US4946942A
Expired / Lapsed
US
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Urethane-protected amino acid-N-carboxyanhydrides
Assignee: Bioresearch Inc
•
Filing: 1988-03-11
•
Granted: 1990-08-07
•
Expires: 2008-03-11
Abstract
Abstract The invention relates to urethane-protected amino acid-N-carboxyanhydride and N-thiocarboxyanhydride compounds which are useful in peptide, polypeptide and protein synthesis. Disclosed herein is the preparation and use of these novel compounds.
Inventors
- 👤 William D. Fuller
- 👤 Michael P. Cohen
- 👤 Fred R. Naider
- 👤 Murray Goodman
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 14:33
CPC Classifications
C; C07; C07D; C07D263/00; C07D263/02; C07D263/08; C07D263/16; C07D263/18; C07D263/20; C07D263/26; C07D263/30; C07D263/34; C07D263/44; C07D277/00; C07D277/02; C07D277/20; C07D277/32; C07D277/34; C07D277/36; C07K; C07K1/00; C07K1/02; C07K1/023; C07K1/04
Claims Analysis
Total Claims: 91
Claim 1
Independent Claim
59 words
A urethane-protected amino acid-N-carboxyanhydride or N-thiocarboxyanhydride having the structure: ##STR9## wherein R and R' are hydrogen, alkyl, cycloalkyl, substituted alkyl, substituted cycloalkyl, aryl, or substituted aryl and at least one of R and R' is other than hydrogen; R" is alkyl, aryl, substituted alkyl or substituted aryl; Z is oxygen or sulfur; and n is 0, 1 or 2.
Claim 2
Dependent Claim
59 words
A urethane-protected amino acid-N-carboxyanhydride or N-thiocarboxyanhydride having the structure: ##STR9## wherein R and R' are hydrogen, alkyl, cycloalkyl, substituted alkyl, substituted cycloalkyl, aryl, or substituted aryl and at least one of R and R' is other than hydrogen; R" is alkyl, aryl, substituted alkyl or substituted aryl; Z is oxygen or sulfur; and n is 0, 1 or 2.
Claim 3
Dependent Claim
21 words
A urethane-protected amino acid-N-carboxyanhydride or N-thiocarboxyanhydride according to claim 1 wherein R" is an alkyl of 1 to 20 carbon atoms.
Claim 4
Dependent Claim
19 words
A urethane-protected amino acid-N-carboxyanhydride or N-thiocarboxyanhydride according to claim 2 wherein R" is lower alkyl or substituted lower alkyl.
Claim 5
Dependent Claim
14 words
A urethane-protected amino acid-N-carboxyanhydride or N-thiocarboxyanhydride according to claim 3 wherein R" is t-butyl.
Claim 6
Dependent Claim
17 words
A urethane-protected amino acid-N-carboxyanhydride or N-thiocarboxyanhydride according to claim 1 wherein R" is aryl or substituted aryl.
Claim 7
Dependent Claim
17 words
A urethane-protected amino acid-N-carboxyanhydride or N-thiocarboxyanhydride according to claim 5 wherein R" is phenyl or substituted phenyl.
Claim 8
Dependent Claim
17 words
A urethane-protected amino acid-N-carboxyanhydride or N-thiocarboxyanhydride according to claim 1 wherein R" is aralkyl or substituted aralkyl.
Claim 9
Dependent Claim
17 words
A urethane-protected amino acid-N-carboxyanhydride or N-thiocarboxyanhydride according to claim 7 wherein R" is benzyl or substituted benzyl.
Claim 10
Dependent Claim
14 words
A urethane-protected amino acid-N-carboxyanhydride or N-thiocarboxyanhydride according to claim 8 wherein R" is p-methoxybenzyl.
Claim 11
Dependent Claim
17 words
A urethane-protected amino acid-N-carboxyanhydride or N-thiocarboxyanhydride according to claim 7 wherein R" is 9-fluorenylmethyl or substituted 9-fluorenylmethyl.
Claim 12
Dependent Claim
30 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 1 wherein at least one of R or R' is the side chain of a protected or unprotected amino acid.
Claim 13
Dependent Claim
21 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of alanine.
Claim 14
Dependent Claim
25 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of arginine or suitably protected arginine.
Claim 15
Dependent Claim
27 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of aspartic acid or suitably protected aspartic acid.
Claim 16
Dependent Claim
25 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of asparagine or suitably protected asparagine.
