Note: Descriptions are shown in the official language in which they were submitted.
~05~213 CASE 841
This invention relates to a method for the preparation
of amino acids starting from the corresponding carbamyl
derivatives
It is known that optically active carbamyl derivatives
of amico acids can be obtained from the corresponding racemic
idantoines by stereo-selective enzymic hydrolys~s, according
to what has been disclosed in the German ~ublished application
DOS 2,422 737 filed 10.5~1974
The carbamyl derivative thus obtained was subsequently
converted into the corresponding aminoacid by merely boiling
i* in an aqueous solution.
However~ the hydrolysis of the carbamyl to aminoacid, as
caused to occur under such conditions, was very slow and required
a rigorous check of the working conditions and, sometimes, gave
rise to by-products with a depression of the yield and ev0n a
partial racemization
An object of the present invention is to provide an
original and simple approach to the conYersion of the carbamyl
derivatives into the corresponding aminoacids, which takes place
under bland conditions such that the as-produced aminoacid still
retains the optical purity of the starting carbamyl derivative.
The method according to this invention comprises the step
of reacting the carba~lyl derivative with oxidi~ing substances
in the presence of an acid-group-containing ion-exchange-resin,
and this fact is surprising to the utmost in that it was known
heretofore that such reactants acted upon the amino group of
the aminoacid to give the corresponding hydroxy acid and that
it was then impossible to convert the carbamyl derivative into
its aminoacid, as the latter was i~nediately converted into the
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hydroxy acid.
On the contrary~ according to the present invention~ it
has been observed that, when operating in the presence of catio-
nic resins under appropria-te pH and temperature conditions,
surprisingly high yields are achieved inasmuch as the aminoacid
is completely exempt from attack by the oxidizing reactant
The method outlined above is carried out by dissolving
the carbamyl derivative, or a salt thereof, in water at a varia-
ble concentration, preferably near saturation. The solution
is supplemented by a quantity of a cationic resin of acidic form
having such an exchange capacity as to bind from 1 to 5 mols of
product~ During *his step, the pH is lowered and the carbamyl
derivative, in an excess amount relative to its solubility~ is
precipitated There are added from l to 1.5 equivalents of
oxidizing agents~ the whole stage being conducted at a-tempera-
ture ranging from 0C to 40C.
As cationic resins, there can be used resins with different
acidic groups, even though sulfonic type resins are preferably
used. Also the oxidizing agent is no problem, even though the
use of nitrous acid or a salt thereof have been preferred in use.
On completion of the reaction, the aminoacid is eluted
from the resin with a base, whereas the resin can be brought to
its acidic form again; from the eluate, the aminoacid is isolated
with simple concentration and crystallization operationsO
The mode of operation as suggested above and further details
will become~ at any rate~ more clearly apparent from a scrutiny
of the following Examples which are given by way of illustration
only and thus are not to be construed as limitations to the
present invention.
EXAMPLE
50 mls of a 25mM solution of N-carbamyl-alpha-alanine
are treated at 0C with 5 mls of a 50mM solution of NaN02 in
~5~ L3
water. The concentration of the aminoacid in the solution
is occasionally measured The concentration, after having
reached a ceiling of 5 mM in the first hour of the reaction~
slowly diminishes and, after 5 hours, drops to 3.2 mM.
Chromatographic analysis of the mixture displays the
presence of a considerable quantity of lactic acid.
EXAMPLE 2
194 grams (l mol) of D-N-carbamyl-phenylglycine having
an optical purity of 99% are slurried in 10 litres of deionized
water, in the presence of 8 litres Amb0rlite I.R. 120 (H~).
By maintaining the solution stirred at room temperature~ there
are added 83 grams (1 2 mol) of sodium nitrite. After about
2 hours, the resin is filtered off, washed twice with 10 liters
of demineralized water and then transferred to a column (diameter
11 centimeters, height l meter ). The resin is then eluted with
2M ammonia: the aminoacid is present in its entirety in the
fraction from 10 to 15 liters of eluate.
The solution of the ammonia salt of D-phenylglycine~
5 liters, is evaporated under reduced pressure to dryness. There
are thus obtained 150 grams ( 99% of theory ) o~ D(-) phenylglycine
having and (alpha ) - 157 ( c - 0 5; HCl lN)~ that is an
optical purity higher than 98% by taking as the (alpha) the
data of the t~chnical literature (Org. Synth. 22~ 23~ 1942 )~
EXAMPLE 3
By adopting the same procedure as set forth in Example 2,
starting from 132 grams (l mol) of L-N-carbamyl-alpha-alanine
having an optical purity of 98~o there are obtained 87 grams
(0.98 mol) of L-alpha-alanine with an (alpha) =~14.3 c = 2 ,
HCl lN) (from the literature (alpha ) 5 =~14.7, J. Chem. Soc
11~ 526, 1918 ). D
EXAMPLE 4
With the same procedure as indicated in Examples 2 and 3
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and starting frQm 160 grams (1 mol) of L-N-carbamyl va~ine
with an optical purity of 97%, there have been obtained 110
grams (0,94 mol ) of L-valine; (alpha) = 28.2 (c = 3; HCl
6N ) from the literature : (alpha) = 28.80, Ber. 3~, 2320,
1906).
EXAMPLE 5
By adopting the same procedure as in Examples 2 and 4~
from 192 grams (1 mol) of L-N-carbamyl methionine~ having an
optical purity as high as 99%~ there have been obtained 145
grams (0.97 mol ) of L-methionine; (alpha) = minus 8.01
~c = o.8, water) (the literature gives (alpha) = minus 8.1l,
J. Am. Chem. Soc.~ S3~ 3490~ 1931)q
EXAMPLE 6
-
With the same procedure as described in ExampleS2 and 4
from 190 grams (1 mol) of L-N-carbamyl glutamic acid having
an optical purity of 98~ there have been obtained 183 grams
(0.96 mol ~ of L-glutamic acid; ~alpha) = 31 (c = l; HCl
6~) (the literature gives (alpha) = ~ 31.2~ Ber.~ 40, 371?,
1907).
