RESUMO
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.
Assuntos
Heptoses/síntese química , Glicosídeos/síntese química , Glicosídeos/química , Heptoses/química , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
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.
Assuntos
Amino Açúcares/química , Amino Açúcares/síntese química , N-Acetilglucosaminiltransferases/metabolismo , N-Acetil-Lactosamina Sintase/metabolismo , Ácido N-Acetilneuramínico/química , Técnicas de Química Sintética , Helicobacter pylori/enzimologia , Neisseria meningitidis/enzimologiaRESUMO
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.
Assuntos
Antivirais/farmacologia , Inibidores Enzimáticos/farmacologia , Guanidina/análogos & derivados , Guanidina/farmacologia , Neuraminidase/antagonistas & inibidores , Zanamivir/análogos & derivados , Zanamivir/farmacologia , Antivirais/síntese química , Antivirais/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Guanidina/química , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Neuraminidase/metabolismo , Relação Estrutura-Atividade , Zanamivir/síntese química , Zanamivir/químicaRESUMO
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.