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1.
Eur J Med Chem ; 187: 111606, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31901334

RESUMO

The goal of this study was to develop novel radioprotective agents targeting the intrinsic apoptotic pathway and thus decreasing the radiation-induced damage. For that purpose, we designed, synthesized and analyzed ten new compounds based on the 1-(4-(2-hydroxyethyl)piperazin-1-yl)-3-phenoxypropan-2-ol leading structure. The cytotoxicity of the newly synthesized substances was tested in vitro on cell lines derived from different progenitor cells by WST-1 proliferation assay. MTT test was utilized to assess half-maximal inhibitory concentrations and maximum tolerated concentrations of novel compounds in A-549 cells. Screening for radioprotective properties was performed using flow-cytometry in MOLT-4 cells exposed to 60Co ionizing gamma radiation. Selected candidates underwent in vivo testing in C57Bl/6 J mice having a positive impact on their immunological status. In summary, we report here promising compounds with radioprotective effect in vivo.


Assuntos
Propanóis/farmacologia , Protetores contra Radiação/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Estrutura Molecular , Propanóis/síntese química , Propanóis/química , Protetores contra Radiação/síntese química , Protetores contra Radiação/química , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Relação Estrutura-Atividade
2.
Chembiochem ; 20(9): 1129-1132, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-30666768

RESUMO

Reactions that were once the exclusive province of synthetic catalysts can increasingly be addressed using biocatalysis. Through discovery of unnatural enzyme reactions, biochemists have significantly expanded the reach of enzymatic catalysis to include carbene transfer chemistries including olefin cyclopropanation. Here we describe hemoprotein cyclopropanation catalysts derived from thermophilic bacterial globins that react with diazoacetone and an unactivated olefin substrate to furnish a cyclopropyl ketone, a previously unreported reaction for enzyme catalysts. We further demonstrate that the resulting cyclopropyl ketone can be converted to a key cyclopropanol intermediate that occurs en route to the anti-hepatitis C drug grazoprevir.


Assuntos
Proteínas de Bactérias/química , Ciclopropanos/síntese química , Hemeproteínas/química , Propanóis/síntese química , Alcenos/química , Compostos Azo/química , Proteínas de Bactérias/genética , Biocatálise , Ciclização , Evolução Molecular Direcionada , Hemeproteínas/genética , Estrutura Molecular , Mutagênese Sítio-Dirigida , Estudo de Prova de Conceito , Quinoxalinas/química , Verrucomicrobia/química
3.
Mol Divers ; 23(1): 147-164, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30094501

RESUMO

The design, synthesis, antinociceptive and ß-adrenoceptor blocking activities of several eugenyloxy propanol azole derivatives have been described. In this synthesis, the reaction of eugenol with epichlorohydrin provided adducts 3 and 4 which were N-alkylated by diverse azoles to obtain the eugenyloxy propanol azole analogues in good yields. Adducts 3 and 4 were also reacted with azide ion to obtain the corresponding azide 6. The 'Click' Huisgen cycloaddition reaction of 6 with diverse alkynes afforded the title compounds in good yields. The synthesized eugenyloxy propanol azole derivatives were in vivo studied for the acute antinociception on male Spargue Dawley rats using tail-flick test. Compounds 5f, 5g, 7b and 11a exhibited potent analgesic properties in comparison with eugenol as a standard drug. In addition, all compounds were ex vivo tested for ß-adrenoceptor blocking properties on isolated left atrium of male rats which exhibited partial antagonist or agonist behaviour compared to the standard drugs. The molecular docking study on the binding site of transient receptor potential vanilloid subtype 1 (TRPV1) has indicated that like capsaicin, eugenyloxy propanol azole analogues exhibited the strong affinity to bind at site of TPRV1 in a "tail-up, head-down" conformation and the presence of triazolyl moieties has played undeniable role in durable binding of these ligands to TRPV1. The in silico pharmacokinetic profile, drug likeness and toxicity predictions carried out for all compounds determined that 5g can be considered as potential antinociceptive drug candidate for future research.


