RESUMEN
We report the synthesis and biological evaluation of a series of (-)-englerinâ A analogues obtained along our previously reported synthetic route based on a stereoselective gold(I) cycloaddition process. This synthetic route is a convenient platform to access analogues with broad structural diversity and has led us to the discovery of unprecedented and easier-to-synthesize derivatives with an unsaturation in the cyclopentyl ring between C4 and C5. We also introduce novel analogues in which the original isopropyl motif has been substituted with cyclohexyl, phenyl, and cyclopropyl moieties. The high selectivity and growth-inhibitory activity shown by these new derivatives in renal cancer cell lines opens new ways toward the final goal of finding effective drugs for the treatment of renal cell carcinoma (RCC).
Asunto(s)
Antineoplásicos Fitogénicos/síntesis química , Sesquiterpenos de Guayano/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Catálisis , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Reacción de Cicloadición , Ensayos de Selección de Medicamentos Antitumorales , Oro/química , Humanos , Sesquiterpenos de Guayano/síntesis química , Sesquiterpenos de Guayano/farmacología , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
Because of the frequent occurrence of cyclopentane subunits in bioactive compounds, the development of efficient catalytic asymmetric methods for their synthesis is an important objective. Introduced herein is a new family of chiral nucleophilic catalysts, biphenyl-derived phosphepines, and we apply them to an enantioselective variant of a useful [4+1] annulation. A range of one-carbon coupling partners can be employed, thereby generating cyclopentenes which bear a fully substituted stereocenter [either all-carbon or heteroatom-substituted (sulfur and phosphorus)]. Stereocenters at the other four positions of the cyclopentane ring can also be introduced with good stereoselectivity. An initial mechanistic study indicates that phosphine addition to the electrophilic four-carbon coupling partner is not the turnover-limiting step of the catalytic cycle.
Asunto(s)
Ciclopentanos/química , Fosfinas/química , Catálisis , Ciclización , Modelos Moleculares , EstereoisomerismoRESUMEN
The copper(I)-catalyzed reaction of alkenyldiazoacetates and iminoiodinanes affords functionalized azetine derivatives. This process is consistent with the formation of an aziridinyldiazoacetate intermediate, which gives rise to the four-membered heterocycles by metal-catalyzed ring expansion. The resulting azetine structure is a direct precursor of azeditine-2-carboxylic acid derivatives (EWG = electron-withdrawing group).
Asunto(s)
Azetinas/química , Cobre/química , Compuestos de Diazonio/química , Iminas/química , Catálisis , Ciclización , Halogenación , Estructura Molecular , Oxidación-ReducciónRESUMEN
The copper(II)-catalyzed reaction of alkenyldiazo compounds with iodosylbenzene leading to ß-oxodiazo derivatives is reported. This process occurs via an unprecedented 1,2-shift of the diazoacetate function. A selection of the synthetic applications of a representative member of this new class of functionalized diazo derivatives in the regioselective synthesis of substituted 1,4-dicarbonyl compounds is also reported.
Asunto(s)
Compuestos Azo/síntesis química , Cobre/química , Compuestos Organometálicos/química , Compuestos Azo/química , Catálisis , Estructura Molecular , Oxidación-Reducción , EstereoisomerismoRESUMEN
The copper(I)-catalyzed regioselective [3 + 2] cyclization of pyridines toward alkenyldiazoacetates leading to functionalized indolizine derivatives is reported. A broad range of pyridine derivatives (including quinoline and isoquinoline) is compatible with this cyclization reaction. The process represents the first successful example of metal-catalyzed cyclization of a π-deficient heterocyclic system with alkenyldiazo compounds.
RESUMEN
Polysubstituted furan derivatives are regioselective obtained from (bis-alkynyl)methyl carboxylates in the presence of catalytic amounts of copper(I) salts. This multistep process is consistent with the intermediacy of a copper(I) (2-furyl)carbene complex which is intercepted by suitable trapping reagents.
RESUMEN
A broad range of substituted 2-cyclopentenone derivatives 3-6 are synthesized by the nickel(0)-mediated [3 + 2] cyclization reaction of chromium alkenyl(methoxy)carbene complexes 1 and internal alkynes 2. The reaction takes place with complete regioselectivity with both unactivated alkynes and activated alkynes (electron-withdrawing and electron-donating substituted alkynes). Representative cycloadducts containing boron and tin substituents are further demonstrated to be active partners in classical Pd-catalyzed C-C coupling processes to allow the production of 2-aryl- and 2-alkynyl-substituted cyclopentenones 9-13.