196,370 research outputs found
The Catalytic efficiency of Free-Base Porphyrins in promoting the N-Aryl oxazolidinones synthesis
No full textBetween other applications oxazolidinones are largely used as intermediates as well as chiral auxiliaries in organic synthesis1 and constitute a class of new antibacterial and antibiotics,2-7 the best pharmaceutical performances are usually observed for N-aryl oxazolidin-2-ones (NAOs), such as Linezolid,8 Tedizolid9 and Toloxatone,10 that are FDA-approved drugs. One of the most interesting methodologies for the synthesis of NAOs is the CO2 cycloaddition to aziridines in order to use this greenhouse gas as a renewable C1 synthetic building block. Recently, we have reported a ruthenium porphyrin-based catalytic procedure for synthesising N alkyl oxazolidin-2-ones11,12 and, during our efforts to extend the same procedure to the synthesis of NAOs, we discovered that this reaction was efficiently promoted by the very convenient TPPH2/TBACl catalytic system (TPPH2=tetraphenyl porphyrin; TBACl=tetrabutyl ammonium chloride). Here, we report the optimization and study scope of the synthesis of N aryl oxazolidin-2-ones, which were obtained either by reacting CO2 with purified N aryl aziridines or by applying a two-steps procedure. The latter methodology consists in the Ru(TPP)CO-catalysed synthesis of N-aryl aziridines that were converted into corresponding NAOs by the TPPH2/TBACl-catalysed cycloaddition of CO2.
1. Z. Vahideh and M. H. Majid, Current Organic Synthesis, 2018, 15, 3-20.
2. F. H. Malik Nasibullah, Naseem Ahmad, Abdul Rahman Khan, and Masihur Rahman, Adv. Sci. Eng. Med., 2015, 7, 91-111.
3. S. J. Pradeep, D. V. Maulikkumar, M. D. Tejas and K. C. Asit, Current Medicinal Chemistry, 2015, 22, 4379-4397.
4. A. Bhushan, N. J. Martucci, O. B. Usta and M. L. Yarmush, Expert Opinion on Drug Metabolism & Toxicology, 2016, 12, 475-477.
5. C. Roger, J. A. Roberts and L. Muller, Clinical Pharmacokinetics, 2018, 57, 559-575.
6. M. Nasibullah, F. Hassan, N. Ahmad, A. R. Khan and M. Rahman, Advanced Science, Engineering and Medicine, 2015, 7, 91-111.
7. K. Michalska, I. Karpiuk, M. Król and S. Tyski, Bioorg. Med. Chem., 2013, 21, 577-591.
8. A. Zahedi Bialvaei, M. Rahbar, M. Yousefi, M. Asgharzadeh and H. Samadi Kafil, J. Antimicrob. Chemother., 2017, 72, 354-364.
9. D. McBride, T. Krekel, K. Hsueh and M. J. Durkin, Expert Opinion on Drug Metabolism & Toxicology, 2017, 13, 331-337.
10. F. Moureau, J. Wouters, D. P. Vercauteren, S. Collin, G. Evrard, F. Durant, F. Ducrey, J. J. Koenig and F. X. Jarreau, European Journal of Medicinal Chemistry, 1992, 27, 939-948.
11. D. Carminati, E. Gallo, C. Damiano, A. Caselli and D. Intrieri, Eur. J. Inorg. Chem., 2018, 2018, 5258-5262.
12. D. Intrieri, C. Damiano, P. Sonzini and E. Gallo, J. Porphyrins Phthalocyanines, 2019, 23, 305-328
SYNTHESIS, CHARACTERIZATION AND CATALYTIC ACTIVITY OF IRON, RUTHENIUM AND COBALT PORPHYRIN COMPLEXES
No full textThe insertion of a nitrene “RN” functionality into a C-H bond represents a valuable tool achieving a wide variety of nitrogen-containing fine chemicals, which frequently present pharmaceutical and/or biological properties. The key point to perform sustainable amination reactions are:
i) The selection of a selective, active and stable catalytic system
ii) The use of nitrene sources presenting high reactivity and atom efficiency.
