Of DL-methionine

Considering that sodium glutamate, like other amino acids, is contained in soy sauce, which is a traditional Japanese food, it is not surprising that Japan should have become interested very early in this type of fermentation. Firms like Ajinomoto and Kyowa Hakko dominate the world market for amino acids and particularly for glutamic acid and l-lysine. It is also through enzymes that the resolution of dl-methionine into its optical isomers is achieved since its laboratory synthesis yields the racemic form. 

Asker AF, Canady D, Cobb C. Influence of dl-methionine on the photostability of ascorbic acid solutions. Drug Dev Ind Pharm 1985 11(12) 2109-2125. 

A series of racemic and optically pure organophosphorus samples were studied by solid-state 31P NMR (97). Analogous to the tartaric acid work, the two optical isomers (+ and -) showed the same 31P NMR spectrum that were distinct from the spectrum of the racemic material. In addition, the issue of quantitative analysis of optical purity was addressed. The conformational analysis of dl-, l-, and D-methionine was studied by solid-state 13C NMR (98). Based on the NMR studies, each crystalline form of DL-methionine consists of a single conformer, which agrees with X-ray diffraction data. 

Acetyl DL-methionine which is used as a substrate for amino acylase activity determination was prepared by acetylation of DL-methionine with acetic anhydride in acetic acid [5]. The rate of enzymatic hydrolysis was determined by measuring the liberated amino acid by ninhydrin method [6] where ascorbic acid was used as oxidizing agent instead of sodium cyanide. The activity curve of pure amino acylase enzyme is shown in Fig. 1 as a continuous line. For determining the effect of metal ions on the activity of amino acylase the following procedure was adopted. 

The fact that Co ions increase the activity of amino acid acylase in resolution of L-methionine from acetyl DL-methionine, shall be applied advantageously in the practical process of enzymatic resolution of DL-methionine. Usually in practical resolution, as cost of enzyme is high, it is desirable to employ a higher substrate concentration and less amount of enzyme which leads to production of L-methionine vith less cost. From the above results it can be concluded that by using Co ions we can reduce the amount of enzyme to a greater extent in enzymatic resolution of L-methionine by using amino acid acylase isolated from Sanzyme. 

Two polymorphs of DL-methionine, the a- and j8-forms, have been known since 1950 as concomitant conformational polymorphs [154-157]. The crystals have almost identical shape, for which reason the second form was discovered by chance. The two forms are almost equally stable, and their crystal structures are also similar (Figure 7-6). 

Figure 7-6. Fragments of crystal structures of polymorphs of DL-methionine (a) - a-, (b) - ji- [I54-I57]...

Mathieson, A.M. The crystal structures of the dimorphs of DL-methionine, Acta Crystallogr. 5... 

The latter authors also found it when serine and/or threonine reacted with sucrose. It was previously identified in other model reactions by treating furfural with hydrogen sulfide and ammonia (Shibamoto, 1977) or by heating rhamnose with ammonia (Shibamoto and Bernhart, 1978). Ho and Hartman (1982) proposed a plausible mechanism for the formation 2,4,5-trimethyloxazole from the reaction of dl-alanine or L-cysteine and 2,3-butanedione. Ho el al. (1982) also studied the formation of oxazoles and oxazolines in the Strecker degradation of dl-methionine and L-cysteine with 2,3-butanedione. In their proposed mechanisms, the authors suggested the formation of intermediate 3-oxazolines. 

Ballance P.E. (1961) Production of volatile compounds related to the flavour of foods from the Strecker degradation of DL-methionine. J. Sci. Food Agric. 12, 532-6. 

Surprisingly little work has been reported on tris(amino acid) complexes of Rh". Reaction of RhClj-SHjO with sodium bicarbonate causes precipitation of Rh203, which forms [Rh(D-ala)j] if heated immediately with D-alanine. Fractional crystallization allows separation of mer(-) and mer +) isomers, as well as some impure fac isomer. Reaction of the Li salt of DL-methionine (Li MeSCH2CH2CH(NH2)COO ) with anhydrous RhClj in refluxing ethanol leads to the precipitation of [Rh(DL-methionine)3], in which the methionines act as anionic bidentates, bonded through the O and N atoms. The solid state reaction of RhClj with glycine is reported to lead to [Rh(gly)j], characterized thermogravimetrically and by IR, UV and H NMR spectroscopy. Several [Rh(en)2 (amino acid)] " complexes have been prepared and resolved (Section 48.6,2.2.ii). ... 

