Capsaicinoids structure-activity relationship

Various studies have evidenced strict structure-activity relationships within capsaicinoids, and the existence of these relationships provided a hint for the existence of a specific receptor [72]. On the other hand, different end-points have been used in the literature, and it is difficult to draw a consistent picture. In vivo assays such as pungency and ocular irritancy, functional assays such as the measurement of calcium currents in dorsal root ganglion neurons, and receptor assays such as the displacement of labeled RTX have been used. The relationship between the results of these assays is, at best, approximate [75]. 

In all these protocols, chemoselective amidation of vanillamine with NMA was achieved in satisfactory yield (about 80 %) by activation of the add to its corresponding chloride, followed by condensation with free vanillamine. Free vanillamine is much less stable than its corresponding chloride, and, owing to its polarity, it is difficult to extrad quantitatively from water solution, with loss of about 20 % of the product routinely observed in the desalification step [59]. Furthermore, the preparation of chlorides from polyunsaturated fatty acids is not trivial, and therefore alternative coupling protocols were investigated in a series of systematic studies dedicated to the structure-adivity relationships of capsaicinoids. 

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