Selenohydroxy acids and their derivatives, applications in nutrition, cosmetics and pharmaceutics

• US 7,381,416 B2
• Filed: 07/22/2005
• Issued: 06/03/2008
• Est. Priority Date: 07/23/2004
• Status: Active Grant

• Current Assignee: Tetrahedron, Inc.
• Original Assignee: Tetrahedron, Inc.
• Inventors: Erdelmeir, Irene, Michel, Jean-Claude, Yadan, Jean-Claude, Moutet, Marc
• Primary Examiner(s): Russel; Jeffrey Edwin
• Application Number:
  US11/187,617
• Publication Number:
  US 20060105960A1
• Time in Patent Office: 1,047 Days
• Field of Search: None
• US Class Current: 424/401
• CPC Class Codes: A23L 33/165 Complexes or chelates
• CPC Class Codes: A61K 31/095 Sulfur, selenium, or tellurium compounds, e.g. thiols
• CPC Class Codes: A61K 8/58 containing atoms other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur or phosphorus
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin
• CPC Class Codes: C07C 391/00 Compounds containing selenium

Abstract

The purpose of this invention is:

• • new selenohydroxy acid compounds and their derivatives;
  • their process for the preparation;
  • use of the new compounds as precursors of L(+)-selenomethionine and/or source of selenium in human or animal nutrition, in cosmetics and pharmaceutics;
  • and nutritional, cosmetic and pharmaceutical compositions containing them.

The new compounds that are the subject of this invention satisfy the general formula (I):

in which

• • n=0, 1 or 2,
  • R₁=OH, OCOR₃, OPO₃H₂, OPO(OR₄)(OR₅), or OR₆,
  • R₂=OH, R₃, or NHR₇,
  • R₃=particularly alkoxyl (C₁-C₂₆), ceramide 1, ceramide 2, ceramide 3, ceramide 4, ceramide 5, ceramide 6a and 6b, S-cysteinyl, or S-glutathionyl, carnitoyl, lipids, polyols,
  • OR₄=OR₅=particularly alkoxyl (C₁-C₂₆), ceramide 1, ceramide 2, ceramide 3, ceramide 4, ceramide 5, ceramide 6a and 6b, S-cysteinyl, or S-glutathionyl, carnitoyl, lipids, polyols,
  • OR₆=pyruvate, lactate, citrate, fumarate, maleate, myristate, palmitate, stearate, palmitoleate, oleate, linoleate, natural fatty acids, or 13-cis retinoate,
  • R₇=H, alkyl, natural amino acids, or natural amines.

Claims

1. Organoselenium compounds of the general formula (I) comprising:

2. Compounds according to claim 1 wherein n is 0.

3. Compounds according to claim 1 wherein R₁ represents OH, OCOR₃, or OR₆, R₃ and R₆ being as defined in claim 1.

4. Compounds according to claim 1 wherein R₁ is OH.

5. Compounds according to claim 1 wherein R₂ is chosen from the group consisting of OH, NHR₇, glyceroyl, monoacylglyceroyl, diacylglyceroyl, coenzyme Q, retinoyl, cholesteroyl, alpha-tocopheroyl, carnitinoyl, sphinganine, sphingosine, phyto-sphingosine, ceramide 1, ceramide 2, ceramide 3, ceramide 4, ceramide 5, ceramide 6a or 6b, ascorbate, S-cysteinyl and S-glutathionyl, R₇ being as defined in claim 1.

6. Compounds according to claim 1 wherein R₂ represents OH.

7. Compounds according to claim 1 of formula (I′

), corresponding to the general formula (I) in which

n=0, 1 or 2,

R₁=OCOR₃, OPO₃H₂, OPO(OR₄)(OR₅), or OR₆,

R₂=R₃, or NHR₇,

R₃=ceramide 1, ceramide 2, ceramide 3, ceramide 4, ceramide 5, ceramide 6a or 6b, S-cysteinyl, or S-glutathionyl, or

8. Compounds according to claim 1 of formula (I″

), corresponding to the general formula (I) in which

n=0, 1 or 2,

R₁=OH,

R₂=OH, or R₃,

R₃=alkoxyl (C₁-C₂₆),

it being understood that when n=1 and R₁=OH, then R₂ cannot be OH.

9. Any one of the compounds of general formula I, as defined in claim 1, with the following name:

L-2-hydroxy-4-methylselenobutyric acid,

D-2-hydroxy-4-methylselenobutyric acid,

DL-2-hydroxy-4-methylselenobutyric acid,

dicyclohexylammonium L-2-hydroxy-4-methylselenobutyrate.

