RESUMEN
The synthesis of a fully oxygenated aconitine D ring precursor from (D)-(+)-glucose is described. The route features a highly diastereoselective alkynyl Grignard ketone addition and a base-mediated enelactone to 1,3-diketone rearrangement.
RESUMEN
Anhydrouridines react with aliphatic amines to give N-alkyl isocytosines, but reported procedures often demand very long reaction times and can be low yielding, with narrow scope. A modified procedure for such reactions has been developed, using microwave irradiation, significantly reducing reaction time and allowing facile access to a diverse range of novel nucleosides on the gram scale. The method has been used to prepare a precursor to a novel analogue of lysidine, a naturally occurring iminonucleoside found in tRNA.
Asunto(s)
Aminas/química , Citosina/análogos & derivados , Lisina/análogos & derivados , Nucleósidos/síntesis química , Nucleósidos de Pirimidina/síntesis química , ARN de Transferencia/química , Citosina/química , Lisina/síntesis química , Lisina/química , Estructura Molecular , Nucleósidos/química , Nucleósidos de Pirimidina/química , ARN de Transferencia/metabolismoRESUMEN
Heterocyclic architectures offer powerful creative possibilities to a range of chemistry end-users. This is particularly true of heterocycles containing a high proportion of sp3-carbon atoms, which confer precise spatial definition upon chemical probes, drug substances, chiral monomers and the like. Nonetheless, simple catalytic routes to new heterocyclic cores are infrequently reported, and methods making use of biomass-accessible starting materials are also rare. Here, we demonstrate a new method allowing rapid entry to spirocyclic bis-heterocycles, in which inexpensive iron(III) catalysts mediate a highly stereoselective C-C bond-forming cyclization cascade reaction using (2-halo)aryl ethers and amines constructed using feedstock chemicals readily available from plant sources. Fe(acac)3 mediates the deiodinative cyclization of (2-halo)aryloxy furfuranyl ethers, followed by capture of the intermediate metal species by Grignard reagents, to deliver spirocycles containing two asymmetric centres. The reactions offer potential entry to key structural motifs present in bioactive natural products.
Asunto(s)
Compuestos Férricos/química , Compuestos Heterocíclicos/síntesis química , Compuestos de Espiro/química , Aminas/química , Catálisis , Ciclización , Éteres/química , Compuestos Heterocíclicos/química , Conformación Molecular , EstereoisomerismoRESUMEN
A new application of Pd-catalysed allylation is reported that enables the synthesis of a range of branched sp3 -functionalised sulfonamides, a compound class for which few reported methods exist. By reacting benzyl sulfonamides with allylic acetates in the presence of Pd0 catalysts and base at room temperature, direct allylation was efficiently performed, yielding products that are analogues of structural motifs seen in biologically active small molecules. The reaction was performed under mild conditions and could be applied to nanomolar sigma-receptor binders, thus enabling a late-stage functionalisation and efficient expansion of drug-like chemical space.
Asunto(s)
Teoría Cuántica , Sulfonamidas/química , Acetatos/química , Compuestos Alílicos/química , Catálisis , Paladio , TemperaturaRESUMEN
A preparatively accessible route to a series of conformationally-locked bicyclic morpholines has been developed. This flexible approach allows for diversification in order for a small array of lead-like scaffolds to be synthesised from readily available key building blocks.
Asunto(s)
Compuestos Bicíclicos con Puentes/química , Morfolinas/química , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Espectroscopía de Resonancia Magnética , Conformación Molecular , Morfolinas/síntesis química , Oxidación-Reducción , EstereoisomerismoRESUMEN
A range of chiral, optically-enriched bicyclic oxabispidines were prepared from (S)-(-)-2,3-epoxypropylphthalimide using an efficient sequence featuring a stereocontrolled intramolecular Mannich reaction as the key transformation.
Asunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes/química , Compuestos Bicíclicos Heterocíclicos con Puentes/síntesis química , Cristalografía por Rayos X , Ciclización , Conformación Molecular , Ftalimidas/química , EstereoisomerismoRESUMEN
Treatment of glycidyl sulfonamides with LDA delivers the corresponding enesulfonamide with good selectivity for the E-isomer, whereas the corresponding carbamates exhibit selectivity for the Z-enecarbamate. An E1cB elimination mechanism proceeding from a substrate-base chelate complex is advanced as rationalisation of the latter set of Z-selective outcomes.