Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Angew Chem Int Ed Engl ; 62(42): e202310436, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37599267

RESUMO

The reactivity of novel chiral lactamide-substituted diselenide-based reagents under oxidative conditions was exploited to develop a metal-free method for the preparation of enantioenriched allenylamides from simple alkynes in good yields, and with enantiomeric excesses up to 99 %. The key of the success in this method is attributed to the hydrogen-bonded lactamide appendages that ensure configurational stability of chiral vinyl selenoxide intermediates for an optimal enantiotopic ß-syn-elimination step.

2.
Angew Chem Int Ed Engl ; 60(27): 14967-14974, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-33851775

RESUMO

Many natural products of plant or microbial origins are derived from enzymatic dearomative oxygenation of 2-alkylphenolic precursors into 6-alkyl-6-hydroxycyclohexa-2,4-dienones. These so-called ortho-quinols cyclodimerize via a remarkably selective bispericyclic Diels-Alder reaction. Whether or not the intervention of catalytic or dirigent proteins is involved during this final step of the biosynthesis of these natural products, this cyclodimerization of ortho-quinols can be chemically reproduced in the laboratory with the same strict level of site-specific regioselectivity and stereoselectivity. This unique yet unified process, which finds its rationale in the inherent chemical reactivity of those ortho-quinols, is illustrated herein by an efficient and bioinspired first chemical synthesis of one of the most structurally complex and synthetically challenging examples of such natural cyclodimers, the bisditerpenoid (+)-maytenone.


Assuntos
Produtos Biológicos/síntese química , Quinolonas/química , Produtos Biológicos/química , Reação de Cicloadição , Dimerização , Estrutura Molecular , Estereoisomerismo
3.
Arch Pharm (Weinheim) ; 353(5): e2000002, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32180262

RESUMO

A series of new nitroimidazole-containing derivatives was synthesized by coupling of 2-[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethylthio]ethanol with diversely substituted benzoic acids. Upon treatment with m-CPBA, 12 of these sulfanyl compounds were further oxidized to their sulfonyl analogs. All the 26 synthetic compounds were examined for in vitro activity against Leishmania (V.) braziliensis and Leishmania (L.) mexicana, and some of them displayed an efficient antileishmanial activity. Among the compounds tested, the catecholic derivative 2-{[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl]sulfanyl}ethyl 3,4-dihydroxybenzoate (9a, LC50 = 13 and 11 µM) and the pyrogallolic derivative 2-{[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl]sulfanyl}ethyl 3,4,5-trihydroxybenzoate (9b, LC50 = 4 and 1 µM) were the most active ones against the two Leishmania strains.


Assuntos
Antiprotozoários/farmacologia , Benzoatos/farmacologia , Leishmania/efeitos dos fármacos , Nitroimidazóis/farmacologia , Antiprotozoários/síntese química , Antiprotozoários/química , Benzoatos/síntese química , Benzoatos/química , Relação Dose-Resposta a Droga , Estrutura Molecular , Nitroimidazóis/síntese química , Nitroimidazóis/química , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade
4.
Angew Chem Int Ed Engl ; 58(47): 16959-16965, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31486231

RESUMO

A facile and highly chemoselective synthesis of doubly activated cyclopropanes is reported where mixtures of alkenes and ß-dicarbonyl-derived iodonium ylides are irradiated with light from blue LEDs. This metal-free synthesis gives cyclopropanes in yields up to 96 %, is operative with cyclic and acyclic ylides, and proceeds with a variety of electronically-diverse alkenes. Computational analysis explains the high selectivity observed, which derives from exclusive HOMO to LUMO excitation, instead of free carbene generation. The procedure is operationally simple, uses no photocatalyst, and provides access in one step to important building blocks for complex molecule synthesis.

5.
Chemistry ; 25(49): 11574-11580, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31407847

RESUMO

The so-called Securinega alkaloids constitute a class of tetracyclic biologically active specialised metabolites isolated principally from subtropical plants belonging to the Phyllanthaceae family. Following a strategy based on alternative hypotheses for their biosynthesis, an easy and time-efficient divergent synthesis enabled access to twelve of those alkaloids featuring (neo)(nor)securinane skeletons. Moreover, this work permitted to reassign the absolute configurations of (+)-virosine B and (-)-episecurinol A.


