A stereospecific synthesis of L-deoxyribose, L-ribose and L-ribosides

Article abstract of DOI:10.1016/S0040-4020(02)00230-2

Using an inexpensive D-galactose from the chiral pool, L-deoxyribose, L-ribose and their derivatives were synthesized via mild reaction conditions. During the synthesis of L-deoxyribose, the key deoxygenation of the 2-hydroxy group of 3,5-O-dibenzyl-methyl-L-arabinofuranoside was performed by reduction of the corresponding triflate with tetrabutylammonium borohydride in high yield. During the synthesis of L-ribose, the key step of inversion of the 2-hydroxy group in the same substrate was carried out by intramolecular S_N2 tandem reaction. Then the L-ribosyl donors were submitted to glycosidations according to Vorbrüggen's conditions to give L-ribosides (L-uridine, L-5-fluorouridine, L-iodouridine, L-thymidine, L-puridine, L-adenosine and L-guanosine) in excellent yields.

Full text of DOI:10.1016/S0040-4020(02)00230-2

TETRAHEDRON
Pergamon
Tetrahedron 58 (2002) 3287±3296
A stereospeci®c synthesis of l-deoxyribose, l-ribose
and l-ribosides
Zhen-Dan Shi, Bing-Hui Yangp and Yu-Lin Wu
State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, People's Republic of China
Received 9 November 2001; revised 31 January 2002; accepted 21 February 2002
AbstractÐUsing an inexpensive d-galactose from the chiral pool, l-deoxyribose, l-ribose and their derivatives were synthesized via mild
reaction conditions. During the synthesis of l-deoxyribose, the key deoxygenation of the 2-hydroxy group of 3,5-O-dibenzyl-methyl-l-
arabinofuranoside was performed by reduction of the corresponding tri¯ate with tetrabutylammonium borohydride in high yield. During the
synthesis of l-ribose, the key step of inversion of the 2-hydroxy group in the same substrate was carried out by intramolecular SN2 tandem
reaction. Then the l-ribosyl donors were submitted to glycosidations according to VorbruÈggen'sconditionsto give l-ribosides (l-uridine,
l-5-¯uorouridine, l-iodouridine, l-thymidine, l-puridine, l-adenosine and l-guanosine) in excellent yields. q 2002 Elsevier Science Ltd.
All rightsreserved.
1. Introduction
derivatives. Up to now, there have been several reports of
syntheses of l-deoxyribose and l-ribose from l-arabi-
nose,13±15 d-glucose,16 d-ribose17 and l-xylose.18 Herein
we reported a stereospeci®c synthesis of l-deoxyribose 2,
l-ribose 3 and l-ribosides from d-galactose 1.
Since the discovery of the acquired immunode®ciency
syndrome (AIDS) infected by human immunode®ciency
virus (HIV), intensive efforts in the search for effective
antiviral agentswhich inhibit the replication of HIV have
been made. Nucleoside analogues with modi®ed sugar
moietieshave become active antiviral drug,susch as
30-azido-30-deoxythymidine (AZT),1 20,30-dideoxycytidine
(ddC),2 and 20,30-didehydro-30-deoxythymidine (d4T).3 All
these nucleoside analogues act by their conversion into the
corresponding 50-triphosphates as competitive inhibitors or
asDNA chain terminators. However, owing to inherent drug
resistance4 and toxicity of the used anti-HIV drugs,5
recently several modi®ed l-nucleosides, such as (2)-(20R,
50S)-1-(2-hydroxymethyl oxathiolan-5-yl)-cytosine (3TC),6
l-thymidine (l-T),7 l-30-thiacytidine (l-3-TC),8 l-5-¯uoro-
30-thia-cytidine (l-FTC),9 l-20,30-dideoxycytidine (l-ddC),10
l-5-¯uoro-20,30-dideoxy-cytidine (l-5-FddC),11 and l-20-
¯uoro-5-methylarabinofuranosyl uracil (l-FMAU)12 have
been developed asmore actively antiviral and lestoxic
agents. Their antiviral mechanism shows that l-nucleosides
are phosphorylated by cellular kinases which interact selec-
tively with viral polymerases but seldomly with cellular
polymerases.
2. Results and discussion
2.1. Proposed synthesis of l-deoxyribose and l-ribose
Comparing their structures (Fig. 1), some useful information
on d-galactose 1 in relation to l-deoxyribose 2 and l-ribose
3 wasacquired. d-Galactose is a hexose while l-deoxy-
ribose and l-ribose are pentoses without C-6; they have
the same con®gurations at C-3 and C-4 but different at
C-2. Therefore, in our synthetic approach, the strategy
employed for the conversion of d-galactose into l-deoxy-
ribose 2 and l-ribose 3, respectively, included two key steps
to effect their structurally different points. One step was
chemoselective oxidative cleavage of the 5,6-diol of
d-galactose and the other was the deoxygenation of the
For these reasons, studies on l-carbohydrates, modi®ed
l-nucleosides, especially l-deoxyribosides, l-ribosides and
their derivatives are being considered. It is also of interest to
synthesize l-deoxyribose, l-ribose, l-ribosides and their
Keywords: synthesis; l-deoxyribose; l-ribose; l-ribosides.
Corresponding author; e-mail: yangbh@pub.sioc.ac.cn
p
Figure 1. Structuresof d-galactose 1, l-deoxyribose 2 and l-ribose 3.
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00230-2

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Z.-D. Shi et al. / Tetrahedron 58 (2002) 3287±3296
2-hydroxy group or the con®gurational inversion of the
2-hydroxy group.
protection of the 3,5-dihydroxyl groupsof compound 6 with
benzyl chloride and methanolysis of the resulting compound
7 with 10% HCl±MeOH, a substrate 8 for deoxygenation of
the 2-hydroxy group wasobtained.
2.2. Synthesis of l-deoxyribose
According to literature,19 1,2,5,6-di-O-isopropylidene-d-
galactofuranose 4 obtained from d-galactose was employed
asthe tsarting material. Then, there were two pathway
chosen for the conversion of compound 4 into compound
6 (Scheme 1). For the ®rst one, chemoselective hydrolysis
and cleavage of the 5,6-O-isopropylidene acetal of 4 with
NaIO4/H5IO6 (1.0 equiv./0.5 equiv.) in one operation20 and
reduction of the corresponding aldehyde 5 with sodium
borohydride furnished l-arabinose derivative 6 in 91%
yield. For the second route, the 5,6-O-isopropylidene acetal
of 4 wasselectively hydrolyzed with 10% AcOH follwed by
NaIO4 cleavage of the resulting glycol and reduction. After
To realize the deoxygenation, several sulfonates (±OTs,
±OMs, ±OTf) prepared from compound 8 were tried as
substrates for the reduction using several reductive agents
(NaBH4, LiAlH4, n-Bu4NBH4) in different solvents (tetra-
hydrofuran, benzene, toluene). The other factorsof reaction
temperature and reaction time were also considered. One of
the sulfonates, tri¯ate 9, wasprevioulsy prepared almots
quantitatively by reaction of 8 with tri¯ic anhydride and
pyridine in CH2Cl2. After a series of attempts at the deoxy-
genation, compound 10 wasacquired by reduction of tri¯ate
9 with tetrabutylammonium borohydride in benzene under
re¯ux for 4 h in 95% yield. Subsequently, l-deoxyribose 2
Scheme 1. Reagents and conditions: (a) NaIO4/H5IO6 (1.0 equiv./0.5 equiv.), EtOAc, rt, 5 h, 94; or 10% AcOH±H2O, rt, 24 h; NaIO4, MeOH, H2O, 3 h,
two steps 92%; (b) NaBH4, MeOH, rt, 2 h, 97%; (c) KOH, BnCl, 1,4-dioxane, re¯ux, 2 h, 96%; (d) 10% HCl±MeOH, rt, 3 h, 98%; (e) Tf2O, py, CH2Cl2,
215±2108C, 4 h, 99%; (f) n-Bu4NBH4, benzene, re¯ux, 4 h, 95%; (g) 10% Pd±C, H2, rt, 3 h, 97%; (h) Dowex [H1], H2O, 608C, 24 h, 98%.
Scheme 2. Reagents and conditions: (a) MsCl, Et3N, rt, overnight, 98%; (b) Ac2O, AcOH, H2SO4, 48C, overnight, 89%; (c) NaOMe, MeOH, rt, 6 h, 86%;
(d) 10% Pd±C, MeOH, H2, 2 h, 97%; (e) Dowex [H1], H2O, 508C, 24 h, 95% yield.

Z.-D. Shi et al. / Tetrahedron 58 (2002) 3287±3296
3289
Scheme 3. Reagents and conditions: (a) Ac2O, py, overnight, rt, 92%; (b) AcOH, Ac2O, H2SO4, 48C, overnight, 76%; (c) for 18a: uracil, TMSOTf, BSA,
CH3CN, 60±658C, overnight, 92%; for 18b: thymine, TMSOTf, BSA, CH3CN, 60±658C, overnight, 88%; for 18c: 5-¯uorouracil, TMSOTf, BSA, CH3CN,
60±658C, overnight, 89%; (d) NH3±H2O, MeOH, 608C, overnight; (e) 10% Pd±C, H2, rt, 3 h, 20a: l-uridine: 92%, two steps; 20b: l-thymidine: 91%, two
steps. 20c: l-5-Fluorouridine: 87%, two steps.
wasprepared by hydrogenation of 11 with 10% palladium±
carbon in methanol, followed by hydrolysis of methyl
glycoside with ion-exchange resin (H1 form) in 98% yield.
AcOH/H2SO4 to afford 1,2,5-tri-O-acetyl-3-O-benzyl-l-
ribofuranose 17 asthe b anomer of a separabale mixture
(a/bˆ1:7), which was used for glycosidation (Scheme 3).
