HU176009B - Process for producing amino-acids - Google Patents

Abstract

The technical problem of preparing amino acids from carbamyl derivatives thereof is solved by reacting such a derivative, which may have been converted to a salt, with an oxidising agent such as nitrous acid in the presence of a cation resin in the acid form.

Description

The present invention relates to a process for the preparation of amino acids from the corresponding N-carbamoyl derivatives.

It is known that optically active carbamoyl derivatives of amino acids can be prepared from the corresponding racemic hydantoin by stereoselective enzymatic hydrolysis (German Patent Application No. 242 27 37).

The resulting carbamoyl derivatives are then converted to the corresponding amino acid by boiling in aqueous solution. 10

However, under these conditions, the hydrolysis of the carbamoyl azide to the amino acid is very slow and the reaction conditions need to be strictly controlled, and in addition, by-products may be formed, resulting in reduced yield and partial racemization.

It is an object of the present invention to provide a novel and readily feasible method for converting carbamoyl derivatives to the corresponding amino acids, which may be accomplished under mild conditions so that the resulting amino acid retains the optical purity of the starting carbamoyl derivative.

According to the invention, the N-carbamoyl derivative is reacted with an alkali metal salt of oxidizing charcoal, in particular in the presence of an acidic group, preferably a sulfonic acid type ion exchange resin. This is surprising, since such reagents are known to act on the amino group of the amino acid and to produce the corresponding hydroxy acid, so that it is impossible to convert the carbamoyl derivative into an amino acid as the latter is immediately converted to the hydroxy acid.

In contrast, it has been found that, if the process is carried out in the presence of a cationic ion exchange resin at an appropriate ρΗ value and temperature, surprisingly high yields are achieved since the amino acid is thus completely protected from the action of the oxidizing agent.

The process is carried out by dissolving the N-carbamoyl derivative or a salt thereof in water in variable amounts, preferably in a near saturated solution. To the solution is added a cation exchange resin in acid form having an ion exchange capacity such that it can bind 1-5 moles of product. During this step, the pH is lowered and the carbamoyl derivative is liberated in excess of its solubility. 1 to 1.5 equivalents of nitric acid as the oxidizing agent are added to the alkali metal salt, and the whole process is carried out at 0-40 ° C.

As the cation exchange resin, it is possible to use resins containing various acidic groups, however, as mentioned above, sulfonic acid type resins are particularly preferred.

After completion of the reaction, the amino acid is dissolved from the resin with a base and the resin can be reconstituted to the acid form. The amino acid can be separated from the eluate by simple concentration and crystallization.

The invention is further illustrated by the following examples, but the scope of the invention is not limited to the examples.

Comparative Example 10 10 ml of a 25 mM solution of N-carbamoyl-α-alanine are treated with 5 ml of a 50 mM aqueous solution of sodium nitrite at 0 ° C. The amino acid concentration of the solution is periodically measured. The concentration reaches a peak of 5 mmol in the first hour of the reaction, then decreases slowly and falls to 3.2 mmol after 5 h.

Chromatographic analysis of the mixture indicated the presence of a significant amount of lactic acid. 20

Example 1

194 g (1 mol) of 99% optical purity of D-N-cobamoylphenyl] icin are suspended in 10 L of deionized water in the presence of 8 L of Amberlite I.R. 120 (H *). The solution was stirred at room temperature while 83 g (1.2 mol) of sodium nitrite were added. After about 2 hours, the resin was filtered off, washed with 2 x 10 liters of demineralized water, and then applied to a column 11 cm in diameter and 1 m long. The resin is then eluted with 2M ammonia solution, the total amount of amino acid being in the 10-15 liter fraction of the eluate. 35

A 5 L solution of the ammonium salt of D-phenylglycine was evaporated to dryness under reduced pressure. Thus, D-phenylglycine (150 g, 99%) having a rotation of [U] q ⁰ = -157 ° (c = 0.5, 1N HCl) this corresponds to greater than 98% optical purity of 40 true according to literature data [Org. Synth., 22, 23 (1942)]

Example 2

The procedure of Example 1 was followed using 132 g (1.1 mol) of 98% optical purity of L-N-carbamoyl-α-alanine. This gives 87 g (0.98 mol) of La-alanine having a [α] θ ° - + 14.3 ° (c = 2, 1N in hydrochloric acid), according to the literature [α] ο® = 14.7. ° (J. Chem. Soc. 113, 526).

/1918./).

Example 3

The procedure of Example 1 was followed, but starting from 160 g (1 mole) of 97% optical purity of L-N-carbamoylvaline. This gives 110 g (0.94 mol) of L-valine having a [α] π ° = - 28.2 ° (c = 3.6n in hydrochloric acid); ° (Bér., 39, 2320 (1906)).

Example 4

The procedure of Example 1 was followed, but starting from 192 g (1 mol) of 99% optical purity of L-N-carbamoylmethionine. 145 g (0.97 mol) of L-methionine are obtained having a [α] D = -8.01 ′ (c = 0.8 in water), according to the literature [α] π = -8.1, 1 [J. Chem. Soc., 53, 3490. (1931) j.

Example 5

The procedure of Example 1 was followed using 190 g (1 mol) of 98% optical purity LN-carbamoyl-glutamic acid as starting material. such as L-glutamic acid, 183 g (0.96 mol) having a rotation of [α] ^θ ο = -31 ° (c = 1,6 N HCl), the literature value [a] ² = -31.2 ° Jj [ Bér., 40, 3717 (1907)].

Claims (1)

Claim: A process for the preparation of amino acids which comprises reacting the N-carbamoyl derivative corresponding to the amino acid with 1 to 1.5 equivalents of an alkaline metal salt of nitric acid in the presence of an acidic group, preferably a sulfonic acid type ion exchange resin.