Capsaicinoids, synthesis

Validation of the role of femloyl-CoA in the synthesis of the vanillin precursor will be detection of the appropriate intermediates and/or enzyme activities in placental extracts that could account for the production of the predicted levels of capsaicinoids. The presence of low levels of monolignol intermediates could be explained by lignin biosynthesis. An alternate route from phenylalanine to vanillin has been considered by some investigators Orlova et al. [68] demonstrated the role of the benzenoid pathway in petunia flowers for the biosynthesis of phenylpropanoid/benzenoid volatiles. 

The substrates for capsaicinoid synthase were first defined by Fujiwake et al. [70] to be vanillylamine and 8-methyl-6-nonenoyl CoA. The synthesis of dihydrocapsaicin and the other naturally occurring variants are achieved by condensation of vanillylamine with the respective branched chain acyl, for example, 8-methylnonanoyl-CoA. The gene for capsaicinoid synthase has been linked to an acyltransferase At3 or Punl) cloned by Kim et al. [66] and mapped to the C locus on chromosome 2 [71, 72], Direct biochemical confirmation of capsaicinoid synthase remains to be established. 

Capsaicinoids start to accumulate 20 days post anthesis and synthesis usually persists through Suit development [59, 62,73], The site of synthesis and accumulation of the capsaicinoids is the epidermal cells of the placenta in the fmit (Fig. 8.5) [60, 72, 73], Ultimately, the capsaicinoids are secreted extracellularly into receptacles between the cuticle layer and the epidermal layer of the placenta [74]. These receptacles of accumulated capsaicinoids are macroscopically visible as pale yellow to orange droplets or blisters on the placenta of many chile types (Fig. 8.5). 

From a biogenetic standpoint, capsaicin is an acylated degraded phenylpropanoid. Both its aromatic and its acyl moiety are the result of unique metabolic processes that, though simple in principle, are still poorly characterized in terms of enzymology and regulation. Since vanillamine (23) is abundant in placental tissues of Capsicum, the only site of biosynthesis of capsaicinoids, the limiting factor for the synthesis of... 

The accumulation of capsaicinoids is also subjected to environmental variables, such as temperature, light, soil moisture, and fertilization level [51]. In general, drought and high night temperatures promote the synthesis of capsaicinoids, explaining the major hotness of peppers gro vn in dry tropical areas compared to those cultivated in more temperate or humid climates. 

In 1989, a different approach was published by Orito [60], in which elaidinization ((Z) —> ( ) double bond isomerization) is used to obtain ( )-MNA from a (Z, )-mixture ofdiastereomers (Scheme 4.6). Gannet had observed that the iodine-induced photoisomerization of the methyl ester of MNA (48) gave only a 7 3 ( /Z) mixture [59], but Orito obtained a better diastereomeric ratio (8 1) using nitrous acid. Remarkably, no double-bond migration to form the more stable trisubstituted olefin was observed. This discovery paved the way to a very simple and general synthesis of the acidic component of capsaicinoids. Thus, a Wittig reaction of the phosphonium salt of a 6-bromohexanoic acid (49) with isobutyraldehyde (SO) afforded a 1 11... 

Other capsaicinoids are available. Pelargonic acid vanillylamide (PAVA or nonivamide), shown in Figure 12.10, is a synthetic form of capsaicin. Nonivamide was first synthesized by Nelson (1919). Nonivamide was originally found to be a minor component in Capsicum annum peppers (Constant and Cordell, 1996) however, the majority of PAVA is derived from synthesis rather than extraction from natural plant sources. As a result, the composition and concentration of PAVA can remain consistent (Haber et al, 2007). 

As for the capsaicin derivatives, it was shown that only the trans isomer is naturally occurring. Biologically, it was reported that purified capsaicin depletes substance P stores in sensory neurons and blocks further synthesis of this neuropeptide. Therapeutically, capsaicin has been used successfully to treat several painful conditions (e.g., rheumatoid arthritis, osteoarthritis, and various peripheral neuropathic disorders).To date, there are no capsaicinoids that have proven to be as potent as the parent compound capsaicin for neuropeptide activity [6]. 

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