Active pharmaceutical ingredients (APIs) constitute a significant and growing global market. In the past few decades, labor costs, concerns regarding chemical waste, and more stringent regulations in developed countries have shifted the production of APIs to emerging economies, notably India and China. Nowadays, Europe and North America rely on imports for the majority of pharmaceuticals. The recent COVID pandemic as well as logistical challenges have called this model into question and have raised the interest in rebalancing distributed global API supply chains and possibly reshoring some API production to Europe and North America. API production often suffers from unfavorable Green Chemistry metrics, owing to complex routes, outdated chemistry for established entities, or lack of maturity of routes for newer entities. The environmental footprint of API synthesis routes benefits from renewables as starting materials. One such abundant renewable material is lignin, which can be converted to phenol and catechol. In addition, waste could be reduced by co-producing APIs in an integrated plant and the use of advanced catalysts. This Perspective demonstrates green production routes from phenol or catechol in four large scale examples: paracetamol (Tylenol (R)), acetyl salicylic acid (Aspirin (R)), amoxicillin (as sole API or as combination with potassium clavulanate (Augmentin (R)), and epinephrine (adrenaline, also as trademark Adrenaline (R)). We compare conventional routes with more modern routes with respect to Green Chemistry metrics. Overall, API production from renewable materials stands to combine low environmental footprint with high quality and economical manufacture of pharmaceuticals.
Production of active pharmaceutical ingredients (APIs) from lignin-derived phenol and catechol