Assuntos
Antagonistas Adrenérgicos beta , Analgésicos , Azóis , Propanóis , Antagonistas Adrenérgicos beta/síntese química , Antagonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/uso terapêutico , Analgésicos/síntese química , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Azóis/síntese química , Azóis/farmacologia , Azóis/uso terapêutico , Simulação por Computador , Desenho de Drogas , Epicloroidrina/química , Eugenol/química , Átrios do Coração/efeitos dos fármacos , Masculino , Simulação de Acoplamento Molecular , Dor/tratamento farmacológico , Propanóis/síntese química , Propanóis/farmacologia , Propanóis/uso terapêutico , Ratos Sprague-Dawley , Canais de Cátion TRPV/metabolismo
4.
Molecules ; 23(11)2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30404134

RESUMO

We present an efficient and green methodology for the synthesis of glycerol monoethers, starting from glycidol and different alcohols, by means of heterogeneous acid catalysis. A scope of Brønsted and Lewis acid catalysts were applied to the benchmark reaction of glycidol and methanol. The selected catalysts were cationic exchangers, such as Nafion NR50, Dowex 50WX2, Amberlyst 15 and K10-Montmorillonite, both in their protonic form and exchanged with Al(III), Zn(II) and Fe(III). Thus, total conversions were reached in short times by using 1 and 5% mol catalyst loading and room temperature, without the need for excess glycidol or the presence of a solvent. Finally, these conditions and the best catalysts were successfully applied to the reaction of glycidol with several alcohols such as butanol or isopropanol.


Assuntos
Ácidos/química , Compostos de Epóxi/síntese química , Glicerol/síntese química , Propanóis/síntese química , Solventes/química , Catálise , Compostos de Epóxi/química , Glicerol/química , Propanóis/química
5.
Angew Chem Int Ed Engl ; 57(48): 15847-15851, 2018 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-30307672

RESUMO

A regioselective, nickel-catalyzed photoredox allylation of secondary, benzyl, and α-alkoxy radical precursors is disclosed. Through this manifold, a variety of linear allylic alcohols and allylated monosaccharides are accessible in high yields under mild reaction conditions. Quantum mechanical calculations [DFT and DLPNO-CCSD(T)] support the mechanistic hypothesis of a Ni0 to NiII oxidative addition pathway followed by radical addition and inner-sphere allylation.


Assuntos
Elétrons , Níquel/química , Propanóis/síntese química , Catálise , Estrutura Molecular , Oxirredução , Processos Fotoquímicos , Propanóis/química , Teoria Quântica
6.
Angew Chem Int Ed Engl ; 57(39): 12921-12924, 2018 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-30117646

RESUMO

Spirocyclic ethers can be found in bioactive compounds. This copper-catalyzed enantioselective alkene carboetherification provides 5,5-, 5,6- and 6,6-spirocyclic products containing fully substituted chiral carbon centers with up to 99 % enantiomeric excess. This reaction features the formation of two rings from acyclic substrates, 1,1-disubstituted alkenols functionalized with either arenes, alkenes, or alkynes, and clearly constitutes a powerful way to synthesize chiral spirocyclic ethers.


Assuntos
Cobre/química , Éteres/química , Propanóis/química , Compostos de Espiro/química , Alcenos/química , Alquinos/química , Catálise , Cristalografia por Raios X , Éteres/síntese química , Conformação Molecular , Propanóis/síntese química , Estereoisomerismo
7.
ChemMedChem ; 13(16): 1723-1731, 2018 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-30043406

