Structure of capsaicin

The spicy flavor of cayenne pepper is due mainly to a substance called capsaicin. The following sequence of steps was used in a synthesis of capsaicin. See if you can deduce the structure of capsaicin on the basis of this synthesis. 

Figure 12.6 Structures of capsaicin, maple lactone, and methyl anthranilate.

The principles learned in this chapter apply to all organic molecules regardless of size or complexity. For example, we now know a great deal about the structure of capsaicin, the spicy component of hot peppers mentioned at the beginning of this chapter. 

Convert this structure of capsaicin to a skeletal formula. 

Fig. 1. The structure of capsaicin indicating the three functionalities which have been investigated for their contribution to the pungent and desensitizing activity of the compound.

Pharmacological studies on gastrointestinal tract, cardiovascular and respiratory systems, thermoregulation, as well as nociception and anaesthesia were summarized by Suzuki and Iwai (1984). Relationship between pungency and chemical structure of capsaicin and its natural as well as synthetic analogues was also a topic... 

The structure of capsaicin is shown on p. 988. Some of the data that were used in its elucidation are presented below. Interpret as much of this information as you can. 

Camphor, molecular model of, 129 specific rotation of, 296 Cannizzaro, Stanislao, 724 Cannizzaro reaction. 724 mechanism of, 724 Caprolactam, nylon 6 from, 1213 Capsaicin, structure of. 78 -curbahlehyde, aldehyde name ending, 696... 

Capsaicin, also known as N-Vanillyl-8-methyl-6-(E)-noneamide, is the most pungent of the group of compounds called capsaicinoids It is a common ingredient in varieties of pepper such as habanero, Thai, tabasco, cayenne etc. One target with which capsaicin interacts is the capsaicin receptor, an ion channel belonging to the superfamily of TRP channels. Because of the structural relation to other TRP channels and because the vanilloid moiety is an essential component of capsaicin, the capsaicin receptor is also called TRPVI or vanilloid receptor (VR1). It is involved in heat and pain perception. 

Now, to return to the orange stain, formed on the surface of a pan by adsorption of capsaicin from a solution (the curry). Such organic dyes are usually unsaturated (see the structure I above), and often comprise an aromatic moiety. The capsaicin, therefore, has a high electron density on its surface. During the formation of the adsorption bond, it is common for this electron cloud to interact with atoms of metal on the surface of the pan. Electron density flows from the dye molecule via the surface atoms to the conduction band of the bulk metal. The arrows on Figure 10.4 represent the direction of flow as electron density moves from the charge centroid of the dye, through the surface atoms on the substrate, and thence into the bulk of the conductive substrate. 

Suzuki T, Fujiwake H, Iwai K (1980) Intracellular localization of capsaicin and its analogues, capsaicinoid, in Capsicum fruit. 1. Microscopic investigation of the structure of the placenta of Capsicum annuum var. annuum cv. Karayatsubusa. Plant Cell Physiol 21 839-853 Ohta Y (1963) Physiological and genetical studies on the pungency of Capsicum IV. Secretory organ, receptacles and distribution of capsaicin in the Capsicum fruits. Jap J Breed 12 179-183... 

Scheme 1 Chemical structures of natural vanilloid receptor agonists a, capsaicin, the irritant principle in hot peppers b, resiniferatoxin (RTX), isolated from the cactuslike plant Euphorbia resinifera c, the triprenyl phenol scutigeral, found in an edible, non-pungent mushroom d, the sesquiterpenoid dialdehyde isovelleral, found in pungent mushrooms.

Figure 30-29 Structures of the active components of cannabis, tetrahydrocannabinol, and cannabidiol, and structures of endogenous cannabinoids and of the vanilloid lipid capsaicin.

The acyl moiety of capsaicin contains only one functional group, a double bond that is redundant for activity. On the contrary, the presence of the double bond is critical for the activity of olvanil, and interesting structure-activity relationships were discovered for this compound. Thus, an analog hydroxylated on the homoallylic carbon is easily available from the amidation of commercial and cheap ricinoleic... 

The expression of TRPVl in supraspinal structures such as PAG, RVM, the LC, and thalamus suggests its involvement in descending and ascending supraspinal pain processing (Cristino et al., 2006 Maione et al., 2006 Mezey et al., 2000 Starowicz et al., 2008). Microinjection of capsaicin into the PAG increases the latency to... 

Jancso G, Jancso-Gabor A (1980) Effect of capsaicin on morphine analgesia- possible involvement of hypothalamic structures. Naunyn Schmiedebergs Arch Pharmacol 311 ... 

Some of these concepts are illustrated in the skeletal structure for capsaicin. As we continue our study of organic chemistry you will see that these fundamental properties about a molecule determine its physical properties and its behavior in chemical reactions. 

Fig.3 Chemical structures of two vanilloid receptor agonists olvanil and capsaicin and of the vanilloid...

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