A-Aminothiol acids

Thus we designed and synthesized a bicyclic pyridoxamine derivative carrying an oriented catalytic side arm (16) [11], Rates for conversion of the ketimine Schiff base into the aldimine, formed with 26 (below) and a-ketovaleric acid, indolepyruvic acid, or pyruvic acid, were enhanced 20-30 times relative to those carried out in the presence of the corresponding pyridoxamine derivatives without the catalytic side arm. With a-ketovaleric acid, 16 underwent transamination to afford D-norvaline with 90% ee. The formation of tryptophan and alanine from indolepyruvic acid and pyruvic acid, respectively, showed a similar preference. A control compound (17), with a propylthio group at the same stereochemical position as the aminothiol side arm in 16, produced a 1.5 1 excess of L-norvaline, in contrast to the large preference for D-amino acids with 16. Therefore, extremely preferential protonation seems to take place on the si face when the catalytic side arm is present as in 16. 

One of the most valuable methods for the preparation of A2-thiazolines is of this class. The reaction of 2-haloalkylamines (334) with thioamides, metal thiocyanates or carbon disulfide give 2-alkyl- or -aryl- (335), 2-amino- (336), and 2-mercapto- (337) A2-thiazolines, respectively (Scheme 218) (17CB804). A method derived from the last procedure leads to a convenient synthesis of 2-phenyl-A2-thiazolines (340) under very mild conditions and consists of the condensation between a-aminothiols (338) and thiobenzoylmercaptoacetic acid (339 Scheme 219) (74TL1863) (this method could be better classified under Type E, Section 4.19.3.2.5). 

When the reaction of an aminophenol with A -ethoxycarbonylthioamide or a dithioate ester is applied to an aminothiophenol, a high yield of benzothiazole is obtained [2860, 2899]. The same substrate is converted into a benzothiazole efficiently at ambient temperature with hydroxamoyl chloride (the chloride of a hydroxamic acid) [3468]. Similar compounds in which the 2-phenyl group is varied are of interest as dye intermediates and are synthesized from quinonoid aminothiols [3477] the chemistry of quinonoid heterocyclcs has been reviewed [2947, 3650]. 

Other Radioprotective Chemicals. The bis-methylthio- and methylthioamino-derivatives of 1-methylquinolinium iodide and l-methylpyridinium-2-dithioacetic acid provide reasonable protection to mice at much lower doses than the aminothiols, which suggests a different mechanism of action (139). One of these compounds, the 2-(methylthio)-2-piperidino derivative of the l-methyl-2-vinyl quinolinium iodide (VQ), interacts with supercoUed plasmic DNA primarily by intercalation. Minor substitutions on the aromatic quinolinium ring system markedly influence this interaction. Like WR-1065, VQ is positively charged at physiological pH, and the DNA-binding affinities of VQ and WR-1065 appear to be similar. 

Several Pd11 complexes with thiolate or thioether derivative ligands have been studied to be applied in the hydroxycarbonylation reaction.394 Aminothiolate complexes of palladium with PPh3 catalyze the conversion of styrene to 2-phenylpropionic acid in high yield and excellent regioselectivity.644 Under mild conditions and in the presence of a catalytic amount of an S, TV-chelated palladium or//zo-amino-arenethiolate complex, styrene reacts with CO and oxalic acid or water to selectively give 2-phenylpropanic aid in high yield.645... 

Pyrimido[4,5-6][l, 4]thiazine can be obtained by a versatile and convenient method reported by Sako, Maki et al. <9iJCS(Pl)2675> treatment of 5-hydroxyuracil (253 X = 0) and 5-hydroxy-isocytosin (253 X = NH) with TV-bromosuccinimide in ethanol followed by the thermal condensation with (i- and y-aminothiols such as 2-aminothiophenol, cysteamine, L-cysteine, and d,l-homocysteine resulted in the formation of the pyrimido[4,5-6][l,4]thiazines (256). This new method for the construction of pyrimido[4,5-6][l, 4]thiazine ring systems was shown to involve the condensation of 5,6-diethoxy-5-hydroxy-5,6-dihydropyrimidin-4(3//)-one intermediates (255) with / -and y-aminothiols which is accelerated in the presence of an acid catalyst (Scheme 42). 

