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ABSTRACTIntroductionBiocatalysis has emerged as a powerful and useful strategy for the synthesis of active pharmaceutical ingredients (APIs). The outstanding developments in molecular biology techniques allow nowadays the screening, large-scale production, and designing of biocatalysts, adapting them to desired reactions. Many enzymes can perform reactions both in aqueous and non-aqueous media, broadening even further the opportunities to integrate them in complex pharmaceutical multi-step syntheses.Areas coveredThis paper showcases several examples of biocatalysis in the pharmaceutical industry, covering examples of different enzymes, such as lipases, oxidoreductases, and transaminases, to deliver active drugs through complex synthetic routes. Examples are critically discussed in terms of reaction conditions, motivation for using an enzyme, and how biocatalysts can be integrated in multi-step syntheses. When possible, biocatalytic routes are benchmarked with chemical reactions.Expert OpinionThe reported enzymatic examples are performed with high substrate loadings (>100 g L−1) and with excellent selectivity, making them inspiring strategies for present and future industrial applications. The combination of powerful molecular biology techniques with the needs of the pharmaceutical industry can be aligned, creating promising platforms for synthesis under more sustainable conditions.

Deep Eutectic Solvents (DES) are expected to play a pivotal role in many future chemical segments, particularly when sustainability aspects are considered. This article provides an overview of the recent granted patents related to DES, which reflects many of the practical applications that can be conceived. In the entire history of DES, more than one hundred patents have been identified, reporting strategies for areas like (bio)refineries, extraction of natural products, purification of effluents, organic synthesis, batteries, materials, etc. In many of these cases, DES are not considered to be mere innocent solvents, but their properties are tuned and adapted for the desired goals. Overall, the patent analysis reflects the potential that DES may have as emerging solutions for the Sustainable Chemistry of the future.

Organocatalysis has emerged during the last decade as a concept with a significant number of synthetic applications. Important driving forces for this growth are that organocatalytic strategies often operate at rather mild reaction conditions, with reduced waste formation, and that processes may lead to high selectivities. In this area, some organocatalytic examples have been reported in the field of ring‐opening polymerizations of lactones, as well as for some (trans)esterifications. These reactions are catalyzed by organic molecules such as α‐hydroxycarboxylic acids, amino acids, 4‐(dimethylamino)pyridine,N‐heterocyclic carbenes, guanidines, or bifunctional thiourea–amines. With regard to α‐hydroxycarboxylic acids, it is believed that these organocatalysts catalyze reactions in a similar fashion to hydrolases, such as lipases or esterases, thus leading to valuable biomimetic catalytic concepts. Importantly, advantages that are inherent to enzymatic catalysis can be combined with a broader range of potential reaction conditions (e.g., solvent‐free), or exploited for the efficient and selective (tailored) modification of synthetically challenging substrates (e.g., ring‐opening polymerizations with cellulose and other polysaccharides as initiators). Furthermore, α‐hydroxycarboxylic acids are readily accessible by biotechnological routes such as fermentation, are nontoxic, and easy to apply. Herein, the uses of these “minimal hydrolases” in catalyzing ring‐opening polymerizations and transesterifications are categorized and discussed. Albeit still at the level of proof‐of‐principle, many interesting practical applications can be conducted according to these biomimetic routes.

Benzaldehyde lyase (BAL) and benzoylformate decarboxylase (BFD) catalyse the asymmetric ligation of aliphatic aldehydes to afford enantiomerically enriched 2-hydroxy ketones. Carboligation of linear aldehydes with both enzymes results in high levels of conversion and in enantioselectivities of up to 80 % ee. In cases involving branched aliphatic aldehydes, BAL enables the carboligation of 3-methylbutanal with a high level of conversion and an enantioselectivity of 89 % ee.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Biocatalysis has been traditionally considered an environment-friendly and industrial toolbox for organic synthesis. However, in many cases these statements are not substantiated with real metrics (e.g. E-factor and productivities). This paper discusses recent developments that may contribute to generate greener biocatalytic applications with industrial interest. Namely, aqueous-based processes with extremely high substrate loadings; solvent-free reactions in which neither solvents nor water are used; and finally, biogenic solvents as well as deep eutectic solvents. From all of them, solvent-free systems are superior both in terms of greenness and industrial use (but they cannot be always implemented). The described systems can be combined in flow (continuous), and with solvent and water recycling, leading to powerful alternatives for future sustainable processes. Overall, providing metrics is key to honestly assess a biotransformation and to put forth further research to improve systems.

Lipase activity, measured as hydrolysis of tributyrin is a valid assay to quantify the lipase activity of a lyophilized crude lipase in hydrolysis reactions but it is not useful to predict the catalytic activity in lipase-catalyzed reactions in organic media. Three factors control the catalytic activity in these media: i) relative proportion of isoenzymes; ii) amount of water in the lyophilized crude enzyme and iii) amount of lipase protein in the commercial powder. Thus we propose two simple reaction tests: i) heptyl oleate synthesis (specific of lipases), ii) enantioselective esterification of (R) or (S) 2-(3-benzoyl)phenyl propionic acid. This methodology is applied to different crude lipases of Candida rugosa, obtained in different fermenter conditions and shows the origin of the unreproducibility of the synthetic data.

Working with real samples:Aqueous solutions of FeCl3–NaCl (or seawater) dehydrate xylose to afford furfural, which can extracted in situ into 2‐MTHF as second phase. Furfural is successfully obtained when aqueous nonpurified xylose effluents directly from lignocellulose fractionation are tested.

Petrochemical‐free commodities:Recent developments in the biosynthetic production of different hydrocarbons by engineered microorganisms offer further examples of how white biotechnology can provide chemicals and biofuels in a sustainable manner by coupling natural cycles or de novo‐designed metabolic routes with industrial interests. Non‐edible and cheap lignocellulosic residues are a renewable feedstock to secure the sustainability of the process.