Current Organic Chemistry - Volume 25, Issue 20, 2021

Recent advances in the metal-catalyzed hydrofunctionalization of alkynes with carboxylic acids are comprehensively reviewed. Both inter- and intramolecular processes, leading respectively to enol esters and lactones, are discussed, as well as the involvement of these transformations in the synthesis of natural products and biologically active molecules, and the assembly of elaborated heterocyclic compounds through cascade processes. Literature published since 2011 is covered.

This account provides a broad overview of the application of solid metal catalysts in synthetic chemistry with a focus on the synthesis of medicinally important scaffolds or building blocks. Heterogeneous catalysis is a fundamental contributor to green or sustainable synthesis. Despite this, many synthetic chemists overwhelmingly focus on homogeneous methods, and due to their unfamiliarity with solid catalysts, many would not consider using them. The primary purpose of this work is to bring solid catalysts and their application possibilities to the attention of synthetic chemists in a format that focuses on reactions, thus building a bridge between the two sides for the benefit of sustainable applications and, eventually, the whole society. The two major parts of this account describe the common types of solid metal catalysts and the applications of these catalysts in sustainable synthesis. The first part gives an overview of the major types of solid metal catalysts, including common hydrogenation catalysts to metal nanoparticles. The second and more extensive part illustrates the use of these catalysts in a thematic order based on reaction types, including hydrogenation, hydrogenolysis, oxidation, metathesis, cross-coupling reactions, and hydroformylation.

Heterocycles are very important scaffolds since many of them exhibit building blocks properties and good biological activities. Various chemical methods have been utilized for their synthesis and out of them, the environmentally benign approaches are highly demanding in view of the importance of green chemistry. There are vast pieces of literature available on sustainable and multi-component synthetic approaches, but it is difficult for a researcher to keep up with research. Therefore, a review article in sustainable and multi-component synthesis of heterocycle was highly required. Herein, we have compiled the work of literatures related to multi-component reaction under solvent free condition, ultrasound assisted, water or ionic liquid mediated conditions.

A microwave-assisted organic synthesis is an alternative approach towards the traditional way of heating to obtain desired bioactive scaffolds as a product. This method has transformed the approaches of organic synthesis, due to shorter reaction time with high product yields, modifications of selectivity, increased product purities, and simplification of workup procedures. The microwave-assisted reactions can be performed under solvent-free conditions. Thus, Microwave-Assisted Organic Synthesis (MAOS) has become the first choice for the medicinal chemist and chemical biologist to use as a tool to perform organic reactions in drug discovery and medicinal chemistry. Microwave-assisted organic synthesis specifically results in the desired products with higher selectivity and purity which may have better pharmacological properties. In this review article, we covered the literature from 2010-till to date, focusing on the use of microwave irradiation in performing organic reactions to deliver various bioactive scaffolds.

Tubulin Polymerization Inhibitors (TPIs) are promising ligands utilized in chemotherapy for modern cancer treatment. However, the current TPIs exhibit many serious side effects that may pose limitations in chemotherapy. Combretastatin A-4 (CA-4) is a natural TPI that binds at the colchicine binding site located on microtubules. The only cis isomer of CA-4 is bio-active; however, due to its short half-life, it isomerizes quickly to its bio-inactive trans geometric isomer. For preventing shortcomings of CA-4, azobenzene based CA-4, called azo-CA-4 (azo-CA-4) is identified as a novel TPI. The geometric isomerization of azo- CA-4 can be controlled upon exposure to ultraviolet (UV) light to remotely control its bioactivity. Cis-azo-CA-4 is 200-500 times more active (IC50 = 0.2-10 μM) than trans-azo-CA-4 (IC50 = 50-110 μM) against various cancer cell lines. Photo-pharmacology uses light to control drug activity, introducing a unique mechanism to develop novel photo-responsive TPIs. Further, the green chemistry approach using ethanol and water as a green solvent in the synthesis of azo-CA-4 delivers advanced methodology in novel TPI development.

Bridged Nucleic Acids (BNA) or Locked Nucleic Acids (LNA) belong to a class of nucleic acid modification that is obtained by connecting the 2'-O and 4'-C of ribose sugar using a methylene bridge. This ‘bridging or locking’ of ribose sugar has a tremendous impact on the biological and biophysical properties of therapeutic nucleic acids. They have enhanced stability against nucleases and also have a higher binding affinity for the target RNA. Owing to these advantages, BNA is one of the most preferred nucleic acids modifications of Antisense Oligonucleotides (ASOs). However, the synthesis of BNA monomers is lengthy and low-yielding and requires extensive protection and deprotection of the sugar functionalities. In this article, we aim to review challenges associated with their synthesis and discuss recent chemical, chemo-enzymatic, and transglycosylation strategies employed for the efficient and cost-effective synthesis of BNA monomers and selected BNA analogues.

In carbohydrate chemistry, the synthesis of complex saccharides with well-defined structures is the most formidable process as it is quite strenuous to isolate carbohydrates in acceptable purity and amounts from natural sources. Therefore, complex saccharides with well-defined structures are often most conveniently accessed through chemical syntheses. This review mainly focuses on the methodologies for one-pot glycosylation into the complex glycans from the non-reducing end to reducing end and vice versa, orthogonal, preactivation based, photochemical as well as hybrid one-pot glycosylation. The main goal of this review in the carbohydrate community was to rapidly synthesize biologically relevant glycans that can be implemented for research in carbohydrate-based vaccine development, diagnostics, as well as drug discovery.

Carbohydrates are fascinating molecular scaffolds known for their diverse applications in chemistry, biology, medicine, technology, and materials science. In addition, owing to the notable features of Room-Temperature Ionic Liquids (RTILs) such as high-yield, short reaction time, simple handling, excellent recyclability, and environmentally benign nature, they have been extensively utilized as green solvents, catalysts, or both in a wide range of organic transformation methodologies for easy access of a diverse range of biologically relevant molecules. This review highlights the importance of RTILs that offer promising solutions in glycoscience, particularly in relevance to the dissolution, functionalization, glycosylation, and modification of carbohydrates as well as their challenges, impact, and future perspectives.