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Efficient TBD-Catalyzed Synthesis of Capsaicin-like Molecules
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1  University of Trento


Capsaicin (= (E)-N-(4-hydroxy‐3‐methoxybenzyl)‐8‐methyl‐6‐nonenamide), the natural compound responsible for the spicy flavor in pepper fruits, has shown antioxidant and weight-reductive properties, cardiovascular benefits, anti-carcinogenic activity and recently pain relief effects. Studies on a series of synthetic capsacinoids indicated that the length of alkyl chain affected piquancy, with the possibility of obtaining non‐pungent capsaicin analogues with interesting bioactivieties.1

We report here on a new efficient procedure for the synthesis of capsaicin analogues, based on the aminolysis of vanillylamine with methyl esters showing structural changes in alkyl chain, catalyzed by the inexpensive and non-toxic triazabicyclo[4.4.0]dec‐5‐ene (TBD).2 The procedure is improved by microwave irradiation, which allows to carry out the reaction under solvent-free conditions and to obtain high yields of products. This is an effective and fast procedure for the access to a wide library of capsaicinoids for further biological evaluations, as well as for a large-scale production.



  1. M.L.Reyes‐Escogido, E. G.Gonzalez‐Mondragon, E.Vazquez‐Tzompantzi, Molecules 2011,16,1253.
  2. C. Sabot, K. A. Kumar, S. Meunier, C. Mioskowski, Tetrahedron Lett. 2007, 48, 3863.
Keywords: capsacinois, MW-assisted synthesis, TBD-catalyst