ABSTRACT
A general and stereospecific homologation strategy for the synthesis of heptopyranosides is reported. The strategy employs the Wittig olefination and proline-catalyzed α-aminoxylation to achieve one carbon elongation and stereoselective hydroxylation at the C6 position, respectively. The L-glycero- and D-glycero-heptopyranosides can be obtained with nearly perfect stereoselectivity. Further study reveals the difference in the chemical shift of the C6 proton of L/D-glycero-heptopyranosyl diastereomers, which is found to be useful for assignment of the configuration of heptopyranosides.
Subject(s)
Heptoses/chemical synthesis , Glycosides/chemical synthesis , Glycosides/chemistry , Heptoses/chemistry , Molecular Structure , Stereoisomerism , Structure-Activity RelationshipABSTRACT
A simple and efficient protocol for the preparative-scale synthesis of various lengths of oligo-N-acetyllactosamine (oligo-LacNAc) and its multi-sialylated extensions is described. The strategy utilizes one thermophilic bacterial thymidylyltransferase (RmlA) coupled with corresponding sugar-1-phosphate kinases to generate two uridine diphosphate sugars, UDP-galactose and UDP-N-acetylglucosamine. By incorporating glycosyltransferases, oligo-LacNAcs and their sialylated analogs were synthesized.
Subject(s)
Amino Sugars/chemistry , Amino Sugars/chemical synthesis , N-Acetylglucosaminyltransferases/metabolism , N-Acetyllactosamine Synthase/metabolism , N-Acetylneuraminic Acid/chemistry , Chemistry Techniques, Synthetic , Helicobacter pylori/enzymology , Neisseria meningitidis/enzymologyABSTRACT
A series of acylguanidine-modified zanamivir analogs were synthesized and their inhibitory activities against the NAs of avian influenza viruses (H1N1 and H3N2) were evaluated. In particular, zanamivir derivative , with a hydrophobic naphthalene substituent, exhibits the best inhibitory activity against group-1 NA with an IC50 of 20 nM.
Subject(s)
Antiviral Agents/pharmacology , Enzyme Inhibitors/pharmacology , Guanidine/analogs & derivatives , Guanidine/pharmacology , Neuraminidase/antagonists & inhibitors , Zanamivir/analogs & derivatives , Zanamivir/pharmacology , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Guanidine/chemistry , Influenza A Virus, H1N1 Subtype/drug effects , Influenza A Virus, H3N2 Subtype/drug effects , Microbial Sensitivity Tests , Molecular Structure , Neuraminidase/metabolism , Structure-Activity Relationship , Zanamivir/chemical synthesis , Zanamivir/chemistryABSTRACT
Inexpensive and readily available sulfonic acids, p-toluenesulfonic acid, and sulfuric acid are versatile and efficient catalysts for the peracetylation of a broad spectrum of carbohydrate substrates in good yield and in a practical time frame. Three appealing features in sulfonic acid-catalyzed acetylation of free sugars were explored including (1) suppression of furanosyl acetate formation for D-galactose and L-fucose; (2) high yielding chemoselective acetylation of sialic acid under appropriate conditions; and (3) peracetylation of amino sugars with different amino protecting functions. Simple one-pot two step acetylation-thioglycosidation methods for the expeditious synthesis of p-tolyl per-O-acetyl thioglycosides were also delineated.
