Synthesis of 2-alkyl amino acids

Details Synthesis of 2-alkyl amino acids Synthesis of 2-alkyl amino acids

2006-02-21

2006-02-21

Solola, Taofiq (Department: 1626)

Organic compounds -- part of the class 532-570 series

Organic compounds

Carboxylic acid esters

C560S012000, C560S019000

Reexamination Certificate

active

07002036

ABSTRACT:
Non-natural amino acids such as 2-alkylated amino acids allow for the synthesis of a wider variety of peptidal and non-peptidal pharmaceutically active agents. A method of preparing a 2-alkyl amino acid involves a Michael-type addition of a nucleophile to a dialkyl 2-methylidenylpropan-1,3-dioate and the conversion of a ester moiety into an amino moiety. The present invention also discloses a method of preparing a class of iron chelating agents related to desferrithiocin, all of which contain a thiazoline ring. In this method, an aryl nitrile or imidate is condensed with cysteine, a 2-alkyl cysteine, or a cysteine ester.

REFERENCES:
patent: 4406905 (1983-09-01), Zähner et al.
patent: 5554753 (1996-09-01), O'Donnell et al.
patent: 5840739 (1998-11-01), Bergeron, Jr.
patent: 5872259 (1999-02-01), Reuter
patent: 5929232 (1999-07-01), Jacobsen et al.
patent: 6083966 (2000-07-01), Bergeron, Jr.
patent: 6159983 (2000-12-01), Bergeron, Jr.
patent: 6383233 (2002-05-01), Reuter
patent: 6428583 (2002-08-01), Reuter
patent: 6521652 (2003-02-01), Bergeron
patent: 6525080 (2003-02-01), Bergeron
patent: 6559315 (2003-05-01), Bergeron
patent: 2003/0088105 (2003-05-01), Krich et al.
patent: 2003/0220504 (2003-11-01), Chorghade et al.
patent: 2003/0225287 (2003-12-01), Chorghade et al.
patent: 2003/0229231 (2003-12-01), Chorghade et al.
patent: 2003/0236404 (2003-12-01), Gimi et al.
patent: 2003/0236426 (2003-12-01), Chorghade et al.
patent: 2003/0236434 (2003-12-01), Gimi et al.
patent: 2003/0236435 (2003-12-01), Gimi et al.
patent: 2004/0002613 (2004-01-01), Chorghade et al.
patent: 2004/0006224 (2004-01-01), Chorghade et al.
patent: 20 20 866 (1971-11-01), None
patent: 30 02 989 (1981-07-01), None
patent: 1 302 467 (2003-04-01), None
patent: 1 292 170 (1972-10-01), None
patent: WO 94/11367 (1994-05-01), None
patent: WO 97/36885 (1997-10-01), None
patent: WO 00/01670 (2000-01-01), None
patent: WO 00/12493 (2000-03-01), None
patent: WO 00/16763 (2000-03-01), None
Bergeron, R., et al., “Desazadesmethyldesferrithiocin Analogues as Orally Effective Iron Chelators,”J. Med. Chem., 42:95-108 (1999).
Bergeron, R. et al., “The Desferrithiocin Pharmacophore,”J. Med. Chem., 37:1411-1417 (1994).
Bergeron, R. et al., “Effects of C-4 Stereochemistry and C-4 Hydroxylation on the Iron Clearing Efficiency and Toxicity of Desferrithiocin Analogues,”J. Med. Chem., 42:2432-2440 (1999).
Bergeron, R. et al., “Synthesis and Biological Evaluation of Naphthyldesferrithiocin Iron Chelators,”J. Med. Chem., 39:1575-1581 (1996).
Bergeron, R. et al., “Evaluation of Desferrithiocin and Its Synthetic Analogues as Orally Effective Iron Chelators,”J. Med. Chem., 34:2072-2078 (1991).
Bergeron, R. et al., “Evaluation of the Desferrithiocin Pharmacophore as a Vector for Hydroxamates,”J. Med. Chem., 42:2881-2886 (1999).
Bergeron, R. et al., “An Investigation of Desferrithiocin Metabolism,”J. Med. Chem., 37:2889-2895 (1994).
Bergeron, R. et al., “A Comparative Study of the Iron-Clearing Properties of Desferrithiocin Analogues with Desferrioxamine B in aCebusMonkey Model,”Blood, 81(8):2166-2173 (1993).
Bergeron, R., et al., “Pharmacokinetics of Orally Administered Desferrithiocin Analogs inCebus ApellaPrimates,”Drug Metabolism and Disposition, 27(12):1496-1498 (1999).
“Aliphatic Nucleophilic Substitution,” InAdvanced Organic Chemistry, by Jerry March (Wiley Interscience), Ch. 10, pp. 433-434 (1992).
“Eliminations,” InAdvanced Organic Chemistry, by Jerry March (Wiley Interscience), Ch. 17, pp. 1012-1014 (1992).
Mulqueen, G. C., et al., “Synthesis of the Thiazoline-based Siderophore (S)-Desferrithiocin,”Tetrahedron, 49(24):5359-5364 (1993).
O'Donnell, M. J., et al., “α-Methyl Amino Acids by Catalytic Phase-Transfer Aklylations,”Tetrahedron Letters, 23(41):4259-4262 (1982).
Ehrler, Juerg, and Farooq, Saleem, “Total Synthesis of Thiangazole,”Synlett, 702-704 (1994).
Kishore, V., et al., “Synthesis of α-Poly-[Nε-(2-aryl-Δ2-thiazoline-4-carbonyl)-ι-lysines] With Antiviral Activity,”Indian Journal of Chemistry 15B: 255-257 (1977).
Zamri, Adel, and Abdallah, Mohamed A., “An Improved Stereocontrolled Synthesis of Pyochelin, Siderophore ofPseudomonas aeruginosaandBurkholderia cepacia,” Tetrahedron 56:249-256 (2000).

Affiliated with

Also associated with

Rating

Synthesis of 2-alkyl amino acids does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Synthesis of 2-alkyl amino acids, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Synthesis of 2-alkyl amino acids will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3671433