Bachem and Novo Nordisk redesign SPPS for green chemistry

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Financial Events Bachem and Novo Nordisk redesign SPPS for green chemistry 03 July 2026 Bachem and Novo Nordisk redesign SPPS for green chemistry

At Bachem, we are committed to sustainability by taking responsibility towards our employees, society, and the environment.

We aim to redesign our processes to minimize the use and generation of hazardous substances and reduce the environmental impact.

In the pharmaceutical industry, solvent consumption contributes significantly to the environmental footprint.

Research is therefore conducted to decrease solvent volumes or replace hazardous solvents with more environmentally benign alternatives.

Both approaches represent impactful innovations in API production processes.

We are a leading company in the development and manufacture of peptide and oligonucleotide APIs.

In peptide manufacturing, our most important technology and core expertise is the solid-phase peptide synthesis SPPS , a well-established method for peptide production.

In an effort to make the SPPS a greener technology, we conducted, in collaboration with our partner Novo Nordisk, three studies to propose solvent alternatives to replace the reprotoxic N,N-dimethylformamide DMF , dichloromethane DCM , and N-methyl-2-pyrrolidone NMP .

These solvents are considered the gold standards in SPPS processes for academic research and industrial production facilities alike.

They have excellent solubilization and stability properties for reagents and are the best choice in terms of resin swelling.

However, they are restricted by the European Chemicals Agency ECHA due to their hazardous nature.

Replacing DMF, DCM, and NMP with a greener alternative represents a major challenge but also offers a significant opportunity to reduce the environmental footprint of peptide manufacturing processes.

In the first study, we identified solvent viscosity and polarity, in combination, as key physicochemical parameters for SPPS.1 SPPS consists of several steps that require different optimal conditions.

The use of binary solvent mixtures enables the desired solvent properties to be achieved in a way that would not be possible with neat solvents alone.

In the search for a DMF substitute in large-scale SPPS, we therefore decided to focus on environmental and safety aspects based on the ECHA-REACH status.

We selected 19 solvents with an acceptable environmental profile herein referred to as green solvents that could be used either neat or as mixtures.

We then evaluated them by investigating reagent solubility, solvent stability, and resin swelling.

In a series of reagent dissolution, resin swelling, amino acid coupling and Fmoc-removal experiments, we showed that combining solvents offers unprecedented opportunities to predict and fine-tune overall solvent properties for different aspects of SPPS.

As a result, we found that binary mixtures of green solvents, e.g.

dimethyl sulfoxide DMSO /ethyl acetate EtOAc , DMSO/1,3-dioxolane DOL , and DMSO/2-methyl tetrahydrofuran 2-Me-THF display polarity and viscosity profiles similar to DMF and are viable, less toxic solvent alternatives for SPPS.

In our second study, we systematically investigated how the composition of green binary solvent mixtures influences Fmoc-removal, amino acid coupling, and common side reactions in SPPS.

We showed th

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