The discovery that enzymes could function efficiently in organic solvents revolutionized their use in industry but represented a change from the natural “green” solvent, water, to a host of environmentally undesirable solvents. Considerable effort is being devoted to making such processes greener again. Bio-based solvents, derived from waste biomass, possess the desirable attributes of traditional organic solvents but are more conducive to a circular bio-based economy. Although biocatalytic oxidations have only been tested in bio-based ether solvents, there is considerable scope for expanding this to include bio-based ester solvents. Alternatively, both ionic liquids and deep eutectic solvents, with tunable properties, are proving very interesting solvents for biocatalytic oxidations. In particular, oxidative depolymerization of lignin, catalyzed by laccases, has been extensively investigated. Finally, designer amphiphiles can facilitate the formation of micelles that act as hydrophobic nanoreactors for performing biocatalytic oxidation processes while surrounded by aqueous buffer as solvent.

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.

Acylated Morita-Baylis-Hillman (MBH) adducts were synthesised and subjected to enzymatic kinetic resolution (EKR) by hydrolysis employing various lipase enzymes: from P. fluorescens, P. cepacia (PCL), C. antarctica A (CAL−A), C. antarctica B (CAL−B) and Novozyme 435. In a number of instances enantiopure Morita-Baylis-Hillman acetates or butyrates and their corresponding hydrolysed MBH adducts were obtained with ee values of >90 %, at ca. 50 % conversion, corresponding to enantiomeric ratio (E) values of >200. Enantioselective transesterification reactions on MBH adducts was achieved using acyl anhydrides in THF or the greener organic solvent 2-MeTHF in the presence of CAL−A. This is the first report of successful lipase-catalysed EKR of aromatic MBH adducts by transesterification in organic medium.

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.