Methyl-thiohydantoin

Free amino acids can be derivatized with isothiocyanates to phenyl- or methyl-thiohydantoin derivatives. The thiohydantoins can be separated on a CSP with poly-[Af-acryloyl-L-phenylalanine ethylester] (Chiraspher ) as a chiral selector [25]. This CSP offers a known selectivity for many five-membered heterocyclic rings. 

Eyem and Sjoquist have suggested the use of short (4.5 m) glass capillary columns and reported the separation of 19 of 20 silylated methyl thiohydantoin (MTH) derivatives of the amino acids (62). The histidine derivative can be separated on the same column by starting at a higher temperature. Separation of some of the silylated PTH derivatives was also demonstrated, though not in as much detail as the MTH derivatives. 

Cristiani, R, Devillanova, RA., Diaz, A. et al. (1990) Charge transfer complexes of some V-methylated thiohydantoins with molecnlar iodine. Heteroat. Chem., 1, 363-367. 

Methyl-2-thiohydantoin (120) (40%) was found to be the hydrolysis product when a concentrated hydrochloric acid solution of 5-amino-2-mercapto-1-methylimidazole (119) was heated under reflux (48JCS2028). 

A study was made of RP-HPLC with constant-potential (1.2 V vs SCE) and pulsed-potential amperometric detection using platinum or gold electrodes, of the derivatives of the common amino acids, obtained from phenyl and methyl isothiocyanates. All the thiohydantoins (98) were oxidized at both electrodes LOD was less than 0.2 pM for lysine and glycine, for 50 pL injection268. 

Fairwell, T., S. Ellis, and R.E. Lovins, Quantitative protein sequencing using mass spectrometry thermally induced formation of thiohydantoin amino acid derivatives from N-methyl- and N-phenylthiourea amino acids and peptides in the mass spectrometer. Anal Biochem, 1973. 53(1) 115-23. 

GLC is an important adjunct to protein sequence determination. Automatic "sequenators" based upon the approach developed by Edman are available and have been described in detail by Niall (60). The Edman degradation, summarized in Equation 9.5, makes use of methyl or phenylisothiocyanate which reacts with the N-terminus of a peptide. Exposure of the isothiocyanate derivative of the protein to acid results in cleavage of the terminal amino acid as a thiaxolinones and exposure of the next amine group on the peptide. Thus, the process can be repetitively carried out, each amino acid removed from the peptide, in a sequential manner. Thiazolinones rearrange in acid medium to form thiohydantoin derivatives of amino acids, some of which may be directly gas chromatographed others must be derivatized typically as trimethylsilyl derivatives. 

A wider range of possibilities of preparing cyclic derivatives is offered by the presence of carboxyl and a-amino groups in the molecule. Substituted 5-oxazolinone (Scheme 4.23) is prepared by refluxing with TFA anhydride, and substituted 5-oxazolidinone (Scheme 4.24)by reaction with (halogenated) acetone [117,118]. Thiohydantoins are formed by reaction with isothiocyanate (Scheme 4.25). If R is methyl or phenyl, then the corresponding methyl- or phenylthiohydantoin is produced. Thiohydantoins are usually not volatile enough and for the purposes of GC analyses must be further modified, e.g., by trimethylsilylation [119,120]. 

N C N c c imidazolef 4,5-di-/-butylimidazole histamine dihydrochloride 2-thiohydantoin l-methyl-2,4,5-trinitroimidazoleas... 

Among radicals from diazoles, in the imidazole series hydantoin, methyl-hydantoin, and thiohydantoin have given various radicals e.g., 159, differing in degree of protonation, upon radiolysis of aqueous solutions.546 Values of... 

The centrosymmetrical AA42 base pair is mostly observed in complexes 9-ethyl-8-bromo-adenine with 9-ethyl-8-bromo-hypoxanthine [EBAEBH1 9-methyl-adenine with l-methyl-4-thiouracil [SURMAD101 and with 2-thiohydantoin [BIFYOE] 9-ethyladenine with parabanic acid [EADPBA] 3-(adenin-9-yl)pro-piontryptamide [ADPRTR]. 

Disposition in the Body. Rapidly and almost completely absorbed after oral administration and converted to the active metabolite methimazole. Almost completely excreted in the urine in 24 hours as metabolites 3-methyl-2-thiohydantoin has been identified as a minor metabolite in urine and plasma. About 3% of a dose is eliminated in the faeces. 

C5H5F302 4,4,4-trifluoro-3-methyl-2-butenoic acid 93404-33-2 25.00 1.3180 1 4522 C5H6N202S 1 -acetyl-2-thiohydantoin 584-26-9 25.00 1.3667 2... 

The N-methyl- and IV-phenylthiourea derivatives of the N-terminal amino acid of a peptide thermally rearrange in the MS ion source to give the thiohydantoin derivative of the terminal amino acid and the shortened peptide [189]. This has been suggested as a sequencing method for the first four acids after which point interference from side products becomes excessive. 

Sun and Lovins [212] studied the elimination of neutral fragments, obtained from amino acids liberated during the Edman degradation, which are transformed into derivatives of methyl- (or phenyl-) thiohydantoin (Fig. 59). 

Figure 59. Production of methyl (or phenyl) thiohydantoin derivatives from polypeptides.

UV spectra have proved that potentially tautomeric thiohydantoins have thione and not mercapto structures, since their spectra are profoundly affected by S-methylation and only slightly by N-methylation.138,133... 

The products of alkylation of thiohydantoins are kinetically controlled and hence are frequently the less stable S-alkyl compounds.138,232 Methylation products of 2-thio- and 2,4-dithiohydantoins exist almost entirely in one tautomeric form (92) or the other (93) depending on the solvent.153 5-Monosubstituted 2,4-dithiohydantoins exist as the tautomer (94), and alkylation takes place on sulfur.221... 

A), 3-[4-(methylthio)-3-butenyl]-5-isobutyl-2-thiohydantoin, (B), 3-[4-(methylthio)-3-butenyl]-5-benzyl-2-thiohydantoin and (C), 3-[4-(methylthio)-3-butenyl]-5-[2-(methyl-thio)ethyl]-2-thiohydantoin. Symbols , Salmonella typhimuriumTA98 was simultaneously incubated with IQ (0.5 pg) and the 3,5-disubstituted 2-thiohydantoins (0-500 pg/ml) for 20 min at 37° C and then cultured for 48 h at the same temperature , the bacterial strain was treated with the same amount of IQ for 20 min at 37° C, rinsed with a buffered saline to eliminate the mutagen, and incubated with the test compounds for an additional 20 min. The bacteria were cultured for 48 h at 37° C. Mutagenicity is expressed in terms of the percentage in the revertant number found with or without the test compounds, where the mutagenicity of IQ is defined as 100%. 

Methyl-5-phenyl-2-thiohydantoin in dioxane added portionwise at 37° with stirring to a suspension of LiBH4 in dioxane, after 0.5-1 hr. acetic acid added, and refluxed 5-10 min. l-methyl-4-phenylimidazoline-2-thione. Y 72%. F. e. and procedure s. J. E. Scott and G. Henderson, Biochem. J. 109, 209 (1968). 

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