RESUMEN
Highly enantioselective synthesis of 3,3'-spirooxindole γ-lactams with three contiguous stereocenters (two quaternary) was achieved. The aza-Michael/Mannich cascade reaction of α-imine-ß-oxobutanamides and methyleneindolinones catalyzed by a bifunctional diaminocyclohexane-derived thiourea catalyst gave the desired products in moderate to good yields (up to 78%), moderate to good diastereoselectivities (up to 10:1 dr), and good to excellent enantioselectivities (up to >99% ee). A gram-scale synthesis and some transformations of 3,3'-spirooxindole γ-lactams were also carried out.
Asunto(s)
Lactamas , Tiourea , Estereoisomerismo , CatálisisRESUMEN
A novel approach to synthesize chiral 1,2-oxazinane spirocyclic scaffolds by organocatalytic [4 + 2] cycloaddition reaction between methyleneindolinones and γ-aminooxy-α,ß-unsaturated ester has been disclosed. Furthermore, a hydrazide 1,4-synthon is designed and synthesized to construct chiral hexahydropyridazin spirocyclic scaffolds with methyleneindolinones via [4 + 2] cycloaddition reaction. Both reactions give corresponding products in good to excellent yield, excellent diastereoselectivity and good enantioselectivity.
RESUMEN
The base-controlled dearomative [3 + 2] cycloaddition reaction between 3-nitroindoles and fumaric acid amide esters has been disclosed by using the dearomatization and aromatization strategy. Three kinds of diverse functionalized pyrrolo[2,3-b]indole derivatives were obtained respectively with excellent chemoselectivities and good diastereoselectivities using different bases.
Asunto(s)
Amidas , Indoles , Reacción de Cicloadición , Ésteres , FumaratosRESUMEN
Heparins are natural and partially degraded polyelectrolytes that consist of sulfated polysaccharide backbones. However, as clinically used anticoagulants, heparins are associated with clinical bleeding risks and thus require rapid neutralization. Protamine sulfate is the only clinically approved antidote for unfractionated heparin (UFH), which not only may cause severe adverse reactions in patients, but also is only partially effective against low molecular weight heparins (LMWHs). We here present the facile synthesis of four porous multicationic dynamic covalent polymers (DCPs) from the condensation of tritopic aldehyde and acylhydrazine precursors. We show that, as new water-soluble polymeric antidotes, the new DCPs can effectively include both UFH and LMWHs and thus reverse their anticoagulating activity, which is confirmed by the activated partial thromboplastin time and thromboelastographic assays as well as mouse tail transection assay (bleeding model). The neutralization activities of two of the DCPs were found to be overall superior to that of protamine and have wider concentration windows and good biocompatibility. This pore-inclusion neutralization strategy paves the way for the development of water-soluble polymers as universal heparin binding agents.
Asunto(s)
Anticoagulantes , Heparina , Animales , Anticoagulantes/farmacología , Anticoagulantes/uso terapéutico , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológico , Heparina/química , Heparina/farmacología , Heparina de Bajo-Peso-Molecular/farmacología , Humanos , Ratones , Polímeros/química , Polímeros/farmacología , Porosidad , AguaRESUMEN
A novel, practical, highly efficient, and transition metal free nitrogen insertion reaction for the synthesis of 2,3-disubstituted quinazolinone derivatives was developed. Diverse functionalized 3-indolinone-2-carboxylates and nitrosoarenes with a wide range of substituted nitrosobenzenes, nitrosopyridines, dibenzofuranyl, or dibenzothienyl nitroso compounds worked smoothly to give 2,3-disubstituted quinazolinone derivatives in good to excellent yields (69-98%). A gram-scale reaction was achieved, and an afloqualone analogue was synthesized under the mild reaction conditions.
RESUMEN
A simple, direct, and highly enantioselective synthesis of spiro-oxindole piperidin-2-one derivatives was achieved through an aza-Michael/Michael cyclization cascade sequence using a squaramide catalyst. The desired products were obtained in excellent yields (up to 99%) and good to high stereoselectivities (up to >20:1 dr and up to 99% ee) under mild conditions.
