CA1120877A - Selective n-acetylisation of amino acids by conversion with ketenes in aqueous solution - Google Patents
Selective n-acetylisation of amino acids by conversion with ketenes in aqueous solutionInfo
- Publication number
- CA1120877A CA1120877A CA000311172A CA311172A CA1120877A CA 1120877 A CA1120877 A CA 1120877A CA 000311172 A CA000311172 A CA 000311172A CA 311172 A CA311172 A CA 311172A CA 1120877 A CA1120877 A CA 1120877A
- Authority
- CA
- Canada
- Prior art keywords
- amino acid
- solution
- amino acids
- process according
- value
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/20—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals substituted additionally by nitrogen atoms, e.g. tryptophane
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Indole Compounds (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE :
A process for the N-acetylisation of amino acids by reaction with ketenes in aqueous solutions. The process of the invention comprises dissolving the amino acid in an approximately equimolar quantity of aqueous alkali liquor to provide a solution having a concentration between 5 and 40 weight percent amino acid, and passing into the solution an approximately equimolar quantity of ketene gas until the pH value of the solution has fallen to the pH value of a corresponding aqueous solution of the pure N-acetyl-amino acid-alkali salt. The resulting solution of N-acetyl-amino acid-alkali salt can be used directly for enzymatic asymmetric hydrolysis for the purpose of producing pure optical isomers of amino acids.
A process for the N-acetylisation of amino acids by reaction with ketenes in aqueous solutions. The process of the invention comprises dissolving the amino acid in an approximately equimolar quantity of aqueous alkali liquor to provide a solution having a concentration between 5 and 40 weight percent amino acid, and passing into the solution an approximately equimolar quantity of ketene gas until the pH value of the solution has fallen to the pH value of a corresponding aqueous solution of the pure N-acetyl-amino acid-alkali salt. The resulting solution of N-acetyl-amino acid-alkali salt can be used directly for enzymatic asymmetric hydrolysis for the purpose of producing pure optical isomers of amino acids.
Description
~Z0877 The known acetylisation of amino acids with acetanhydride or acetylchloride in aqueous solutions or in organic solvents leads in moderate to in part very bad yields to impure products. Equimolar amounts of the bi-product arise.
The reagent must, as a rule, be used in excess. The product must be purified and cleared of bi-products which i5 extremely expensive especially in the case of the production of optically active amino acids described below. In the event of acetylisation and purification of optically active amino acids a considerable racemisation takes place.
It has now been discovered that amino acida in aqueous solution of their water-soluble metal salts, preferably their sodium or calcium salts, can be acetylised in the amino groups with ketenes and without excess reagent quickly, simply and completely, without producing troublesome bi-products.
According to the invention, there is thus provided a process for the N-acetylisation of amino acids by reaction with ketenes in aqueous solutions, which cornprises dissolving the amino acid in an approximately equimolar quantity of aqueous alkali liquor to provide a solution having a concentration between 5 and 40 weight percent amino acid, and passing into the solution an approximately equimolar quantity of ketene gas until the pH
value of the solution has fallen to the pH value of a corresponding aqueous solution of the pure ~-acetyl-amino acid-alkali salt.
The reaction can be carried out particularly simply in the following manner: the amino acid is dissolved in an equimolar quantity of aqueous alkali liquor, to provide a solution having a concentration between 5 and 40 weight percent amino acid and even more preferably about 20 weight percent. Then a flow of ketene gas is passed through the solution until the pH value of the solution has fallen to the pH value of a corresponding aqueous '~
1~;26~877 solution of the pure N-acetyl-amino acid alkali-salt having the same concentration. An equimolar quantity of ketene is used, which in general lies within the error limit of approx. 2 %.
Surprisingly so few bi-products arise from this that the e~uivalent is determinable in this simple manner. Furthermore, the determining of the end of the reaction despite the exi~qtence of heavily buffered solutions through a lowering of the pH with only a small ketene addition is clearly identifiable, whilst before the end point with large additional ketene quantities only a slow drop in the pH is determined. It is very advantageous to adhere to the equivalent precisely although the process can also be carried out with deviations from the equivalent of e.g.
