Stereoselective synthesis of both enantiomers of 1,4-anhydro-alditols, 1,4-anhydro-2-amino-alditols and D- and L-isonucleosides from 2,3-O-isopropylidene-D-glyceraldehyde using iodine-induced cyclization as the key step

Article abstract of DOI:10.1016/S0957-4166(01)00283-X

We have stereoselectively prepared the enantiomeric 1,4-anhydro-alditols (-)-15 and (+)-15, 1,4-anhydro-2-amino-aldi-tols (-)-19 and (+)-19, and isonucleosides (-)-22, (+)-22 and 25, from 2,3-O-isopropylidene-D-glyceraldehyde. The key step was the iodine-

Full text of DOI:10.1016/S0957-4166(01)00283-X

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 1635–1643
Stereoselective synthesis of both enantiomers of
1,4-anhydro-alditols, 1,4-anhydro-2-amino-alditols and
D
- and
L
-isonucleosides from 2,3-O-isopropylidene-
D
-glyceraldehyde
using iodine-induced cyclization as the key step
Fernando Bravo, Yolanda D´ıaz and Sergio Castillo´n*
Departament de Qu´ımica Anal´ıtica i Qu´ımica Orga`nica, Facultat de Qu´ımica, Universitat Rovira i Virgili,
Pl. Imperial Tarraco 1, 43005 Tarragona, Spain
Received 25 May 2001; accepted 19 June 2001
Abstract—We have stereoselectively prepared the enantiomeric 1,4-anhydro-alditols (−)-15 and (+)-15, 1,4-anhydro-2-amino-aldi-
tols (−)-19 and (+)-19, and isonucleosides (−)-22, (+)-22 and 25, from 2,3-O-isopropylidene- -glyceraldehyde. The key step was
D
the iodine-induced cyclization of 4-pentene-1,2,3-triols 2 and 3 to give, respectively, the tetrahydrofuran derivatives 4 and 5. In
these compounds we have optimized the substitution of iodine for oxygen-bearing groups. Results were best when we used
potassium superoxide as a nucleophile. © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
mon method is to reduce methyl glycosides by treating
them with triethylsilane in the presence of a Lewis acid
(Scheme 1).4a,6a,6c,7 The starting material for synthesiz-
Isonucleosides are a novel class of nucleosides that have
attracted great interest.1 Over the last few years many
isonucleoside derivatives, such as exomethylene-,2
branched-,3 4%-thio-,4 pyranosyl-,5 and others (Fig. 1)
have been prepared. Isonucleosides are promising ther-
apeutic reagents, as some of them combine strong and
selective anti-HIV and anti-HSV activity, together with
higher stability towards acids and enzymatic deamina-
tion. (S,S)-iso-ddA6 is a good example (Fig. 1); its
anti-HIV activity is similar to that of ddA, and it has
no apparent toxicity. The enantiomeric (R,R)-iso-ddA
is also active.
ing deoxyderivatives is usually
hydroxy derivatives, it is -ribose. Alditol cyclization
D-xylose, while for
D
under Mitsunobu conditions has also been reported.3f
1,4-Anhydro-alditols are also synthesized through ring
opening–ring closing protocols of sugar precur-
sors.3c,3d,8 Only a few reports describe the asymmetric
synthesis of 1,4-anhydro-alditol units. 1,2,4-Butane-
triol,9 bis-epoxides,4a and glycidol,6b have been obtained
by asymmetric synthesis and used to synthesize iso-
nucleosides (Scheme 1).
The base can be directly introduced by nucleophilic
substitution of a sulfonate with base salts.10 This proce-
dure is efficient for deoxyisonucleosides and purinic
The 1,4-anhydro-alditol moieties in isonucleosides are
usually prepared from carbohydrates. The most com-
Figure 1.
* Corresponding author. Tel.: 34-977-559556; fax: 34-977-559563; e-mail: castillon@quimica.urv.es
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00283-X

1636
F. Bra6o et al. / Tetrahedron: Asymmetry 12 (2001) 1635–1643
Scheme 1.
bases. For pyrimidinic bases, however, yields are lower.
An alternative procedure involves preparing aminoaldi-
tols11 by introducing an amino group, and further con-
structing the base. The ring opening of an epoxide
with a base salt3c,3d or ammonia,12 and the substitution
of an alcohol with a base under Mitsunobu condi-
tions4b,5d,6b,10c have also been reported.
produced the bicyclo derivative 6 via intramolecular
substitution (Scheme 3). Similarly, any attempt to pro-
tect the hydroxyl group in basic medium led to the
bicyclic compound 6. The hydroxyl group was then
protected in acid medium by reaction with ethyl vinyl
ether to give 7 as a diastereomeric mixture.
Attempts at the substitution of iodine in compound 7
by reaction with potassium benzoate resulted in forma-
tion of the furan derivative 13, together with small
amounts of the substitution product 8 (Table 1, entry 1;
Scheme 4). Using potassium p-nitrobenzoate as a nucle-
ophile also produced the furan as the major product
(entry 2), with small amounts of compound 9. The
presence of the endocyclic oxygen and the b-tertiary
carbon hinder the substitution reaction.3a
Herein, we report the synthesis of enantiomeric 1,4-
anhydro-pentitols and 1,4-anhydro-2-amino-pentitols
from 2,3-O-isopropylidene-
common starting material, and their transformation
into enantiomeric - and -isonucleosides.
D-glyceraldehyde as the
D
L
2. Results and discussion
We recently reported the stereoselective synthesis of
isomeric substituted tetrahydrofurans 4 and 5 by
iodine-induced cyclization of the appropriately pro-
tected pentene-triols 2 and 3, respectively (Scheme 2).13
Triols 2 and 3 were obtained from 2,3-O-isopropyli-
dene- -glyceraldehyde 1 by reaction with vinylmagne-
D
sium bromide, protection of the generated hydroxyl
group as its benzyl ether and subsequent acetal
hydrolysis.
Tetrahydrofurans 4 and 5 can be transformed into
1,4-anhydro-pentitols by iodine substitution. The initial
assays, which involved the treatment of compound 4
with potassium benzoate or potassium p-nitrobenzoate,
Scheme 3.
Scheme 2.

F. Bra6o et al. / Tetrahedron: Asymmetry 12 (2001) 1635–1643
1637
Scheme 4.
Table 1. Results of iodine substitution reactions of com-
pound 7
2). When we used potassium superoxide, the nucleo-
philic substitution was fast and efficient, although the
ethyl ethoxide group migrated after the reaction mix-
ture was treated with water, to provide a mixture of
compounds 10 and 11. We solved this problem by
treating the reaction mixture with dilute aqueous HCl
to deprotect the acetal group, to give 1,4-anhydro-pen-
titol 12 in 88% yield.
