Applications methyl glyoxalate

One of the drawbacks of DHAP aldolases is their strict specificity toward the donor substrate DHAP. DHAP is chemically unstable, particularly under alkaline conditions, and decomposes into inorganic phosphate and methyl glyoxal, both of which may inhibit the aldolase [4cj. Although the preparation [22] and synthetic applications of DHAP have reached a high degree of sophistication and efficiency [4h, 6e,i, 23], the preferred choice is by far the inexpensive unphosphorylated DHA nucleophile, which reduces costs and improves the atom economy of the process, especially when the phosphate group of the product must be removed in a separate reaction. In this connection, we focused our efforts on RhuA and FSA from E. coli [24]. 

Investigation of the mechanism of these reactions has suggested ways in which the yields can be improved. Acidic conditions (pH 2) will prevent Cannizzaro rearrangement of any glyoxal-type species and also serve to hydrolyse any Schiff bases which result from side reactions of aldehyde and amine. Conditions should be adjusted so that the rate of hydrolysis of linear products is equal to the rate of cyclocondensation, allowing accumulation of the imidazole products. From glyoxal, formaldehyde and ammonium chloride the yield of imidazole can be inereased to 85% by careful control of the conditions. With an appropriate alkylammonium chloride, 1-substituted imidazoles are also accessible (e.g. 1-methyl (56%), 1-isopropyl (46%), 1-cyclohexyl (49%), 1-n-butyl (55%), 1-t-butyl (25%)). The process may have some applications, but yields drop off with branched alkyl compounds [22 j. Imidazolium salts are also available under similar conditions when two molar equivalents of a primary alkylamine are used [23]. 

Preparations of some A-substituted 2-oxo-l, 2-dihydropyrazines have been discussed in Section 11.2 from the reactions of di-, tri-, and tetrapeptides with glyoxal (380-382) and Cheeseman and co-workers (1111) have described the preparation of 1-benzyl-3-hydroxy-2-oxo-l, 2-dihydropyrazine (83) (and similarly its 1-methyl analogue) from ethyl A-(2, 2 -dimethoxyethyl)oxamate and benzyl-amine through A-benzyl-A -(2, 2-dimethoxyethyl)oxamide (84) by the application of a standard procedure (482). 

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