Application of bio-based solvents for biocatalysed synthesis of amides with Pseudomonas stutzeri lipase (PSL)

Bio-based solvents were investigated for the biocatalysed amidation reactions of various ester-amine combinations by Pseudomonas stutzeri lipase (PSL). Reactions were undertaken in a range of green and potentially bio-based solvents including terpinolene, p-cymene, limonene, 2-methyl THF, ɣ-valerolactone, propylene carbonate, dimethyl isosorbide, glycerol triacetate and water. Solvent screenings demonstrated the importance and potential of using non-polar bio-based solvents for favouring aminolysis over hydrolysis; whilst substrate screenings highlighted the unfavourable impact of reactants bearing bulky para- or 4-substituents. Renewable terpene-based solvents (terpinolene, p-cymene, D-limonene) were demonstrated to be suitable bio-based media for PSL amidation reactions. Such solvents could provide a greener and more sustainable alternative to traditional petrochemical derived non-polar solvents. Importantly, once the enzyme (either PSL or CALB) binds with a bulky para-substituted substrate, only small reagents are able to access the active site. This therefore limits the possibility for aminolysis to take place, thereby promoting the hydrolysis. This mechanism of binding supports the widely accepted 'Ping Pong - Bi Bi' mechanism used to describe enzyme kinetics. The work highlights the need to further investigate enzyme activity in relation to para- or 4-substituted substrates. A priority in PSL chemistry remains a methodology to tackle the competing hydrolysis reaction

Tools and techniques for solvent selection: green solvent selection guides

Driven by legislation and evolving attitudes towards environmental issues, establishing green solvents for extractions, separations, formulations and reaction chemistry has become an increasingly important area of research. Several general purpose solvent selection guides have now been published with the aim to reduce use of the most hazardous solvents. This review serves the purpose of explaining the role of these guides, highlighting their similarities and differences. How they can be used most effectively to enhance the greenness of chemical processes, particularly in laboratory organic synthesis and the pharmaceutical industry, is addressed in detail

Biocatalysis in bio-derived solvents: An improved approach for medium optimisation

An improved multi-parameter approach to the correlation of enzymatic activity and solvent properties is proposed. The development of the correlation facilitated the introduction of renewable solvents in a CALB catalysed synthesis of fatty esters