Protection and Activation of Hydroxycinnamic Acids in Water

Abstract

Hydroxycinnamic acids such as p-coumaric, ferulic, sinapic and caffeic acids were protected as carbonates and activated as mixed carbonic anhydrides in water at RT by adding a base and isobutyl chloroformate. These anhydrides were used for amine and C-protected α-amino acid acylation to give O-carbonate protected phenolic amides. Acylation of free α-amino acids was performed in acetone-water in high yields producing the Ocarbonate protected N-hydroxycinnamoyl-α-amino acids. Pure derivatives were obtained in many cases directly by crystallization. Free phenolic compounds were rapidly obtained by carbonate deprotection with piperidine. The method offers a novel route for amide bond formation in water and the direct functionalization of hydroxycinnamic acid families with free αamino acids, providing a facile preparation of precious natural bioactive derivatives. 3 a 3 b 92 83 Caffeic Caffeic R-PEA Gly-OEt 4 a 4 b 88 68 b[a] Isolated carbonate protected products [b] 2 h coupling ChemistrySelect Communications

Synthesis of Customizable Macromolecular Conjugates as Building Blocks for Engineering Metal–Phenolic Network Capsules with Tailorable Properties

“…The protected PEG–caffeamide building blocks ([PEG n –iBoc–caffeamide] 2/4/8 ) were isolated by precipitation and analyzed before deprotection (see Figures S1–S26 for synthetic details and analysis of the end-functional PEG-amine and protected and isolated PEG–caffeamide building blocks). In the case of small molecules, a one-pot conjugation followed by deprotection is typically conducted. ,− However, in the present work, we implemented a two-step strategy to monitor the formation of the carbamate side product. This is formed upon the reaction of the amine with carbonate groups during the coupling step, in this case yielding [iBoc–PEG n carbamate] arms (as shown in Scheme S2).…”

Sustainable Chemical Derivatization of Hydroxycinnamic Acids

“…Instead of using acetone as a solvent, we can also use ionic reagents in water, such as free amino acids. [21] These indications require presenting new results from the derivatization studies conducted on select trans-HCAm family members in ethyl acetate and acetone. The derivatives accessible with this new methodology are illustrated in Scheme 1: the protected HCAm-ester 4, the protected HCAm-amide 6, the protected HCAm-azide 5, the protected HCAm conjugate with amino acids 7, and the phenols-protected HCAm 3.…”

“…In a recent study, we introduced an innovative synthetic procedure for trans‐HCAm‐amide formation in water, [21] eliminating the need for additives and employing an alkyl chloroformate and triethylamine as a protection‐activation system. However, applying this procedure in water presents solubility challenges and complexities, making ethyl acetate essential for product extraction and purification in laboratory‐scale experiments.…”

“…Instead of using acetone as a solvent, we can also use ionic reagents in water, such as free amino acids [21] …”

A Straightforward Access to New Amides of the Melanin Precursor 5,6-Dihydroxyindole-2-carboxylic Acid and Characterization of the Properties of the Pigments Thereof

“…Yet, amidation of a carboxylic acid featuring additionally an o -diphenol functionality poses several difficulties, since the OH groups may act as competitive nucleophiles, but mostly because the reaction conditions are typically alkaline, favoring oxidation of the catechol, so that rigorous air exclusion is required. Recently, a successful synthetic protocol applied to caffeic acid reported the protection of the OH groups before the amidation step [ 27 ]. Other studies on different catechol systems described a variety of reaction conditions using different coupling agents (e.g., N,N′-dicyclohexylcarbodiimide (DCC)/4-dimethylaminopyridine (DMAP) [ 28 ], or ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)/hydroxybenzotriazole (HOBt) [ 29 ] or benzotriazol-(1-yloxy)tris (dimethylamino) phosphonium hexafluorophosphate [ 30 , 31 ]).…”