RESUMO
The veterinary drug Alfaprostol and prostaglandin PGF2α have been synthesized in just nine steps. The strategy involved the conjugate addition of an alkyne to a bicyclic enal, available in three steps by a proline-catalyzed aldol reaction of succinaldehyde. In the case of Alfaprostol, this resulted in the shortest synthesis reported to date. For PGF2α, this approach improved our previous route by making the 1,4-addition and ozonolysis more operationally simple.
RESUMO
Full details of the total synthesis of the Schisandraceae nortriterpenoid natural product rubriflordilactoneâ A are reported. Palladium- and cobalt-catalyzed polycyclizations were employed as key strategies to construct the central pentasubstituted arene from bromoendiyne and triyne precursors. This required the independent assembly of two AB ring aldehydes for combination with a common diyne component. A number of model systems were explored to investigate these two methodologies, and also to establish routes for the installation of the challenging benzopyran and butenolide rings.
Assuntos
Schisandraceae/química , Triterpenos/síntese química , 4-Butirolactona/análogos & derivados , 4-Butirolactona/química , Catálise , Cobalto/química , Ciclização , Espectroscopia de Ressonância Magnética , Paládio/química , Schisandraceae/metabolismo , Estereoisomerismo , Triterpenos/químicaRESUMO
Two enantioselective total syntheses of the nortriterpenoid natural product rubriflordilactoneâ A are described, which use palladium- or cobalt-catalyzed cyclizations to form the CDE rings, and converge on a late-stage synthetic intermediate. These key processes are set up through the convergent coupling of a common diyne component with appropriate AB-ring aldehydes, a strategy that sets the stage for the synthetic exploration of other members of this family of natural products.
Assuntos
Produtos Biológicos/síntese química , Triterpenos/síntese química , Produtos Biológicos/química , Catálise , Cobalto/química , Ciclização , Kadsura/química , Paládio/química , Schisandra/química , Estereoisomerismo , Triterpenos/químicaRESUMO
An enantioselective synthesis of the AB ring system common to the majority of the Schisandra nortriterpenoid natural products is reported. Key steps include a stereospecific ring opening of a trisubstituted epoxide and the use of a ß-lactone to enable installation of the gem-dimethyl functionality of the B ring. An acetalization strategy played a key role in a late-stage biomimetic AB ring bicyclization.
Assuntos
Produtos Biológicos/síntese química , Schisandra/química , Triterpenos/síntese química , Produtos Biológicos/química , Catálise , Ciclização , Lactonas/química , Estrutura Molecular , Estereoisomerismo , Triterpenos/químicaRESUMO
Benzimidazoles are prepared by intramolecular N-arylations of amidines mediated by potassium hydroxide in DMSO at 120 °C. In this manner, diversely substituted products have been obtained in moderate to very good yields.
RESUMO
From insects to cancer: N-Cyano sulfoximines were evaluated for COX inhibition and antiproliferative activity against a panel of cancer cell lines. The most active compound exhibited potent COX-2 inhibition, some selectivity for COX-2 over COX-1, only slight cytotoxicity towards healthy cells (HaCaT skin cells), and no mutagenic potential (as determined by an Ames assay).
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/farmacologia , Nitrilas/química , Nitrilas/farmacologia , Compostos de Enxofre/química , Compostos de Enxofre/farmacologia , Animais , Antineoplásicos/toxicidade , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/toxicidade , Humanos , Insetos , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Prostaglandina-Endoperóxido Sintases/metabolismoRESUMO
The development of complementary palladium- and cobalt-catalyzed approaches to tricyclic arylsilanes suitable for elaboration into the CDE ring systems of rubriflordilactones A and B is reported. Microwave conditions are required to effect a cobalt-catalyzed triyne cyclotrimerization, which critically depends on the substitution pattern of the triyne termini. Mild conditions to elaborate these arylsilanes to the CDE cores of the natural products are described.
Assuntos
Paládio/química , Triterpenos/síntese química , Catálise , Estrutura Molecular , Schisandra/química , Estereoisomerismo , Triterpenos/químicaRESUMO
A simple, practical and efficient continuous-flow hydration-condensation protocol was developed for the synthesis of α,ß-unsaturated ketones starting from alkynes and aldehydes by employing a heterogeneous catalyst in a flow microwave. The procedure presents a straightforward and convenient access to valuable differently substituted chalcones and can be applied on multigram scale.