: C 53.77, H
6.77, N11.76; found: C 53.57, H 6.75, N12.06.
1-{2',3'-Dideoxy-2'-fluoro-3'-[hydroxy(2-methylpropyl)amino]-b-d-arabinofuranosyl}-5-fluorouracil (b-
42). GPF, with b-35: 76%. White solid. 1H-NMR (CD3OD): 8.08 (dd, J ˆ 1.8, 6.8, HÀC(6)); 6.04 (ddd, J ˆ
1.7, 3.9, 18.0, HÀC(1')); 5.44 (ddd, J ˆ 1.7, 3.7, 53.1, HÀC(2')); 4.18 (m, HÀC(4')); 3.92 (dd, J ˆ 3.6, 12.6,
1 HÀC(5')); 3.75 (dd, J ˆ 4.4, 12.4, 1 HÀC(5')); 3.51 (ddd, J ˆ 1.7, 6.2, 27.4, HÀC(3')); 2.67 (dd, J ˆ 6.2, 12.8, 1 H
of CH2N); 2.46 (dd, J ˆ 7.7, 12.4, 1 H of CH2N); 1.89 (m, CH); 0.97, 0.94 (2d, J ˆ 2.2 each, 2 Me). 13C-NMR
(CD3OD): 159.8 (C(4)); 150.8 (C(2)); 143.8, 139.2 (C(5)); 128.1, 127.4 (C(6)); 95.4, 91.6 (C(2')); 86.6, 86.3

Helvetica Chimica Acta Vol. 87 (2004)
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(C(1')); 81.5, 81.4 (C(4')); 74.0, 73.6 (C(5')); 67.9 (C(3')); 63.1 (CH2N); 27.7 (CH), 21.4, 21.3 (2 Me). Anal. calc.
for C13H19F2N3O5 ¥ 0.5 H2O: C 45.48, H 5.87, N12.24; found: C 45.60, H 5.55, N12.17.
1-{2',3'-Dideoxy-2'-fluoro-3'-[hydroxy(2-methylpropyl)amino]-a-d-arabinofuranosyl}-5-fluorouracil (a-
42). GPF, with a-35: 70%. White solid. 1H-NMR (CD3OD): 7.89 (d, J ˆ 6.7, HÀC(6)); 6.09 (d, J ˆ 15.6,
HÀC(1')); 5.45 (dt, J ˆ 1.9, 50.5, HÀC(2')); 4.54 (m, HÀC(4')); 3.74 (m, 2 HÀC(5')); 3.44 (ddd, J ˆ 2.0, 4.6,
24.6, HÀC(3')); 2.57 (dd, J ˆ 6.2, 12.5, 1 H of CH2N); 2.46 (dd, J ˆ 7.5, 12.4, 1 H of CH2N); 1.93 (m, CH); 0.93
(dd, J ˆ 4.6, 6.6, 2 Me). 13C-NMR (CD3OD): 160.0, 159.5 (C(4)); 151.0 (C(2)); 144.2, 139.5 (C(5)); 127.0, 126.3
(C(6)); 100.5, 96.9 (C(2')); 93.0, 92.2 (C(1')); 86.3, 86.2 (C(4')); 75.2, 74.7 (C(5')); 68.1 (C(3')); 64.2 (CH2N); 27.6
(CH); 21.4, 21.3 (2 Me). Anal. calc. for C13H19F2N3O5 ¥ 0.4 H2O: C 45.59, H 5.83, N12.27; found: C 45.85, H 5.59,
N12.58.
K. Z. acknowledges the Outstanding Young Scholarship from NSFC (No. 30125043), the Basic Research
Project (No. 2002CCA01500) of the MOST, and the Cheung Kong Scholars Programme for financial support.
S. P. acknowledges the MacCracken Fellowship of the New York University.
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ReceivedJuly 14, 2003