Synthesis of 2-alkylcysteine via substituted thiazoline ester

Details Synthesis of 2-alkylcysteine via substituted thiazoline ester Synthesis of 2-alkylcysteine via substituted thiazoline ester

2005-04-12

2005-04-12

Richter, Johann (Department: 1621)

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

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C548S146000, C562S553000, C562S536000

Reexamination Certificate

active

06878828

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. In one embodiment, the present invention relates to a method of preparing a 2-alkylcysteine comprising condensing cysteine with an aryl nitrile to form a 2-arylthiazoline-4-carboxylic acid, esterifying the 2-arylthiazoline-4-carboxylic acid using a substituted or unsubstituted alcohol group comprising one or more chiral carbons, and alkylating at the 4-position of the thiazoline ring to form a 2-aryl-4-alkyl-thiazoline-4-carboxylic acid ester. The chiral templates present in the thiazoline carboxylic acid ester can provide face selectivity, and consequently desired stereochemistry, during the delivery of an alkyl group to the 4-position of the thiazoline ring. 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 one embodiment, an aryl nitrile is condensed with cysteine or a 2-alkyl cysteine.

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: 20030088105 (2003-05-01), Krich et al.
patent: 20030220504 (2003-11-01), Chorghade et al.
patent: 20030225287 (2003-12-01), Chorghade et al.
patent: 20030229231 (2003-12-01), Chorghade et al.
patent: 20030236404 (2003-12-01), Gimi et al.
patent: 20030236426 (2003-12-01), Chorghade et al.
patent: 20030236434 (2003-12-01), Gimi et al.
patent: 20040002613 (2004-01-01), Chorghade et al.
patent: 20040006224 (2004-01-01), Chorghade et al.
patent: 20040024224 (2004-02-01), 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 9411367 (1994-05-01), None
patent: WO 9736885 (1997-10-01), None
patent: WO 0001670 (2000-01-01), None
patent: WO 0012493 (2000-03-01), None
patent: WO 0016763 (2000-03-01), None
Ino et al., Total Synthesis of the Antimycoplasma Antibiotic Micacocidin, Tetrahedron letters 1998 39(21) 3509-3512.*
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)-L-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).
Bergeron, R., et al., “Desazademethyldesferrithiocin 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).
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).
U.S. Appl. No. 10/439,263, Mukund S. Chorghade, Rayomand H. Gimi, Peter McDonnell and Paul Wolstenholme-Hogg, filed May 15, 2003.

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