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A Short and Flexible Route to Aza‐β‐(1→6)‐ C ‐disaccharides: Selective α‐Glycosidase Inhibitors
Author(s) -
Leeuwenburgh Michiel A.,
Picasso Sylviane,
Overkleeft Herman S.,
van der Marel Gijsbert A.,
Vogel Pierre,
van Boom Jacques H.
Publication year - 1999
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/(sici)1099-0690(199905)1999:5<1185::aid-ejoc1185>3.0.co;2-a
Subject(s) - chemistry , reductive amination , hydrogenolysis , ketose , glycoside hydrolase , amination , diol , stereochemistry , biocatalysis , enzyme , catalytic hydrogenation , organic chemistry , catalysis , aldose , glycoside , reaction mechanism
The syntheses of azaMan‐β‐(1→6)‐ C ‐Glc ( 4 ), azaGlc‐β‐(1→6)‐ C ‐Glc ( 5 ), and azaGal‐β‐(1→6)‐ C ‐Glc ( 6 ) based upon double reductive amination of acetylenic carbohydrate‐derived diketones is described. The required diketones are obtained by addition of the acetylenic sugar anion derived from dibromoolefin 7 to benzyl‐protected mannopyranolactone, glucopyranolactone, or galactopyranolactone, followed by reduction of the ketose and oxidation of the resulting diol. Ensuing double reductive amination and hydrogenolysis affords the target compounds in reasonable to good yields. Enzyme inhibition tests show that neither of the three compounds 4 , 5 , and 6 inhibit β‐glycosidases, while moderate to good inhibitory activities were found on α‐glycosidases, the most active being 6 (α‐galactosidase: K i = 0.092 μ M ).