Preparation of 5-telluropentopyranose sugars from common pentose starting materials

Article abstract of DOI:10.1016/S0040-4039(02)00708-6

2,3,4-Tri-O-benzyl-1,5-dideoxy-5-telluro-D-arabinose (5) and 2,3,4-tri-O-benzyl-1,5-dideoxy-5-telluro-L-arabinose (7) are readily prepared by treatment of D- and L-2,3,4-tri-O-benzyl-1,5-di-O-methanesulfonylarabitol with sodium telluride (Na₂Te) in ethanol.

Full text of DOI:10.1016/S0040-4039(02)00708-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 3799–3800
Preparation of 5-telluropentopyranose sugars from common
pentose starting materials
Oanh T. K. Nguyen and Carl H. Schiesser*
School of Chemistry, The University of Melbourne, Victoria 3010, Australia
Received 13 February 2002; revised 23 March 2002; accepted 10 April 2002
Abstract—2,3,4-Tri-O-benzyl-1,5-dideoxy-5-telluro-
D-arabinose (5) and 2,3,4-tri-O-benzyl-1,5-dideoxy-5-telluro-L-arabinose (7)
are readily prepared by treatment of - and -2,3,4-tri-O-benzyl-1,5-di-O-methanesulfonylarabitol with sodium telluride (Na2Te)
D
L
in ethanol. © 2002 Elsevier Science Ltd. All rights reserved.
It is well accepted that carbohydrates play an important
role in a vast array of biological processes. Modified
carbohydrates such as nitrogen, phosphorus and sulfur
containing monosaccharides are of interest due to their
wide variety of pharmacological activity and physio-
chemical properties. Examples include 5-deoxy-5-thio-
ties,5 and have provided effective treatments for several
diseases including Kwashiokor6 (a protein malnutrition
disorder) and Keshan Disease7 (a form of cardiomy-
opathy), there is yet no known physiological function
associated with tellurium.8 Indeed, only a handful of
organic tellurides have been examined with the aim of
developing compounds with medical use.9–13 In addi-
tion, many organotellurides exhibit glutathione perox-
idase (GSHpx) like activity superior to selenium
containing mimics of GSHpx, such as Ebselen,14,15 and
are powerful antioxidants in vitro.16
D
-glucose, which has been shown to be a potent
inhibitor of cellular
D-glucose transport and also selec-
tively toxic to hypoxic tumor cells.1 Other examples
include nojirimycin and analogues, which are antibacte-
rial agents and have been proposed as chemotherapeu-
tic agents to treat HIV infection.2
As part of ongoing work, and given the inherent poten-
tial of tellurium-containing carbohydrates, we thought
it would be interesting to prepare the hitherto unknown
1,5-dideoxy-5-telluro-D-pentopyranose series of sugars,
analogues of the previously prepared selenosugars (1).
We reported recently that 2,3,4-tri-O-benzyl-1,5-
Accordingly,
O-benzyl-5-O-methanesulfonyl-
D-arabinose was converted into 2,3,4-tri-
dideoxy-5-seleno-
zyl-5-deoxy-5-seleno-
and 2) are readily prepared by thermolysis of the
corresponding 2,3,4-tri-O-benzyl-5-benzylseleno-
D
-pentopyranose and 2,3,4-tri-O-ben-
D
-arabitol
(3)
as
D
-pentopyranose sugars (e.g.
1
described previously.4 Subsequent conversion into the
dimesylate (4) was achieved in 89% yield by the action
of methanesulfonyl chloride and DMAP under stan-
dard conditions. To our delight, further reaction of
D
-
pent-1-yl formate, or by treatment of 2,3,4-tri-O-
benzyl - 5 - benzylseleno - 5 - deoxypentopyranose with
samarium(II) iodide in THF;3,4 these procedures repre-
sent the most efficient methods to date for preparing
these rare selenium-substituted carbohydrate systems.
2,3,4-tri-O-benzyl-1,5-di-O-methanesulfonyl-D-arabitol
(4) with sodium telluride (Na2Te), prepared by the
reduction of tellurium metal with sodium borohydride
in ethanol,17 afforded the required 2,3,4-tri-O-benzyl-
1,5-dideoxy-5-telluro- -arabinose (5) in 82% yield after
D
While selenium-containing compounds are well estab-
lished as having important roles as new generation
pharmaceuticals, exhibiting antioxidant, anti-inflamma-
tory, hepatoprotectant, antiviral and antitumor proper-
purification by flash chromatography (Scheme 1). The
125Te NMR spectrum of tellurosugar (5) revealed a
single resonance at l 77.3 consistent with the formation
of the telluropane ring system,18 while the 13C NMR
spectrum displayed the expected number of signals,
including resonances at l –6.1 and –2.4, consistent with
* Corresponding author. E-mail: carlhs@unimelb.edu.au
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00708-6

