7-AminoCephalosporanic acid (7-ACA): Cephalosporin C

First isolated in 1948 by Brotzu in Cagliari (Italy), Cephalosporins belong to the Beta-lactam class of antibiotics. Second only to the penicillins, Cephalosporin C is manufactured on a very large scale with several thousands of tonnes per year.

Most of the bulk processes start with the fermentation of Cephalosporin C which is then recovered and transformed in 7-ACA which then serves as the nucleus for many of the synthetic Cephalosporin antibiotics available today.

Currently in their third generation, cephalosporin antibiotics are active against a wide range of bacteria. Originally, the commercial processes were based on solvent extraction. However, as this is a more complicated system as compared to the penicillins, current process are based on the more selective capabilities of polymeric media.

Key Points

Closely related Impurities: The fermentation of Cephalosporin C produces two closely related molecules - Desacetyl- and Desacetoxy-. These impurities can be separated by careful optimisation of the process conditions on the principal adsorption column where the enhanced chromatography of Amberlite XAD1600 would be of interest.

Yield and throughput: Cephalosporin C is not thermal stable, particularly at low pH or at pH>8. An important consideration is therefore the process cycle time and overall yield in the recovery process. Dow experts can help optimise the process to minimise losses.

Enzyme immobilisation: Dow can supply polymeric enzyme supports.

Purification of Semi-synthetic Cephalosporins: Using the same types of polymers as those used in the initial recovery process, Dow can offer advise and support for the downstream chromatographic purification.

Product Guidelines

Pre-column: Amberlite™ XAD™1180N

Main adsorption column: Amberlite™ XAD™1600N, Amberlite™ XAD™16N

Decolourisation: Amberlite™ FPA53

Enzyme immobilisation: Duolite™ A568

Purification of Semi-synthetic Cephalosporin: Amberchrom™ products.

Related Information

A New Cost Effective Adsorbent for the Capture and Purification of Antibiotics

Poster Session PREP 2008

Abstract: The purification of antibiotics such as Cephalosporin C from complex fermentation broths can be accomplished effectively using chromatographic adsorbents. A new chromatographic adsorbent, Amberlite™XAD™18, has recently been introduced for the purification of antibiotics. Amberlite™ XAD™18 is a highly cross linked, polystyrenic adsorbent that has high capacity and excellent selectivity. Additionally the particle size distribution of this new adsorbent allows the use of either fixed bed column mode or simulated moving bed (SMB) operation. This work will demonstrate the utility of Amberlite™ XAD™18 for the purification of antibiotics. Read more (pdf file: 99 kb).

References

WO9950271 Novel process for the fermentative production of cephalosporin, DSM N.V.
Inventor(s):BOOGERS, Ilco, Adrianus, Lambertus, Antonius ; VAN DE SANDT, Emilius, Johannes, Albertus, Xaverius ; SCHIPPER, Dick

US3914157, Preparation of anbibiotics by fermentation, Merck & Co., Inc.
Inventor(s):Stapley, Edward O. ;Mata, Justo M.