+ 5 or even + 10 %. The conversion to N-acetyl-amino acid lies at 97 to 100 % and is thus considerably higher than in the 'cnown processes. -According to the process of the invention any a-amino acid arising naturally as well as unknown in nature, independent-ly of natural origin or synthetic production, and racemater as well as optically active amino acids can be acetylised. In as far as these amino acids contain further functional groups such as aliphatic hydroxyl groups or an indolyl-~H-group, this group is not acetylised in a very favourable manner.
T~eprocess can therefore be carried out selectively for the a-amino groups.
Particularly favourable results are obtained with optically active amino acids, e.g. tryptophane.
It is therefore particularly simple and advantageous to determine the end point of the reaction according to the invention by measuring the pH value in the respective reaction solution. It is most preferable not to fall short of the end point or to fall short thereof only slightly by 0.1 to 0.5 pH units. ;
11~877 For most amino acids, the end point lies just above pH 7 in 1 molar solution.
The reaction can be carried out at temperatures between the freezing point and the boiling point of the amino acid solutions used. As a result, the optimum temperature differs somewhat according to each amino acid used; usually, it is between 20 and 90C.
The solution of the amino acid to be acetylised will in general contain S to 40, preferably 10 to 30 and still more preferably 15 to 25 weight percent amino acid. Usually, the amino acid is dissolved in approximately an equimolar amount of alkali liquor before the acetylisation, however, a slight excess of alkali is possible at the beginning or until just before the end of the reaction as long as all the amino acid remains accessible through dissolving during the reaction. Then the end product of the reaction is determined by means of other reasonable methods.
For the further raising of the conversion intensity before ketenisation or also after tne end-pH has been reached,
The reagent must, as a rule, be used in excess. The product must be purified and cleared of bi-products which i5 extremely expensive especially in the case of the production of optically active amino acids described below. In the event of acetylisation and purification of optically active amino acids a considerable racemisation takes place.
It has now been discovered that amino acida in aqueous solution of their water-soluble metal salts, preferably their sodium or calcium salts, can be acetylised in the amino groups with ketenes and without excess reagent quickly, simply and completely, without producing troublesome bi-products.
According to the invention, there is thus provided a process for the N-acetylisation of amino acids by reaction with ketenes in aqueous solutions, which cornprises dissolving the amino acid in an approximately equimolar quantity of aqueous alkali liquor to provide a solution having a concentration between 5 and 40 weight percent amino acid, and passing into the solution an approximately equimolar quantity of ketene gas until the pH
value of the solution has fallen to the pH value of a corresponding aqueous solution of the pure ~-acetyl-amino acid-alkali salt.
The reaction can be carried out particularly simply in the following manner: the amino acid is dissolved in an equimolar quantity of aqueous alkali liquor, to provide a solution having a concentration between 5 and 40 weight percent amino acid and even more preferably about 20 weight percent. Then a flow of ketene gas is passed through the solution until the pH value of the solution has fallen to the pH value of a corresponding aqueous '~
1~;26~877 solution of the pure N-acetyl-amino acid alkali-salt having the same concentration. An equimolar quantity of ketene is used, which in general lies within the error limit of approx. 2 %.
Surprisingly so few bi-products arise from this that the e~uivalent is determinable in this simple manner. Furthermore, the determining of the end of the reaction despite the exi~qtence of heavily buffered solutions through a lowering of the pH with only a small ketene addition is clearly identifiable, whilst before the end point with large additional ketene quantities only a slow drop in the pH is determined. It is very advantageous to adhere to the equivalent precisely although the process can also be carried out with deviations from the equivalent of e.g.
+ 5 or even + 10 %. The conversion to N-acetyl-amino acid lies at 97 to 100 % and is thus considerably higher than in the 'cnown processes. -According to the process of the invention any a-amino acid arising naturally as well as unknown in nature, independent-ly of natural origin or synthetic production, and racemater as well as optically active amino acids can be acetylised. In as far as these amino acids contain further functional groups such as aliphatic hydroxyl groups or an indolyl-~H-group, this group is not acetylised in a very favourable manner.
T~eprocess can therefore be carried out selectively for the a-amino groups.
Particularly favourable results are obtained with optically active amino acids, e.g. tryptophane.
It is therefore particularly simple and advantageous to determine the end point of the reaction according to the invention by measuring the pH value in the respective reaction solution. It is most preferable not to fall short of the end point or to fall short thereof only slightly by 0.1 to 0.5 pH units. ;
11~877 For most amino acids, the end point lies just above pH 7 in 1 molar solution.