Asunto(s)
Compuestos de Espiro , Ciclización , Oxindoles , Piperidonas , EstereoisomerismoRESUMEN
Two metal porous organic polymers (POPs) that contain the [Ru(bpy)3]2+ cores are prepared via one-pot Suzuki-Miyaura coupling reactions. Both Ru-POPs are thermally stable at up to 340 °C in air and do not dissolve in all solvents tested. One of the POPs has been revealed to be highly effective and reusable as a heterogeneous photocatalyst for visible light-driven enantioselective alkylation of aldehydes. After 10 cycles, the catalyst still maintains the enantioselectivity, while the activity just decreases slightly.
RESUMEN
Herein, we report stoichiometric investigations embodying the first highly enantioselective aryl-aryl coupling facilitated by a gold complex. With up to 91% ee, this is the first demonstration of a transmetalation and C(sp2)-C(sp2) reductive elimination sequence with high enantioselectivity using a gold complex. The results offer a basis for development of enantioselective gold-catalyzed aryl-aryl coupling reactions.
RESUMEN
A series of chiral spiroketal bisphosphine ligands containing 1,1'-spirobi(3 H,3' H)isobenzofuran backbones was accessed through asymmetric synthesis and subsequently tested in enantioselective Rh-catalyzed hydrogenation of α-dehydroamino acid esters. The ligand providing the highest enantioselectivity (up to 99.5%) was obtained in seven steps in an overall 38% yield. The synthesis could be performed on a gram scale, and no kinetic resolution of enantiomers is required. Overall, the developed ligand provides an easily accessible alternative to SDP ligands as well as other chiral bisphosphine ligands.
RESUMEN
The highly enantioselective preparation of spirooxindoles bearing α,α-disubstituted α-amino-ß-keto esters was achieved through [4 + 1] annulation of oxindoles and α-imine-ß-oxo-γ,δ-unsaturated esters under mild conditions in good yields (up to 82%) and stereoselectivities (up to >20:1 dr, 96% ee). The reaction is amenable to gram scale synthesis using catalyst loading as low as 1 mol %. The corresponding chiral α,α-disubstituted α-amino-ß-keto esters could be easily transformed into cyclopenta[ b]indole derivatives without erosion of enantiopurity.
RESUMEN
An asymmetric route to (-)-α-lycorane and (-)-zephyranthine, and a formal total synthesis of (+)-clivonine were achieved. A pivotal intermediate, which serves as a potent precursor for the divergent syntheses of these natural products, was accessed by a diastereoselective Pd-catalyzed cinnamylation of an N-tert-butanesulfinyl imine.
Asunto(s)
Alcaloides/síntesis química , Alcaloides de Amaryllidaceae/síntesis química , Fenantridinas/síntesis química , Alcaloides/química , Alcaloides de Amaryllidaceae/química , Cristalografía por Rayos X , Modelos Moleculares , Estructura Molecular , Fenantridinas/química , EstereoisomerismoRESUMEN
Highly diastereoselective palladium catalyzed cinnamylation of N-tert-butanesulfinyl imines with cinnamyl acetates has been established to provide enantioenriched ß-aryl homoallylic amines. The synthetic application of this stragety has been successfully demonstrated in the concise total syntheses of antitumor natural products (+)-lycoricidine and (+)-7-deoxypancratistatin.
RESUMEN
A Michael-Mannich-hemiaminalization-dehydration cascade reaction was developed for the construction of spirooxindole benzoquinolizine derivatives. Additionally, spirooxindole benzoindolizidine was prepared conveniently through a ring-contracted rearrangement reaction from spirooxindole benzoquinolizine.
RESUMEN
The practical asymmetric synthesis of amathaspiramides B, D, and F has been accomplished by utilizing an aza-Barbier allylation as the key step to construct the common intermediate with two adjacent stereocenters. A kinetically controlled cyclization to build the challenging thermodynamically less stable 8R-hemiaminal moiety is also important in the synthesis of amathaspiramide D. The route is readily scalable, and gram quantity of the final product D has been prepared.
