The Pepper Alkaloids

Since the cis-cis acid is intermediate in stability between the trans-trans which is the most stable and the cis-trans acids which are the most labile, it follows that piperine and chavicine are the pipeiidides of the two most stable forms (3). Piperine is therefore the piperidide of the aP-trans-yB-trans acid and chaidcine, the piperidide of the a -cis B-ds acid. 

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In the pepper alkaloid group, several new amides have been isolated from Achillea spp. One of them, from A, biebersteinil Afan, is the piperideide(19)Others include (20) (from A. ly caonica Boiss, et Heldr.), and the hitherto structurally unencountered acetylenic amides (21) and (22) (from A. spinulifolia Fenzl ex... 

Zsila F, Hazai E, Sawyer L. Binding of the pepper alkaloid to bovine beta-lactoglobulin Circular dichroism spectroscopy and molecular modeling study. J AgrFood Chem 2005 53(26) 10179-85. 

Nuts have many uses, both industrial and domestic. For instance, the ivory nut, or tagua, is a source material for the manufacture of buttons and turnery articles. The kola nut supplies ingredients for popular cola beverages in the United States (see Carbonated beverages). StTychnos nux-vomica provides the important medicine and poison, strychnine. The areca or betel nut is chewed by the Indian and Malayan people as a narcotic a slice of the nut is placed in a leaf of the pepper plant Piper betle) together with a pinch of lime the mixture is an acrid, astringent narcotic that dyes the mouth red, blackens and destroys the teeth. The areca nut contains, among other alkaloids, arecoline, an active anthelminthic widely used in veterinary practice for the treatment of tapeworm infections. 

The preparation of a special chapter in this series on the constituents of pepper (6) led us to ignore pepper alkaloids. After publication of the chapter, we discovered that it dealt with the alkaloids of red pepper species (Capsicum, So-lanaceae), which are not pyrrolidines, and the purpose of this addendum is to provide a survey of the pyrrolidine alkaloids contained in black pepper species Piper, Piperaceae. 

The chemistry of pepper has long been studied and the pungent principle of black pepper—a piperidine alkaloid, piperine 134—was isolated as early as 1877 (201). Its synthesis from the acid and piperidine was accomplished in 1882. (202). The corresponding pyrrolidine alkaloid trichostachyne (135) was isolated some 100 years later from several Piper species (see below). The cooccurence of piperidine and pyrrolidine alkaloids is a common feature of the chemistry of pepper. In many cases, the crude alkaloid extract is first cleaved with acids or bases and then each alkaloid is reconstituted by selective amidation. For the sake of unity, this chapter will be limited to comments on pyrrolidines, even in cases where they are minor alkaloids. 

The total syntheses of these pepper alkaloids are not those of pyrrolidines but rather syntheses of their acid parts. Thus dihydrowisanidine (137) has been prepared by a series of reactions, the key step of which is the formation of the carbon-carbon double bond by a Wittig-Homer reaction (217, 218). Schemes 41 and 42 summarize two syntheses of okolasine from sesamolmethyl ether (279) of course, routes to okolasine also yield the corresponding piperidine alkaloid wisanine. Molybdenum-catalyzed elimination of allylic acetate (149) yielded (E,E)-diene ester 150 en route to trichonine (220) worthy of note is the use of an aluminum amide in the preparation of amide 143 from ester 150 (Scheme 43). 

Many human populations have only encountered some mixtures of NPs relatively recently— the first Europeans to encounter chilli peppers, many beans, pineapples, bananas, tobacco and so forth did so only a few hundred years ago. The solanine alkaloids (and other NPs) in potato or tomato were unknown to Asians, Africans and Europeans until very recently, yet these populations seemed untroubled by these novel chemicals. Tomato fruits were initially considered to be poisonous when introduced to Europe and it was only in the nineteenth century that they became widely adopted as a food plant. 

In addition to the amides responsible for the sharp taste of peppers, alkaloids of various types including aporphines have been found in the family. 

