As you make dinner and clean, chop, and measure out your ingredients, little piles of waste grow on the counter or get ferried to the trashcan or compost bin. Pharmaceutical companies produce their own waste, sometimes in the form of solvents and unwanted byproducts, as they synthesize drug molecules.
To help pharma chemists find less wasteful routes to their products, members of the American Chemical Society’s Green Chemistry Institute have developed a web-based tool to predict the efficiencies of syntheses (ChemRxiv 2019, DOI: 10.26434/chemrxiv.7594646.v1). ACS publishes C&EN.
The group, which included representatives from 10 major pharma companies, collected data from those companies’ processes and the literature to build a database of about 2,000 reactions commonly used to make drugs. They used a metric called process mass intensity (PMI)—the ratio of the mass of materials used in a reaction to the mass of the products—as a measure of the efficiency of each reaction.
When users input a proposed synthetic route, the app calculates the estimated PMI of each step and the overall process, including uncertainties for the values. For instance, the tool predicted a PMI of 1,202 for a process to make Bristol-Myers Squibb’s drug brivanib alaninate. The actual PMI was 1,488, which fell within the app’s 95% confidence interval. PMIs for six of the 15 real-world processes tested by the researchers fell within the app’s 95% confidence interval.
“[The tool’s] chief value lies not in the exact value of any one prediction made, but in the ease with which it allows chemists to compare potential routes,” says Helen Sneddon, a scientific director specializing in green chemistry at GlaxoSmithKline and a member of the ACS GCI who was not an author of the paper. Juan Colberg, a green chemistry project leader at Pfizer who works with one of the paper’s authors, says the app could save chemists time by identifying which routes are likely to be greenest before they test them in the lab.
The authors declined to speak with C&EN except to confirm the scientific accuracy of our reporting to comply with the embargo policies of the journal where they have submitted their manuscript.