RESUMO

To introduce the 3-[18 F]fluoro-2-hydroxypropyl moiety into positron emission tomography (PET) radiotracers, we performed automated synthesis of (rac)-, (R)-, and (S)-[18 F]epifluorohydrin ([18 F]1) by nucleophilic displacement of (rac)-, (R)-, or (S)-glycidyl tosylate with 18 F- and purification by distillation. The ring-opening reaction of (R)- or (S)-[18 F]1 with phenol precursors gave enantioenriched [18 F]fluoroalkylated products without racemisation. We then synthesised (rac)-, (R)-, and (S)- 2-{5-[4-(3-[18 F]fluoro-2-hydroxypropoxy)phenyl]-2-oxobenzo[d]oxazol-3(2H)-yl}-N-methyl-N-phenylacetamide ([18 F]6) as novel radiotracers for the PET imaging of translocator protein (18 kDa) and showed that (R)- and (S)-[18 F]6 had different radioactivity uptake in mouse bone and liver. Thus, (rac)-, (R)-, and (S)-[18 F]1 are effective radiolabelling reagents and can be used to develop PET radiotracers by examining the effects of chirality on their in vitro binding affinities and in vivo behaviour.


Assuntos
Compostos de Epóxi/química , Hidrocarbonetos Fluorados/farmacologia , Propanóis/farmacologia , Compostos Radiofarmacêuticos/farmacologia , Animais , Osso e Ossos/metabolismo , Encéfalo/metabolismo , Compostos de Epóxi/síntese química , Radioisótopos de Flúor , Hidrocarbonetos Fluorados/síntese química , Hidrocarbonetos Fluorados/química , Hidrocarbonetos Fluorados/metabolismo , Camundongos , Estrutura Molecular , Tomografia por Emissão de Pósitrons/métodos , Propanóis/síntese química , Propanóis/química , Propanóis/metabolismo , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/metabolismo , Receptores de GABA/metabolismo , Estereoisomerismo , Distribuição Tecidual
8.
Org Biomol Chem ; 16(31): 5691-5698, 2018 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-30047974

RESUMO

An efficient Rh(iii)-catalyzed dehydrative C-H allylation of indoles with allyl alcohols via ß-hydroxide elimination under oxidant-free conditions has been developed. This method features very mild reaction conditions, excellent regioselectivity and stereoselectivity, and compatibility with various functional groups. In addition, the directing group can be removed under mild reaction conditions, which further underscores the synthetic utility of this method.


Assuntos
Compostos Alílicos/química , Hidróxidos/química , Indóis/química , Propanóis/química , Ródio/química , Compostos Alílicos/síntese química , Catálise , Hidróxidos/síntese química , Indóis/síntese química , Propanóis/síntese química , Estereoisomerismo
9.
Org Biomol Chem ; 16(21): 3921-3946, 2018 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-29745946

RESUMO

A synthesis of non-racemic ß-alkyl-ß-aryl allyl alcohols and their transformation into allylamines bearing a quaternary stereogenic center is reported. The allyl alcohols were prepared either by Cu-catalyzed enantioselective reduction of enones or by sequential alkylation/hydrostannylation/Stille coupling of non-racemic propargyl alcohols. The prepared ß-alkyl-ß-aryl allyl alcohols were converted (after carbamoylation) to the corresponding allylamine derivatives through cyanate-to-isocyanate rearrangement/nucleophilic addition with complete chirality transfer. Varying the nucleophilic agents allowed the preparation of various allylamine derivatives, including carbamates, amides, formamides, ureas, and free amines. The ozonolysis/oxidation of the resulting allylamines provided non-racemic quaternary α-amino acids.


Assuntos
Alilamina/síntese química , Aminoácidos/síntese química , Propanóis/síntese química , Alilamina/análogos & derivados , Aminoácidos/química , Cianatos/química , Isocianatos/química , Oxirredução , Propanóis/química , Estereoisomerismo
10.
Eur J Med Chem ; 152: 489-514, 2018 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-29754074

