RESUMO
This study focuses on the synthesis of 1,7- and 3,4-indole-fused lactones via a simple and efficient reaction sequence. The functionalization of these "oxazepino-indole" and "oxepino-indole" tricycles is carried out by palladium catalysed CC coupling, nucleophilic substitution or 1,3-dipolar cycloaddition. The evaluation of their activity against Mycobacterium tuberculosis shows that the "oxazepino-indole" structure is a new inhibitor of M. tuberculosis growth in vitro.
Assuntos
Antibacterianos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
An approach for the preparation of polysubstituted indole-2-carbonitriles through a cross-coupling reaction of compounds 1-(but-2-ynyl)-1H-indole-2-carbonitriles and 1-benzyl-3-iodo-1H-indole-2-carbonitriles is described. The reactivity of indole derivatives with iodine at position 3 was studied using cross-coupling reactions. The Sonogashira, Suzuki-Miyaura, Stille and Heck cross-couplings afforded a variety of di-, tri- and tetra-substituted indole-2-carbonitriles.
RESUMO
In this study, we screen three heterocyclic structures as potential inhibitors of UDP-galactopyranose mutase (UGM), an enzyme involved in the biosynthesis of the cell wall of Mycobacterium tuberculosis. In order to understand the binding mode, docking simulations are performed on the best inhibitors. Their activity on Mycobacterium tuberculosis is also evaluated. This study made it possible to highlight an "oxazepino-indole" structure as a new inhibitor of UGM and of M. tuberculosis growth in vitro.
Assuntos
4-Butirolactona/análogos & derivados , Antituberculosos/síntese química , Inibidores Enzimáticos/síntese química , Indóis/síntese química , Transferases Intramoleculares/antagonistas & inibidores , Tuberculose/tratamento farmacológico , 4-Butirolactona/síntese química , 4-Butirolactona/farmacologia , Antituberculosos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/farmacologia , Humanos , Indóis/farmacologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/enzimologia , Ligação ProteicaRESUMO
Natural O-alkyl-glycerolipids, also known as alkyl-ether-lipids (AEL), feature a long fatty alkyl chain linked to the glycerol unit by an ether bond. AEL are ubiquitously found in different tissues but, are abundant in shark liver oil, breast milk, red blood cells, blood plasma, and bone marrow. Only a few AEL are commercially available, while many others with saturated or mono-unsaturated alkyl chains of variable length are not available. These compounds are, however, necessary as standards for analytical methods. Here, we investigated different reported procedures and we adapted some of them to prepare a series of 1-O-alkyl-glycerols featuring mainly saturated alkyl chains of various lengths (14:0, 16:0, 17:0, 19:0, 20:0, 22:0) and two monounsaturated chains (16:1, 18:1). All of these standards were fully characterized by NMR and GC-MS. Finally, we used these standards to identify the AEL subtypes in shark and chimera liver oils. The distribution of the identified AEL were: 14:0 (20-24%), 16:0 (42-54%) and 18:1 (6-16%) and, to a lesser extent, (0.2-2%) for each of the following: 16:1, 17:0, 18:0, and 20:0. These standards open the possibilities to identify AEL subtypes in tumours and compare their composition to those of non-tumour tissues.
Assuntos
Cromatografia Gasosa/normas , Óleos de Peixe/química , Glicerídeos/síntese química , Fígado/química , Tubarões , AnimaisRESUMO
Starting from (Z)-1-trimethylsilyl-3-bromopenta-2,4-diene, a lithium-bromine exchange reaction followed by addition onto carbonyl compounds provided the corresponding dienyl alcohols. A Peterson-type γ-elimination promoted by a catalytic amount of trimethylsilyl triflate cross-conjugated gave triene systems ([3]dendralene) which rapidly reacted with the appropriate dienophiles to yield tandem intermolecular Diels-Alder cycloadducts.
Assuntos
Compostos Policíclicos/síntese química , Compostos de Trimetilsilil/química , Compostos de Trimetilsilil/síntese química , Catálise , Compostos de Trimetilsilil/metabolismoRESUMO
An efficient and rapid synthesis of the CDEF ring system of lactonamycinone is reported via a highly chemo- and diastereoselective intermolecular Diels-Alder cycloaddition between trans-1,2-disilyloxybenzocyclobutene and the appropriate γ-alkylidenebutenolide. The feasibility and the total chemoselectivity of the [4 + 2] cycloaddition for the construction of a spirolactone moiety via an intramolecular approach (IMDA) using both partners is also described demonstrating the versatility of the γ-alkylidenebutenolide building block.