Entry
Conditions
Products
Yields (%)
1
2
3
4
5
KBzO
Kp-NO2BzO
(Bu3Sn)2O/AgNO3
KNO2, 18-crown-6
Co(II)(salen), NaBH4,
NaOH, O2
8, 13
9, 13
–
–
2
25, 69
30, 50
–
–
37
The primary hydroxyl group in compound 12 was
protected by reaction with benzoyl chloride to give
compound 14 (Scheme 5). The configuration of the
secondary alcohol in 14 was inverted by formation of
the triflate derivative, reaction with KNO2 and hydroly-
sis of the nitrite intermediate to give compound (−)-15
in a total yield of 50%.
6
7
KO2, 18-crown-6, PPh3,
H2O
KO2, 18-crown-6, PPh3,
HCl
10, 11
53, 24
88
12
We then used bis(tributyltin)oxide in the presence of
silver nitrate,14 but we obtained a complex mixture after
several days of reaction (entry 3). The reaction of 7
with potassium nitrite, following a similar procedure to
that used for inverting the configuration of secondary
alcohols,15 also gave a complex mixture. We also inves-
tigated the substitution of iodine using radical condi-
tions by treating 7 with NaBH4, a catalytic amount of
Co(II)(salen), and flushing with dry air. After treatment
with acid to deprotect the acetal group, compound 2
was isolated (entry 5). This result can be explained by
the formation of a carbanion, instead of a radical and
subsequent b-elimination, which opens the ring, and is
the opposite of the process that forms 4 from 2 (Scheme
We also used this method starting from the iodo deriva-
tive 5. In this case, intramolecular nucleophilic substitu-
tion cannot take place, and compound 5 was treated
without protection with potassium superoxide in
DMSO to give compound 16 (Scheme 5) in 89% yield.
Protecting the primary alcohol by reaction with benzoyl
chloride afforded 1,4-anhydro-alditol (+)-15 in 74%
yield. The NMR spectrum and the melting point of
compounds (−)-15 and (+)-15 were identical, and spe-
cific rotation values were very close in absolute value
but with opposite sign ([h]2D5=−20.2 for (−)-15 and
[h]2D5=+21.8 for (+)-15), which confirms their enan-
tiomeric nature.
Scheme 5.

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F. Bra6o et al. / Tetrahedron: Asymmetry 12 (2001) 1635–1643
Bimolecular nucleophilic substitution starting from a
sulfonate is the most common way of introducing the
base in isonucleoside synthesis.6c,7b,8 For this, alcohols
(−)-15 and (+)-15 were treated with tosyl chloride to
obtain tosylates (−)-17 and (+)-17 in 83 and 98% yield,
respectively (Scheme 6).
Mitsunobu conditions.6b However, when we treated
(−)-15 with 3-benzoylthymine using these conditions,
isonucleosides were not obtained.
We then decided to introduce an amino group from
which the different pyrimidinic and purinic bases could
be built up.11 Compounds (−)-17 and (+)-17 were
treated with sodium azide in DMF in the presence of
15-crown-5 to provide azido derivatives (−)-18 and
(+)-18 in goods yields. These compounds were reduced
by treatment with triphenylphosphine–water16 to afford
the 1,4-anhydro-2-amino-alditols (−)-19 and (+)-19,
respectively, in >90% yield.
To obtain the isonucleoside, we initially treated tosylate
(−)-17 with the potassium salt of adenine, the base that
usually produces better yields in this reaction, but only
deprotection of the benzoate group was observed. We
tried several reaction conditions, but detected no
nucleoside. We had obtained good yields in the synthe-
sis of (S,S)-iso-ddA by introducing the bases under
Scheme 6.

F. Bra6o et al. / Tetrahedron: Asymmetry 12 (2001) 1635–1643
1639
Treating compounds (−)-19 and (+)-19 with trans-
methoxyacryloyl chloride and silver isocyanate afforded
enantiomers (−)-20 and (+)-20, respectively. These were
treated first in acid and then in basic medium to give
the isonucleosides (+)-21 and (−)-21. Hydrogenolysis of
these compounds led to the unprotected enantiomeric
isonucleosides (+)-22 and (−)-22 in excellent yields.
NaHCO3 (8 mL), brine (8 mL) and water (16 mL). The
organic phase was separated, dried with MgSO4,
filtered and evaporated to dryness. The residue was
purified by MPLC using a linear gradient [hexane to
hexane/ethyl acetate (4:1)] to obtain diastereoisomeric
mixture 7 as a syrup (2.13 g, 96%). Data from the
spectrum of the diastereomeric mixture. 1H NMR
(CDCl3, 300 MHz): l 7.5–7.2 (m, 10H, 2×Ph), 5.0–4.5
(m, 6H, 2×CH2Ph, 2×Hacetal), 4.5–3.8 (m, 10H, 2×H-5,
2×H-5%, 2×H-4, 2×H-3, 2×H-2), 3.7–3.2 (m, 8H, 2×
OCH2Me, 2×H-6, 2×H-6%), 1.4–1.1 (m, 12H, 4×CH3);
13C NMR (CDCl3, 75.4 MHz): l 138.3, 138.0, 128.4,
128.3, 128.0, 127.9, 127.8, 127.7 (2×Ph), 99.7, 99.2
(2Cacetal), 80.5, 80.2 (2×C-2), 78.2 (C-3, 2 C), 75.3, 74.1
(2×CH2Ph), 73.8, 73.6 (2×C-5), 70.6, 69.8 (2×C-4), 61.4,
59.7 (2×OCH2Me), 20.1 (CH3), 19.9 (CH3), 15.1 (CH3,
2C), 4.1, 3.8 (2×C-6).
Purinic nucleosides were also obtained by reaction of
(−)-19 with 5-amino-4,6-dichloropyrimidine and then
with trimethylorthoformate in acid medium, to give the
6-chloropurine derivative 23 in 42% yield. The 6-
chloropurine moiety in 23 was converted by reaction
with ammonia in methanol with concomitant deprotec-
tion of the primary hydroxyl group to give 24. Finally
treating 24 under hydrogenolytic conditions provided
the fully deprotected isonucleoside 25.