According to the VorbruÈggen method,21 the b-N-glycosidic
bound linkage were formed by the l-ribosyl donor 17 and
the protected bases. We therefore obtained 18a±c by
the treatment of 17 with the bases of uracil, thymine and
5-¯uorouracil, respectively, in the presence of TMSOTf and
BSA (N,O-bis-thrimethylsilylacetamide) in good yields
(92, 88, 89% for 18a±c, respectively). Then l-uridine
20a, l-thymidine 20b and l-5-¯uorouridine 20c were
obtained by deacetylation of 18a±c with NH3±H2O/
MeOH and debenzylation with 10% palladium±carbon in
methanol in high yield (92, 91, 87%, for 20a±c respectively.
2.3. Synthesis of l-ribose
l-Ribose was synthesized starting from the key intermediate
compound 8 (Scheme 2). The most important task was to
realize the con®guration inversion of the 2-hydroxyl group
in compound 8. Inversion of the 2-hydroxyl group was
attempted by several methods including oxidation/reduction
proceduresand methodsof Mitsunobu and intermolecular
SN1 reaction, but unfortunately all of these were unsuccess-
ful. An idea of inversion of the 2-hydroxyl group by using
the chirality of C-1 occurred, which would be effected by a
tandem reaction.
For some bases sensitive to debenzylation, like 5-iodouracil
and purines, another synthetic route was applied (Scheme
4). Protection of the triol 15 with acetic anhydride and
pyridine and treatment of the resulting triacetate 21 with
Ac2O/AcOH/H2SO4 afforded a separable mixture (a/bˆ
1:4) of tetra-O-acetyl-l-ribose, with the b anomer 22 asa
Preparation of compound 12 by methanesulfonylation of
compound 8 and then acetylation of compound 12 with
Ac2O, AcOH and H2SO4 gave only the 1,5-diacetate 13,
with no monoacetate, in 89% yield. Hydrolysis of diacetate
13 followed by inversion of con®guration of the 2-hydroxyl
group using NaOMe/MeOH solution gave compound 14 in
86% yield. Thisreaction experienced mechanims of the
intramolecular SN2 tandem reaction. Two kindsof C-1
alkoxide and C-5 alkoxide were formed by removing
1,5-diacetate of compound 13 under the basic solution,
but only structural advantage of C-1 alkoxide attacked
methanesulfonyloxy group of C-2 from its back position,
with producing the 1,2-epoxide intermediate. Thisinter-
mediate was unstable under the reaction system and easily
reacted regioselectively at the C-1 position with surround-
ing methoxyl alkoxide, then produced compound 14.
After the same procedures of debenzylation and hydrolysis
of methyl glycoside, l-ribose 3 was synthesized. The
resulting structure was con®rmed by comparison with a
commercial sample from Aldrich.
Scheme 4. Reagents and conditions: (a) Ac2O, py, overnight, rt, 90%;
(b) Ac2O, AcOH, H2SO4, 48C, overnight, 74%; (c) for 23a: 5-iodouracil,
TMSOTf, BSA, CH3CN, 60±658C, overnight, 94%; for 23b: purine,
TMSOTf, BSA, CH3CN, 60±658C, overnight, 83%; for 23c: 6-N-benzoyl-
adenine, TMSOTf, MFSTA, CH3CN, 60±658C, overnight, 81%; for 23d:
2-N-6-O-diphenylcarbamoylguanine,22 TMSOTf, BSA, toluene, 3 h, 808C,
86%; (d) NH3/H2O, MeOH, 608C, overnight, 24a: l-iodouridine: 93%; 24b:
l-puridine: 91%; 24c: l-adenosine: 94%; 24d: l-guanosine: 91%.
2.4. Synthesis of l-ribosides
Diacetate 16 wasprepared by diacetylation of the two
hydroxyl groupsof compound 14 and treated with Ac2O/

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Z.-D. Shi et al. / Tetrahedron 58 (2002) 3287±3296
Table 1. Bases structures of the synthesized ribosides and their derivatives
Base
Compound no.
18a
19a
20a
18b
19b
20b
18c
19c
20c
23a
24a
23b
24b
Base
Compound no.
23c
24c
23d
24d
suitable l-ribosyl donor. Using the same procedures for
glycosidation, we acquired the derivatives of l-ribosides
(23a±d) in good yield (94, 83, 81, 86% for 23a±d, respec-
tively) on different bases (5-iodouracil, purine, N6-benzoyl-
adenine and N2-O6-diphenylcarbamoylguanine), selecting
the reagentsof BSA and MFSTA ( N-methyl-N-trimethyl-
silyltri¯uoroacetamide) and different solvents. After depro-
tection of 23a±d, l-iodouridine 24a, l-puridine 24b,
l-adenosine 24c and l-guanosine 24d were afforded in
high yield (93, 91, 94, 91% for 24a±d, respectively).
Laboratory at the Shanghai Institute of Organic Chemistry.
Flash column chromatography was performed on silica gel
(10±40 mm) using a mixture of petroleum ether and ethyl
acetate or dichloromethane and methanol asthe eluent.
Solventsand reagentswere puri®ed and dried by standard
methodsprior to use.
4.1.1. 1,2-Isopropylidene-5-oxo-b-l-arabinofuranose (5).
A solution of d-galactofuranose 4 (5.20 g, 20.0 mmol) in
ethyl acetate (50 mL) was added to a well-stirred suspension
of NaIO4 (4.2 g, 20.0 mmol) and H5IO6 (2.28 g, 10.0 mmol)
in ethyl acetate (50 mL). After 5 h at room temperature, the
mixture wasworked up by ®ltering and evaporating the
solution. The residue was chromatographed (ethyl acetate/
petroleum etherˆ1:1) to give aldehyde 5 (3.538 g, 94%) asa
In order to be read more easily, structures of bases of the
above synthesized l-ribosides and their derivatives were
shown in Table 1.
20
colorless oil. [a]D ˆ222.8 (c 1.2, MeOH); MS (EI) m/z
188 (M1), 173 (M12CH3); IR (®lm, cm21): 3402 (brs),
3. Conclusion
1
2990, 1733; H NMR (300 MHz, CDCl3) d 9.71 (s, 1H,
HC(5)), 6.05 (d, J1,2ˆ3.5 Hz, 1H, HC(1)), 4.56 (d, J1,2ˆ
3.5 Hz, 1H, HC(2)), 4.45 (s, 1H, HC(4)), 4.38 (s, 1H,
HC(3)), 1.37 (s, 3H, CH3), 1.27 (s, 3H, CH3); HRMS (EI):
(M12CH3), found 173.0431. C7H9O5 requires173.0412.
From the easily available 1,2,5,6-di-O-isopropylidene-d-
galactofuranose 4 we synthesized l-deoxyribose via eight
steps in 75% overall yield and l-ribose via nine steps in 57%
overall yield. We also successfully carried out the key steps
of chemoselective hydrolysis and cleavage of the terminal
isopropylidene acetal of compound 4 and the key steps of
the inversion and deoxygenation of the 2-hydroxy group of
compound 8. Owing to these mild reaction conditions,
cheap reagents and good yields, these procedures provide
a practical synthesis of l-deoxyribose, l-ribose and l-ribo-
sides. The biological activity of the l-ribosides and their
derivatives are being assessed.
4.1.2. 1,2-Isopropylidene-b-l-arabinofuranose (6). To a
solution of aldehyde 5 (10.23 g, 54.41 mmol) in methanol
(200 mL) wasadded NaBH (6.59 g, 173 mmol). After the
4
mixture wasstirred at room temperature for 2 h, 10% AcOH
wasadded to neutralize the mixture. Then the mixture was
concentrated in vacuo and the residue was puri®ed by ¯ash
chromatography (CH2Cl2/MeOHˆ15:1) to give alcohol 6
20
(10.03 g, 97%) asa colorlessoil. [ a]D ˆ228.9 (c 1.2,
MeOH) [lit.19 [a]D ˆ228.9 (H2O)]; IR (®lm, cm21):
20
1
3397 (brs), 2940; MS (EI) m/z 175 (M12CH3); H NMR
4. Experimental
4.1. General
(300 MHz, CDCl3) d 5.95 (d, J1,2ˆ4.1 Hz, 1H, HC(1)), 4.59
(d, J1,2ˆ4.1 Hz, 1H, HC(2)), 4.27 (d, J3,4ˆ2.5 Hz, 1H,
HC(3)), 4.11 (m, 1H, HC(4)), 3.82 (dd, J4,5aˆ6.9 Hz,
J5a,5bˆ11.8 Hz, 1H, HC(5a)), 3.75 (dd, J4,5bˆ5.2 Hz,
J5a,5bˆ11.8 Hz, 1H, HC(5b)), 1.54 (s, 3H, CH3), 1.34 (s,
3H, CH3).
IR spectra were recorded on a Digilab FT-IR instrument. 1H
NMR spectra were recorded on a Bruker AM-300
(300 MHz) and assigned in ppm (d) down®eld relative to
TMS as internal standard. Optical rotations were measured
at room temperature. MS spectra were conducted on a
HP-5989A and VG QUATTRO mass spectrometers.
Microanalyses were performed in the Microanalytical
4.1.3. 1,2-Isopropylidene-3,5-O-dibenzyl-b-l-arabino-
furanose (7). To a solution of alcohol 6 (12.454 g,
65.54 mmol) in anhydrous1,4-dioxane (75 mL) was

Z.-D. Shi et al. / Tetrahedron 58 (2002) 3287±3296
3291
added benzyl chloride (75 mL) and powdered potassium
hydroxide (45 g). The mixture wasre¯uxed under argon
for 2 h. The dioxane was distilled and the residue was
cooled and ice-water (150 mL) wasadded, then extracted
with ether (4£100 mL) and the combined organic layers
were washed with brine, dried over Na2SO4. The solvent
wasremoved in vacuo and the reisdue waspuri®ed by
HC(3), HC(4)), 3.64±3.48 (m, 2H, HC(5)), 3.42 (s, 2.19H,
OCH3, a-anomer), 3.38 (s, 0.81H, b-anomer); Anal. calcd
for C21H23O7SF3: C, 52.94; H, 4.83. Found: C, 53.05; H,
4.83.
