Current Organic Chemistry - Volume 28, Issue 5, 2024

Heterocyclic compounds containing nitrogen and their derivatives have been a rich source of medicines. Pyrazole, a five-membered ring structure, offers a variety of functionalities as well as stereo-chemical complexity. Studies conducted over the past 10 years revealed that an increasing amount of research has been performed on different pyrazole derivatives and their physiological and pharmacological activities. The objective of these studies is to uncover the full potential of pyrazole derivatives by elucidating the many druglike properties and their link between the structure and mode of action. Here, we discuss different ways of synthesizing pyrazole derivatives. Due to recent advances in synthetic medicinal chemistry, this class of compounds can be readily developed and becomes a viable target for the discovery of novel drugs.

The cheaper and less-toxic metals of group 4 compared with common metals used in catalysis are increasingly applied in catalysis, resulting in the development of many novel greener transformations. Zirconium is abundant, non-toxic, and exhibits a remarkably diversified chemical reactivity among these metals. Since the first asymmetric zirconium-catalyzed reaction disclosed by Nugent in 1992, a wide variety of chiral zirconium catalysts have been proven to be capable of promoting many types of highly enantioselective transformations, spanning from standard reactions, such as Friedel-Crafts reactions, cycloadditions, aldol reactions, Mannich reactions, epoxidations, nucleophilic additions to carbonyl compounds and derivatives, cyanations, ring-opening reactions, hydroxylations, hydroformylations, carboaluminations among others, to more modern and complex domino and tandem processes. This review aims to collect the major progress achieved in the field of enantioselective transformations of all types promoted by chiral zirconium catalysts, covering the literature since the beginning of 2003 and illustrating the power of these non-toxic catalysts to provide high enantioselectivity in almost all kinds of asymmetric organic reactions. It is divided into ten parts, focussing consecutively on enantioselective Friedel-Crafts reactions, cycloadditions, aldol reactions, Mannich reactions, epoxidations, additions of alkylzinc reagents to imines, cyanations, ring-opening reactions, hydroxylations, and domino/ tandem reactions. The diversity of these transformations well reflects that of the products synthesized. For example, chiral indole and pyrrole derivatives were prepared from Friedel-Crafts reactions; pyranones, pyridones and pyrazolidines from cycloadditions; β-hydroxy α-diazo carbonyl compounds, β- hydroxy (thio)esters and β-hydroxy-α-amino acid derivatives from aldol reactions; β-amino (thio)esters from Mannich reactions; functionalized epoxides from epoxidations; amines from additions of alkylzinc reagents to imines; amino nitriles from cyanations; 1,2-diamines and β-vinyloxy alcohols from ring-opening processes; 2- hydroxy 1-indanones from hydroxylations; various amines, 1,3-anti-diol monoesters, β-amino esters, α,β- dihydroxy acid derivatives, α-amino ketones, indoles, cyclopentane and aryl α-aminophosphonates from domino/ tandem reactions. Furthermore, the utility of these novel methodologies was demonstrated in the total synthesis of numerous essential bioactive products, such as (+)-prelactone C, (+)-9-deoxygoniopypyrone, (+)- coniine, vancomycin, (+)-fusarisetin A, mycolipenic acid, onchidin, indoxacarb, tachykinin receptor antagonists, cerebroprotecting agent MS-153, and L-erythro-sphingosine. The advances achieved in the last three decades demonstrate that the non-toxicity, abundance, and efficiency of zirconium make its application in catalysis suiting the growing demand for more environmentally benign processes, offering the real opportunity to replace other toxic and expensive metals in the near future.

Cyclodextrins (CDs), which are a type of cyclic oligosaccharides, are widely used in supramolecular chemistry. For example, they can be used to encapsulate volatile compounds, such as drugs, within their hydrophobic cavity. This encapsulation reduces the volatility of the compounds and helps to retain their desired properties. Due to its extraordinary properties, cyclodextrins have been utilized as catalysts in numerous organic synthesis processes. An intrinsic objective of organic chemists is to optimize the efficacy of organic synthesis through the mitigation of chemical waste and energy expenditure. Utilizing water as a green solvent is, therefore, economical, environmentally sustainable, and secure. It appears that employing water in conjunction with a recyclable catalyst is the most effective method for supramolecular catalysis. As a consequence, we focused this review on the use of water as a solvent and cyclodextrin as a polymer catalyst to produce quinoxaline derivatives in an environmentally friendly and sustainable manner.

Amines are “derivatives of ammonia” and important key intermediates for applications in the industrial, pharmaceutical, electronics, etc. They have been used to synthesize industrially important azo dyes, which are used to color various materials. Moreover, amine functionality is present in several important biological molecules. Biogenic amines are found in living organisms and play essential physiological functions in the body. They are prepared from the amination and transamination reaction of carbonyl compounds such as aldehydes and ketones and the decarboxylation reaction of amino acids. Thus, the various applications and requirements of essential amine scaffolds paid attention to researchers to develop novel synthetic protocols to synthesize these compounds. In organic chemistry, various methods synthesize amines; however, green synthetic methods have recently become a trend. By writing this review, our main focus was to provide a brief on the importance of some biogenic amines and the synthesis of both amines via green synthetic methods.

Naturally and synthetically obtained lipophilic α-amino acids exhibit diverse properties and applications in academia and industry. Unnatural hydrophobic/lipophilic amino acids lacking polarity in their side chains manifest the biologically significant structure of peptides and proteins. The hydrophobic effect of lipophilic amino acids stabilizes the structure of proteins, peptides, and enzymes during their indigenous folding-unfolding phenomena. The presence of these amino acids in the backbone of protein and peptide-derived drug delivery systems such as lysine-derived surfactants and glycodendrimers can also enhance the cell penetration of drugs of interest. Cationic poly-l-lysine dendrimers, α-amino oleic acid, and a naturally occurring cyclic heptadepsipeptide HUN-7293 are recognized as promising biomaterials for developing prodrugs and also serve as biocompatible surfactants in the food, cosmetic and pharmaceutical industries. The synthesis of unnatural lipophilic amino acids, N-lauroyl sarcosine, N-lauroyl glutamic acid, N-octylglycine, N-myristoyl glycine etc. has gained attention for preparing novel compounds for advanced academic, industrial, and societal applications. This review article discusses the applications and synthesis of hydrophobic/lipophilic α-amino acids using ester enolate Claisen rearrangement, chiral auxiliary, chiral pool, chiral catalysts, and many more relevant methodologies.