Process for preparing cephalosporanic acid derivatives using alpha-ketoacid derivatives
AssigneeBioferma Murcia S.A.
InventorsAlvaro Sanchez-Ferrer, Jose Aniceto Lopez-Mas, Francisco Garcia-Carmona
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Abstract
A process for preparing cephalosporanic acid derivatives comprises the steps of enzymatically converting a 3-thiolated cephalosporin C compound of formula III:— 1 into a 3-thiolated-α-ketoadipyl-7-aminocephalosporanic acid derivative of formula IV: 2 wherein R is a heterocyclic group comprising at least a nitrogen atom. Compounds of formula IV are used in the preparation of cephalosporin C antibiotics and derivatives thereof.
Claims62
A process for preparing cephalosporanic acid derivatives comprising the steps of:—
- enzymatically converting a 3-thiolated cephalosporin C compound of formula III:—
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- into a 3-thiolated-α-ketoadipyl-7-aminocephalosporanic acid derivative of formula IV:
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- wherein r is a heterocyclic group comprising at least a nitrogen atom.
A compound of the Formula:—
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- wherein in formula IV, R is 1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl.
A compound of the Formula:—
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- wherein in formula IV, R is 1-methyl-1H-tetrazol-5-yl.
Use of an intermediate compound of the formula:—
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- in a process for preparing cephalosporin C antibiotics wherein in formula IV R is 5-methyl-1,3,4-thiadiazol-2-yl.
A process for preparing 3-thiolated cephalosporanic acid derivatives comprising the steps of;—
- enzymatically converting a compound of formula III
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- into a 3-thiolated-α-ketoadipyl-7-aminocephalosporanic acid derivative of formula IV:
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- and enzymatically converting a compound of formula IV to form a 3-thiolated 7-ACA compound of formula I
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- wherein R is a heterocyclic group comprising at least one nitrogen atom and R1 and R2 are both hydrogen atoms or one of them is a hydrogen atom and the other is an acyl donor.
A process for preparing cephalosporanic acid derivatives comprising the steps of:—
- reacting cephalosporin C with a thiol compound of the general formula II
- R—SH II
- wherein R is a heterocyclic group comprising at least one nitrogen atom,
- to form a 3-thiolated cephalosporin Compound of formula III
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- wherein R is as defined above,
- and, after formation of the compound of formula III removing excess thiol of formula II.
A compound of the Formula:—
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- wherein in formula III R is 5-methyl-1,3,4-thiadiazol-2-yl.
A compound of the Formula:—
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- wherein in formula III R is 1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl.
A process for preparing cephalosporanic acid dervatives comprising the step of:
- enzymatically converting a compound of formula IV
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- to form a compound of formula I
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- wherein R is a heterocyclic group comprising at least one nitrogen atom and R1 and R2 are both hydrogen atoms or one of them is a hydrogen atom and the other is an acyl donor.
Dependencies are inferred from the claim text.