A convenient synthesis of L-ribose from D-fructose

Article abstract of DOI:10.1016/j.tet.2011.04.012

An efficient method for the stereoselective synthesis of L-ribose was accomplished starting from commercially inexpensive D-fructose. The intermediates in the process can serve as versatile precursors for the preparation of L-nucleoside analogues.

Full text of DOI:10.1016/j.tet.2011.04.012

Tetrahedron 67 (2011) 4031e4035
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journal homepage: www.elsevier.com/locate/tet
A convenient synthesis of
L
-ribose from -fructose
D
*
Ramu Sridhar Perali , Suresh Mandava, Ramakrishna Bandi
School of Chemistry, University of Hyderabad, Hyderabad 500 046, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 March 2011
Received in revised form 31 March 2011
Accepted 6 April 2011
Available online 12 April 2011
An efficient method for the stereoselective synthesis of L-ribose was accomplished starting from com-
mercially inexpensive
D-fructose. The intermediates in the process can serve as versatile precursors for
the preparation of -nucleoside analogues.
L
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
L
-Sugars
-Ribose
L
D
-Fructose
Stereoselective synthesis
1. Introduction
Recently, NOX-E36, a 40-meric
veloped to target the chemokine MCP-1 for treating inflammatory
diseases like lupus nephritis.10 Apparently the advantages of
-nu-
cleoside analogues are their less cytotoxicity and higher metabolic
stability over -nucleosides while maintaining comparable and
sometimes greater antiviral activity. One of the essential starting
materials for the synthesis of all these -nucleoside based antiviral
agents is a conveniently protected -ribose.
L-RNA oligonucleotide was de-
Nucleoside analogues based on modifications of heterocyclic
bases and/or modifications on the sugar moiety of natural nucleo-
sides are found to be prominent drugs in the management of several
L
D
viral infections.1 In the beginning of 90s replacement of
D
-ribose in
natural nucleosides with the corresponding sugar enantiomer,
-ribose, leading to the formation of -nucleosides, has opened
a new era in development of novel antiviral agents. Since then,
a large number of -nucleoside analogues have been synthesized
and their antiviral activities were evaluated.2 As a result, clevu-
dine (1, -arabinofuranosyluridine,
-FMAU, 20-fluoro-5-methyl-
-Fd4C,
-20,30-
L
L
L
L
Several good synthetic methods were reported for
L
-ribose11
L
-arabinose,12 -xylose,13
L
starting from chiral pool
L-sugars, such as
L
L
b-L
Chart 1),3 is in the market and elvucitabine (2,
L
L
Dideoxy-20,30-didehydro-5-fluorocytidine)4 in under phase II clini-
cal trials4c for the treatment of HBV infection due to their potent
inhibitory activity against chronic hepatitis B virus (HBV) DNA
O
Cl
NH3
NH
NH2
N
F
HO
NH
O
HO
N
O
N
HO
O
polymerase. Two other
Val- -dC, 3-O-valinyl-
-20-deoxycytidine)5 and telbivudine (4,
-thymidine)6 were proven to be extremely specific and selective
anti-HBV agents with exceptional safety profile. R1518 6,7 a valine
ester prodrug of levovirin (5, 1-( -ribofuranosyl)-1,2,4-triazole-3-
carboxamide)8 was found to exhibit anti-HCV activity is currently
undergoing clinical trials. An -ribofuranosyl benzimidazole namely
L
-nucleoside analogues, valtorcitabine (3,
N
O
O
O
L
L
L-dT,
O
Cl H3N
HO
F
L
O
2
Valtorcitabine
3
L-Fd4C
Clevudine
1
(Elvucitabine)
O
(val-L-dC)
b-L
Cl
Cl
O
NH
O
NH2
L
N
N
HO
maribavir (7, 1H-b-L-ribofuranoside-2-isopropylamino-5,6-dichlor-
N
N
O
N
O
obenzimidazole)9 was found to be a potent and selective oral anti-
viral drug to inhibit cytomegalovirus (CMV) infection (Chart 1).
