Catalytic enantioselective diboration, disilation and silaboration: new opportunities for asymmetric synthesis

This article summarizes recent developments in the area of catalytic enantioselective reactions of unsaturated organic substrates with diboron, silylboron, and disilane reagents. These reactions provide new routes to the functionalization of prochiral substrates and therefore offer new strategies in asymmetric organic synthesis.     

Mechanochemistry for Synthesis

Mechanochemical solvent‐free reactions by milling, grinding or other types of mechanical action have emerged as a viable alternative to solution chemistry. Mechanochemistry offers not only a possibility to eliminate the need for bulk solvent use, and reduce the generation of waste, but it also unlocks the door to a different reaction environment in which synthetic strategies, reactions and molecules previously not accessible in solution, can be achieved. This Minireview examines the potential of mechanochemistry in chemical and materials synthesis, by providing a cross‐section of the recent developments in using ball milling for the formation of molecules and materials based on covalent and coordination bonds.     

Protein glycosylation: new challenges and opportunities

Protein glycosylation is the most complex post-translational modification process. More than 50% of proteins in humans are glycosylated, while bacteria such as E. coli does not have this modification machinery. Many small-molecule natural products also require glycosylation in order to express their function. Development of effective synthetic tools for use in understanding the effect of glycosylation on the structure and function of biomolecules will lead to the development of new strategies to tackle major problems associated with carbohydrate-mediated biological recognitions.     

Mechanochemistry as a versatile and scalable tool for nanomaterials synthesis: Recent achievements in Košice,Slovakia

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Developing new metal-based therapeutics: challenges and opportunities

Unexpected side effects and problems experienced in clinical trials have created a difficult environment for those developing new pharmaceuticals and, as a consequence, the number of new chemical entities being registered has fallen to a historic low. Those developing metal-based therapeutics will face the same difficulties, but this environment also provides many opportunities for creative solutions to be applied to overcoming the problems and concerns. In this perspective, these challenges and opportunities are considered in the context of examples of a number of classes of metal-based therapeutics.     

Frontiers and opportunities in chemoenzymatic synthesis

Natural product biosynthetic pathways have evolved enzymes with myriad activities that represent an expansive array of chemical transformations for constructing secondary metabolites. Recently, harnessing the biosynthetic potential of these enzymes through chemoenzymatic synthesis has provided a powerful tool that often rivals the most sophisticated methodologies in modern synthetic chemistry and provides new opportunities for accessing chemical diversity. Herein, we describe our research efforts with enzymes from a broad collection of biosynthetic systems, highlighting recent progress in this exciting field.     

Mechanochemistry of dissolution: Kinetic aspect

The previous thermodynamic consideration of the mechanochemical effect of dissolution and the calculation of the chemical affinity of dissolution under the conditions of strain are supplemented by the analysis of the process kinetics. A typical, for modern experiment, case of dissolution (evaporation) of a bent plate is examined. Based on the expressions for the chemical affinity, the rate equations for two-sided and one-sided (with insulation of one of the plate sides) dissolution are derived. The relationship between the dissolution rate and the thickness and curvature of a plate is established. The effect of the strain sign related to the existence of surface tension is found by comparing the dissolution rates on the convex and concave plate sides at both two-sided and one-sided dissolution.     

Mechanochemistry: An efficient method of solvent-free synthesis of 3-amino-2,4-dicarbonitrile-5-methylbiphenyls

3-Amino-2,4-dicarbonitrile-5-methylbiphenyls are synthesized by a three-component reaction of aromatic aldehydes, malononitrile, and acetone in the presence of catalytic NaOMe under grindstone method. The yields are excellent; the procedure is simple, efficient, and environmentally benign; and all the reactions go to completion within 2–3 min.     

