التفاصيل البيبلوغرافية
| العنوان: |
Method of producing amino acids and amino-acid derivatives |
| Patent Number: |
6,121,487 |
| تاريخ النشر: |
September 19, 2000 |
| Appl. No: |
09/361,711 |
| Application Filed: |
July 28, 1999 |
| مستخلص: |
The present invention is relative to a chemical method of producing compounds of the general formula (I) ##STR1## starting from compounds of the general formula (II) and (III) ##STR2## under radical conditions. Products I are used as intermediates in the synthesis of bioactive substances. |
| Inventors: |
Vogt, Annegret (Morristown, NJ); Altenbach, Hans-Josef (Wuppertal, DEX); Kirschbaum, Michael (Gross-Gerau, DEX); Hahn, Michael-Gottfried (Cologne, DEX); Matthaus, Mike Siegfried Paul (Wuppertal, DEX); Hermann, Andreas Rainer (Wuppertal, DEX) |
| Assignees: |
Degussa-Huls Aktiengesellschaft (DEX) |
| Claim: |
What is claimed is |
| Claim: |
1. A method of producing enantiomer-enriched amino acids and amino-acid derivatives of formula (I) or acid addition salts thereof ##STR13## in which *=center of asymmetry |
| Claim: |
X=O or NH |
| Claim: |
R.sup.1 =H, (C.sub.1 -C.sub.6) alkyl, benzyl or (C.sub.3 -C.sub.6) alkoxycarbonylmethyl, and |
| Claim: |
R.sup.2 =H or (C.sub.1 -C.sub.6) alkyl, which can be interrupted or substituted with heteroatoms, which heteroatoms can be substituted themselves singly or multiply with (C.sub.1 -C.sub.3) alkyl, (C.sub.2 -C.sub.6) alkenyl, (C.sub.1 -C.sub.6) haloalkyl, halogen, aryl, which can be substituted singly or multiply with (C.sub.1 -C.sub.3) alkyl, hydroxy, halogen or (C.sub.1 -C.sub.3) alkoxy, aralkyl, which for its part can be substituted singly or multiply with (C.sub.1 -C.sub.3) alkyl, hydroxy, halogen or (C.sub.1 -C.sub.3) alkoxy, heteroaralkyl, and |
| Claim: |
R.sup.3 signifies H, OH |
| Claim: |
from diastereomer-enriched nitrons of the general formula (II) ##STR14## in which * and R.sup.1 have the significance indicated above, wherein |
| Claim: |
the nitron of the general formula (II) is reacted with a hydrazine derivative of the general formula (III) ##STR15## in which R.sup.2 has the meaning indicated above in a solvent in the presence of a radical starter or under electrochemical conditions to obtain diastereomer-enriched compounds of the general formula (IV) ##STR16## in which R.sup.1 and R.sup.2 have the meanings indicated above and R.sup.3 =OH, and the resulting product is subsequently hydrolyzed or first reduced to compounds of the general formula (IV), in which R.sup.1 and R.sup.2 have the meanings indicated above and R.sup.3 =H, and then hydrolyzed. |
| Claim: |
2. The method according to claim 1, wherein the radical substitution is carried out at temperatures between -78.degree. C. and +150.degree. C. |
| Claim: |
3. The method according to claim 1, wherein a two-phase system of toluene/water is used as solvent. |
| Claim: |
4. The method according to claim 2, wherein a two-phase system of toluene/water is used as solvent. |
| Claim: |
5. The method according to claim 1, wherein an oxidizing agent is used as radical starter. |
| Claim: |
6. The method according to claim 3, wherein an oxidizing agent is used as radical starter. |
| Claim: |
7. The method according to claim 1, wherein the reduction is carried out by means of catalytic hydrogenation by means of Pd/C. |
| Claim: |
8. The method according to claim 5, wherein the reduction is carried out by means of catalytic hydrogenation by means of Pd/C. |
| Claim: |
9. The method according to claim 1, wherein the hydrolysis is carried out in an acidified solvent. |
| Claim: |
10. The method according to claim 5, wherein the hydrolysis is carried out in an acidified solvent. |
| Claim: |
11. The method according to claim 1, wherein in the case of IV with R.sup.3 =H the hydrolysis is carried out in aqueous hydrochloric acid. |
| Claim: |
12. The method according to claim 10, wherein in the case of IV with R.sup.3 =H the hydrolysis is carried out in aqueous hydrochloric acid. |
| Claim: |