N
O
RO
HO
HN
HO
HO
OH
HO
OH
5
R = H Levovirin
O
4
Telbivudine
(L-dT)
Maribavir
7
H
N
C
R =
6
R1518
* Corresponding author. Tel.: þ91 40 6679 4823; fax: þ91 40 2301 2460; e-mail
address: prssc@uohyd.ernet.in (R.S. Perali).
Chart 1. L-Ribose derived pharmaceuticals either in the market or under clinical trials.
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.04.012

4032
R.S. Perali et al. / Tetrahedron 67 (2011) 4031e4035
and
D
D
-sugars, for instance
D
-ribose,14
D
-glucose,15
D
-galactose,16 and
1522 in good yield (85% over two steps). Compound 15 upon
-mannose.17 However, the high prices of
L-ribose indicate the re-
reaction with NaBH4 at ꢀ78 ꢁC in ethanol23 underwent a stereo-
selective reduction producing the 2,3-anti alcohol 1624 as a single
diastereomer. Ozonolysis of the olefin in 16 gave 2,3-O-iso-
quirement of an alternative synthetic method, which is simple, ef-
ficient, and inexpensive. Even though, molybdenum catalyzed
epimerization of
method to produce
exchange resin and a recovery step for the starting material makes
the preparation cumbersome. Owing to the importance of -ribose
in drug development, herein we wish to report an efficient method
for the stereoselective synthesis of -ribose and its derivatives from
commercially inexpensive raw material, -fructose. Furthermore,
the present synthesis involves easy workup and purification tech-
L
-arabinose18 (Bílik reaction) is one of the efficient
propylidene-5-O-(tert-butyldimethylsilyl)-L
-ribose 1724,25 as an
anomeric mixture in 86% yield. Acetylation of the anomeric
alcohol using acetic anhydride resulted 1-O-acetyl-2,3-O-iso-
L-ribose, its separation equipment using an ion-
L
propylidene-5-O-(tert-butyldimethylsilyl)-b-L-ribofuranose 18 as
single diastereomer.26 On the other hand a one-pot deprotection
L
of acetonide and TBDMS using acetic acid at 60 ꢁC provided pure
L-
D
ribose 1927 in 91% yield (Scheme 2).
niques, which can be adaptable for large scale production of L-ribose.
2. Results and discussion
As shown in Scheme 1,
isopropylidene-
-fructose 919 by the conventional method.
Pyridinium dichromate mediated oxidation of 9 to give 1,2:4,5-di-O-
isopropylidene-
-erythro-2,3-hexodiulo-2,6-pyranose 1019 followed
by stereoselective reduction afforded 1,2:4,5-di-O-isopropylidene-
psicopyranose 1119 in excellent yield. Isomerization of pyranose 11
D-fructose 8 was converted to 1,2:4,5-di-O-
D
D
D-
to its furanose isomer 1,2:3,4-di-O-isopropylidene-D-psicofuranose
1219,20 was accomplished using catalytic HClO4 in acetone and 2,2-
dimethoxy propane.21 Substitution of the primary hydroxyl group in
12 with iodine using I2/Ph3P/imidazole under reflux in toluene pro-
vided 6-deoxy-6-iodo-1,2:3,4-di-O-isopropylidene-
D-psicofuranose
1319,20 in 95% yield.
Scheme 2. Synthesis of L-ribose.
3. Conclusion
In conclusion, an efficient synthetic method for the production
-ribose in an overall yield of 21.5% from -fructose was
-nucleoside analogues is in
of
L
D
developed. Further, the preparation of
progress.
