ABSTRACT
Highly regioselective 1,3-dipolar cycloadditions between d-arabinose-derived nitrones and d-mannitol-derived trans-olefins have been utilized to synthesize isofagomine-pyrrolidine hybrid sugars, hydroxymethylated analogues of (-)-steviamine and analogues of (+)-hyacinthacine C5. All of the new compounds were subsequently tested against several commercially available glycosidases, and some of them showed good and selective glycosidase inhibition.
Subject(s)
Carbohydrates/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Glycoside Hydrolases/antagonists & inhibitors , Imino Pyranoses/chemical synthesis , Imino Sugars/chemical synthesis , Indolizidines/chemical synthesis , Pyrrolidines/chemical synthesis , Pyrrolizidine Alkaloids/chemical synthesis , Carbohydrates/chemistry , Cycloaddition Reaction , Enzyme Inhibitors/chemistry , Glycoside Hydrolases/chemistry , Imino Pyranoses/chemistry , Imino Sugars/chemistry , Indolizidines/chemistry , Molecular Structure , Pyrrolidines/chemistry , Pyrrolizidine Alkaloids/chemistry , StereoisomerismABSTRACT
The importance of glycosidase inhibitors and especially the bicyclic molecules has led to design and assessment of many analogs of naturally occurring molecules. This review focuses on the synthesis and enzyme inhibitions of a few selected (synthetic or non-naturally occurring) molecules that have been reported in the last decade, which allow one to draw some connection between varying the structural features and their effect on glycosidase inhibitions. It is expected that further improvements based on these features could lead to improved inhibitors.
Subject(s)
Azabicyclo Compounds/chemical synthesis , Carbasugars/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Glycoside Hydrolases/antagonists & inhibitors , Azabicyclo Compounds/chemistry , Carbasugars/chemistry , Enzyme Inhibitors/chemistry , Glycoside Hydrolases/metabolism , Indolizidines/chemistry , Structure-Activity RelationshipABSTRACT
Glycals have been transformed into a variety of functionalized substrates which have been found to be useful in synthesizing some aminosugars, N-glycopeptides, nitrosugars and some iminosugars which are potential glycosidase inhibitors. An account of work that has been done in our laboratory is briefly discussed here.
Subject(s)
Amino Sugars/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Glycosides/chemistry , Glycosides/chemical synthesis , Imino Sugars/chemical synthesis , Nitro Compounds/chemical synthesis , Amino Sugars/chemistry , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Glycoside Hydrolases/antagonists & inhibitors , Glycoside Hydrolases/metabolism , Imino Sugars/chemistry , Imino Sugars/pharmacology , Molecular Structure , Nitro Compounds/chemistryABSTRACT
New syntheses of (-)-deoxoprosophylline, (+)-2-epi-deoxoprosopinine, and (2R,3R)- and (2R,3S)-3-hydroxypipecolic acids are reported. Utilization of the chiral functionalities of Perlin aldehydes, derived from 3,4,6-tri-O-benzyl glycals, has been done along with chemoselective saturation of olefins and reductive aminations as key steps.
