Method of improving stability of sweet enhancer and composition containing stabilized sweet enhancer
The present invention includes methods of stabilizing one or more sweet enhancers when they are exposed to a light source as well as liquid compositions containing one or more sweet enhancers and one or more photostabilizers.
1. A method of improving stability or reducing degradation of a sweet enhancer in a liquid composition comprising contacting a photostabilizer with the sweet enhancer in the liquid composition, wherein:
the photostabilizer is selected from the group consisting of a chromone derivative, a coumarine derivative, a phenylpropenoic carbonyl compound, and a combination thereof; and
the sweet enhancer having structural formula (Ia) or (I′ a), or a salt or solvate thereof:
wherein:
A is —OR 1 , —NR 1 C(O)R 2 , —NHOR 1 , —NR 1 R 2 , —NR 1 CO 2 R 2 , —NR 1 C(O)NR 2 R 3 , —NR 1 C(S)NR 2 R 3 or —NR 1 C(═NH)NR 2 R 3 ;
B is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, acyl, substituted acyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, or substituted heteroarylalkyl;
C is —OR 7 , —SR 7 , —SOR 7 , —SO 2 R 7 , —SO 3 R 7 , —C(O)NR 7 R 8 , —CO R 7 , —NR 7 CO 2 R 8 , —NR 7 C(O)NR 8 R 9 , —NR 7 C(═NH)NR 8 R 9 , —SO 2 NR 7 R 8 , —NR 7 SO 2 R 8 , —NR 7 SO 2 NR 8 R 9 , —B(OR 7 )(OR 8 ), —P(O)(OR 7 )(OR 8 ), —P(O)(R 7 )(OR 8 ), or heteroaryl;
R 1 , R 2 , R 3 , R 7 , R 8 , and R 9 are independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, acyl, substituted acyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl; or alternatively, R 1 and R 2 , R 2 and R 3 , R 7 and R 8 , or R 8 and R 9 , together with the atoms to which they are bonded, form a cycloheteroalkyl or substituted cycloheteroalkyl ring;
R 21 is hydrogen, alkyl, substituted alkyl, halo, —CN, —OR 25 ;
R 22 is hydrogen, alkyl, substituted alkyl, halo, —CN, —OR 27 ;
R 23 is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, acyl, substituted acyl, halo, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, —CN, —OR 29 , —SR 29 , —SOR 29 , —SO 2 R 29 , —OC(O)R 29 , —NR 29 R 30 , —C(O)NR 29 R 30 , —C(O)R 29 , —CO 2 R 29 , —SO 2 NR 29 R 30 , —NR 29 SO 2 R 30 , —B(OR 29 )(OR 30 ), —P(O)(OR 29 )(OR 30 ) or —P(O)(R 29 )(OR 30 );
R 24 is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, acyl, substituted acyl, halo, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, —CN, —OR 31 , —SR 31 , —SOR 31 , —SO 2 R 31 , —OC(O)R 31 , —NR 31 R 32 , —C(O)NR 31 R 32 , —C(O)R 31 , —CO 2 R 31 , —SO 2 NR 31 R 32 , —NR 31 SO 2 R 32 , —B(OR 31 )(OR 32 ), —P(O)(OR 31 )(OR 32 ) or —P(O)(R 31 )(OR 32 ); or alternatively R 23 and R 24 , taken together with the atoms to which they are attached, form a cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, or substituted cycloheteroalkyl ring; and
R 25 , R 27 , R 29 , R 30 , R 31 , and R 32 are independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, acyl, substituted acyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, or substituted heteroarylalkyl; or alternatively R 25 and R 27 , R 27 and R 29 , R 29 and R 30 , R 29 and R 31 , or R 31 and R 32 , together with the atoms to which they are attached, form a cycloheteroalkyl or substituted cycloheteroalkyl ring.
2. A method of improving stability or reducing degradation of a sweet enhancer in a liquid composition comprising contacting a photostabilizer with the sweet enhancer in the liquid composition, wherein:
the photostabilizer is selected from the group consisting of a chromone derivative, a coumarine derivative, a phenylpropenoic carbonyl compound, and a combination thereof; and
the sweet enhancer having structural formula (Ib) or (I′b), or a salt or solvate thereof:
wherein:
A is —OR 1 , —NR 1 C(O)R 2 , —NHOR 1 , —NR 1 R 2 , —NR 1 CO 2 R 2 , —NR 1 C(O)NR 2 R 3 , —NR 1 C(S)NR 2 R 3 or —NR 1 C(═NH)NR 2 R 3 ;
B is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, acyl, substituted acyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, or substituted heteroarylalkyl;
C is —OR 7 , —SR 7 , —SOR 7 , —SO 2 R 7 , —SO 3 R 7 , —C(O)NR 7 R 8 , —CO 2 R 7 , —NR 7 CO 2 R 8 , —NR 7 C(O)NR 8 R 9 , —NR 7 C(═NH)NR 8 R 9 , —SO 2 NR 7 R 8 , —NR 7 SO 2 R 8 , —NR 7 SO 2 NR 8 R 9 , —B(OR 7 )(OR 8 ), —P(O)(OR 7 )(OR 8 ), —P(O)(R 7 )(OR 8 ), or heteroaryl;
R 1 , R 2 , R 3 , R 7 , R 8 , and R 9 are independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, acyl, substituted acyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl; or alternatively, R 1 and R 2 , R 2 and R 3 , R 7 and R 8 , or R 8 and R 9 , together with the atoms to which they are bonded, form a cycloheteroalkyl or substituted cycloheteroalkyl ring;
L 1 is alkylene or substituted alkylene;
L 2 is —NR 34 —, —O—, —S—, —NR 34 —C(O)—, —C(O)—NR 34 —, —O—C(O)—, —C(O)—O—, —NR 34 —C(O)—O—, —O—C(O)—NR 34 —, —NR 34 —C(O)—NR 35 —, —O—C(O)—O—, -heterocyclylene-C(O)—, or -(substituted heterocyclylene)-C(O)—;
R 33 is alkyl, substituted alkyl, carbocyclyl, substituted carbocyclyl; aryl, substituted aryl, arylalkyl, substituted arylalkyl, heterocyclyl, substituted heterocyclyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, or substituted heteroarylalkyl; and
R 34 and R 35 are independently hydrogen, alkyl, substituted alkyl, carbocyclyl, substituted carbocyclyl; aryl, substituted aryl, arylalkyl, substituted arylalkyl, heterocyclyl, substituted heterocyclyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, or substituted heteroarylalkyl.
