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US4411925A Expired / Lapsed US ⏱️ 0.0 years remaining

Branched amides of L-aspartyl-d-amino acid dipeptides

Assignee: Danisco Finland Oy
•
Filing: 1980-11-05
•
Granted: 1983-10-25
•
Expires: 2000-11-05
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Abstract

Abstract Amides of L-aspartyl-D-amino acid dipeptides of the formula <IMAGE> (I) and physiologically acceptable cationic and acid addition salts thereof wherein Ra is methyl, ethyl, n-propyl or isopropyl; R is a branched member selected from the group consisting of fenchyl, diisopropylcarbinyl, d-methyl-t-butylcarbinyl, d-ethyl-t-butylcarbinyl, di-t-butylcarbinyl, 2-methylthio-2,4-dimethylpentan-3-yl, <IMAGE> <IMAGE> <IMAGE> <IMAGE> <IMAGE> said amides are potent sweeteners having advantages over the prior art, edible compositions containing them, methods for their use in edible compositions and novel amine and amide intermediates useful in their production.

Inventors

  • 👤 Thomas M. Brennan
  • 👤 Michael E. Hendrick

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-06 11:04
CPC Classifications
C; C07; C07D; C07D307/00; C07D307/02; C07D307/26; C07D307/30; C07D307/32; A; A23; A23L; A23L27/00; A23L27/30; A23L27/31; A23L27/32; C07C; C07C323/00; C07C323/23; C07C323/24; C07C323/25; C07C45/00; C07C45/004; C07C45/27; C07C45/29; C07C45/292; C07C45/61; C07C45/62; C07C45/63; C07C45/64; C07C45/67; C07C45/673; C07C45/68; C07C45/72; C07C45/74; C07C45/75; C07C49/00; C07C49/04; C07C49/16; C07C49/17; C07C49/173; C07C49/29; C07C49/293; C07C49/385; C07C49/39; C07C49/395; C07C49/403; C07C49/413; C07C49/523; C07C49/587; C07C49/647; C07D307/04; C07D307/18; C07D307/22; C07D331/00; C07D331/04; C07D333/00; C07D333/02; C07D333/04; C07D333/26; C07D333/30; C07D333/32; C07D333/36; C07D335/00; C07D335/02; C07K; C07K5/00; C07K5/04; C07K5/06; C07K5/06104; C07K5/06113; Y; Y10; Y10S; Y10S426/00; Y10S426/804; Y10S530/00; Y10S530/801

