Patent EP0144170A1 successfully refreshed from Google Patents.
EP0144170A1
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EP
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Biosynthesis of unnatural cephalosporins
Assignee: Queen's University
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Filing: 1984-11-08
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Granted: —
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Expires: 2004-11-08
Abstract
Abstract A process for producing unnatural penicillins and cephalosporin derivatives thereof in which peptide analogs of ACV in which the L-a-aminodipyl moiety is replaced by L-S-carboxymethyl cysteine or other substituents, are reacted with cyclase, epimerase and ring expansion enzyme isolated from a cell free extract of a prokaryotic organism such as S. clavuligerus. The product depends upon the presence or absence of co-factors such as ferrous ion, a-ketoglutarate, and ascorbate. In an alternative embodiment, a penicillin analog having the formula may be reacted with L-cysteine to produce an analog of isopenicillin N which may be reacted with the enzyme reagent to produce the desired penicillin or cephalosporin.
Inventors
- 👤 Saul Wolfe
- 👤 Donald Westlake
- 👤 Susan Jensen
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-06 08:52
CPC Classifications
C; C07; C07K; C07K5/00; C07K5/04; C07K5/06; C07K5/06139; A; A61; A61P; A61P31/00; A61P31/04; C12; C12N; C12N9/00; C12P; C12P35/00; C12P35/06; C12P37/00; A61K; A61K38/00
Claims Analysis
Total Claims: 19
Claim 1
Independent Claim
85 words
A process for producing penicillins of the formula where X = S , SO, SO 2 , O, NH, NR, PO, PR, Se, SeO or SeO 2 and R = alkyl or aryl characterized in that a peptide starting material having the formula where X and R are as above defined, is reacted with cyclase, epimerase and a ring expansion enzyme isolated from a cell free extract of a prokaryotic organism for sufficient time and in the presence of sufficient co-factors to provide said penicillin.
Claim 2
Dependent Claim
85 words
A process for producing penicillins of the formula where X = S , SO, SO 2 , O, NH, NR, PO, PR, Se, SeO or SeO 2 and R = alkyl or aryl characterized in that a peptide starting material having the formula where X and R are as above defined, is reacted with cyclase, epimerase and a ring expansion enzyme isolated from a cell free extract of a prokaryotic organism for sufficient time and in the presence of sufficient co-factors to provide said penicillin.
Claim 3
Dependent Claim
89 words
A process for producing cephalosporins of the formula where X = S, SO, SO 2 , O, NH, NR, PO, PR, Se, SeO or SeO 2 and R = alkyl or aryl characterized in that a peptide starting material having the formula where X and R are as above defined, is reacted with cyclase, epimerase and a ring expansion enzyme isolated from a cell free extract of a prokaryotic organism for sufficient time and in the presence of a-ketoglutarate, ferrous ion and ascorbate so as to produce said cephalosporin.
Claim 4
Dependent Claim
89 words
A process for producing cephalosporins of the formula where X = S, SO, SO 2 , O, NH, NR, PO, PR, Se, SeO or SeO 2 and R = alkyl or aryl characterized in that a peptide starting material having the formula where X and R are as above defined, is reacted with cyclase, epimerase and a ring expansion enzyme isolated from a cell free extract of a prokaryotic organism for sufficient time and in the presence of a-ketoglutarate, ferrous ion and ascorbate so as to produce said cephalosporin.
Claim 5
Dependent Claim
89 words
A process for producing cephalosporins of the formula where X = S, SO, S0 2 , 0, NH, NR, PO, PR, Se, SeO or SeO 2 and R = alkyl or aryl characterized in that a peptide starting material having the formula where X and R are as above defined, is reacted with cyclase, epimerase and a ring expansion enzyme isolated from a cell free extract of a prokaryotic organism for sufficient time and in the presence of a-ketoglutarate, ferrous ion and ascorbate so as to produce said cephalosporin.
Claim 6
Dependent Claim
89 words
A process for producing cephalosporins of the formula where X = S, SO, S0 2 , 0, NH, NR, PO, PR, Se, SeO or SeO 2 and R = alkyl or aryl characterized in that a peptide starting material having the formula where X and R are as above defined, is reacted with cyclase, epimerase and a ring expansion enzyme isolated from a cell free extract of a prokaryotic organism for sufficient time and in the presence of a-ketoglutarate, ferrous ion and ascorbate so as to produce said cephalosporin.
