RESUMO
The first enantioselective total synthesis of penostatin E has been accomplished. Two highly efficient and diastereoselective reactions, a Hosomi-Sakurai allylation and an intramolecular Pauson-Khand reaction, were utilized for the construction of the basic carbon framework of the target molecule as the key steps. A late-stage introduction of the side chain and a successful base-promoted elimination reaction afforded an efficient synthetic route to (+)-penostatin E.
Assuntos
Alcenos/química , Indenos/química , Indenos/síntese química , Dicroísmo Circular , Espectroscopia de Ressonância Magnética , Estrutura Molecular , EstereoisomerismoRESUMO
Total synthetic studies on natural products with promising biological profiles, coupled with their intriguing structural features, are described. The target molecules dealt with in this article are five helianane-type sesquiterpenes (heliannuols A, D and K and heliespirones A and C) and three meroterpenes (breviones A, B and C) with allelopathic activity, as well as four cytotoxic polyketides (lasonolide A and aspergillides A, B and C) and two pyrrolidinoindoline alkaloids (physostigmine and psychotrimine) with acetylcholine esterase inhibitory and antibacterial activities.
Assuntos
Alcaloides/síntese química , Produtos Biológicos/síntese química , Técnicas de Química Sintética/métodos , Policetídeos/síntese química , Sesquiterpenos/síntese química , Terpenos/síntese química , Alcaloides/química , Alcaloides/farmacologia , Animais , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Humanos , Policetídeos/química , Policetídeos/farmacologia , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Estereoisomerismo , Terpenos/química , Terpenos/farmacologiaRESUMO
The first enantioselective total syntheses of pygmaeocins B and C have been accomplished using an efficient and highly diastereoselective intramolecular Heck cyclization for the construction of a quaternary stereogenic center and the functionalized A-ring of the natural products as the key step.
Assuntos
Produtos Biológicos/química , Diterpenos/química , Diterpenos/síntese química , Ciclização , Espectroscopia de Ressonância Magnética , EstereoisomerismoRESUMO
The reaction of propargylic carbonates with 4-hydroxy-2-pyrones in the presence of a palladium catalyst is described. By the choice of the reaction temperature, two types of the substituted furo[3,2-c]pyran-4-one derivatives were regioselectively synthesized, respectively.
Assuntos
Paládio/química , Pargilina/análogos & derivados , Pargilina/química , Pironas/química , Catálise , Ciclização , Estrutura Molecular , Pironas/síntese química , EstereoisomerismoRESUMO
A novel and highly diastereoselective intramolecular carbamoylketene/alkene [2 + 2] cycloaddition has been developed, and the methodology was successfully applied to the enantioselective syntheses of (-)-esermethole and Takayama's intermediate for (+)-psychotrimine.
Assuntos
Alcenos/química , Alcaloides Indólicos/síntese química , Fisostigmina/análogos & derivados , Pirróis/química , Catálise , Alcaloides Indólicos/química , Estrutura Molecular , Fisostigmina/síntese química , Fisostigmina/química , EstereoisomerismoRESUMO
This'll fix it: efficient fixation of atmospheric CO(2) has been achieved by the reaction of propargylic amines with a silver/DBU dual-catalyst system. Various oxazolidinones were synthesized in moderate to good yields by using substituted propargylic amines.
Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/química , Oxazolidinonas/síntese química , Pargilina/química , Prata/química , Aminas , Dióxido de Carbono , Catálise , Estrutura Molecular , EstereoisomerismoRESUMO
Total synthesis of debromoflustramines B and E has been accomplished by using a platinum-catalyzed addition reaction of o-aminophenylboronic acid with the allene and an intramolecular carbamoylketene-alkene [2 + 2] cycloaddition for the construction of the basic carbon framework of the target alkaloids as the key steps.