The reaction can be carried out at temperatures between the freezing point and the boiling point of the amino acid solutions used. As a result, the optimum temperature differs somewhat according to each amino acid used; usually, it is between 20 and 90C.
The solution of the amino acid to be acetylised will in general contain S to 40, preferably 10 to 30 and still more preferably 15 to 25 weight percent amino acid. Usually, the amino acid is dissolved in approximately an equimolar amount of alkali liquor before the acetylisation, however, a slight excess of alkali is possible at the beginning or until just before the end of the reaction as long as all the amino acid remains accessible through dissolving during the reaction. Then the end product of the reaction is determined by means of other reasonable methods.
For the further raising of the conversion intensity before ketenisation or also after tne end-pH has been reached,
2-10 and preferably 4-6 mol % alkali liquor should preferably be added and the reaction is completed up to the end-pH value in any case. The conversions amount to 98.5 to 100 %.
A particular advantage of the N-acetyl-amino acid-metal salt solutions produced in thi~ way is that these solutions can be used directly and without a purification after standardising to the desixed pH value and concentration for the selective enzymatic separation of the N-acetyl group and thereby for the rectification of optically active amino acids, since they contain only approx. 0.5 % free amino acid in the configuration which is not desired and no bi-products to obstruct the enzymatic separation.
A further advantage is that optically active amino acids can be acetylised especially according to the process at low 1~2~8~7 temperatures e.g. in the range of 0-20C, without any racemisation taking place. If the optically active amino acids are used in solution in an equivalent quantity of aqueous alkali and an equimolar amount of ketene is introduced until the end pH value is reached, then no racemisation takes place at higher temperatures ( e.g. 50C) either.
The resulting solutions can be used directly for enzymatic asymmetric hydrolysis for the purpose of producing pure optical isomers of amino acids, for which previous purification of the substrate solutions is surprisingly not necessary.
The following non-restrictive examples illustrate the invention :
304.4 g (2 mol) D-phenylglycine is dissolved in 2 mol , caustic soda solution. The concentration of the caustic soda solution is selected so that the solution contains a) 15 and b) 25 weight percent D,L~phenylglycine. Both solutions are divided and a ketene is introduced into the divided solution at 70C and 90C respectively. By using 2.0-2.05 mol ketene the pH value of the solution falls below 7. The solution contains only 2 to 4 g more of non-acylised D,L-phenylglycine (0.7-1.3%
of that which is used). Conversion 98.7 - 99.3 %. The pH
value falls during the reaction in dixect relation to the ketene quantity added. Upon reaching the equivalent in the region of 2.0-2.05 mol ketene small quantities of ketene produce a sharp fall in the pH.
?
EXAMPLE 2 (Use) When this solution of ~a-N-acetyl-D,L-phenylglycine is raised to pH 7.0 by the addition of alkali liquor and the 1~20877 concentration is adjusted to a) 2.5 and b) 10 and c) 25 weight percent acetyl-amino acid then the L-form of the N-acetyl-amino acid is separated by the action of AMAN0-acylase into free L-amino acid and sodium acetate. The separation develops in the same way as in corresponding solutions, produced from purified N-acetyl-D,L-phenylglycine and caustic soda solution.
The D-form remains unaltered as N-acetyl-amino acid so that L- and D-form are easily separable.
330.4 (2 mol) D,L-phenylalanine is dissolved in ~ mol caustic soda solution. The D,L-phenylalanine concentration is adjusted to approx. 20 weight percent. ~ ketene is intorduced into the solu*ion at a) 20C, b) 45C and c) 70C. ~y using 2.0-2.05 mol ketene the pH value of the solution falls below 7.
0.1 Mol approx. 20 weight percent caustic soda solution is added and a further ketene is introduced until a value less than pH 7 is reached. The solution still contains 1.5-5 g non-acetylised D,L-phenylalanine (0.5-1.5% of that which is used).
Conversion: 98.5-99.5 %.
EXAMPLE 4 (Use) The Na-N-acetyl-D,L-phenylglycine solutions produced by means of pH adjustment and dilution from the solutions according to Example 3 are utilized as a substrate for AMAN0-acylases as do corresponding solutions from purified N-acetyl-D,L-phenylalanine and caustic soda solution.
-Example 3 is repeated but 2.1 mol caustic soda solution is added right at the beginning.
Conversion : 98 - 99.5%.
l~Z0877 Example 1 is repeated but instead ~f 2 mol, 2.1 mol caustic soda solution is added right at the beginning.
