Alkaloids reference compounds

Remarks-. The commercial alkaloid reference compounds (e.g. hydrastine (32)) frequently show additional zones of minor alkaloids or degradation products. 

One of the most instructive examples related to the mystery of chemical-mediated relations between plants and animals was described by Meinwald. Alkaloids (natural compounds traditionally referred to as secondary , i.e. non-important, metabolites) are amply produced by various plants. In many cases, alkaloids have been shown to be part of a defense system against various herbivores. However, some plant-eating insects learned to break through this... 

It should be stated that the treatment which follows is in no sense exhaustive either as to the properties, etc., of the alkaloids referred to, or as to the methods and reactions by which the constitution, when known, has been established. All that is attempted here is a brief presentation of the more common and important members, their origin and properties and their constitution as rel, ted to compounds we have previously studied. 

Figure 3. Structure of alkaloids known from Aconitum naviculare (References, compound 1-6 Gao et al. 2004 7-8 Cao et al., 2008 and 9-11 Dall Acqua et al., 2008).

Berbamine was evaluated in BALB/c mice infected with Letshmartia amazonensis (IFLA/BR/67/PH8 or MHOM/GF/84/CAY-H-142) or L. venezuelensis (VE/74/PM-H3). The treatments were initiated one day after parasitic infection at an alkaloid concentration of 100 mg/kg/day for fourteen days, and the reference compound (meglumine antimonate) at 200 mg/kg/day. Berbamine was found to be less potent than meglumine antimonate against L. amazonensis, and the alkaloid did not show significant activity against L. venezuelensis [334]. 

The term opium alkaloids has been used rather loosely to cover all narcotic analgesics, whether they be synthetic compounds, partially synthetic, or extracted from plant material. To be precise, we should really only use the term for those natural compounds which have been extracted from opium—the sticky exudate obtained from the poppy (Papaver somniferum). The term alkaloid refers to a natural product which contains a nitrogen atom and is therefore basic in character. There are, in fact, several thousand alkaloids which have been extracted and identified from various plant sources and examples of some of the better known alkaloids are shown in Fig. 12.1. These compounds provide a vast library of biologically active compounds which can be used as lead compounds into many possible fields of medicinal chemistry. However, we are only interested at present in the alkaloids derived from opium. 

Brucine has a weaker convulsive effect (about 1/50). Since this alkaloid has a very bitter taste, it is used as a reference compound for the determination of the bitter value of drugs. 

Seven monoindole Strychnos alkaloids, namely matadine (35), serpentine (36), alstonine (39), melinonine F (40), normelinonine F (41), 5,6-dihydroflavopereirine (42) and strychnoxanthine (43) as well as the hemisynthetic Nb-methyharmalane, together with cryptolepine (37) as reference compound, were tested for their in vitro antiplasmodial activity... 

All alkaloids were found to have little activity compared to the reference compound. The strong DNA intercalating activity of 37 is believed to be responsible for its high degree of antiplasmodial activity... 

LXII to the accepted reference compound L(+)-benzoylalanine. The configuration of the related opium alkaloids laudanosine, codamine, and lau-danidine may therefore be written as follows ... 

Table 4 lists GC systems used for the analysis of terpenoid indole alkaloids and Fig. 4 illustrates a GC separation of a mixture of reference compounds. 

GC-MS is the method of choice for identification of the components in complex mixtures of tropane alkaloids combining the high resolution power of capillary columns with the specificity of the mass detectors. It allows identification of tropane alkaloids without using of standard compounds. Isomers (at positions C3 and C6/7) are tentatively identified by Kovats retention indexes and cochromatography with reference compounds [16, 17]. In some cases, tentative identification of new tropane alkaloids has been possible by GC-MS [16, 24—26]. In fact, this is the only way to assess the minor or trace compounds, which are difficult or impossible to isolate. More than 30 0 tropane alkaloids can be detected in a single species by GC-MS [19]. GC-MS chromatogram of alkaloid extracts of D. stramonium L. hairy roots and representative MS spectra are presented in Fig. 7.1. 