Assuntos
Alcaloides/biossíntese , Alcaloides/química , Euphorbiaceae/química , Euphorbiaceae/metabolismo , Mesilatos/química , Conformação Molecular , Estereoisomerismo
6.
Chemistry ; 25(11): 2852-2858, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30589145

RESUMO

The facile and convenient preparation of both enantiomers of a [7]helicene scaffold from inexpensive (l)-(+)-tartaric acid and 4-methylstyrene is described. These helical structures were transformed into bis-iodinated ether derivatives in order to explore their potential as precursors of novel chiral organoiodane reagents or as iodoarene pre-catalysts. Promising results were obtained in hydroxylative phenol dearomatization/[4+2] cycloaddition cascade and dearomative spirolactonization reactions with encouraging enantiomeric excesses.

7.
J Org Chem ; 82(22): 11816-11828, 2017 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-28991470

RESUMO

A concise synthesis of two scyphostatin analogues is achieved from readily available ortho-substituted phenols. Key features include an asymmetric and biomimetic hydroxylative phenol dearomatization (HPD) reaction promoted by a chiral salen-type bis(λ5-iodane) reagent, followed by an in situ regio- and diastereocontrolled epoxidation.


Assuntos
Amidas/síntese química , Iodo/química , Fenóis/química , Pironas/síntese química , Amidas/química , Estrutura Molecular , Pironas/química , Estereoisomerismo
8.
Angew Chem Int Ed Engl ; 56(44): 13833-13837, 2017 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-28857392

RESUMO

The first total synthesis of the 2,3,5-O-(S,R)-nonahydroxytriphenoylated (NHTP) C-glucosidic ellagitannin (-)-vescalin was accomplished through a series of transformations mimicking the sequence of events leading to its biogenesis. The key steps of this synthesis encompass a Wittig-mediated ring opening of a glucopyranosic hemiacetal, a C-glucosidation event through a phenolic aldol-type reaction, and a Wynberg-Feringa-Yamada-type oxidative phenolic coupling, which forged the NHTP unit of (-)-vescalin.

9.
Chemistry ; 23(54): 13309-13313, 2017 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-28715080

RESUMO

The preparation of new chiral biphenylic λ3 -iodane reagents bearing transferable alkynyl ligands is described. These reagents transfer their carbon-based ligands onto ß-ketoesters with an enantiomeric excess (ee) up to 68 %, and most remarkably, enable the dearomative alkynylation of naphthols in good to high yields up to 84 % ee.

10.
J Org Chem ; 82(7): 3990-3995, 2017 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-28282146

RESUMO

Two model ortho-quinol acetates were easily prepared by iodane-mediated acetoxylative phenol dearomatization and evaluated for their reactivity toward various aryl-based nucleophiles, i.e., aryl metallic reagents and phenolic derivatives. Novel modes of reactivity, allowing the formation of biaryl linkages, were revealed and here exploited for the synthesis of two natural phenolics.


Assuntos
Acetatos/química , Produtos Biológicos/síntese química , Hidroquinonas/química
11.
Chemistry ; 23(8): 1820-1829, 2017 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-27859805

RESUMO

The development of new near infrared (NIR) dyes is crucial for diverse applications and especially bioimaging, as they absorb and emit light in the "therapeutic window" (650-950 nm). We report here a new family of NIR fluorophores that has been obtained by hybridising hemicyanines with epicocconone. Emission wavelengths of these hybrid dyes is in the range 715-795 nm and is combined with large Stokes' shifts (75-95 nm). The absorption and emission wavelength can be modulated according to the hemicyanine moiety and adding sulfonic acid moieties enhances water solubility. We demonstrate their application in the sensitive detection of proteins in gel electrophoresis and the staining of specific cellular organelles in confocal microscopy. These results are particularly encouraging and bring forward a new fluorescent skeleton for chemical biology.