Claims Analysis

Total Claims: 95
Claim 1
Independent Claim 462 words
An L-aspartyl-D-amino acid dipeptide amide of the formula ##STR412## and the physiologically acceptable cationic and acid addition salts thereof, wherein R a is methyl, ethyl, n-propyl or isopropyl; and R is a branched member selected from the group consisting of fenchyl, diisopropylcarbinyl, d-methyl-t-butylcarbinyl, d-ethyl-t-butylcarbinyl, di-t-butylcarbinyl, 2-methylthio-2,4-dimethylpentan-3-yl, ##STR413## where at least one of R 3 , R 4 , R 5 , R 6 is alkyl having from one to four carbon atoms and the remainder are hydrogen or alkyl having from one to four carbon atoms, X is O, S, SO, SO 2 , C═O or CHOH; m is zero, 1, 2, 3 or 4, n and p are each zero, 1, 2 or 3 where the sum of n+p is not greater than 3 and the sum of the carbon atoms in R 3 , R 4 , R 5 and R 6 is not greater than six, and when both of R 3 and R 4 or R 5 and R 6 are alkyl they are methyl or ethyl, ##STR414## where one of R 7 , R 8 , R 9 is alkyl having from one to four carbon atoms and the remainder are hydrogen or alkyl having from one to four carbon atoms and the sum of the carbon atoms in R 7 , R 8 and R 9 is not greater than six, ##STR415## where m and q are the same or different and each have the values previously defined for m, ##STR416## where each of R 12 and R 13 are methyl or ethyl, or R 12 is hydrogen and R 13 is alkyl having from one to four carbon atoms, Z is 0 or NH and t is 1 or 2, ##STR417## where w is 1, 2, 3 or 4, R 14 and R 16 are each alkyl having from one to four carbon atoms, R 15 is hydrogen, OH, or alkyl having from one to two carbon atoms, where the sum of the carbon atoms in R 14 , R 15 and R 16 is not greater than six and when both of R 14 and R 15 are alkyl they are methyl or ethyl, and ##STR418## where R 17 and R 19 are alkyl having from one to four carbon atoms, R 18 and R 20 are hydrogen or alkyl having from one to two carbon atoms, taken separately, A is OH and B is hydrogen, OH or methyl and when taken together A and B are ##STR419## where the sum of the carbon atoms in R 17 , R 18 , R 19 and R 20 is not greater than six and when both of R 17 and R 18 or R 19 and R 20 are alkyl they are methyl or ethyl.
Claim 2
Dependent Claim 462 words
An L-aspartyl-D-amino acid dipeptide amide of the formula ##STR412## and the physiologically acceptable cationic and acid addition salts thereof, wherein R a is methyl, ethyl, n-propyl or isopropyl; and R is a branched member selected from the group consisting of fenchyl, diisopropylcarbinyl, d-methyl-t-butylcarbinyl, d-ethyl-t-butylcarbinyl, di-t-butylcarbinyl, 2-methylthio-2,4-dimethylpentan-3-yl, ##STR413## where at least one of R 3 , R 4 , R 5 , R 6 is alkyl having from one to four carbon atoms and the remainder are hydrogen or alkyl having from one to four carbon atoms, X is O, S, SO, SO 2 , C═O or CHOH; m is zero, 1, 2, 3 or 4, n and p are each zero, 1, 2 or 3 where the sum of n+p is not greater than 3 and the sum of the carbon atoms in R 3 , R 4 , R 5 and R 6 is not greater than six, and when both of R 3 and R 4 or R 5 and R 6 are alkyl they are methyl or ethyl, ##STR414## where one of R 7 , R 8 , R 9 is alkyl having from one to four carbon atoms and the remainder are hydrogen or alkyl having from one to four carbon atoms and the sum of the carbon atoms in R 7 , R 8 and R 9 is not greater than six, ##STR415## where m and q are the same or different and each have the values previously defined for m, ##STR416## where each of R 12 and R 13 are methyl or ethyl, or R 12 is hydrogen and R 13 is alkyl having from one to four carbon atoms, Z is 0 or NH and t is 1 or 2, ##STR417## where w is 1, 2, 3 or 4, R 14 and R 16 are each alkyl having from one to four carbon atoms, R 15 is hydrogen, OH, or alkyl having from one to two carbon atoms, where the sum of the carbon atoms in R 14 , R 15 and R 16 is not greater than six and when both of R 14 and R 15 are alkyl they are methyl or ethyl, and ##STR418## where R 17 and R 19 are alkyl having from one to four carbon atoms, R 18 and R 20 are hydrogen or alkyl having from one to two carbon atoms, taken separately, A is OH and B is hydrogen, OH or methyl and when taken together A and B are ##STR419## where the sum of the carbon atoms in R 17 , R 18 , R 19 and R 20 is not greater than six and when both of R 17 and R 18 or R 19 and R 20 are alkyl they are methyl or ethyl.