L
4. Experimental section
4.1. General
All the reactions were carried out under inert atmosphere with
dry solvents under anhydrous conditions unless otherwise men-
tioned. Acetone was distilled from potassium permanganate,
CH2Cl2 was distilled from calcium hydride, ethanol was distilled
from sodium ethoxide followed magnesium, pyridine was distilled
from KOH and toluene was distilled from sodium. TLC was run on
Silica Gel 60 F254 (Merck) and the spots were detected by staining
with H2SO4 in methanol (5%, v/v) or phosphomolybdic acid in
ethanol (5%, w/v) and heat. Silica gel (100e200 mesh) was used as
a stationary phase for column chromatography. NMR spectra were
recorded at 25 ꢁC on a Bruker AvanceIII 400 (400 MHz for 1H and
100 MHz for 13C) or 500 (500 MHz for 1H and 125 MHz for 13C)
Scheme 1. Synthesis of 6-deoxy-6-iodo-1,2:3,4-di-O-isopropylidene-D-psicofuranose 13.
Zinc mediated fragmentation of 13 in THF/H2O (9:1) under
sonication gave
a-hydroxy ketone 14. However, substantial de-
composition of compound 14 was observed during column chro-
matography. Due to this a one-pot metal mediated fragmentation
followed by protection of the free hydroxyl group with tert-
butyldimethylsilyl (TBDMS) was carried out to produce compound
instrument with CDCl3 or D2O as solvent and residual CHCl3
(dH
7.26 ppm) or D2O (dH 4.79 ppm) as internal standard for 1H and

R.S. Perali et al. / Tetrahedron 67 (2011) 4031e4035
4033
CDCl3 (dC 77.0 ppm) as internal standard for 13C. Chemical shifts are
given in (ppm) and coupling constants (J) in hertz. IR spectra were
recorded on JASCO FT/IR-5300. Elemental analyses were recorded
on a Thermo Finnigan Flash EA 1112 analyzer. Mass spectra were
recorded on Shimadzu-LCMS-2010A mass spectrometer.
was partitioned between Et2O (100 mL) and water (50 mL) and the
water layer was extracted with Et2O (3ꢂ50 mL). The combined Et2O
layers were washed with brine, dried over anhydrous Na2SO4, fil-
tered, and evaporated. The crude product was purified by flash
column chromatography on silica gel to give compound 12 (15.8 g,
71.8%) as a white solid. Rf (20% EtOAc/hexane) 0.75; dH (400 MHz,
CDCl3): 4.92 (d, 1H, J¼5.6 Hz), 4.66 (d, 1H, J¼6 Hz), 4.30e4.36 (m,
2H), 4.08 (d, 1H, J¼10.6 Hz), 3.76 (br d, 1H, J¼12.4 Hz), 3.65 (td, 1H,
J¼3.2, 10.4 Hz), 3.20 (dd, 1H, J¼2.8, 10.4 Hz), 1.52 (s, 3H), 1.45 (s, 3H),
1.41 (s, 3H), 1.33 (s, 3H). dC (100 MHz, CDCl3): 113.4, 112.3, 111.7,
86.8, 85.8, 81.6, 69.9, 63.9, 26.5, 26.3, 26.1, 24.8.
d
4.1.1. 1,2:4,5-Di-O-isopropylidene-
D
-fructopyranose (9)19. To a stir-
red suspension of -fructose 8 (150 g, 0.83 mol) in a mixture of
D
acetone (3 L) and 2,2-dimethoxy propane (60.26 mL, 0.49 mol) at
0 ꢁC was added 70% perchloric acid (35 mL, 0.40 mol) dropwise. The
reaction mixture was stirred for 6 h while slowly allowing it to
25 ꢁC. After completion of the reaction (by TLC) the mixture was
quenched with concd ammonium hydroxide (39.2 mL) and the
solvents were evaporated to give a crystalline residue, which was
dissolved in CH2Cl2 (1.6 L). The solution was washed with brine
(2ꢂ150 mL), dried over anhydrous Na2SO4, and evaporated. The
crude product was recrystallized from CH2Cl2/hexane to give 9
(130 g, 60%) as white needles. dH (500 MHz, CDCl3): 4.21 (dd, 1H,
J¼2, 6 Hz), 4.18 (d, 1H, J¼9 Hz), 4.13 (dd, 1H, J¼5.6, 7.5 Hz), 4.10
(d, 1H, J¼2.5 Hz), 4.01 (d, 1H, J¼13.5 Hz), 3.97 (d, 1H, J¼9 Hz), 3.66
(dd, 1H, J¼7, 8 Hz), 2.00 (d, 1H, J¼8.5 Hz), 1.53 (s, 3H), 1.51 (s, 3H),
1.43 (s, 3H), 1.36 (s, 3H). dC (125 MHz, CDCl3): 111.7, 109.1,104.4, 77.1,
73.2, 72.0, 70.1, 60.5, 27.8, 26.2, 26.2, 25.8.
