Alkaloids piperidine family

The Piperidine Family. It was noted in section 3.2.1.2 that the piperidine ring is biosynthesized from the amino add lysine, and the example of coniine biosynthesis was given in that section. On the pathway to coniine (3.14), a highly toxic compound isolated from the hemlock tree is the ketone derivative 3.13 this happens to be the well-known alkaloid pelletierine, which is isolated from the pomegranate tree (Scheme 3.7). It has found use in the treatment of parasitic infections (called an anthelmintic agent). 

Several species pertaining to the sub-family Myrmicinae (e.g., Solenopsis spp., Monomorium spp.) are characterized by a venom rich in dialkylated saturated nitrogen heterocycles (e.g., piperidine, pyrrolidine, indolizidine, pyrrolizidine). Exhaustive lists of these alkaloids have already been published [114-116]. Since then, only a few more of these alkaloids have been reported from a few further species. 

Heterocycles which are not biosynthesized in humans, but which are natural products produced by other life forms, are very important in the history of drug design. This is particularly true of alkaloids containing a piperidine ring. These include coniine (8.87, extracted from poison hemlock, Conium maculatum, a member of the Umbelliferae carrot family), atropine (from Atropa belladonna and other genera of the Solanaceae plant family the plant was called belladonna [ beautiful woman ] since it was used by... 

Nomicotine, an organocatalyst studied by Dickerson and co-workers (Entry 5 [52, 58d], Appendix 7.B), reinforces the important principle that even catalysts from Nature can present problems when it comes to toxicity. The family of nicotinic receptor agonists (Figure 7.9) contains several chiral pyrrolidines and piperidines with the potential to act as asymmetric aldol catalysts. Nomicotine, which can be isolated from plants such as tobacco, or readily synthesized by demethylation of the maj or tobacco alkaloid nicotine, was investigated in some depth as an aldol catalyst by Dickerson and Janda in 2002 [52]. 

Not much is known of its chemistry. Positive tests for alkaloids have been obtained in several species S-hydroxytryptamine has been identified in Urlica the substance responsible for the burning sensation from the leaves of Laporlea is a complex octapeptidc piperidine derivatives are found in the family as well. 

Alder reaction [524, 525]. Danishefsky et al. have used nitroso dienophiles for the synthesis of mitomycin K and antibiotics of the FR 900482 family, the latter ones are structurally unique aziridino-l,2-oxazine derivatives [526-529]. An approach directed to the cephalotaxus alkaloids has been worked out by Fuchs et al. [530], and several indolizidine alkaloids have been prepared by Keck s [531] and Kibayashi s groups [532,533]. Kibayashi et al. also synthesised Nuphar piperidine alkaloids in enantiomerically pure form by means of an asymmetric nitroso Diels-Alder reaction [534]. 

There are many pyrrolidine alkaloids derived from ornithine and another large family of piperidine alkaloids derived from lysine by similar pathways involving... 

Most amphibian alkaloids are not as complex in structure as the steroidal batrachotoxins and samandarines. Of the 300 known amphibian alkaloids, most have been characterized from the skin extracts of frogs of the family Dendrobatidae and, hence, have been referred to as dendrobatid alkaloids. The major bicyclic classes of dendrobatid alkaloids are the histrionicotox-ins, decahydroquinolines, and pumiliotoxin-A class. Because of the presence of a piperidine ring in most dendrobatid alkaloids, they also have been referred to as piperidine-based alkaloids. 

Lysine and the Piperidine Alkaloids.—The amino-acid lysine serves as the precursor of a piperidine ring in the biosynthesis of a large number of alkaloids. Several alkaloid families are under active investigation and because the attack on this problem is taking place on several fronts, progress is difficult to follow. 

The first total synthesis of racemic histrionicotoxin (58), the parent structure in a family of related spirocyclic alkaloids isolated from the skins of Dendrobates histrionicus, utilized the Eschenmoser reaction to generate the anchor of what would become the enyne group extending from the a-position of the piperidine nucleus. The spirothiolactam intemiediate (77) was condensed with ethyl 2-bromoace-toacetate in the presence of sodium bicarbonate to produce (78) in good yield (Scheme 18). Prior to further reaction on the vinylogous carbamate, the pendent allylic acetate was elalx>rated to the enyne (79). Subsequent deacylation and enyne protection yielded spirobicycle (80), which gave a 1 1 mixture of isomers upon reduction. The desired diastereomer (81) was isolated and subsequently converted to racemic histrionicotoxin (58). 

The lupin(e) alkaloids are a group of alkaloids possessing quinolizidine ring or piperidine ring in molecules. This group of compounds comprises ca. 200 structurally related alkaloids that represent 2% of the 10000 known alkaloids in nature [1]. These alkaloids are distributed in the family Leguminosae, subfamily Papilionoideae (Lotoideae, Faboideae, Papilionatae), in particular, in the species in the more primitive tribes of the Papilionoideae, but not in the other subfamilies Caesalpinioideae or Mimosoideae. 

The Pyridine Famiiy. The tobacco alkaloids are the best representatives of this family. We have already viewed the structures of several of these alkaloids in Figure 3.1. They may have a pyrrrolidine ling as in nicotine or a piperidine ring as in anabasine attached to the 3-position of pyridine. They are biosynthesized from nicotinic add (Scheme 3.8). 

Because they exhibit various fascinating biological activities [1], polyhydroxylated alkaloids that mimic sugar structure arouse a growing interest in the last few years. Naturally occurring iminosugars are classified in five structural families polyhydroxylated pyrrolidines, piperidines, indolizidines, nor-tropanes, and pyrrolizidines (fused pyrrolidines with N at the bridgehead) alkaloids [2]. The pyrrolizidine skeleton with a hydroxyl substituent at C-3 is relatively rare in Nature and appears to be restricted to specific families, while piperidine and pyrrolidine skeleton are conunon in many species. 

Punica alkaloids a group of piperidine alkaloids, originally isolated from the bark of the pomegranate tree (Punica granatum L., official drug Cortex grana-ti), and subsequently isolated from other plant families. Decoctions of the drug, or the isolated alkaloids. 

The Lobelia alkaloids were first detected by Procter in 1850. At the begiiming of the twentieth century, Wieland and Scheuing isolated the first alkaloids from L. inflata. The most important alkaloid of the family Lobeliaceae is lobeline, which is an a, ai-disubstituted piperidine. Further, other alkaloids of L. inflata have been isolated, with their structures described [29, 34, 35]. 

The typical alkaloids of the family Lobeliaceae have a piperidine skeleton. There are alkaloid bases disubstituted in the a, aj-position (i.e., in C2 and Cg) and those monosubstituted in the a-position (C2) (Figs. 11.23, 11.24] [36]. 

The tropane alkaloids comprise a large well-defined structurally group of natural products, occurred mainly in family Solanaceae but also are found in the families Convolvulaceae, Erythroxylaceae, Proteaceae, Rhizophoraceae, etc. [1], Common structural element of these alkaloids is the tropane skeleton, crnisisting of a pyrrolidine and piperidine ring sharing the nitrogen atom and two carbon atoms. The systematic name of the tropane skeleton is 8-methyl-8-azabicyclo[3.2.1.]octane (Fig. 12.1). Currently, the number of these alkaloids is more than 200 [2-4]. 

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