Acid salts of...

Details Acid salts of... Acid salts of...

1998-09-04

2001-01-30

Wong, Leslie (Department: 1761)

Food or edible material: processes, compositions, and products

Products per se, or processes of preparing or treating...

Noncarbohydrate sweetener or composition containing same

C560S040000, C560S041000

Reexamination Certificate

active

06180156

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to novel sweeteners. In particular, the invention relates to acid salts of the N-alkylated aspartame derivative, N-[N-(3,3-di-methylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester, i.e., neotame. The invention also relates to a liquid low calorie sweetener containing such salts.
2. Related Background Art
It is known that various N-substituted derivatives of aspartame, such as disclosed in U.S. Pat. No. 5,480,668, are useful as sweetening agents. In particular, the N-alkylated aspartame derivative, N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester, is known as an extremely potent sweetening agent since its sweetening potency, on a weight basis, has been reported to be at least 50 times that of aspartame and about 10,000 times that of sucrose.
Since sweetening agents are often employed in aqueous solutions and beverages, it is important that they have an acceptable dissolution rate and an effective level of solubility to be commercially practicable. U.S. Pat. Nos. 4,029,701 and 4,031,258 describe inorganic salts of dipeptides that provide improved solubility in aqueous solution while maintaining the sweet property of the dipeptide. U.S. Pat. No. 4,448,716 describes certain dipeptide sweetener-metal complexes that provide improved dissolution and solubility. U.S. Pat. No. 4,153,737 describes concentrated solutions of dipeptide salts in a non-aqueous system (concentrated liquid low calorie sweetener). N-[N-(3,3-dimethyl-butyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester, however, is not disclosed or suggested.
Structurally, N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester and aspartame differ in that, in N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester, a bulky neohexyl substituent is present on the amine nitrogen.
This structural difference results in dramatic differences in the physical and chemical properties of these compounds. For example, the melting point of N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester is 80° C., while that of aspartame is 248° C. In addition, N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester has much higher solubility in organic solvents than aspartame, and a much lower solubility in water. It is also known that N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester has a higher stability than aspartame under some pH conditions, as described in U.S. Pat. No. 5,480,688. The pronounced difference in sweetness between the two compounds is further evidence of their chemical dissimilarity.
Moreover, it is also known that a primary amino group such as the one on aspartame (pKa 7.7) generally has a different pKa than those from a secondary amino group such as the one on N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester (pKa 8.1). Moreover, the pKa's of an amino acid are known to have a profound impact on food applications (Labuza, T. P. and Basisier, M. W., 1992, “Physical Chemistry of Foods”, H. G. Schwartzber and R. W. Hartel (Eds.), Marcel Dekker, Inc., New York). It is also well known that a secondary amine group can not form Schiff base type compounds with carbonyl compounds while a primary amine may. Furthermore, N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester exhibits physiologically different behavior than aspartame as exemplified by the dramatic difference in sweetness. These differences are clearly indicative that the characteristics and properties of one can not be said to suggest those of the other.
While N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester is a highly potent sweetener, it is sparingly soluble in water and can give rise to dusting problems. Therefore, there is a need for N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester derivatives that have good dissolution and solubility properties in aqueous systems, and avoid dusting problems often encountered with fine powders.
SUMMARY OF THE INVENTION
This invention relates to dipeptide sweeteners that are salts of N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester possessing good dissolution and solubility properties in aqueous systems. In particular, the salts of N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester of this invention are represented by the formula
wherein X
−
is selected from the group consisting of Cl
−
, HSO
4
−
, H
2
PO
3
−
, citrate, HCO
3
−
, furmarate, malate, maleiate, tartarate, acetate, benzoate or gluconate. The invention is also related to a liquid low calorie sweetener containing the acid salts of this invention.


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patent: 4153737 (1979-05-01), Berg et al.
patent: 4448716 (1984-05-01), Tsau
patent: 5480668 (1996-01-01), Nofre et al.
patent: 5510508 (1996-04-01), Claude et al.
patent: 5728862 (1998-03-01), Prakash
patent: 07680141A1 (1997-04-01), None
Benedetti, E. et al., “The Structure of New Dipeptide Taste Ligands”, American Peptide Symposium, Nashville, TN, (Jun. 1997) P233 p. 2-127.

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