Hydantoin analogue

Sutherland, J.J. and Weaver, D.F. (2003) Development of quantitative structure-activity relationships and classification models for anticonvulsant activity of hydantoin analogues./. Chem. Inf. Comput. Sci., 43, 1028-1036. 

Thiazoles may also be intermediate in some other imidazole syntheses <87CJC282>. Dimroth rearrangement of 5-aminothiazoles ((255), (256)) gives hydantoin analogues <86BSBll29>. While 2,4-disubstituted thiazole A(-oxides are converted by aryl isocyanates into imidazoles, the 2,5-isomers are unreactive (Scheme 191) <82CPB1722>. 

The aldehyde 145 has been made by reduction of the nitrile with DIBAL, and was used as a precursor for the hydantoin analogue 146 of showdomycin, obtained as a mixture of diastereoisomers.l A full account has been given of the use of a siinilar aldehyde to produce an... 

The 4-methylthio analogue and some hydantoin analogues of 3 -fluoro-3 -deoxythymidine (FLT) have been prepared by condensation methods. 

C-nmr data have been recorded and assigned for a great number of hydantoin derivatives (24). As in the case of H-nmr, useful correlations between chemical shifts and electronic parameters have been found. For example, Hammett constants of substituents in the aromatic portion of the molecule correlate weU to chemical shifts of C-5 and C-a in 5-arylmethylenehydantoins (23). Comparison between C-nmr spectra of hydantoins and those of their conjugate bases has been used for the calculation of their piC values (12,25). N-nmr spectra of hydantoins and their thio analogues have been studied (26). The N -nmr chemical shifts show a linear correlation with the frequencies of the N—H stretching vibrations in the infrared spectra. 

The mixture of D and L optical forms of this hydroxy analogue of methionine is converted to the calcium salt which is used in animal feed supplements. Cyanohydrins react with ammonium carbonate to form hydantoins (2), which yield amino acids upon hydrolysis. Commercial DL-methionine [59-57-8] is produced by hydrolysis of the hydantoin of 3-meth5ithiopropionaldehyde [3268-49-3]. 

Sulfahydantoins 87 and 88 are analogues of hydantoins and provide heterocyclic scaffolds with a great potential for the construction of bioactive compounds. A total of 28 derivatives, with crude purity generally higher than 85%, were prepared by parallel synthesis using an oxime resin as a solid support (Scheme 46) . The results constitute the first report of successful Mitsunobu reactions and reductive alkylations on the oxime resin. 

B.J. Whittle, S. Moncada, K. Mullane, J.R. Vane, Platelet and cardiovascular activity of the hydantoin BW245C, a potent prostaglandin analogue. Prostaglandins 25 (1983) 205. 

Coyle and Bryant have reported the efficient synthesis of a triazabicyclo[3.3.0]octane system by the photocyclization of hydantoin derivatives. Thus irradiation of (295), synthesized by standard Mannich procedures, afforded the bicyclooctanes (296) in moderate to good yields. The process, akin to Norrish Type II behaviour, is a 1,6-hydrogen transfer followed by bonding in the resultant biradical (297). The bis-Mannich base compound (298) also photocyclizes, yielding (299). Coyle and his co-workers have also successfully applied the known reactivity of phthalimides to yield polycyclic compounds. Thus irradiation of (300) affords the cyclized compound (301). This can be converted into the protoberberine alkaloid skeleton (302) by treatment with aqueous HCl. The crown ether analogues (303) and (304) have... 

Zha C, Brown GB, Brouillette WJ. Synthesis and structure-activity relationship studies for hydantoins and analogues as voltage-gated sodium channel ligands. J Med Chem 2004 47 6519-28. 

Photoelectron spectroscopy has demonstrated that there is no linear correlation between the ionization energies and p values of azoles <84JHC269>. The gas phase photoelectron spectra of a series of hydantoin derivatives (32) have been compared with those of model compounds, and with the results of HAM/3 and CNDO/S calculations. Evidence is found for significant interactions between the 7r-orbitals and the chalcogen atoms for sulfur and selenium derivatives. In contrast, n-orbitals of the nitrogen atoms are localized in the whole series of compoimds, especially in the oxy analogues and in monosubstituted derivatives <88JST(175)447>. 

