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1.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361740

RESUMO

There is a challenging need for the development of new alternative nanostructures that can allow the coupling and/or encapsulation of therapeutic/diagnostic molecules while reducing their toxicity and improving their circulation and in-vivo targeting. Among the new materials using natural building blocks, peptides have attracted significant interest because of their simple structure, relative chemical and physical stability, diversity of sequences and forms, their easy functionalization with (bio)molecules and the possibility of synthesizing them in large quantities. A number of them have the ability to self-assemble into nanotubes, -spheres, -vesicles or -rods under mild conditions, which opens up new applications in biology and nanomedicine due to their intrinsic biocompatibility and biodegradability as well as their surface chemical reactivity via amino- and carboxyl groups. In order to obtain nanostructures suitable for biomedical applications, the structure, size, shape and surface chemistry of these nanoplatforms must be optimized. These properties depend directly on the nature and sequence of the amino acids that constitute them. It is therefore essential to control the order in which the amino acids are introduced during the synthesis of short peptide chains and to evaluate their in-vitro and in-vivo physico-chemical properties before testing them for biomedical applications. This review therefore focuses on the synthesis, functionalization and characterization of peptide sequences that can self-assemble to form nanostructures. The synthesis in batch or with new continuous flow and microflow techniques will be described and compared in terms of amino acids sequence, purification processes, functionalization or encapsulation of targeting ligands, imaging probes as well as therapeutic molecules. Their chemical and biological characterization will be presented to evaluate their purity, toxicity, biocompatibility and biodistribution, and some therapeutic properties in vitro and in vivo. Finally, their main applications in the biomedical field will be presented so as to highlight their importance and advantages over classical nanostructures.


Assuntos
Materiais Biocompatíveis/síntese química , Portadores de Fármacos/síntese química , Nanoestruturas/química , Peptídeos/síntese química , Técnicas de Síntese em Fase Sólida/métodos , Sequência de Aminoácidos , Animais , Materiais Biocompatíveis/farmacocinética , Portadores de Fármacos/farmacocinética , Composição de Medicamentos/métodos , Humanos , Nanoestruturas/administração & dosagem , Nanoestruturas/ultraestrutura , Tamanho da Partícula , Peptídeos/farmacocinética , Distribuição Tecidual
2.
Angew Chem Int Ed Engl ; 54(23): 6862-6, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-25907260

RESUMO

The first organocatalyzed trapping of CO2 through C-C and C-O bond formation is reported. Alkynyl indoles together with catalytic amounts of an organic base and five equivalents of CO2 resulted in the formation new heterocyclic structures. These tricyclic indole-containing products were successfully prepared under mild reaction conditions from aromatic, heteroaromatic, and aliphatic alkynyl indoles with complete regioselectivity. Further investigations suggest that C-C bond formation is the initial intermolecular step, followed by lactone-forming C-O bond formation.


Assuntos
Alcinos/química , Compostos Azabicíclicos/química , Dióxido de Carbono/química , Compostos Heterocíclicos/síntese química , Indóis/química , Indóis/síntese química , Catálise , Ciclização , Compostos Heterocíclicos/química , Estrutura Molecular
3.
J Am Chem Soc ; 136(16): 6142-7, 2014 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-24702475

RESUMO

A protocol for the efficient and selective reduction of carbon dioxide to carbon monoxide has been developed. Remarkably, this oxygen abstraction step can be performed with only the presence of catalytic cesium fluoride and a stoichiometric amount of a disilane in DMSO at room temperature. Rapid reduction of CO2 to CO could be achieved in only 2 h, which was observed by pressure measurements. To quantify the amount of CO produced, the reduction was coupled to an aminocarbonylation reaction using the two-chamber system, COware. The reduction was not limited to a specific disilane, since (Ph2MeSi)2 as well as (PhMe2Si)2 and (Me3Si)3SiH exhibited similar reactivity. Moreover, at a slightly elevated temperature, other fluoride salts were able to efficiently catalyze the CO2 to CO reduction. Employing a nonhygroscopic fluoride source, KHF2, omitted the need for an inert atmosphere. Substituting the disilane with silylborane, (pinacolato)BSiMe2Ph, maintained the high activity of the system, whereas the structurally related bis(pinacolato)diboron could not be activated with this fluoride methodology. Furthermore, this chemistry could be adapted to (13)C-isotope labeling of six pharmaceutically relevant compounds starting from Ba(13)CO3 in a newly developed three-chamber system.


