Claims
- 1. Process for the preparation of a compound with the formula: in which W is Q(CH3)3 where Q is N or P or W is NH3 Y is hydrogen or one of the following groups: —R1, —COR1, —CSR1, —COOR1, —CSOR1, —CONHR1, —CSNHR1, —SOR1, —SO2R1, —SONHR1, —SO2NHR1, where R1 is a straight or branched, saturated or unsaturated alkyl containing from 1 to 20 carbon atoms, optionally substituted with an A1 group, where A1 is selected from the group consisting of halogen, C6-C14 aryl or heteroaryl, aryloxy or heteroaryloxy, which can optionally be substituted with straight or branched, saturated or unsaturated lower alkyl or alkoxy, containing from 1 to 20 carbon atoms, halogens; said process comprises the following steps: a) conversion of D-aspartic or L-aspartic acid to N—Y substituted D-aspartic or L-aspartic acid; b) conversion of the N—Y substituted D-aspartic or L-aspartic acid to the respective anhydride; c) reduction of the anhydride obtained in step b) to the corresponding 3-(NH—Y)-lactone; d) opening of the lactone obtained in step c) to yield the corresponding D-or L-3-(NH—Y)-amino-4-hydroxybutyric acid; e) transformation of the 4-hydroxy group of the D- or L-3-(NH—Y)-amino-4-hydroxybutyric acid into a leaving group; f) substitution of the leaving group in position 4 of the D- or L-3-(NH—Y)-aminobutyric acid with a trimethylammonium group, or trimethylphosphonium group; g) hydrolysis of the ester group; and, if so desired, h) restoration of the amino groups.
- 2. The process according to claim 1, in which step c is directly followed by step c′) consisting in the opening of the lactone to yield the corresponding D- or L-4-X-3-(N—Y)-aminobutyric acid, where X is a leaving group and in which step c′) is followed by steps f)-h).
- 3. The process according to claim 1, in which step f) is followed by step i) consisting in hydrolysis of the ester and deprotection of the 3-amino group to yield R or S aminocarnitine or phosphonium aminocarnitine directly.
- 4. The process according to claim 1, in which group Y is tosyl.
- 5. The process according to claim 1 in which the leaving group is iodine.
- 6. The process according to claim 1, in which the process is conducted without purification of intermediate products.
- 7. The process of claim 1 including the additional step of one pot hydrolysis of the ester and protective group on N group at position 3.
- 8. A process for the preparation of a compound with the formula: in which W is Q(CH3)3 where Q is N or P or W is NH3 Y is hydrogen or one of the following groups: —R1, —COR1, —CSR1, —COOR1, —CSOR1, —CONHR1, —CSNHR1, —SOR1, —SO2R1, —SONHR1, —SO2NHR1, where R1 is a straight or branched, saturated or unsaturated alkyl containing from 1 to 20 carbon atoms, optionally substituted with an A1 group, where A1 is selected from the group consisting of halogen, C6-C14 aryl or heteroaryl, aryloxy or heteroaryloxy, which can optionally be substituted with straight or branched, saturated or unsaturated lower alkyl or alkoxy, containing from 1 to 20 carbon atoms, halogens; said process comprises the following steps: a) conversion of D-aspartic or L-aspartic acid to N—Y substituted D-aspartic or L-aspartic acid; b) conversion of the N—Y substituted D-aspartic or L-aspartic acid to the respective anhydride; c) reduction of the anhydride obtained in step b) to the corresponding 3-(NH—Y)-lactone; d) opening of the lactone obtained in step c) to yield the corresponding D-or L-3-(NH—Y)-amino-4-hydroxybutyric acid; e) transformation of the 4-hydroxy group of the D- or L-3-(NH—Y)-amino-4-hydroxybutyric acid into a leaving group; l) substitution of the leaving group in position 4 of the D- or L-3-(NH—Y)-aminobutanoic acid with an azido group; m) reduction of the azido group to amino group and concurrent hydrolysis of the ester group, and if so desired, n) restoration of the amino group.
- 9. The process according to claim 8, in which step c is directly followed by step c′) consisting in the opening of the lactone to yield the corresponding D- or L-4-X-3-(N—Y)-aminobutyric acid, where X is a leaving group.
- 10. The process according to claim 8, in which group Y is a tosyl.
- 11. The process according to claim 8 in which steps l)-n) allow the preparation of a chiral synthon.
- 12. The process according to claim 11 in which the chiral synthon is R or S 3,4-diaminobutyric acid.
- 13. The process according claim 8 in which the leaving group is iodine.
- 14. The process according to claim 8, in which said process is conducted without purification of the intermediate products.
- 15. A compound of the formula:
Priority Claims (1)
Number |
Date |
Country |
Kind |
RM99A0418 |
Jun 1999 |
IT |
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Parent Case Info
This application is a continuation-in-part of application Ser. No. 10/338,045 filed Jan. 8, 2003, abandoned, which is a continuation-in-part of Ser. No. 10/018,794 filed Dec. 21, 2001, now U.S. Pat. No. 6,528,684 which is a 35 USC §371 of PCT/IT00/00258 filed Jun. 23, 2000.
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
4413142 |
Fiorini et al. |
Nov 1983 |
A |
6528684 |
Giannessi et al. |
Mar 2003 |
B1 |
Foreign Referenced Citations (1)
Number |
Date |
Country |
0 636 603 |
Feb 1995 |
EP |
Non-Patent Literature Citations (1)
Entry |
Charles W. Jefford et al.; “The Enantioselective Synthesis of Beta-Amino Acids, Their Alpha-Hydroxy Derivatives and the N-Terminal Components of Bestatin and Microginin”; Helvetica Chimica Acta, vol. 79, 1996; pp. 1203-1216; XP002152295. |
Continuation in Parts (2)
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Number |
Date |
Country |
Parent |
10/338045 |
Jan 2003 |
US |
Child |
10/372627 |
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US |
Parent |
10/018794 |
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US |
Child |
10/338045 |
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US |