Synthesis and evaluation of new alkylamides derived from alpha-hydroxysanshool, the pungent molecule in szechuan pepper

J Agric Food Chem. 2009 Mar 11;57(5):1982-9. doi: 10.1021/jf803067r.

Abstract

Szechuan pepper is widely used in Asia as a spice for its pleasant pungent and tingling sensations, produced by natural alkylamides called sanshools. alpha-Hydroxysanshool, the main alkylamide found in the pericarp of the fruit, stimulates sensory neurons innervating the mouth by targeting two chemosensitive members of the transient receptor potential (TRP) channels, TRPV1 and TRPA1. As it was previously found that configuration of the unsaturations in the alpha-hydroxysanshool alkyl chain is required for TRPA1 but not TRPV1 selectivity, this study aimed at obtaining more potent and selective TRPA1 agonists using alpha-hydroxysanshool as a starting material. This paper reports the preparation of new alkylamides derived from sanshool and their efficacy in stimulating TRPA1 and TRPV1 receptors. The data provide knowledge of the main sanshool chemical functionalities required for TRP channel activation, but they also evidence new selective and potent TRPA1 agonists based on alpha-hydroxysanshool.

MeSH terms

  • Amides / chemistry
  • Calcium Channels / genetics
  • Calcium Channels / metabolism
  • Cell Line
  • Flavoring Agents / chemical synthesis*
  • Flavoring Agents / chemistry
  • Humans
  • Nerve Tissue Proteins / agonists
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Plant Extracts / chemical synthesis*
  • Plant Extracts / chemistry
  • Polyunsaturated Alkamides / chemical synthesis*
  • Polyunsaturated Alkamides / chemistry
  • TRPA1 Cation Channel
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism
  • Transient Receptor Potential Channels / agonists
  • Transient Receptor Potential Channels / genetics
  • Transient Receptor Potential Channels / metabolism
  • Zanthoxylum / chemistry*

Substances

  • Amides
  • Calcium Channels
  • Flavoring Agents
  • Nerve Tissue Proteins
  • Plant Extracts
  • Polyunsaturated Alkamides
  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Transient Receptor Potential Channels
  • sanshool