The increasingly apparent negative impact of human activities on the environment has heightened the urgency for the chemistry community to adopt greener and more sustainable practices. The E-factor can still be considered a valuable tool in this drive, particularly because of its broad acceptance and familiarity amongst both industrial and academic chemists. An important factor in broadening the adoption of green principles is ensuring that the academics responsible for training the next generation of chemists prioritise green and sustainable practices in their undergraduate and post graduate laboratories. Green metrics must be easy to use to motivate the broader chemistry community to develop greener syntheses. For maximum impact to be achieved the detail of the exact green metrics applied are less important than their adoption by the broader chemical community. Of growing importance is the replacement of fossil resources with renewable alternatives to reduce greenhouse gas emission that is a significant driver of climate change. The C factor is used to compare the carbon footprints of different routes to a particular product.

The greenness and sustainability of three different routes for the synthesis of (3R,3aS,6aR)-hexahydrofuro [2,3-b] furan-3-ol (bis-furan alcohol), an advanced intermediate for a group of HIV protease inhibitors, including the FDA approved darunavir, used in antiretroviral (ARV) therapy, were compared. The method involved a comparison of (i) waste generated using theE-factor and relative to industrial benchmarks using the innovative Green Aspiration Level (iGAL™) method, (ii) solvent usage on the basis of solvent intensity (SI) and properties according to the GSK solvent guide, and (iii) Green Motion™ scores according to the MANE methodology.