Recent Advances in the Synthesis of Hydantoins: The State of the Art of a Valuable Scaffold

Abstract

The review highlights the hydantoin syntheses presented from the point of view of the preparation methods. Novel synthetic routes to various hydantoin structures, the advances brought to the classical methods in the aim of producing more sustainable and environmentally friendly procedures for the preparation of these biomolecules, and a critical comparison of the different synthetic approaches developed in the last twelve years are also described. The review is composed of 95 schemes, 8 figures and 528 references for the last 12 years and includes the description of the hydantoin-based marketed drugs and clinical candidates.

Mechanoenzymatic Transformations in the Absence of Bulk Water: A More Natural Way of Using Enzymes

“…Much more akin to low η conditions of liquid‐assisted mechanochemistry, enzymes secreted by microorganisms thrive on moist surfaces, and intracellular enzymes function in highly concentrated, organized environments. This observation is consistent with the ongoing change in our understanding of chemical transformations, with the growing realization that many reactions readily proceed in solvent‐less mechanochemical environments . Indeed, mechanochemistry, which was recently proposed to be involved in the emergence of small organic molecules on the early Earth, has successfully provided routes to chemical selectivity, as well as reactions or molecules that have otherwise been considered difficult or even impractical to access.…”

“…It is our view that solvent-less environments found in liquidassistedg rinding and/ora ging in moist air,a re more effective than conventional dilute solutions in replicating the natural environmento fm any enzymes.M uch more akin to low h conditions of liquid-assisted mechanochemistry,e nzymes secreted by microorganisms thrive on moist surfaces, and intracellular enzymes functioni nh ighly concentrated, organized environments.T his observation is consistent with the ongoing change in our understanding of chemical transformations, [161] with the growingr ealization that many reactions readily proceed in solvent-less mechanochemicale nvironments. [18,115,[162][163][164][165][166][167][168] Indeed, mechanochemistry,w hichw as recently proposed to be involved in the emergence of small organic molecules on the early Earth, [169] has successfully provided routes to chemical selectivity, [19,170,171] as well as reactions [172,173] or molecules [174][175][176] that have otherwiseb een considered difficult or even impractical to access. Although mechanoenzymatic reactivity is in a very early stage of development, it has already sparked as ignificanta mount of interest, [177] and provided simple solutions to streamline industrial processing of, for example, lignocellulosic material.…”

Enantioselective Synthesis of 5,5‐Disubstituted Hydantoins by Brønsted Base/H‐Bond Catalyst Assisted Michael Reactions of a Design Template

“…[10] On the other hand, hydantoins are also interesting from ap urely chemicalp oint of view. [11] 5-Substituted hydantoins have been employed in the context of molecular recognition, [12] as chiral auxiliaries in organic synthesis, [13] and as constituents of optically active polymers [14] andm etal complexes. [15] Structurally, they can be viewed as masked a-aminoa cids, and as such, 5substituted hydantoins also serve as precursors to unnatural aamino acidd erivatives.…”

Microwave Synthesis and Antibacterial Activities of Some Imidazolidine Derivatives Containing 1,3,4-Oxadiazole Moiety

“…Imidazolidines have antitumor, antiarrhytmic and antiandrogenic activity. The activity of imidazolidin-2,4-diones (hydantoin) depends on the nature of substitution of imidazolidine ring [9]. Among imidazolidine-2-ones phenytoin is known as antiepileptic drug and antihypertensive substance [10].…”