4.1.5. 6-Deoxy-6-iodo-1,2:3,4-di-O-isopropylidene-
D
-psicofuranose
-psicofur-
(13)19. To
a
mixture of 1,2:3,4-di-O-isopropylidene-
D
anose 12 (13 g, 49.98 mmol), triphenylphosphine (39.33 g,
149.94 mmol), and imidazole (9.74 g, 149.94 mmol) in toluene (1 L)
at 80 ꢁC was added iodine (25.39 g, 99.96 mmol) portion wise for
a period of 1 h. Once the addition was completed the reaction
mixture was refluxed for 7 h. Upon completion of the reaction, it
was brought to 25 ꢁC and aqueous saturated Na2CO3 solution
(800 mL) was added. After the solution become clear iodine was
added slowly until the organic layer became colored. Stirred for
10 min, sodium thiosulfate was added until decolorization occurs.
The mixture was transferred to a separating funnel and the organic
layer was diluted with toluene. The organic layer was washed with
water dried over anhydrous MgSO4, and concentrated. Et2O and
hexane were added to precipitate out the triphenylphosphine ox-
ide. Filtration and concentration followed by column chromatog-
raphy afforded compound 13 (17.5 g, 95%) as a pale yellow color
liquid that was solidified after 7 days at 0 ꢁC. Rf (10% EtOAc/hexane)
0.69; dH (400 MHz, CDCl3): 4.78 (d, 1H, J¼5.6 Hz), 4.60 (d, 1H,
J¼5.6 Hz), 4.34 (dd, 1H, J¼6, 10 Hz), 4.24 (d, 1H, J¼10 Hz), 4.00
(d, 1H, J¼10 Hz), 3.25 (dd, 1H, J¼6, 10 Hz), 3.20 (t, 1H, J¼10 Hz), 1.45
(s, 3H), 1.41 (s, 3H), 1.35 (s, 3H), 1.30 (s, 3H). dC (100 MHz, CDCl3):
113.7, 112.7, 111.7, 86.1, 85.4, 83.4, 69.6, 26.4, 26.3, 26.3, 25.0, 6.8.
Low-resolution MS (EI): m/z: 371 (Mþþ1). Anal. Calcd for
C12H19IO5: C, 38.93; H, 5.17. Found: C, 38.85; H, 5.23.