Conversion: 99 %.
330.4 g (2 mol) L-phenylalanine is dissolved in 2.1 mol caustic soda solution. The L-phenylalanine concentration is adjusted to approx. 20 weight percent. A ketene is introduced into the solution at a temperature rising from 5C to 15C. By using 2.1-2.15 mol ketene the pH value of the solution falls below 7. Conversion : 98.5 %. From the solution N-acetyl-L-phe,nylalanine with 50 % concentrated hydrochloric acid is precipitated and purified with cold, chloride-free water. ~rield:
80 %. Acid Number: estimated : 271, found: 270.
Specific~rotation ~ a~ D: + 51.5, Lit.: + 50 - 52ff.
(1% in ethanol) (Jade, EII 14, S.247) : ~ , ~20 Example 7 is repeated but D-phenylglycine is acetylised -instead of L-phenylalanine.
Conversion: 98% / ~ D : ~ 190, Lit. : -195.
(Jade, E I 14, S. 591) , Example 7 is repeated but instead of L-phenylalanine L-alanine is acetylised.
Conversion: 98 %.
EXAMPLE 10 ', Example 3 is repeated but D,L-serine is acetylised 112~877 instead of D,L-phenylalanine. N-acetyl-serine is obtained, the OH group of which is not acetylised.
Example 3 is repeated but D,L-tryptophane is acetylised.
Na-acetyltryptophane is obtained, the indole group of which is not acetylised.
Conversion; 98 %.
Example 7 is repeated but L-tryptophane is acetylised.
Conversion: 98.5: J Yield: 93 %, Acid Number: estimated: 227, found: 227.
Example 7 is repeated but L-methoinine is acetylised.
Yield: 78 %, Acid Number: estimated: 293, found 295, /- ~ 20: _ 27.5 (4% in H2O) As a comparison: DOS 25 29 854: Yield: 69%, / a~ D -21 165.2 g (1 mol) L-phenylalanine is dissolved in 1 mol caustic soda solution. The concentration of the caustic soda solution is selected so that the solution contains 20 weight percent L-phenylalanine. A ketene is introduced into thq solution at 50C. By using 1.0-1.02 mol ketene the pH value of the solution falIs below 7.
Conversion: -98%. N-acetyl-L-phenylalanine is precipitated from the solution with 50% concentrated hydrochloric acid and purified by washing with cold, chloride-free water.
Yield: 80%. Characteristic data: as in Example 7.
A particular advantage of the N-acetyl-amino acid-metal salt solutions produced in thi~ way is that these solutions can be used directly and without a purification after standardising to the desixed pH value and concentration for the selective enzymatic separation of the N-acetyl group and thereby for the rectification of optically active amino acids, since they contain only approx. 0.5 % free amino acid in the configuration which is not desired and no bi-products to obstruct the enzymatic separation.
A further advantage is that optically active amino acids can be acetylised especially according to the process at low 1~2~8~7 temperatures e.g. in the range of 0-20C, without any racemisation taking place. If the optically active amino acids are used in solution in an equivalent quantity of aqueous alkali and an equimolar amount of ketene is introduced until the end pH value is reached, then no racemisation takes place at higher temperatures ( e.g. 50C) either.
The resulting solutions can be used directly for enzymatic asymmetric hydrolysis for the purpose of producing pure optical isomers of amino acids, for which previous purification of the substrate solutions is surprisingly not necessary.
The following non-restrictive examples illustrate the invention :
304.4 g (2 mol) D-phenylglycine is dissolved in 2 mol , caustic soda solution. The concentration of the caustic soda solution is selected so that the solution contains a) 15 and b) 25 weight percent D,L~phenylglycine. Both solutions are divided and a ketene is introduced into the divided solution at 70C and 90C respectively. By using 2.0-2.05 mol ketene the pH value of the solution falls below 7. The solution contains only 2 to 4 g more of non-acylised D,L-phenylglycine (0.7-1.3%
of that which is used). Conversion 98.7 - 99.3 %. The pH
value falls during the reaction in dixect relation to the ketene quantity added. Upon reaching the equivalent in the region of 2.0-2.05 mol ketene small quantities of ketene produce a sharp fall in the pH.
?
