ABSTRACT
The chemoenzymatic regioselective acylation of Neu5Ac followed by SmI2-mediated C-glycosylation on a solid support is described for five C-glycosides. This method should facilitate the construction of combinatorial libraries of inhibitors of neuraminidase activity and hemagglutinin interaction as potential antiviral agents.
Subject(s)
Glycosides/chemical synthesis , Neuraminic Acids/chemistry , Acylation , Models, Chemical , Molecular Structure , Neuraminidase/antagonists & inhibitorsABSTRACT
2,2,2-Trifluorodiazoethane was investigated as a reagent for sulfo group protection on hexosamine monosaccharides. The synthesis of glucosamine and galactosamine building blocks fully differentiated for glycosaminoglycan synthesis and the synthesis of glycosyl donors are described. The compatibility of trifluoroethylsulfonate under a variety of reaction conditions has also been investigated. [structure: see text]
Subject(s)
Glycosaminoglycans/chemical synthesis , Hexosamines/chemistry , Monosaccharides/chemical synthesis , Sulfuric Acid Esters/chemistry , Azo Compounds/chemistry , Carbohydrate Conformation , Galactosamine/chemical synthesis , Glucosamine/chemical synthesisABSTRACT
Heparin and low molecular weight heparins are major clinical anticoagulants and the drugs of choice for the treatment of deep venous thrombosis. The discovery of an antithrombin binding domain in heparin focused interest on understanding the mechanism of heparin's antithrombotic/ anticoagulant activity. Various heparin-mimetic oligosaccharides have been prepared in an effort to replace polydisperse heparin and low molecular weight heparins with a structurally-defined anticoagulant. The goal of attaining a heparin-mimetic with no unwanted side-effects has also provided motivation for these efforts. This article reviews structure-activity relationship (SAR) of structurally-defined heparin-mimetic oligosaccharides.
Subject(s)
Anticoagulants , Blood Coagulation/drug effects , Heparin , Oligosaccharides , Animals , Anticoagulants/chemistry , Anticoagulants/pharmacology , Heparin/chemistry , Heparin/pharmacology , Humans , Molecular Structure , Oligosaccharides/chemistry , Oligosaccharides/pharmacology , Structure-Activity RelationshipABSTRACT
Glycosaminoglycans, highly charged polycarboxylated, polysulfated polysaccharides, are an important class of therapeutic agents and investigational drug candidates. Heparin has been widely used as a clinical anticoagulant for over 60 years. Low molecular weight heparins have begun to displace heparin and recently a synthetic heparin pentasaccharide was approved for clinical use in Europe. In addition to heparin (and the related heparan sulfate glycosaminoglycan), dermatan sulfate, chondroitin sulfate, hyaluronan and their derivatives are all in various stages of clinical evaluation. This review focuses on the chemical and chemoenzymatic synthesis of glycosaminoglycan oligosaccharides. Recent advances in functional group protection chemistry, conversion of D-gluco to L-ido or D-galacto configurations, glycosylation reactions and the preparation and use of novel starting materials in acidic oligosaccharide synthesis are discussed.