The pungency of the fruits of black pepper (Piper nigrum Piperaceae), a widely used condiment, is mainly due to the piperidine alkaloid piperine (Figure 6.24). In this structure, the piperidine ring forms part of a tertiary amide structure, and is incorporated via piperidine itself, the reduction product of A1 -pipcridcine (Figure 6.22). 

Many of the world s population (more than 200 million people worldwide) chew betel nut quid, a combination of areca nut, betel pepper leaf (from Piper betle), hme paste, and tobacco leaf. The major alkaloid of the areca nut, arecoline, can produce chohnergic adverse effects (such as bronchoconstriction) (1) as well as antagonism of anticholinergic agents (2). The lime in the betel quid causes hydrolysis of arecohne to arecaidine, a central nervous system stimulant, which accounts, together with the essential oil of the betel pepper, for the euphoric effects of chewing betel quid. 

Piplartine (3), another pepper alkaloid, is dimerised on irradiation with ultraviolet light to the compound (4), which occurs as a natural product in its ov/n right - as an extractive from P. tuberculatum (R.B.-Filho, M.P. DeSouza and M.E.O. Mattos, Phytochem., 1981, 20, 345). 

A short, convenient, stereoselective synthesis of pepper-derived alkaloids has been carried out by condensing piperonal with the ylide from methyl (E)-4-(diethylphosphono)-2-butenoate to give methyl (E,E)-5-(1,3-benzodioxol-5-yl)-2,4-pentadienoate, which on methoxide-catalysed aminolysis (piperidine, pyrrolidine, etc.) gave the required alkaloid. 

Syntheses of a variety of naturally occurring polyene and polyenyne amides have been reported. Pepper alkaloids have been obtained using the Wittig reaction and phosphonate, e.g., (167), - routes. 

Cuscohygrine has been isolated for the first time from the roots of Solanum carolinense. The guinea pepper alkaloid okolasine, which is the pyrrolidine amide (1) of 6-methoxypiperic acid, has been synthesized by the standard procedure of reaction of the acid chloride with pyrrolidine. The acid was reached by two routes from 2-methoxy-4,5-methylenedioxybenzaldehyde. ... 

Chonpathompikunlert P, Wattanathom J, Muchimapura S. Pipeline, the main alkaloid of Thai black pepper, protects against neurodegeneration and cognitive impairment in animal model of cognitive deficit like condition of Alzheimer s disease. Food Chem Toxicol 2010 48(3) 798-802. 

Piperine piperic acid piperidide, a Piper alkaloid (see), the chief alkaloid of black pepper Piper nigrum) and responsible for its sharp taste. Af, 285.35, m.p. 16°C. Both double bonds are irons (Fig.). The cis-cis isomer, earlier called chavicine, does not occur naturally. 

Substances toxic to all individuals are called toxic substances or toxins. Once a toxic substance has contacted the body it may have either acute (immediate) or chronic (long term) effects. Most of food-born toxins are substances with low acute toxicity (such as the pungent alkaloid piperine in black pepper), although some may present chronic effects, such as hepatotoxic pyrrohzidine alkaloids in plants (such as comfrey and coltsfoot species) or cause pathological changes to the respiratory system (e.g., tobacco smoke). 

The corresponding A -piperideinium cation (41), probably the universal intermediate in piperidine, quinolizidine, and lycopodium alkaloid biosynthesis, is susceptible to nucleophilic attack much like its V-methyl-A -pyrrolinium cation counterpart in pyrrolidine and tropane alkaloid biosynthesis. Moreover, A -piperideine (40) might be reduced to piperidine (42), which now in turn might serve as nucleophilic species. For example, condensation of piperidine (42) with piperoyl-CoA catalyzed by piperidine V-piperoyltransferase (EC 2.3.1.145) yields piperine (43), the main alkaloid found in black pepper where it is responsible for the characteristic pungent taste. 

Colourless liquid with a characteristic ammo-niacal smell m.p. 9 C, b.p. 106°C. Miscible with water. It is present in pepper as the alkaloid piperine from which it can be obtained by healing with alkali. It can also be prepared by the reduction of pyridine, either electrolytically or by other means. Piperidine is a strong base, behaving like the aliphatic amines. 

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