4.1.6. Methyl 3,5-O-dibenzyl-2-deoxy-l-ribofuranoside
(10). To a solution of 9 (857 mg, 1.80 mmol) in anhydrous
benzene (15 mL) wasadded n-Bu4NBH4 (1.38 g, 54 mmol).
The mixture wasre¯uxed for 4 h under argon. The reaction
mixture waspoured into ice-water (50 mL). The aqueous
water wasextracted with CH 2Cl2 (3£100 mL). The
combined organic layerswere wahsed with water, brine,
and dried over Na2SO4. The solvent was removed in
vacuo. The residue was puri®ed by ¯ash chromatography
(ethyl acetate/petroleum etherˆ1:12) to give b-anomer
(212 mg, 36%), a-anomer (281 mg, 48%) and recovered
starting material (72 mg, 11%). The yield was 95%.
¯ash chromatography (ethyl acetate/petroleum etherˆ
20
1:20) to give 7 (23.30 g, 96%) asa yellow oil. [ a]D
ˆ
217.8 (c 0.90, MeOH) [lit.23 [a]D ˆ210.4 (c 0.8,
20
CHCl3)]; IR (®lm, cm21): 3032, 2939, 1497; MS (EI) m/z
371 (M111), 370 (M1); H NMR (300 MHz, CDCl3) d
1
7.34±7.27 (m, 10H, Ph), 5.91 (d, J1,2ˆ4.1 Hz, 1H, HC(1)),
4.66 (d, J1,2ˆ4.1 Hz, 1H, HC(2)), 4.62±4.53 (m, 4H,
CH2OPh), 4.28 (td, J3,4ˆ3.0 Hz, J4,5ˆ6.3 Hz, 1H, HC(4)),
4.04 (d, J3,4ˆ3.0 Hz, 1H, HC(3)), 3.64 (d, J4,5ˆ6.3 Hz, 2H,
HC(5)), 1.45 (s, 3H, CH3), 1.33 (s, 3H, CH3); Anal. calcd for
C22H26O5: C, 71.35; H, 7.03. Found: C, 71.92; H, 6.95.
20
b-anomer: [a]D ˆ214.3 (c 0.8, MeOH) [d-enantiomer:
lit.24 [a]D ˆ252 (c 0.5, CHCl3)]; IR (®lm, cm21): 3032,
20
1
4.1.4. 3,5-O-Dibenzyl-methyl-l-arabinofuranoside (8). A
solution of 7 (7.84 g, 21.19 mmol) in 10% (w/w) hydrogen
chloride in methanol (200 mL) wasstirred at room tempera-
ture for 3 h. After the addition of NaHCO3 (20 g), the
mixture was concentrated to dryness. Ice-water was added
to the residue, then extracted with ethyl acetate (4£100 mL)
and the combined organic layerswere washed with brine,
dried over Na2SO4. The solvent was removed in vacuo and
the residue was puri®ed by ¯ash chromatography (ethyl
acetate/petroleum etherˆ1:3) to give 8 (7.158 g, 98%) as
2908, 1497; MS (EI) m/z 328 (M1); H NMR (300 MHz,
CDCl3) d 7.38±7.26 (m, 10H, Ph), 5.10 (dd, J1,2aˆ5.1 Hz,
J1,2bˆ2.1 Hz, 1H, HC(1)), 4.60±4.56 (m, 4H, OCH2Ph),
4.26 (m, 1H, HC(3)), 4.14 (m, 1H, HC(4)), 3.58±3.47 (m,
2H, HC(5)), 3.30 (s, 3H, OCH3), 2.25±2.09 (m, 2H, HC(2a),
HC(2b)); Anal. calcd for C20H24O4: C, 73.17; H, 7.32.
20
Found: C, 73.01, H, 7.14. a-anomer: [a]D ˆ258.0 (c
0.8, MeOH) [d-enantiomer: lit.24 [a]D ˆ1106 (c 0.5,
20
1
CHCl3)]; H NMR (300 MHz, CDCl3) d 7.36±7.26 (m,
10H, Ph), 5.07 (d, J1,2aˆ5.4 Hz, 1H, HC(1)), 4.58±4.46
(m, 4H, OCH2Ph), 4.25 (dd, J2a,3ˆ8.7 Hz, J3,4ˆ4.3 Hz,
1H, HC(3)), 3.97 (m, 1H, HC(4)), 3.57±3.47 (m, 2H,
HC(5)), 3.41 (s, 3H, OCH3), 2.27±2.17 (m, 2H, HC(2a),
HC(2b)).
20
a colorless oil. [a]D ˆ272.1 (c 1.5, MeOH); IR (®lm,
1
cm21): 3443 (brs), 3032, 2915; MS (EI) m/z 344 (M1); H
NMR (300 MHz, CDCl3) d 7.36±7.25 (m, 10H, Ph), 4.92 (s,
0.57H, HC(1), a-anomer), 4.87 (d, J1,2ˆ4.7 Hz, 0.43H,
HC(1), b-anomer), 4.78±4.46 (m, 4H, OCH2Ph), 4.28 (dd,
J2,3ˆ2.5 Hz, J3,4ˆ5.2 Hz, 1H, HC(3)), 4.14 (m, 1H, HC(3)),
3.86 (m, 1H, HC(4)), 3.67 (dd, J4,5aˆ2.2 Hz, J5a,5bˆ10.4 Hz,
1H, HC(5a)), 3.44 (dd, J4,5bˆ2.5 Hz, J5a,5bˆ10.4 Hz, 1H,
HC(5b)), 3.42 (s, 3H, OMe); Anal. calcd for C20H24O5: C,
69.77; H, 6.98. Found: C, 69.77; H, 7.08.
4.1.7. Methyl 2-deoxy-l-ribofuranoside (11). To a solu-
tion of 10 (383 mg, 1.167 mmol) in MeOH (16 mL) was
added 10% Pd±C (100 mg). The mixture wastisrred
under H2 for 3 h at room temperature. The reaction was
worked up by ®ltering and concentrating in vacuo. The
residue was puri®ed by ¯ash chromatography (CH2Cl2/
MeOHˆ10:1) to give 11 (168 mg, 97%) asa white solid.
4.1.5.
3,5-O-Dibenzyl-2-O-tri¯ate-methyl-l-arabino-
20
furanoside (9). A 250 mL three-neck round bottom ¯ask
equipped with two addition funnelswascharged with
pyridine (0.80 mL, 10.23 mmol) and anhydrousCH 2Cl2
(50 mL) under argon. A solution of tri¯ic anhydride
(1.0 mL, 6.5 mmol) in CH2Cl2 (40 mL) wasplaced in one
addition funnel. The sugar 8 (2.037 g, 5.92 mmol) dissolved
in CH2Cl2 (40 mL) wasplaced in the other addition funnel.
The ¯ask was cooled to 210 to 2158C in an ice/salt bath
and the tri¯ic anhydride solution was added dropwise for
30 min. The mixture wasstirred for another 15 min. Then
sugar solution was added dropwise for 30 min and stirring
continued for additional 4 h. The reaction mixture was
poured into ice-water (300 mL). The aqueouslayer was
extracted with CH2Cl2 (2£400 mL). The combined extract
[a]D ˆ248 (c 0.8, MeOH); IR (KBr) nmax 3393 (brs),
1
2935; MS (EI) m/z 148 (M1), 117 (M12OMe); H NMR
(300 MHz, D2O) d 5.22 (m, 1H, HC(1)), 4.29 (m, 1H, H(3)),
4.07 (m, 1H, HC(4)), 3.64±3.56 (m, 2H, HC(5)), 3.37 (s,
3H, OMe), 2.38±1.87 (m, 2H, HC(2)) [lit.25]; HRMS (EI):
(M12OMe), found 117.0552. C5H9O3 requires117.0559.
4.1.8. l-2-Deoxyribose (2). To a solution of 11 (140 mg,
0.95 mmol) in 10 mL water wasadded Dowex reisn [H
1
form] (200 mg). The mixture wasstirred at 60 8C for 24 h.
The reaction wasworked up by ®ltering and concentrating
in vacuo. The residue was puri®ed by ¯ash chromatography
(CH2Cl2/MeOHˆ5:1) to give 2 (124 mg, 98%) asa white
20
solid. [a]D ˆ164.5 (c 1.9, MeOH) [d-enantiomer: lit.26
20
1
wasdried over Na SO4 and the residue puri®ed by ¯ash
[a]D ˆ259 (c 1, H2O)]; H NMR (300 MHz, CD3OD) d
5.36 (dd, J1,2aˆ3.2 Hz, J1,2bˆ4.3 Hz, 0.4H, HC(1)), 4.91
(dd, J1,2aˆ3.2 Hz, J1,2bˆ7.2 Hz, 0.6H, HC(1)), 4.24±3.93
(m, 2H, HC(3), HC(4)), 3.90±3.51 (m, 2H, HC(5)), 2.35±
1.83 (m, 2H, HC(2a), HC(2b)).
