CA1178951A - Chelating agents and method - Google Patents
Chelating agents and methodInfo
- Publication number
- CA1178951A CA1178951A CA000369261A CA369261A CA1178951A CA 1178951 A CA1178951 A CA 1178951A CA 000369261 A CA000369261 A CA 000369261A CA 369261 A CA369261 A CA 369261A CA 1178951 A CA1178951 A CA 1178951A
- Authority
- CA
- Canada
- Prior art keywords
- ch2cooh
- chelating agent
- amide derivative
- amino acid
- acid analog
- 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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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Abstract A simple method for making EDTA, ED3A or DTPA
analogs from amide derivatives of alpha amino acids is disclosed. These EDTA, ED3A or DTPA analogs are useful chelating agents, and preferably are useful as bifunctional chelating agents which may be attached to biological molecules and which form physiologically stable chelates with a variety of metal ions.
analogs from amide derivatives of alpha amino acids is disclosed. These EDTA, ED3A or DTPA analogs are useful chelating agents, and preferably are useful as bifunctional chelating agents which may be attached to biological molecules and which form physiologically stable chelates with a variety of metal ions.
Claims (24)
1. A stereospecific method of making an optically active chelating agent comprising:
providing an amide derivative of an optically active alpha amino acid, said amide derivative having a carbonyl group and an alpha carbon, said alpha carbon defining an L or D stereochemical configuration for said amide derivative;
reducing said carbonyl group of said amide derivative with borane to produce a diamine having a pair of amine moieties with said alpha carbon therebetween, said alpha carbon continuing to define either said L or D stereo-chemical configuration for said diamine; and, reacting said diamine with a carboxymethylating agent to form an ethylenediamine tetraacetic acid analog, an ethylenediamine triacetic acid analog, or a diethylene-triamine pentaacetic acid analog with said alpha carbon retaining either said L or D stereochemical configuration and recovering therefrom said ethylenediamine tetraacetic acid analog, said ethylenediamine triacetic acid analog or said diethylenetriamine pentaacetic acid analog as a sub-stantially optically pure product.
providing an amide derivative of an optically active alpha amino acid, said amide derivative having a carbonyl group and an alpha carbon, said alpha carbon defining an L or D stereochemical configuration for said amide derivative;
reducing said carbonyl group of said amide derivative with borane to produce a diamine having a pair of amine moieties with said alpha carbon therebetween, said alpha carbon continuing to define either said L or D stereo-chemical configuration for said diamine; and, reacting said diamine with a carboxymethylating agent to form an ethylenediamine tetraacetic acid analog, an ethylenediamine triacetic acid analog, or a diethylene-triamine pentaacetic acid analog with said alpha carbon retaining either said L or D stereochemical configuration and recovering therefrom said ethylenediamine tetraacetic acid analog, said ethylenediamine triacetic acid analog or said diethylenetriamine pentaacetic acid analog as a sub-stantially optically pure product.
2. The method as in claim 1 wherein said amide derivative is L-tyrosinamide.
3. The method as in claim 1 wherein said amide derivative is L-phenylalaninamide or L-p-nitrophenylalaninamide.
4. The method as in claim 1 wherein the reducing with borane includes converting said diamine to a dihydro-chloride form prior to the reacting step.
5. The stereospecific method as in claim 1 wherein:
said amide derivative has the structure where R is an alpha amino acid side group, or an analog thereof, and R1 is -H, -CH2CH20H or -CH2CH2NH2, said diamine has the structure where the nitrogen atoms may be protonated, and said ethylenediamine tetraacetic acid analog, said ethylenediamine triacetic acid analog or diethylenetriamine pentaacetic acid analog formed in the reacting step has the structure where R2 is -CH2COOH, -CH2CH20H or -CH2CH2N(CH2COOH)2.
said amide derivative has the structure where R is an alpha amino acid side group, or an analog thereof, and R1 is -H, -CH2CH20H or -CH2CH2NH2, said diamine has the structure where the nitrogen atoms may be protonated, and said ethylenediamine tetraacetic acid analog, said ethylenediamine triacetic acid analog or diethylenetriamine pentaacetic acid analog formed in the reacting step has the structure where R2 is -CH2COOH, -CH2CH20H or -CH2CH2N(CH2COOH)2.
6. The stereospecific method of claim 1 wherein:
the amide derivative, diamine and ethylenediamine tetraacetic acid analog, said ethylenediamine triacetic acid analog or said diethylenetriamine pentaacetic acid analog have an L stereoconfiguration.
the amide derivative, diamine and ethylenediamine tetraacetic acid analog, said ethylenediamine triacetic acid analog or said diethylenetriamine pentaacetic acid analog have an L stereoconfiguration.
7. The stereospecific method of claim 6 wherein:
the amide derivative is derived from tyrosine, phenylalanine, tryptophan, cysteine, lysine, methyl tyrosine, methyl tryptophan or p-nitro phenylalanine.
the amide derivative is derived from tyrosine, phenylalanine, tryptophan, cysteine, lysine, methyl tyrosine, methyl tryptophan or p-nitro phenylalanine.
8. A chelating agent of the formula:
wherein R2 is -CH2COOH, -CH2CH20H or -CH2CH2N(CH2COOH)2, whenever prepared by the method of claim 5 or an obvious chemical equivalent.
wherein R2 is -CH2COOH, -CH2CH20H or -CH2CH2N(CH2COOH)2, whenever prepared by the method of claim 5 or an obvious chemical equivalent.