4.1.2. 1,2:4,5-Di-O-isopropylidene-
D
-erythro-2,3-hexodiulo-2,6-pyra-
nose (10)19. A solution of 1,2:4,5-di-O-isopropylidene-
D
-fructose
9 (40 g, 0.15 mol) in dry CH2Cl2 (320 mL) was added to a mixture of
pyridinium dichromate (42 g, 0.11 mol) and acetic anhydride
(48.5 mL, 0.51 mol) in dry CH2Cl2 (500 mL) under nitrogen atmo-
sphere. The resulting mixture was stirred under reflux until the
complete conversion (w6 h), then cooled to 25 ꢁC and solvent was
removed in vacuo. Et2O was added (1 L) to the solid residue and the
mixture was filtered over Celite. The Celite bed was washed several
times with Et2O. Removal of Et2O under vacuum provided the crude
compound, which was purified by column chromatography using
EtOAc/hexane (4:1) to give pure 10 (38.5 g, 97%) as a white solid. Rf
(20% EtOAc/hexane) 0.63; dH (400 MHz, CDCl3): 4.72 (d, 1H,
J¼5.6 Hz), 4.61 (d, 1H, J¼5.6 Hz), 4.54 (dd, 1H, J¼1.6, 5.6 Hz), 4.38
(dd, 1H, J¼2, 13.2 Hz), 4.12 (d, 1H, J¼13.2 Hz), 3.98 (d, 1H, J¼9.6 Hz),
1.54 (s, 3H), 1.45 (s, 3H), 1.39 (s, 6H). dC (100 MHz, CDCl3): 196.9,
113.8, 110.6, 104.1, 77.9, 75.8, 70.0, 60.0, 27.1, 26.5, 26.1, 26.0.
4.1.6. (4R,5R)-1-(2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)-2-(tert-
butyldimethylsilyloxy)ethan-1-one (15)22. To a solution of 6-de-
oxy-6-iodo-1,2:3,4-di-O-isopropylidene- -psicofuranose 13 (6.0 g,
D
16.21 mmol) in THF/water (9:1 v/v, 420 mL), zinc dust (10.6 g,
162.1 mmol) was added. The resulting suspension was sonicated at
40 ꢁC until TLC showed complete consumption of starting material
(w2 h). The reaction mixture was cooled to 25 ꢁC and treated with
Et2O (500 mL) and water (100 mL) and filtered through a plug of
Celite to separate the Et2O and water layers. The aqueous layer was
extracted with Et2O (3ꢂ200 mL). The combined organic layers were
4.1.3. 1,2:4,5-Di-O-isopropylidene-
-psicopyranose (11)19. To a stir-
D
red solution of 10 (22 g, 85.2 mmol) in ethanol (220 mL) was added
NaBH4 (1.6 g, 42.3 mmol) at 15 ꢁC. After stirring at this temperature
for 1 h the solvent was evaporated under reduced pressure. Et2O
(132 mL) and saturated NH4Cl solution (80 mL) were added to the
residue. The mixture was again stirred for 4 h at 25 ꢁC. Et2O layer
was recovered and the aqueous layer was extracted with Et2O
(3ꢂ50 mL). The combined Et2O layers were dried over anhydrous
Na2SO4 and evaporated. The crude product was recrystallized in
hexane to give compound 11 (21.3 g, 96%) as a white solid. Rf (20%
EtOAc/hexane) 0.33; dH (400 MHz, CDCl3): 4.42 (dd,1H, J¼4, 6.4 Hz),
4.22 (m, 2H), 3.93e4.02 (m, 3H), 3.73 (dd, 1H, J¼4, 6.4 Hz), 2.43 (d,
1H, J¼6.4 Hz), 1.53 (s, 3H), 1.47 (s, 3H), 1.38 (s, 3H), 1.35 (s, 3H). dC
(100 MHz, CDCl3): 111.0, 109.4, 104.8, 72.9, 72.1, 71.8, 68.6, 61.1, 26.4,
26.1, 25.9, 25.0.
