Piper alkaloids

Piper alkaloids a group of alkaloids occurring in various species of Piper, especially black pepper Piper nigrum). Structurally, P.a. consist of an aromatic carboxylic acid with an unsaturated side chain (e.g. piperic acid, sinapic acid) in amide linkage with a basic component, usually piperidine. The chief representative is Piperine (see). 

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. 

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. 

Anderson first hydrolysed piperine by alkalis into a base and an acid, which were named by Babo and Keller piperidine and piperic acid respectively. The chemistry of these products is so well known that it need not be discussed here. The alkaloid was synthesised by Rugheimer by the action of piperoyl chloride on pijieridine. 

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. 

Piper methysticum Forst is a bush tree from Polynesia, known under the local name of kawa-kawa its roots are used in the preparation of an inebriating social beverage called kava, the active principles of which are not alkaloids. Two alkaloids were isolated from the root 1-cinnamoylpyrrolidine (138) and 1 -(m-methoxycinnamoyl)pyrrolidine (139) (208). Their structures were determined by spectroscopic means as well as by total synthesis. 

These alkaloids bear close resemblance to peepuloidine (140), the main alkaloid of Piper peepuloides Roxb., a medicinal plant from India. The main structural problem with 140 was the location of the five benzenic substituents,... 

Piper trichostachyon C.DC. from India contains a variety of pyrrolidine alkaloids in its stem and leaves. Among these one finds trichostachyne (135) (210), its C2 homolog 1-piperettylpyrrolidine (141) (211), tricholein (142) (212), and a long-chain dienamide trichonine or l-pyrrolidinyl-(E, )-eicosa-2,4-di-enamide (143) (213). 

Alkaloids with the piperidine nucleus, such as pelletierine (Punica grana-tum), lobelanine Lobelia inflata) and piperine Piper nigrum), have a typical biosynthesis pathway. It starts with L-lysine and continues via cadaverine (biogenic amine), A -piperideine and A -piperidinium cations and lobelanine, to be synthesized as lobeline. Piperine is synthesized from A -piperideine via piperidine (Figure 49). For the transformation from A -piperideine to A -piperideine cation, the residue from acetyl-CoA is needed, together with SAM activity in the transformation to lobelanine. Piperine is synthesized from piperidine through the formation of amide. 

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). 

Areca nuts (betel nuts) are the seeds of Areca catechu (Palmae/Arecaceae), a tall palm cultivated in the Indian and Asian continents. These nuts are mixed with lime, wrapped in leaves of the betel pepper (Piper betle) and then chewed for their stimulant effect, and subsequent feeling of well-being and mild intoxication. The teeth and saliva of chewers stain bright red. The major stimulant alkaloid is arecoline (up to 0.2%) (Figure 6.36), the remainder of the alkaloid content (total about 0.45%) being composed of related reduced pyridine... 

The two sulfur-containing amides entadamides A (93) and B (94) have been isolated from the seeds and entadimides A and C (95) from the leaves of Entada phaseoloides Merr. (valid name Entada rheedii Spreng.) (Legu-minosae) (99-101). The known isobutylamide alkaloid pellitorine (N-isobutyl-2 ,4 -decadienamide) is found in the aerial parts of Piper ri-besoides Wall. (102). Pellitorine has also been isolated from the fruits of P. 

Several new alkaloids have been isolated from pepper species. Tricholeine, for example, occurring in the stems of Piper trichostachyon, is the pyrrolidine amide (2) of fra s-9-(3,4-methylenedioxyphenyl)-A8-nonenoic acid, the structure being established by spectroscopic and degradative studies.4 Piper guineense seeds contain okolasine (6-methoxytrichostachine) (3),5 which is probably identical to the earlier known wisanidine. 4,5-Dihydro-wisanidine (4) is also found in the same... 

A review of recent chemistry of Indian Piper spp. has appeared it includes some pyrrolidine alkaloids.8 The synthesis of tricholeine (6), an alkaloid of P. trichostachyon, has been reported the pathway is summarized in Scheme 2.9... 

Sharma s group has also synthesized guineensine, which is the alkaloid produced by both Piper guineense and P. officinarum.14 The isolation of trans- and cis-(—)-clovamides and their deoxy-analogues from the bark of Dalbergia... 

Heliotropin, Piperonal.— Heliotropin receives its other name of piperonal from its relation to compounds occurring in pepper. In black pepper, Piperus nigra there is present an alkaloid known as piperine (p. 888). From this alkaloid an acid, piperic acid, is obtained. This acid is a methylene di-ether containing an alpha unsaturated side chain as in iso-eugenole, etc. On oxidation the side chain breaks at the double bond, as has been explained, and yields an aldehyde which is piperonal. 

Protocatechuic Acid.—One of the di-hydroxy benzoic acids is related to vanillin, which we have already studied. The acid is known as protocatechuic acid, and derives its name from the fact that it may be obtained from a gum or resin, known as gum catechin by fusion with potash, i.e. by heat and oxidation in presence of an alkali. A large variety of plant products including alkaloids essential oils, gums, resins and tannins yield this acid. The following may be mentioned gum catechin, gum benzoin, guaiac resin, myrrh, piperine or piperic acid, vanillin, cafe-tannic acid. These natural sources at once suggest a relationship to vanillin (p. 661) and heliotropin (p. 662). It is the acid corresponding to protocatechuic aldehyde, 3-4-di-hydroxy benzal-dehyde (p. 661), which explains the relationship just mentioned. Its constitution, is then ... 

This compound, the hexa-hydro pyridine has just been referred to, and also previously, in connection with penta-methylene di-amine (p. 194). In both these connections its constitution has been established. As its name indicates, it is obtained from pepper in which it is present in amide combination with an acid known as piperic acid. The compound thus formed is the alkaloid of black pepper and is called pipeline. 

The fruit of the plant Piper nigrum is the common black pepper of the household. This fruit yields an alkaloid known as pipeline present to about 4 to 9 per cent in commercial pepper. On hydrolysis the alkaloid yields piperidine or hexa-hydro pyridine and an acid known as piperic acid. Piperine is thus considered as a piperidine amide of piperic acid. Physiologically this alkaloid acts like quinine but is less active and is uncertain. It is only rarely used in medicine. 

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. 

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