Substitution in the hydantoin ring. Part VIII. Alkylation

Orazi, Orfeo O.; Corral, Renée A.; Schuttenberg, Herman

doi:10.1039/p19740000219

Cited by 12 publications

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“…19 The alkylation at the N-1 position required harsh conditions involving the use of sodium hydride in dimethylformamide to give N-1 and N-3 disubstituted products. 20 Exclusive formation of N-1 alkylated hydantoin necessitates a very tedious, time-consuming, and long process that normally follows the protection-deprotection strategy. 21 The first step involves the protection of the N-3 position by making the use of aryl sulfonyl chlorides in the presence of triethylamine and DMAP (Scheme 1).…”

Section: Substitution In Hydantoins At N-1 and N-3 Positionsmentioning

confidence: 99%

“…The enzymatic hydrolysis of hydantoin is mostly performed using D-hydantoinase and D-N-carbamoylase (Scheme 2, pathway B). 35 D-Hydantoinase first selectively cleaves Dhydantoins to afford N-carbamoyl-D-amino acids (21) which, in the presence of D-N-carbamoylase, is converted into free Damino acids (20). D-p-hydroxyphenyl glycine is the valuable precursor for penicillins and cephalosporins which is commercially obtained by this technique.…”

Section: Synlett Accountmentioning

confidence: 99%

“…Hence, the first alkylation with an alkyl halide in the presence of a mild base (usually potassium carbonate) generally takes place at the N-3 position (Scheme 1). 19 Alkylation at the N-1 position requires harsher conditions involving the use of sodium hydride in N,Ndimethylformamide to give N-1 and N-3 disubstituted products. 19 The exclusive formation of N-1 alkylated hydantoins necessitates a laborious, time-consuming, and lengthy process that normally involves a protection-deprotection strategy.…”

Section: Substitution Of Hydantoins At the N-1 And N-3 Positionsmentioning

confidence: 99%

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Designed Synthesis of Diversely Substituted Hydantoins and Hydantoin-Based Hybrid Molecules: A Personal Account

Kumar¹

2021

Synlett

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Hydantoin and its analogs such as thiohydantoin and iminohydantoin have received substantial attention both from a chemical and biological point of view. Several compounds of this class have shown useful pharmacological activities such as anticonvulsant, antitumor, antiarrhythmic, herbicidal, and others that lead in some cases to clinical applications. Because of broad-spectrum activities, intensive research efforts have been dedicated in industry and academia to the synthesis and structural modifications of hydantoin and its derivatives. Realizing the importance of hydantoin in organic and medicinal chemistry, we also initiated a research program to successfully design and develop the new routes/methods resulting in the formation of hydantoin, thiohydantoin, and iminohydantoin substituted at different positions particularly at the N-1 position without following protection-deprotection strategy. Given the fact that the combination of two or more pharmacophoric groups may lead to hybrid molecules which result in a mixed mechanism of action on the biological target. We, therefore, further extended the developed strategy for the synthesis of new types of hydantoin-based hybrid molecules by combining hydantoin with a triazole, isoxazoline, and phosphate scaffolds as another pharmacophoric group to exploit diverse biological functions.

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Section: Substitution In Hydantoins At N-1 and N-3 Positionsmentioning

confidence: 99%

Section: Synlett Accountmentioning

confidence: 99%

Section: Substitution Of Hydantoins At the N-1 And N-3 Positionsmentioning

confidence: 99%

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Designed Synthesis of Diversely Substituted Hydantoins and Hydantoin-Based Hybrid Molecules: A Personal Account

Kumar¹

2021

Synlett

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“…The chemical reagents used in the synthesis were purchased from E. Merck (Darmstadt, Germany) and Aldrich (Milwaukee, MI, USA). 2,4-TZD (II) [6], substituted-2,4-TZD (IVa-f) (6-8) and substituted-2,4-imidazolidinedione (Va-f) [6,[9][10][11][12] were synthesized according to the literature.…”

Section: Chemical Analysismentioning

confidence: 99%

Synthesis and Antidiabetic Activity of Some New Chromonyl-2,4-thiazo-lidinediones

Bozdağ‐Dündar

Ceylan–Ünlüsoy

Verspohl

et al. 2011

Arzneimittelforschung

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A series of chromonyl-2,4-thiazolidinediones (VIa-f) and chromonyl-2,4-imidazolidinediones (VIIa-f) was prepared by Knoevenagel reaction of substituted benzyl-2,4-thiazolidinediones (IVa-f) and substituted benzyl-2,4-imidazolidinediones (Va-f) with chromone-3-carboxaldehyde (I). The prepared compounds were tested for their insulinotropic activities in INS-1 cells. Compounds VIa, VIb, VId and VIIe (at lower concentration; 1 microg/ml) were able to increase insulin release in the presence of 5.6 mmol/l glucose; their effects were lower than that of glibenclamide (CAS 10238-21-8). The activity of the most potent compound (VId) was still 9% less than that of glibenclamide.

