Mauricio M. Victor

Efficient synthesis of 1,3,5-oxygenated synthons from dimethyl 3-oxoglutarate: first use of borane-dimethyl sulfide complex as a regioselective reducing agent of 3-oxygenated glutarate derivatives

The selective reduction of dimethyl 3-oxoglutarate was accomplished in different levels. A high yielding sodium borohydride reduction of the keto group is fully described leading to dimethyl 3-hydroxyglutarate. When borane-dimethyl sulfide (BMS) complex was used, a diol or a triol compound can be obtained by selective or total reduction of 3-hydroxy- or 3-oxoglutarate, respectively, allowing an efficient and practical route to 1,3,5-oxygenated compounds.

Reação da cânfora com boroidreto de sódio: uma estratégia para o estudo da estereoquímica da reação de redução

Reduction of camphor to a mixture of borneol and isoborneol was performed using NaBH4 as the reducing agent under suitable conditions. Although more effective reduction was accomplished using toxic methanol, an alternative non-toxic ethanolic system is described. This experiment is important to introduce undergraduate students in reductive procedures, and can be used to show details on stereoselective procedures on carbonyl moieties (facial diastereoselectivity, Burgi-Dunitz trajectory, diastereomeric excess).Reduction of camphor to a mixture of borneol and isoborneol was performed using NaBH4 as the reducing agent under suitable conditions. Although more effective reduction was accomplished using toxic methanol, an alternative non-toxic ethanolic system is described. This experiment is important to introduce undergraduate students in reductive procedures, and can be used to show details on stereoselective procedures on carbonyl moieties (facial diastereoselectivity, Burgi-Dunitz trajectory, diastereomeric excess).

An on-line system using ion-imprinted polymer for preconcentration and determination of bismuth in seawater employing atomic fluorescence spectrometry

This work proposes an on-line preconcentration system using ion-imprinted polymer (IIP) for determination of bismuth in seawater employing atomic fluorescence spectrometry (AFS). The polymer was synthesized using 2- (5-bromo-2-pyridylazo) -5-diethylaminophenol (Br-PADAP) for complex formation, ethylene glycol dimethacrylate (EGDMA), cross-linking reagent and methacrylic acid (AMA) reagents, used as the functional monomer, 2,2-azobisisobutyronitrile was used as the radical initiator. The polymer was characterized employing the Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The determination of bismuth was performed employing hydride generation atomic fluorescence spectrometry (HG AFS) and the experimental conditions were optimized using a Box Behnken design involving the factors sample pH, eluent concentration and sodium tetrahydroborate concentration. So, using the optimized conditions the system allows the determination of bismuth with limits of detection and quantification of 26 and 88u202fngu202fL-1, a preconcentration factor of 19.8. All these parameters were determined using a sample volume of 25u202fmL. The precision expressed as relative standard deviation (RSD%) was 3.7% for a bismuth(III) solution of concentration 0.25u202fµgu202fL-1. The system proposed was applied for the determination of bismuth in four seawater samples collected in Salvador City, Bahia State, Brazil. The concentrations obtained varied from 0.38 to 0.45u202fμgu202fL-1. The accuracy was evaluated by addition/recovery test, and the recoveries found varied from 92% to 101%.

SÍNTESES TOTAIS NO BRASIL EMPREGANDO ACOPLAMENTOS CRUZADOS MEDIADOS POR PALÁDIO

This article aims to show the selected total syntheses of organic compounds conducted by Brazilian researchers, performed in Brazil, which have employed a palladium catalyzed cross-coupling reaction as key step. We intended to thus create an account, although restricted to the use of palladium, showing the evolution and current state of art of Synthetic Organic Chemistry in Brazil, which has advanced and accept the challenge of total synthesis of increasingly complex molecules, registering growth and maturity of this area among Brazilian researchers.

Diastereosseletividade na redução de enonas bicíclicas com hidretos volumosos

Reduction of five substituted octalones employing lithium tri-sec-butylborohydride (L-selectride®) in THF and ethyl ether led to allylic alcohols with moderate diastereoselectivity. The stereoselectivity of addition of bulky hydrides showed to be different from most examples in the literature and was strongly influenced by substitution on the octalone ring.

Substituent influence on the diastereoselectivity of the alkylation of cyclic chiral imines

A alta diastereosseletividade, normalmente observada na reacao de alquilacao de iminas quirais derivadas de cetonas ciclicas, nao e observada no caso de cetonas com substituintes quirais. A influencia do tamanho do substituinte foi estudada com iminas preparadas a partir da (5R)-2,5-dimetilciclohexanona e (5R)-carvomentona com ambos enantiomeros da 1-feniletilamina (PEA). Usando metil vinil cetona como eletrofilo, um caso matched foi observado com a imina derivada da (S)-PEA. Entretanto, o ed depende fortemente do substituinte no caso mismatched partindo-se da (R)-PEA. O aumento do volume do substituinte leva a diminuicao do ed na ordem i Pr– < CH 2 =C(CH 3 )– < Me–. Os resultados sao explicados pela hipotese de um controle estereoeletronico a favor de um ataque axial ao tautomero enamina. O equilibrio conformacional da enamina aparenta ser crucial para explicar os dados experimentais. No caso matched somente um conformero e esperado enquanto a mistura dos conformeros e postulada no caso mismatched. The normal very high diastereoselectivity of alkylation reaction of chiral imines derived from cyclic ketones is not observed in the case of substituted chiral ketones. The influence of the substituent size was studied for imines prepared from (5R)-2,5-dimethylcyclohexanone and (5R)-carvomenthone with both enantiomers of 1-phenylethylamine (PEA). Using methyl vinyl ketone as electrophile a matched situation was observed with (S)-PEA imine derivative. However, the de is strongly dependent of the substituent in the mismatched case, starting from (R)-PEA. Enlargement of substituent size leads to lowering de in the order i Pr– < CH 2 =C(CH 3 )– < Me–. The results are reasoned by the assumption of a stereoelectronic control in favour of an axial attack at enamine tautomer. The conformational equilibrium of enamine seems to be crucial to explain experimental data. In matched case only one conformer is expected while a mixture of conformers is postulated in the mismatched one.