4.2. (3R,4R,5R)-4-(Benzyloxy)-5-(hydroxymethyl)-
tetrahydrofuranol 12
3. Conclusion
In summary, starting from a common precursor (2,3-O-
isopropylidene-D-glyceraldehyde), we have synthesized
Melted 18-crown-6 (1.48 g, 5.60 mmol) and potassium
superoxide (400 mg, 5.63 mmol) were added to a solu-
tion of the diastereomeric mixture 7 (569 mg, 1.40
mmol) in anhydrous dimethylsulfoxide (14 mL). After 1
min the reaction mixture was diluted with ethyl ether
and poured into brine. The organic phase was sepa-
rated and the aqueous phase was extracted with ethyl
acetate. Triphenylphosphine (a few mg) was added to
the organic phase, which was then washed with
aqueous HCl (1N), water, dried with MgSO4 and evap-
orated. The resulting reaction crude was purified by CC
(CH2Cl2/MeOH 50:1) to obtain 12 as a syrup (275 mg,
enantiomeric 1,4-anhydro-alditols (−)-15 and (+)-15,
1,4-anhydro-2-aminoalditols (−)-19 and (+)-19, and
isonucleosides (+)-22, (−)-22, and 25. The synthesis of
(+)-22 from the pentenetriol 2 required 12 steps and the
overall yield was 8%. Its enantiomer (−)-22 required ten
steps from the pentenetriol 3 and the overall yield was
27%. Compound 25 was prepared in nine steps from 3
in an overall yield of 10%.
1
4. Experimental
88%); [h]2D5=−25.4 (c 1.70, CHCl3); H NMR (CDCl3,
300 MHz): l 7.5–7.3 (m, 5H, Ph), 4.76 (d, 1H, JAB
=
General comments: melting points are uncorrected.
Optical rotations were measured at 25°C in 10 cm cells.
1H and 13C NMR spectra were recorded in a 300 and
400 MHz (75.4 and 100.5 MHz, respectively) appara-
tus. Coupling constants are given in hertz (Hz). Ele-
mental analyses were determined at the Servei de
Recursos Cient´ıfics (Universitat Rovira i Virgili). TLC
was carried out on aluminium sheets precoated with
silica gel 60 F254. Flash column chromatography was
performed using Kieselgel 60 (particle size: 40–63 mm).
Radial chromatography was performed on 1, 2 or 4
mm plates of silica gel, depending on the amount of
product. Band separation was monitored by UV.
Medium-pressure chromatography (MPLC) was per-
formed using silica gel 60 A CC (6–35 mm). All chro-
matographic solvents were distilled at atmospheric
pressure prior to use. Dry solvents were obtained by
conventional methods.17
11.8 Hz, CH2Ph), 4.53 (d, 1H, JAB=11.8 Hz, CH2Ph),
4.23 (bs, 1H, H-3), 4.21 (dd, 1H, J4,5=7.7 Hz, J3,4=5.0
Hz, H-4), 4.07 (dt, 1H, J5,6:J5,6%=3.3 Hz, H-5), 3.95
(dd, 1H, J2,2%=10.3 Hz, J2,3=1.2 Hz, H-2), 3.80 (m, 2H,
H-2%, H-6), 3.71 (dd, 1H, J6,6%=12.2 Hz, J5,6%=3.4 Hz,
H-6%), 3.14 (bs, 1H, OH), 2.14 (bs, 1H, OH); 13C NMR
(CDCl3, 75.4 MHz): l 137.2, 128.5, 128.0, 127.7 (Ph),
78.9 (C-4), 78.2 (C-5), 73.3 (C-2), 72.5 (CH2Ph), 69.2
(C-3), 60.9 (C-6). Anal. calcd for C12H16O4: C, 64.27;
H, 7.19. Found: C, 63.92, H, 7.21%.
4.3. (3R,4R,5R)-5-[(Benzoyloxy)methyl]-4-(benzyloxy)-
tetrahydrofuran-3-ol 14
A solution of diol 12 (192 mg, 0.86 mmol) in anhydrous
pyridine (1 mL) was cooled at −20°C and benzoyl
chloride (100 mL, 0.86 mmol) was then added. After 1.5
h the reaction was quenched by pouring into aqueous
HCl (1N) and extracted five times with CH2Cl2. The
organic phase was dried with MgSO4 and evaporated.
The remaining residue was purified by CC (hexane/
ethyl acetate 2:1) to obtain 14 as a syrup (183 mg,
4.1. (2S,3S,4R)-3-Benzyloxy-4-((1R/S)-(1-ethoxy)-
ethoxy)-2-(iodomethyl)tetrahydrofuran 7
1
Ethyl vinyl ether (1.6 mL, 16.71 mmol) was added to a
solution of 4 (1.82 g, 5.44 mmol) in anhydrous CH2Cl2.
Pyridinium p-toluenesulfonate (140 mg, 0.56 mmol)
was then added, and the reaction was maintained at rt
for 3 h. The reaction was quenched by adding ethyl
ether (20 mL), and washed with saturated aqueous
65%); [h]2D5=+13.4 (c 1.80, CHCl3); H NMR (CDCl3,
300 MHz): l 8.06 (d, 2H, J=8.4 Hz, Ph), 7.5 (t, 1H,
J=7.2 Hz, Ph), 7.4 (t, 2H, J=7.6 Hz, Ph), 7.4–7.2 (m,
5H, Ph), 4.69 (s, 2H, 2×CH2Ph), 4.64 (dd, 1H, J6,6%
=
11.7 Hz, J5,6=3.9 Hz, H-6), 4.49 (dd, 1H, J6,6%=11.7
Hz, J5,6%=7.2 Hz, H-6%), 4.38–4.26 (m, 2H, H-5, H-3),

1640
F. Bra6o et al. / Tetrahedron: Asymmetry 12 (2001) 1635–1643
1
4.21 (dd, 1H, J=6.3 Hz, J%=5.4 Hz, H-4), 3.93 (dd,
1H, J2,2%=10.0 Hz, J2,3=3.2 Hz, H-2), 3.85 (dd, 1H,
syrup (58 mg, 89%); mp 45–47°C; H NMR (CDCl3,
300 MHz): l 7.4–7.2 (m, 5H, Ph), 4.68 (d, 1H, JAB
=
J2,2%=10.0 Hz, J2%,3=4.5 Hz, H-2%), 2.74 (d, 1H, J3,OH
=
11.8 Hz, CH2Ph), 4.52 (d, 1H, JAB=11.8 Hz, CH2Ph),
4.36 (dt, 1H, J2,3=4.1 Hz, J3,4:J2%,3=2.0 Hz, H-3),
4.18 (q, 1H, J4,5:J5,6:J5,6%=5.0 Hz, H-5), 4.12 (dd,
1H, J2,2%=9.8 Hz, J2,3=4.4 Hz, H-2), 4.00 (dd, 1H,
6.0 Hz, OH); 13C NMR (CDCl3, 75.4 MHz): l 166.2
(CꢀO), 136.7, 132.8, 129.8, 129.4, 128.4, 128.1, 128.1,
127.7 (Ph), 78.9 (C-4), 77.0 (C-5), 73.6 (C-2), 72.5
(CH2Ph), 70.3 (C-3), 63.9 (C-6). Anal. calcd for
C19H20O5: C, 69.50; H, 6.14. Found: C, 69.55, H,
6.47%.