A soln. of DL-methionine, 3 moles diethyl azodicarboxylate, ethanol, and water stirred 3 hrs. at room temp. DL-methionine sulfoxide. Y 97,5%. - The reaction is dependent on the presence of a proton-donating group. F. e. and limitations s. R. Axen, M. Chaykovsky, and B. Witkop, J. Org. Chem. 52, 4117 (1967). 

Yokota, M., Takahashi, Y., Sato, A., Kubota, N., Masumi, F. and Takeuchi, H. (1998) Purity drop in optical resolution of DL-methionine by the diastereomer method. Chemical Engineering Science, 53, 1473-1497. 

Kinetic and Mechanistic Studies on the Reaction of DL-Methionine with [(H20)(tap)2Ru0Ru(tap)2(H20)] in Aqueous Medium at Physiological pH... 

Ru(tap)J (complex 2) of DL-methionine, and complex 1 is shown in Figure 1. The composition of 2 in solution was determined by Job s method of continuous variation and the metal ligand ratio was found to be 2 1. The pH of the solution was adjusted by adding NaOH/HClO, and the measurements were carried out with the help of a Sartorius make digital pH meter (PB 11) with an accuracy of 0.01 unit. 

The alkaline Fe(CN)6 oxidations, described hereafter, were found to be first order in Fe(CN)g ion. The oxidation of DL-methionine (Meth) was fractional order both in Meth and OH ions. The mechanism assumed the formation of an adduct, of Fe(CN)6 and Meth, which decomposed to a radical in the rate-determining step. Further oxidation of the radical in the fast step resulted in the product methionine sulfoxide. The same reaction catalysed by Ru(III) was first order in Ru(III), had a fractional order in OH , and slowed with increasing methionine concentrations. The proposed mechanism suggested the formation of a complex between [Ru(H20)50H] +, the reactive Ru(III) species, and Meth. The product was methionine sulfone nitrile. The outer-sphere Ru(III)-catalysed oxidation of L-proline to glutamic acid was first order in Ru(III), fractional order in OH , and of zero order in proline.The oxidation of serine and threonine was first order in amino acid and zero order in OH . The reactivities of serine and threonine... 

Figure 6.11 The chemical synthesis of DL-methionine. From Yamamoto, A. (1978), in Encyclopedia of Chemical Technology, Vol. 2, 403...

Figure 6.28 Process for the resolution of DL-methionine with amino acid acylase...

A new type of enzymatic synthesis of peptides has been found by Brenner et Esters of DL-methionine or DL-threonine incubated... 

A number of Ir(lll)-, Ru(lll)- and Os(VIII)-catalysed redox studies of organic compounds by alkaline hcf are reported. The rates of Ir(III)-catalysed oxidations of arginine and lysine show Michaelis-Menten dependence in amino acids and increase with ionic strength the proposed mechanism assumes the formation of an lr(IIl)-amino acid complex. This study was also published by the authors in another journal. The Ir(in)-catalysed alkaline oxidation of OL-methionine (met) by hcf to methionine sulfone is fractional order in met. The reaction rates increase with increase in OH coneentration. The active species of oxidant and catalyst are [FeCCN) ] and [IrClgCHjOljOH]", respectively. The results of the uncatalysed oxidation of DL-methionine (met) are similar to those of the catalysed reaction. 

The oxidation of DL-methionine by sodium iV-chlorotoluene-p-sulfonamide (CAT) in alkaline medium catalysed by OSO4 shows a first-order dependence each on CAT and methionine, an inverse fl actional-order dependence on HO , and a fractional-order dependance on 0s04. " The oxidation of mono-, di-, and tri-ethanolamine (MEA, DEA, and TEA, respectively) by CAT " and sodium A-bromotoluenesulfonamide (bromamine-T, BAT) " in alkaline buffer is first order in oxidant and fractional order each in substrate and HO. The oxidation rate increased in the order di- > tri- > mono- and suitable mechanisms consistent with the kinetic data have been proposed. Osmium(Vni)-catalysed oxidation of propane-1,3-diol by CAT in alkaline medium proceeds via hydride-ion abstraction fi om the a-carbon of the diol. " ... 

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