Hybrid Metal Catalysts as Valuable Tools in Organic Synthesis: An Overview of the Recent Advances in Asymmetric C─C Bond Formation Reactions.

Carbon-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.

Chemoenzymatic approach towards the synthesis of the antitumor and antileishmanial marine metabolite (+)-Harzialactone A via the stereoselective, biocatalyzed reduction of a prochiral ketone.

As a rich source of biological active compounds, marine natural products have been increasingly screened as candidates for developing new drugs. Among the several marine products and metabolites, (+)-Harzialactone A has drawn considerable attention for its antitumor and antileishmanial activity. In this work a chemoenzymatic approach has been implemented for the preparation of the marine metabolite (+)-Harzialactone A.

Alternative Strategy to Obtain Artificial Imine Reductase by Exploiting Vancomycin/D-Ala-D-Ala Interactions with an Iridium Metal Complex.

Based on the supramolecular interaction between vancomycin (Van), an antibiotic glycopeptide, and D-Ala-D-Ala (DADA) dipeptides, a novel class of artificial metalloenzymes was synthesized and characterized. The presence of an iridium(III) ligand at the -terminus of DADA allowed the use of the metalloenzyme as a catalyst in the asymmetric transfer hydrogenation of cyclic imines. In particular, the type of link between DADA and the metal-chelating moiety was found to be fundamental for inducing asymmetry in the reaction outcome, as highlighted by both computational studies and catalytic results.

Vancomycin-Iridium (III) Interaction: An Unexplored Route for Enantioselective Imine Reduction.

The chiral structure of antibiotic vancomycin (Van) was exploited as an innovative coordination sphere for the preparation of an IrCp* based hybrid catalysts. We found that Van is able to coordinate iridium (Ir(III)) and the complexation was demonstrated by several analytical techniques such as MALDI-TOF, UV, Circular dichroism (CD), Raman IR, and NMR. The hybrid system so obtained was employed in the Asymmetric Transfer Hydrogenation (ATH) of cyclic imines allowing to obtain a valuable 61% () in the asymmetric reduction of quinaldine .

Cascade Reaction by Chemo- and Biocatalytic Approaches to Obtain Chiral Hydroxy Ketones and 1,3-Diols.

A chemo- and biocatalytic cascade approach was applied for the stereoselective synthesis of hydroxy ketones and the corresponding 1,3-diols. A new class of tridentate N,N,O ligands was used with copper(II) complexes for the asymmetric β-borylation of α,β-unsaturated compounds. The complex containing ligand emerged as the best performer, and it gave the organoborane derivatives with good values.

Synthesis and Biological Evaluation of New Natural Phenolic (2E,4E,6E)-Octa-2,4,6-trienoic Esters.

In the present study the esterification of the OH groups of resveratrol, caffeic acid, ferulic acid, and β-sitosterol with an antioxidant polyconjugated fatty acid, (2E,4E,6E)-octa-2,4,6-trienoic acid, was achieved. As the selective esterification of OH groups of natural compounds can affect their biological activity, a selective esterification of resveratrol and caffeic acid was performed by an enzymatic approach. The new resulting compounds were characterized spectroscopically (FT-IR, NMR mono, and bidimensional techniques); when necessary the experimental data were integrated by quantum chemical calculations.

Self-assembly of an amphipathic ααβ-tripeptide into cationic spherical particles for intracellular delivery.

The development of molecular carriers able to carry molecules directly into the cell is an area of intensive research. Cationic nanoparticles are effective delivery systems for several classes of molecules, such as anticancer agents, oligonucleotides and antibodies. Indeed, a cationic charge on the outer surface allows a rapid cellular uptake together with the possibility of carrying negatively charged molecules.

New insights into glycopeptide antibiotic binding to cell wall precursors using SPR and NMR spectroscopy.

Glycopeptide antibiotics, such as vancomycin and teicoplanin, are used to treat life-threatening infections caused by multidrug-resistant Gram-positive pathogens. They inhibit bacterial cell wall biosynthesis by binding to the D-Ala-D-Ala C-terminus of peptidoglycan precursors. Vancomycin-resistant bacteria replace the dipeptide with the D-Ala-D-Lac depsipeptide, thus reducing the binding affinity of the antibiotics with their molecular targets.

Cytotoxic effect of (1-methyl-1H-imidazol-2-yl)-methanamine and its derivatives in Pt(II) complexes on human carcinoma cell lines: a comparative study with cisplatin.

The synthesis and pharmacological characterisation of (1-methyl-1H-imidazol-2-yl)-methanamine and its derivatives in Pt(II) complexes are described. Six out of eleven new Pt(II) complexes showed a significant cytotoxic effect on NCI-H460 lung cancer cell line with EC50 values between 1.1 and 0.

Chemoenzymatic deacylation of ramoplanin.

The chemoenzymatic deacylation of ramoplanin A2 is described for the first time: ramoplanin A2 was Boc-protected and hydrogenated to Boc-protected tetrahydroramoplanin, which was subsequently deacylated using an acylase from Actinoplanes utahensis NRRL 12052. The chemoenzymatic process proceeded with 80% overall yield, which favourably compares with the previously described chemical deacylation.

Biotransformations of lipoglycopeptides to obtain novel antibiotics.

The emergence of resistance among Gram-positive pathogens towards glycopeptide antibiotics has stimulated the research of second-generation molecules with improved activity and expanded antimicrobial spectrum. In this paper we investigate biotransformations as a way to generate novel teicoplanin- and A40926-like molecules. A range of commercial enzymes, fungi and actinomycetes were tested on A40926 and on its semi-synthetic derivatives (MDL 63,246 and dalbavancin).

Steroid hydroxylations with Botryodiplodia malorum and Colletotrichum lini.

An improved procedure for the microbial hydroxylations of dehydroepiandrosterone (DHEA, 1) and 15 beta,16 beta-methylene-dehydroepiandrosterone (2) was studied using whole cells of Botryodiplodia malorum and Colletotrichum lini. C. lini catalyzed 7 alpha- and 15 alpha-hydroxylation of 1 and 7 alpha-hydroxylation of 2, while B.

Reactivity and stability of mycelium-bound carboxylesterase from Aspergillus oryzae.

The reactivity and thermostability of a novel mycelium-bound carboxylesterase from lyophilized cells of Aspergillus oryzae are explored in organic solvent. Ethanol acetylation was selected as reference esterification reaction. High carboxylesterase activity cells were used as biocatalyst in batch esterification tests at 12.