J
4,5=4.8 Hz, J3,4=1.5 Hz, H-4), 3.86 (dd, 1H, J6,6%=
12.1 Hz, J5,6=5.4 Hz, H-6), 3.79 (dd, 1H, J6,6%=12.1
Hz, J5,6%=4.8 Hz, H-6%), 3.72 (dd, 1H, J2,2%=9.8 Hz,
J
2%,3=2.4 Hz, H-2%), 3.0 (bs, 1H, OH), 2.8 (bs, 1H, OH);
4.4. (3S,4R,5R)-5-[(Benzoyloxy)methyl]-4-(benzyloxy)-
tetrahydrofuran-3-ol (−)-15
13C NMR (CDCl3, 75.4 MHz): l 137.4, 128.6, 128.0,
127.6 (Ph), 85.2 (C-4), 80.0 (C-5), 74.9 (C-3), 73.3 (C-2),
72.3 (CH2Ph), 61.6 (C-6). Anal. calcd for C12H16O4: C,
69.27; H, 7.50. Found: C, 69.42, H, 7.50%.
Anhydrous pyridine (140 mL, 1.73 mmol) was added to
a solution of 14 (122 mg, 0.37 mmol) in anhydrous
CH2Cl2 (1.5 mL) under an argon atmosphere. The
resulting solution was cooled in ice/salt for 10 min.
Triflic anhydride (70 mL, 0.42 mmol) was then added
dropwise, and the reaction was allowed to warm to rt.
After 30 min the reaction mixture was filtered over a
neutral silica gel pad and the solution was evaporated
to dryness. The resulting syrup was dissolved in DMF
(12 mL) and potassium nitrite (190 mg, 2.23 mmol),
and 18-crown-6 (100 mg, 0.38 mmol) was added. The
reaction mixture was stirred at rt until it became homo-
geneous and greenish (1 h approx.). The reaction was
quenched by adding water (40 mL, 2.20 mmol) via
syringe and maintaining the stirring overnight. The
reaction mixture was then poured into an aqueous
solution of ammonium chloride and was extracted five
times with CH2Cl2. The organic phase was dried with
MgSO4 and evaporated. The resulting reaction crude
was purified by CC (hexane/ethyl acetate 2:1) to obtain
15 as a white powder (61 mg, 50%); mp 74–76°C;
[h]2D5=−20.2 (c 1.10, CHCl3); 1H NMR (CDCl3, 300
MHz): l 8.04 (d, 2H, J=7.2 Hz, Ph), 7.56 (t, 1H,
J=7.4 Hz, Ph), 7.42 (t, 2H, J=7.5 Hz, Ph), 7.34–7.26
(m, 5H, Ph), 4.69 (d, 1H, J=12.0 Hz, CH2Ph), 4.64–
4.46 (m, 3H, H-6, H-6%, H-5), 4.56 (d, 1H, J=12.0 Hz,
CH2Ph), 4.42 (bs, 1H, H-3), 4.21 (dd, 1H, J2,2%=9.8 Hz,
4.6. (3R,4S,5S)-5-[(Benzoyloxy)methyl]-4-(benzyloxy)-
tetrahydrofuran-3-ol (+)-15
The procedure used for preparing (−)-15 was followed
starting from (+)-16 (65 mg, 0.29 mmol), anhydrous
pyridine (1 mL) and benzoyl chloride (35 mL, 0.30
mmol) to obtain (+)-15 as a white solid (70 mg, 74%);
mp 75–76°C; [h]2D5=+21.8 (c 1.215, CHCl3). Anal. calcd
for C19H20O5: C, 69.50; H, 6.14. Found: C, 69.63, H,
6.51%.
4.7. (2R,3S,4S)-2-[(Benzoyloxy)methyl]-3-(benzyloxy)-4-
(p-toluensulfonyloxy)tetrahydrofuran (−)-17
A solution of alcohol (−)-15 (108 mg, 0.33 mmol) in
anhydrous pyridine (1 mL) was cooled at −10°C for 1 h
and tosyl chloride (190 mg, 0.50 mmol) was then added.
The reaction mixture was maintained at 4°C for 3 days
and then quenched by pouring it into HCl 1N. The
aqueous solution was extracted with CH2Cl2, and the
organic phase was dried with MgSO4, filtered and
evaporated. The residue was purified by CC (hexane/
ethyl acetate 5:1) to obtain (−)-17 as a syrup (132 mg,
83%); [h]2D5=−32.50 (c 1.178, CHCl3); 1H NMR
(CDCl3, 300 MHz): l 7.98 (d, 2H, J=7.8 Hz, Bz), 7.78
(d, 2H, J=8.0 Hz, Ts), 7.56 (t, 1H, J=7.4 Hz, Bz), 7.42
(t, 2H, J=7.5 Hz, Bz), 7.35 (d, 2H, J=8.0 Hz, Ts),
7.32–7.22 (m, 5H, Ph), 5.01 (dt, 1H, J5,4=4.4 Hz,
J4,3:J5%,4=1.6 Hz, H-4), 4.61 (d, 1H, JAB=12.0 Hz,
CH2Ph), 4.52 (dd, 1H, J6,6%=11.4 Hz, J2,6=5.1 Hz,
H-6), 4.46 (dd, 1H, J6,6%=11.4 Hz, J2,6%=6.4 Hz, H-6%),
4.45 (d, 1H, JAB=12.0 Hz, CH2Ph), 4.33 (ddd, 1H,
J2,6%=6.4 Hz, J2,6=5.1 Hz, J3,2=4.2 Hz, H-2), 4.22 (dd,
1H, J3,2=4.2 Hz, J4,3=1.2 Hz, H-3), 4.18 (dd, 1H,
J2,3=4.2 Hz, H-2), 3.99 (dd, 1H, J4,5=4.2 Hz, J3,4=1.8
Hz, H-4), 3.78 (dd, 1H, J2,2%=9.8 Hz, J2%,3=1.9 Hz,
H-2%), 2.00 (bs, 1H, OH); 13C NMR (CDCl3, 75.4
MHz): l 166.5 (CꢀO), 137.4, 133.0, 129.9, 129.6, 128.5,
128.3, 127.9, 127.6 (Ph), 84.4 (C-4), 77.9 (C-5), 74.3
(C-3), 73.7 (C-2), 72.0 (CH2Ph), 63.5 (C-6). Anal. calcd
for C19H20O5: C, 69.50; H, 6.14. Found: C, 69.25, H,
6.36%.
4.5. (3R,4S,5S)-4-(Benzyloxy)-5-(hydroxymethyl)-
tetrahydrofuran-3-ol (−)-16
J5,5%=10.8 Hz, J5,4=4.4 Hz, H-5), 3.81 (dd, 1H, J5,5%=
10.8 Hz, J5%,4=1.8 Hz, H-5%), 2.44 (s, 3H, CH3); 13C
NMR (CDCl3, 75.4 MHz): l 166.2 (CꢀO), 145.4, 136.8,
133.2, 133.0, 130.0, 129.7, 129.6, 128.5, 128.3, 128.1,
127.8, 127.7 (Ar), 82.1 (C-3), 81.4 (C-4), 78.1 (C-2), 72.1
(CH2Ph), 70.9 (C-5), 62.6 (C-6), 21.6 (CH3). Anal. calcd
for C26H26O7S: C, 64.72; H, 5.43; S, 6.64. Found: C,
64.63; H, 6.51; S, 6.73%.