Claim 17
Dependent Claim
25 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of cysteine or suitably protected cysteine.
Claim 18
Dependent Claim
21 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of cystine.
Claim 19
Dependent Claim
27 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of glutamic acid or suitably protected glutamic acid.
Claim 20
Dependent Claim
25 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of glutamine or suitably protected glutamine.
Claim 21
Dependent Claim
25 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of histidine or suitably protected histidine.
Claim 22
Dependent Claim
21 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of isoleucine.
Claim 23
Dependent Claim
24 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of a suitably protected lysine.
Claim 24
Dependent Claim
21 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of leucine.
Claim 25
Dependent Claim
21 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of methionine.
Claim 26
Dependent Claim
21 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of norleucine.
Claim 27
Dependent Claim
24 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of a suitably protected ornithine.
Claim 28
Dependent Claim
21 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of phenylalanine.
Claim 29
Dependent Claim
25 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of serine or suitably protected serine.
Claim 30
Dependent Claim
25 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of threonine or suitably protected threonine.
Claim 31
Dependent Claim
25 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of tryptophan or suitably protected tryptophan.
Claim 32
Dependent Claim
25 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of tyrosine or suitably protected tyrosine.
Claim 33
Dependent Claim
21 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of valine.
Claim 34
Dependent Claim
25 words
A urethane-protected amino acid N-carboxyanhydride or N-thiocarboxyanhydride according to claim 11 wherein R or R' is the side chain of homoserine or suitably protected homoserine.
Claim 35
Dependent Claim
1 words
N-9-fluorenylmethyloxycarbonyl-L-leucine-N-carboxyanhydride.
Claim 36
Dependent Claim
1 words
N-9-fluorenylmethyloxycarbonyl-L-leucine-N-carboxyanhydride.
Claim 37
Dependent Claim
1 words
N-9-fluorenylmethyloxycarbonyl-L-alanine-N-carboxyanhydride.
Claim 38
Dependent Claim
1 words
N-9-fluorenylmethyloxycarbonyl-L-alanine-N-carboxyanhydride.
Claim 39
Dependent Claim
1 words
N-α-(9-fluorenylmethyloxycarbonyl)-N-ε-t-butyloxycarbonyl-L-lysine-N-carboxyanhydride.
Claim 40
Dependent Claim
1 words
N-α-(9-fluorenylmethyloxycarbonyl)-N-ε-t-butyloxycarbonyl-L-lysine-N-carboxyanhydride.
Claim 41
Dependent Claim
1 words
N-benzyloxycarbonyl-L-alanine-N-carboxyanhydride.
Claim 42
Dependent Claim
1 words
N-benzyloxycarbonyl-L-alanine-N-carboxyanhydride.
Claim 43
Dependent Claim
1 words
N-benzyloxycarbonyl-L-leucine-N-carboxyanhydride.
Claim 44
Dependent Claim
1 words
N-benzyloxycarbonyl-L-leucine-N-carboxyanhydride.
Claim 45
Dependent Claim
1 words
N-phenyloxycarbonyl-L-valine-N-carboxyanhydride.
Claim 46
Dependent Claim
1 words
N-phenyloxycarbonyl-L-valine-N-carboxyanhydride.
Claim 47
Dependent Claim
1 words
N-ethyloxycarbonyl-L-alanine-N-carboxyanhydride.
Claim 48
Dependent Claim
1 words
N-ethyloxycarbonyl-L-alanine-N-carboxyanhydride.
Claim 49
Dependent Claim
1 words
N-benzyloxycarbonyl-L-phenylalanine-N-carboxyanhydride.
Claim 50
Dependent Claim
1 words
N-benzyloxycarbonyl-L-phenylalanine-N-carboxyanhydride.
Claim 51
Dependent Claim
1 words
N-phenyloxycarbonyl-L-alanine-N-thiocarboxyanhydride.
Claim 52
Dependent Claim
1 words
N-phenyloxycarbonyl-L-alanine-N-thiocarboxyanhydride.
Claim 53
Dependent Claim
1 words
N-(9-fluorenylmethyloxycarbonyl)-O-t-butyl-L-threonine-N-carboxyanhydride.
Claim 54
Dependent Claim
1 words
N-(9-fluorenylmethyloxycarbonyl)-O-t-butyl-L-threonine-N-carboxyanhydride.
Claim 55
Dependent Claim
1 words
N-9-fluorenylmethyloxycarbonyl-β-alanine-N-carboxyanhydride.
