RESUMEN
Keto sugar nucleotides (KSNs) are common and versatile precursors to various deoxy sugar nucleotides, which are substrates for the corresponding glycosyltransferases involved in the biosynthesis of glycoproteins, glycolipids, and natural products. However, there has been no KSN synthesized chemically due to the inherent instability. Herein, the first chemical synthesis of the archetypal KSN TDP-4-keto-6-deoxy-d-glucose (1) is achieved by an efficient and optimized route, providing feasible access to other KSNs and analogues, thereby opening a new avenue for new applications.
Asunto(s)
Glucosa , Nucleótidos , GlicosiltransferasasRESUMEN
A streamlined total synthesis of the naturally occurring antitumor agents trioxacarcins is described, along with its application to the construction of a series of designed analogues of these complex natural products. Biological evaluation of the synthesized compounds revealed a number of highly potent, and yet structurally simpler, compounds that are effective against certain cancer cell lines, including a drug-resistant line. A novel one-step synthesis of anthraquinones and chloro anthraquinones from simple ketone precursors and phenylselenyl chloride is also described. The reported work, featuring novel chemistry and cascade reactions, has potential applications in cancer therapy, including targeted approaches as in antibody-drug conjugates.
Asunto(s)
Aminoglicósidos/farmacología , Antraquinonas/farmacología , Antineoplásicos Fitogénicos/farmacología , Descubrimiento de Drogas , Aminoglicósidos/síntesis química , Aminoglicósidos/química , Antraquinonas/síntesis química , Antraquinonas/química , Antineoplásicos Fitogénicos/síntesis química , Antineoplásicos Fitogénicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Estructura Molecular , Relación Estructura-ActividadRESUMEN
New versatile and selective methods for the syntheses of substituted amino- and methoxyphenolic anthraquinones (I-IV) based on fusion of cyanophthalides (V) and semiquinone aminals (VI, VII) under basic conditions are described.
Asunto(s)
Aminas/síntesis química , Antraquinonas/síntesis química , Fenoles/síntesis química , Aminación , Aminas/química , Antraquinonas/química , Benzofuranos/síntesis química , Benzofuranos/química , Fenoles/químicaRESUMEN
A unified and bioinspired oxidative cyclization strategy was used in the first total syntheses of naturally occurring 12-epi-hapalindoleâ Q isonitrile, hapalonamideâ H, deschloro 12-epi-fischerindoleâ I nitrile, and deschloro 12-epi-fischerindoleâ W nitrile, as well as the structural revision of the latter. Hapalindolesâ H and Q were also synthesized.
Asunto(s)
Productos Biológicos/síntesis química , Indoles/síntesis química , Productos Biológicos/química , Indoles/químicaRESUMEN
The first total synthesis of sespenine, a rare indole sesquiterpenoid from a mangrove endophyte, has been accomplished. A bioinspired aza-Prins/Friedel-Crafts/retro Friedel-Crafts cascade reaction assembles the bridged tetrahydroquinoline core. Further investigations on the aza-Prins cyclization imply that the C3 configuration of the hydroxyindolenine intermediate is crucial to the biosynthesis of sespenine and its congener xiamycinâ A.