Melted 18-crown-6 (310 mg, 1.17 mmol) and potassium
superoxide (83 mg, 1.17 mmol) was added to a solution
of 5 (97 mg, 0.29 mmol) in anhydrous DMSO (3 mL).
After 5 min at rt, the reaction was quenched by pouring
it into brine and extracted three times with ethyl ace-
tate. The aqueous solution was acidified with aqueous
HCl (1N) and extracted with ethyl acetate.
Triphenylphosphine (a few mg) was added to the
organic phase, which was dried with MgSO4 and evapo-
rated. The resulting crude product was purified by CC
(CH2Cl2 to CH2Cl2/MeOH 50:1) to obtain (−)-16 as a
4.8. (2S,3R,4R)-2-[(Benzoyloxy)methyl)]-3-(benzyloxy)-
4-(p-toluensulfonyloxy)tetrahydrofuran (+)-17
The procedure used for preparing (−)-17 was followed
starting from (+)-15 (195 mg, 0.59 mmol), anhydrous

F. Bra6o et al. / Tetrahedron: Asymmetry 12 (2001) 1635–1643
1641
pyridine (1 mL) and tosyl chloride (340 mg, 0.90 mmol)
to give (+)-17 as a syrup (280 mg, 98%); [h]2D5=+31.5 (c
1.230, CHCl3). Anal. calcd for C26H26O7S: C, 64.72; H,
5.43; S, 6.64. Found: C, 64.58; H, 6.41; S, 6.59%.
3500 (s), 2924 (m), 2856 (m), 1714 (s), 1449 (s), 1270 (s),
1114 (m), 707 (m). Anal. calcd for C19H21NO4: C,
69.71; H, 6.47; N, 4.28. Found: C, 69.61; H, 6.61; N,
4.20%.
4.9. (2R,3R,4R)-4-Azido-2-[(benzoyloxy)methyl]-3-(ben-
zyloxy)tetrahydrofuran (−)-18
4.12. (2S,3S,4S)-4-Amino-2-[(benzoyloxy)methyl]-3-
(benzyloxy)tetrahydrofuran (+)-19
To a solution of 17 (111 mg, 0.23 mmol) in anhydrous
DMSO (1 mL), NaN3 (45 mg, 0.69 mmol) and 15-
crown-5 (140 mL, 0.70 mmol) was added. The reaction
mixture was heated to 100°C overnight, quenched by
pouring it into brine, and the resulting solution was
extracted five times with ethyl ether. The organic phase
was dried with MgSO4, filtered and evaporated. The
residue was purified by CC (hexane/ethyl acetate 5:1) to
afford (−)-18 as a syrup (72 mg, 89%); 1H NMR
(CDCl3, 300 MHz): l 8.04 (d, 2H, J=8.1 Hz, Bz), 7.55
(t, 1H, J=7.5 Hz, Bz), 7.42 (t, 2H, J=7.4 Hz, Bz),
7.4–7.2 (m, 5H, Ph), 4.82 (d, 1H, JAB=11.8 Hz,
CH2Ph), 4.63 (d, 1H, JAB=11.8 Hz, CH2Ph), 4.62 (dd,
1H, J6,6%=11.7 Hz, J2,6=3.9 Hz, H-6), 4.50 (dd, 1H,
J6,6%=11.7 Hz, J2,6%=7.5 Hz, H-6%), 4.4–4.3 (m, 2H, H-5,
H-2), 4.0–3.9 (m, 3H, H-5%, H-4, H-3); 13C NMR
(CDCl3, 75.4 MHz): l 166.3 (CꢀO), 136.9, 133.0, 129.9,
129.6, 128.5, 128.3, 128.1, 127.8 (Ph), 79.3 (C-2), 77.6
(C-3), 73.8 (CH2Ph), 69.2 (C-5), 63.9 (C-6), 61.0 (C-4);
IR (CH2Cl2, cm−1): 2924 (m), 2107 (s), 1717 (s), 1455
(m), 1328 (w), 1266 (s), 1104 (m), 967 (w), 703 (m), 545
(w).
A similar procedure to that used in the preparation of
(−)-19 was followed starting from (+)-18 (72 mg, 0.20
mmol), anhydrous THF (1 mL), triphenylphosphine (75
mg, 0.29 mmol) and water (60 mL, 3.33 mmol) to give
(+)-19 as a white solid (64 mg, 96%); mp 50–53°C;
[h]2D5=+6.5 (c 1.1045, CHCl3). Anal. calcd for
C19H21NO4: C, 69.71; H, 6.47; N, 4.28. Found: C,
69.41; H, 6.71; N, 4.09%.
4.13. (2R,3R,4R)-2-[(Benzoyloxy)methyl]-3-(benzyloxy)-
4-[[[(3-methoxy-1-oxo-2-(E)-propenyl)amino]carbonyl]-
amino]tetrahydrofuran (−)-20
trans-Methoxyacryloyl chloride (34 mg, 0.28 mmol)
was added under an argon atmosphere to a suspension
of silver isocyanate (65 mg, 0.43 mmol) in anhydrous
toluene (1 mL). The reaction mixture was heated under
reflux for 0.5 h and cooled to rt. Compound 19 (31 mg,
0.09 mmol) dissolved in DMF (1 mL) was then added.
The reaction was maintained for 1 day at rt and then
evaporated under vacuum. The residue was purified by
CC (CH2Cl2 to CH2Cl2/MeOH 50:1) to give (−)-20 as a
white solid (39 mg, 91%); mp 119–121°C; [h]2D5=−32.5
1
4.10. (2S,3S,4S)-4-Azido-2-[(benzoyloxy)methyl]-3-(ben-
zyloxy)tetrahydrofuran (+)-18
(c 1.520, CHCl3); UV (CHCl3) umax 244 nm; H NMR
(CDCl3, 400 MHz): l 9.61 (s, 1H, NH), 9.25 (d, 1H,
JNH,3=7.6 Hz, NH), 8.04 (d, 2H, J=8.0 Hz, Bz), 7.70
A similar procedure to that used for the preparation of
(−)-17 was followed starting from (+)-17 (186 mg, 0.39
mmol), anhydrous DMSO (1 mL), NaN3 (75 mg, 1.15
mmol) and 15-crown-5 (230 mL, 1.15 mmol) to afford
(+)-18 as a syrup (114 mg, 84%).