Assuntos
Benzopiranos/química , Carbocianinas/química , Corantes Fluorescentes/química , Furanos/química , Cetonas/química , Proteínas/química , Coloração e Rotulagem , Animais , Benzopiranos/síntese química , Carbocianinas/síntese química , Bovinos , Linhagem Celular Tumoral , Eletroforese em Gel de Poliacrilamida , Furanos/síntese química , Humanos , Cetonas/síntese química , Microscopia de Fluorescência , Soroalbumina Bovina/química , Espectroscopia de Luz Próxima ao Infravermelho
12.
J Org Chem ; 81(12): 5190-201, 2016 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-27213834

RESUMO

Amenable to late-stage preparation of analogues, a flexible and convergent total synthesis of (±)-aureothin is presented. The strategy was based on a desymmetrization of α,α'-dimethoxy-γ-pyrone by a process combining 1,4-addition and alkylation of vinylogous enolate to stereoselectively reach the backbone of the target. Palladium-catalyzed cyanation of an elaborated and isomerizable E,Z dienyl motif followed by Pinner cyclization enabled the construction of the tetrahydrofuran motif while a first approach based on a late-stage oxidation was unsuccessful.


Assuntos
Antifúngicos/síntese química , Cromonas/síntese química , Alquilação , Catálise , Reação de Cicloadição , Furanos/síntese química , Espectroscopia de Ressonância Magnética , Oxirredução , Paládio , Estereoisomerismo
13.
Org Lett ; 18(5): 1120-3, 2016 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-26907848

RESUMO

The first total and biomimetic synthesis of the natural bis(sesquiterpene) (-)-bacchopetiolone (revised structure) was completed through a highly diastereoselective hydroxylative phenol dearomatization/[4+2]-dimerization cascade conversion of (+)-curcuphenol using a novel C2-symmetrical chiral Salen-type bis(λ(5)-iodane).


Assuntos
Sesquiterpenos/síntese química , Acetofenonas/química , Catálise , Ciclização , Estrutura Molecular , Fenóis/química , Sesquiterpenos/química , Estereoisomerismo
14.
Top Curr Chem ; 373: 25-74, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26809622

RESUMO

This chapter highlights recent developments in phenol dearomatization using organoiodane reagents and a selection of applications in natural product synthesis.


Assuntos
Produtos Biológicos/síntese química , Indicadores e Reagentes , Compostos de Iodo/química , Fenol/química , Alcaloides/síntese química , Ciclização , Quinonas/síntese química
15.
J Am Chem Soc ; 136(43): 15248-56, 2014 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-25271695

RESUMO

Epicocconone is a natural latent fluorophore that is widely used in biotechnology because of its large Stokes shift and lack of fluorescence in its unconjugated state. However, the low photostability and quantum yields of epicocconone have limited its wider use, and in the absence of a total synthesis, this limitation has been a long-standing problem. Here we report a general strategy for the synthesis of epicocconone analogues that relies on a 2-iodoxybenzoic acid-mediated dearomatization and on the replacement of the triene tail of the natural product by an aromatic ring. This design element is general and the synthesis is straightforward, providing ready access to libraries of polyfunctional fluorophores with long Stokes shifts based on the epicocconone core. Our structural modifications resulted in analogues with increased photostability and quantum yields compared with the natural product. Staining proteomic gels with these new analogues showed significant lowering of the detection limit and a 30% increase in the number of low-abundance proteins detected. These epiccoconone analogues will substantially improve the discovery rate of biomarker needles in the proteomic haystack.


Assuntos
Benzopiranos/química , Benzopiranos/síntese química , Desenho de Fármacos , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Furanos/química , Furanos/síntese química , Cetonas/química , Cetonas/síntese química , Técnicas de Química Sintética , Ciclização , Estabilidade de Medicamentos , Espectrometria de Fluorescência , Termodinâmica
16.
Angew Chem Int Ed Engl ; 53(37): 9860-4, 2014 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-25047148

