Cyrene: A Green Solvent for the Synthesis of Bioactive Molecules and Functional Biomaterials

Abstract

In the panorama of sustainable chemistry, the use of green solvents is increasingly emerging for the optimization of more eco-friendly processes which look to a future of biocompatibility and recycling. The green solvent Cyrene, obtained from biomass via a two-step synthesis, is increasingly being introduced as the solvent of choice for the development of green synthetic transformations and for the production of biomaterials, thanks to its interesting biocompatibility, non-toxic and non-mutagenic properties. Our review offers an overview of the most important organic reactions that have been investigated to date in Cyrene as a medium, in particular focusing on those that could potentially lead to the formation of relevant chemical bonds in bioactive molecules. On the other hand, a description of the employment of Cyrene in the production of biomaterials has also been taken into consideration, providing a point-by-point overview of the use of Cyrene to date in the aforementioned fields.

Keywords: cyrene; green chemistry; green synthesis; nanomaterials; sustainable chemistry.

Scheme 2

Synthesis of amides from acid chlorides in Cyrene.

Figure 1

Structure of Cyrene and its most relevant “green” properties.

Scheme 1

Chemical process from cellulose to Cyrene.

Figure 2

Reactivity of Cyrene; (a) reactivity of carbonyl group of Cyrene; (b) enol-type reactivity of Cyrene; (c) reduction of Cyrene; (d) oxidation of Cyrene.

Scheme 3

HATU/DIPEA-mediated synthesis of amides and peptides in Cyrene.

Scheme 4

Synthesis of ureas from isocyanates.

Scheme 5

Synthesis of isothiocyanates from isocyanide and elemental sulfur.

Scheme 6

Sonogashira reaction using Cyrene.

Scheme 7

Suzuki–Miyaura cross-coupling in Cyrene as the medium.

Scheme 8

Heck reaction between iodobenzene and styrene in Cyrene.

Scheme 9

Baylis–Hillman reaction.

Scheme 10

Difluoromethylation of heteroarenes and acetylenes with TMSCHF₂ using Cyrene as the medium.

Scheme 11

Fluorination reaction.

Scheme 12

Green synthesis of the antidepressant drug Bupropion.

Scheme 13

Menschutkin reaction using Cyrene as the solvent.

Scheme 14

Formylation of amines with CO₂ and phenylsilane in Cyrene, and its application to the synthesis of benzothiazoles.

Scheme 15

Microwave-assisted multicomponent reaction to form bipyridine analogues.

Scheme 16

Biocatalyzed reduction of α-ketoesters to α-hydroxyesters in Cyrene.

Scheme 17

Lipase-catalyzed esterification of benzoic acid and glycerol using Cyrene as the reaction medium.

Figure 3

Hydration of Cyrene and formation of PLGA-NPs.

Figure 4

Liquid-phase exfoliation method providing higher loading.

Figure 5

Schematic representation of the MOF’s structure.

Scheme 18

Cyrene self-aldol condensation.

Scheme 19

Chemical modifications of kraft lignin in Cyrene.