A stereospecific synthesis of L-ribose and L-ribosides from D-galactose

Article abstract of DOI:10.1016/S0040-4039(01)01623-9

An inexpensive D-galactose was converted into L-ribose and its derivatives via mild reaction conditions. The L-ribosyl donor was submitted to a glycosidation according to Vorbrüggen's conditions to give L-ribosides in high yields.

Full text of DOI:10.1016/S0040-4039(01)01623-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 7651–7653
A stereospecific synthesis of
L
-ribose and -ribosides from
L
D
-galactose
Zhen-Dan Shi, Bing-Hui Yang* 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, China
Received 11 July 2001; accepted 30 August 2001
Abstract—An inexpensive
donor was submitted to a glycosidation according to Vorbru¨ggen’s conditions to give
Science Ltd. All rights reserved.
D
-galactose was converted into
L
-ribose and its derivatives via mild reaction conditions. The
L
-ribosyl
L-ribosides in high yields. © 2001 Elsevier
Recently, the use of
sponding nucleosides in medicinal applications has
greatly increased. In particular, several modified
L
-carbohydrates and their corre-
According to our observations, there exists some useful
information of -galactose 2 in relation to -ribose 1,
i.e. -galactose is a hexose while -ribose is a pentose
without C-6 and with configurations at both C-3 and
C-4 the same, while C-2 is different. Therefore, the key
D
L
D
L
nucleosides derived from
-1-(2-hydroxymethyloxathiolan-5-yl)-cytosine (3TC),1
-thymidine ( -3%-thiacytidine ( -5-
-T),2 -3-TC),3,4
fluoro-3%-thia-cytidine ( -2%,3%-dideoxycytidine
-FTC),5
- ddC),6
- 5 - fluoro - 2%,3% - dideoxy - cytidine ( - 5-
FddC),7,8 and
-2%-fluoro-5-methylarabinofuranosyl
uracil (
-FMAU),9 have shown great potential as useful
antiviral agents. In addition, due to the stereoselectivity
of enzymes, -ribose modified oligoribonucleotides
become attractive candidates for diagnostic and thera-
peutic uses because -RNA ligands remain uncleaved in
biological fluids.10 For these reasons,
-carbohydrates,
modified -nucleosides, especially -ribose and its
derivatives are of interest. Up to now, several syntheses
of -ribose and -ribosides from
-arabinose,11–13
glucose,14 -ribose,15 -xylose16 have been reported and
herein we report a stereospecific synthesis of -ribose 1
and -ribosides from -galactose 2.
L
-sugars, such as (−)-(2%R,5%S)
L
L
L
L
L
conversion of D-galactose into L-ribose in our synthetic
L
L
approach includes oxidation cleavage and reduction at
5,6-diol of galactose and the configuration inversion at
2-hydroxy group of resulting arabinose. The synthetic
(L
L
L
L
L
route to
L-ribose is depicted in Scheme 1.
L
At first, we obtained compound 3, 1,2,5,6-di-O-iso-
propylidene-
D
-galactofuranose from
D-galactose as
L
described in the literature.17 Chemoselective cleavage of
the 5,6-O-isopropylidene diol of 3 with NaIO4/HIO4
(1.0 eq./0.5 eq.)-ether in one operation or with 10%
AcOH followed by NaIO4 cleavage of the resulting
glycol and then reduction of the aldehyde with sodium
L
L
L
L
L
L
D-
D
L
borohydride in one-pot furnished
L-arabinose deriva-
L
tive 4 in 85–92% yield. After some conversions includ-
ing the protection of 3,5-dihydroxyl groups with benzyl
chloride, methanolysis, and methanesulfonylation, a
substrate (7) for configuration inversion was obtained.
L
D
Configuration inversion of the 2-hydroxyl group in
compound 7 was attempted by several methods includ-
ing Mitsunobu method and oxidation/reduction proce-
dure, but all of these were unsuccessful. We therefore
reacted 7 with Ac2O, AcOH and H2SO4, this gave only
the 1,5-diacetate 8, but not the 1-acetate, in 89% yield.
The inversion of 2-OH configuration and the hydrolysis
of the diacetate took place with NaOMe/MeOH for the
intramolecular SN2 reaction of methanesulfonyloxy
group with C-1 alkoxide. Then, L-ribose was prepared
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01623-9