3800
O. T. K. Nguyen, C. H. Schiesser / Tetrahedron Letters 43 (2002) 3799–3800
Scheme 1.
aliphatic carbon atoms attached to tellurium.19 In addi-
tion, 5 proved to be optically active, with an [h]2D2 value
of –57.
References
1. (b) Whistler, R. L.; Lake, W. C. Biochem. J. 1970, 130, 919;
(b) Kim, J. H.; Kim, S. H.; Hahn, W. W. Science 1978, 200,
206; (c) Hughes, A. B.; Rudge, A. J. Nat. Prod. Rep. 1994,
135.
2. Inouye, S.; Tsuruoka, T.; Ito, T.; Niida, T. Tetrahedron
1968, 23, 2125.
3. Schiesser, C. H.; Zheng, S.-L. Tetrahedron Lett. 1999, 40,
5059.
4. Lucas, M. A.; Nguyen, O. T. K.; Schiesser, C. H.; Zheng,
S.-L. Tetrahedron 2000, 56, 3995.
5. Kirsi, J. J. Antimicrob. Agent. Chemother. 1983, 24, 353.
6. (a) Schwartz, K. Federation Proc. 1961, 1, 666; (b) Schwartz,
K.; Porter, L. A. Bioinorg. Chem. 1974, 3, 145.
7. Free Radicals in Biology and Medicine; Halliwell, B.;
Gutteridge, J. M. C., Eds.; Oxford: New York, University
Press, 1996.
8. Maciel, E. N.; Bolzan, R. C.; Braga, A. L.; Rocha, J. B.
T. J. Biochem. Mol. Toxicol. 2000, 14, 310.
9. Detty, M. R.; O’Regan, M. B. The Chemistry of Hetero-
cyclic Compounds; Wiley-Interscience: New York, 1994;
Vol. 53.
10. Knapp, F. F., Jr.; Ambrose, K. R.; Callahan, A. P. J. Nucl.
Med. 1980, 21, 251.
11. Knapp, F. F., Jr.; Ambrose, K. R.; Callahan, A. P.; Ferren,
L. A.; Grigsby, R. A.; Irgolic, K. J. J. Nucl. Med. 1981,
22, 988.
Unfortunately, 5 proved to be sufficiently labile to
prevent the acquisition of quality microanalytical data;
indeed, 5 appears to decompose by extrusion of elemen-
tal tellurium even on standing in the freezer. In addi-
tion, we were unable to observe a molecular ion by
various mass spectrometric techniques, including elec-
trospray ionization. Therefore, in order to provide con-
clusive evidence for its formation, tellurosugar (5) was
further reacted with bromine in carbon tetrachloride to
provide the significantly more stable 2,3,4-tri-O-benzyl-
1,5-dideoxy-5-(dibromotelluro)- -arabinose (6) as an
D
orange sticky oil, unsuitable for X-ray analysis. Satisfy-
ingly, dibromide (6) displayed a single signal at l 748.8
in its 125Te NMR spectrum as well as a a signal at m/z
597.0265 in its high resolution ESI spectrum, consistent
with the loss of bromine from the molecular ion and
providing strong evidence that we have indeed pre-
pared the hitherto unknown telluroarabinose ring sys-
tem (5).
In a similar manner,
2,3,4-tri-O-benzyl-1,5-dideoxy-5-telluro-
L
-arabinose was converted into
-arabinose (7).
L
As expected, 7 exhibited identical spectroscopic proper-
ties to its enantiomer (5), the exception being the sign
of its optical rotation; 7 proved to have an [h]2D2 value
of +46.
12. Kirsch, G.; Goodman, M. M.; Knapp, F. F., Jr.
Organometallics 1983, 2, 357.
13. Albeck, A.; Weitman, H.; Sredni, B.; Albeck, M. Inorg.
Chem. 1998, 37, 1704.
We are currently examining the antioxidant properties
of tellurosugars (5, 7) and are exploring the preparation
of analogous tellurosugars derived from ribose and
xylose.
14. Engman, L.; Stern, D.; Cotgreave, I. A.; Andersson, C. M.
J. Am. Chem. Soc. 1992, 114, 9737.
15. Seiyaku, D. Drug. Future 1995, 20, 1057.
16. Vessman, K.; Ekstro¨m, M.; Berglund, M.; Andersson, C.
M.; Engman, L. J. Org. Chem. 1995, 60, 4461.
17. Davies, A. G.; Schiesser, C. H. J. Organomet. Chem. 1990,
389, 301.
Acknowledgements
18. Luthra, N. P.; Odom, J. P. In The Chemistry of Organic
Selenium and Tellurium Compounds; Patai, S.; Rappoport,
Z., Eds.; Wiley-Interscience: Chichester, 1986; Vol. 1.
19. Lucas, M. A.; Schiesser, C. H. J. Org. Chem. 1996, 61, 5754.
We thank the Australian Research Council for financial
support.