2
chromatography (ethyl acetate/petroleum etherˆ1:15)
20
gave 9 (2.790 g, 99%) asa yellow oil. [ a]D ˆ2124 (c
1.9, MeOH); IR (®lm, cm21): 3034, 2935, 1498, 1419;
1
MS (EI) m/z 476 (M1); H NMR (300 MHz, CDCl3) d
7.38±7.22 (m, 10H, Ph), 5.20 (s, 0.73H, HC(1), a-anomer),
5.09 (m, 1H, HC(2)), 5.00 (d, J1,2ˆ4.4 Hz, 0.23H, HC(1),
b-anomer), 4.73±4.48 (m, 4H, OCH2Ph), 4.21±4.11 (m, 2H,
4.1.9. Methyl 3,5-O-dibenzyl-2-O-methanesulfonyl-l-
arabinofuranoside (12). To a solution of 8 (5.00 g,

3292
Z.-D. Shi et al. / Tetrahedron 58 (2002) 3287±3296
14.53 mmol) in anhydrousCH Cl2 (125 mL) wasadded
2
10% Pd±C (150 mg). The mixture wastsirred under H
for 2 h at room temperature. The reaction wasworked up
by ®ltering and concentrating in vacuo. The residue was
2
triethylamine (5.6 mL, 40 mmol) and methanesulfonyl
chloride (1.66 mL, 21.8 mmol). The solution was stirred at
room temperature overnight. Then the solution was diluted
with CH2Cl2 (200 mL), washed with water, brine, dried over
Na2SO4. The solvent was removed in vacuo and the residue
waspuri®ed by ¯ash chromatography (ethyl acetate/petro-
leum etherˆ1:4) to give 12 (6.01 g, 98%) asa yellow oil.
puri®ed by ¯ash chromatography (CH2Cl2/MeOHˆ8:1) to
20
give 15 (818 mg, 97%) asa white solid. [ a]D ˆ164.8 (c
2.0, H2O) [lit.27 [a]D ˆ146 (c 1.9, H2O)]; IR (KBr): nmax
20
3392 (brs), 2936. MS (EI) m/z 164 (M1), 133 (M12OMe);
1H NMR (300 MHz, DMSO-d6) d 4.61 (d, J1,2ˆ2.9 Hz, 1H,
HC(1)), 3.75±3.70 (m, 3H, HC(2), HC(3), HC(4)), 3.63 (dd,
J4,5aˆ3.6 Hz, J5a,5bˆ11.8 Hz, HC(5a)), 3.56 (m, 1H,
HC(5b)), 3.33 (s, 3H, OMe); HRMS (EI): (M12OMe),
found 133.0501. C5H9O6 requires133.0508.
20
[a]D ˆ272.7 (c 1.5, MeOH); IR (®lm, cm21): 3032, 2937,
1
1497, 1364; MS (EI) m/z 423 (M111), 421 (M121); H
NMR (300 MHz, CDCl3) d 7.34±7.28 (m, 10H, Ph), 5.09
(s, 0.67H, HC(1), a-anomer), 5.01 (m, 1H, HC(2)), 4.96
(d, J1,2ˆ4.4 Hz, 0.33H, b-anomer), 4.76±4.49 (m, 4H,
OCH2Ph), 4.22 (m, 1H, HC(3)), 4.13 (m, 1H, HC(4)),
3.67±3.53 (m, 2H, HC(5)), 3.43 (s, 2H, OCH3, a-anomer),
3.40 (s, 1H, OCH3, b-anomer), 3.04 (s, 1H, CH3, b-anomer),
2.94 (s, 2H, CH3, a-anomer); Anal. calcd for C21H26O7S: C,
59.72; H, 6.16. Found: C, 59.79; H, 6.19.
4.1.13. l-Ribose (3). To a solution of 15 (750 mg, 4.57
mmol) in H2O (40 mL) wasadded Dowex resin [H form]
1
(1.20 g). The mixture wastsirred at 50 8C for 24 h. The
reaction wasworked up by ®ltering and concentrating in
vacuo. The residue was puri®ed by ¯ash chromatography
(CH2Cl2/MeOHˆ4:1) to give 3 (653 mg, 95%) asa white
solid. [a]D ˆ119.2 (c 2.0, H2O) [lit.26 [a]D ˆ119 (c 2.0,
H2O)]; IR (KBr) nmax 3510 (brs), 2939; MS (EI) m/z 151
20
20
4.1.10. 1,5-O-Diacetyl-3-O-benzyl-2-O-methanesulfonyl-
l-arabinofuranose (13). Glacial acetic acid (30 mL) and
Ac2O (7.6 mL) were added to 12 (6.01 g, 14.24 mmol).
The mixture wastsirred for 5 min at 0 8C, then H2SO4
(1.2 mL) wasadded dropwise during 30 min. The mixture
wasstirred until the precipitation occurred, then kept over-
night at 48C. Ice-water (200 mL) wasadded and stirred for
30 min, then the mixture wasextracted with CH 2Cl2
(3£200 mL). The combined organic layerswere wahsed
with a cold sat. NaHCO3 solution (3£200 mL), brine,
dried over Na2SO4. The solvent was removed in vacuo
and the residue puri®ed by ¯ash chromatography (ethyl ace-
tate/petroleum etherˆ1:3) gave 13 (5.10 g, 89%) asa color-
(M111), 133 (M12OH); H NMR (300 MHz, CD3OD) d
1
4.93 (d, J1,2ˆ5.0 Hz, 0.57H, HC(1), b-anomer), 4.78 (d,
J1,2ˆ1.5 Hz, 0.43H, HC(1), a-anomer), 3.94±3.82 (m, 2H,
HC(2), HC(3)), 3.77±3.61 (m, 2H, HC(4), HC(5a)), 3.48
(m, 1H, HC(5b)); Anal. calcd for C5H10O5´0.1H2O: C,
39.53; H, 6.72. Found: C, 39.51; H, 6.79.
4.1.14. Methyl 2,5-O-diacetyl-3-O-benzyl-b-l-ribofurano-
side (16). To a solution of 14 (4.46 g, 19.12 mmol) in pyri-
dine (60 mL) wasadded Ac O (16 mL). The mixture was
2
stirred at room temperature overnight. The mixture was
evaporated in vacuo. Then a cold sat. NaHCO3 solution
(100 mL) wasadded to the reisdue. The mixture was
extracted with CH2Cl2 (3£100 mL), washed with CuSO4
solution, brine, dried over Na2SO4. The solvent was
removed in vacuo. The residue was puri®ed by ¯ash
chromatography (ethyl acetate/petroleum etherˆ1:10) to
less oil. [a]D ˆ152.5 (c 1.5, MeOH); IR (®lm, cm21):
20
1
3030, 2939, 1740, 1355; MS (EI) m/z 343 (M12OAc); H
NMR (300 MHz, CDCl3) d 7.38±7.35 (m, 5H, Ph), 6.24 (s,
1H, HC(1)), 5.14 (d, J2,3ˆ1.6 Hz, 1H, H(2)), 4.78 (d, Jˆ
11.9 Hz, 1H, OCH2Ph), 4.62 (d, Jˆ11.9 Hz, 1H, OCH2Ph),
4.40 (m, 1H, HC (4)), 4.27 (dd, J4,5aˆ3.8 Hz, J5a,5b
ˆ
20
12.3 Hz, 1H, HC(5a)), 4.18 (m, 1H, HC(3)), 4.15 (dd,
J4,5bˆ5.3 Hz, J5a,5bˆ12.3 Hz, 1H, HC(5b)), 3.14 (s, 3H),
2.14 (s, 3H, OAc), 2.05 (s, 3H, OAc); HRMS (EI):
(M12OAc±Ac), found 300.0668. C13H16SO6 requires
300.0631.
give 16 (5.571 g, 86%) asa colorlesoil. [ a]D ˆ213.1
(c 1.0, MeOH); IR (®lm, cm21): 3034, 2938, 1751, 1744,
1
1498; MS (EI) m/z 338 (M1), 307 (M12OMe); H NMR
(300 MHz, CDCl3) d 7.35±7.29 (m, 5H, Ph), 5.21 (d,
J2,3ˆ4.3 Hz, 1H, HC(2)), 4.86 (s, 1H, HC(1)), 4.61 (d, Jˆ
11.4 Hz, 1H, OCH2Ph), 4.43 (d, Jˆ11.4 Hz, 1H, OCH2Ph),
4.29 (d, J4,5aˆ3.1 Hz, J5a,5bˆ11.5 Hz, 1H, HC(5a)), 4.21
(ddd, J3,4ˆ7.8 Hz, J4,5aˆ3.1 Hz, J4,5bˆ6.1 Hz, 1H, HC(4)),
4.12 (dd, J2,3ˆ4.3 Hz, J3,4ˆ7.8 Hz, 1H, HC(3)), 4.06 (dd,
J4,5bˆ6.1 Hz, J5a,5bˆ11.6 Hz, 1H, HC(5b)), 3.34 (s, 3H,
OMe), 2.13 (s, 3H, OAc), 2.05 (s, 3H, OAc); Anal. calcd
for C17H22O7: C, 60.36; H, 6.51. Found: C, 60.39; H, 6.62.
4.1.11. Methyl 3-O-Benzyl-b-l-ribofuranoside (14). To a
solution of 13 (2.50 g, 6.22 mmol) in methanol (50 mL) was
added NaOMe/MeOH solution (100 mL, 18.7 mmol). The
mixture wasstirred at room temperature for 6 h. HCl (1 mol/
L) solution was added to neutralize the mixture. The
mixture wasconcentrated in vacuo and the reisdue was
puri®ed by ¯ash chromatography (CH2Cl2/MeOHˆ30:1)
20
to give 14 (1.378 g, 87%) asa yellow reisdue. [ a]D
ˆ
4.1.15. 1,2,5-O-Triacetyl-3-O-benzyl-b-l-ribofuranose
(17). Compound 16 (2.814 g, 8.31 mmol) wastreated as
the preparation of compound 13. Puri®cation by ¯ash
chromatography (ethyl acetate/petroleum etherˆ1:4) gave
19.1 (c 0.5, MeOH); IR (®lm, cm21): 3415 (brs), 3032,
2931. MS (EI) m/z 254 (M1); 1H NMR (300 MHz,
CDCl3) d 7.41±7.31 (m, 5H, Ph), 4.87 (s, 1H, HC(1)),
4.56 (s, 2H, OCH2Ph), 4.23±4.11 (m, 2H, HC(3), HC(4)),
4.04 (d, J2,3ˆ4.2 Hz, 1H, HC(2)), 3.77 (dd, J4,5aˆ2.2 Hz,
J5a,5bˆ12.0 Hz, 1H, HC(5a)), 3.55 (dd, J4,5bˆ3.3 Hz,
J5a,5bˆ12.0 Hz, 1H, HC(5b)), 3.40 (s, 3H, OMe); HRMS
(EI): (M1), found 254.1154. C13H18O5 requires254.1178.
