Deep Eutectic Solvents for the Enzymatic Synthesis of Sugar Esters: A Generalizable Strategy?

Abstract

Sugar (fatty acid) esters are industrially relevant compounds, with a cumbersome production process due to the solubility issues of the substrates, which forces the use of environmentally unfriendly reaction media. Herein, deep eutectic solvents (DESs) are considered as a promising solution: several literature examples use glucose and different acyl donors to illustrate the efficient synthesis of sugar esters in classic DESs like choline chloride/urea (ChCl/U). However, this paper discloses that when sugars like lactose or other disaccharides are used, enzymes cannot efficiently perform (trans)esterifications in DESs, while the same reaction can proceed in mixtures like pyridine/ tetrahydrofuran (Py/THF). This could be explained by computational solubility studies and molecular dynamics simulations of both reaction media, showing two effects: (i) on the one hand, large acyl donors (more than C10) display poor solubility in DESs and (ii) on the other hand, disaccharides interact with DES components. Thus, the DES affects the conformation of lactose (compared to the conformation observed in the Py/THF mixture), in such a way that the enzymatic reaction results impaired. Despite that classic DESs (e.g., ChCl/U) may not be useful for generalizing their use in saccharide ester syntheses, the achieved theoretical understanding of the reaction may enable the design of future DESs that can combine enzyme compatibility with ecofriendliness and efficiency in sugar chemistry.

Stereoselective Catalytic Synthesis of Bioactive Compounds in Natural Deep Eutectic Solvents (NADESs): A Survey across the Catalytic Spectrum

“…On the downside, a recent study from Ubialli's group addressed the problems involved in the synthesis of sugar fatty acid esters from disaccharides, like lactose, using choline chloride-based NADES [29]. They encountered difficulties in conducting this transformation using standard Novozym lipases (Scheme 4).…”

Biocatalysis for the Synthesis of Active Pharmaceutical Ingredients in Deep Eutectic Solvents: State-of-the-Art and Prospects

“…Also, due to the robustness and cofactor-independency, most hydrolases are used either in purified form or in crude isolated form. Pleasantly, large quantities of industrially marketable compounds have been produced [76], such as esters as flavor additives [167,168], glycolipids as surfactants [90,[97][98][99][100]169], biodiesel [104,106,107,170,171], bio-based polyesters and polymers [99,101,172], and pharmaceutical and cosmeceutical intermediates [91,96,[173][174][175][176][177][178].…”

“…Some comprehensive review articles on the topic of 'combining enzymes and DESs for organic synthesis' were published recently [88]. These organic syntheses target miscellaneous valuable chemicals including pharmaceutical-relevant compounds [89,90], cosmetics [81,[91][92][93], food industrial chemicals [94][95][96], surfactants [97][98][99][100], polymers [101][102][103], biodiesel [104][105][106][107][108], and so on. To complement these works, this review is dedicated to biocatalysis in DESs with a specific focus on syntheses of various building blocks for APIs, potential pro-drugs, and pharmaceutical-relevant compounds.…”

Eutectogels as Promising Materials in Biocatalysis

“…[8] The unique industrially valuable advantages of many DES, such as low cost, easy preparation, low volatility, and non-toxicity, make them particularly attractive as enzymatic reaction media, and it has become a trending topic nowadays. [9][10][11] Several review articles addressing biocatalysis in DES have been published for interested readers. [12][13][14][15][16][17] In this context, we see an unparalleled opportunity for pushing this field toward enzyme immobilization into DEShosting soft materials, called "eutectogels", benefiting from the well-known advantages of solid supports such as higher enzyme stability, broader biocatalyst applicability, recycling, and continuous operation possibilities.…”

“…DES has been demonstrated to enhance substrate solubility and stability of different enzymes, including hydrolases, oxidoreductases, peroxidases, transferases, and lyases, spanning from single to multistep transformations involving organocatalyst/enzyme and metal/enzyme combinations [8] . The unique industrially valuable advantages of many DES, such as low cost, easy preparation, low volatility, and non‐toxicity, make them particularly attractive as enzymatic reaction media, and it has become a trending topic nowadays [9–11] . Several review articles addressing biocatalysis in DES have been published for interested readers [12–17] …”