13. The method according to claim 1, wherein in the case of IV with R.sup.3 =OH the hydrolysis is carried out by means of hydrochloric acid in alcoholic solution. |
| Claim: |
14. The method according to claim 11, wherein in the case of IV with R.sup.3 =OH the hydrolysis is carried out by means of hydrochloric acid in alcoholic solution. |
| Claim: |
15. The method according to claim 1, wherein menthone produced after the hydrolysis is recycled. |
| Claim: |
16. The method according to claim 14, wherein menthone produced after the hydrolysis is recycled. |
| Claim: |
17. The method according to claim 1, wherein the oxidation to the compound of general formula (II) is carried out by means of magnesium monoperoxyphthalic acid (MMPP) or using methyltrioxorhenium (MeReO.sub.3) in the presence of H.sub.2 O.sub.2. |
| Claim: |
18. The method according to claim 15, wherein the oxidation to the compound of general formula (II) is carried out by means of magnesium monoperoxyphthalic acid (MMPP) or using methyltrioxorhenium (MeReO.sub.3) in the presence of H.sub.2 O.sub.2. |
| Claim: |
19. A method of producing enantiomer-enriched amino acids or acid addition salts of formula (I) ##STR17## in which *=center of asymmetry |
| Claim: |
R.sup.2 =H, (C.sub.1 -C.sub.6) alkyl, which can be interrupted or substituted with heteroatoms, which heteroatoms can be substituted themselves singly or multiply with linear or branched (C.sub.1 -C.sub.3) alkyl, (C.sub.2 -C.sub.6) alkenyl, (C.sub.1 -C.sub.6) haloalkyl, halogen, aryl, which can be substituted singly or multiply with (C.sub.1 -C.sub.3) alkyl, hydroxy, halogen or (C.sub.1 -C.sub.3) alkoxy, aralkyl which for its part can be substituted singly or multiply with ((C.sub.1 -C.sub.3) alkyl, hydroxy, halogen or (C.sub.1 -C.sub.3) alkoxy, heteroaralkyl and |
| Claim: |
R.sup.3 represents H or OH |
| Claim: |
wherein compounds of the general formula (IV) ##STR18## which were produced according to the method of claim 1 and in which R.sup.1 and R.sup.2 have the meanings indicated above and R.sup.3 =OH are eliminated to produce compounds of the general formula (V) ##STR19## in which R.sup.1 and R.sup.2 have the meanings indicated above, and are subsequently reduced and hydrolyzed. |
| Claim: |
20. The method according to claim 1 wherein said heteroatoms are selected from the group consisting of N, P, O, S and Si. |
| Claim: |
21. The method according to claim 1 wherein said aryl is naphthyl or phenyl. |
| Claim: |
22. The method according to claim 1 wherein said aralkyl is 2-naphthylmethyl, benzyl or, 1,1- or 1,2-phenethyl. |
| Claim: |
23. The method according to claim 1 wherein said heteroaralkyl is N-protected 3-indolylmethyl. |
| Claim: |
24. The method according to claim 5 wherein said oxidizing agent is selected from the group consisting of sodium peroxodisulfate, potassium peroxdisulfate, sodium percarbonate and sodium perborate. |
| Claim: |
25. The method according to claim 6 wherein said oxidizing agent is selected from the group consisting of sodium peroxodisulfate, potassium peroxodisulfate, sodium percarbonate and sodium perborate. |
| Claim: |
26. The method according to claim 19 wherein said heteroatoms are selected from the group consisting of N, P, O, S and Si. |
| Claim: |
27. The method according to claim 19 wherein said aryl is naphthyl or phenyl. |
| Claim: |
28. The method according to claim 19 wherein said aralkyl is 2-naphthylmethyl, benzyl or 1,1- or 1,2-phenethyl. |
| Claim: |
29. The method according to claim 19 wherein said heteroaralkyl is N-protected 3-indolylmethyl. |
| Current U.S. Class: |
562/575; 562/623; 560/155; 560/170; 560/173 |
| Current International Class: |
C07C22908 |
| Other References: |
Database CAPLUS on STN, Acc. No. 1988:611481, Dotani et al., [A process for the preparation of alpha-amino acid amides by hydrolysis of 4-imidazolidinones.] JP 6305 1339 A2 (abstract), Mar. 4, 1988. |
| Primary Examiner: |
Barts, Samuel |
| Assistant Examiner: |
Davis, Brian J. |
| Attorney, Agent or Firm: |
Pillsbury Madison & Sutro LLP |
| رقم الانضمام: |
edspgr.06121487 |
| قاعدة البيانات: |
USPTO Patent Grants |