Claim 3
Dependent Claim 82 words
A compound according to claim 1 wherein R is a member selected from the group consisting of ##STR420## where R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , A, B, X, Z, m, n, p, q, t and w are as previously defined.
Claim 4
Dependent Claim 10 words
A compound according to claim 2 wherein R is ##STR421##
Claim 5
Dependent Claim 13 words
A compound according to claim 1 wherein R is diisopropylcarbinyl, d-methyl-t-butylcarbinyl or di-t-butylcarbinyl.
Claim 6
Dependent Claim 10 words
A compound according to claim 2 wherein R is ##STR422##
Claim 7
Dependent Claim 16 words
A compound according to claim 5 wherein A is OH and B is hydrogen or methyl.
Claim 8
Dependent Claim 25 words
A compound according to claim 6 wherein R 17 , R 18 , R 19 and R 20 are each methyl and B is hydrogen.
Claim 9
Dependent Claim 11 words
The compound according to claim 7 wherein R a is methyl.
Claim 10
Dependent Claim 13 words
The compound according to claim 5 wherein A and B are each OH.
Claim 11
Dependent Claim 21 words
A compound according to claim 9 wherein R 17 , R 18 , R 19 and R 20 are each methyl.
Claim 12
Dependent Claim 11 words
The compound according to claim 10 wherein R a is methyl.
Claim 13
Dependent Claim 14 words
A compound according to claim 5 wherein A and B taken together form ##STR423##
Claim 14
Dependent Claim 21 words
A compound according to claim 12 wherein R 17 , R 18 , R 19 and R 20 are each methyl.
Claim 15
Dependent Claim 11 words
A compound according to claim 13 wherein R a is methyl.
Claim 16
Dependent Claim 10 words
A compound according to claim 12 wherein R is ##STR424##
Claim 17
Dependent Claim 11 words
A compound according to claim 15 wherein R 15 is OH.
Claim 18
Dependent Claim 21 words
A compound according to claim 16 wherein w is 2 or 3 and R 14 and R 16 are each methyl.
Claim 19
Dependent Claim 15 words
The compound according to claim 17 wherein R a is methyl and w is 3.
Claim 20
Dependent Claim 10 words
A compound according to claim 2 wherein R is ##STR425##
Claim 21
Dependent Claim 15 words
A compound according to claim 19 wherein R 12 and R 13 are each methyl.
Claim 22
Dependent Claim 18 words
The compound according to claim 20 wherein R a is methyl, t is 1 and Z is O.
Claim 23
Dependent Claim 10 words
A compound according to claim 4 wherein R is diisopropylcarbinyl.
Claim 24
Dependent Claim 11 words
The compound according to claim 22 wherein R a is methyl.
Claim 25
Dependent Claim 10 words
A compound according to claim 4 wherein R is d-methyl-t-butylcarbinyl.
Claim 26
Dependent Claim 11 words
The compound according to claim 24 wherein R a is methyl.
Claim 27
Dependent Claim 10 words
A compound according to claim 4 wherein R is di-t-butylcarbinyl.
Claim 28
Dependent Claim 11 words
The compound according to claim 26 wherein R a is methyl.
Claim 29
Dependent Claim 10 words
A compound according to claim 3 wherein R is ##STR426##
Claim 30
Dependent Claim 10 words
A compound according to claim 28 wherein R is ##STR427##
Claim 31
Dependent Claim 18 words
A compound according to claim 29 wherein R 7 , R 8 and R 9 are each methyl.
Claim 32
Dependent Claim 11 words
The compound according to claim 30 wherein R a is methyl.
Claim 33
Dependent Claim 10 words
A compound according to claim 3 wherein R is ##STR428##
Claim 34
Dependent Claim 10 words
A compound according to claim 32 wherein R is ##STR429##
Claim 35
Dependent Claim 11 words
The compound according to claim 33 wherein R a is ethyl.
Claim 36
Dependent Claim 11 words
The compound according to claim 33 wherein R a is methyl.
Claim 37
Dependent Claim 10 words
A compound according to claim 3 wherein R is ##STR430##
Claim 38
Dependent Claim 10 words
