RESUMEN
[reaction: see text] A total synthesis of (+)-bullatacin has been accomplished via a diastereoselective [3+2] annulation reaction of the highly enantiomerically enriched allylsilane 3 and racemic aldehyde 4, which provides the key bis-tetrahydrofuran fragment 15 with > or = 20:1 ds.
Asunto(s)
Aldehídos/química , Alquenos/química , Furanos/síntesis química , Silanos/química , Boro/química , Furanos/química , Hidroxilación , Cinética , Estructura Molecular , EstereoisomerismoRESUMEN
[reaction: see text] The protiodesilylation of unactivated C(sp3)-SiMe2Ph bonds proceeds efficiently by treatment with tetrabutylammonium fluoride in wet DMF or THF via isolable dimethylsilanol intermediates.
Asunto(s)
Furanos/química , Compuestos de Amonio Cuaternario/química , Silanos/química , Estructura Molecular , Relación Estructura-ActividadRESUMEN
SAR about the B-ring of a series of N(2)-aroyl anthranilamide factor Xa (fXa) inhibitors is described. B-ring o-aminoalkylether and B-ring p-amine probes of the S1' and S4 sites, respectively, afforded picomolar fXa inhibitors that performed well in in vitro anticoagulation assays.
Asunto(s)
Antitrombina III/síntesis química , Inhibidores del Factor Xa , Colorantes Fluorescentes/farmacología , ortoaminobenzoatos/farmacología , Anticoagulantes/química , Antitrombina III/química , Sitios de Unión , Química Farmacéutica/métodos , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Colorantes Fluorescentes/síntesis química , Humanos , Cinética , Modelos Químicos , Conformación Molecular , Relación Estructura-Actividad , ortoaminobenzoatos/síntesis químicaRESUMEN
A highly stereoselective total synthesis of (+)-asimicin (1) is reported. The synthesis features two chelate-controlled [3 + 2] annulation reactions-one of which (e.g., 2 + 3) constitutes a key, convergent fragment assembly step-that establish all of the stereochemistry of the bis-tetrahydrofuran unit of the natural product.
Asunto(s)
Furanos/síntesis química , Silanos/química , EstereoisomerismoRESUMEN
[Structure: See text] Double asymmetric [3 + 2]-annulation reactions of chiral beta-silyloxyallylsilanes with chiral 2-tetrahydrofuranyl carboxaldehydes have been studied, leading to the stereocontrolled synthesis of six diastereomeric bis-tetrahydrofuran structures corresponding to the core subunits of members of the Annonaceous acetogenin family of natural products. Transition-state models are proposed to account for the stereoselectivity of the double-stereodifferentiating [3 + 2]-annulation reactions.
Asunto(s)
Aldehídos/química , Compuestos Alílicos/química , Alcoholes Grasos/química , Furanos/síntesis química , Lactonas/química , Silanos/química , Acetogeninas , Quelantes , Furanos/química , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Conformación MolecularRESUMEN
Several non-amidino S1 derivatives of the 1,2-diaminobenzene-based scaffold (4) were synthesized and evaluated for their ability to bind to the active site and inhibit the human protease factor Xa. A subset of these compounds were also evaluated for their anticoagulant effects in human plasma as measured by prothrombin time (PT).