The Bucherer–Bergs Multicomponent Synthesis of Hydantoins—Excellence in Simplicity

Abstract

Hydantoins and their hybrids with other molecules represent a very important group of heterocycles because they exhibit diverse biological and pharmacological activities in medicinal and agrochemical applications. They also serve as key precursors in the chemical or enzymatic synthesis of significant nonnatural α-amino acids and their conjugates with medical potential. This review provides a comprehensive treatment of the synthesis of hydantoins via the Bucherer–Bergs reaction including the Hoyer modification but limited to free carbonyl compounds or carbonyl compounds protected as acetals (ketals) and cyanohydrins used as starting reaction components. In this respect, the Bucherer–Bergs reaction provides an efficient and simple method in the synthesis of important natural products as well as for the preparation of new organic compounds applicable as potential therapeutics. The scope and limitations, as well as a comparison with some other methods for preparing hydantoins, are also discussed.

Designing and Anti‐Inflammatory Effectiveness of Novel Phenytoin Derivatives via One Pot Multicomponent Reaction

“…[1][2][3] Phenytoin derivatives, another analog which has thiol group and hydantoin derivatives form a huge field of broadly medicinal and pharmaceutical applications this because phenytoin and its derivatives have a therapeutic application. [1,2,4] particularly, the glycolylureas which has substitution in 5-position, for example as methetoin (1methyl-5-ethyl-5-phenylhydantoin), mephenytoin (3-methyl-5ethyl-5-phenylhydantoin), ethylphenylhydantoin (5-ethyl-5phenylhydantoin) or norantoin (5-phenyl-3-methylhydantoin) have been valuably precursors of a considerable diversity of heterocyclic compounds that are supplementary an extensive field for biological effectiveness with including of anticonvulsant, [5] antiarrhythmic, [6] and anti-tumor activities. [7] The most famous one is glycolylurea, 5,5-diarylhydantoin, dilantins which have highly activity as anticonvulsant component having effectiveness of treatment for generalizing convulsive and psychomotor epilepsy.…”

“…Relying on the nature and kind of substitutional group on the heterocyclic nucleus, these components may show pharmaceutically and biologically effectiveness with a diversity uses [1–3] . Phenytoin derivatives, another analog which has thiol group and hydantoin derivatives form a huge field of broadly medicinal and pharmaceutical applications this because phenytoin and its derivatives have a therapeutic application [1,2,4] . particularly, the glycolylureas which has substitution in 5‐position, for example as methetoin (1‐methyl‐5‐ethyl‐5‐phenylhydantoin), mephenytoin (3‐methyl‐5‐ethyl‐5‐phenylhydantoin), ethylphenylhydantoin (5‐ethyl‐5‐phenylhydantoin) or norantoin (5‐phenyl‐3‐methylhydantoin) have been valuably precursors of a considerable diversity of heterocyclic compounds that are supplementary an extensive field for biological effectiveness with including of anticonvulsant, [5] antiarrhythmic, [6] and anti‐tumor activities [7] .…”

Enantioseparation of syn- and anti-3,5-Disubstituted Hydantoins by HPLC and SFC on Immobilized Polysaccharides-Based Chiral Stationary Phases

“…The hydantoin ring also constitutes the core structure of various natural products, mostly isolated from different marine organisms, but also from bacteria [31]. For example, hemimycallins A and B were isolated from marine sponge Hemimycale arabica [26], mukanadine B was isolated from marine sponge Agelas nakamurai [32], midpacamide from Fidijan sponge Agelas mauritiana [33], and parazoanthines A-J from the Mediterranean Sea anemone Parazoanthus axinellae [34,35].…”

Chemoenzymatic enantioselective synthesis of phenylglycine and phenylglycine amide by direct coupling of the Strecker synthesis with a nitrilase reaction

“…Several chemical methods have been described for the synthesis of (non-proteinogenic) amino acids. The Bucherer-Bergs reaction uses ketones (or aldehydes), cyanide, and ammonium carbonate as starting material for the synthesis of hydantoins, which can be used as precursors in the chemical or enzymatical synthesis of amino acids (Kalnik et al, 2021). In the Erlenmeyer-Plöchl synthesis an aromatic aldehyde and an aromatic carboxylic acid react in the presence of acetic acid anhydride to an azalactone which can be subsequently converted to an α-amino acid (Corti et al, 2021;Han et al, 2021).…”