Synthetic toolbox: Route selection

Issues on a small scale

Within medicinal chemistry, the need to synthesise small amounts of a large number of analogues in a short time period can often lead to preference for tried and tested methodologies.  This can be to the detriment of efficiency and often using reagents that would not be suitable for use on a larger scale due to, for example, safety issues.  However green chemistry and medicinal chemistry are not mutually exclusive and adoption of green methodologies at an early stage in drug design provides the opportunity not only to reduce the environmental impact of small scale discovery research, but also to facilitate a smoother transition when promising candidates are scaled-up.  To put this into context, it has been estimated that the drug discovery stage of the pharmaceutical industry as a whole produces between 200,000 and 2 million kg of waste on a yearly basis (based on annual worldwide production of active pharmaceutical ingredient and typical mass intensities from the ACS GCI Pharmaceutical Roundtable (ACS GCIPR) companies and taking into consideration annual new drug applications (NDAs), candidate survival rates and the ranges of weights of APIs produced for each R&D stage).[1] 


  1. B. W. Cue, Green Chemistry Strategies for Medicinal Chemists, in Green Techniques for Organic Synthesis and Medicinal Chemistry, John Wiley & Sons, Ltd, 2012, pp. 551-572.