7652
Z.-D. Shi et al. / Tetrahedron Letters 42 (2001) 7651–7653
Scheme 1. Reagents and conditions: (a) 10% AcOH-H2O, rt, 24 h; (b) NaIO4, MeOH, H2O, rt, 1h; (c) NaBH4, MeOH, H2O, 3
h, three steps in 92% yield; (b%) NaIO4/HIO4 (1.5 eq.), Et2O, rt, 4h; (d) KOH, BnCl, 1,4-dioxane, reflux, 2 h, 95%; (e) 10%
HCl-MeOH, rt, 3h, 96%; (f) MsCl, Et3N, rt, overnight, 98%; (g) Ac2O, AcOH, H2SO4, 4°C, overnight, 89%; (h) NaOMe, MeOH,
rt, 6 h, 83%; (i) 10% Pd-C, MeOH, H2, 2 h; (j) Dowex [H+], H2O, 50°C, 24 h, two steps in 95% yield.
by debenzylation of 9 with 10% palladium-carbon in
methanol followed by hydrolysis of methyl glycoside
with ion-exchange resin (H+ form) in 95% yield. The
resulting structure was confirmed by comparison with a
commercial sample (Aldrich). In conclusion we have
method,18 the b-N-glycosidic bond linkages are made
by the -ribosyl donor 12 and the protected bases. We
L
therefore obtained 13a, b, c by treatment of 12 with the
protected bases, respectively, in the presence of
TMSOTf and BSA (N,O-bis-trimethylsilylacetamide) in
good yields (92%, 88%, 89% for 13a, b, c, respectively).
synthesized
L-ribose from D-galactose, an inexpensive
material, by using cheap reagents under mild reaction
conditions.
The L-ribosides were obtained by deacetylation with
NH3-H2O/MeOH and then debenzylation using 10%
palladium-carbon in methanol in high yield (92%, 91%,
87% for 14a, b, c, respectively).19
Scheme 2 shows the syntheses of -ribosides 14. Diac-
L
etate 11 was prepared by the treatment of 9 with acetic
anhydride and pyridine and converted to 1,2,5-tri-O-
For some bases, sensitive to debenzylation, like purine,
5-iodouracil, N6-benzoyl-adenine, N2-O6-diphenylcar-
bamoylguanine, we resorted to another synthetic route
acetyl-3-O-benzyl-
L
-ribofuranoside 12 as an isolable
mixture (a:b=1:11). According to the Vorbru¨ggen
Scheme 2. Reagents and conditions: (a) Ac2O, py, overnight, rt, 92%; (b) AcOH, Ac2O, H2SO4, 4°C, overnight, 83%; (c) Base,
TMSOTf, BSA, solvent, overnight; (d) NH3-H2O, MeOH, 60°C, overnight; (e) 10% Pd-C, H2, rt, 3 h
Scheme 3. Reagents and conditions: (a) Ac2O, py, overnight, rt, 90%; (b) Ac2O, AcOH, H2SO4, 4°C, overnight, 74%; (c) B,
TMSOTf, solvents; (d) NH3/H2O, MeOH, 60°C, overnight.