Claim 56
Dependent Claim
1 words
N-9-fluorenylmethyloxycarbonyl-β-alanine-N-carboxyanhydride.
Claim 57
Dependent Claim
1 words
N-t-butyloxycarbonyl-L-alanine-N-carboxyanhydride.
Claim 58
Dependent Claim
1 words
N-t-butyloxycarbonyl-L-alanine-N-carboxyanhydride.
Claim 59
Dependent Claim
1 words
N-(t-butyloxycarbonyl)-O-benzyl-L-serine-N-carboxyanhydride.
Claim 60
Dependent Claim
1 words
N-(t-butyloxycarbonyl)-O-benzyl-L-serine-N-carboxyanhydride.
Claim 61
Dependent Claim
2 words
N-phenyloxycarbonyl-1-amino-1-carboxy cyclohexane-N-carboxyanhydride.
Claim 62
Dependent Claim
2 words
N-phenyloxycarbonyl-1-amino-1-carboxy cyclohexane-N-carboxyanhydride.
Claim 63
Dependent Claim
2 words
N-ethyloxylcarbonyl-α-aminoisobutyric acid-N-carboxyanhydride.
Claim 64
Dependent Claim
2 words
N-ethyloxylcarbonyl-α-aminoisobutyric acid-N-carboxyanhydride.
Claim 65
Independent Claim
106 words
A method for the synthesis of a polypeptide chain wherein an amino acid component is allowed to react with a second similar or dissimilar amino acid component and the process repeated until the desired polypeptide is obtained, the improvement comprising using as the protected amino acid component in at least one of said reactions a compound having the structure: ##STR10## wherein R and R' are hydrogen, alkyl, aryl, substituted alkyl, or substituted aryl and at least one of R and R' is other than hydrogen; R" is alkyl, aryl, substituted alkyl or substituted aryl; Z is oxygen or sulfur; and n is 0, 1 or 2.
Claim 66
Independent Claim
106 words
A method for the synthesis of a polypeptide chain wherein an amino acid component is allowed to react with a second similar or dissimilar amino acid component and the process repeated until the desired polypeptide is obtained, the improvement comprising using as the protected amino acid component in at least one of said reactions a compound having the structure: ##STR10## wherein R and R' are hydrogen, alkyl, aryl, substituted alkyl, or substituted aryl and at least one of R and R' is other than hydrogen; R" is alkyl, aryl, substituted alkyl or substituted aryl; Z is oxygen or sulfur; and n is 0, 1 or 2.
Claim 67
Dependent Claim
20 words
A method according to claim 49 wherein R" is an alkyl, or substituted alkyl of 1 to 20 carbon atoms.
Claim 68
Dependent Claim
15 words
A method according to claim 50 wherein R" is lower alkyl or substituted lower alkyl.
Claim 69
Dependent Claim
10 words
A method according to claim 50 wherein R" is t-butyl.
Claim 70
Dependent Claim
13 words
A method according to claim 49 wherein R" is aryl or substituted aryl.
Claim 71
Dependent Claim
13 words
A method according to claim 53 wherein R" is phenyl or substituted phenyl.
Claim 72
Dependent Claim
13 words
A method according to claim 49 wherein R" is aralkyl or substituted aralkyl.
Claim 73
Dependent Claim
13 words
A method according to claim 55 wherein R" is benzyl or substituted benzyl.
Claim 74
Dependent Claim
10 words
A method according to claim 55 wherein R" is p-methoxybenzyl.
Claim 75
Dependent Claim
13 words
A method according to claim 55 wherein R" is 9-fluorenylmethyl or substituted 9-fluorenylmethyl.
Claim 76
Dependent Claim
25 words
A method according to claim 49 wherein at least one of R or R' is the side chain of a protected or unprotected amino acid.
Claim 77
Independent Claim
143 words
A method for the solid phase synthesis of a polypeptide chain on a soluble or insoluble support wherein a protected amino acid component is coupled by condensation reaction to the support containing substituent groups reactive with the carboxyl terminus end of said amino acid component. The coupled protected amino acid component is deprotected, neutralized if necessary, and a second similar or dissimilar protected amino acid component coupled to said deprotected amino acid compound, and the process repeated until the desired polypeptide is obtained, the improvement comprising using as the protected amino acid component in at least one of said reactions a compound having the structure: ##STR11## wherein R and R' are hydrogen, alkyl, cycloakyl, substituted alkyl, substituted cycloalkyl, aryl, or substituted aryl; R" is alkyl, aryl, substituted alkyl or substituted aryl; Z is oxygen or sulfur; and n is 0, 1 or 2.
