US4554351A
Expired / Lapsed
US
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Method for the total synthesis of cyclosporins, novel cyclosporins and novel intermediates and methods for their production
Assignee: Novartis AG
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Filing: 1983-05-05
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Granted: 1985-11-19
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Expires: 2003-05-05
Abstract
Abstract A method for the total synthesis of cyclosporins, in particular Cyclosporin A, cyclosporins produced in accordance with the method of the invention and novel intermediates, in particular novel [1S, 2R, 3R]- and [1R, 2S, 3S]-1-nitrilo-1-carbonyl-3-methyl-2-oxy-heptanes and -hept-5-enes, employed in the method of the invention.
Inventors
- 👤 Roland Wenger
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 16:11
CPC Classifications
C; C07; C07D; C07D263/00; C07D263/02; C07D263/08; C07D263/16; C07D263/18; C07D263/20; C07C; C07C255/00; C07C29/00; C07C29/09; C07C29/10; C07C43/00; C07C43/02; C07C43/03; C07C43/14; C07C43/178; C07C45/00; C07C45/27; C07C45/29; C07C45/30; C07C45/61; C07C45/67; C07C45/673; C07C47/00; C07C47/20; C07C47/26; C07C47/263; C07C47/277; C07D303/00; C07D303/02; C07D303/12; C07D303/18; C07D303/20; C07D303/22; C07D317/00; C07D317/08; C07D317/10; C07D317/12; C07D317/14; C07D317/18; C07D317/20; C07D317/22; C07D317/26; C07D317/30; C07K; C07K5/00; C07K5/04; C07K5/06; C07K5/06008; C07K5/06017; C07K5/06034; C07K7/00; C07K7/64; C07K7/645; C07B; C07B2200/00; C07B2200/07; C07B2200/09; Y; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/19; Y10S930/27
Claims Analysis
Total Claims: 9
Claim 1
Independent Claim
122 words
A compound of formula III wherein --x--y-- is --CH 2 --CH 2 -- or --CH═CH--, R 1 is hydrogen or methyl, X 1 is hydroxy or a carboxy protecting group suitable for peptide synthesis or a carboxy activating group suitable for peptide synthesis, X 2 is hydrogen or an N-protecting group suitable for peptide synthesis, and X 3 is hydrogen or an O-protecting group suitable for peptide synthesis or (X 2 +X 3 ) is a protecting group suitable for peptide synthesis bridging the 2-N and 3-O functions or (X 2 +R 1 ) is a divalent N-protecting group suitable for peptide synthesis, and wherein the positions 2, 3 and 4 have the configuration S,R and R or R,S and S respectively.
Claim 2
Dependent Claim
122 words
A compound of formula III wherein --x--y-- is --CH 2 --CH 2 -- or --CH═CH--, R 1 is hydrogen or methyl, X 1 is hydroxy or a carboxy protecting group suitable for peptide synthesis or a carboxy activating group suitable for peptide synthesis, X 2 is hydrogen or an N-protecting group suitable for peptide synthesis, and X 3 is hydrogen or an O-protecting group suitable for peptide synthesis or (X 2 +X 3 ) is a protecting group suitable for peptide synthesis bridging the 2-N and 3-O functions or (X 2 +R 1 ) is a divalent N-protecting group suitable for peptide synthesis, and wherein the positions 2, 3 and 4 have the configuration S,R and R or R,S and S respectively.
Claim 3
Dependent Claim
20 words
A compound according to claim 1 in which X 1 is hydroxy and X 2 and X 3 are hydrogen.
Claim 4
Dependent Claim
37 words
A compound according to claim 1 in which X 1 is hydroxy or a carboxy activating group and X 2 is an N-protecting group or X 1 is a carboxy protecting group and X 2 is hydrogen.
Claim 5
Dependent Claim
64 words
A compound according to claim 1 of formula III ##STR43## wherein --x--y--, R 1 , X 1 , X 2 , and X 3 are as defined in claim 25, with the proviso that at least one of X 1 , X 2 , X 3 , X 2 +X 3 or X 2 +R 1 is a protecting group suitable for peptide synthesis.