A compound according to claim 36 wherein m is 2.
Claim 39
Dependent Claim 22 words
A compound according to claim 37 wherein R 3 , R 4 , R 5 , and R 6 are each methyl.
Claim 40
Dependent Claim 11 words
The compound according to claim 38 wherein R a is methyl.
Claim 41
Dependent Claim 30 words
A compound according to claim 37 wherein R 3 , R 4 and R 5 are each hydrogen and R 6 is alkyl having from one to four carbon atoms.
Claim 42
Dependent Claim 15 words
A compound according to claim 40 wherein R 6 is methyl, ethyl, isopropyl or t-butyl.
Claim 43
Dependent Claim 16 words
The compound according to claim 41 wherein R a is methyl and R 6 is isopropyl.
Claim 44
Dependent Claim 28 words
The compound according to claim 37 wherein R a is methyl, R 3 and R 5 are each hydrogen and R 4 and R 6 are each methyl.
Claim 45
Dependent Claim 10 words
A compound according to claim 36 wherein m is 3.
Claim 46
Dependent Claim 21 words
A compound according to claim 44 wherein R 3 , R 4 , R 5 and R 6 are each methyl.
Claim 47
Dependent Claim 11 words
The compound according to claim 45 wherein R a is methyl.
Claim 48
Dependent Claim 30 words
A compound according to claim 44 wherein R 3 , R 4 and R 5 are each hydrogen and R 6 is alkyl having from one to four carbon atoms.
Claim 49
Dependent Claim 13 words
A compound according to claim 47 wherein R 6 is isopropyl or t-butyl.
Claim 50
Dependent Claim 11 words
A compound according to claim 48 wherein R a is methyl.
Claim 51
Dependent Claim 31 words
A compound according to claim 44 wherein R 3 and R 5 are each hydrogen and R 4 and R 6 are each alkyl having from one to four carbon atoms.
Claim 52
Dependent Claim 15 words
A compound according to claim 50 wherein R 4 and R 6 are each methyl.
Claim 53
Dependent Claim 11 words
The compound according to claim 51 wherein R a is methyl.
Claim 54
Dependent Claim 16 words
A compound according to claim 50 wherein R 4 is methyl and R 6 is isopropyl.
Claim 55
Dependent Claim 11 words
The compound according to claim 53 wherein R a is methyl.
Claim 56
Dependent Claim 30 words
A compound according to claim 44 wherein R 3 is hydrogen and R 4 , R 5 and R 6 are each alkyl having from one to four carbon atoms.
Claim 57
Dependent Claim 18 words
A compound according to claim 55 wherein R 4 , R 5 and R 6 are each methyl.
Claim 58
Dependent Claim 11 words
The compound according to claim 56 wherein R a is methyl.
Claim 59
Dependent Claim 25 words
A compound according to claim 44 wherein R 3 and R 4 are each hydrogen and R 5 R 6 are each methyl or ethyl.
Claim 60
Dependent Claim 20 words
The compound according to claim 58 wherein R a is methyl and R 5 and R 6 are each methyl.
Claim 61
Dependent Claim 10 words
A compound according to claim 3 wherein R is ##STR431##
Claim 62
Dependent Claim 17 words
A compound according to claim 60 wherein X is O, n is 1 and p is zero.
Claim 63
Dependent Claim 21 words
A compound according to claim 61 wherein R 3 , R 4 , R 5 and R 6 are each methyl.
Claim 64
Dependent Claim 11 words
The compound according to claim 62 wherein R a is methyl.
Claim 65
Dependent Claim 21 words
A compound according to claim 60 wherein X is S or SO 2 , n is 1 and p is zero.
Claim 66
Dependent Claim 21 words
A compound according to claim 64 wherein R 3 , R 4 , R 5 and R 6 are each methyl.
Claim 67
Dependent Claim 15 words
The compound according to claim 65 wherein R a is methyl and X is S.
Claim 68
Dependent Claim 21 words
A compound according to claim 60 wherein X is S or SO 2 , and n and p are each zero.
Claim 69
Dependent Claim 21 words
A compound according to claim 67 wherein R 3 , R 4 , R 5 and R 6 are each methyl.
Claim 70
Dependent Claim 13 words
A compound according to claim 68 wherein R a is methyl or ethyl.
Claim 71
Dependent Claim 15 words
The compound according to claim 69 wherein R a is methyl and X is S.
Claim 72
Dependent Claim 17 words
The compound according to claim 69 wherein R a is methyl and X is SO 2 .
Claim 73
Dependent Claim 20 words
A compound according to claim 60 wherein X is S or SO 2 and n and p are each 1.
Claim 74