Assuntos
Furanos/química , Quinonas/química , Alquilação , Ciclização , Indóis/síntese química , Estrutura Molecular , Naftoquinonas/síntese química , Espironolactona/química , EstereoisomerismoRESUMO
In the presence of copper(I) iodide, heteroaromatic ß-iodo-α,ß-unsaturated carboxylic acid systems opposed to terminal alkyne afford selectively 6-endo-dig cyclization products via a tandem coupling oxacyclization reaction.
Assuntos
Química Farmacêutica/métodos , Indóis/síntese química , Piranos/síntese química , Tiofenos/síntese química , Alcinos/química , Ácidos Carboxílicos/química , Catálise , Cobre/química , Ciclização , Iodetos/química , Espectroscopia de Ressonância Magnética , EstereoisomerismoRESUMO
A general and efficient Cu(I)-mediated cross-coupling and heterocyclization reaction of 3-iodoimidazo[1,2-a]pyridine-2-carboxylic acid, and terminal alkynes was developed under very mild conditions. This method allows the introduction in one pot of a third ring fused in positions 2 and 3 of the imidazo[1,2-a]pyridine core with reasonable yields and total regioselectivity. This procedure does not require the use of any expensive supplementary additives, and is palladium-free.
Assuntos
Cobre/química , Imidazóis/química , Piridonas/química , Catálise , Ciclização , Estrutura Molecular , Paládio/químicaRESUMO
The first diastereoselective synthesis of the antimicrobial and cytotoxic agent (-)-caulerpenynol has been achieved in relatively few steps from the commercially available (S)-malic acid.
Assuntos
Alcinos/síntese química , Antibacterianos/síntese química , Antineoplásicos/síntese química , Butadienos/síntese química , Alcinos/química , Antibacterianos/química , Antineoplásicos/química , Butadienos/química , EstereoisomerismoRESUMO
The reaction of 1-trimethylsilylbuta-2,3-diene with tin tetrachloride, antimony trichloride or antimony pentachloride gave the corresponding buta-1,3-dien-2-yl halostannane or stibine derivatives; this ligand exchange was extended to other beta-allenylsilanes.
RESUMO
The present study reports on the formation of supramolecular fibers from a novel cyclen-based ligand and metal salts. In particular, the fibers were shown to stabilize supramolecular porous materials of low density. It was also demonstrated that these fibers could be functionalized by radical polymer growth on their surface. Such new supramolecular fibers constitute a simple and tunable starting material for the synthesis of 1D core-shell objects.
Assuntos
Nanofibras/química , Ciclamos , Compostos Heterocíclicos/química , Ligantes , Metais/química , Metacrilatos/química , Nanofibras/ultraestrutura , PorosidadeRESUMO
Three-component reactions with 3,4-diiodoalk-2-enoic derivatives, primary amines, and terminal alkynes proceeded to give trisubstituted pyrroles in fair to good yields in the presence of palladium and copper catalysts under mild reaction conditions.
Assuntos
Paládio/química , Pirróis/síntese química , Alcinos/química , Aminas/química , Catálise , Cobre/química , Ciclização , Pirróis/químicaRESUMO
A general route to alpha-pyrones and 3-substituted isocoumarins from (Z)-iodovinylic acids 1a-f or 2-iodobenzoic acids 4a-c is described, including compounds bearing a substituent on the aromatic ring. Treatment of (Z)-beta-iodovinylic acids 1a-f or 2-iodobenzoic acids 4a-c with various allenyltributyltin reagents in the presence of palladium acetate, triphenylphosphine, and tetrabutylammonium bromide in dimethylformamide provided good yields of the corresponding alpha-pyrones 3a-k or 3-substituted isocoumarins 5a-g via tandem Stille reaction and 6-endo-dig oxacyclization.
Assuntos
Isocumarinas/síntese química , Pironas/síntese química , Ciclização , Espectroscopia de Ressonância Magnética , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
(Z)-Ethyl-3-perfluoroalkyl-3-magnesiated crotonates were prepared from (Z)-ethyl-3-perfluoroalkyl-3-iodo enoates by iodine-magnesium exchange reaction with isopropylmagnesium bromide in THF at -78 degrees C. These new reagents reacted with a range of electrophiles, leading to polyfunctional products bearing a perfluoroalkyl group.
RESUMO
Palladium-catalyzed stereoselective annulation of a functional vinylstannane by acyl chlorides gives the corresponding alpha-pyran-2-ones in good yields. This annulation most probably proceeds through a Stille reaction/cyclization sequence.