dried over anhydrous Na2SO4, and concentrated to give crude a-
hydroxy ketone 14 as a yellow oil (3.0 g). Rf (30% EtOAc/hexane)
0.27; dH (400 MHz, CDCl3): 5.57e5.64 (m, 1H), 5.43 (dd, 1H,
J¼16.8 Hz), 5.26 (d, 1H, J¼10.4 Hz), 4.87 (m, 1H), 4.71 (d, 1H,
J¼8.4 Hz), 4.52 (dd, 1H, J¼4.8, 20.4 Hz), 4.22 (d, 1H, J¼4.8, 20.4 Hz),
2.88 (t, 1H, J¼4.8Hz), 1.60 (s, 3H), 1.39 (s, 3H). dC (100 MHz, CDCl3):
209.2, 131.2, 119.1, 110.9, 81.7, 78.4, 67.9, 26.5, 24.4. The oily residue
(3 g) was redissolved in CH2Cl2 (50 mL), imidazole (4.41 g,
54.86 mmol) and tert-butyldimethylsilyl chloride (4.48 g,
32.38 mmol) were added sequentially. The reaction mixture was
stirred overnight at 25 ꢁC and quenched with saturated NH4Cl so-
lution (50 mL). The organic layer was separated and the aqueous
layer was extracted with CH2Cl2 (3ꢂ20 mL). Combined organic
layers were washed with brine then dried over anhydrous Na2SO4
and filtered. The crude product was purified by flash column
chromatography using EtOAc/hexane (1:24) to afford pure ketone
15 (4.15 g, 85% from 13) as a colorless liquid. Rf (10% EtOAc/hexane)
4.1.4. 1,2:3,4-Di-O-isopropylidene-
-psicofuranose (12)21. To a stir-
D
red solution of compound 11 (22 g, 84.61 mmol) in a mixture of
acetone (230 mL) and 2,2-dimethoxy propane (5.48 mL,
44.98 mmol) at 0 ꢁC was added 70% perchloric acid (1.32 mL,
14.38 mmol) dropwise. The reaction mixture was stirred for 3 h
while slowly allowing it to 25 ꢁC. After completion of the reaction
(by TLC) the mixture was quenched with concd, ammonium hy-
droxide (2.53 mL) and the solvents were evaporated. The residue
0.62; IR (neat): 3088, 2932, 2895,1738, 1645, 1572,1464, 1381 cmꢀ1
.

4034
R.S. Perali et al. / Tetrahedron 67 (2011) 4031e4035
dH (400 MHz, CDCl3): 5.64e5.72 (m, 1H), 5.40 (d, 1H, J¼16.8 Hz),
5.23 (d, 1H, J¼10.4 Hz), 4.87 (m, 2H), 4.45 (d, 1H, J¼18.8 Hz), 4.20
(d, 1H, J¼18.8 Hz), 1.59 (s, 3H), 1.38 (s, 3H), 0.91 (s, 9H), 0.06 (br s,
6H). dC (100 MHz, CDCl3): 206.4, 132.6, 118.8, 110.2, 81.8, 78.1, 68.5,
26.9, 25.8, 24.8, 18.3, ꢀ5.4, ꢀ5.5. Low-resolution MS (EI): m/z: 301
(Mþþ1). Anal. Calcd for C15H28O4Si: C, 59.96; H, 9.39. Found: C,
59.78; H, 9.45.
After complete disappearance of starting material the reaction
mixture was concentrated and traces of acetic acid was removed
by co-evaporation with toluene. The compound was dissolved in
water (25 mL) and washed with CH2Cl2 (2ꢂ15 mL). Concentration
of the water layer provided pure -ribose 19 (0.45 g, 91%) as
L
a white solid. Major isomer dC (100 MHz, D2O): 93.7, 70.9, 68.8,
67.1, 62.9.
4.1.7. (4S,5R)-1-(2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)-2-(tert-
butyldimethylsilyloxy)-1(S)-ethan-1-ol (16)24. A solution of ketone
15 (4 g, 13.33 mmol) in ethanol (40 mL) was added to NaBH4 (1 g,
26.66 mmol) dissolved in ethanol (80 mL) at ꢀ78 ꢁC. After 2 h the
reaction was quenched with saturated NH4Cl solution (10 mL) and
allowed it to 25 ꢁC. The reaction mixture was concentrated under
reduced pressure to give a thick semi solid. EtOAc (150 mL) and water
(50 mL) were added and the organic layer was separated and the
aqueous layer was extracted with EtOAc (3ꢂ50 mL). The combined
organic layers were dried over anhydrous Na2SO4, filtered and the
solvent was concentrated under reduced pressure. The crude product
was purified by flash column chromatography using EtOAc/hexane
(3:97) to give alcohol 16 (3.42 g, 85%) as a colorless liquid. Rf (10%
EtOAc/hexane) 0.58; IR (neat): 3562, 2986, 2934, 2858, 1645, 1464,
Acknowledgements
This work was supported by the Department of Science and
Technology (DST) FAST track project grant No. SR/FTP/SC-64/2007.