Claim 6
Dependent Claim
50 words
A compound according to claim 1, wherein R 1 and --x--y-- have the meanings given in claim 8, with the proviso that, when R 1 is methyl and --x--y-- is --CH 2 --CH 2 -- or --CH═CH--, the positions 2, 3 and 4 have the configuration R,S and S respectively.
Claim 7
Dependent Claim
29 words
A compound according to claim 2 selected from the group consisting of: (2S,3R,4R,6E)-3-hydroxy-4-methyl-2-methylamino-oct-6-enoic acid; (2R,3S,4S,6E)-3-hydroxy-4-methyl-2-methylamino-oct-6-enoic acid; (2S,3R,4R,6Z)-3-hydroxy-4-methyl-2-methylamino-oct-6-enoic acid; (2R,3S,4S,6Z)-3-hydroxy-4-methyl-2-methylamino-oct-6-enoic acid; (2S,3R,4R)-3-hydroxy-4-methyl-2-methylamino-octanoic acid; (2R,3S,4S)-3-hydroxy-4-methyl-2-methylamino-octanoic acid; (2S,3R,4R,6E)-3-hydroxy-4-methyl-2-amino-oct-6-enoic acid; and (2R,3S,4S,6E)-3-hydroxy-4-methyl-2-amino-oct-6-enoic acid.
Claim 8
Dependent Claim
35 words
A compound according to claim 4 wherein X 1 is hydroxy or a carboxy-activating group and the 2-N function is in N-protected form, or X 1 is a carboxy-protecting group and X 2 is hydrogen.
Claim 9
Dependent Claim
41 words
A compound according to claim 7, selected from the group consisting of: (4R,5S)-4-(hex-2E-en-5R-yl)-1-methyl-2-oxo-oxazolin-5-carboxylic acid; (4S,5R)-4-(hex-2E-en-5S-yl)-1-methyl-2-oxo-oxazolin-5-carboxylic acid; (4R,5S)-4-(hex-2Z-en-5R-yl)-1-methyl-2-oxo-oxazolin-5-carboxylic acid; (4S,5R)-4-(hex-2Z-en-5S-yl)-1-methyl-2-oxo-oxazolin-5-carboxylic acid; (4R,5S)-4-(2R-hexyl)-1-methyl-2-oxo-oxazolin-5-carboxylic acid; (4S,5R)-4-(2S-hexyl)-1-methyl-2-oxo-oxazolin-5-carboxylic acid; (4R,5S)-4-(hex-2E-en-5R-yl)-2-oxo-oxazolin-5-carboxylic acid; (4S,5R)-4-(hex-2E-en-5S-yl)-2-oxo-oxazolin-5-carboxylic acid; (4R,5S)-4-(hex-2E-en-5R-yl)-1,2-trimethyl-oxazolin-5-carboxylic acid; (4S,5R)-4(hex-2E-en-5S-yl)-1,2-trimethyl-oxazolin-5-carboxylic acid; (2S,3R,4R,6E)-2-(N-t.-butyloxy-carbonyl)-methylamino-3-hydroxy-4-methyl-oct-6-enoic acid; (2R,3S,4S,6E)-2-(N-t.-butyloxy-carbonyl)-methylamino-3-hydroxy-4-oct-6-enoic acid; (2S,3R,4R,6E)-2-(N-t.-butyloxy-carbonyl)-amino-3-hydroxy-4-methyl-oct-6-enoic acid; and (2R,3S,4S,6E)-2-(N-t.-butyloxy-carbonyl)-amino-3-hydroxy-4-methyl-oct-6-enoic acid.
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| 3.5 Years (Year 4) | 1988-11-18 | 1989-05-20 | 1989-11-19 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1992-11-18 | 1993-05-20 | 1993-11-19 | $3760.00 | Window Closed / Lapsed |
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