Assuntos
Dióxido de Carbono/química , Monóxido de Carbono/química , Césio/química , Fluoretos/química , Temperatura , Catálise , Pressão
4.
Chemistry ; 19(52): 17926-38, 2013 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-24265100

RESUMO

Reaction conditions for the three-component synthesis of aryl 1,3-diketones are reported applying the palladium-catalyzed carbonylative α-arylation of ketones with aryl bromides. The optimal conditions were found by using a catalytic system derived from [Pd(dba)2] (dba=dibenzylideneacetone) as the palladium source and 1,3-bis(diphenylphosphino)propane (DPPP) as the bidentate ligand. These transformations were run in the two-chamber reactor, COware, applying only 1.5 equivalents of carbon monoxide generated from the CO-releasing compound, 9-methylfluorene-9-carbonyl chloride (COgen). The methodology proved adaptable to a wide variety of aryl and heteroaryl bromides leading to a diverse range of aryl 1,3-diketones. A mechanistic investigation of this transformation relying on 31P and 13C NMR spectroscopy was undertaken to determine the possible catalytic pathway. Our results revealed that the combination of [Pd(dba)2] and DPPP was only reactive towards 4-bromoanisole in the presence of the sodium enolate of propiophenone suggesting that a [Pd(dppp)(enolate)] anion was initially generated before the oxidative-addition step. Subsequent CO insertion into an [Pd(Ar)(dppp)(enolate)] species provided the 1,3-diketone. These results indicate that a catalytic cycle, different from the classical carbonylation mechanism proposed by Heck, is operating. To investigate the effect of the dba ligand, the Pd0 precursor, [Pd(η3-1-PhC3H4)(η5-C5H5)], was examined. In the presence of DPPP, and in contrast to [Pd(dba)2], its oxidative addition with 4-bromoanisole occurred smoothly providing the [PdBr(Ar)(dppp)] complex. After treatment with CO, the acyl complex [Pd(CO)Br(Ar)(dppp)] was generated, however, its treatment with the sodium enolate led exclusively to the acylated enol in high yield. Nevertheless, the carbonylative α-arylation of 4-bromoanisole with either catalytic or stoichiometric [Pd(η3-1-PhC3H4)(η5-C5H5)] over a short reaction time, led to the 1,3-diketone product. Because none of the acylated enol was detected, this implied that a similar mechanistic pathway is operating as that observed for the same transformation with [Pd(dba)2] as the Pd source.


Assuntos
Brometos/química , Paládio/química , Catálise , Estrutura Molecular , Oxirredução , Estereoisomerismo
5.
J Org Chem ; 77(17): 7232-40, 2012 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-22892031

RESUMO

Transition-metal-catalyzed C-H amination via nitrene insertion allows the direct transformation of a C-H into a C-N bond. Given the ubiquity of C-H bonds in organic compounds, such a process raises the problem of regio- and chemoselectivity, a challenging goal even more difficult to tackle as the complexity of the substrate increases. Whereas excellent regiocontrol can be achieved by the use of an appropriate tether securing intramolecular addition of the nitrene, the intermolecular C-H amination remains much less predictable. This study aims at addressing this issue by capitalizing on an efficient stereoselective nitrene transfer involving the combination of a chiral aminating agent 1 with a chiral rhodium catalyst 2. Allylic C-H amination of terpenes and enol ethers occurs with excellent yields as well as with high regio-, chemo-, and diastereoselectivity as a result of the combination of steric and electronic factors. Conjugation of allylic C-H bonds with the π-bond would explain the chemoselectivity observed for cyclic substrates. Alkanes used in stoichiometric amounts are also efficiently functionalized with a net preference for tertiary equatorial C-H bonds. The selectivity, in this case, can be rationalized by steric and hyperconjugative effects. This study, therefore, provides useful information to better predict the site of C-H amination of complex molecules.

6.
Chem Soc Rev ; 40(4): 1926-36, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21234469

RESUMO

Catalytic C-H amination has recently emerged as a unique tool for the synthesis of amines. This tutorial review highlights the existing protocols catalyzed by metal complexes (rhodium, copper, ruthenium, manganese and palladium) allowing diastereo- and enantioselective C-H amination. Substrate-, catalyst- and reagent-controlled methodologies are detailed. They involve either catalytic nitrene C-H insertion or C-H activation.

7.
Dalton Trans ; 39(43): 10401-13, 2010 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-20931128

RESUMO

Stereoselective catalytic intermolecular C-H amination of complex molecules is reported. Site-selective functionalizations occur with very good yields up to 91% and excellent d.e.s up to 99%. However, the precise nature of the nitrene C-H insertion remains a matter of debate despite several physical organic experiments.


Assuntos
Carbono/química , Hidrogênio/química , Iminas/química , Alcanos/química , Aminação , Benzeno/química , Catálise , Estereoisomerismo , Especificidade por Substrato , Terpenos/química
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