RESUMEN
Tunicamycins, which are nucleoside natural products, inhibit both bacterial phospho-N-acetylmuraminic acid (MurNAc)-pentapeptide translocase (MraY) and human UDP-N-acetylglucosamine (GlcNAc): polyprenol phosphate translocase (GPT). The improved synthesis and detailed biological evaluation of an MraY-selective inhibitor, 2, where the GlcNAc moiety was modified to a MurNAc amide, has been described.
Asunto(s)
Antibacterianos/síntesis química , Antibacterianos/farmacología , Proteínas Bacterianas/antagonistas & inhibidores , Transferasas/antagonistas & inhibidores , Tunicamicina/síntesis química , Tunicamicina/farmacología , Proteínas Bacterianas/química , Línea Celular , Técnicas de Química Sintética , Humanos , Modelos Moleculares , Conformación Molecular , Estructura Molecular , Relación Estructura-Actividad , Transferasas/química , Transferasas (Grupos de Otros Fosfatos Sustitutos)RESUMEN
Tunicamycins are nucleoside natural products and show antibacterial, antiviral and antitumor activities, which are attributed to their inhibition of enzymatic reactions between polyisoprenyl phosphate and UDP-GlcNAc or UDP-MurNAc-pentapeptide. Because of their various intriguing biological activities, tunicamycins have potential as therapeutic agents for infectious diseases or cancers. Structurally, tunicamycins have a unique structure composed of an undecodialdose skeleton, a lipid chain and a GlcNAc fragment linked by a 1,1-ß,α-trehalose-type glycosidic bond. In this mini review, we summarize the total chemical syntheses and biosynthetic studies of tunicamycins.
Asunto(s)
Streptomyces/metabolismo , Tunicamicina/biosíntesis , Tunicamicina/síntesis química , Familia de Multigenes , Streptomyces/genéticaRESUMEN
Herbicidin B and fully prtected tunicaminyluracil, which were undecose nucleoside antibiotics, were synthesized using a samarium diiodide (SmI2) mediated aldol reaction with the use of alpha-phenylthioketone as an enolate. The characteristics of the SmI2-mediated aldol reaction are that the enolate can be regioselectively generated and the aldol reaction proceeds under near neutral condition. This reaction is proved to be a powerful reaction for the synthesis of complex nucleoside antibiotics. The synthesis of caprazol, the core structure of caprazamycins, was conducted by the strategy including beta-selective ribosylation without using a neighboring group participation and the construction of a diazepanone by a modified reductive amination. Our synthetic route would provide a range of key analogues with partial structures to define the pharmacophore, which can be a lead for the development of more effective anti-bacterial agents.