I happened to notice a post on LinkedIn about an ACS Webinar last week entitled ‘Sustainable Manufacturing – Green Chemistry Breakthroughs in Pharma’. I’m glad I did as the two talks were excellent (as you’d expect considering they featured the 2024 Peter J. Dunn Award winners). If you’re interested in making your own processes more sustainable but aren’t aware of the Peter J Dunn Award or the ACS Green Chemistry Institute (ACS GCI), I urge you to look them up.  The ACS GCI has developed a number of invaluable tools which are available via their website.  When I was in the lab, I had the reagents guide bookmarked and looked at it almost daily for hints and tips. Both speakers gave engaging accounts of how their project teams had made enormous improvements to process metrics and highlighted the ACS GCI tools they had used.

In the Boehringer Ingelheim case, a key building block was required in ton quantities to support several projects but the initial route relied on SFC separation of a racemate to deliver the required enantiomer. A new route was devised which made use of a catalytic asymmetric allylation to establish the stereocentre in high yield. The endgame strategy telescoped 5 transformations which realised a one-pot process, greatly reducing solvent usage and waste generation. Some seriously impressive metrics were shared (PMI reduced by 98%!) showing the impact of good route design.

The GSK example was from their Blenrep antibody drug conjugate project. The cytotoxic component, SG9, contains 5 amide bonds and 9 stereocentres so there is much less opportunity to redesign a synthesis, more the focus was on improving the process.  The biggest contributor to PMI was the multiple column chromatographic purifications employed.  To further complicate matters, SG9 and its later intermediates are high potency molecules so GSK employed a strategy whereby the final four steps were telescoped to minimise isolation and handling of the high potency intermediates. Many improvements were made to the existing process which resulted in huge reductions in PMI, water and energy usage.

I look forward to hearing or reading about the 2025 Award winners next year!