Claim 7
Dependent Claim
71 words
: A process for producing analogs of penicillin-N having the formula Where X = S, SO, SO 2 , O, NH, NR, PO, PR, Se, SeO or SeO 2 and R = alkyl or aryl characterized in that an analog of isopenicillin-N having the formula where X and R are as above defined, is reacted with an epimerase ring expansion enzyme isolated from a cell-free extract of a prokaryotic cephalosporin-producing organism.
Claim 8
Dependent Claim
71 words
: A process for producing analogs of penicillin-N having the formula Where X = S, SO, SO 2 , O, NH, NR, PO, PR, Se, SeO or SeO 2 and R = alkyl or aryl characterized in that an analog of isopenicillin-N having the formula where X and R are as above defined, is reacted with an epimerase ring expansion enzyme isolated from a cell-free extract of a prokaryotic cephalosporin-producing organism.
Claim 9
Dependent Claim
69 words
A process for providing cephalosporins of the formula where X = S, SO, SO 2 , O, NH, NR, PO, PR, Se, SeO or SeO 2 and R = alkyl or aryl characterized in that an analog of isopenicillin-N having the formula where X and R are as above defined, is reacted with epimerase and a ring expansion enzymeisolated from a cell free extract of a prokaryotic cephalosporin-producint organism.
Claim 10
Dependent Claim
69 words
A process for providing cephalosporins of the formula where X = S, SO, SO 2 , O, NH, NR, PO, PR, Se, SeO or SeO 2 and R = alkyl or aryl characterized in that an analog of isopenicillin-N having the formula where X and R are as above defined, is reacted with epimerase and a ring expansion enzymeisolated from a cell free extract of a prokaryotic cephalosporin-producint organism.
Claim 11
Dependent Claim
30 words
A process as claimed in any of Claims 1 to 5 characterized in that said prokaryotic organism is selected from the group comprising S. clavuligerus, S. cattleya and S. lipmanii.
Claim 12
Dependent Claim
73 words
A process for producing δ-(L-carboxymethyl- .cysteinyl)-L-cysteinyl-D-valine and dimers thereof characterized by (a) partially protecting amino and α-carboxymethylcysteinyl groups in L-carboxymethylcysteine by addition of protecting groups; (b) forming a fully protected tripeptide by coupling said partially protected L-carboxymethyl cysteine with partially protected L-cysteinyl-D-valine; (c) detritylating said fully protected tripeptide by reaction with iodine; and (d) completely deprotecting said tripeptide by treatment of said detritylated product with formic acid so as to produce δ-(L-carboxymethylcysteinyl)-L-cysteinyl-D-valine disulfide.
Claim 13
Dependent Claim
73 words
A process for producing δ-(L-carboxymethyl- .cysteinyl)-L-cysteinyl-D-valine and dimers thereof characterized by (a) partially protecting amino and α-carboxymethylcysteinyl groups in L-carboxymethylcysteine by addition of protecting groups; (b) forming a fully protected tripeptide by coupling said partially protected L-carboxymethyl cysteine with partially protected L-cysteinyl-D-valine; (c) detritylating said fully protected tripeptide by reaction with iodine; and (d) completely deprotecting said tripeptide by treatment of said detritylated product with formic acid so as to produce δ-(L-carboxymethylcysteinyl)-L-cysteinyl-D-valine disulfide.
Claim 14
Dependent Claim
1 words
6-(L-carboxymethylcysteinyl)-L-cysteinyl-D-valine.
Claim 15
Dependent Claim
1 words
6-(L-carboxymethylcysteinyl)-L-cysteinyl-D-valine.
Claim 16
Dependent Claim
28 words
A cephalosporin of the formula where X= S, SO, SO 2 , 0, NH, NR, PO, PR, Se, SeO, or SeO 2 and R = alkyl or aryl.
Claim 17
Dependent Claim
28 words
A cephalosporin of the formula where X= S, SO, SO 2 , 0, NH, NR, PO, PR, Se, SeO, or SeO 2 and R = alkyl or aryl.
Claim 18
Dependent Claim
23 words
An orally absorbable pharmaceutical composition characterized in that it comprises a cephalosporin of the formula in admixture with a pharmaceutically acceptable carrier therefor.
Claim 19
Dependent Claim
23 words
An orally absorbable pharmaceutical composition characterized in that it comprises a cephalosporin of the formula in admixture with a pharmaceutically acceptable carrier therefor.
References Cited (Backward Citations)
US4307192A
Cited
EP0102216A2
Cited
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