Mechanochemistry and Eco-Bases for Sustainable Michael Addition Reactions

The Michael addition reaction was revisited with a full focus on sustainability combined with efficiency, using mechanochemistry in mild conditions. First, the synthesis of cyclopentenone derivatives was chosen as a model reaction to find optimal conditions in mechanochemistry while using classical but weak bases. The reaction was efficient (84–95% yields), fast (2–6 h), solvent free, and required 0.1 equivalent of base. Aiming to reach greener conditions, classical bases were then replaced using new bio-sourced bases, called Eco-bases, that were easily prepared from plants and led to heterogeneous catalysts. The composition and structure of Eco-bases were characterized by MP-AES, XRPD, EBSD/EDS, HRTEM/EDX and ion chromatography. Interestingly, a high ratio of potassium was observed with the presence of K₂Ca(CO₃)₂ for the most effective Eco-base. The new Eco-bases were used for the mechanical-assisted construction of functionalized alkenone derivatives. The versatility of the method has been successfully applied with good to excellent yields to different Michael donors and acceptors. Eco-bases were recycled and reused four times with the same performances. Combining Eco-bases and mechanochemistry in Michael addition reactions allowed reaching a maximum degree of sustainability (efficient, rapid, low catalyst loading, solvent-free reactions with bio-sourced catalysts) and participating in the development of mechanochemistry in sustainable chemistry.     

The [1, 3] O-to-C rearrangement: opportunities for stereoselective synthesis

The relay of stereochemistry of a breaking C-O bond into a forming C-C bond is well-known in the context of [3, 3] sigmatropic shifts; however, this useful strategy is less well-known in other types of molecular rearrangements. Though the first successful example of a [1, 3] O-to-C rearrangement was reported more than 100 years ago, this class of reactions has received less attention than its [3, 3] counterpart. This perspective analyzes the various methods used for the activation and [1, 3] rearrangement of vinyl ethers with an emphasis on mechanism and applications to stereoselective synthesis. We also highlight our own contributions to this area.     

Dynamic combinatorial libraries: new opportunities in systems chemistry

Combinatorial chemistry is a tool for selecting molecules with special properties. Dynamic combinatorial chemistry started off aiming to be just that. However, unlike ordinary combinatorial chemistry, the interconnectedness of dynamic libraries gives them an extra dimension. An understanding of these molecular networks at systems level is essential for their use as a selection tool and creates exciting new opportunities in systems chemistry. In this feature article we discuss selected examples and considerations related to the advanced exploitation of dynamic combinatorial libraries for their originally conceived purpose of identifying strong binding interactions. Also reviewed are examples illustrating a trend towards increasing complexity in terms of network behaviour and reversible chemistry. Finally, new applications of dynamic combinatorial chemistry in self-assembly, transport and self-replication are discussed.     

Mechanochemistry and mechanical activation of solids

Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2228–2245, October, 1990.     

Natural products and Pharma 2011: strategic changes spur new opportunities

Although natural products have been marginalized by major pharmaceutical companies over the last 20-30 years, the changing landscape of drug discovery now favors a greatly enhanced role for Nature's privileged structures. Screening for drug leads in phenotypic screens provides the best opportunity to realize the value of natural products. Advances in total synthesis, especially function-oriented syntheses and biosynthetic technologies offer new avenues for the medicinal chemical optimization of biologically active secondary metabolites. Genomic research has given new insights into biosynthetic processes as well as providing evidence that a wealth of unrealized biosynthetic potential remains to be explored. As Pharma strives to develop innovative and highly effective new drugs, natural products will be increasingly valued as sources of novel leads whose further development will be expedited by emerging technologies.     

High oxidation state organometallic chemistry in aqueous media: new opportunities for catalysis and electrocatalysis

Molybdenum has been used as a case study for the rational development of a new domain of organometallic chemistry, combining oxo-stabilized high oxidation state metals and aqueous media. The pH-dependent conversion of oxo, hydroxo, and aqua ligands allows the opening of free coordination sites, while the use of a redox active metal opens possible pathways for coupled proton and electron transfer to and from activated substrates. While our work has so far only concentrated on synthesis and analytical investigations, the development of catalytic and electrocatalytic processes in water or aqueous media is a promising application of this new research area.     

Rapid and cleaner synthesis of 1,4‐dihydropyridines in aqueous medium

The present investigation deals with a novel water soluble Lewis acid complex, Zn[(L)proline]₂ catalyzed Hantzsch 1,4‐dihydropyridine derivatives syntheses in aqueous medium assisted by microwave irradiation. The microwave promoted syntheses in aqueous medium afforded moderate to excellent yield (up to 98%) within short reaction time and allowed the reaction to take place with low microwave power (200 W). This synthetic methodology provides easier separation of products and the catalyst exhibits recycling ability without loss of its catalytic activity up to five reaction cycles. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:267–271, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20197