EP0075160A2
Expired / Lapsed
EP
⏱️ 0.0 years remaining
Process for recovering a dipeptide derivative
Assignee: Tosoh Corp
•
Filing: 1982-09-02
•
Granted: —
•
Expires: 2002-09-02
Abstract
Abstract A process for recovering a dipeptide derivative comprises admixing an organic solvent capable of forming a binary phase system with water with an aqueous mixture containing as a solid component a dipeptide ester derivative of the formula wherein R, is a lower alkyl group, R 2 is a side chain group of an amino acid, n is 1 or 2, X is a benzyloxycarbonyl group which can have a nuclear substituent and Y is a hydrogen ion or an ammonium derivative ion of the formula wherein R 3 is a side chain group of an amino acid and R. is a lower alkyl group, settling the resulting admixture to form 1. an organic solvent phase containing in a solid state a substantial amount of dipeptide derivative of the formula wherein R 1 , R 2 , n and X are as defined above and Z is a hydrogen ion or an ammonium derivative ion of the formula wherein R 3 and R. are as defined above, and 2. an aqueous phase, separating the organic solvent phase from the aqueous phase, and recovering the dipeptide derivative from the organic solvent phase.
Inventors
- 👤 Kiyotaka Oyama
- 👤 Shigeaki Irino
- 👤 Norio Hagi
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-28 18:19
CPC Classifications
C; C07; C07K; C07K5/00; C07K5/04; C07K5/06; C07K5/06104; C07K5/06113; C07K5/06121; C07K5/0613; Y; Y10; Y10S; Y10S530/00; Y10S530/801
Claims Analysis
Total Claims: 36
Claim 1
Independent Claim
194 words
1) A process for recovering a dipeptide derivative which comprises admixing an organic solvent capable of forming a binary phase system with. water with an aqueous mixture containing as a solid component a dipeptide ester derivative of the formula wherein R 1 is a lower alkyl group, R 2 is a side chain group of an amino acid, n is 1 or 2, X is a benzyloxycarbonyl group which can have a nuclear substituent and Y is a hydrogen ion or an ammonium derivative ion of the formula wherein R 3 is a side chain group of an amino acid and R 4 is a lower alkyl group, settling the resulting admixture to form (1) an organic solvent phase containing in a solid state a substantial amount of dipeptide derivative of the formula wherein R 1 , R 2 1 n and X are as defined above and Z is a hydrogen ion or an ammonium derivatve ion of the formula wherein R 3 and R4 are as defined above, and (2) an aqueous phase, separating the organic solvent phase from the aqueous phase, and recovering the dipeptide derivative from the organic solvent phase.
Claim 2
Dependent Claim
194 words
1) A process for recovering a dipeptide derivative which comprises admixing an organic solvent capable of forming a binary phase system with. water with an aqueous mixture containing as a solid component a dipeptide ester derivative of the formula wherein R 1 is a lower alkyl group, R 2 is a side chain group of an amino acid, n is 1 or 2, X is a benzyloxycarbonyl group which can have a nuclear substituent and Y is a hydrogen ion or an ammonium derivative ion of the formula wherein R 3 is a side chain group of an amino acid and R 4 is a lower alkyl group, settling the resulting admixture to form (1) an organic solvent phase containing in a solid state a substantial amount of dipeptide derivative of the formula wherein R 1 , R 2 1 n and X are as defined above and Z is a hydrogen ion or an ammonium derivatve ion of the formula wherein R 3 and R4 are as defined above, and (2) an aqueous phase, separating the organic solvent phase from the aqueous phase, and recovering the dipeptide derivative from the organic solvent phase.
Claim 3
Dependent Claim
27 words
2) The process according to Claim 1, wherein the organic solvent is used in an amount allowing the peptide derivative to substantially remain in a solid state.
Claim 4
Dependent Claim
19 words
3) The process according to Claim 2, wehrein the moiety in the formulas (I) and (III) is in L,L-configuration.
Claim 5
Dependent Claim
40 words
4) The process according to Claim 3, wherein Y and Z are both the ammonium derivative ion of the formula wherein R 3 is a side chain group of an amino acid and R 4 is a lower alkyl group.
Claim 6
Dependent Claim
33 words
5) The process according to Claim 4, wherein the organic solvent is a ketone which is capable of forming a binary phase system with water, an aliphatic or aromatic hydrocarbon, or an ether.