Z.-D. Shi et al. / Tetrahedron Letters 42 (2001) 7651–7653
7653
(Scheme 3). Protection of the triol 10 with acetic anhy-
dride and pyridine furnished the triacetate 15 and treat-
J.-P.; Cheng, Y.-C. Antimicrob. Agents Chemother. 1995,
39, 979.
10. Nolte, A.; Klubman, S.; Bald, R.; Erdmann, V. A.;
Furste, J. P. Nature Biotechnology 1996, 14, 1116.
11. Abe, Y.; Takizawa, T.; Kunieda, T. Chem. Pharm. Bull.
1980, 28, 1324.
12. Holy, A.; Sorm, F. Coll. Czech. Chem. Commun. 1969,
34, 3383; ibid. 1972, 37, 4072; ibid. 1973, 38, 423.
13. Visser, G. M.; Van, W. J.; Van, B. C. A.; Van, B. J. Recl.
Trav. Chim. Pays Bas. 1986, 105, 528.
14. Pitsch, S. Helv. Chem. Acta 1997, 80, 2286.
15. Jung, M. E.; Xu, Y. Tetrahedron Lett. 1997, 38, 4199.
16. Moyroud, E.; Strazewski, P. Tetrahedron 1999, 55, 1277.
17. Morgenlie, S. Acta Chem. Scand. 1973, 27, 3609.
18. (a) Vorbru¨ggen, H.; Krolikiewicz, K.; Bennua, B. Chem.
Ber. 1981, 114, 1234; (b) Vorbru¨ggen, H. Acta Biochim.
Polon. 1996, 43, 25.
ment of 15 with Ac2O/AcOH/H2SO4 afforded
separable mixture 16 (a:b=1:7) of tetra-O-acetyl-
a
L
-
ribose. Using the same procedures for glycosidation, we
acquired the
(83–94%) on different bases, selecting BSA (N,O-bis-
trimethylsilylacetamide), MFSTA (N-methyl-N-
L
-ribosides (17a, b, c, d) in good yield
trimethylsilyl-trifluoroacetamide) and different solvents
(acetonitrile or toluene). The deprotected products 18a,
b, c, d were obtained in high yields (91–94%).
Thus we have synthesized
available 3 in ten steps and in 57% overall yield. These
procedures provide a practical synthesis of -ribose and
-ribosides
L-ribose from the easily
L
its derivatives. The biological activity of the
and their derivatives are being assessed.
L
19. All new compounds gave satisfactory spectral and micro-
analytical data. Selected data for compound 9: [h]2D0=
+9.1(c 0.5, MeOH); IR (film, cm−1): 3415, 3032, 1455;
1H NMR (300 MHz, CDCl3): l 7.41–7.31 (m, 5H, Ph),
4.87 (s, 1H, H-1), 4.56 (s, 2H, OBn), 4.23–4.11 (m, 2H,
H-3, H-4), 4.04 (d, 1H, J2,3=4.2 Hz, H-2), 3.77 (dd, 1H,
Acknowledgements
We thank the State Ministry of Science and Technology
of China for financial support.
J
4,5a=2.2 Hz, J5a,5b=12.9 Hz, H-5a), 3.55 (dd, 1H,
4,5b=3.3 Hz, J5a,5b=12.0 Hz, H-5b), 3.40 (s, 3H, OMe);
J
HRMS (m/z) calcd. for C13H18O5: 254.1177; found:
References
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H-2, H-3), 3.77–3.61 (m, 2H, H-4, H-5a), 3.48 (m, 1H,
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1
MeOH); IR (KBr): wmax 3197 (brs), 1748 cm−1; H NMR
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5H, Ph), 7.14 (s, 1H, H-6), 5.85 (d, 1H, J1%,2%=3.3 Hz,
H-1%), 5.37 (dd, 1H, J1%,2%=3.3 Hz, J2%,3%=5.2 Hz, H-2%),
4.62 (d, 1H, J=11.3 Hz, OBn), 4.46 (d, 1H, J=11.3 Hz,
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=
6.3 Hz, J5a%,5b%=11.8 Hz, H-5b%), 2.14 (s, 3H, OAc), 2.04
(s, 3H, OAc), 1.91 (s, 3H, CH3); MS (EI): m/z 307
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pound 14b: [h]2D0=+15.6 (c 1.1, MeOH); 1H NMR (300
Hz, DMSO-d6): l 11.31 (s, 0.25H, NH), 7.74 (s, 1H,
H-6), 5.78 (d, 1H, J1%,2%=5.6Hz, H-1%), 4.03 (t, 1H, J1%,2%
=
5.5 Hz, J 2%,3%=5.3 Hz, H-2%), 3.96 (t, 1H, J2%,3%=4.9 Hz,
J3%4%=3.9 Hz, H-3%), 3.80 (q, 1H, J3%,4%=3.9 Hz, J4%,5a%=3.4
Hz, J4%,5a%=3.4 Hz, J4%,5b%=3.4 Hz, H-4%), 3.63 (dd, 1H,
J4%,5a%=3.4 Hz, J5a%,5b%=12.1 Hz, H-5a%), 3.53 (dd, 1H,
J4%,5b%=3.4 Hz, J5a%,5b%=12.1 Hz, H-5b%), 1.77 (s, 3H,
CH3); MS (EI): m/z 258 (M+); Anal. calcd for
C10H14O6N2·0.25H2O: C, 45.71, H, 5.52, N, 10.67; found:
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