1,720,973 research outputs found
Catalytic strategies for the synthesis of carnosine derivatives
Full text linkL-Carnosine is a naturally occurring endogenous dipeptide formed by the combination of β-alanine and L-histidine, particularly in tissues with high oxidative metabolism such as muscles and the brain. By neutralizing free radicals and reducing oxidative stress—factors associated with various age-related conditions—it is believed to offer cellular protection1. The Global L-Carnosine Market size was estimated to be around USD 35.87 million in 2022, with projections indicating future growth at a compound annual growth rate of 6.45% until 2030. Thus, the development of synthetic methods able to afford L-Carnosine and its derivatives in enantiopure form is attracting interest and investments from both academia and industry. The contribution offers both the points of view applied to the attempt to achieve such a goal. The first part was focused on the development of a second-generation process for the synthesis of L-Carnosine. A series of nitrile precursor reduction studies was performed utilized gaseous H2 and commercially available (Pd, Rh, etc). As final scope, the optimization of the reaction conditions was performed, including a method for the isolation of the product as chromatographic separation and/or crystallization of the corresponding salt. Asymmetric hydrogenation using transition metal catalysts is a significant transformation in both academia and industry. Its high efficiency, atom economy, and broad substrate scope make this methodology appealing for both fields. In the second part, starting from an unsaturated precursor, different rhodium catalysts based on non-commercially available diphosphine were applied to the synthesis of enantiopure L-Carnosine derivatives with e.e. up to 95%
One-pot chemoenzymatic synthesis of enantiopure aryl- and alkyl-azaarenes pharmaceutical intermediates
Full text linkOne-pot reactions are distinctive processes in which multiple sequential reactions occur within a single reaction vessel. Crucially, each reaction begins only after the completion of the previous one, ultimately yielding the desired final product without requiring intermediate purification. This approach not only shortens the overall synthesis time but also enhances total yield and minimizes chemical waste, making it a more environmentally sustainable strategy [1,2]. Following this successful approach, a one-pot reaction was designed and set up in two steps for the preparation of enantio-enriched 3,3-azaaryl-1-aryl-propanols and 3,3-azaaryl-1-alkyl-propanols containing a pyridine core. The first step of the one-pot protocol provided the addition of phenyl boronic acid to a carbonyl-activated alkenyl azaarenes (1-4) using [Rh(coe)(S)-TetraMeBITIANP] as catalyst [3] reaching up to 80% e.e. and quantitative conversion, a prerequisite to perform in the same reactor the second step, i.e. the asymmetric reduction of the prochiral keto group. In the case of propanones 1a and 2a the enantioselective reduction was realized by a ruthenium diamine complex under ATH (Asymmetric Transfer Hydrogenation) conditions in aqueous media, affording the anti-diasteromers in up to 90% e.e. Meanwhile, a biocatalytic approach for the reduction of carbonyl group of the products 3a-4a in R configuration was realized screening different yeasts. In this case, Torulopsis molischiana CBS 837 provided the products in anti-configuration with a molar conversion up to 95% and excellent enantiopurity (up to 99% e.e.) in 24h [4]
One-pot reactions in catalysis: a valuable tool for the synthesis of enantiopure intermediates for pharmaceutical applications
Full text linkOne-pot reactions stand out as processes in which several sequential reactions are conducted in a single reaction vessel and most importantly each reaction can only start after the previous one is completed thus leading to the desired final product without the need of any purification of the intermediates. This approach allows in principle to shorten the total synthesis time and generally leads to an increase in the total yield and to a reduction in the amount of chemical waste formed, resulting beneficial from an environmental point of view (Acc. Chem. Res. 2021, 54, 6, 1385–1398). Starting from these concepts of time and pot economy, the combo of chemo- and biocatalytic approach-based on a copper catalyst and Rhodotorula rubra yeast respectively- was applied to the stereoselective synthesis of key intermediates such as 1,3 diols in excellent enantio- and diastereomeric excess (ChemistryOpen 2018, 7, 393-400) . Following the same successful approach, we have recently developed a one-pot reaction in two steps for the preparation of enantio-enriched 3,3-azaaryl-1-aryl-propanols and 3,3-azaaryl-1-alkyl-propanols containing a pyridine core. After the enantioselective addition of the phenylboronic acid to 3-azaarylprop-2-en-1-ones obtained in good yields and enantiopurity by exploiting a chiral rhodium-diphosphine catalyst (New J. Chemistry 2021, 45, 18769-18775), the subsequent carbonyl reduction was carried out by a ruthenium complex for the aryl derivatives or by a Tourolopsis genera yeast in the case of the alkyl compounds, thus affording the desired products, key intermediates for pharmaceutical applications