17 (b-anomer, 2.318 g, 76%) and its a-anomer (584 mg,
20
17%) asa colorlesoil.
MeOH); IR (®lm, cm21): 3030, 2939, 1747, 1455; MS
b-anomer: [a]D ˆ222.3 (c 0.8,
1
(EI) m/z 307 (M12OAc); H NMR (300 MHz, CDCl3) d
7.37±7.27 (m, 5H, Ph), 6.15 (s, 1H, HC(1)), 5.32 (d, J2,3ˆ
4.4 Hz, 1H, HC(2)), 4.65 (d, Jˆ11.3 Hz, 1H, OCH2Ph),
4.46 (d, Jˆ11.3 Hz, 1H, OCH2Ph), 4.29 (dd, J4,5aˆ3.4 Hz,
4.1.12. Methyl b-l-ribofuranoside (15). To a solution of
14 (1.305 g, 5.14 mmol) in methanol (60 mL) wasadded
J5a,5bˆ10.0 Hz, 1H, HC(5a)), 4.27 (dd, J4,5bˆ3.0 Hz, J5a,5b
ˆ

Z.-D. Shi et al. / Tetrahedron 58 (2002) 3287±3296
3293
1
11.0 Hz, 1H, HC(5b)), 4.14±4.09 (m, 2H, HC(3), HC(4)),
2.15 (s, 3H, OAc), 2.08 (s, 3H, OAc), 2.03 (s, 3H, OAc);
Anal. calcd for C18H22O8 C, 59.02; H, 6.01. Found: C,
(M12base); H NMR (300 MHz, CDCl3) d 8.81 (s, 1H,
NH), 7.69 (d, Jˆ6.3 Hz, 1H, HC(6)), 7.38±7.29 (m, 5H,
0
0
0
0
0
Ph), 5.93 (dd, J1 ,2 ˆ2.6 Hz, J1 ,4 ˆ1.2 Hz, 1H, HC(1 )),
1
0
0
0
0
0
58.96; H, 6.11. a-anomer: H NMR (300 MHz, CDCl3) d
5.38 (dd, J1 ,2 ˆ2.6 Hz, J2 ,3 ˆ5.1 Hz, 1H, HC(2 )), 4.65
7.37±7.33 (m, 5H, Ph), 7.06 (d, J1,2ˆ4.9 Hz, 1H, HC(1)),
5.43 (t, J1,2ˆJ2,3ˆ5.0 Hz, 1H, HC(2)), 5.28 (m, 1H, HC(4)),
4.68 (d, 1H, Jˆ11.4 Hz, 1H, OCH2Ph), 4.61 (d, Jˆ11.4 Hz,
1H, OCH2Ph), 4.44 (dd, J4,5aˆ3.3 Hz, J5a,5bˆ12.1 Hz,
HC(5a)), 4.13 (dd, J4,5bˆ6.2 Hz, J5a,5bˆ12.1 Hz, 1H,
HC(5b)), 3.84 (t, J2,3ˆJ3,4ˆ5.2 Hz, 1H, HC(3)), 2.13 (s,
3H, OAc), 2.06 (s, 3H, OAc), 2.02 (s, 3H, OAc).
(d, Jˆ11.5 Hz, 1H, OCH2Ph), 4.44 (d, Jˆ11.5 Hz, 1H,
OCH2Ph), 4.31±4.25 (m, 3H, HC(40), HC(5a0), HC(5b0)),
0
0
0
0
0
4.04 (dd, J2 ,3 ˆ5.2 Hz, J3 ,4 ˆ7.2 Hz, 1H, HC (3 )), 2.18 (s,
3H, OAc), 2.03 (s, 3H, OAc); HRMS (EI): (M12base±Ac),
found 264.0998. C14H16O5 required 264.0991.
4.1.19. 30-O-Benzyl-b-l-thymidine (19b). Compound 18b
(382 mg, 0.884 mmol) wasodslivsed in MeOH/THF
(v/vˆ2:1, 6 mL), then NH3 (35% in water, 11 mL) was
added. The mixture wasstirred overnight at 60 8C in a sealed
tube. After evaporation to dryness, the residue was puri®ed
by ¯ash chromatography (CH2Cl2/MeOHˆ10:1) to afford
4.1.16. 20,50-O-Diacetyl-30-O-benzyl-b-l-uridine (18a).
Compound 17 (364 mg, 1.0 mmol) and uracil (334 mg,
3.0 mmol) were co-evaporated three timeswith anhydrous
CH3CN under argon. AnhydrousCH 3CN (16 mL) and BSA
(0.74 mL, 3.0 mmol) were added at room temperature. The
mixture wastsirred at 60±65 8C until the base dissolved.
TMSOTf (174 mL, 1.48 mmol) wasadded, the mixture
stirred overnight at 658C. CH2Cl2 (150 mL) wasadded
and the mixture was washed with sat. NaHCO3 solution
and dried over Na2SO4. The solvent was removed in
vacuo and the residue was puri®ed by ¯ash chromatography
(ethyl acetate/petroleum etherˆ2:1) to afford 18a (383 mg,
20
19b (286 mg, 93%) asa white foam. [ a]D ˆ227.5 (c
1.6, MeOH); IR (KBr) nmax 3419 (brs), 3030, 2929, 1472;
MS (EI) m/z 349 (M11H); H NMR (300 MHz, CDCl3) d
1
9.63 (s, 1H, NH), 7.35±7.32 (m, 6H, Ph, HC(6)),05.63 (d,
0
0
0
J1 ,2 ˆ5.2 Hz, 1H, HC(1 )), 5.29 (m, 1H, HC(4 )), 4.68
(d, Jˆ11.7 Hz, 1H, OCH2Ph), 4.63 (d, Jˆ11.7 Hz, 1H,
0
0
0
0
OCH2Ph), 4.48 (dd, J2 ,3 ˆ5.4 Hz, J3 ,4 ˆ5.8 Hz, 1H,
HC(30)), 4.20 (dd, J1 ,2 ˆ4.3 Hz, J2 ,3 ˆ5.4 Hz, 1H,
HC(20)), 3.87 (m, 1H, HC(5a0)), 3.64 (m, 1H, HC(5b0));
Anal. calcd for C17H20O6N2: C, 58.62; H, 5.75; N, 8.05.
Found: C, 58.18; H, 5.75; N, 7.73.
0
0
0
0
20
92%) asa white foam. [ a]D ˆ2190.5 (c 2.4, MeOH); IR
(KBr) nmax 3034, 2828, 1680, 1466, 1380; MS (EI) m/z 419
(M111), 359 (M12OAc), 307 (M12base); 1H NMR
(300 MHz, CDCl3) d 9.07 (s, 1H, NH), 7.40 (d, J5,6ˆ
8.1 Hz, 1H, HC(6)), 7.37±7.29 (m, 5H, Ph), 5.84 (d,
4.1.20. 30-O-Benzyl-b-l-uridine (19a). Compound 18a
(235 mg, 0.562 mmol) and NH3 (35% in water, 7 mL)
were treated as described above. Puri®cation by ¯ash
chromatography (CH2Cl2/MeOHˆ8:1) gave 19a (179 mg,
0
0
0
J1 ,2 ˆ3.0 Hz, 1H, HC(1 )), 5.74 (dd, J3,5ˆ2.0 Hz, J5,6ˆ
0
0
0
0
8.0 Hz, 1H, HC(5)), 5.41 (dd, 1H, J1 ,2 ˆ3.0 Hz, J2 ,3
ˆ
5.4 Hz, 1H, HC(20)), 4.63 (d, Jˆ11.6 Hz, 1H, OCH2Ph),
20
0
0
4.46 (d, Jˆ11.6, 1H, OCH2Ph), 4.30 (d, J4 ,5a ˆ4.1 Hz,
95%) asa white foam. [ a]D ˆ210.6 (c 0.6, MeOH); IR
0
0
0
0
J5a ,5b ˆ13.1 Hz, 1H, HC(5a )), 4.26±4.20 (m, 2H, HC(4 ),
HC(5b0)), 4.13 (m, 1H, HC(30)), 2.16 (s, 3H, OAc), 2.03 (s,
3H, OAc); HRMS (EI): (M12base), found 307.1182.
C14H17O5 requires307.1172.
(KBr) nmax 3389 (brs), 3037, 2819, 1464; MS (EI) m/z 335
(M111), 223 (M12base); 1H NMR (300 MHz, DMSO-d6)
d 10.15 (s, 0.16H, NH), 7.89 (d, J5,6ˆ8.1 Hz, 1H, HC(6)),
0
0
0
7.40±7.28 (m, 5H, Ph), 5.83 (d, J1 ,2 ˆ5.8 Hz, 1H, HC(1 )),
5.66 (d, J5,6ˆ8.1 Hz, 1H, HC(5)), 4.71 (d, Jˆ12.1 Hz, 1H,
4.1.17. 20,50-O-Diacetyl-30-O-benzyl-b-l-thymidine (18b).
Compound 17 (334 mg, 0.913 mmol) and thymine (345 mg,
2.74 mmol) were treated asdescribed above. Puri®cation by
OCH2Ph), 4.58 (d, Jˆ12.1 Hz, 1H, OCH2Ph), 4.23
0
0
0
0
0
(t, J1 ,2 ˆ5.6 Hz, J2 ,3 ˆ5.4 Hz, 1H, HC(2 )), 4.03 (m, 1H,
HC(40)), 3.92 (dd, J2 ,3 ˆ4.6 Hz, J3 ,4 ˆ4.1 Hz, 1H, HC(3 )),
0
0
0
0
0
0
0
0
0
0
¯ash chromatography (ethyl acetate/petroleum etherˆ3:2)
3.62 (dd, J4 ,5a ˆ3.3 Hz, J5a ,5b ˆ12.1 Hz, 1H, HC(5a )), 3.53
20
0
0
0
0
0
afforded 18b (346 mg, 88%) asa white foam. [ a]D
ˆ
(dd, J4 ,5b ˆ3.0 Hz, J5a ,5b ˆ12.1 Hz, 1H, HC(5 )); HRMS
(EI): (M12OBn), found 227.0668. C9H11O5N2 requires
227.0670.