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“…Hidantoínas mono-alquiladas em N1 podem ser obtidas por proteção do nitrogênio imida com um grupo amino metil, seguido da alquilação do nitrogênio da amida e da remoção do grupo protetor por hidrólise alcalina suave. 19 Alquilações em N1 são conhecidas em compostos hidantoínicos substituídos 20 …”

Section: N-alquilaçãounclassified

Estrutura, reatividade e propriedades biológicas de hidantoínas

Oliveira¹,

Silva²,

Hernandes³

et al. 2008

Quím. Nova

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Recebido em 27/9/06; aceito em 10/8/07; publicado na web em 19/3/08 STRUCTURE, REACTIVITY AND BIOLOGICAL PROPERTIES OF HIDANTOINES. Hydantoin (imidazolidine-2,4-dione) is a 2,4-diketotetrahydroimidazole discovered by Baeyer in 1861. Thiohydantoins and derivatives were prepared, having chemical properties similar to the corresponding carbonyl compounds. Some biological activities (antimicrobial, anticonvulsant, schistosomicidal) are attributed to the chemical reactivity and consequent affinity of hydantoinic rings towards biomacromolecules. Therefore, knowledge about the chemistry of hydantoins has increased enormously. In this review, we present important aspects such as reactivity of hydantoins, acidity of hydantoins, spectroscopy and cristallographic properties, and biological activities of hydantoin and its derivatives.Keywords: hydantoin; reactivity; biological properties. INTRODUÇÃOOs fármacos são substâncias usadas para impedir ou curar doenças em homens e animais. A introdução de novos fármacos na terapêutica é necessária para o aperfeiçoamento do tratamento de doenças já existentes ou recém-identificadas ou, ainda, para a implementação de tratamentos mais seguros e eficazes. Desde a Antigüidade, diversas civilizações possuíam coleções de produtos naturais que usavam como tratamentos para os diversos males. Em particular, no final do século XIX, a busca por medicamentos menos tóxicos resultou na introdução de substâncias sintéticas na terapêutica e seu uso foi amplamente disseminado no século XX. 1 Em estatísticas da área de química medicinal, 2 em 2001, cerca de 85% dos fármacos disponíveis na terapêutica moderna são de origem sintética, isto sem considerar aqueles oriundos de processos de semi-síntese. Neste contexto, diversas substâncias sintéticas são obtidas a partir de derivações de anéis heterocíclicos, dentre as quais, destaca-se a hidantoína (Figura 1a) devido à sua potencialidade como protótipo para o desenvolvimento de novos fármacos.A hidantoína foi descoberta por Baeyer, em 1861, enquanto pesquisava as reações do ácido úrico e corresponde ao 2,4-dicetotetra-hidro-imidazol, embora seja também denominada imidazolidina-2,4-diona. A primeira fórmula estrutural da hidantoína foi sugerida por Kolbe, em 1870, tendo sido modificada por Strecker, que, neste mesmo ano, propôs uma nova fórmula que é aceita até hoje. A partir dessa época, o sistema anelar hidantoínico tem sido intensivamente estudado tanto no tocante aos aspectos químicos, quanto biológicos. 3A substituição dos átomos de oxigênio carbonílicos da hidantoína por átomos de enxofre origina três tio-derivados: a 2-tio-hidantoína (2-tioxo-imidazolidin-4-ona) (Figura 1b), a 4-tiohidantoína (4-tioxo-imidazolidin-2-ona) (Figura 1c) e a 2,4-ditiohidantoína (imidazolidina-2,4-ditiona) (Figura 1d).A primeira tio-hidantoína sintética, a 2-tio-hidantoína (2-tioxoimidazolidin-4-ona), foi obtida por Klason (1890) pelo aquecimento do hidrocloreto de etil-aminoacetato em presença de tiocianato de potássio. 4 Mais tarde, em 1911, três novos trabalhos pub...

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Substitution in the hydantoin ring. Part VIII. Alkylation

Cited by 12 publications

References 0 publications

Designed Synthesis of Diversely Substituted Hydantoins and Hydantoin-Based Hybrid Molecules: A Personal Account

Designed Synthesis of Diversely Substituted Hydantoins and Hydantoin-Based Hybrid Molecules: A Personal Account

Synthesis and Antidiabetic Activity of Some New Chromonyl-2,4-thiazo-lidinediones

Estrutura, reatividade e propriedades biológicas de hidantoínas

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