3. A method of improving stability or reducing degradation of a sweet enhancer in a liquid composition comprising contacting a photostabilizer with the sweet enhancer in the liquid composition, wherein:
the photostabilizer is selected from the group consisting of a chromone derivative, a coumarine derivative, a phenylpropenoic carbonyl compound, and a combination thereof; and
the sweet enhancer having structural formula (Ic), (I′c), (Id), or (I'd), or a salt or solvate thereof:
wherein:
A is —OR 1 , —NR 1 C(O)R 2 , —NHOR 1 , —NR 1 R 2 , —NR 1 CO 2 R 2 , —NR 1 C(O)NR 2 R 3 , —NR 1 C(S)NR 2 R 3 or —NR 1 C(═NH)NR 2 R 3 ;
B is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, acyl, substituted acyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, or substituted heteroarylalkyl;
C is —OR 7 , —SR 7 , —SOR 7 , —SO 2 R 7 , —SO 3 R 7 , —C(O)NR 7 R 8 , —CO 2 R 7 , —NR 7 CO 2 R 8 , —NR 7 C(O)NR 8 R 9 , —NR 7 C(═NH)NR 8 R 9 , —SO 2 NR 7 R 8 , —NR 7 SO 2 R 8 , —NR 7 SO 2 NR 8 R 9 , —B(OR 7 )(OR 8 ), —P(O)(OR 7 )(OR 8 ), —P(O)(R 7 )(OR 8 ), or heteroaryl;
R 1 , R 2 , R 3 , R 7 , R 8 , and R 9 are independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, acyl, substituted acyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl; or alternatively, R 1 and R 2 , R 2 and R 3 , R 7 and R 8 , or R 8 and R 9 , together with the atoms to which they are bonded, form a cycloheteroalkyl or substituted cycloheteroalkyl ring; and
R 33 is alkyl, substituted alkyl, carbocyclyl, substituted carbocyclyl; aryl, substituted aryl, arylalkyl, substituted arylalkyl, heterocyclyl, substituted heterocyclyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, or substituted heteroarylalkyl.
4. A method of improving stability or reducing degradation of a sweet enhancer in a liquid composition comprising contacting a photostabilizer with the sweet enhancer in the liquid composition, wherein:
the photostabilizer is selected from the group consisting of a chromone derivative, a coumarine derivative, a phenylpropenoic carbonyl compound, and a combination thereof; and
the sweet enhancer having structural formula (Ie), or a salt or solvate thereof:
wherein:
R 1 and R 2 are independently hydrogen or C 1 to C 6 alkyl;
L is C 1 to C 12 alkylene or substituted C 1 to C 12 alkylene;
M is —NR 4 —C(O)— or —C(O)—NR 4 —;
R 4 is hydrogen or C 1 to C 6 alkyl; or alternatively, when M is —NR 4 —C(O)—, R 4 and one or more atoms of L, together with the nitrogen to which they are attached, form a 5- to 8-membered heterocyclic ring which is optionally substituted and contains one to three heteroatoms selected from nitrogen, oxygen, and sulfur; and
R 3 is C 1 to C 12 alkyl, substituted C 1 to C 12 alkyl, 5- to 8-membered heterocyclyl, or substituted 5- to 8-membered heterocyclyl; or alternatively, when M is —C(O)—NR 4 —, R 4 and one or more atoms of R 3 , together with the nitrogen to which they are attached, form a 5- to 8-membered heterocyclic ring which is optionally substituted and contains one to three heteroatoms selected from nitrogen, oxygen, and sulfur.
5. The method of claim 4 , wherein the compound of formula (Ie) is represented by structural Formula (IeB):
wherein:
L is C 1 to C 12 alkylene or substituted C 1 to C 12 alkylene;
R 4 is hydrogen or C 1 to C 6 alkyl; and
R 3 is C 1 to C 12 alkyl, substituted C 1 to C 12 alkyl, 5- to 8-membered heterocyclyl, substituted 5- to 8-membered heterocyclyl; or alternatively, R 4 and one or more atoms of R 3 , together with the nitrogen to which they are attached, form a 5- to 8-membered heterocyclic ring which is optionally substituted and contains one to three heteroatoms selected from nitrogen, oxygen, and sulfur.
6. A method of improving stability or reducing degradation of a sweet enhancer in a liquid composition comprising contacting a photostabilizer with the sweet enhancer in the liquid composition, wherein:
the photostabilizer is selected from the group consisting of a chromone derivative, a coumarine derivative, a phenylpropenoic carbonyl compound, and a combination thereof; and
the sweet enhancer having structural formula selected from the group consisting of
or a salt or solvate of any of the foregoing.