Assuntos
Alcaloides/síntese química , Alcenos/química , Alcaloides Indólicos/síntese química , Alcaloides/química , Ciclização , Alcaloides Indólicos/química , Estrutura Molecular , EstereoisomerismoRESUMO
A full account of the development of a novel type of the intramolecular Hosomi-Sakurai reactions of the substrates with a p-benzoquinone and an allylsilane moieties connected by an ether linkage is described. This transformation proceeds via an addition-elimination sequence and provides the products with two stereogenic centers through a 1,3(or 1,4)-asymmetric induction in good to excellent diastereoselectivities. A reasonable mechanistic possibility for the reaction, determination of the stereochemistry for the product, and scope and limitation of the transformation are also discussed. The methodology developed here can successfully be applied to the enantiocontrolled total synthesis of the natural enantiomers of (-)-heliespirone A and (+)-heliespirone C, which have been isolated from sunflower Helianthus annuus L. as allelochemicals.
Assuntos
Alcenos/química , Benzoquinonas/química , Sesquiterpenos/química , Sesquiterpenos/síntese química , Silanos/química , Benzoquinonas/síntese química , Catálise , Estrutura Molecular , EstereoisomerismoRESUMO
An enantioselective synthesis of 8-epi-xanthatin (9) has been accomplished starting from the bicyclic lactone 3, which has been used for the synthesis of other xanthanolides, sundiversifolide (4) and diversifolide (5), through a synthetic route without the use of a selenium species. Additionally we have evaluated antimicrobial activities of five natural xanthanolides and their derivatives. Although the synthetic xanthanolides did not show any activity against methicillin-resistant Staphylococcus aureus (MRSA), some of the synthetic intermediates did exhibit moderate antimicrobial activities.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Furanos/química , Furanos/farmacologia , Antibacterianos/síntese química , Antifúngicos/síntese química , Fungos/efeitos dos fármacos , Furanos/síntese química , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Micoses/tratamento farmacológico , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , EstereoisomerismoRESUMO
The first total synthesis of penostatin B has been accomplished by using a highly diastereoselective Pauson-Khand reaction and an efficient relay ring-closing metathesis for the construction of the basic carbon skeleton of the natural product as the key steps.
Assuntos
Benzopiranos/síntese química , Carbono/química , Estrutura Molecular , EstereoisomerismoRESUMO
A recent report has described that S-15176 (N-[(3,5-di-tert-butyl-4-hydroxy-1-thiophenyl)]-3-propyl-N'-(2,3,4-trimethoxybenzyl) piperazine), an anti-ischemic agent, inhibits the mitochondrial permeability transition (PT) induced by not only Ca(2+) and inorganic phosphate, but also by tert-butylhydroperoxide or phenylarsine oxide [Morin et al. (Biochem Pharmacol 72:911-918, 2006)]. In the present study, we tested the effects of S-15176 on the PT induced by Ag(+), PT of which is not suppressed by cyclosporin A or oligomycin. S-15176 was effective in suppressing the PT and the subsequent cytochrome c release induced by Ag(+), and hence, it was concluded to be a more universal PT inhibitor than cyclosporin A or oligomycin. In addition to the PT-suppression activity, S-15176 also showed weak protonophoric activity. Thus, we further tested to investigate whether the hydroxyl group of S-15176 was involved in its PT-suppression or weak protonophoric activities. The methylated derivative of S-15176 also showed both PT suppression and weak protonophoric activities; hence, the hydroxyl group of S-15176 was concluded not to be involved in these activities.
Assuntos
Ciclosporina/farmacologia , Citocromos c/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Piperazinas/metabolismo , Piperazinas/farmacologia , Prótons , Prata/farmacologia , Animais , Cálcio/farmacologia , Relação Dose-Resposta a Droga , Íons , Masculino , Metilação/efeitos dos fármacos , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/ultraestrutura , Poro de Transição de Permeabilidade Mitocondrial , Nefelometria e Turbidimetria , Oligomicinas/farmacologia , Ratos , Ratos WistarRESUMO
The reaction of 2-alkynyl-1-azaspiro[2.3]hexanes with a platinum catalyst is described. 1,4,5,6-Tetrahydrocyclopenta[b]pyrroles having a variety of substituents were conveniently synthesized via a cascade cyclization/ring-expansion process.
Assuntos
Ciclopentanos/síntese química , Hexanos/química , Platina/química , Pirróis/síntese química , Compostos de Espiro/química , Catálise , Ciclização , Ciclopentanos/química , Estrutura Molecular , Pirróis/química , EstereoisomerismoRESUMO
The reaction of propargylic acetates with 2-oxocyclohex-3-enecarboxylates in the presence of a palladium catalyst is described. Substituted 7-methylenebicyclo[3.2.1]oct-3-en-2-ones were synthesized in a highly diastereoselective manner.
Assuntos
Acetatos/química , Compostos Bicíclicos com Pontes/síntese química , Ácidos Cicloexanocarboxílicos/síntese química , Octanos/química , Paládio/química , Catálise , Ciclização , Ligantes , Metilação , Modelos Moleculares , Estrutura Molecular , EstereoisomerismoRESUMO
The second-generation enantioselective total synthesis of aspergillide C, a new type of 14-membered macrolide isolated from a marine-derived fungus, has been accomplished in a longest linear sequence of 15 steps from a chiral building block in 19% overall yield employing the 6-exo-trig transannular oxy-Michael reaction as the key step.
Assuntos
Macrolídeos/química , Macrolídeos/síntese química , Piranos/química , EstereoisomerismoRESUMO
Enantiocontrolled total syntheses of the breviones A, B, and C have been accomplished using a highly diastereoselective oxidative coupling of an α-pyrone with a tricyclic diene prepared from an optically pure Wieland-Miescher ketone derivative through the 7-endo-trig mode of acyl radical cyclization.
Assuntos
Diterpenos/química , Diterpenos/síntese química , Compostos Policíclicos/química , Compostos Policíclicos/síntese química , Pironas/química , Pironas/síntese química , Compostos de Espiro/química , Compostos de Espiro/síntese química , Ciclização , Estereoisomerismo , Especificidade por SubstratoAssuntos
Antineoplásicos/síntese química , Macrolídeos/síntese química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Concentração Inibidora 50 , Macrolídeos/química , Macrolídeos/farmacologia , Camundongos , Estrutura Molecular , EstereoisomerismoRESUMO
Recently, increasing evidence suggests that the antihypertensive drug nifedipine acts as a protective agent for endothelial cells, and that the activity is unrelated to its calcium channel blocking. Nifedipine is unstable under light and reportedly decomposes to a stable nitrosonifedipine (NO-NIF). NO-NIF has no antihypertensive effect, and it has been recognized as a contaminant of nifedipine. The present study for the first time demonstrated that NO-NIF changed to a NO-NIF radical in a time-dependent manner when it interacted with human umbilical vein endothelial cells (HUVECs). The electron paramagnetic resonance (EPR) signal of NO-NIF radicals in HUVECs showed an asymmetric pattern suggesting that the radicals were located in the membrane. The NO-NIF radicals had radical scavenging activity for 1,1-diphenyl-2-picrylhydrazyl, whereas neither NO-NIF nor nifedipine did. In addition, the NO-NIF radical more effectively quenched lipid peroxides than NO-NIF or nifedipine. Furthermore, NO-NIF attenuated the superoxide-derived free radicals in HUVECs stimulated with LY83583, and suppressed iron-nitrilotriacetic acid (Fe-NTA)-induced cytotoxicity in rat pheochromocytoma (PC12) cells. Our findings suggest that NO-NIF is a candidate for a new class of antioxidative drugs that protect cells against oxidative stress.
Assuntos
Antioxidantes/química , Antioxidantes/metabolismo , Nifedipino/química , Nifedipino/metabolismo , Fotólise , Animais , Antioxidantes/farmacologia , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Nifedipino/farmacologia , Células PC12 , Fotólise/efeitos dos fármacos , RatosRESUMO
Highly substituted chromans have been constructed in a highly stereoselective manner by a palladium-catalyzed reaction of propargylic carbonates with 2-(2-hydroxyphenyl)acetates. Enantioselective reactions also successfully proceeded to give the optically active chromans with high enantioselectivity.
Assuntos
Acetatos/química , Carbonatos/química , Cromanos/química , Paládio/química , Catálise , Ciclização , Estereoisomerismo , Especificidade por SubstratoRESUMO
The N-Heterocyclic carbene-catalysed oxidative carboxylation of arylaldehydes with water successfully proceeded when a sulfoxylalkyl-substituted imidazolium salt was used as the catalyst. The reactions can be run in the absence of oxidant, and a variety of arylaldehydes having an electron-withdrawing group were converted to the corresponding carboxylic acids.