New catalytic strategies for one-pot total synthesis of L-carnosine
No full textThe global market of L-Carnosine is experiencing a steady growth driven by its spreading applications in nutrition, therapeutics, and cosmetics. L-Carnosine, a dipeptide composed of β-alanine and L-histidine plays key roles in oxidative stress reduction and energy metabolism with a therapeutic potential extending to conditions like diabetes, Alzheimer’s, and Parkinson’s diseases. In an attempt to develop a more sustainable synthetic pathway able to afford L-Carnosine in satisfactory yield and enantiopurity, we set up a one-pot protocol starting from compound 14, ethyl methyl (Z)-2-(2-cyanoacetamido)-3-(1H-imidazol-4-yl)acrylate, synthesized as a Privileged Precursor (PP) of L-Carnosine. The asymmetric reduction of the C=C bond in PP with [RhCOD(R,R)-Ephos]+TfO-, followed by the hydrogenation of the CN moiety using a Rh/C heterogeneous catalyst under basic conditions, afforded the desired product with an overall 68% yield and up to 73% e.e. as confirmed by HPLC-MS analysis. Although the developed protocol reduces synthetic and purification steps, further optimization is still ongoing to enable industrial application
Hybrid Metal Catalysts as Valuable Tools in Organic Synthesis: An Overview of the Recent Advances in Asymmetric C─C Bond Formation Reactions
No full textCarbon–carbon bond formation represents a key reaction in organic synthesis, resulting in paramount importance for constructing the carbon backbone of organic molecules. However, traditional metal-based catalysis, despite its advantages, often struggles with issues related to efficiency, selectivity, and sustainability. On the other hand, while biocatalysis offers superior selectivity due to an extraordinary recognition process of the substrate, the scope of its applicable reactions remains somewhat limited. In this context, Artificial Metalloenzymes (ArMs) and Metallo Peptides (MPs) offer a promising and not fully explored solution, merging the two fields of transition metal catalysis and biotransformations, by inserting a catalytically active metal cofactor into a customizable protein scaffold or coordinating the metal ion directly to a short and tunable amino acid (Aa) sequence, respectively. As a result, these hybrid catalysts have gained attention as valuable tools for challenging catalytic transformations, providing systems with new-to-nature properties in organic synthesis. This review offers an overview of recent advances in the development of ArMs and MPs, focusing on their application in the asymmetric carbon–carbon bond-forming reactions, such as carbene insertion, Michael additions, Friedel–Crafts and cross-coupling reactions, and cyclopropanation, underscoring the versatility of these systems in synthesizing biologically relevant compounds
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
New fluorinated platinum compounds as promising anticancer warriors against orphan tumors
Full text linkOrphan tumours are characterized by limitation or lack of efficacy of the standard chemotherapeutics. Among them, Glioblastoma (GBM) and pancreatic cancer are two of the main aggressive orphan tumours, considering that the only available treatment includes maximal safe surgical resection, followed by radiotherapy and chemotherapy based on classical platinum drugs, as cisplatin. Unfortunately, the survival rate remains very poor (5-6% maximum).[1][2]
Based on this consideration, the design and synthesis of platinum compounds characterized by unconventional structures could represent a promising strategy for increasing the efficacy against these kinds of tumors.
Recently we projected and evaluated new cationic platinum complexes based on the 8-aminoquinoline core with (Pt-IV)[3] showing a very interesting in vitro activity against GBM (U87-MG IC50 5.3 ± 0.55 μM). Considering that the main issues in cancer treatment stems from a reduced bioavailability, starting from the lead compound Pt-IV, we decided to expand the synthetic scope to two new series (1 and 2) in which the diamine core has been modified adding a fluorine atom in different positions in order to change the solubility of the complex and its biological activity with the aim to develop new therapeutic warriors against orphan tumors.[4
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