The Morita-Baylis-Hillman Reaction: Advances and Contributions from Brazilian Chemistry

Santos, Marília S.; Coelho, Fernando; Lima-Júnior, Cláudio Gabriel; Vasconcellos, Mário L. A. A.

doi:10.2174/157017941206150828114416

Cited by 22 publications

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“…However, the slow step of the mechanism and the transition state structure has been the main source of controversy [ 7 ]. To date, the slow step has been proposed to change between the aldol step (step 2) and the elimination step (step 3).…”

Section: Resultsmentioning

confidence: 99%

“…In fact, depending on various parameters, such as the Michael acceptor used as the reagent, solvents, addition or not of phenolic additives, temperature (may be reversible or not), many different catalysts, etc. [ 7 ], MBHR is an exquisite reaction and each reaction must have its experimental parameters carefully optimized as an individual problem. However, some facts are incontestable: the MBHR between methyl acrylate reacting with p -bromobenzaldehyde is reversible at elevated temperatures [ 21 ]; several MBHR are faster at 0 °C than at room temperature [ 23 , 24 ]; and the type of solvent (aprotic or protic) [ 25 , 26 ] and the phenol or naphthol additives modifies the reactions rate.…”

Section: Resultsmentioning

confidence: 99%

“…The Morita-Baylis-Hillman adducts (MBHAs) are being explored as drug candidates against several diseases, one of them being leishmaniasis [ 5 ]. These compounds are prepared from the Morita-Baylis-Hillman reaction [ 6 , 7 ] in green conditions from aldehydes (among other electrophiles) or alkenes connected to electron attractor groups (EAG, like methyl acrylate, acrylonitrile, and others) under basic catalysis (DABCO being the most common base, Scheme 1 ).…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of 16 New Hybrids from Tetrahydropyrans Derivatives and Morita˗Baylis˗Hillman Adducts: In Vitro Screening against Leishmania donovani

et al. 2017

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Leishmaniases are a group of neglected tropical diseases (NTDs) caused by protozoan parasites from >20 Leishmania species. Visceral leishmaniasis (VL), also known as kala-aza, is the most severe form of leishmaniasis, usually fatal in the absence of treatment in 95% of cases. The Morita-Baylis-Hillman adducts (MBHAs) are being explored as drug candidates against several diseases, one of them being leishmaniasis. We present here the design, synthesis and in vitro screening against Leishmania donovani of sixteen new molecular hybrids from analgesic/anti-inflammatory tetrahydropyrans derivatives and Morita-Baylis-Hillman adducts. First, acrylates were synthesized from analgesic/anti-inflammatory tetrahydropyrans using acrylic acid under TsOH as a catalyst (70%–75% yields). After the 16 new MBHAs were prepared in moderate to good yields (60%–95%) promoted by microwave irradiation or low temperature (0 °C) in protic and aprotic medium. The hybrids were evaluated in vitro on the promastigote stage of Leishmania donovani by determining their inhibitory concentrations 50% (IC50), 50% hemolysis concentration (HC50), selectivity index (HC50/IC50,), and comparing to Amphotericin B, chosen as the anti-leishmanial reference drug. The hybrid which presents the bromine atom in its chemical structure presents high leishmanicide activity and the high selectivity index in red blood cells (SIrb > 180.19), compared with the highly-toxic reference drug (SIrb = 33.05), indicating that the bromine hybrid is a promising compound for further biological studies.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis of 16 New Hybrids from Tetrahydropyrans Derivatives and Morita˗Baylis˗Hillman Adducts: In Vitro Screening against Leishmania donovani

et al. 2017

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“…Biological antileishmaniasis activities (measured by the IC 50 ) for a series of 12 nitroaromatic compounds ( Figure 1 )—adducts of Morita–Baylis–Hillman (MBHA) reaction—have been previously reported by researchers [ 25 , 26 , 27 ]. For this series, electrochemical studies were performed in aprotic media ( N , N -dimethylformamide plus tetrabutylammonium perchlorate 0.1 mol·L −1 for supporting electrolyte) using cyclic voltammetry with a conventional three-electrode cell and Ag|AgCl,Cl − (0.1 mol·L −1 ) as reference electrode at 25 °C (±2 °C).…”

