Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-05-31
2001-09-11
Powers, Fiona T. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06288240
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates generally to the preparation of certain prolines and, more particularly, to the preparation of the sodium salt of 2-hydroxy-5-oxoproline.
BACKGROUND OF THE INVENTION
The metabolite 2-hydroxy-5-oxoproline (2-oxoglutaramate) was discovered several decades ago in animal livers and kidneys and investigated in these tissues. A limited understanding of its function in animals was developed from these studies; in cells this material appears to be made by the physiologically irreversible transamination of glutamine. The compound appears to play a role in the regulation of tissue glutamine levels and in ammoniagenesis; that is, the amide nitrogen in glutamine is a major source of urinary ammonia. See, e.g., “The Glutamine Tranaminase-&ohgr;-Amidase Pathway” by Arthur J. L. Cooper and Alton Meister, CRC Critical Reviews in Biochemistry, pages 281-303, January 1977, and “Occurrence Of Glutamine-2-Oxoacid Transaminase Activity In The Blue-Green Alga
ANABAENA CYLINDRICA
” by Masayuki Ohmori et al., J. Gen Appl. Microbiol. 31, 171 (1985).
More recently, 2-hydroxy-5-oxoproline has been found to have significant effect on plant growth. See, e.g., “Use Of Prolines For Improving Growth And Other Properties Of Plants And Algae” by Pat J. Unkefer, Thomas J. Knight, and Rodolfo A. Martinez, U.S. Patent and Trademark Office Ser. No. 09/493,039, filed on Jan. 27, 2000, where the inventors describe the use of the chemical class of compounds known as prolines for improving plant properties and performance.
In the past, 2-hydroxy-5-oxoproline has been synthesized using enzymatic procedures which are slow and difficult to control. See, e.g., A. L. Cooper and Alton Meister, supra.
The reaction of Fremy's Salt with glutamic acid to yield (21%) an &agr;-ketoacid of glutamic acid is described in “Oxidation of &agr;-Amino Acids and &agr;-Hydroxy Acids By Fremy's Salt. A Model For Oxidases?” by Angel Garcia-Raso, J. Org. Chem. 51, 4285 (1986). More particularly, &agr;-glutamic acid was used as the starting material and the following reactions were observed:
However, the final product does not cyclize.
Accordingly, it is an object of the present invention to provide a method for synthesizing 2-hydroxy-5-oxoproline and analogs thereof in an inexpensive, bulk process.
Additional objects, advantages and novel features of the invention will be set forth in part in the description which follows, and in part will become apparent to those skilled in the art upon examination of the following or may be learned by practice of the invention. The objects and advantages of the invention may be realized and attained by means of the instrumentalities and combinations particularly pointed out in the appended claims.
SUMMARY OF THE INVENTION
To achieve the foregoing and other objects, and in accordance with the purposes of the present invention, as embodied and broadly described herein, the method for preparing 2-hydroxy-5-oxoproline hereof is performed in a single step reaction of Fremy's Salt (potassium nitrosodisulphonate) with either glutamine or 2-pyrrolidone-5-carboxylic acid. Fremy's salt (potassium nitrosodisulphonate) is available commercially, or can be readily synthesized.
Benefits and advantages of the present invention include an inexpensive, essentially quantitative, readily performed, single-step synthetic procedure for preparing large quantities of 2-hydroxy-5-oxoproline.
DETAILED DESCRIPTION
The present invention includes an efficient, inexpensive procedure for preparing 2-hydroxy-5-oxoproline and analogs thereof. The compound is synthesized in a single step by the action of Fremy's salt (potassium nitrosodisulphonate) on either glutamine or on 2-pyrrolidone-5-carboxylic acid. Fremy's salt (potassium nitrosodisulphonate) is available commercially, or can be synthesized in accordance with the procedure described in “Nitrosodisulphonates, Part I. Fremy's Salt (Potassium Nitrosodisulphonate)” by W. Moser and R. A. Howie, J. Chem. Soc. A 3039 (1968).
REFERENCES:
Cooper et al., J. Biol. Chem., 248, 1973, 8499-8505.*
U.S. Patent and Trademark Office Serial No. 09/493,039 “Use of Prolines For Improving Growth And Other Properties Of Plants And Algae” by Pat J. Unkefer, Thomas J. Knight, and Rodolfo A. Martinez, filed on Jan. 27, 2000.
Arthur J.L. Cooper and Alton Meister, “The Glutamine Tranaminase-&ohgr;-Amidase Pathway” CRC Critical Reviews in Biochemistry, pp. 281-303, Jan. 1977.
Masayuki Ohmori et al., “Occurrence Of Glutamine-2-Oxoacid Transaminase Activity In The Blue-Green AlgaANABAENA CYLINDRICA”, J. Gen Appl. Microbiol. 31, 171 (1985).
Angel Garcia-Raso, “Oxidation of &agr;-Amino Acids and &agr;-Hydroxy Acids By Fremy's Salt. A Model For Oxidases?”, J. Org. Chem. 51, 4285 (1986).
W. Moser and R.A. Howie, “Nitrosodisulphonates, Part I. Fremy's Salt (Potassium Nitrosodisulphonate)”, J. Chem. Soc. A 3039 (1968).
Martinez Rodolfo A.
Unkefer Pat J.
Freund Samuel M.
Powers Fiona T.
The Regents of the University of California
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