Alkaloids, isolation, general

Intramolecular Mannich reactions of iminium 1 and acyliminium ions (see Section D.1.4.5.) with electron-rich double bonds are important reactions in the synthesis of naturally occurring alkaloids. In general, the iminium ions are not isolated but produced as intermediates. 

The genera of Aconitum (commonly known as Monkshood) and Delphinium, and to a lesser extent Rumex, Consolida, and Spiraea, have long been recognized as a rich source of alkaloid natural products [1], The diterpenoid alkaloids are generally classified into two major groups the Ci9-diterpenoid alkaloids (sometimes referred to as the Cig-norditerpenoid alkaloids) and the C2o-diterpenoid alkaloids. Within the C2o-diterpenoid alkaloids, at least 11 separate classes have been isolated, including the hetisine alkaloids (Chart 1.1). 

Classical studies by Sir Henry Dale demonstrated that the receptors activated by muscarine, an alkaloid isolated from the mushroom Amanita muscaria, are the same receptors activated by ACh released from parasympathetic nerve endings, from which the general notion that muscarinic agonists have parasympathomimetic properties was born. This conclusion is true but incomplete, and we now know that muscarinic receptors have a broader distribution and many functional roles. To understand the actions of cholinomimetic drugs it is essential to recognize that muscarinic receptors (1) mediate the activation of effectors by ACh released from parasympathetic nerve... 

General synthetic methodologies leading mainly to racemic alkaloids within each group already exist. There are as yet, no syntheses reported for the new alkaloids isolated possessing complex structures such as those encountered in galasine (529), (+)-10b-hydroxygalwesine (530), (-)-obesine (570) and cripowellins A (572) and B (573). 

The use of ion exchange resins combined with supercritical extraction results in an attractive isolation technique. Since the pyrrolizidine alkaloids are generally basic, the process described here could be used for the isolation of other members of this class, and for other basic alkaloids. In designing a process using ion exchange resins, it is important that the co-solvent not deactivate the resin. In our example, water and ethanol are acidic in carbon dioxide and, therefore, do not deactivate the acidic resin. An industrial process based on this concept could be quite efficient and inexpensive since pressure reduction and subsequent solvent recompression are unnecessary (Figure 11). 

Whether herbivory is definitely associated with alkaloid content or not in a universal pattern, it is known that total alkaloid accumulation generally decreases with altitude (Chandra and Purohit, 1980 Carey and Wink, 1994.) and latitude -with an increasing toxicity of the isolates- (Levin, 1976 Levin and York, 1978) in the few cases so far studied. 

An isoquinoline system condensed to a tropolone is the skeleton for a tropoloisoquinoline alkaloid. The general structure of the five alkaloids of this type known so far are derivatives of the tautomers of 10-hydroxy-9H-azuleno[l,2,3-i,j]isoquinolin-9-one (42) and 9-hydroxy-10H-azuleno[l,2,3 i,j]isoquinoline-10-one (43) [88]. Recently, the first tropone-isquinoline alkaloid, pareitropone (44) has been isolated from the roots of the South American Menispermaceae, Cissampebs pareira [48]. 

The antimicrobial activity of aporphine alkaloids in general has been tested and oxoaporphines were the most active [108]. Some of these alkaloids are found to be toxic for mammalian cells in tissue cultures [109]. In another study of antimicrobial activity of fourteen benzylisoquinoline alkaloids, two oxoaporphines isolated from species of South American Menispermaceae, lysicamine (10) and O-methylmoschatoline (homomoschatoline) (11), had activity against cocci and gram positive bacilli, including Mycobacterium phlei [110]. 

The free bases are soluble in lipophilic organic solvents, like chloroform. The different solubility for bases and salts is used for isolation and purification. Alkaloids are generally colourless solid materials. Some alkaloids that do not contain oxygen, like coniine, nicotine and sparteine, are liquid, and berberine and chelidonine are intensely yellow. Several alkaloids, e.g. strychnine and quinine, have a very bitter taste. Alkaloids give precipitates with heavy metals like mercury and bismuth. DragendorfPs reagent is used to show the presence of alkaloids. 

Acridone Alkaloids.—No general review on this group has appeared for at least five years, but discoveries of individual alkaloids have been recorded" and a discussion of antitumour properties of certain bases has been published." Alkaloids have been isolated from Acronychia baueri Bauerella australiana), A. haplophylla, " Haplophyllum dubium, and Teclea natalensis With the exception of T. natalensis, which has yielded the first known acridone type with oxygenation in ring a (24), all other plant species have been shown to contain known alkaloids. 

New, simple isoquinoline alkaloids isolated and assigned structures during the period under review include thalactamine (I), thalifoline (N-methyl derivative of 2 R = Me, R = H), and noroxyhydrastinine (2 RR = CH2), from Thalic-trum minus, and bases of general structure (3) listed in Table 1 have been identified in Peyote. ... 