Claim 7
Dependent Claim
35 words
6) The process according to Claim 5, wherein the organic solvent is used in an amount less than 10 parts and not less than 1 part, respectively by weight based on the dipeptide ester derivative.
Claim 8
Dependent Claim
44 words
7) The process according to Claim 6, wherein R 1 and R 4 are methyl groups, R 2 and R 3 are benzyl groups, n is 1, X is a benzyloxycarbonyl group, and Y and Z are in L-, L- and D-, or D-configuration.
Claim 9
Dependent Claim
19 words
8) The process according to Claim 8, wherein the organic solvent is toluene, methyl isobutyl ketone or isopropyl ether.
Claim 10
Dependent Claim
29 words
9) The process according to Claim 6, wherein the aqueous mixture further contains a protease, and which further comprises recovering the protease from the aqueous phase after the phase-separation.
Claim 11
Dependent Claim
44 words
10) The process according to Claim 9, wherein R 1 and R 4 are methyl groups, R 2 and R 3 are benzyl groups, n is 1, X is a benzyloxycarbonyl group, and Y and Z are in L-, L- and D-, or D-configuration.
Claim 12
Dependent Claim
19 words
11) The process according to Claim 10, wherein the organic solvent is toluene, methyl isobutyl ketone or isopropyl ether.
Claim 13
Dependent Claim
30 words
12) The process according to Claim 4, wherein, after the phase separation, the aqueous phase is subjected to a ultrafiltration to obtain a concentrated protease solution to recover the same.
Claim 14
Dependent Claim
173 words
13) The process according to Claim 12, which further comprises reacting an amino acid ester of the formula wherein R 1 is a lower alkyl group and R 2 is a side chain group of an amino acid, the amino acid ester containing at least one being in L-configuration, with an N-protected L-aminodicarboxylic acid of the formula wherein X is a benzyloxycarbonyl group which can have a nuclear substituent and n is 1 or 2, in the presence of a protease in an aqueous medium at a pH, at which the protease exerts the enzymatic activity, to produce an aqueous mixture containing (1) a dipeptide ester derivative of the formula wherein R 1 is a lower alkyl group, R 2 is a side chain group of an amino acid, X is a benzyloxycarbonyl group which can have a nuclear substituent and n is 1 or 2, the dipeptide ester derivative being in a solid state, and (2) the protease, and subjecting the thus resulting aqueous mixture to the admixing with the organic solvent.
Claim 15
Dependent Claim
32 words
14) The process according to Claim 13, wherein the organic solvent is a ketone which is capable of forming a binary system with water, an aliphatic or aromatic hydrocarbon, or an ether.
Claim 16
Dependent Claim
38 words
15) The process according to Claim 14, wherein the organic solvent is used in an amount less than 10 parts and not less than 1 part, respectively by weight based on the amount of the dipeptide ester derivative.
Claim 17
Dependent Claim
55 words
16) The process according to Claim 15, wherein R 1 is a methyl group, R 2 is a benzyl group,, n is 1, X is a benzyloxycarbonyl group, the amino acid ester is in L- or L- and D-configuration, and the moiety of the dipeptide ester derivative is in L-, L- and D-, or D-configuration.
Claim 18
Dependent Claim
15 words
17) The process according to Claim 3, wherein Y and Z are both hydrogen ions.
Claim 19
Dependent Claim
60 words
18) The process according to Claim 17, wherein the organic solvent is a ketone capable of forming a binary phase system with water, an aliphatic or aromatic hydrocarbon, or an ether, which solvent is used in an amount less than 10 parts and not less than 1 part, respectively by weight based on the amount of the dipeptide ester derivative.
Claim 20
Dependent Claim
28 words
19) The process according to Claim 18, wherein R 1 is a methyl group, R 2 is a benzyl group, n is 1, X is a benzyloxycarbonyl group.
Claim 21
Dependent Claim
54 words
20) The process according to Claim 3, wherein Y is the ammonium derivative ion of the formula (II) and Z is a hydrogen ion, which further comprises, at the time of the admixing of the organic solvent with the aqueous mixture, adding a brdnsted acid to the aqueous mixture together with the organic solvent.