223.4 (c 0.6, MeOH); IR (KBr) nmax 3197 (brs), 2903,
1748, 1649, 1465, 1373; MS (EI) m/z 372 (M12AcOH),
307 (M12base); 1H NMR (300 MHz, CDCl3) d 8.59 (s, 1H,
NH), 7.38±7.30 (m, 5H,0 Ph), 7.14 (s, 1H, HC(6)), 5.85 (d,
4.1.21. 30-O-Benzyl-b-l-5-¯uorouridine (19c). Compound
18c (207 mg, 0.475 mmol) and NH3 (35% in water, 6 mL)
were treated as described above. Puri®cation by ¯ash
chromatography (CH2Cl2/MeOHˆ13:1) gave 19c (152 mg,
0
0
0
0
0
0
J1 ,2 ˆ3.3 Hz, 1H, HC(1 )), 5.37 (dd, J1 ,2 ˆ3.3 Hz, J2 ,3
ˆ
5.2 Hz, 1H, HC(20)), 4.62 (d, Jˆ11.3 Hz, 1H, OCH2Ph),
0
0
4.46 (d, Jˆ11.3 Hz, 1H, OCH2Ph), 4.31 (dd, J4 ,5a
ˆ
20
0
0
0
4.1 Hz, J5a ,5b ˆ13.1 Hz, 1H, HC(5a )), 4.25±4.19 (m, 2H,
91%) asa white foam. [ a]D ˆ278.8 (c 1.8, MeOH); IR
HC(30), HC(40)), 4.15 (dd, J4 ,5b ˆ6.3 Hz, J5a ,5b ˆ12.8 Hz,
1H, HC(5b0)), 2.14 (s, 3H, OAc), 2.04 (s, 3H, OAc), 1.91 (s,
3H, CH3); Anal. calcd for C21H24O8N2: C, 58.33; H,5.56; N,
6.48. Found: C, 58.22; H, 5.56; N, 6.32.
(KBr) nmax 3449 (brs), 3066, 1474; MS (EI) m/z 353
0
0
0
0
(M111), 223 (M12base); H NMR (300 MHz, CD3OD)
1
d 8.30 (d, J5,6ˆ6.9 Hz, 1H, HC(6)), 7.43±7.29 (m, 5H,
0
0
0
0
0
Ph), 5.93 (dd, J1 ,2 ˆ5.8 Hz, J1 ,4 ˆ1.5 Hz, 1H, HC(1 )),
4.76 (d, Jˆ11.8 Hz, 1H, OCH2Ph), 4.64 (d, Jˆ11.8 Hz,
4.1.18. 20,50-O-Diacetyl-30-O-benzyl-b-l-5-¯urouridine
(18c). Compound 17 (350 mg, 0.96 mmol) and 5-¯urouracil
(373 mg, 2.87 mmol) were treated asdecsribed above.
Puri®cation by ¯ash chromatography (ethyl acetate/petro-
leum etherˆ2:1) gave 18c (371 mg, 89%) asa white foam.
1H, OCH2Ph), 4.31 (t, J1 ,2 ˆ4.9 Hz, J2 ,3 ˆ5.0 Hz, 1H,
0
0
0
0
HC(20)), 4.15 (ddd, J3 ,4 ˆ4.9 Hz, J4 ,5a ˆ2.8 Hz, J4 ,5b
ˆ
0
0
0
0
0
0
1.5 Hz, 1H, HC(40)), 4.06 (t, J2 ,3 ˆ5.0 Hz, J3 ,4 ˆ4.9 Hz,
0
0
0
0
1H, HC(30)), 3.85 (dd, J4 ,5a ˆ2.8 Hz, J5a ,5b ˆ12.3 Hz, 1H,
0
0
0
0
HC(5a0)), 3.68 (dd, J4 ,5b ˆ1.5 Hz, J5a ,5b ˆ12.1 Hz, 1H,
HC(5b0)); HRMS (EI): (M12base), found 223.0970.
C12H15O4 requires223.0969.
0
0
0
0
20
[a]D ˆ244.2 (c 1.0, MeOH); IR (KBr) nmax 3013, 2919,
1739,1716, 1463, 1376; MS (EI) m/z 437 (M111), 307

3294
Z.-D. Shi et al. / Tetrahedron 58 (2002) 3287±3296
4.1.22. b-l-Thymidine (20b). To a solution of 19b
(200 mg, 0.575 mmol) in MeOH (10 mL) wasadded 10%
Pd±C (50 mg). The mixture wasstirred under H 2 for 1 h at
room temperature. The reaction wasworked up by ®ltering
and concentrating in vacuo. The residue was puri®ed by
¯ash chromatography (CH2Cl2/MeOHˆ4:1) to give 20b
pound 21 (1.045 g, 3.60 mmol) wastreated asthe prepara-
tion of compound 13. Puri®cation by ¯ash chromatography
(ethyl acetate/petroleum etherˆ1:3) gave 22 (910 mg, 77%)
asa colorlessoil. [
a]D ˆ140.8 (c 1.7, MeOH) [lit.31
20
20
[a]D ˆ112.1 (c 2.47, CHCl3)]; IR (®lm, cm21): 2931,
1748; MS (EI) m/z 259 (M12OAc); H NMR (300 MHz,
1
20
(147 mg, 98%) asa white oslid. [ a]D ˆ115.6 (c 1.1,
CDCl3) d 6.17 (s, 1H, HC(1)), 5.40±5.33 (m, 2H, HC(2),
HC(3)), 4.39 (m, 1H, HC(4)), 4.34 (dd, J4,5aˆ3.3 Hz,
J5a,5bˆ12.0 Hz, 1H, HC(5a)), 4.15 (dd, J4,5bˆ5.1 Hz,
J5a,5bˆ12.0 Hz, 1H, HC(5b)), 2.15 (s, 3H, OAc), 2.08 (s,
3H, OAc), 2.03 (s, 3H, OAc); Anal. calcd for C13H18O9:
C, 49.06; H, 5.66. Found: C, 48.98; H, 5.69.
20
MeOH) [d-enantiomer: lit.28 [a]D ˆ29.7 (c 1.66, H2O)];
1
MS (EI) m/z 258 (M1); H NMR (300 MHz, DMSO-d6) d
0
0
11.31 (s, 0.25H, NH), 7.74 (s, 1H, HC(6)), 5.78 (d, J1 ,2
0
ˆ
5.6 Hz, 1H, HC(10)), 4.03 (t, J1 ,2 ˆ5.5 Hz, J2 ,3 ˆ5.3 Hz,
0
0
0
1H, HC(20)), 3.96 (dd, J2 ,3 ˆ4.9 Hz, J3 ,4 ˆ3.9 Hz, 1H,
0
0
0
0
HC(30)), 3.80 (q, J3 ,4 ˆ3.9 Hz, J4 ,5a ˆ3.4 Hz, J4 ,5b
ˆ
0
0
0
0
0
0
3.4 Hz, 1H, HC(40)), 3.63 (dd, J4 ,5a ˆ3.4, J5a ,5b ˆ12.1 Hz,
4.1.27. 20,30,50-O-Triacetyl-b-l-5-iodouridine (23a).
Compound 22 (112 mg, 0.352 mmol) and 5-iodouracil
(251 mg, 1.06 mmol) were treated asthe preparation of
compound 18a. Puri®cation by ¯ash chromatography
(ethyl acetate/petroleum etherˆ1:1) afforded 23a (164 mg,
0
0
0
0
1H, HC(5a0)), 3.53 (dd, J4 ,5b ˆ3.4 Hz, J5a ,5b ˆ12.2 Hz, 1H,
HC(5b0)); Anal. calcd for C10H14O6N2´0.25H2O: C, 45.71;
H, 5.52; N, 10.67. Found: C, 45.89; H, 5.44; N, 10.33.
0
0
0
0
20
4.1.23. b-l-Uridine (20a). Compound 19a (157 mg,
0.470 mmol) wastreated asdecsribed above. Puri®cation
by ¯ash chromatography (CH2Cl2/MeOHˆ4:1) gave 20a
94%) asa white foam. [ a]D ˆ1144.1 (c 3.2, MeOH); IR
(KBr) nmax 2906, 1750, 1720, 1693; MS (EI) m/z 497
(M111); 1H NMR (300 MHz, CDCl3) d 7.90 (s, 1H,
20
0
0
0
(111 mg, 97%) asa white foam. [ a]D ˆ214.3 (c 0.4,
HC(6)), 6.08 (d, J1 ,2 ˆ4.7 Hz, 1H, HC(1 )), 5.37±5.29 (m,
2H, HC(20), HC(30)), 4.48±4.28 (m, 3H, HC(40), HC(5a0),
HC(5b0)), 2.26 (s, 3H, OAc), 2.14 (s, 3H, OAc), 2.12 (s, 3H,
OAc); HRMS (EI): (M12AcOH), found 436.9846.
C15H17O9N2I requires436.9877.
