Glaxo process

This work led on to a Glaxo process patent for the preparation of cephalexin (VI) using DPM protection17 (Scheme 4). The Ulverston process was developed through the pilot plant phase and proven to give high-quality Cephalexin. Moreover, the DPM ester wastes were shown to be readily oxidizable to benzophenone using aqueous nitric acid.18 Successful plant trials followed to compare both the DPM and PNB options. 

However, SB-462795 is no longer in the Glaxo Smith Kline development pipeline - most likely the reason why the GSK researchers were allowed to publish details of this process campaign. 

An alternative two-step biocatalytic route, first developed at Glaxo in the 1970s, utilized a D-amino acid oxidase and an amidase to provide 7-ACA under physiological conditions (Scheme 1.12). This process has since been established in several companies, with minor modifications. In fact, 7-ACA was manufactured by GSK at Ulverston (Cumbria, UK) using both the chemical and biocatalytic processes in parallel for a period of 2 years during which time the environmental benefits of the biocatalytic process were assessed (see Section 1.6). 

The present review illustrates that UV-vis based process analytical technology is widely discussed, but published examples are still scarce. The pharmaceutical industry, driven by the FDA s PAT initiative, can be seen as a forerunner. This is reflected by the observation that many references in this chapter are (co-) authored by representatives from pharmaceutical companies like Glaxo Wellcome and GlaxoSmithKline, ° " ° Astra Zeneca, Novartis and Eli Lilly. ... 

More recently, Glaxo SmithKline patented an efficient fermentation rente for the biosynthetic prodnetion of thymidine (thymine-2-desoxyriboside). Key to the invention is a recombinant strain that efficiently produces high titers of thymidine by blocking some enzymes in the thymidine regulating pathway. This microbial process has now replaced the chemical route and has enabled gsk to supply the anti-AIDS drug AZT (zidovudine) to third-world countries at low cost. 

A microorganism with the required activity was found as Glaxo were already developing esterases to convert cephalosporin C into desacetyl cephalosporin C and some of these proved able to prodnce cefuroxime and to be cost effective on a process scale (Figure 4.9). 

This process has been operated successfully by Glaxo on a commercial scale for over 17 years. An important advance has been the development of an acid stable form of cefuroxime by esterification of the C4 ester group that has allowed the production of products suitable for oral administration. This new product Cefuroxime axetil (trade name Zinnat) has rapidly achieved market sales of ca. 300 in 1990-91... 

Eli Lilly was the discoverer of cephalexin. They used p-nitrobenzyl (PNB) protection of die penicillin carboxyl group in their manufacturing process. Glaxo had rights to this process, as well as to market... 

Over my many years in the chemical process development business, I encountered several invaluable consultants. Notable were those in Glaxo (in addition to Sir Derek)—Professors ERH Jones (Oxford University), Maurice Stacey (Birmingham University), and Dr. (later Professor) Richard Stoodley (Newcastle University and University of Manchester Institute of Science and Technology). The latter visited us more in a lecturing capacity but was always scrupulously careful in what he said about penicillin chemistry since he also consulted for Glaxo s then arch rival, Beecham. 

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