Some N-3-substituted hydantoins, such as 95, lead to N-bridgehead bicycles (96), which are oxygen analogues of levamisole and are powerful alkylating agents.234 The intramolecular process is controlled by the thermodynamic stabilities of the two possible bicyclic products resulting from N- or O-alkylation.97... 

Since the discovery of hydantoin in 1861, when Baeyer isolated it in his uric acid studies, that system has been an important precursor of a-amino acids owing to its lability toward alkali, especially for those acids that are difficult to prepare by other methods.300 Furthermore, the stereochemical courses of the Bucherer-Bergs and Read methods of synthesis for hydantoins (Section II,E), permit the preparation of epimeric amino acids.301-305 Some of these amino acids have been tested as possible tumor growth inhibitors,306,307 as metabolism-resistant amino acid analogues for transport system studies,72,308... 

Hydantoins and other imidazole analogues of prostaglandins of type 146 and 147 have been synthesized as racemic compounds.355 The less polar diastereoisomer of 146b is a potent inhibitor of platelet aggregation in human platelet-rich plasma. 

Although the side chain reactions in this series are similar to those in quinoxaline chemistry, the cyclization of ureides such as compound 129 to the hydantoin 130 occurs more readily in the pyrido[2,3-i)]pyrazine series. Boiling dilute hydrochloric acid converts 129 into acid-stable 130, whereas it hydrolyzes the quinoxaline analogue of 129 to the corresponding carboxylic acid. Compounds of both series are readily hydrolyzed to the acid by aqueous alkali. ... 

An unexpected feature of the chemistry of the above ureido ester analogues was the apparent ease with which they underwent at least partial racemization at the a-carbon during alkaline hydrolysis to ureido acids. Support for the conclusion that racemization was taking place came from a combination of direct polarometric measurements on the ureido diacids (low rotation in comparison with MTX and folic acid) and indirect evidence that hydrolysis was proceeding via a hydantoin intermediate. Thus, when the ester (VI.9) was heated in MeOH or CHCI3 in the presence of the strong organic base l,5-diazabicyclo[3.4.0]non-5-ene, a product formed in 61% yield which was tentatively identified as (VI.15). Alkaline hydrolysis of (VI.15) yielded (VI.8). 

As evidenced above, the interest in peyote has shown no abatement over the past year. The 56 identified constituents of this resourceful cactus have been tabu-lated. The amino-acid analogue of mescaline, 3,4,5-trimethoxyphenethylalanine (14 R = Me, R = OMe) has been prepared in three steps and in good yield from hydantoin and 3,4,5-trimethoxybenzaldehyde. G.c.-m.s. examination... 

Olefination reactions of the phosphonates (254) and (255) derived from hydantoin and 1-methylhydantoin, respectively, provide good yields of the expected C-5 unsaturated hydantoin derivatives (256), generally as mixtures of isomers. 52 Heterocyclic analogues, e.g. (257), of pulvinones and, e.g. (258), of permethylated pulvinic acids have been synthesized by Wadsworth-Emmons reactions of the phosphonates (259) and (260), themselves prepared directly from substituted maleic anhydrides. 55 The reaction of ylide (261) with aldehydes to give (262) has been used as a key... 

Various analogues of the hydantoins have been prepared by the Wellcome group. For example the piperazinedione (138) was... 

The hydantoinases are particularly useful enzymes because the hydan-toins are intermediates in the synthesis of many amino acids. Enzymes with specificities for the D- or the L-enantiomers are available. The enzyme from Pseudomonas striata is most active against dihydrouracil, and it is possible that this is its natural substrate. The most active substrates amongst the hydantoins are those formed from the neutral aliphatic amino acids, but several phenylglydne analogues are also hydrolysed. 

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