RESUMO

Design, synthesis, structure-activity relationship, cytotoxicity studies, in silico drug-likeness, genotoxicity screening, and in vivo studies of new 1-aryl-3-substituted propanol derivatives led to the identification of nine compounds with promising in vitro (55, 56, 61, 64, 66, and 70-73) and in vivo (66 and 72) antimalarial profiles against Plasmodium falciparum and Plasmodium berghei. Compounds 55, 56, 61, 64, 66 and 70-73 exhibited potent antiplasmodial activity against chloroquine-resistant strain FCR-3 (IC50s < 0.28 µM), and compounds 55, 56, 64, 70, 71, and 72 showed potent biological activity in chloroquine-sensitive and multidrug-resistant strains (IC50s < 0.7 µM for 3D7, D6, FCR-3 and C235). All of these compounds share appropriate drug-likeness profiles and adequate selectivity indexes (77 < SI < 184) as well as lack genotoxicity. In vivo efficacy tests in a mouse model showed compounds 66 and 72 to be promising candidates as they exhibited significant parasitemia reductions of 96.4% and 80.4%, respectively. Additional studies such as liver stage and sporogony inhibition, target exploration of heat shock protein 90 of P. falciparum, targeted delivery by immunoliposomes, and enantiomer characterization were performed and strongly reinforce the hypothesis of 1-aryl-3-substituted propanol derivatives as promising antimalarial compounds.


Assuntos
Antimaláricos/farmacologia , Sistemas de Liberação de Medicamentos , Parasitemia/tratamento farmacológico , Plasmodium berghei/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Propanóis/farmacologia , Animais , Antimaláricos/síntese química , Antimaláricos/química , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Camundongos , Estrutura Molecular , Parasitemia/parasitologia , Testes de Sensibilidade Parasitária , Plasmodium berghei/crescimento & desenvolvimento , Plasmodium falciparum/crescimento & desenvolvimento , Propanóis/síntese química , Propanóis/química , Relação Estrutura-Atividade
11.
Bioorg Med Chem Lett ; 28(2): 85-93, 2018 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-29233651

RESUMO

We disclose the optimization of a high throughput screening hit to yield benzothiazine and tetrahydroquinoline sulfonamides as potent RORγt inverse agonists. However, a majority of these compounds showed potent activity against pregnane X receptor (PXR) and modest activity against liver X receptor α (LXRα). Structure-based drug design (SBDD) led to the identification of benzothiazine and tetrahydroquinoline sulfonamide analogs which completely dialed out LXRα activity and were less potent at PXR. Pharmacodynamic (PD) data for compound 35 in an IL-23 induced IL-17 mouse model is discussed along with the implications of a high Ymax in the PXR assay for long term preclinical pharmacokinetic (PK) studies.


Assuntos
Compostos Bicíclicos com Pontes/farmacologia , Desenho de Drogas , Propanóis/farmacologia , Receptores do Ácido Retinoico/agonistas , Receptores de Esteroides/agonistas , Sulfonamidas/farmacologia , Animais , Compostos Bicíclicos com Pontes/síntese química , Compostos Bicíclicos com Pontes/química , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Humanos , Receptores X do Fígado/agonistas , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Estrutura Molecular , Receptor de Pregnano X , Propanóis/síntese química , Propanóis/química , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química
12.
J Nat Prod ; 80(5): 1623-1630, 2017 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-28463511

RESUMO

Tedarene A is a macrocyclic diaryl ether heptanoid isolated from the marine sponge Tedania ignis showing an inhibitory effect against nitric oxide production. The first total synthesis of tedarene A was achieved starting from the commercially available 3-(4-methoxyphenyl)propan-1-ol in nine steps and 15.3% overall yield. The synthetic sequence featured an E,Z-dienic bond introduction and a macrocyclization under Ullman conditions. During the synthesis, the E,E-isomer of tedarene A was also obtained and fully characterized.


Assuntos
Diarileptanoides/síntese química , Diarileptanoides/isolamento & purificação , Éteres/química , Poríferos/química , Propanóis/síntese química , Animais , Diarileptanoides/química , Estrutura Molecular , Propanóis/química , Estereoisomerismo
13.
Chemistry ; 23(30): 7180-7184, 2017 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-28393406

RESUMO

8-Membered cyclic ethers are found in a wide range of natural products; however, they are challenging synthetic targets due to enthalpic and entropic barriers. The gold(I)-catalyzed intramolecular dehydrative alkoxylation of ω-hydroxy allylic alcohols was explored to stereoselectively construct α,α'-cis-oxocenes and further applied in a formal synthesis of (+)-laurencin. The gold(I)-catalyzed intramolecular dehydrative alkoxylation may constitute an alternative method for the synthesis of molecular building blocks and natural products that contain highly functionalized 8-membered cyclic ethers.


