Pharmaceutical green chemistry in peptide synthesis – A snapshot on the role of solvents in SPPS
Solid phase peptide synthesis (SPPS) is a widely used technology for the production of peptides at lab and industrial level. During the last 15 years several research groups worked on the development of environmentally friendly protocols for large scale production. New protective groups as well as coupling agents have been introduced at industrial level. In the attempt to make greener the SPPS technology, several more sustainable solvents have been proposed to replace the reprotoxic DMF or NMP and to limit acetonitrile/water for the purification step. In this work, the results of these studies have been summarized to outline future possible scenarios in pharmaceutical drug manufacturing.
Process sustainability represents a fundamental issue to be considered in pharmaceutical industry during the design of industrial synthesis. Green metrics and EH&S parameters are nowadays used to evaluate the entire supply chain from basic chemicals to the final Active Pharmaceutical Ingredients (APIs). Green metrics, in addition to other factors, like cost and quality (GMP) are critical to assess the medium/long term sustainability. This is a necessary activity to guarantee the market and the patient against costs/price fluctuation and market shortage (1), clearly representing a must for critical care medicine. Pharmaceutical green chemistry is an area where the collaboration between academia and industry is fundamental to identify the main advances and performing methodologies (2). As reported by Sheldon in 2004, the pharmaceutical industry is the most environmental impactful sector if compared to bulk and fine chemicals (3). The environmental i ... ...