• Archives of Pharmacal Research
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• v.17 no.4
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• pp.281-283
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• 1994

5-sec-butylthiomethyl-5-alkyl (methyl or phenyl) hydantoins (3-x) were prepared by the reaction of sec-buylthiomethyl alkyl (methyl or phenyl) ketone (1-2), potassium cyanide and ammonium carbonate. 3-(2-Bromoethyl) hydantoins (5-6) were the reaction products of 5-sec-buythiomethyl-5-alkyl (methyl or phenyl) hydantoin and 1, 2-dibromothane in the presence of potassium hydroxide. Alkylation of 5 and 6 with an excess of alkyl (methyl or ethyl iodide in THF with sodium hydride as base gave three 1-alkyl (methyl or ethyl)-3-(2-bromoethyl) hydantoins (7-9). Treatment of the 2-bromothyl group with potassium thioacelate and triethylamine gave three 1-alkyl (methyl or ethyl)-3-92-acetylthioethyl) hydantoins (10-12). Hydrolysis of the 2-acetylthiuoethyl group with sodium hydroxide in methanol afforded the three 1-alkyl (methyl or ethyl)-3-(2-mercaptorthyl) hydantoins.

• Bulletin of the Korean Chemical Society
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• v.28 no.5
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• pp.751-757
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• 2007

To develop new COX-2 inhibitors, 1,5-diarylhydantoins and 1,5-diaryl-2-thiohydantoins were synthesized from phenylacetic acids by esterification, bromination, C-N bond formation and cyclization. Esters 1-3 were efficiently synthesized from the starting materials by reflux in absolute methanol for 3 h containing concentrated sulfuric acid as catalyst. Bromination was carried out with N-bromosuccinimide at rt in dichloromethane. Bromides 4-6 were reacted with aniline, p-anisidine, sulfanilamide in ethanol (or N,N-dimethylformamide) to provide the amines 7-15. Hydantoins and 2-thiohydantoins 16-46 were synthesized from amines 7-15 by treating them with potassium isocyanate (or potassium thiocyanate) and triethylamine. The synthetic process from alkyl α-anilinophenylacetate 7-15 to 3-alkylhydantoins was carried out in a one-pot reaction using alkyl isocyanate (alkyl isothiocyanate).

• Journal of Microbiology and Biotechnology
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• v.19 no.12
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• pp.1497-1505
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• 2009

The thermophile Bacillus fordii MH602 was screened for stereospecifically hydrolyzing DL-5-substituted hydantoins to L-$\alpha$-amino acids. Since the reaction occurs at higher temperature, the advantages for enhancement of substrate solubility and for racemization of DL-5-substituted hydantoins during the conversion were achieved. The hydantoin metabolism gene cluster from thermophile is firstly reported in this paper. The genes involved in hydantoin utilization (hyu) were isolated on an 8.2-kb DNA fragment by restriction site-dependent PCR, and six ORFs were identified by DNA sequence analysis. The hyu gene cluster contained four genes with novel cluster organization characteristics: the hydantoinase gene hyuH, putative transport protein gene hyuP, hyperprotein gene hyuHP, and L-carbamoylase gene hyuC. The hyuH and hyuC genes were heterogeneously expressed in E. coli. The results indicated that hyuH and hyuC are involved in the conversion of DL-5-substituted hydantoins to an N-carbamyl intermediate that is subsequently converted to L-$\alpha$-amino acids. Hydantoinase and carbamoylase from B. fordii MH602 compared respectively with reported hydantoinase and carbamoylase showed the highest identities of 71% and 39%. The novel cluster organization characteristics and the difference of the key enzymes between thermopile B. fordii MH602 and other mesophiles were presumed to be related to the evolutionary origins of concerned metabolism.

• Journal of the Korean Chemical Society
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• v.41 no.12
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• pp.679-681
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• 1997

• Archives of Pharmacal Research
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• v.5 no.2
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• pp.103-106
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• 1982

By the reaction of 15 with 3-halohydantoins (4-14) in N, N-dimethylformamide, which were prepared from corresponding hydantoins, 3-bromo-5, 5-dimethylhydantoin was found to be the most convenient reagent for halolactonization reaction.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.344.1-344.1
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• 2002

We report the synthesis of several new 3-aminohydantoinyl-1.2-benzothiazine derivatives and propose an another mechanism of the cyclization to the hydantoins for the development candidates of COX-2 inhibitors. 3-Aminohydantoins 3a-d were prepared through cyclization of the condensation products that were formed by heating amino acids and tert-bytyl carbazate in quinoline according to the method of Lalezari. (omitted)

• YAKHAK HOEJI
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• v.48 no.2
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• pp.135-140
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• 2004

For the development of new COX-2 inhibitors, 1,5-diarylhydantoins 5a∼5c and 1,5-diaryl-2-thiohydantoin 6a∼6c were synthesized from commercially available phenylacetic acids through esterification, bromination, C-N bond formation and cyclization. Esters 2a∼c were efficiently synthesized from the starting materials 1a∼c by refluxing in absolute methanol for 3 hours with catalytic concentrated sulfuric acid. Bromination of 2a∼c was carried out with use of N-bomosuccinimide at rt in dichloromethane. The bromine of 3a∼c was substituted with aniline in ethanol or N,N-dimethylformamide to provide 4a∼c. Hydantoins and 2-thiohydantoins were synthesized from 4a∼c by treatment of potassium isocyanate or potassium thiocyanate in dil-ethanol with triethylamine.

• YAKHAK HOEJI
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• v.27 no.4
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• pp.309-314
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• 1983

Six hydantoin derivatives, 3-(2-chloroethyl) hydantoin (6a), 3-(2-chloroethyl)-5-isopropylhydantoin (6b), 3-(2-chloroethyl)-5-isobutylhydantoin (6c), 3-(2-chloroetbyl)5-(2-butyl) hydantoin (6d), 3-(2-chloroethyl)-5-benzylhydantoin (6e), 3-(2-chloroethyl)-5-(indolyl-3-methyl) hydantoin (6f), were prepared by the treatment of the corresponding salt of amino acids with 2-chloroethyl isocyanate in cold water, followed by refluxing in concentrated HCl solution. Anticancer activity of the synthesized hydantoin derivatives were examined on murine leukemia L1210 cells growing in Fischer medium. Among them, 3-(2-chloroethy)-5-isobutyl-hydantoin (6c) showed substantially low $ED_{50}$ value of $9.6{\mu}g/ml$.

• Archives of Pharmacal Research
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• v.16 no.4
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• pp.322-326
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• 1993

For the development of new antinflammatory and analgesic drugs, new 5-alkylthio (or sulfonyl) methyl-5-m-methoxyphenylhydantoin-3-acetic acid derivatives(alkyl; ethyl, propyl, butyl) were prepared. The 5,5 -disubstituted hydantoins which were used as starting materials, were prepared acording to Bucherer-Berg method. The reaction of ethyl chloroacelate with these compounds gave 3-acetate and the subsequent hydrolysis with dilute sodium hydroxide resulted in hydantoin 3-acetate and the subsequent hydrolysis with dilute sodium hydroxide resulted in hydantoin 3-acetic acid derivatives. Through the same procedure of equivalent hydroxide resulted in hydantoin 3-acetic acid derivatives. Through the same procedure of equivelent hydantions or the oxidation of 5-alkylthiohydantoin ocmpounds described above, 5-alkylsulfonylme-thyl-5-m-methoxyphenylhydantoin-30acetic acid derivatives were also synthesized.