RESUMO
The biological relevance of sulfur containing carbohydrates is gaining substantial attention. Thus the new developments, especially in the synthetic and medicinal chemistry of thio-sugars are critically important for carbohydrate drug design. New studies of biological processes including biosynthetic reactions and enzyme control mechanisms, discovered during the last few years clearly contributed to an understanding of their biological roles. These roles of carbohydrates and thio-sugars in particular through biological processes and diseases are becoming better understood now. These new trends will provide tremendous opportunities for the development of carbohydrates as new potential drugs. The main objective of this article is to address these new promising advances
Assuntos
Glucosinolatos/química , Glucosinolatos/síntese química , Tioglicosídeos/química , Tioglicosídeos/síntese química , Aminoglicosídeos , Antibacterianos/química , Configuração de Carboidratos , Sequência de Carboidratos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Glucosinolatos/uso terapêutico , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Neuraminidase/antagonistas & inibidores , Tioglicosídeos/uso terapêuticoRESUMO
alpha-1-Thio-L-fucose derivative 4 and 5 as new alpha-fucosidase inhibitors (K1 = 4.6, and 5.9 microM) have been synthesized in three steps by base catalyzed coupling with bromonitromethane followed by reduction of the nitro group with sodium borohydride/cobalt chloride complex and acetylation.
Assuntos
Desenho de Fármacos , Inibidores Enzimáticos/síntese química , Fucose/análogos & derivados , alfa-L-Fucosidase/antagonistas & inibidores , Animais , Bovinos , Inibidores Enzimáticos/farmacologia , Fucose/síntese química , Fucose/farmacologia , HumanosRESUMO
6-Amino-1,5-anhydro-6-deoxy-D-glucitol (11) was prepared from 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide (1) in six steps. Reduction of 1 with tributyltin hydride, followed by deacetylation, monomolar tosylation, and reacetylation, afforded 2,3,4-tri-O-acetyl-1,5-anhydro-6-O-toluene-p-sulfonyl-D-glucitol (9). Alternatively, tritylation of 1,5-anhydro-D-glucitol, followed by acetylation, detritylation, and tosylation, gave 9. Mesylation gave 8. Treatment of 8 or 9 with azide anion afforded the azide 10, reduction of which with tributyltin hydride gave 11, which was mesylated or tosylated, and then deacetylated to give the 6-methane-sulfonamido or 6-toluene-p-sulfonamido derivative. Similarly, mesylation or tosylation of 3,4,6-tri-O-acetyl-2-amino-1,5-anhydro-2-deoxy-D-glucitol (20) gave the 2-methanesulfonamido or 2-toluene-p-sulfonamido derivatives. Treatment of 11 and 20 with sulfur trioxide-pyridine afforded the sulfoamino derivatives, deacetylation of which gave sugar analogs of cyclamate-like compounds.
Assuntos
Glucosamina/análogos & derivados , Glucosamina/síntese química , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Rotação Ocular , Relação Estrutura-AtividadeRESUMO
3-C-(Hydroxymethyl)erythritol was prepared from 3-C-(hydroxymethyl)-2,3-O-isopropylidene-D-erythro-tetrofuranose (4) by hydrolysis followed by reduction, or by reduction followed by hydrolysis. Monotosylation of 4, followed by reduction with lithium aluminum hydride and hydrolysis, afforded 3-C-methylerythritol.