RESUMEN
A new method for the construction of five-membered spirocyclic oxindoles is based on a Michael-Mannich cascade reaction of a ketimine intermediated catalyzed by a bifunctional quinine-derived squaramide. The desired products were obtained in excellent yields (up to 94%) and stereoselectivities (up to >20:1 d.r., >99% ee). A scaled-up variant also proceeded smoothly showing that the one-pot reaction might find application in the synthesis of bioactive-compound libraries.
Asunto(s)
Iminas/química , Indoles/síntesis química , Nitrilos/química , Quinina/análogos & derivados , Compuestos de Espiro/síntesis química , Catálisis , Dominio Catalítico , Indoles/química , Estructura Molecular , Quinina/química , Compuestos de Espiro/química , EstereoisomerismoRESUMEN
A highly efficient approach for the construction of indolizidines and quinolizidines bearing a bridged quaternary stereocenter has been established in a one-pot fashion using aldehydes, nitroalkenes, and cyclic ketimines with excellent enantioselectivities and in high yields. Moreover, this method could be applied to the synthesis of indolizidines in the gram scale.
Asunto(s)
Aldehídos/química , Alcaloides/síntesis química , Alquenos/química , Iminas/química , Indolicidinas/química , Nitrilos/química , Quinolizidinas/química , Alcaloides/química , Cristalografía por Rayos X , Conformación Molecular , EstereoisomerismoRESUMEN
An organocatalytic cascade reaction was established for the construction of indoloquinolizidine derivatives bearing five contiguous stereocenters from readily available aliphatic aldehydes, nitroethylenes, and tryptamine. This one-pot process gave 30-55% overall yields with excellent d.r. (>20 : 1 in all cases) and ee (91-98%). Additionally, quaternary stereogenic carbon center-containing indoloquinolizidines were prepared through NBS-mediated cyclization of one of the intermediates.
Asunto(s)
Aldehídos/química , Etilenos/química , Indolquinonas/síntesis química , Quinolizidinas/síntesis química , Triptaminas/química , Técnicas de Química Sintética/métodos , EstereoisomerismoRESUMEN
A four-component asymmetric α-aminoxylation/aza-Michael/Mannich cascade reaction for the construction of fully substituted chiral tetrahydro-1,2-oxazine derivatives was accomplished in high yields with excellent enantio- and diastereoselectivities under mild conditions. The 1,2-oxazine derivative could be transformed to the corresponding multifunctional chiral amino alcohol by N-O cleavage and fused-tricyclic 4-amino-substituted tetrahydroquinolines in good yields with excellent stereoselectivities followed by a Friedel-Crafts reaction. Also a 4-alkoxy-substituted tetrahydroquinoline was achieved by C-4 inversion of a 4-amino-substituted tetrahydroquinoline.
Asunto(s)
Oxazinas/síntesis química , Compuestos Policíclicos/química , Quinolinas/química , Catálisis , Estructura Molecular , Oxazinas/química , EstereoisomerismoRESUMEN
A highly efficient method for the asymmetric synthesis of chiral quaternary carbon-containing homoallylic and homopropargylic amines under mild conditions was achieved with good yields and high diastereoselectivities.
Asunto(s)
Aminas/química , Compuestos Alílicos/química , Iminas/química , Nitrilos/química , Zinc/químicaRESUMEN
A highly efficient cascade process of Michael-aza-Henry-hemiaminalization-dehydration was established for the construction of enantiopure tetrahydropyridines using the combination of prolinol trimethylsilyl ether and cinchona alkaloid catalysts. This new approach allowed for the application of aliphatic imines, generated in situ from aldehydes and amines. Good yields (up to 90%), high enantio- (up to >99% ee) and diastereoselectivities (>99 : 1 d.r. in all cases) were achieved for a broad spectrum of substrates under mild conditions.