RESUMO

The long-standing quest for chiral hypervalent organoiodine compounds (i.e., iodanes) as metal-free reagents for asymmetric synthesis continues. Although remarkable progress has recently been made in organoiodine-catalyzed reactions using a terminal oxidant in stoichiometric amounts, there is still a significant need for "flaskable" chiral iodane reagents. Herein, we describe the synthesis of new iodobinaphthyls and iodobiphenyls, their successful and selective DMDO-mediated oxidation into either λ(3)- or λ(5)-iodanes, and the evaluation of their capacity to promote asymmetric hydroxylative phenol dearomatization (HPD) reactions. Most notably, a C2-symmetrical biphenylic λ(5)-iodane promoted the HPD-induced conversion of the monoterpene thymol into the corresponding ortho-quinol-based [4+2] cyclodimer (i.e., bis(thymol)) with enantiomeric excesses of up to 94%.

17.
J Mol Model ; 20(8): 2342, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25038631

RESUMO

The reaction mechanism of diastereoselective oxidative dearomatization by iodoxybenzoic acid of key compounds involved in the total synthesis of epicocconone analogs, which are efficient fluorophores with a wide range of applications in protein staining and separation, was studied using density functional theory. In particular, the conformational space was investigated, as was the role of the so-called hypervalent twist move, which is thought to be the rate-determining step. Both kinetic and thermodynamical aspects of the mechanism were considered from static and dynamic viewpoints, including solvent effects. The results were then rationalized using conceptual density functional theory and Bader's atoms-in-molecules framework, which demonstrated how complementary these two approaches are when studying organic chemistry reactions theoretically.


Assuntos
Hidrocarbonetos Aromáticos/química , Iodobenzoatos/química , Modelos Teóricos , Benzopiranos/química , Cátions , Furanos/química , Iodobenzenos , Cetonas/química , Oxirredução , Estereoisomerismo , Termodinâmica
18.
J Phys Chem A ; 118(4): 757-64, 2014 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-24446675

RESUMO

Through-space charge transfers upon photon absorption in aminated epicocconone analogues, which serve as promising proteins markers, are investigated within time-dependent density functional theory using total densities differences and various point-charge models (with a special emphasis on Bader's atoms-in-molecules theory). In particular, the distances and the amounts of charge transfer, as well as the transition dipole moments, are discussed from a methodological point of view, and their values are subsequently linked with the chemical structures of these efficient fluorophores. Finally, on the basis of these theoretical findings, several hints for the future improvement of the photochemical properties of these analogues are advanced.


Assuntos
Benzopiranos/química , Corantes Fluorescentes/química , Furanos/química , Cetonas/química , Benzopiranos/síntese química , Simulação por Computador , Transporte de Elétrons , Corantes Fluorescentes/síntese química , Furanos/síntese química , Cetonas/síntese química , Modelos Moleculares , Conformação Molecular , Teoria Quântica
19.
J Phys Chem B ; 117(48): 14951-9, 2013 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-24168431

RESUMO

Engineering the properties of fluorescent probes through modifications of the fluorophore structure has become a subject of interest in recent times. By doing this, the photophysical and photochemical properties of the modified fluorophore can be understood and this can guide the design and synthesis of better fluorophores for use in biotechnology. In this work, the electronic spectra and fluorescence decay kinetics of four analogues of the fluorescent natural product epicocconone were investigated. Epicocconone is unique in that the native state is weakly green fluorescent, whereas the enamine formed reversibly with proteins is highly emissive in the red. It was found that the ultrafast dynamics of the analogues depends profoundly on the H-bonding effect of solvents and solvent viscosity though solvent polarity also plays a role. Comparing the steady state and time-resolved data, the weak fluorescence of epicocconone in its native state is most likely due to the photoisomerization of the hydrocarbon side chain, while the keto enol moiety also has a role to play in determining the fluorescence quantum yield. This understanding is expected to aid the design of better protein stains from the same family.


Assuntos
Benzopiranos/química , Produtos Biológicos/química , Corantes Fluorescentes/química , Furanos/química , Cetonas/química , Proteínas/química , Benzopiranos/síntese química , Produtos Biológicos/síntese química , Fluorescência , Corantes Fluorescentes/síntese química , Furanos/síntese química , Cetonas/síntese química , Cinética , Estrutura Molecular
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...