Synthesis and Evaluation of Antifungal and Antitrypanosomastid Activities of Symmetrical 1,4-Disubstituted-1,2,3-Bistriazoles Obtained by CuAAC Conditions

BACKGROUNDnThe trypanosomatids, such as the protozoan Leishmania spp., have a demand by ergosterol, which is not present in the membrane from mammal cells. The suppression of the synthesis of ergosterol would be a new target of compounds with leishmanicidal activity, and bistriazole has shown trypanocidal activity by this mechanism. The incidence of fungal infections has increased at an alarming rate over the last decades. This is related both to the growing population of immune-compromised individuals and to the emergence of strains that are resistant to available antifungals. Therefore, there is a challenge for the search of potential new antifungal agents.nnnOBJECTIVEnThe study aimed to synthesize 1,4-disubstituted-1,2,3-bistriazoles by optimized copper( I)-catalyzed alkyne-azide cycloaddition (CuAAC) and evaluate their antifungal and antitrypanosomastid activities.nnnMETHODnThe synthesis of symmetrical bistriazoles with diazides as spacers was planned to be performed following the CuAAC reaction strategy. For evaluation of best conditions for the synthesis of symmetrical bistriazoles hex-1-yne 2 was chosen as leading compound, and a variety of catalysts were employed, choosing (3:1) alkyne:diazide stoichiometric relationship employing CuSO4.5H2O as the best condition. For the preparation of diversity in the synthesis of symmetrical bistriazoles, a 1,3-diazide-propan-2-ol 1a and 1,3-diazidepropane 1b were reacted with seven different alkynes, furnishing eleven symmetrical bistriazoles 9-13a,b and 14a. All compounds were essayed to cultures of promastigotes of L. amazonensis (1 x 106 cells mL-1) in the range of 0.10 - 40.00 µg mL-1 and incubated at 25ºC. After 72 h of incubation, the surviving parasites were counted. For antifungal assay, the minimum inhibitory concentrations (MIC) for yeasts and filamentous fungi were determined. Each compound was tested in 10 serial final concentrations (64 to 0.125 µg mL-1).nnnRESULTSnEleven 1,4-disubstituted-1,2,3-bistriazoles were synthesized and their structures were confirmed by IR, 1H and 13C-NMR and Mass spectral analysis. The antifungal and antitrypanosomastid activities were evaluated. The best result to antifungal activity was reached by bistriazole 11a that showed the same MIC of fluconazole (32 µg mL-1) against Candida krusei ATCC 6258, an emerging and potentially multidrug-resistant fungal pathogen. Due to their intrinsically biological activity versatility, five derivatives compounds showed leishmanicidal inhibitory activity between 15.0 and 20.0% at concentrations of 20 and 40.0 µg mL-1. Among these compounds the derivative 13a showed best IC50 value of 63.34 µg mL-1 (182.86 µM).nnnCONCLUSIONnThe preliminary and promising results suggest that bistriazole derivatives, especially compound 13a, could represent an innovative scaffold for further studies and development of new antifungal and anti-parasitic drug candidates.

ORGANIC CHEMISTRY IN BRAZIL: ITS CONTRIBUTION IN THE TOTAL SYNTHESIS OF NATURAL PRODUCTS SINCE THE BRAZILIAN CHEMICAL SOCIETY FOUNDATION

ORGANIC CHEMISTRY IN BRAZIL: ITS CONTRIBUTION IN THE TOTAL SYNTHESIS OF NATURAL PRODUCTS SINCE THE BRAZILIAN CHEMICAL SOCIETY FOUNDATION. An overview of the achivements in the field of the total synthesis of natural products in Brazil in the last 40 years is presented. These contributions are described on different classes of natural products since the birth of Brazilian Chemical Society in 1977. It was intended to create a brief review showing the evolution and current state of the art of Organic Chemistry in Brazil, registering growth and maturity of this area among Brazilian researchers, as well as the contribution of Brazilian organic chemical community in the new fields of this science.

Terpene Esters from Natural Products: Synthesis and Evaluation of Cytotoxic Activity.

Natural steroids and triterpenes such as b-sitosterol, stigmasterol, lupeol, ursolic and betulinic acids were transformed into its hexanoic and oleic esters, to evaluate the influence of chemical modification towards the cytotoxic activities against tumor cells. The derivatives were evaluated against five tumor cell lines [OVCAR-8 (ovarian carcinoma); SF-295 (glioblastoma); HCT-116 (colon adenocarcinoma); HL-60 (leukemia); and PC-3 (prostate carcinoma)] and the results showed only betulinic acid hexyl ester exhibits cytotoxic potential activity.

TOTAL SYNTHESIS IN BRAZIL EMPLOYING PALLADIUM CROSS-COUPLING AS KEY STEP

This article aims to show the selected total syntheses of organic compounds conducted by Brazilian researchers, performed in Brazil, which have employed a palladium catalyzed cross-coupling reaction as key step. We intended to thus create an account, although restricted to the use of palladium, showing the evolution and current state of art of Synthetic Organic Chemistry in Brazil, which has advanced and accept the challenge of total synthesis of increasingly complex molecules, registering growth and maturity of this area among Brazilian researchers.