10. Compounds according to claim 1 in the form of sodium or calcium or magnesium salts.

11. A process for the preparation of organoselenium compounds of the general formula (I) as defined in claim 1 further comprising at least one of the following steps:

(1) the reaction of (D,L)-2-R₁-butyrolactone or one of its enantiomers (D or L), where R₁ is as defined in claim 1,

either with an alkaline methylselenolate salt of formula (IIa)

CH₃—

Se⁻

M⁺ 

 

(IIa)

in which M represents an atom of an alkaline metal, to obtain a compound of formula (Ia) in the form of an alkaline salt

12. A process according to claim 11 wherein the selenium reagent is:

either a methyl selenolate salt which is optionally generated in situ;

or produced from selenium metal Se(0) and an alkyl salt in an aprotic solvent;

or from a dimethyl diselenide (CH₃Se)₂ in the presence of a reducing agent;

or a selenocyanate salt which is optionally generated in situ;

or from selenium metal Se(0) and a cyanide salt;

or added to the medium as such,

or a selenide or diselenide salt,

or a selenosulfate salt.

13. A process according to claim 11 wherein the selenium reagent is lithium methyl selenolate or potassium selenocyanate.

15. A process for the preparation of L-(+)-selenomethionine starting from 2-hydroxy-4-methylseleno-butyric acid of formula (I) as defined in claim 1, or one of its alkaline salts of formula (Ia),

16. A method for use of compounds of general formula (I) as defined in claim 1, comprising administering to an animal and/or human the compounds of general formula (I), or their salts with pharmaceutically acceptable acids and bases as a source of selenomethionine, L(+) selenomethionine, and/or selenium.

17. A method for use according to claim 16, wherein n is 0 in compounds of general formula (I).

18. A method for use according to claim 16 wherein the compounds of general formula (I) or their salts are administered to the animal and/or human in the form of food complements or additives for human or animal food.

19. A method for use according to claim 16 wherein the compounds of general formula (I) or their salts are administered to the animal and/or human in the form of complements or additives for cosmetic products.

20. A method for use of the compounds according to claim 7, wherein the method comprises administering to an animal and/or human cosmetic products comprising compounds corresponding to the general formula (I′

).

21. A method for use according to claim 16 wherein the compounds of general formula (I) or their salts are administered as drugs.

22. A method for use of the compounds according to claim 7, the method comprising administering to an animal and/or human drugs comprising the compounds corresponding to the general formula (I′

).

23. A method for use of the compounds according to claim 8, the method comprising administering to an animal and/or human food complements or additives for human or animal food comprising compounds of the general formula (I″

).

24. Nutritional compositions containing at least one of the compounds of formula (I) as defined claim 1 as an active constituent or additive.

25. Nutritional compositions containing at least one of the compounds of formula (I″

) as defined in claim 8 or at least one of their sodium or calcium or magnesium salts, as an active constituent or additive.

26. Cosmetic compositions containing at least one of the compounds of formula (I) as defined in claim 1, as an active constituent or additive.

27. Cosmetic compositions containing at least one of the compounds of formula (I′

) as defined in claim 7, as an active constituent or additive.

28. Pharmaceutical compositions containing at least one of the compounds of formula (I) as defined in claim 1, as an active constituent or additive.

29. Pharmaceutical compositions containing at least one of the compounds of formula (I′

) as defined in claim 7, as an active constituent or additive.

31. A process according to claim 11, wherein the selenium reagent is:

either a methyl selenolate salt which is optionally generated in situ;

or produced from selenium metal Se(0) and an alkyl salt in an aprotic solvent comprising tetrahydrofurane (THF);

or from a dimethyl diselenide (CH₃Se)₂ in the presence of a reducing agent comprising sodium borohydride in an aprotic solvent comprising THF;

or a selenocyanate salt comprising potassium selenocyanate which is optionally generated in situ;

or from selenium metal Se(0) and a cyanide salt comprising potassium cyanide,

or added to the medium as such,

or a selenide or diselenide salt comprising sodium or lithium selenide or diselenide,

or a selenosulfate salt comprising sodium selenosulfate.

32. A method for use according to claim 16 comprising administering to an animal and/or human the compounds of general formula (I), or their salts with pharmaceutically acceptable acids and bases as a source of L(+) selenomethionine.

14. As new industrial compounds,

(a) compounds of formula

30. An organoselenium compound having general formula (I) comprising: