Mechanochemistry: a green and efficient tool to obtain curcumin derivaties with a functionalized ω-poly(ethylene glycol) Aniele de Moura a , Caroline Gagilieri a , Luiz Octávio Terciotti a , Daniel Rinaldo b and Flávio Junior Caires a,b a School of Sciences, Chemistry Department, Brazil, b Institute of Chemistry,UNESP-São Paulo State University, Brazil Curcumin is a yellow polyphenolic compound, present in Curcuma longa L. (turmeric) rhizome.¹ This compound displays a broad spectrum of biological activity, among them: antioxidant, anti-inflammatory, antitumor, and antibacterial activity; however, it is soluble in water, resulting in low bioavailability.¹ In this way, several authors have synthesized curcumin derivatives aiming to improve their properties and/or solubility. An alternative is the functionalization of these compounds with poly (ethylene glycol), which can improve its solubility in water.² However, the syntheses of Schiff bases, functionalization of poly (ethylene glycol), and also Steglich esterification, are commonly proceeded in solution, requiring long time synthesis. 1,3 Based on these, this works deals with the mechanochemical syntheses of a curcumin Schiff Base (DCG), a ω-poly (ethylene glycol) functionalized (PEG_SA), and then by esterification of the synthesized curcumin Schiff base (DCG_MONO and DCG_DIES). All the syntheses were carried out on a Retsch Mixer Mill MM 400 (Retsch, Germany), in 10 mL stainless steel or zirconium oxide jars, using one stainless steel or zirconium oxide ball. The synthesis of DCG was proceeded by milling curcumin and Glycine. After the synthesis, the compound was purified by washing with water. The synthesis of PEG_SA was carried out by milling PEG 8000 and succinic anhydride in the presence of triethylamine. The product was purified by organic extraction (water: toluene), then the aqueous solution was evaporated and purified PEG_SA was obtained. Finally, the esters (DCG_MONO and DCG_DIES) were obtained by the Steglich esterification protocol (Figure 1). The esterification was proceeded by milling PEG_SA with 4-dimethylaminopyridine (DMAP-1 st step), then it was added N,N'-Dicyclohexylcarbodiimide (DCC) in the jar (2 nd step), the 3 rd step of the reaction is followed by the addition of DCG in the jar. To obtain DCG_ MONO it was used 1 mmol of DCG, while to obtain DCG_DIES it was used 2 mmol of DCG. The purification of
the products was proceeded using cold dichloromethane. Figure 1: Reaction synthesis scheme of DCG_MONO and DCG_DIES.
All the products were characterized by FTIR and ¹H NMR, which confirmed the obtention of the suggested structures. By these results, the authors conclude that the mechanochemical method was an efficient tool that makes possible the obtention of different compounds class by solid-state reactions. References 1. A review on biological activities of Schiff base, hydrazone, and oxime derivatives of curcumin. 2020. 2. Solid-state mechanochemical ω-functionalization of poly(ethylene glycol). 2017. 3. One-pot synthesis of Curcumin-NSAIDs prodrug, spectroscopic characterization, conformational analysis, chemical reactivity, intramolecular interactions and first order hyperpolarizability by DFT method. 2016.
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© The Author(s), 2022
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