Claim 78
Independent Claim
143 words
A method for the solid phase synthesis of a polypeptide chain on a soluble or insoluble support wherein a protected amino acid component is coupled by condensation reaction to the support containing substituent groups reactive with the carboxyl terminus end of said amino acid component. The coupled protected amino acid component is deprotected, neutralized if necessary, and a second similar or dissimilar protected amino acid component coupled to said deprotected amino acid compound, and the process repeated until the desired polypeptide is obtained, the improvement comprising using as the protected amino acid component in at least one of said reactions a compound having the structure: ##STR11## wherein R and R' are hydrogen, alkyl, cycloakyl, substituted alkyl, substituted cycloalkyl, aryl, or substituted aryl; R" is alkyl, aryl, substituted alkyl or substituted aryl; Z is oxygen or sulfur; and n is 0, 1 or 2.
Claim 79
Dependent Claim
20 words
A method according to claim 60 wherein R" is an alkyl or substituted alkyl of 1 to 20 carbon atoms.
Claim 80
Dependent Claim
15 words
A method according to claim 61 wherein R" is lower alkyl or substituted lower alkyl.
Claim 81
Dependent Claim
10 words
A method according to claim 62 wherein R" is t-butyl.
Claim 82
Dependent Claim
13 words
A method according to claim 60 wherein R" is aryl or substituted aryl.
Claim 83
Dependent Claim
13 words
A method according to claim 64 wherein R" is phenyl or substituted phenyl.
Claim 84
Dependent Claim
13 words
A method according to claim 60 wherein R" is aralkyl or substituted aralkyl.
Claim 85
Dependent Claim
13 words
A method according to claim 66 wherein R" is benzyl or substituted benzyl.
Claim 86
Dependent Claim
10 words
A method according to claim 66 wherein R" is p-methoxybenzyl.
Claim 87
Dependent Claim
13 words
A method according to claim 66 wherein R" is 9-fluorenylmethyl or substituted 9-fluorenylmethyl.
Claim 88
Dependent Claim
25 words
A method according to claim 60 wherein at least one of R or R' is the side chain of a protected or unprotected amino acid.
Claim 89
Independent Claim
103 words
A method of preparing urethane-protected amino acid N-carboxyanhydrides or N-thiocarboxyanhydrides having the structure: ##STR12## wherein R and R' are hydrogen, alkyl, cycloalkyl, substituted alkyl, substituted cycloalkyl, aryl, or substituted aryl; R" is alkyl, aryl, substituted alkyl or substituted aryl; Z is oxygen or sulfur; and n is 0, 1 or 2, comprising reacting an amino acid N-carboxyanhydride or N-thiocarboxyanhydride having the structure: ##STR13## wherein R, R', Z and n are as designated above, with a haloformate having the structure: ##STR14## wherein X is halogen and R" is as designated above, in an inert diluent, under anhydrous conditions and in the presence of N-methylmorpholine.
Claim 90
Independent Claim
103 words
A method of preparing urethane-protected amino acid N-carboxyanhydrides or N-thiocarboxyanhydrides having the structure: ##STR12## wherein R and R' are hydrogen, alkyl, cycloalkyl, substituted alkyl, substituted cycloalkyl, aryl, or substituted aryl; R" is alkyl, aryl, substituted alkyl or substituted aryl; Z is oxygen or sulfur; and n is 0, 1 or 2, comprising reacting an amino acid N-carboxyanhydride or N-thiocarboxyanhydride having the structure: ##STR13## wherein R, R', Z and n are as designated above, with a haloformate having the structure: ##STR14## wherein X is halogen and R" is as designated above, in an inert diluent, under anhydrous conditions and in the presence of N-methylmorpholine.
Claim 91
Dependent Claim
18 words
A method according to claim 71 wherein the urethane-protected amino acid N-carboxyanhydride reaction product is recovered by crystallization.
References Cited (Backward Citations)
US4267344A
Cited
US4038282A
Cited
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1993-08-06 | 1994-02-05 | 1994-08-07 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-08-06 | 1998-02-05 | 1998-08-07 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-08-06 | 2002-02-05 | 2002-08-07 | $7700.00 | Window Closed / Lapsed |