9, A method as defined in claim 5 wherein the carbon to which R is attached of said first compound defines an L
stereochemical configuration.
stereochemical configuration.
10. A chelating agent according to claim 8 wherein the carbon atom to which R is attached defines an L stereo-chemical configuration, whenever prepared by the method of claim 9 or an obvious chemical equivalent.
11. A method as defined in claim 5 wherein the carbon atom to which R is attached of said first compound defined a D
stereochemical configuration.
stereochemical configuration.
12. A chelating agent according to claim 8 wherein the carbon atom to which R is attached defines a D stereo-chemical configuration, whenever prepared by the method according to claim 11 or an obvious chemical equivalent.
13. A method of making a chelating agent of the structure wherein R1 = -CH2COOH, -CH2CH20H or -CH2CH2N(CH2COOH)2 and R is an alpha amino acid side group, which method comprises carrying out the method of claim 1 wherein said amide derivative has the structure wherein R and R1 are as defined above.
14. A method according to claim 13 wherein said alpha amino acid side group includes an aromatic ring.
15. A method according to claim 14 wherein said aromatic ring of said alpha amino acid side group has a reactive substituent thereon selected from the group consisting of -NCS, -O?CH2X, -NH?CH2X, -N?, -CO2H and -NH2, wherein X is a halogen.
16. A method according to claim 13 wherein said alpha amino acid side group corresponds to that of tyrosine, phenylalanine, alanine, tryptophan, cysteine, lysine, methyl tyrosine, methyl tryptophan or p-nitro phenyl-alanine.
17. A chelating agent of the structure wherein R1 = -CH2COOH, -CH2CH2OH or -CH2CH2N(CH2COOH)2 and R is an alpha amino acid side group, whenever pre-pared by the method of claim 13 or an obvious chemical equivalent.
18. A chelating agent according to claim 17 wherein said alpha amino acid side group includes an aromatic ring, whenever prepared by the method of claim 14 or an obvious chemical equivalent.
19. A chelating agent according to claim 17 wherein said alpha amino acid side group includes an aromatic ring having a reactive substituent thereon selected from the group consisting of -NCS, -O?CH2X, -NHClCH2X, -N?, -CO2H
and -NH2; whenever prepared by the method of claim 15 or an obvious chemical equivalent.
and -NH2; whenever prepared by the method of claim 15 or an obvious chemical equivalent.
20. A chelating agent according to claim 17 wherein said alpha amino acid side group corresponds to that of tyrosine, phenylalanine, alanine, tryptophan, cysteine, lysine, methyl tyrosine, methyl tryptophan or p-nitro phenylalanine, whenever prepared by the method of claim 16 or an obvlous chemical equivalent.
21. A method of preparing an optically active and sub-stantially optically pure, bifunctional chelating agent having the structure wherein R1=-CH2COOH, -CH2CH2OH or -CH2CH2N(CH2COOH)2, and R2 is a covalent bond-forming moiety, which method comprises carrying out the method of claim 1 employing the following compound as said amide derivative:
wherein R1 and R2 are as defined above, and said carboxymethylating agent is bromoacetic acid.
wherein R1 and R2 are as defined above, and said carboxymethylating agent is bromoacetic acid.
22. A method according to claim 21 wherein the group R2 of said amide derivative is an amino or carboxy group.
23. An optically active and substantially optically pure, bifunctional chelating agent having the structure wherein R1 = -CH2COOH, -CH2CH2OH or -CH2CH2N(CH2COOH)2, and R2 is a covalent bond-forming moiety: whenever produced by the method of claim 21 or an obvious chemical equivalent.
24. A chelating agent according to claim 23 wherein R2 is an amino or carboxyl group, whenever prepared by the method according to claim 22 or an obvious chemical equivalent.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13168480A | 1980-03-18 | 1980-03-18 | |
| US131,684 | 1980-03-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1178951A true CA1178951A (en) | 1984-12-04 |
Family
ID=22450557
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000369261A Expired CA1178951A (en) | 1980-03-18 | 1981-01-26 | Chelating agents and method |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1178951A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3640708A1 (en) * | 1986-11-28 | 1988-06-09 | Schering Ag | IMPROVED METAL PHARMACEUTICALS |
| EP0315220A1 (en) * | 1985-04-26 | 1989-05-10 | GANSOW, Otto A. | Method of forming a metal chelate protein conjugate |
| WO1990007342A1 (en) * | 1988-12-23 | 1990-07-12 | The Dow Chemical Company | Process for preparing isothiocyanato functionalized metal complexes |
-
1981
- 1981-01-26 CA CA000369261A patent/CA1178951A/en not_active Expired
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0315220A1 (en) * | 1985-04-26 | 1989-05-10 | GANSOW, Otto A. | Method of forming a metal chelate protein conjugate |
| DE3640708A1 (en) * | 1986-11-28 | 1988-06-09 | Schering Ag | IMPROVED METAL PHARMACEUTICALS |
| WO1990007342A1 (en) * | 1988-12-23 | 1990-07-12 | The Dow Chemical Company | Process for preparing isothiocyanato functionalized metal complexes |
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| MKEX | Expiry |