First mechanosynthesis of piperlotines A, C, and derivatives through solvent-free Horner-Wadsworth-Emmons reaction

Abstract

Piperlotines are natural products characterized by an α,β-unsaturated amide moiety. These compounds found wide applications in Medicinal Chemistry like antibacterials, cytotoxic agents, anticoagulants, among others. To date, diverse methods of synthesis have been reported for piperlotines, but involving the use of catalysts, hazard reagents, anhydrous media or coupling reagents. Thus, in this work, we developed a greener method of synthesis of piperlotines A, C, and derivatives, through mechanochemical activation under solvent-free conditions. The reaction of a β-amidophosphonate, K₂CO₃, and an aromatic aldehyde afforded target compounds in moderate to good yields (46-77%), in an open atmosphere by grinding. It is worth to mention that this mechanochemical process was under thermodynamic control because just E isomer was isolated for every reaction. Moreover, synthesized piperlotines have been predicted by means of chemoinformatic analysis as potential therapeutic agents for the treatment of arthritis or cancer.

Graphical Abstract

KEYWORDS:

• Green chemistry
• mechanochemistry
• Horner-Wadsworth-Emmons reaction
• Piper genus
• arthritis

Additional information

Funding

The authors thank CONACyT and Secretaría de Educación Pública of Mexico for financial support via project INFRA-2015-01-252013 and F-PROMEP-39/Rev-04 SEP.