H2O) [lit.18 [a]546 ˆ216 (c 0.55, H2O)]; MS (EI) m/z
25
244 (M1), 227 (M12OH), 133 (M12base); 1H NMR
(300 MHz, DMSO-d6) d 7.87 (d, J5,6ˆ8.2 Hz, 1H, HC(6)),
0
0
0
5.78 (d, J1 ,2 ˆ5.2 Hz, 1H, HC(1 )), 5.64 (d, J5,6ˆ8.2 Hz,
0
0
0
0
1H, HC(5)), 4.02 (t, J1 ,2 ˆ5.2 Hz, J2 ,3 ˆ5.2 Hz, 1H,
HC(20)), 3.96 (dd, J2 ,3 ˆ4.9 Hz, J3 ,4 ˆ4.2 Hz, 1H,
4.1.28. 20,30,50-O-Triacetyl-b-l-puridine (23b). Com-
pound 22 (171 mg, 0.538 mmol) and purine (195 mg,
1.62 mmol) were treated asdecsribed above. Puri®cation
by ¯ash chromatography (CH2Cl2/MeOHˆ12:1) gave 23b
0
0
0
0
HC(30)), 3.80 (q, J3 ,4 ˆ3.6 Hz, J4 ,5a ˆ3.3 Hz, J4 ,5b
ˆ
ˆ
ˆ
0
0
0
0
0
0
0
0
3.3 Hz, 1H, HC(40)), 3.62 (dd, J4 ,5a ˆ3.3 Hz, J5a ,5b
0
0
0
12.1 Hz, 1H, HC(5a0)), 3.54 (dd, J4 ,5b ˆ3.3 Hz, J5a ,5b
0
0
0
20
12.2 Hz, 1H, HC(5b0)); HRMS (EI): (M12H2O), found
(169 mg, 83%) asa white foam. [ a]D ˆ120.3 (c 3.0,
20
226.0590. C9H10O5N2 requires226.0595.
MeOH) [d-enantiomer: lit.32 [a]D ˆ210.8 (c 1.5,
MeOH)]; IR (KBr) nmax 3105, 1750,1641; MS (EI) m/z
1
4.1.24. b-l-5-Fluorouridine (20c). Compound 19c (126
mg, 0.361 mmol) wastreated asdecsribed above. Puri®-
cation by ¯ash chromatography (CH2Cl2/MeOHˆ4:1)
378 (M1), H NMR (300 MHz, CDCl3) d 9.17 (s, 1H,
HC(6)), 9.00 (s, 1H, HC(2)), 8.25 (s, 1H, HC(8)), 6.25 (d,
0
0
0
0
0
0
0
J1 ,2 ˆ5.2 Hz, 1H, HC(1 )), 5.98 (t, J1 ,2 ˆ5.2 Hz, J2 ,3
ˆ
20
5.5 Hz, 1H, HC(20)), 5.68 (t, J2 ,3 ˆ5.5 Hz, J3 ,4 ˆ4.7 Hz,
0
0
0
0
gave 20c (91 mg, 95%) asa white foam. [ a]D ˆ28.2 (c
0.7, H2O) [d-enantiomer: lit.29 [a]D ˆ117 (c 2.0, H2O)];
1H, HC(30)), 4.48±4.43 (m, 2H, HC(40), HC(5a00)), 4.37
20
MS (EI) m/z 263 (M111); 1H NMR (300 MHz, CD3OD) d
(dd, J4 ,5b ˆ5.2 Hz, J5a ,5b ˆ12.9 Hz, 1H, HC (5b )), 2.15
(s, 3H, OAc), 2.11 (s, 3H, OAc), 2.07 (s, 3H, OAc);
HRMS (EI): (M12base), found 259.0818. C11H15O7
requires259.0777.
0
0
0
0
0
0
8.32 (d, J5,6ˆ7.0 Hz, 1H, HC(6)), 5.90 (dd, J1 ,2 ˆ3.8 Hz,
0
0
0
0
J1 ,4 ˆ1.6 Hz, 1H, HC(1 )), 4.20±4.15 (m, 2H, HC(2 ),
HC(3)), 4.02 (m, 1H, HC(40)), 3.88 (dd, J4 ,5a ˆ2.6 Hz,
0
0
0
0
0
0
0
J5a ,5b ˆ12.2 Hz, 1H, HC(5a )), 3.76 (dd, J4 ,5b ˆ2.6 Hz,
1
J5a ,5b ˆ12.2 Hz, 1H, HC(5b )); HRMS (EI): (M 2base),
4.1.29.
20,30,50-O-Triacetyl-N6-benzoyl-b-l-adenosine
(23c). Compound 22 (172 mg, 0.541 mmol) and 6-N-
0
found 133.0501. C5H9O4 requires133.0513.
0
0
benzoyladenine (384 mg, 1.62 mmol) were co-evaporated
three timeswith anhydrousCH CN under argon. Anhydrous
4.1.25. Methyl 2,3,5-O-triacetyl-b-l-ribofuranoside (21).
Compound 15 (717 mg, 4.37 mmol) wastreated asthe
preparation of compound 16. Puri®cation by ¯ash chroma-
tography (ethyl acetate/petroleum etherˆ1:5) gave 21
3
CH3CN (5 mL) and MFTSA (0.60 mL, 3.14 mmol) were
added at room temperature. The mixture wastsirred at
60±658C until the base dissolved. TMSOTf (0.15 mL,
0.80 mmol) wasadded, the mixture tsirred overnight at
658C. CH2Cl2 (100 mL) wasadded and the mixture was
washed with sat. NaHCO3 solution, dried over Na2SO4.
The solvent was removed in vacuo. The residue was puri®ed
by ¯ash chromatography (CH2Cl2/MeOHˆ15:1) to afford
20
(1.321 g, 98%) asa colorlesoil. [ a]D ˆ123.8 (c 0.8,
MeOH) [lit.30 [a]D ˆ114.6 (c 2.3, MeOH)]; IR (®lm,
22
cm21): 2943, 1749, 1442; MS (EI) m/z 290 (M1), 259
(M12OMe); 1H NMR (300 MHz, CDCl3) d 5.34 (dd,
J2,3ˆ4.8 Hz, J3,4ˆ6.6 Hz, 1H, HC(3)), 5.23 (d, J2,3ˆ
20
4.8 Hz, 1H, HC(2)), 4.91 (s, 1H, HC(1)), 4.37 (dd, J4,5a
ˆ
23c (218 mg, 81%) asa white foam. [ a]D ˆ116.8 (c,
3.8 Hz, J5a,5bˆ11.5 Hz, 1H, HC(5a)), 4.30 (m 1H, HC(4)),
4.11 (dd, J4,5bˆ5.3 Hz, J5a,5bˆ11.5 Hz, 1H, HC(5b)), 3.39
(s, 3H, OMe), 2.12 (s, 3H, OAc), 2.10 (s, 3H, OAc), 2.06 (s,
3H, OAc).
MeOH); IR (KBr) nmax 3005, 1749, 1612, 1583; MS (EI)
m/z 497 (M1), 438 (M12OAc); 1H NMR (300 MHz,
CDCl3) d 9.20 (brs, 1H, NH), 8.81 (s, 1H, HC(8)), 8.20
0
0
(s, 1H, HC(2)), 8.05±7.51 (m, 5H, Ph), 6.27 (d, J1 ,2
0
ˆ
5.5 Hz, 1H, HC(10)), 5.97 (t, J1 ,2 ˆ5.5 Hz, J2 ,3 ˆ5.2 Hz,
0
0
0
0
0
0
0
4.1.26. 1,2,3,5-O-Tetracetyl-b-l-ribofuranose (22). Com-
1H, HC(20)), 5.68 (dd, J2 ,3 ˆ5.2 Hz, J3 ,4 ˆ4.4 Hz, 1H,

Z.-D. Shi et al. / Tetrahedron 58 (2002) 3287±3296
3295
0
HC(30)), 4.48±4.37 (m, 3H, HC(40), HC (5a0), HC(5b0)),
2.16 (s, 3H, OAc), 2.14 (s, 3H, OAc), 2.09 (s, 3H, OAc);
HRMS (EI): (M12base), found 259.0818. C11H15O7
requires259.0830.
J4 ,5a ˆ3.0 Hz, J5a ,5b ˆ12.2 Hz, 1H, HC(5a )), 3.93 (dd,
0
0
0
0
0
0
0
0
0
J4 ,5b ˆ3.3 Hz, J5a ,5b ˆ12.3 Hz, 1H, HC(5b )).
Acknowledgements
4.1.30. N2-Acetyl-6-O-diphenylcarbamoyl-20,30,50-O-tri-
acetyl-b-l-guanosine (23d). Compound 22 (107 mg,
0.336 mmol) and N2-acetyl-O6-diphenylcarbamoylguanine
(190 mg, 0.51 mmol) were treated asdecsribed above.
Puri®cation by ¯ash chromatography (ethyl acetate/petro-
leum etherˆ2:1) gave 23d (187 mg, 86%) asa white foam.
We thank the state ministry of science and technology of
china for ®nancial support.
References
20
[a]D ˆ16.2 (c 0.4, MeOH); IR (KBr) nmax 3107, 1744,
1622; MS (EI) m/z 259 (M12base); H NMR (300 MHz,
1
1. Furman, P. A.; Fyle, J. A.; St. Clair, M. H.; Weinhold, K.;
Rideout, J. L.; Freeman, G. A.; Nusinoff-Lehrman, S.;
Bolognesi, D. P.; Broder, S.; Mitsuya, H.; Barry, D. W.
Proc. Natl Acad. Sci. USA 1986, 83, 8333.
CDCl3) d 8.20 (brs, 1H, NH), 8.06 (s, 1H, HC(8)), 7.45±
0
0
0
7.20 (m, 10H, NPh2), 6.11 (d, J1 ,2 ˆ4.7 Hz, 1H, HC(1 )),
0
0
0
0
0
5.90 (t, J1 ,2 ˆ5.2 Hz, J2 ,3 ˆ5.2 Hz, 1H, HC(2 )), 5.73 (t,
0
0
0
0
0
J2 ,3 ˆ5.0 Hz, J3 ,4 ˆ5.0 Hz, 1H, HC(3 )), 4.49±4.43 (m,
2. Yarchoan, R.; Perno, C. F.; Thomas, R. V.; Klecker, R. W.;
Allain, R. P.; Wills, R. J.; McAtee, N.; Fishl, M. A.; Dubinsky,
R.; McNeely, M. C.; Mitsuya, H.; Pluda, J. M.; Lawley, T. J.;
Leuther, M.; Safai, B.; Collins, J. M.; Myers, C. E.; Broder, S.