Fukuyama [5] obtained the thioester 35 from the reaction of the thiocarboxylic acid anion 34 with the / -lactone compound 17. After acidic deprotection of the Boc group, the thiazoline ring is successfully closed in benzene under Dean-Stark conditions (35 —> 33) in yields between 60 and 80 %. Ehrler [6] and Pattenden [7] choose a more classical way. They close the thiazoline ring by condensation of the aminothiol hydrochloride 5 x HCl with a nitrile. The yields are generally modest (45 and 55 %) except in one case [6]. Installation of the necessary nitrile function hinders its repetitive use, as this procedure causes a considerable loss of material. Heathcock [8] and Ehrler [6 choose the thiol-amide 37 as a key compound. Titanium tetra-... 

Pyridine-4-thiocarboxamide is reduced in two, two-electron steps in acidic medium at the potential of the second wave, reduction gives 4-aminomethylpyridine. The product of reduction at the first wave is believed to be the aminothiol [126]. These three cases show that the preparative outcome of an amide reduction is strongly dependent on the substituents at the amide group and that the changes manifest themselves in the chemical step [Eq. (32)]. For the amides of aromatic carboxylic acids, the reduction potential may be gleaned from a comprehensive compilation [127]. 

When one part of toluene-2 4-diamine is baked with 2 to 4 parts of sulphur at a temperature between 190 and 250 C (374 to 482 F) for 15 to 24 hours, and the crude product is extracted with aqueous caustic soda or sodium sulphide, a sulphur dye known as Immedial Orange C (C.I. SULPHUR ORANGE 1) is extracted. The dye, when heated with an alkali, yields an ortho-aminothiol which can be isolated in a pure state in the form of its lactam after it has been treated with chloracetic acid, and it has been established that it has the structure shown in (2). 

An unusual construction of the thiazine nucleus is illustrated by the synthesis of a number of 5/ >o-indole derivatives (272). Here 3-thiopropanoic acid, which provides the sulfur and three carbon atoms, reacts with 3-iminoindolin-2-ones (273) to give aminothiols (274), which then lactamize (Scheme 52). The 3-iminoindolin-2-ones are formed in situ by the condensation of arylamines with isatins (275) <86H2479>. 

It has been shown that the presence of chloride ion (hydrochloride salts of aminothiols are often used) in addic solution decreases S—S cleavage and increases ammonia yields with cystine . (Ammonia is a major product of both e q and OH attack on amino acids and peptides not having thiol or disulphide groups. )... 

Hgure4. Pseudoproline formation at the ligation side by a C-terminal aldehyde peptide reacting with a 1,2-aminothiol peptide at acidic pH. The reactive carboxyl and amino termini are positioned in close proximity for spontaneous peptide bond formation through an entropy-driven intramolecular 0- Alacyl transfer. 

The thiol promoters may be deactivated under typical conditions used to attach them to the catalysts. Nevertheless, the sulphur-protected mercaptan promoters attached to the ion-exchange resins can be used [25]. The other possibility is the modification of the ion-exchange resin with thiazolidines [26]. In the presence of the acidic catalysts thiazolidine is hydrolyzed to 2-aminoethanethiol and acetone. So prepared catalysts show high activity and the high selectivity for BPA synthesis (even more than 95%) and they afford high purity product. Currently, the most often used promoters are 2,2-dimethyl-l,3-thiazolidine and cysteamine (Figure 7.5). The later promoter is the simplest stable aminothiol, naturally formed as a degradation product of the amino acid cysteine [27]. 

These can be formed from aldehydes and ketones and an aminothiol under acid catalysis with azeotropic water removal [89, 206]. In the pyridoxal series the use of Af-substituted aminothiols has enabled a distinction between two different aldehyde groups the unprotected one could be reduced with sodium borohydride, and the protected group was apparently left unchanged during phosphorylation of the resulting primary alcohol it could then be removed by alkali [207]. 

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