Abstract
Deoxynojirimycin (1) and two new related 4-O-hexosaminyl-containing disaccharide mimics, beta-d-TalNAc-(1-->4)-DNJ (4) and beta-d-ManNAc-(1-->4)-DNJ (5), have been studied as agonists of natural killer (NK) cell receptors. As a positive and unexpected result, DNJ (1) displayed a remarkable activation effect towards both NKR-P1A (rat) and CD69 (human) receptors, and a quite similar activity was found for 4 and 5. The synthesis of the two disaccharide mimics is based on an approach that avoids the glycosylation step using known intermediates arising from lactose. The key stage of the synthesis involves the construction of the DNJ unit through an initial C-5 oxidation of the reducing d-glucopyranosyl unit followed by a stereoselective double-reductive aminocyclization of the 1,5-dicarbonyl disaccharide intermediates.
Copyright 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-Deoxynojirimycin / chemical synthesis
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1-Deoxynojirimycin / chemistry
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1-Deoxynojirimycin / pharmacology
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Animals
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Antigens, CD / metabolism*
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Antigens, Differentiation, T-Lymphocyte / metabolism*
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Disaccharides / chemistry
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Glucosamine / analogs & derivatives*
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Glucosamine / chemical synthesis
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Glucosamine / chemistry
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Glucosamine / pharmacology
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Glycosylation
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Hexosamines / chemical synthesis
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Hexosamines / chemistry*
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Hexosamines / pharmacology
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Humans
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Lectins, C-Type / agonists
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Lectins, C-Type / metabolism*
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Monosaccharides / chemistry
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Oxidation-Reduction
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Rats
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Receptors, Immunologic / antagonists & inhibitors
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Receptors, Immunologic / metabolism*
Substances
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD69 antigen
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Disaccharides
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Hexosamines
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Klrb1a protein, rat
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Lectins, C-Type
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Monosaccharides
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Receptors, Immunologic
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deoxynojirimycine
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1-Deoxynojirimycin
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Glucosamine