Section: Introductionmentioning

confidence: 84%

One-Electron Reduction Potentials: Calibration of Theoretical Protocols for Morita–Baylis–Hillman Nitroaromatic Compounds in Aprotic Media

et al. 2018

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Nitroaromatic compounds—adducts of Morita–Baylis–Hillman (MBHA) reaction—have been applied in the treatment of malaria, leishmaniasis, and Chagas disease. The biological activity of these compounds is directly related to chemical reactivity in the environment, chemical structure of the compound, and reduction of the nitro group. Because of the last aspect, electrochemical methods are used to simulate the pharmacological activity of nitroaromatic compounds. In particular, previous studies have shown a correlation between the one-electron reduction potentials in aprotic medium (estimated by cyclic voltammetry) and antileishmanial activities (measured by the IC50) for a series of twelve MBHA. In the present work, two different computational protocols were calibrated to simulate the reduction potentials for this series of molecules with the aim of supporting the molecular modeling of new pharmacological compounds from the prediction of their reduction potentials. The results showed that it was possible to predict the experimental reduction potential for the calibration set with mean absolute errors of less than 25 mV (about 0.6 kcal·mol−1).

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“…In the last ten years, our research group has been continuously dedicated to the design, synthesis and biological evaluation of Morita-Baylis-Hillman adducts (MBHAs) as antileishmanial treatments and as treatments against other parasitic NTDs [7]. The Morita-Baylis-Hillman reaction (MBHR, Scheme 1) has been consolidated as an efficient methodology for C-C bond formation [7,8,9]. Polyfunctional MBHA products are obtained in one step by the MBHR by using nucleophilic catalysis (DABCO is the most common catalyst) under metal-free conditions and may be performed in an aqueous solvent mixture or in a solvent-free medium.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and In Vitro Anti Leishmania amazonensis Biological Screening of Morita-Baylis-Hillman Adducts Prepared from Eugenol, Thymol and Carvacrol

et al. 2016

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Leishmaniasis represents a series of severe neglected tropical diseases caused by protozoa of the genus Leishmania and is widely distributed around the world. Here, we present the syntheses of Morita-Baylis-Hillman adducts (MBHAs) prepared from eugenol, thymol and carvacrol, and their bioevaluation against promastigotes of Leishmania amazonensis. The new MBHAs are prepared in two steps from essential oils in moderate to good yields and present IC 50 values in the range of 22.30-4.71 µM. Moreover, the selectivity index to the most potent compound is very high (SIrb > 84.92), far better than that of Glucantime ® (SIrb 1.39) and amphotericin B (SIrb = 22.34). Conformational analysis were carried out at the M062X//6-31+G(d,p) level of theory to corroborate a hypothesis about the nitroaromatic bioreduction mechanism.

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The Morita-Baylis-Hillman Reaction: Advances and Contributions from Brazilian Chemistry

Cited by 22 publications

References 0 publications

Synthesis of 16 New Hybrids from Tetrahydropyrans Derivatives and Morita˗Baylis˗Hillman Adducts: In Vitro Screening against Leishmania donovani

Synthesis of 16 New Hybrids from Tetrahydropyrans Derivatives and Morita˗Baylis˗Hillman Adducts: In Vitro Screening against Leishmania donovani

One-Electron Reduction Potentials: Calibration of Theoretical Protocols for Morita–Baylis–Hillman Nitroaromatic Compounds in Aprotic Media

Synthesis and In Vitro Anti Leishmania amazonensis Biological Screening of Morita-Baylis-Hillman Adducts Prepared from Eugenol, Thymol and Carvacrol

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