The last characteristic is well exhibited by organic azides (RN3)1 which transfer a nitrene functionality to an organic skeleton by yielding eco-friendly N2 as the only stoichiometric by-product. The reaction of RN3 with organic compounds can be thermally or photochemically promoted2 but, to improve the reaction selectivity, the presence of a metal catalyst is required. Amongst the catalysts used to achieve these chemical transformations,3, 4 metal porphyrins show a good catalytic efficiency coupled with a very high chemical stability.5 In the last decade, in our research group, we have studied the efficiency of cobalt6, 7 and ruthenium8 porphyrin complexes in catalysing the amination of a wide class of substrates by using ayl azides as nitrene sources. In this research project we have in-depth investigated the behavior of these catalysts in allylic9, inter10- and intra11 benzilic aminations.
First, we have explored the catalytic activity of Ru(TPP)CO (TPP = dianion of tetraphenylporphyrin) in intermolecular benzylic amination reactions10, several benzylic substrates were reacted with different aryl azides employing the hydrocarbon as the reaction solvent and the catalytic ratio Ru(TPP)CO/azide = 4:50. It was observed that Ru(TPP)CO was also active in the amination of benzylic substrates containing an endocyclic benzylic C-H bond. The corresponding amines have been isolated in good yields.
To investigate the mechanism of the benzylic amination catalyzed by Ru(TPP)CO, a kinetic study was undertaken. The analysis of kinetics and reaction selectivities indicated the formation of an active ruthenium (VI) imido complex as a catalytic intermediate. More in-depth studies will be necessary to better clarify the reaction mechanism of the amination of benzylic C-H bonds.
Since Ru(TPP)CO has demonstrated to be a good catalyst in benzylic amination reactions we have subsequently studied the activity of this catalyst in allylic amination reactions9. Believing that an important step for the improvement of the catalytic efficiency of the reported methodology is the comprehension of the reaction mechanism, we first studied the catalyst reactivity towards the components of a model reaction, cyclohexene and azide. No catalyst modification was observed by 1H NMR when Ru(TPP)CO was suspended in cyclohexene and refluxed for a couple of hours, on the other hand, the reaction between Ru(TPP)CO and an 3,5(CF3)2C6H3N3 excess yielded the bis imido complex Ru(TPP)(NAr)2 which showed a catalytic activity similar or even better than that described for Ru(TPP)CO, his precursor.
To assess if the formation of a bis-imido complex is a general reaction, we have also studied the reactivity of Ru(TPP)CO towards other aryl azides discovering that the nature of the active intermediate strongly depends on the electronic nature of the employed azide. We discovered the formation of another bis-imido complex in the reaction of Ru(TPP)CO with 4 CF3C6H4N3 but several experimental evidences indicate also the existence of a mono-imido ruthenium (IV) intermediate. This mono-imido complex can react with another molecule of aryl azide generating the bis-imido complex, or can form the complex Ru(TPP)(ArNH2)CO by hydrogen atom abstraction reactions.
To shed some light into the Ru(TPP)CO catalysed allylic amination of cyclohexene, a kinetic study was undertaken employing two different arylazides as nitrogen source: 4 CF3C6H4N3 and 3,5-(CF3)2C6H4N3. In the first case the observed kinetics indicates the rate determine step of the reaction being the formation of the mono-imido complex that very quickly reacts with the olefin forming the allylic amine and regenerating Ru(TPP)CO. We suggest that Ru(TPP)CO is in equilibrium with the mono-amino complex for the presence of the aniline as reaction side-product. In the second case the kinetic was more complex than the previous discussed, in fact, the first order dependence was observed only for low concentrations of olefin. This behaviour indicates the coexistence of at least two mechanisms that contemporaneously occur with the prevalence of one or the other depending on the olefin concentration.