Supplementary data
Supplementary data associated with this article can be found in
online version at doi:10.1016/j.tet.2011.04.012.
References and notes
1. (a) Wang, P.; Hong, J. H.; Cooperwood, J. S.; Chu, C. K. Antiviral Res. 1998, 40, 19;
ꢀ
(b) Mathe, C.; Gosselin, G. Antiviral Res. 2006, 71, 276.
1371 cmꢀ1
.
dH (400MHz,CDCl3):6.01e6.09(m,1H),5.41(dt,1H, J¼1.6,
2. (a) Furman, P. A.; Painter, G. R. Int. Antiviral News 1995, 3, 74; (b) Nair, V.;
Jahnke, T. S. Antimicrob. Agents Chemother. 1995, 39, 1017; (c) Graciet, J.-C.;
Schinazi, R. F. Adv. Antiviral Drug Des. 1999, 3, 1; (d) Zemlicka, J. Pharmacol. Ther.
2000, 85, 251; (e) Cheng, Y.-C. Antiviral Chem. Chemother. 2001, 12, 5; (r) Gu-
mina, G.; Chong, Y.; Choo, H.; Song, G.-Y.; Chu, C. K. Curr. Top. Med. Chem. 2002,
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3. Chu, C. K.; Ma, T.; Shanmuganathan, K.; Wang, C.; Xiang, Y.; Pai, S. B.; Tao, G.-Q.;
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Clevudine has been marketed in South Korea and the philippines under the
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been discontinued.
17.2 Hz), 5.28 (d, 1H, J¼10.4 Hz), 4.68 (t, 1H, J¼6.4 Hz), 4.05 (dd, 1H,
J¼6.4, 8.8 Hz), 3.80 (dd,1H, J¼2.8, 9.6 Hz), 3.61e3.70 (m, 2H), 2.51 (d,
1H, J¼5.2 Hz), 1.46 (s, 3H), 1.35 (s, 3H), 0.91 (s, 9H), 0.08 (br s, 6H). dC
(100 MHz, CDCl3): 134.1, 117.5, 108.7, 78.7, 77.4, 69.5, 64.3, 27.8, 25.8,
25.4,18.3, ꢀ5.4, ꢀ5.5. Low-resolution MS (EI): m/z: 303 (Mþþ1). Anal.
Calcd for C15H30O4Si: C, 59.56; H, 10.00. Found: C, 59.38, 10.12.
4.1.8. 2,3-O-Isopropylidene-5-O-(tert-butyldimethylsilyl)-L-ribose
(17)24,25. A stirred solution of alcohol 16 (3.2 g, 10.59 mmol) in dry
CH2Cl2 (90 mL) was cooled to ꢀ78 ꢁC and ozone was passed until
persistence of the blue color. At the same temperature dimethyl
sulfide (5 mL) was added and the temperature was slowly allowed
to 25 ꢁC. Removal of CH2Cl2 followed by flash column chromatog-
raphy afforded acetal 17 (2.78 g, 86%) as a colorless liquid. Rf (10%
EtOAc/hexane) 0.36; major isomer: dH (400 MHz, CDCl3): 5.27 (d,
1H, J¼10.2 Hz), 4.78 (d, 1H, J¼10.2 Hz), 4.69 (d, 1H, J¼6 Hz), 4.50 (d,
1H, J¼6 Hz), 4.34 (br s, 1H), 3.75 (m, 2H), 1.47 (s, 3H), 1.31 (s, 3H),
0.92 (s, 9H), 0.14 (s, 3H), 0.13 (s, 3H). dC (100 MHz, CDCl3): 112.0,
103.4, 87.5, 86.9, 81.7, 64.7, 26.4, 25.8, 24.8, 18.2, ꢀ5.6, ꢀ5.7. Low-
resolution MS (EI): m/z: 305 (Mþþ1). Anal. Calcd for C14H28O5Si:
C, 55.23; H, 9.27. Found: C, 55.14, 9.32.
