ORGANIC
LETTERS
2010
Vol. 12, No. 7
1632-1635
Potent Glucosidase Inhibitors:
De-O-sulfonated Ponkoranol and Its
Stereoisomer
Razieh Eskandari,† Douglas A. Kuntz,‡ David R. Rose,‡,§ and B. Mario Pinto*,†
Department of Chemistry, Simon Fraser UniVersity, Burnaby, British Columbia,
Canada V5A 1S6, Department of Medical Biophysics, UniVersity of Toronto and
DiVision of Molecular and Structural Biology, Ontario Cancer Institute, Toronto,
Ontario, Canada M5G 2M9, and Department of Biology, UniVersity of Waterloo,
Waterloo, Ontario, Canada N2L 3G1
Received February 16, 2010
ABSTRACT
Ponkoranol, a glucosidase inhibitor isolated from the plant Salacia reticulata, comprises a sulfonium ion with an internal sulfate counterion.
An efficient synthetic route to de-O-sulfonated ponkoranol and its 5′-stereoisomer is reported, and it is shown that these compounds are
potent glucosidase inhibitors that inhibit a key intestinal human glucosidase, the N-terminal catalytic domain of maltase glucoamylase, with
Ki values of 43 ( 3 and 15 ( 1 nM, respectively.
Compounds isolated from medicinal plants can provide the
lead structures for drug development programs.1,2 For
example, the aqueous extracts of the roots and stems of the
large woody climbing plant Salacia reticulata, known as
Kothalahimbutu in Singhalese, have been used in the
Ayurvedic system of Indian medicine in Sri Lanka and
Southern India for the treatment of Type-2 diabetes.3,4
Several glucosidase inhibitors have been isolated from the
water-soluble fraction of this plant extract and also other
plants that belong to the Salacia genus such as Salacia
chinensis, Salacia prinoides, and Salacia oblonga which
explain, at least in part, the antidiabetic property of the
aqueous extracts of these plants.5-7 Thus far, six components
have been isolated from the plant S. reticulata, namely
salaprinol (1),7 salacinol (2),6 ponkoranol (3),7 kotalanol (4),5
de-O-sulfonated kotalanol (5),8 and de-O-sulfonated salacinol
(6)9 (Figure 1), all of which possess a common structural
motif that comprises a 1,4-anhydro-4-thio-D-arabinitol and
† Simon Fraser University.
(5) Matsuda, H.; Li, Y. H.; Murakami, T.; Matsumura, N.; Yamahara,
‡ University of Toronto and Ontario Cancer Institute.
§ University of Waterloo.
J.; Yoshikawa, M. Chem. Pharm. Bull. 1998, 46, 1399–1403
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J.; Tanabe, G.; Muraoka, O. Tetrahedron Lett. 1997, 38, 8367–8370
(7) Yoshikawa, M.; Xu, F. M.; Nakamura, S.; Wang, T.; Matsuda, H.;
Tanabe, G.; Muraoka, O. Heterocycles 2008, 75, 1397–1405
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(3) Chandrasena, J. P. C. The Chemistry and Pharmacology of Ceylon
and Indian Medicinal Plants; H&C Press: Colombo, Sri Lanka, 1935
(4) Jayaweera, D. M. A. Medicinal Plants Used in Ceylon-Part 1;
National Science Council of Sri Lanka: Colombo, 1981
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10.1021/ol1004005 2010 American Chemical Society
Published on Web 03/10/2010