Claim 22
Dependent Claim
60 words
21) The process according to Claim 20, wherein the organic solvent is a ketone capable of forming a binary phase system with water, an aliphatic or aromatic hydrocarbon, or an ether, which solvent is used in an amount less than 10 parts and not less than 1 part, respectively by weight based on the amount of the dipeptide ester derivative.
Claim 23
Dependent Claim
33 words
22) The process according to Claim 21, wherein the brdnsted acid is used in an amount ranging from about 1 to about 10 equivalents based on the molarity of the dipeptide ester derivative.
Claim 24
Dependent Claim
36 words
23) The process according to Claim 22, wherein water in the aqueous mixture is in an amount ranging from about 1 to about 10 parts by weight based on the amount of the dipeptide ester derivative.
Claim 25
Dependent Claim
21 words
24) The process according to Claim 23, wherein hydrochloric acid, sulfuric acid or acetic acid is used as the brdnsted acid.
Claim 26
Dependent Claim
52 words
25) The process according to Claim 24, wherein R 1 and R 4 are methyl groups, R 2 and R 3 are benzyl groups, n is 1, X is a benzyloxycarbonyl group, and Z is the ammonium derivative ion of the formula (IV) which is in L-, L- and D-, or D-confiuguration.
Claim 27
Dependent Claim
39 words
26) The process according to Claim 25, which further comprises, after the phase-separation, recovering from the aqueous phase an amino acid ester of the formula wherein R 4 is a methyl group and R 3 is a benzyl group.
Claim 28
Dependent Claim
145 words
27) The process according to Claim 4, which further comprises, after the separation of the organic solvent phase from the aqueous phase, adding and mixing water and a brdnsted acid to the separated organic solvent phase and subjecting the mixture to phase separation to form (1) a second organic solvent phase containing a dipeptide ester derivative of the formula wherein R 1 is a lower alkyl group, R 2 is a side chain group of an amino acid, n is 1 or 2, X is a benzyloxycarbonyl group which can have a nuclear substituent, and (2) a second aqueous phase containing an amino acid ester ion of the formula wherein R 4 is a lower alkyl group and R 3 is a side chain group of an amino acid, separating the resulting phases and recovering the final dipeptide derivative from the second organic solvent phase.
Claim 29
Dependent Claim
61 words
28) The process according to Claim 27, wherein the organic solvent is a ketone which can form a binary phase system with water, an aliphatic or aromatic hydrocarbon, an ether or a mixture thereof, which solvent is used in an amount less than 10 parts and not less than 1 part, respectively based on the amount of the dipeptide ester derivative.
Claim 30
Dependent Claim
35 words
29) The process according to Claim 28, wherein the amount of water in the aqueous mixture ranging from about 1 to about 10 parts by weight based on the amount of the dipeptide ester derivative.
Claim 31
Dependent Claim
33 words
30) The process according to Claim 29 wherein the brdnsted acid is used in an amount ranging from about 1 to about 10 equivalents based on the molarity of the dipeptide ester derivative.
Claim 32
Dependent Claim
45 words
31) The process according to Claim 30, wherein the water which is added with the brønsted acid to the first organic solvent phase, is in an amount ranging from about 1 to about 10 parts by weight based on the amount of the dipeptide derivative.
Claim 33
Dependent Claim
45 words
32) The process according to Claim 31, wherein R 1 and R4 are methyl groups, R 2 is a benzyl group, R 3 is a methyl, isopropyl, isobutyl, benzyl or p-hydroxybenzyl group, X is a benzyloxycarbonyl group or a p-methoxybenzyloxycarbonyl group and n is 1.
Claim 34
Dependent Claim
31 words
33) The process according to Claim 32, wherein the organic solvent is toluene, methyl isobutyl ketone or diisopropyl ether, and the brønsted acid is hydrochloric acid, sulfuric acid or acetic acid.
Claim 35
Dependent Claim
37 words
34) The process according to Claim 33, which further comprises recovering an amino acid ester of the formula wherein R 3 is a benzyl group and R 4 is a methyl group, from the second aqueous phase.
Claim 36
Dependent Claim
16 words
35) The process according to Claim 9, 12 or 13 wherein the protease is a metalloprotease.
References Cited (Backward Citations)
No citation records indexed.
USPTO Annuity & Maintenance Windows
Maintenance schedule is calculated for granted US utility patents.