Lancet 1988, 1, 76.
2H, HC(40), HC(5a0)), 4.41 (dd, J4 ,5b ˆ6.3 Hz, J5a ,5b
ˆ
0
0
0
0
11.7 Hz, 1H, HC(5b0)), 2.47 (s, 3H, NHAc) 2.15 (s, 3H,
OAc), 2.09 (s, 3H, OAc), 2.05 (s,3H, OAc).
Compound 23a±d wastreated asthe preparation of
compound 19a. Puri®cation by ¯ash chromatography
(CH2Cl2/MeOHˆ4:1) afforded 24a±d aswhite foams.
3. Lin, T.-S.; Schinazi, R. F.; Prusoff, W. H. Biochem. Pharma-
col. 1987, 36, 2713.
4. Arts, A. J.; Wainberg, M. A. Antimicrob. Agents. Chemother.
1996, 40, 527.
20
4.1.31. b-l-5-Iodouridine (24a). Yield: 93%. [a]D
ˆ
5. Styrt, B. A.; Piazza-Hepp, T. D.; Chikami, G. K. Antiviral Res.
1998, 40, 19.
167.6 (c 2.2, MeOH) [d-enantiomer: lit.33 [a]D ˆ227.5
25
(c 0.13, H2O)]; MS (EI) m/z 370 (M1); MS (ESI) m/z 393.0
6. Schinazi, R. F.; Chu, C. K.; Deck, A.; Mcmillan, A.; Mathis,
R.; Cannon, D.; Jeong, L. S.; Beach, J. W.; Choi, W.-B.;
Yeola, S.; Liotta, D. C. Antimicrob. Agents. Chemother.
1992, 36, 672.
1
(M11Na); H NMR (300 MHz, CD3OD) d 8.71 (s, 1H,
0
0
0
HC(6)), 6.07 (d, J1 ,2 ˆ3.5 Hz, 1H, HC(1 )), 4.39±4.34 (m,
2H, HC(20), HC(30)), 4.24 (m, 1H, HC(400)), 4.07 (dd,
0
0
0
0
J4 ,5a ˆ2.6 Hz, J5a ,5b ˆ12.2 Hz, 1H, HC(5a )), 3.94 (dd,
7. Spadari, S.; Maga, G.; Focher, F.; Ciarroocchi, G.;
Manservigi, R.; Arcamone, F.; Capobinaco, M.; Carcuro, A.;
Colonna, F.; Iotti, S.; Garbesi, A. J. Med. Chem. 1992, 35,
4214.
0
0
0
0
0
J4 ,5b ˆ2.5 Hz, J5a ,5b ˆ12.2 Hz, 1H, HC(5b )).
20
4.1.32. b-l-Puridine (24b). Yield: 91%. [a]D ˆ136.0 (c
1.2, MeOH) [d-enantiomer: lit.34 [a]D ˆ246.8 (c 2.0,
35
8. (a) Chang, C.-N.; Doong, S.-L.; Zhou, J. H.; Beach, J. W.;
Jeong, L. S.; Chu, C. K.; Tsai, C.-H.; Cheng, Y.-C. J. Biol.
Chem. 1992, 267, 13938. (b) Beach, J. W.; Jeong, L. S.; Alves,
A. J.; Pohl, D.; Kim, H. O.; Chang, C.-N.; Coong, S.-L.;
Schinazi, R. F.; Cheng, Y.-C.; Chu, C. K. J. Org. Chem.
1992, 57, 2217.
H2O)]; MS (EI) m/z 235 (M12OH); MS (ESI) m/z 252.1
(M1); 1H NMR (300 MHz, CD3OD) d 9.31 (s, 1H, HC(6)),
9.13 (s, 1H, HC(2)), 8.99 (s, 1H, HC(8)), 6.37 (d,
0
0
0
0
0
0
0
J1 ,2 ˆ5.5 Hz, 1H, HC(1 )), 4.95 (t, J1 ,2 ˆ5.3 Hz, J2 ,3
ˆ
5.3 Hz, 1H, HC(20)), 4.58 (dd, J2 ,3 ˆ5.1 Hz, J3 ,4 ˆ3.7 Hz,
0
0
0
0
1H, HC(30)), 4.37 (m, 1H, HC(40)), 4.10 (dd, J4 ,5a ˆ3.0 Hz,
0
0
9. Furman, P. A.; Davis, M.; Liotta, D. C.; Paff, M.; Frick, L. W.;
Nelson, D. J.; Dornsife, R. E.; Wurster, J. A.; Wilson, L. J.;
Fyfe, J. A.; Tuttle, J. V.; Miller, W. H.; Conderay, L.; Averett,
D. R.; Schinzai, R. F.; Painter, G. R. Antimicrob. Agents
Chemother. 1992, 36, 2686.
0
0
0
0
0
J5a ,5b ˆ12.3 Hz, 1H, HC (5a )), 3.98 (dd, J4 ,5b ˆ3.3 Hz,
0
0
0
J5a ,5b ˆ12.3 Hz, 1H, HC(5b )).
20
4.1.33. b-l-Adenosine (24c). Yield: 94%. [a]D ˆ130.7 (c
0.65, MeOH) [lit.18 [a]546 ˆ187 (c 0.45, 1.25 M NaOH)];
25
10. Mansuri, M. M.; Farina, V.; Starrett Jr, J.; Benigni, D. A.;
Brankovan, V.; Martin, J. C. Bioorg. Med. Chem. Lett. 1991,
1, 65.
MS (EI) m/z 250 (M12OH); MS (ESI) m/z 290.1
1
(M11Na); H NMR (300 MHz, DMSO-d6) d 8.57 (s, 1H,
0
0
HC(8)), 8.42 (s, 1H, HC(2)), 6.20 (d, J1 ,2 ˆ6.5 Hz,
11. (a) Lin, T.-S.; Luo, M.-Z.; Liu, M.-C.; Pai, B.; Dustchman,
G. E.; Cheng, Y.-C. J. Med. Chem. 1994, 37, 798.
(b) Gosselin, G.; Schinazi, R. F.; Sommadossi, J.-P.; Mathe,
C.; Bergogne, M.-C.; Aubertin, A.-M.; Kirn, A.; Imbach, J.-L.
Antimicrob. Agents Chemother. 1994, 38, 1292.
12. Chu, C. K.; Ma, T. W.; Shanmuganathan, K.; Wang, C. G.;
Xiang, Y. J.; Pai, S. B.; Yao, G.-Q.; Sommaclossi, J.-P.;
Cheng, Y.-C. Antimicrob. Agents. Chemother. 1995, 39, 979.
13. Abe, Y.; Takizawa, T.; Kunieda, T. Chem. Pharm. Bull. 1980,
28, 1324.
1H, HC(10)), 4.95 (dd, J1 ,2 ˆ6.2 Hz, J2 ,3 ˆ5.2 Hz, 1H,
0
0
0
0
HC(20)), 4.52 (dd, J2 ,3 ˆ5.0 Hz, J3 ,4 ˆ2.7 Hz, 1H,
0
0
0
0
HC(30)), 4.36 (m, 1H, HC(40)), 4.06 (dd, J4 ,5a ˆ2.7 Hz,
0
0
0
0
0
0
0
J5a ,5b ˆ12.4 Hz, 1H, HC(5a )), 3.94 (dd, J4 ,5b ˆ2.9 Hz,
0
0
0
J5a ,5b ˆ12.4 Hz, 1H, HC(5b )).
20
4.1.34. b-l-Guanosine (24d). Yield: 91%. [a]D ˆ18.3 (c
25
0.5, MeOH) [lit.18 [a]546 ˆ180 (c 0.85, 1.25 M NaOH)];
MS (EI) m/z 283 (M1); MS (ESI) m/z 306.1 (M11Na); H
NMR (300 MHz, CD3OD) d 8.71 (s, 1H, HC(8)), 6.04 (d,
1
14. (a) Holy, A.; Sorm, F. Collect. Czech. Chem. Commun. 1969,
34, 3383. (b) Holy, A.; Sorm, F. Collect. Czech. Chem.
Commun. 1972, 37, 4072. (c) Holy, A.; Sorm, F. Collect.
Czech. Chem. Commun 1973, 38, 423.
0
0
0
0
0
0
0
J1 ,2 ˆ5.9 Hz, 1H, HC(1 )), 4.79 (t, J1 ,2 ˆ5.1 Hz, J2 ,3
ˆ
5.4 Hz, 1H, HC(20)), 4.48 (dd, J2 ,3 ˆ5.1 Hz, J3 ,4 ˆ3.4 Hz,
0
0
0
0
1H, HC(30)), 4.28 (q, Jˆ3.1 Hz, 1H, HC (40)), 4.04 (dd,

3296
Z.-D. Shi et al. / Tetrahedron 58 (2002) 3287±3296
15. Visser, G. M.; Van, W. J.; Van, B. C. A.; Van, B. J. Recl. Trav.
Chim. Pays-Bas 1986, 105, 528.
26. Aldrich catalog number for l-ribose: 28, 712-1, Aldrich
catalog number for d-deoxyribose: 12, 164-9.
27. Walker, T. E.; Hogenkamp, H. P. Carbohydr. Res. 1974, 32,
413.
16. Pitsch, S. Helv. Chem. Acta 1997, 80, 2286.
17. Jung, M. E.; Xu, Y. Tetrahedron Lett. 1997, 38, 4199.
18. Moyroud, E.; Strazewski, P. Tetrahedron 1999, 55, 1277.
19. Morgenlie, S. Acta Chem. Scand. 1973, 27, 3609.
20. A modi®cation of our previousmethod: Wu, W. L.; Wu, Y. L.
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