Assuntos
Produtos Biológicos/síntese química , Éteres Cíclicos/síntese química , Ouro/química , Oxocinas/síntese química , Produtos Biológicos/química , Catálise , Éteres Cíclicos/química , Oxocinas/química , Propanóis/síntese química , Propanóis/química , Estereoisomerismo
14.
J Am Chem Soc ; 138(49): 15881-15884, 2016 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-27960316

RESUMO

An enantioselective intermolecular coupling of oxygen nucleophiles and allylic alcohols to give ß-aryloxycarbonyl compounds is disclosed using a chiral pyridine oxazoline-ligated palladium catalyst under mild conditions. As opposed to the formation of traditional Wacker-type products, enantioselective migratory insertion is followed by ß-hydride elimination toward the adjacent alcohol. Deuterium labeling experiments suggest a syn-migratory insertion of the alkene into the Pd-O bond. A broad scope of phenols, various allylic alcohols, and an alkyl hydroperoxide are viable coupling partners in this process.


Assuntos
Paládio/química , Fenóis/síntese química , Propanóis/síntese química , Catálise , Estrutura Molecular , Fenóis/química , Propanóis/química , Estereoisomerismo
15.
Org Biomol Chem ; 14(28): 6769-79, 2016 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-27337038

RESUMO

A concise synthetic strategy has been developed for the synthesis of the macrolactone core 2 of a unique polyketide callyspongiolide 1. The key features of the strategy included an Evan's asymmetric alkylation, diastereoselective Michael type alkylation, Brown's asymmetric allylation reaction, an allylic alkylation of an activated Z-allylic alcohol and an intramolecular Z-selective intramolecular H-W-E olefination.


Assuntos
Macrolídeos/síntese química , Alcenos/síntese química , Alcenos/química , Alquilação , Técnicas de Química Sintética , Macrolídeos/química , Propanóis/síntese química , Propanóis/química , Estereoisomerismo
16.
J Am Chem Soc ; 138(11): 3655-8, 2016 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-26958737

RESUMO

Chiral iridium complexes modified by SEGPHOS catalyze the 2-propanol-mediated reductive coupling of branched allylic acetates 1a-1o with formaldehyde to form primary homoallylic alcohols 2a-2o with excellent control of regio- and enantioselectivity. These processes, which rely on enantiotopic π-facial discrimination of σ-allyliridium intermediates, represent the first examples of enantioselective formaldehyde C-C coupling beyond aldol addition.


Assuntos
Acetatos/química , Compostos Alílicos/química , Formaldeído/química , Propanóis/síntese química , Catálise , Irídio/química , Metilação , Oxirredução , Estereoisomerismo
17.
Arch Pharm (Weinheim) ; 349(3): 211-23, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26853441

RESUMO

ß-Adrenergic receptor antagonists are important therapeutics for the treatment of cardiovascular disorders. In the group of ß-blockers, much attention is being paid to the third-generation drugs that possess important ancillary properties besides inhibiting ß-adrenoceptors. Vasodilating activity of these drugs is produced through different mechanisms, such as nitric oxide (NO) release, ß2 -agonistic action, α1 -blockade, antioxidant action, and Ca(2+) entry blockade. Here, a study on evaluation of the cardiovascular activity of five new compounds is presented. Compound 3a is a methyl and four of the tested compounds (3b-e) are dimethoxy derivatives of 1-(1H-indol-4-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol. The obtained results confirmed that the methyl and dimethoxy derivatives of 1-(1H-indol-4-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol and their enantiomers possess α1 - and ß1 -adrenolytic activities and that the antiarrhythmic and hypotensive effects of the tested compounds are related to their adrenolytic properties.