The existence of two mechanisms was also supported by a DFT investigation.13 The theoretical study confirms that the first step of the cycle is the formation of a mono-imido complex RuIV(TPP)(NAr)(CO) which can undergo a singlettriplet interconversion to confer a diradical character to the “ArN” ligand. Hence, the activation of the allylic C-H bond of cyclohexene (C6H10) occurs through a C H•••N adduct detected as a Transition State. The formation of the desired allylic amine follows a “rebound” mechanism in which the nitrogen and carbon atoms radicals couple to yield the organic product. The release of the allylic amine restores the initial Ru(TPP)(CO) complex and allows the catalytic cycle to resume by the activation of another azide molecule. On the singlet PES, the CO ligand may be however dismissed from the mono-imido complex RuIV(TPP)(NAr)(CO)SN opening the way to an alternative catalytic cycle which also leads to allylic amine through comparable key steps. A second azide molecule occupies the freed coordination site of Ru(TPP)(NAr)SN to form the bis-imido complex Ru(TPP)(NAr)2, which is also prone to the intersystem crossing with the consequent C-H radical activation. The process continues till the azide reactant is present. The interconnected cycles have similarly high exergonic balances.
The reaction scope of the benzylic amination has been then explored studying the intramolecular amination reaction of biphenyl azides containing benzylic C-H bonds.11 This reaction allows the synthesis of N heterocyclic compounds such as dihydrophenanthridines and phenanthridines. Phenanthridines are an important class of compounds from a biological point of view. They present a significant antitumor activity and are the basis of DNA-binding. Several challenges remain to be overcome to efficiently synthesise this class of molecules, in fact, whilst many methods to access five-membered rings are known, methodologies to yield six and seven-nitrogen membered rings in few steps remain rare.
In this research project we have also studied the development of new synthetic methodologies to obtain new porphyrin frameworks and this part of my work has been developed in collaboration with Dr. Bernard Boitrel (University of Rennes, France). Some years ago we reported on the catalytic efficiency of chiral cobalt(II)-binaphthyl porphyrins in asymmetric cyclopropanations, and recorded positive data encouraging us to synthesise a structurally related chiral porphyrin.
This new porphyrin has one C2 axis within the porphyrin plane and exhibits an open space on each side for substrate access and at the same time a steric chiral bulk surrounding the N-core. The reaction of the opprhyrin with FeBr2 afforded the FeIII(OMe) complex by the initial formation of the iron (II) porphyrin complex which was oxidised by the atmospheric oxygen in the presence of CH3OH yielding the desired complex in a quantitative yield. The catalytic activity of the iron complex was initially tested in the model reaction of α methylstyrene with ethyl diazoacetate (EDA).
This new chiral iron porphyrin-based catalyst performed olefin stereoselective cyclopropanations with excellent yields (up to 99%), enantio- and diasteroselectivities (eetrans up to 87%, trans/cis ratios up to 99:1) and outstanding TON and TOF values (up to 20,000 and 120,000/h respectively).
To the best of our knowledge, the outstanding values of TON and TOF (20,000 and 120,000/h respectively) have never been reported for metallo-porphyrin catalysed cyclopropanations and the robustness of the catalyst under an inert atmosphere allowed three catalytic recycles. Finally, high cyclopropane yields were obtained without using an olefin excess in accordance with the industrial request for sustainable processes, especially when expensive olefins are involved. Studies are ongoing to expand the reaction scope, including testing the cyclopropanation of several olefins by differently substituted diazo derivatives.
References
1. S. Cenini, E. Gallo, A. Caselli, F. Ragaini, S. Fantauzzi and C. Piangiolino, Coord. Chem. Rev., 2006, 250, 1234-1253.