Dependent Claim 31 words
The compound according to claim 72 wherein R a is methyl, X is S, R 3 and R 5 are each hydrogen and R 4 and R 6 are each methyl.
Claim 75
Dependent Claim 17 words
A compound according to claim 60 wherein X is C═O and n and p are each zero.
Claim 76
Dependent Claim 26 words
The compound according to claim 74 wherein R a is methyl and R 3 , R 4 , R 5 and R 6 are each methyl.
Claim 77
Dependent Claim 16 words
A compound of claim 60 wherein X is CHOH and n and p are each zero.
Claim 78
Dependent Claim 26 words
The compound according to claim 76 wherein R a is methyl and R 3 , R 4 , R 5 and R 6 are each methyl.
Claim 79
Dependent Claim 22 words
A composition for sweetening edible materials which comprises a sweetening amount of a compound according to claim 1 and a non-toxic carrier.
Claim 80
Dependent Claim 12 words
A composition according to claim 78 wherein said compound is L-aspartyl-D-alanine N-(dicyclopropylcarbinyl)amide.
Claim 81
Dependent Claim 12 words
A composition according to claim 78 wherein said compound is L-aspartyl-D-alanine N-(2,2,4,4-tetramethylthietan-3-yl)amide.
Claim 82
Dependent Claim 12 words
A composition according to claim 78 wherein said compound is L-aspartyl-D-alanine N-(2,2,4,4-tetramethyl-1,1-dioxothietan-3-yl)amide.
Claim 83
Dependent Claim 29 words
A composition for sweetening edible materials which comprises a sweetening amount of a mixture of a compound according to claim 1 and saccharin or a physiologically acceptable salt thereof.
Claim 84
Dependent Claim 17 words
A composition according to claim 82 wherein said compound is L-aspartyl-D-alanine N-(dicyclopropylcarbinyl)amide, L-aspartyl-D-alanine N-(2,2,4,4-tetramethylthietan-3-yl)amide or L-aspartyl-D-alanine N-(2,2,4,4-tetramethyl-1,1-dioxothietan-3-yl)amide.
Claim 85
Dependent Claim 12 words
A composition according to claim 83 wherein said compound is L-aspartyl-D-alanine N-(dicyclopropylcarbinyl)amide.
Claim 86
Dependent Claim 22 words
A composition according to claim 84 wherein said compound and said saccharin are in a weight ratio of from 1:1 to 1:9.
Claim 87
Dependent Claim 20 words
A sweetened edible composition which comprises an edible material and a sweetening amount of a compound according to claim 1.
Claim 88
Dependent Claim 20 words
A sweetened edible composition which comprises an edible material and a sweetening amount of a compound according to claim 3.
Claim 89
Dependent Claim 16 words
A sweetened edible composition according to claim 86 wherein said edible material is a carbonated beverage.
Claim 90
Dependent Claim 16 words
A sweetened edible composition according to claim 87 wherein said edible material is a carbonated beverage.
Claim 91
Dependent Claim 19 words
A sweetened edible composition according to claim 89 wherein said compound is L-aspartyl-D-alanine N-(dicyclopropylcarbinyl)amide, L-aspartyl-D-alanine N-(2,2,4,4-tetramethylthietan-3-yl)amide or L-aspartyl-D-alanine N-(2,2,4,4-tetramethyl-1,1-dioxothietan-3-yl)amide.
Claim 92
Dependent Claim 20 words
A method for sweetening edible materials which comprises adding thereto a sweetening amount of a compound according to claim 1.
Claim 93
Dependent Claim 12 words
A method according to claim 91 wherein said compound is L-aspartyl-D-alanine N-(dicyclopropylcarbinyl)amide.
Claim 94
Dependent Claim 12 words
A method according to claim 91 wherein said compound is L-aspartyl-D-alanine N-(2,2,4,4-tetramethylthietan-3-yl)amide.
Claim 95
Dependent Claim 12 words
A method according to claim 91 wherein said compound is L-aspartyl-D-alanine N-(2,2,4,4-tetramethyl-1,1-dioxothietan-3yl)amide.

References Cited (Backward Citations)

US3959245A Cited
US3907766A Cited
US3971822A Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1986-10-24 1987-04-25 1987-10-25 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1990-10-24 1991-04-25 1991-10-25 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 1994-10-24 1995-04-25 1995-10-25 $7700.00 Window Closed / Lapsed

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