Investigation of Enantioselectivity Using TADDOL Derivatives as Chiral Ligands in Asymmetric Cyanation Reactions.

This study investigates the enantioselectivity challenges of asymmetric cyanation reactions using TADDOL derivatives as chiral ligands, specifically focusing on the cyanosilylation of aldehydes and the cyanation of imines. Despite extensive optimization efforts, the highest achieved ee was only modest, peaking at 71% for the cyanosilylation reaction, while the cyanation of imines consistently resulted in racemic mixtures. Our comprehensive analysis, supported by experimental data and computational modeling, reveals significant barriers to enhancing the enantioselectivity. The results highlight a complex interplay between ligand structure and reaction conditions, demonstrating that even promising ligands such as TADDOL derivatives face substantial challenges in these reaction types. This study underscores the importance of understanding the mechanistic details through computational insights to guide future improvements in asymmetric catalysis.

Exploration of novel cationic amino acid-enriched short peptides: design, SPPS, biological evaluation and in silico study.

Antimicrobial resistance (AMR) represents a critical challenge worldwide, necessitating the pursuit of novel approaches to counteract bacterial and fungal pathogens. In this context, we explored the potential of cationic amino acid-enriched short peptides, synthesized via solid-phase methods, as innovative antimicrobial candidates. Our comprehensive evaluation assessed the antibacterial and antifungal efficacy of these peptides against a panel of significant pathogens, including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pyogenes, Candida albicans, and Aspergillus niger. Utilizing molecular docking techniques, we delved into the molecular interactions underpinning the peptides' action against these microorganisms. The results revealed a spectrum of inhibitory activities, with certain peptide sequences displaying pronounced effectiveness across various pathogens. These findings underscore the peptides' potential as promising antimicrobial agents, with molecular docking offering valuable insights into their mechanisms of action. This study enriches antimicrobial peptide (AMP) research by identifying promising candidates for further refinement and development toward therapeutic application, highlighting their significance in addressing the urgent issue of AMR.

Synthesis and Evaluation of Biological Activities for a Novel 1,2,3,4-Tetrahydroisoquinoline Conjugate with Dipeptide Derivatives: Insights from Molecular Docking and Molecular Dynamics Simulations.

Peptide synthesis has opened new frontiers in the quest for bioactive molecules with limitless biological applications. This study presents the synthesis of a series of novel isoquinoline dipeptides using advanced spectroscopic techniques for characterization. These compounds were designed with the goal of discovering unexplored biological activities that could contribute to the development of novel pharmaceuticals. We evaluated the biological activities of novel compounds including their antimicrobial, antibacterial, and antifungal properties. The results show promising activity against Escherichia coli and potent antibacterial activity against MTCC 443 and MTCC 1688. Furthermore, these compounds demonstrate strong antifungal activity, outperforming existing standard drugs. Computational binding affinity studies of tetrahydroisoquinoline-conjugated dipeptides against E. coli DNA gyrase displayed significant binding interactions and binding affinity, which are reflected in antimicrobial activities of compounds. Our integrative significant molecular findings from both wet and dry laboratories would help pave a path for the development of antimicrobial therapeutics. The findings suggest that these isoquinoline-conjugated dipeptides could be excellent candidates for drug development, with potential applications in the fight against bacterial and fungal infections. This research represents an exciting step forward in the field of peptide synthesis and its potential to discover novel bioactive molecules with significant implications for human health.

Enantioselective synthesis of tetrahydrocarbazoles via trienamine catalysis and their anxiolytic-like activity.

The first study about the anxiolytic activity of two chiral tetrahydrocarbazoles is presented. This new chiral compounds were prepared through an organocatalytic strategy via trienamine activation. The in situ ortho-quinodimethane species, formed by the condensation of the N-protected 2-methylindole acrylaldehyde with a sterically hindred diarylsilylprolinol ether derivative as catalyst, easily participate in a Diels-Alder reaction with the ethyl cyanophenyl acrylate as dienophile, in good yields and excellent stereoselectivity. These compounds showed activity against anxiety and mood disorders that can possibly contribute in the discovery of new drugs. In addition, the use of N-protected 2-methylindole acrylaldehyde will set a new base for the synthesis of medically and pharmacologically important tetrahydrocarbazoles via trienamine catalysis.

BODIPY as electron withdrawing group for the activation of double bonds in asymmetric cycloaddition reactions.

In this work we have found that a BODIPY can be used as an electron withdrawing group for the activation of double bonds in asymmetric catalysis. The synthesis of cyclohexyl derivatives containing a BODIPY unit can easily be achieved via trienamine catalysis. This allows a new different asymmetric synthesis of BODIPY derivatives and opens the door to future transformation of this useful fluorophore. In addition, the Quantum Chemistry calculations and mechanistic studies provide insights into the role of BODIPY as an EWG.