2. B. C. G. Soderberg, Curr. Org. Chem., 2000, 4, 727-764.
3. T. G. Driver, Org. Biomol. Chem., 2010, 8, 3831-3846.
4. S. Cenini, F. Ragaini, E. Gallo and A. Caselli, Curr. Org. Chem., 2011, 15, 1578-1592.
5. S. Fantauzzi, A. Caselli and E. Gallo, Dalton Trans., 2009, 5434-5443.
6. A. Caselli, E. Gallo, S. Fantauzzi, S. Morlacchi, F. Ragaini and S. Cenini, Eur. J. Inorg. Chem., 2008, 3009-3019.
7. P. Zardi, D. Intrieri, A. Caselli and E. Gallo, J. Organomet. Chem., 2012, 716, 269-274.
8. S. Fantauzzi, E. Gallo, A. Caselli, C. Piangiolino, F. Ragaini and S. Cenini, Eur. J. Org. Chem., 2007, 6053-6059.
9. D. Intrieri, A. Caselli, F. Ragaini, P. Macchi, N. Casati and E. Gallo, Eur. J. Inorg. Chem., 2012, 569-580.
10. D. Intrieri, A. Caselli, F. Ragaini, S. Cenini and E. Gallo, J. Porphyrins Phthalocyanines, 2010, 14, 732-740.
11. D. Intrieri, M. Mariani, A. Caselli, F. Ragaini and E. Gallo, Chem. Eur. J., 2012, 18, 10487-10490.
12. F. Ragaini, A. Penoni, E. Gallo, S. Tollari, C. L. Gotti, M. Lapadula, E. Mangioni and S. Cenini, Chem. Eur. J., 2003, 9, 249-259.
13. G. Manca, E. Gallo, D. Intrieri, C. Mealli; ACS, manuscript submitted
14. D. Intrieri, S. Le Gac, A. Caselli, E. Rose, B. Boitrel, E. Gallo; Chem.Commun.,manuscript submitted
The "semi-minimal pruned hedge (SMPH)", a novel grapevine training system, tested on cv. Sangiovese (V. vinifera L.)
No full textIn a previous three-year study on cv. Sangiovese (V. vinifera L.), the degree of adaptation to minimal pruning (MP) compared with conventional spur-pruning (CSP) was investigated in the Central Po Valley in northern Italy (Intrieri et al., 2001). Despite a marked reduction in bud sprouting, shoot fruitfulness and cluster weight, the MP vines, in which more than 600 nodes per m of row were left, showed an alternate bearing pattern coupled with large crop-linked variation of grape quality. However, the clusters of MP vines were distinctly less compact than those produced by CSP and this feature was crucial in preventing massive bunch rot even in wet season. Since all Sangiovese clones are currently characterized by dense or very dense clusters, the MP looks like an effective tool to induce looser clusters, but it was clear that future work will have to assess to counterbalance the drawbacks related to alternate bearing pattern and the delayed or incomplete ripening without loosing the feature of less compact clusters.
According to this principle, a novel grapevine training system featuring a hedge-wall 120 high x 20 cm in depth was tested on cv. Sangiovese. Designed for integral mechanised pruning and harvesting as the classic MP, but also for a more severe winter pruning, the new system was called the ‘semi-minimal pruned hedge’ (SMPH) and was shaped since 1998 starting from a spur-pruned cordon vines, by attaching a few of the preceding year’s canes to the horizontal trellis wires. The hedge shape was maintained over time by pruning the sides and top with mechanical cutter bars. Three years after the first pruning a specific study was performed, in which SMPH was compared against CSP featuring 18 count nodes per vine and per meter of row. Over the period 2000-2002, the nodes left on SMPH were 320 per m of row.
As expected, the hedged vines showed a consistently earlier leaf-area expansion in spring and a larger leaf area per vine at the end of shoot growth. Measurements of single-leaf photosynthetic capacity evinced no significant differences between the two systems, thereby indicating a greater take-up potential of the SMPH vines. Accordingly, the average yield of the SMPH vines was about 30% higher than the CSP’s, but no differences in final ripening were found. These results were confirmed during the 2002 season, in a parallel work (Filippetti et al., 2004), in which photosynthesis and dry matter production of the SMPH and of the CSP were modelled by the software Stella (High Performance System Inc. USA) and showed that SMPH had an higher dry matter accumulation compared to CSP all along the season. Overall, the SMPH clusters appeared smaller over the trial years, with less compact berries and free of botrytis (bunch rot) attacks with respect to CSP’s. In addition, a preliminary experiment on mechanical harvesting of the SMPH with an over-row horizontal shaking unit was successfully performed at the end of 2002 season.