EXAMPLE 2 (Use) When this solution of ~a-N-acetyl-D,L-phenylglycine is raised to pH 7.0 by the addition of alkali liquor and the 1~20877 concentration is adjusted to a) 2.5 and b) 10 and c) 25 weight percent acetyl-amino acid then the L-form of the N-acetyl-amino acid is separated by the action of AMAN0-acylase into free L-amino acid and sodium acetate. The separation develops in the same way as in corresponding solutions, produced from purified N-acetyl-D,L-phenylglycine and caustic soda solution.
The D-form remains unaltered as N-acetyl-amino acid so that L- and D-form are easily separable.
330.4 (2 mol) D,L-phenylalanine is dissolved in ~ mol caustic soda solution. The D,L-phenylalanine concentration is adjusted to approx. 20 weight percent. ~ ketene is intorduced into the solu*ion at a) 20C, b) 45C and c) 70C. ~y using 2.0-2.05 mol ketene the pH value of the solution falls below 7.
0.1 Mol approx. 20 weight percent caustic soda solution is added and a further ketene is introduced until a value less than pH 7 is reached. The solution still contains 1.5-5 g non-acetylised D,L-phenylalanine (0.5-1.5% of that which is used).
Conversion: 98.5-99.5 %.
EXAMPLE 4 (Use) The Na-N-acetyl-D,L-phenylglycine solutions produced by means of pH adjustment and dilution from the solutions according to Example 3 are utilized as a substrate for AMAN0-acylases as do corresponding solutions from purified N-acetyl-D,L-phenylalanine and caustic soda solution.
-Example 3 is repeated but 2.1 mol caustic soda solution is added right at the beginning.
Conversion : 98 - 99.5%.
l~Z0877 Example 1 is repeated but instead ~f 2 mol, 2.1 mol caustic soda solution is added right at the beginning.
Conversion: 99 %.
330.4 g (2 mol) L-phenylalanine is dissolved in 2.1 mol caustic soda solution. The L-phenylalanine concentration is adjusted to approx. 20 weight percent. A ketene is introduced into the solution at a temperature rising from 5C to 15C. By using 2.1-2.15 mol ketene the pH value of the solution falls below 7. Conversion : 98.5 %. From the solution N-acetyl-L-phe,nylalanine with 50 % concentrated hydrochloric acid is precipitated and purified with cold, chloride-free water. ~rield:
80 %. Acid Number: estimated : 271, found: 270.
Specific~rotation ~ a~ D: + 51.5, Lit.: + 50 - 52ff.
(1% in ethanol) (Jade, EII 14, S.247) : ~ , ~20 Example 7 is repeated but D-phenylglycine is acetylised -instead of L-phenylalanine.
Conversion: 98% / ~ D : ~ 190, Lit. : -195.
(Jade, E I 14, S. 591) , Example 7 is repeated but instead of L-phenylalanine L-alanine is acetylised.
Conversion: 98 %.
EXAMPLE 10 ', Example 3 is repeated but D,L-serine is acetylised 112~877 instead of D,L-phenylalanine. N-acetyl-serine is obtained, the OH group of which is not acetylised.
Example 3 is repeated but D,L-tryptophane is acetylised.
Na-acetyltryptophane is obtained, the indole group of which is not acetylised.
Conversion; 98 %.
Example 7 is repeated but L-tryptophane is acetylised.
Conversion: 98.5: J Yield: 93 %, Acid Number: estimated: 227, found: 227.
Example 7 is repeated but L-methoinine is acetylised.
Yield: 78 %, Acid Number: estimated: 293, found 295, /- ~ 20: _ 27.5 (4% in H2O) As a comparison: DOS 25 29 854: Yield: 69%, / a~ D -21 165.2 g (1 mol) L-phenylalanine is dissolved in 1 mol caustic soda solution. The concentration of the caustic soda solution is selected so that the solution contains 20 weight percent L-phenylalanine. A ketene is introduced into thq solution at 50C. By using 1.0-1.02 mol ketene the pH value of the solution falIs below 7.
Conversion: -98%. N-acetyl-L-phenylalanine is precipitated from the solution with 50% concentrated hydrochloric acid and purified by washing with cold, chloride-free water.
Yield: 80%. Characteristic data: as in Example 7.