Monoamino-alkaloids have been isolated, in general, from the feebly basic fractions. It was in this way that Voticky and Tomko " isolated an amino-pregnane, irehine, from the leaves of B. sempervirens. Irehine was earlier extracted from the leaves of an Apocynacea, Funtumia elastica Other alkaloids isolated from different Buxus species are derivatives of methyl-pregnanes, and a few amongst them have been already described. ... 

Methods for alkaloid isolation in Australian laboratories have in general followed classical lines, but the literature contains some useful modifications of standard procedures that were designed to facilitate the extraction of plant material and the recovery and purification of the alkaloids present, and to overcome various types of problems involved in the processes. 

The mass spectra of nine pyrrolizidine alkaloids have been discussed, and their fragmentation patterns elucidated.14 In general, the results are consistent with those obtained earlier,15,16 and they are being used to identify the gross structure of pyrrolizidine alkaloids isolated from Danish rough-leaved plants. 

Table 5 summarizes results of protopine alkaloid isolation studies. The structures assigned to the two alkaloids isolated from both Fumaria parviflora and F. vaillantii are of immediate interest and concern.221 The detailed study of the Papaver genus is of general chemotaxonomic interest.69... 

Marine natural products have been extensively reviewed in many monographs and journals (1-17). Kobayashi and Ishibashi have reviewed marine alkaloids in general in this series (16), and our recent review (17) provides an account of toxic alkaloids of marine origin. This chapter is intended to provide the reader a brief description of the isolation, structure elucidation, synthetic studies, and biological screening of important classes of steroidal alkaloids and amines of marine origin. 

The chemist who plans to work on the constitution of alkaloids is generally confronted with three main problems first the location of a suitable plant source, second the isolation of the plant bases from this source, and third the resolution of this mixture of alkaloids into its pure components. 

The final chapter, by Itokawa, Takeya, Hitotsuyanagi, and Morita, reviews the various macrocyclic peptide alkaloids isolated from plants. In addition to a general overview of the many new peptide and amide alkaloids that have been isolated recently from a diverse range of plant families, this review places particular emphasis on the structure-activity relationships, the conformational analysis, and the antitumor activity of the RA series of cyclic oligopeptides from Rubia spp. 

The presence of almost 100 alkaloids in this genus (Tables I-VII) means that approximately a third of the total number of alkaloids isolated from Amaryllidaceae have been found in the genus Narcissus. Amaryllidaceae alkaloids are present in all the species and varieties of Narcissus studied. In general, a series of related alkaloids is found in each plant often a few major metabolites and several minor components, which differ in the position of their substitutents. Up to now, about 40 wild species and around 100 cultivars have been studied in relation to the presence of alkaloids (Tables VIII and IX), which means that more than half of the Narcissus species or varieties have still to be explored in this aspect. 

Isolation, Identification, and Structure Elucidation of Alkaloids A General Overview... 

Isolation of Alkaloids Biosynthetic Origin of Alkaloids Some General Reactions Involved in the Formation of Alkaloids... 

Isolation procedures for Sceletium alkaloids have generally relied on column chromatography over alumina and/or silica gel for the separation and purification of the major alkaloids, with rqieated preparative-layer chromatography often necessary for separation of the minor bases. In one instance high-pressure liquid chromatography was used for purification of an alkaloid. This latter technique is likely to find increasing application in the future for isolation of the minor alkaloids of this family. 

The first lycopodium alkaloid was isolated from the club moss Lycopodium complanatum by Bodeker as early as 1881 [18] much later its structure was shown to be lycopodine [19]. Since the first comprehensive review on lycopodium alkaloids was published in 1968 [20], new structures have been isolated and the chemistry and biology of this class of compounds have been reviewed several times [6-9, 21], According to Ayer [6], the lycopodium alkaloids are generally considered to comprise of four major classes. Compounds 1-4 are representatives of each group lycopodine 1 (class 1), lycodine 2 (class IT), fawcettimine 3 (class III), and phlegmarine 4 (miscellaneous class IV). 

The following remarks, although written specifically with indole alkaloids in mind, are good for alkaloids in general and basically true for any isolation problem. At some time during the workup of a plant extract advantage is taken of that property of the looked for substance(s) which will enable its separation from the other products. For an alkaloid one normally takes advantage of its basicity unless some other incidental property can be effectively used. In its simplest form an extract of the plant in a water immiscible solvent is washed with aqueous acid which upon subsequent basification affords the alkaloids. 

The biosynthesis of lycopodium, quinohzine, pyridine, or a-pyridone-type alkaloids isolated from Lycopodium species, shares some common steps with the biosynthesis of the previously mentioned piperidine alkaloids [28, 35, 36], The first general intermediate for all lycopodium alkaloids is the piperidine alkaloid pelletierine (45). Again, besides the... 

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