(d, 1H, J2%,3%=12.2 Hz, H-3%), 7.56 (t, 1H, J=7.4 Hz,
Bz), 7.43 (t, 2H, J=7.8 Hz, Bz), 7.4–7.2 (m, 5H, Ph),
5.33 (d, 1H, J2%,3%=12.2 Hz, H-2%), 4.78 (d, 1H, JAB
=
11.6 Hz, CH2Ph), 4.62–4.52 (m, 2H, H-4, H-6a,
CH2Ph), 4.48 (dd, 1H, J6a,6b=11.8 Hz, J2,6b=7.3 Hz,
H-6b), 4.34 (dt, 1H, J2,6b=7.3 Hz, J3,2:J2,6a=4.8 Hz,
H-2), 4.25 (t, 1H, J4,3:J3,2=5.2 Hz, H-3), 4.05 (dd,
1H, J5a,5b=8.4 Hz, J5a,4=7.2 Hz, H-5a), 3.86 (t, 1H,
J5a,5b:J5b,4=8.0 Hz, H-5b), 3.74 (s, 1H, OCH3); 13C
NMR (CDCl3, 100.5 MHz): l 167.6 (CꢀO), 166.3
(CꢀO), 163.8 (C-3%), 155.2 (CꢀO), 136.9, 133.0, 129.8,
129.6, 128.5, 128.4, 128.3, 128.1 (Ph), 97.3 (C-2%), 78.9
(C-3), 77.9 (C-2), 74.4 (C-5), 70.3 (CH2Ph), 63.6 (C-6),
57.9 (OCH3), 52.2 (C-4). Anal. calcd for C24H26N2O7:
C, 63.43; H, 5.77; N, 6.26. Found: C, 63.11; H, 5.92; N,
5.92%.
4.11. (2R,3R,4R)-4-Amino-2-[(benzoyloxy)methyl]-3-
(benzyloxy)tetrahydrofuran (−)-19
Triphenylphosphine (70 mg, 0.27 mmol) was added to a
solution of (−)-18 (69 mg, 0.20 mmol) in anhydrous
THF (1 mL). The reaction mixture was maintained at rt
for 2.5 h. Water (60 mL, 3.33 mmol) was then added
and the reaction mixture was heated under reflux for 1
h. The solvent was evaporated and the residue was
purified by CC (CH2Cl2 and then CH2Cl2/MeOH 50:1)
to obtain 19 as a white solid (58 mg, 91%); mp 53–
1
54°C; [h]2D5=−7.1 (c 0.824, CHCl3); H NMR (CDCl3,
4.14. (2S,3S,4S)-2-[(Benzoyloxy)methyl]-3-(benzyloxy)-
4-[[[(3-methoxy-1-oxo-2-(E)-propenyl)amino]carbonyl]-
amino]tetrahydrofuran (+)-20
300 MHz): l 8.05 (d, 2H, J=8.4 Hz, Bz), 7.56 (t, 1H,
J=7.5 Hz, Bz), 7.43 (t, 2H, J=7.6 Hz, Bz), 7.4–7.2 (m,
5H, Ph), 4.70 (s, 2H, CH2Ph), 4.60 (dd, 1H, J6,6%=11.5
Hz, J2,6=5.0 Hz, H-6), 4.50 (dd, 1H, J6,6%=11.5 Hz,
A similar procedure to that used for the preparation of
(−)-19 was followed starting from (+)-19 (156 mg, 0.48
mmol) trans-methoxyacryloyl chloride (172 mg, 1.42
mmol), silver isocyanate (330 mg, 2.20 mmol) and
DMF (2 mL) to give (+)-20 as a white solid (193 mg,
89%); mp 118–120°C; [h]2D5=+30.7 (c 0.832, CHCl3).
Anal. calcd for C24H26N2O7: C, 63.43; H, 5.77; N, 6.26.
Found: C, 63.13; H, 5.93; N, 6.24%.
J2,6%=7.2 Hz, H-6%), 4.36 (dt, 1H, J2,6%=7.2 Hz, J3,2
:
J2,6=4.8 Hz, H-2), 4.05 (t, 1H, J4,3:J3,2=4.6 Hz, H-3),
3.94 (bs, 1H, H-4), 3.65–3.55 (m, 2H, H-5, H-5%), 1.58
(bs, 2H, NH2); 13C NMR (CDCl3, 75.4 MHz): l 166.4
(CꢀO), 137.5, 133.0, 129.9, 129.6, 128.5, 128.3, 128.1,
127.9 (Ph), 80.3 (C-3), 78.8 (C-2), 74.3 (C-5), 72.5
(CH2Ph), 64.1 (C-6), 54.7 (C-4); IR (CH2Cl2, cm−1):

1642
F. Bra6o et al. / Tetrahedron: Asymmetry 12 (2001) 1635–1643
4.15. 1-[(3R,4R,5R)-4-(Benzyloxy)-5-(hydroxymethyl)-
tetrahydrofuran-3-yl]uracil (+)-21
4.18. 1-[(3S,4S,5S)-4-Hydroxy-5-(hydroxymethyl)-
tetrahydrofuran-3-yl]uracil (−)-22
Aqueous H2SO4 (2 M, 2 mL) was added to a solution
of (−)-20 (89 mg, 0.20 mmol) in dioxane (2 mL). The
reaction mixture was heated under reflux for 18 h,
cooled, neutralized with aqueous NaOH solution (2 M)
and the solvent was evaporated under vacuum. The
residue was dissolved in ethanol and the solids were
filtered off. The solution was evaporated and the
residue purified by radial chromatography (CH2Cl2/
MeOH 50:1) to give (+)-21 as a white foam (43 mg,
69%); mp 45°C (dec.); [h]2D5=+81.6 (c 1.513, CHCl3);
UV (CHCl3) umax 266 nm; 1H NMR (CDCl3, 300
MHz): l 10.04 (bs, 1H, NH), 7.61 (d, 1H, J5,6=8.1 Hz,
H-6), 7.4–7.2 (m, 5H, Ph), 5.72 (d, 1H, J5,6=8.1 Hz,
H-5), 5.46 (td, 1H, J2¦,3%:J3%,4%=6.9 Hz, J2%,3%=3.5 Hz,
H-3%), 4.43 (d, 1H, JAB=11.4 Hz, CH2Ph), 4.40 (m, 1H,
H-4%), 4.35 (d, 1H, JAB=11.4 Hz, CH2Ph), 4.10 (dd,
1H, J2%,2¦=10.6 Hz, J2%,3%=3.5 Hz, H-2%), 4.0–3.8 (m,
4H, H-2%, H-5%, H-6%, H-6¦), 2.4 (bs, 1H, OH); 13C
NMR (CDCl3, 75.4 MHz): l 163.7 (CꢀO), 151.5 (CꢀO),
143.5 (C-6), 136.1, 128.7, 128.5, 128.0 (Ph), 101.8 (C-5),
82.2 (C-5%), 78.7 (C-4%), 74.2 (CH2Ph), 70.0 (C-2%), 61.0
(C-6%), 55.8 (C-3%). Anal. calcd for C16H18N2O5: C,
60.37; H, 5.70; N, 8.80. Found: C, 60.17; H, 5.83; N,
8.65%.