Alkaloids are physiologically active nitrogen-containing compounds produced by plants. The term alkaloid refers to the alkali-like or basic characteristics we have seen for amines. Certain alkaloids are used in anesthetics, in antidepressants, and as stimulants, and many are habit forming. 

As shown in Chart 5.1, a wide variety of alkaloid skeleta are derivable from Type I precursor and tryptamine by further ring closures. It is worth pointing out that in so far as they have been investigated, they all have had the same stereochemistry for the carbon equivalent to C-15 of yohimbine. In this chapter, certain tetrahydro-j8-carboline alkaloids, viz., the yohimbines, their ring E seco equivalents and ring E oxygen heterocycles will be discussed since they show much chemistry in common. Over the years most of their degradation products have been synthesized, they have been interrelated, their absolute stereochemistries derived, and some have been synthesized. For these reasons they have become valuable reference compounds. 

Modern concepts have been extended to the chemistry of heterocyclic compounds more slowly than to the chemistry of aromatic and aliphatic systems, but efforts are now being made to classify and explain the properties and reactions of heterocyclic compounds in terms of these newer ideas (cf. reference 11). However, many of the most important heterocyclic compounds are potentially tautomeric, and elucidation of their tautomeric composition must precede a logical treatment of their properties. Further, many natural products such as the nucleic acids and alkaloids contain potentially tautomeric groups and information of this type is needed for a detailed explanation of th reactions which they undergo,... 

The nomenclature used to describe the fused benzene-pyrrole-pyridine system of the compounds under discussion has been repeatedly modified, and the compounds have been numbered in an astonishing variety of ways since Perkin and Robinson introduced the name carboline for the ring system, which was encountered for the first time in the harmala alkaloids. In the earliest version of carboline nomenclature, the parent compound of the series, whose trivial name was norharman, was referred to as 4-carboline and numbered as in 1. Harmine (2) then became ll-methoxy-3-methyl-4-carboline. 

A list of most of the known natural compounds (e.g., terpenes, alkaloids, carbohydrates) to which structures have been assigned, along with structural formulas, melting points, optical rotations, and references, is provided in Devon and Scott, Handbook of Naturally Occurring Compounds , 3 vols.. Academic Press, New York, 1972. 

Compounds Sample Plate Eluent Alkaloids Detection Remarks Reference... 

Purine is the parent heterocyclic compound of the methylxanthines, which are often referred to as the purine alkaloids.1-7 Purine is also the parent compound of some of the base constituents of the nucleotides, which in turn are part of the nucleic acids RNA and DNA. Thus, it appears that the purine alkaloids have similar precursors to nucleic acids. 

The tropane alkaloids are a well-recognized group of structurally related natural products. Long before elucidation of the structures, the mydriatic and anesthetic action of several compounds was exploited (6). The very extensive literature covering the pharmacological properties of the tropane alkaloids will be considered only briefly in this chapter. Readers with a deeper interest in the subject are referred to other publications (7-14) and to the references given in Section VII. 

Pseudopelletierine has been obtained from the bark of the pomegranate tree (Punica granatum L.).2-5 The synthesis of the alkaloid from glutaraldehyde, methylamine, and calcium acetonedicarboxylate was first achieved by Menzies and Robinson.6 The synthetic method subsequently was improved by Schopf and Lehmann,7 and others.8 9 The condensation of a dialdehyde with an amine and acetonedicar-boxylic acid to form a heterobicyclic compound (an alkaloid or alkaloid analog, usually employing mild or so-called physiological conditions) is sometimes referred to as a Robinson-Schopf synthesis. 

Alkaloids of the plumeran type are interesting because compounds with opposite stereochemistry were isolated from different plants. In some cases, a racemic form was also found besides the optically active one. The racemic forms are indicated by the prefix rac before the name and relative number. The generally accepted biogenetic numbering system proposed by Le Men and Taylor (76) is used through this article. This chapter refers to literature through June 1984. 

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