4. (a) Lin, T.-S.; Luo, M.-Z.; Liu, M.-C.; Zhu, Y.-L.; Gullen, E.; Dutschman, G. E.;
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ꢀ
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5. Bryant, M. L.; Bridges, E. G.; Placidi, L.; Faraj, A.; Loi, A.-G.; Pierra, C.; Dukhan, D.;
Gosselin, G.; Imbach, J.-L.; Hernandez, B.; Juodawlkis, A.; Tennant, B.; Korba, B.;
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4.1.9. 1-O-Acetyl-2,3-O-isopropylidene-5-O-(tert-butyldime-
thylsilyl)-b-L
-ribofuranose (18)26. To a stirred solution of acetal 17
(0.5 g, 1.64 mmol) in dry pyridine (20 mL) at 0 ꢁC was added acetic
anhydride (0.62 mL, 6.57 mmol). The reaction mixture was stirred
overnight and concentrated under reduced pressure. EtOAc
(100 mL) and water (30 mL) were added. The organic layer was
separated and the aqueous layer was extracted with EtOAc
(3ꢂ25 mL). The combined organic layers were washed with satu-
rated CuSO4 solution, brine, and dried over anhydrous Na2SO4. The
solution was filtered and concentrated to give compound 18 (0.55 g,
98%) as a colorless oil. Rf (10% EtOAc/hexane) 0.55; dH (400 MHz,
CDCl3): 6.14 (s, 1H), 4.76 (d, 1H, J¼6.4 Hz), 4.66 (d, 1H, J¼6.4 Hz),
4.28 (dd, 1H, J¼5.2, 7.6 Hz,), 3.66 (dd, 1H, J¼4.8, 10.4 Hz), 3.52 (dd,
1H, J¼8, 10.8 Hz), 2.07 (s, 3H), 1.47 (s, 3H), 1.32 (s, 3H), 0.88 (s, 9H),
0.05 (s, 6H). dC (100 MHz, CDCl3): 169.5, 112.7, 102.6, 88.1, 85.1, 81.6,
63.5, 26.5, 25.8, 25.1, 21.2, 18.2, ꢀ5.4. Low-resolution MS (EI): m/z:
347 (Mþþ1). Anal. Calcd for C16H30O6Si: C, 55.46; H, 8.73. Found: C,
55.61, 8.64.
13. Moyroud, E.; Strazewski, P. Tetrahedron 1999, 55, 1277.
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4.1.10.
L
-Ribose (19)27. A solution of acetal 17 (1 g, 3.28 mmol) in
80% aqueous acetic acid (25 mL) was stirred at 60 ꢁC overnight.

R.S. Perali et al. / Tetrahedron 67 (2011) 4031e4035
4035
20. Pushpakiran, G.; Akihide, Y.; Kenji, M.; Devendar, R.; Kazuya, A.; Sarah, F. J.;
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25. The compound was confirmed by comparing the NMR with an enantiomer of
compound 17 Williams, D. B. G.; Caddy, J.; Blann, K. Carbohydr. Res. 2005, 340,
1305.
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26. The configuration at anomeric centre was assigned by comparing the NMR
spectra with the known enantiomer Chevallier, O. P.; Migaud, M. E. Beilstein J.
Org. Chem. 2006, 2 No. 14.
27.
L-Ribose was also confirmed by matching the NMR spectra of synthetic with
commercially available Aldrich sample.