A similar procedure was followed starting from (+)-21
(61 mg, 0.19 mmol), Pd/C (10%, 60 mg) and MeOH (6
mL) to give (−)-22 as a syrup (41 mg, 94%); [h]2D5=
−85.2 (c 0.720, MeOH). Anal. calcd for C9H12N2O5: C,
47.37; H, 5.30; N, 12.28. Found: C, 47.10; H, 5.16; N,
12.06%.
4.19. 9-[(3S,4S,5S)-5-[(Benzoyloxy)methyl]-4-(benzyl-
oxy)tetrahydrofuran-3-yl]-6-chloropurine 23
The amine (+)-13 (170 mg, 0.52 mmol) was dissolved in
anhydrous butanol (2 mL) and then triethylamine (2
mL) was added. After a few minutes at rt 5-amino-4,6-
dichloropyrimidine (105 mg, 0.64 mmol) was added,
and the mixture obtained was heated under reflux for
72 h. The reaction was cooled to rt and then hot ethyl
acetate was added. A precipitate appeared on standing
which was filtered off. The filtrate was concentrated
and the resulting residue purified by CC (hexane/ethyl
acetate 1:1) to obtain 148 mg of an inseparable mixture.
This mixture was directly treated with trimethylortho-
formate (3 mL) and concentrated HCl (80 mL) for 3
days. The reaction mixture was then directly purified by
CC (CH2Cl2/MeOH 15:1) to give 23 as a syrup (101
mg, 42% yield for the two steps); [h]2D5=−56.2 (c 1.296,
1
4.16. 1-[(3S,4S,5S)-4-(Benzyloxy)-5-(hydroxymethyl)-
tetrahydrofuran-3-yl]uracil (−)-21
CHCl3); UV (CHCl3) umax 266 nm; H NMR (CDCl3,
300 MHz): l 8.67 (s, 1H, H-8), 8.36 (s, 1H, H-2), 8.08
(d, 2H, J=7.2 Hz, Bz), 7.59 (t, 1H, J=7.4 Hz, Bz), 7.46
(t, 2H, J=7.86 Hz, Bz), 7.2–6.8 (m, 5H, Ph), 5.52 (q,
1H, J2%,3%:J2¦,3%:J3%,4%=6.4 Hz, H-3%), 4.70 (dd, 1H,
A similar procedure to that used for the preparation of
(+)-21 was followed, starting from (+)-20 (159 mg, 0.65
mmol), H2SO4 (2 M, 3.5 mL), and dioxane (3.5 mL) to
give (−)-21 as a white foam (80 mg, 72%); mp 45°C
(dec.); [h]2D5=−83.5 (c 1.214, CHCl3). Anal. calcd for
C16H18N2O5: C, 60.37; H, 5.70; N, 8.80. Found: C,
60.43; H, 5.85; N, 8.61%.
J
J
6%,6¦=11.7 Hz, J5%,6%=5.1 Hz, H-6%), 4.64 (dd, 1H,
6%,6¦=11.7 Hz, J5%,6¦=6.6 Hz, H-6¦), 4.52–4.43 (m, 2H,
H-4%, H-5%), 4.34 (d, 1H, JAB=11.6 Hz, CH2Ph), 4.33
(dd, 1H, J2%,2¦=9.6 Hz, J2%,3%=6.3 Hz, H-2%), 4.22 (dd,
1H, J2%,2¦=9.6 Hz, J2%,3¦=7.5 Hz, H-2¦), 4.05 (d, 1H,
J
AB=11.6 Hz, CH2Ph); 13C NMR (CDCl3, 75.4 MHz):
4.17. 1-[(3R,4R,5R)-4-Hydroxy-5-(hydroxymethyl)-
tetrahydrofuran-3-yl]uracil (+)-22
l 166.1 (CꢀO), 151.6 (C-2), 150.8 (C-4), 144.8 (C-8),
135.3, 133.2, 129.6, 128.4, 128.2, 128.1, 127.9 (Ar), 79.8
(C-4%), 77.4 (C-5%), 74.4 (C-2%), 69.9 (CH2Ph), 62.6 (C-
6%), 55.6 (C-3%). Anal. calcd for C24H20ClN4O4: C, 62.00;
H, 4.55; Cl, 7.63; N, 12.31. Found: C, 62.23; H, 4.61;
Cl, 7.86; N, 12.21%.
To a solution of (+)-21 (37 mg, 0.12 mmol) in MeOH (3
mL) was added Pd/C (10%, 40 mg). The reaction
mixture was maintained overnight under hydrogen (1
atm) with vigorous stirring. The catalyst was removed
by filtration and the solvent was evaporated. The
residue was purified by radial chromatography
(CH2Cl2/MeOH 8:1) to give (+)-22 as a syrup (24 mg,
90%); [h]2D5=+83.1 (c 0.835, MeOH); UV (MeOH) umax
4.20. 6-Amino-9-[(3S,4S,5S)-4-benzyloxy-5-(hydroxy-
methyl)tetrahydrofuran-3-yl]purine 24
A solution of 23 (82 mg, 0.18 mmol) in MeOH satu-
rated with ammonia (3 mL) was allowed to stand at rt
overnight. The solvent was then evaporated and the
residue was purified by CC (CH2Cl2/MeOH 20:1 to
10:1) to give compound 24 (31 mg, 52%); [h]2D5=−46.3
1
272 nm; H NMR (CD3OD, 300 MHz): l 7.66 (d, 1H,
J
5,6=7.8 Hz, H-6), 5.65 (d, 1H, J5,6=7.8 Hz, H-5), 5.24
(dt, 1H, J2¦,3%=8.0 Hz, J2%,3%:J3%,4%=5.8 Hz, H-3%), 4.44
(dd, 1H, J3%,4%=6.0 Hz, J4%,5%=4.2 Hz, H-4%), 4.08 (dd,
1H, J2%,2¦=9.8 Hz, J2%,3%=5.8 Hz, H-2%), 3.98 (dd, 1H,
1
(c 1.353, MeOH); UV (CHCl3) umax 270 nm; H NMR
J
2%,2¦=9.8 Hz, J2¦,3%=8.0 Hz, H-2¦), 3.90 (dt, 1H, J5%,6¦
=
=
(CD3OD, 400 MHz): l 8.17 (s, 1H, H-8), 8.16 (s, 1H,
H-2), 7.2–6.8 (m, 5H, Ph), 5.38 (dt, 1H, J2%,3%=7.2 Hz,
J2¦,3%:J3%,4%=6.0 Hz, H-3%), 4.43 (dd, 1H, J3%,4%=5.6 Hz,
J4%,5%=4.8 Hz, H-4%), 4.34 (d, 1H, JAB=11.2 Hz,
CH2Ph), 4.29 (dd, 1H, J2%,2¦=9.6 Hz, J2%,3%=6.0 Hz,
H-2%), 4.17–4.12 (m, 2H, H-2¦, H-5%), 3.99 (d, 1H,
6.7 Hz, J4%,5%:J5%,6%=4.4 Hz, H-5%), 3.84 (dd, 1H, J6%,6¦
11.6 Hz, J5%,6%=4.4 Hz, H-6%), 3.77 (dd, 1H, J6%,6¦=11.6
Hz, J5%,6¦=6.7 Hz, H-6¦); 13C NMR (CD3OD, 75.4
MHz): l 162.3 (C-4), 149.8 (C-2), 146.1 (C-6), 101.3
(C-5), 84.6 (C-5%), 71.8 (C-4%), 69.6 (C-2%), 61.7 (C-6%),
58.9 (C-3%). Anal. calcd for C9H12N2O5: C, 47.37; H,
5.30; N, 12.28. Found: C, 47.12; H, 5.60; N, 12.11%.
