alpha- and beta-homogalactonojirimycins (alpha- and beta-homogalactostatins): Synthesis and further biological evaluation

The homoiminosugars alpha- and beta -homogalactonojirimycins were prepared from a common intermediate, tetra-O-benzyl-D-galacto-heptenitol 6, by way of highly stereoselective reaction sequences involving, as the key steps, an internal amidomercuralion (a-epimer) and a double reductive amination (beta -epimer). alpha -Homogalactonojirimycin retains a large part of the potent activity of the parent galactonojirimycin and 1-deoxygalactonojirimycin as an inhibitor of alpha -galaclosidases. However, by contrast with the parent iminosugars, it does not inhibit beta -galactosidases, with the exception of the Jack beans enzyme. beta -Homogalactonojirimycin is a weak cc-galactosidase inhibitor and is completely devoid of activity towards P-galactosidases. Thus, a marked selectivity toward one family of enzymes has been achieved by the addition of an alpha -CH2OH group in the structure of the parent iminosugars. (C) 2001 Elsevier Science Ltd. All rights reserved.


Published in:
Bioorganic & Medicinal Chemistry, 9, 5, 1269-1278
Year:
2001
ISSN:
0968-0896
Keywords:
Note:
ICOA, Fac Sci, F-45067 Orleans 2, France. SUNY Binghamton, Dept Chem, Binghamton, NY 13902 USA. Univ Lausanne, Inst Chim Organ, CH-1015 Lausanne, Switzerland. Hokuriku Univ, Fac Pharmaceut Sci, Kanazawa, Ishikawa 92011, Japan.
Laboratories:




 Record created 2005-11-09, last modified 2018-03-17


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