L-buthionine-S-sulfoximine and methods of making

Details L-buthionine-S-sulfoximine and methods of making L-buthionine-S-sulfoximine and methods of making

1993-05-05

1994-03-15

Shippen, Michael L.

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

Organic compounds

Carboxylic acids and salts thereof

562556, C07C31500, C07B 5500

Patent

active

052947360

ABSTRACT:
The pure isomers L-buthionine-S-sulfoximine and L-buthionine-R-sulfoximine are provided. The L-S-isomer has utility, for example, in causing the depletion of glutathione, a major protectant molecule in tumors and certain parasites. The L-R-isomer has utility as a compound decreasing further uptake and thus effect of the L-S-isomer and for causing glutathione depletion specific to the kidney. The isolation of pure isomers from L-buthionine-SR-sulfoximine enables treatment at lower dosages without cross effects.
The pure L-buthionine-S-sulfoximine isomer is obtained from L-buthionine-SR-sulfoximine by recrystallization preferably by forming a solution of L-buthionine-SR-sulfoximine in water at a concentration of 0.8 M and cooling to form crystals enriched in the L-R-isomer and a filtrate enriched in L-S-isomer, drying the filtrate to obtain a solid, dissolving the solid in ethanol, adding trifluoroacetic acid to form acid salt and provide solvent, then adding hexane to cause crystal formation, then converting the crystals to the free zwitterion using ion exchange resin.
Both isomers can be separated concurrently by reverse phase chromotography in Cu.sup.++ /D-proline buffers.

REFERENCES:
Christensen, B. W., et al, Chemical Communications, pp. 169-170 (1969).
Griffith, W. W., The Journal of Biological Chemistry, vol. 257, No. 22, pp. 13704-13712 (1982).
Richman, P. G., et al, The Journal of Biological Chemistry, vol. 248, No. 19, 6684-6690 (1973).
Griffith, O. W., Anal. Biochem. 106, 207-212 (1980).
Glutathione Centennial Molecular Perspectives and Clinical Implications (Taniguchi, N., et al, eds.), 1989, Academic Press, pp. 285-299 (Chapter titled "L-Buthionine-SR-Sulfoximine: Mechanism of Action, Resolution of Diastereomers and Use as a Chemotherapeutic Agent," by Owen W. Griffith).
Bump, E. A., et al, Int. J. Radiation Oncology Biol., Phys., vol. 8, 439-442 (1982).
Ozols, R. F., et al, Biochemical Pharmacology, vol. 36, No. 1, 147-153(1987).
Kramer, R. A., et al, Int. J. Radiation Oncology Biol. Phys. vol. 16, 1325-1329(May 1989).
McNally, N. J., et al, Int. J. Radiation Oncology Biol. Phys., vol. 16, 1331-1334(May 1989).
Arrick, B. A., et al, J. Exp. Med, vol. 153, 720-725(Mar. 1981).
Brodie, A. E., et al, Toxicology and Applied Pharmacology, 77, 381-387, 1985.
Anderson, M. E., et al, Proc. Natl. Acad. Sci. USA, vol. 80, pp. 707-711, Feb. 1983.

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