Assuntos
Antiarrítmicos/química , Anti-Hipertensivos/química , Etilaminas/química , Indóis/química , Propanóis/química , Vasodilatadores/química , Animais , Antiarrítmicos/síntese química , Antiarrítmicos/farmacologia , Anti-Hipertensivos/síntese química , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Etilaminas/síntese química , Etilaminas/farmacologia , Indóis/síntese química , Indóis/farmacologia , Modelos Moleculares , Propanóis/síntese química , Propanóis/farmacologia , Ensaio Radioligante , Ratos , Receptores Adrenérgicos alfa 1/química , Receptores Adrenérgicos alfa 1/metabolismo , Receptores Adrenérgicos beta 1/química , Receptores Adrenérgicos beta 1/metabolismo , Estereoisomerismo , Relação Estrutura-Atividade , Vasodilatadores/síntese química , Vasodilatadores/farmacologia
18.
Eur J Med Chem ; 101: 604-15, 2015 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-26204508

RESUMO

The synthesis of the new radiotracer precursor 4-Br-NITTP and the radiolabeling of the new tracer 1-(4-bromo-2-nitroimidazol-1-yl)-3-[(18)F]fluoropropan-2-ol (4-Br-[(18)F]FMISO) is reported. The cyclic voltammetry behaviour, neuronal cell toxicity, transport through the brain endothelial cell monolayer, in vivo PET imaging and preliminary calculations of the tracer uptake for a rodent model of stroke were studied for the new compound and the results were compared to those obtained with [(18)F]FMISO, the current gold standard PET hypoxia tracer. The new PET brain hypoxia tracer is more easily reduced, has higher CLogP than [(18)F]FMISO and it diffuses more rapidly through brain endothelial cells. The new compound is non-toxic to neuronal cells and it allows the in vivo mapping of stroke in mice with higher sensitivity. 4-Br-[(18)F]FMISO is a good candidate for further development in ischemic stroke.


Assuntos
Modelos Animais de Doenças , Hipóxia Encefálica/diagnóstico por imagem , Nitroimidazóis/farmacocinética , Tomografia por Emissão de Pósitrons/métodos , Propanóis/farmacocinética , Acidente Vascular Cerebral/diagnóstico por imagem , Animais , Linhagem Celular , Masculino , Camundongos , Estrutura Molecular , Nitroimidazóis/síntese química , Nitroimidazóis/química , Propanóis/síntese química , Propanóis/química , Ratos , Ratos Endogâmicos F344
19.
Molecules ; 20(6): 9890-905, 2015 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-26029858

RESUMO

The lithiation of 2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethyl diisopropylcarbamate (1) is achieved freely by sec-butyllithium in diethylether with high lk-diastereoselectivity: the bicyclic chelate complexes 3a and 3b are reacted with electrophiles to form optically active precursors 4a and 4b with >95% diastereoselectivity. In addition, tertiary diamines can undergo an external complexation in contest with the internal oxygen ligand, leading to improved stereoselectivities. The further reactions of lithiated carbamates with trans alkenyl-9-BBN derivatives after 1,2 metallate rearrangements, gave the key intermediate α-substituted allylic boranes 7. Subsequent allylboration of aldehydes gave (Z)-anti-homoallylic alcohols 8 in good yield and excellent d.r.


Assuntos
Boranos/síntese química , Butanóis/química , Carbamatos/química , Compostos Organometálicos/química , Propanóis/síntese química , Quelantes/química , Éteres , Ligantes , Estrutura Molecular , Oxigênio/química , Estereoisomerismo
20.
Org Biomol Chem ; 13(17): 5012-21, 2015 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-25823536

RESUMO

In refluxing 9 : 1 (v/v) H2O-1,4-dioxane and without an additional catalyst, the rearrangements of various types of cyclopropyl carbinols were attempted. It was found that the reactions generally gave homoallylic alcohols in good to very high chemical yields. Rearrangements of bicyclic or tricyclic cyclopropyl carbinols readily gave the desired ring-expanded cyclic homoallylic alcohols which are difficult to synthesize by other means.


Assuntos
Ciclopropanos/química , Metanol/química , Propanóis/síntese química , Água/química , Estrutura Molecular , Propanóis/química
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