All the above data suggest interesting practical application for the SMPH system, because of its adaptability to full mechanization and for the positive findings in regard to vine physiology and grape yield and quality, as well as to lower susceptibility to bunch rot
Iron-Catalyzed Cyclopropanation of Alkenes by Carbene Transfer Reactions
No full textThe present chapter deals with the catalytic activity of iron complexes to promote carbene transfer reactions for the synthesis of cyclopropane containing molecules. We report herein an overview of the most active cyclopropanation catalysts including iron porphyrinoids, iron complexes of nitrogen ligands and Lewis acidic iron compounds. The analysis of reported data highlights the efficiency of many iron-based catalytic processes in terms of reaction chemo- and stereoselectivities. However, iron catalysts have been undeveloped compared to other transition metal catalysts therefore there is ample opportunity to develop new and fascinating sustainable catalytic processes based on iron
In vitro acquired cellular senescence and aging-specific phenotype can be distinguished on the basis of specific mRNA expression
No full textEffetti della iperossigenazione precoce su mosti e vini ottenuti da uve bianche raccolte a macchina e pigiadiraspate in campo
No full textIron-catalysed Cyclopropanation of Alkenes by Carbene Transfer Reactions
No full textThe present chapter deals with the catalytic activity of iron complexes to promote carbene transfer reactions for the synthesis of cyclopropane containing molecules. We report herein an overview of the most active cyclopropanation catalysts including iron porphyrinoids, iron complexes of nitrogen ligands and Lewis acidic iron compounds. The analysis of reported data highlights the efficiency of many iron-based catalytic processes in terms of reaction chemo- and stereoselectivities. However, iron catalysts have been undeveloped compared to other transition metal catalysts therefore there is ample opportunity to develop new and fascinating sustainable catalytic processes based on iron
Effects of cluster thinning on grape composition: preliminary experiences on Sangiovese grapevines
No full textEffects of cluster thinning on grape and wine quality has been widely explored in relations to several factors (cultivar, time of application, environmental conditions). Results have shown that yield reduction and quality improvement are not always strictly related, especially when unthinned vines are characterized by a balanced vegetative/productive ratio.The trial was conducted over a two-year period (2003-2004) on cv Sangiovese, spur-pruned cordon trained (1 m x 2.8 m spaced) in a hillside vineyard near Bologna. In the first year the vines were adjusted to 15 clusters per plant after fruit set and at veraison the plants were randomly divided in three groups: a) T1, thinned at 10 clusters per vine; b) T2, thinned at 5 clusters per vines and c) CK, unthinned vines. The same treatments were applied in the second year of experiments.The two years average data as concern the ratio between total leaf area and production at harvest was 2.0, 3.5 and 1.3 m2/kg in T1, T2 and CK respectively, while sugar content of grapes (°Brix) was 22.7 in T1, 23.1 in T2 and 21.8 in CK. Berry skin analysis showed a tendency to a decreasing in trisubstituited anthocyanins (delphinidin-3-glucoside, petunidin-3-glucoside and malvidin-3-glucoside) and an increasing of disubstituited anthocyanins (peonidin-3-glucoside and cyanidin-3-glucoside) in thinned vines, as compared to control, especially in 2004. In the same year total anthocyanins were 1685 mg/kg, 1680 mg/kg and 1243 mg /kg in T1, T2 and CK respectively. Sensorial analysis of wine obtained from microvinification in 2003 showed no significative differences between the treatments. Microvinifications of musts and evaluations of 2004 wines are actually in progress.[...
Metabolic indices of polyunsaturated fatty acids: current evidence, research controversies, and clinical utility
No full textThe n-3 and n-6 polyunsaturated fatty acids (PUFA) are among the most studied nutrients in human metabolism. In the past few decades, prospective studies and controlled trials have supported the view that the effects of these essential fatty acids are clinically relevant. PUFA profiles in different blood compartments are reflections of both diet and metabolism, and their levels may be related to disease risk. Despite widespread interest, there is no consensus regarding which biomarkers best reflect PUFA status in the body. The measurement of PUFA levels is not straight-forward, and a wide variety of indices have been used in clinical studies, producing conflicting results. A major source of heterogeneity among studies is associated with research design, sampling, and laboratory analyses. To date, the n-3 index, n-6/n-3 ratio, and arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio are the most promising biomarkers associated with PUFA metabolism. Although hotly debated, these indices may be considered at least markers, if not risk factors, for several diseases, especially cardiovascular events and brain disorders. Here, we summarize the most updated evidence of n-3 and n-6 PUFA effects on human health, reviewing current controversies on the aforementioned indices and whether they can be considered valuable predictors of clinical outcomes
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