J
AB=11.2 Hz, CH2Ph), 3.87–3.84 (m, 2H, H-6%, H-6¦);
13C NMR (CD3OD, 100.5 MHz): l 157.0 (C-6), 153.6

F. Bra6o et al. / Tetrahedron: Asymmetry 12 (2001) 1635–1643
1643
(C-2), 150.8 (C-4), 141.9 (C-8), 137.9, 129.1, 128.9,
128.8 (Ph), 119.5 (C-5), 83.8 (C-4%), 79.1 (C-5%), 75.0
(C-2%), 70.4 (CH2Ph), 61.4 (C-6%), 57.1 (C-3%). Anal.
calcd for C17H19N5O3: C, 59.81; H, 5.61; N, 20.52.
Found: C, 60.01; H, 5.50; N, 20.21%.
4. (a) Jung, M. E.; Kretschik, O. J. Org. Chem. 1998, 63,
2975–2981; (b) Yamada, K.; Sakata, S.; Yoshimura, Y. J.
Org. Chem. 1998, 63, 6891–6899.
5. (a) Sugimura, H. Nucleosides Nucleotides 2000, 19, 629–
635; (b) Jung, M.; Kiankarimi, M. J. Org. Chem. 1998,
63, 8133; (c) Pre´vost, N.; Rouessac, F. Tetrahedron Lett.
1997, 38, 4215–4218; (d) Andersen, M. W.; Daluge, S.
M.; Kerremans, L.; Herdewijn, P. Tetrahedron Lett. 1996,
37, 8147–8150.
4.21. 6-Amino-9-[(3S,4S,5S)-4-hydroxy-5-(hydroxy-
methyl)tetrahydrofuran-3-yl]purine 25
6. (a) Nair, V.; Nuesca, Z. M. J. Am. Chem. Soc. 1992, 114,
7951–7953; (b) D´ıaz, Y.; Bravo, F.; Castillo´n, S. J. Org.
Chem. 1999, 64, 6508–6511; (c) Bolon, P. J.; Sells, T. B.;
Nuesca, Z. M.; Purdy, D. F.; Nair, V. Tetrahedron 1994,
50, 7747–7764.
7. (a) Jones, M. F.; Noble, S. A.; Robertson, C. A.; Storer,
R.; Hichcok, R. M.; Lamont, R. B. J. Chem. Soc.,
Perkin. Trans. 1 1992, 1427; (b) Nuesca, Z. M.; Nair, V.
Tetrahedron Lett. 1994, 35, 2485–2488; (c) Zhang, J.;
Nair, V. Nucleosides Nucleotides 1997, 16, 1091–1094; (d)
Purdy, D. E.; Zintek, L. B.; Nair, V. Nucleosides Nucle-
otides 1994, 13, 109–126; (e) Talekar, R. R.; Wightman,
R. H. Nucleosides Nucleotides 1997, 16, 495–505.
8. (a) Huryn, D. M.; Sluboski, B. C.; Tam, S. Y.; Todaro,
L. J.; Weigele, M. Tetrahedron Lett. 1989, 30, 6259–6262;
(b) Jeon, G. S.; Nair, V. Tetrahedron 1996, 52, 12643–
12650.
To a solution of 24 (27 mg, 0.079 mmol) in MeOH (2
mL), Pd/C (10%, 27 mg) was added. The reaction
mixture was maintained overnight under hydrogen (1
atm) with vigorous stirring. The catalyst was filtered off
and the solvent was evaporated. The residue was dis-
solved in ethanol and the resultant solution was filtered
and evaporated The residue was purified by radial
chromatography (CH2Cl2/MeOH 8:2) to give 25 as a
foam (18 mg, 89%); [h]D25=−26.6 (c 0.275, MeOH); UV
1
(CH3OH) umax 262 nm; H NMR (CD3OD, 400 MHz):
l 8.26 (s, 1H, H-8), 8.21 (s, 1H, H-2), 5.33 (td, 1H,
J
3%,4=5.2 Hz, J3%,2%:J3%,2¦=8.0 Hz, H-3%), 5.49 (dd, 1H,
J4%,3%=5.2 Hz, J4%,5%=4.0 Hz, H-4%), 4.32 (pseudo t, 1H,
J2%,3%:J2%,2¦=8.0 Hz, H-2%), 4.25 (pseudo t, 1H, J2¦,3%
J2¦,2%=8.0 Hz, H-2¦), 4.14 (ddd, 1H, J5%,6¦=6.8 Hz,
J5%,6%=4.8 Hz, J5%,4%=4.0 Hz, H-5%), 3.87 (dd, 1H, J6%,6¦
:
=
12.0 Hz, J6%,5%=4.8 Hz, H-6%), 3.81 (dd, 1H, J6¦,6%=12.0
Hz, J6¦,5%=6.8 Hz, H-6¦); 13C NMR (CD3OD, 100.5
MHz): l 157.4 (C-6), 153.8 (C-2), 151.3 (C-4), 142.5
(C-8), 119.6 (C-5), 83.4 (C-5%), 71.82 (C-4%), 69.6 (C-2%),
62.0 (C-6%), 58.5 (C-3%). Anal. calcd for C10H13N5O3: C,
47.81; H, 5.22; N, 27.87. Found: C, 47.99; H, 5.26; N,
28.20%.
9. Zheng, X.; Nair, V. Tetrahedron 1999, 55, 11803–11818.
10. (a) Zintek, L. B.; Jahnke, T. S.; Nair, V. Nucleosides
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