Claims (10)
1. A process for the N-acetylisation of amino acids by reaction with ketenes in aqueous solutions, which comprises dissolving the amino acid in an approximately equimolar quantity of aqueous alkali liquor to provide a solution having a concentration between 5 and 40 weight percent amino acid, and passing into the solution an approximately equimolar quantity of ketene gas until the pH value of the solution has fallen to the pH value of a corresponding aqueous solution of the pure N-acetyl-amino acid-alkali salt.
2. Process according to claim 1, wherein the solution has a concentration in amino acid of 15 to 25 weight percent.
3. Process according to Claim 1, wherein the reaction is carried out at temperatures between the freezing point and the boiling point of the solutions used.
4. Process according to Claim 1, wherein 2-10 mol-%
alkali liquor is added and ketenes are repeatedly added until the desired pH value is reached.
alkali liquor is added and ketenes are repeatedly added until the desired pH value is reached.
5. Process according to Claim 1, wherein solutions of optically active amino acids are acetylised without racemisation.
6. Process according to Claim 1, wherein solutions of optically active amino acids are acetylised at temperatures between 0 and 20°C without racemisation.
7. Process according to Claim 1, wherein D,L-phenylalanine is used as the amino acid.
8. Process according to Claim 1, wherein D,L-tryptophane is used as the amino acid.
9. Process according to Claims 5 or 6, wherein L-methionine is used as the amino acid.
10. A process for the production of pure optical isomers of amino acids, which comprises subjecting the solution of N-acetyl-amino acid - alkali salt obtained in Claim 1 to an enzymatic asymmetric hydrolysis.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP2741081.7 | 1977-09-13 | ||
| DE19772741081 DE2741081A1 (en) | 1977-09-13 | 1977-09-13 | PROCESS FOR COMPLETE, SELECTIVE N-ACETYLATION OF AMINO ACIDS BY REACTION WITH KETES IN AQUATIC SOLUTION |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1120877A true CA1120877A (en) | 1982-03-30 |
Family
ID=6018776
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000311172A Expired CA1120877A (en) | 1977-09-13 | 1978-09-12 | Selective n-acetylisation of amino acids by conversion with ketenes in aqueous solution |
Country Status (8)
| Country | Link |
|---|---|
| JP (1) | JPS5448712A (en) |
| BE (1) | BE870441A (en) |
| CA (1) | CA1120877A (en) |
| DE (1) | DE2741081A1 (en) |
| FR (1) | FR2402645A1 (en) |
| GB (1) | GB1587680A (en) |
| IT (1) | IT1106908B (en) |
| NL (1) | NL7809296A (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2740380A1 (en) * | 1977-09-08 | 1979-03-15 | Dynamit Nobel Ag | PROCESS FOR RACEMIZATION OF OPTICALLY ACTIVE N-ACYL-AMINO ACIDS IN AQUATIC SOLUTION |
| DE3318933C1 (en) * | 1983-05-25 | 1984-06-07 | Degussa Ag, 6000 Frankfurt | Process for the separation of L-leucine and L-isoleucine |
| HU190864B (en) * | 1983-12-08 | 1986-11-28 | Alkaloida Vegyeszeti Gyar | Process for production of phenil-alanin derivatives |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| YU35105B (en) * | 1972-04-24 | 1980-09-25 | Krka Tovarna Zdravil | Process for preparing acetylamine derivatives of 2,4,6-triiodo-benzoic acid |
-
1977
- 1977-09-13 DE DE19772741081 patent/DE2741081A1/en not_active Withdrawn
-
1978
- 1978-05-26 GB GB23497/78A patent/GB1587680A/en not_active Expired
- 1978-08-29 FR FR7824934A patent/FR2402645A1/en not_active Withdrawn
- 1978-09-11 JP JP11159978A patent/JPS5448712A/en active Pending
- 1978-09-12 IT IT51061/78A patent/IT1106908B/en active
- 1978-09-12 NL NL7809296A patent/NL7809296A/en not_active Application Discontinuation
- 1978-09-12 CA CA000311172A patent/CA1120877A/en not_active Expired
- 1978-09-13 BE BE190451A patent/BE870441A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| GB1587680A (en) | 1981-04-08 |
| BE870441A (en) | 1979-01-02 |
| NL7809296A (en) | 1979-03-15 |
| JPS5448712A (en) | 1979-04-17 |
| IT1106908B (en) | 1985-11-18 |
| DE2741081A1 (en) | 1979-03-22 |
| IT7851061A0 (en) | 1978-09-12 |
| FR2402645A1 (en) | 1979-04-06 |
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