Slaframine alkaloids

The mass spectra of indolizine alkaloids have been reviewed in detail (B-75MI30800). Some principles may be taken from the fragmentation pattern of slaframine, given in Scheme 3. 

The indolizines constitute the core structure of many naturally occurring alkaloids, such as (-)-slaframine, (-)- dendroprimine, indalozin 167B and coniceine. There are a number of different routes to the synthesis of indolizines and they are most commonly synthesised by sequential N-quaternisation, intramolecular cyclocondensation reactions or the cycloaddition reaction of /V-acyl/alkyl pyridinium salts. 

Ergot alkaloids Slaframine Claviceps purpurea Rhizoctonia legminicola Many cereal foods... 

Polyhydroxyindolizidines and slaframine form a group of alkaloids that displays a large spectrum of biological activity [39]. 

Pyrrolizidines compounds have been produced in connection with syntheses of other types of natural products. For example, Gensler and Hu prepared the dioxopyrrolizidine ester (46) as an intermediate in the synthesis of ( + )-slaframine, an indolizidine alkaloid obtained from cultures of Rhizoctonia leguminicola. The pyrrolidone ester (47), prepared from l-glutamic acid [Eq. (14)], was optically active, but the cyclized product, formed in quantitative yield from 47, was completely racemized. The synthesis of 2-acetyl-1,3-dioxopyrrolizidine (48) was carried out by Kruger and Arndt to assist with their investigations on model compounds aimed toward the total synthesis of a-cyclopiazonic acid, the main toxic principle of Penicillium cyclopium The spectra of the product (48) obtained in 30% overall yield was typical of an intramolecularly H-bonded enolized )S-... 

The following post-1986 reviews in this treatise provide the antecedents for several sections of this chapter. The important contribution of Takahata and Momose in Volume 44, entitled "Simple Indolizidine Alkaloids", covered the period 1986 to 1992, but dealt only with Elaeocarpus alkaloids, slaframine, polyhydroxylated indoUzidines such as swainsonine and castanospermine, and alkdoids fiiom ants and amphibians (2). This partial update is especially valuable as a guide to published totd syntheses of these alkaloids. Materi of relevance is also to be found in a number of reviews on more specialized topics. Numata and Ibuka reviewed the chemistry of alkaloids from ants and other insects in Volume 31... 

Other natural indolizidine alkaloids comprise the fungi indolizidines (slaframine type alkaloids), Fig. (18), polyhydroxylated indolizidines (usually isolated from the plant genera Eleocarpus, Astragalus and Iponuga), and marine type indolizidines. 

Slaframine (87), an alkaloid which stimulates excess salivation in livestock foraging on fungus-infected red clover, has been synthesized (Scheme 5). The... 

It is well known that alkyl azides also behave as 1,3-dipoles in intramolecular thermal cycloaddition reactions. The formation of two carbon-nitrogen bonds leads to triazolines, which are usually not stable. They decompose after the loss of nitrogen to aziridines, diazo compounds, and heterocyclic imines. There are a limited number of examples reported in which the triazoline was isolated [15]. The dipolar cycloaddition methodology has been extremely useful for the synthesis of many natural products with interesting biological activities [16], In recent years, the cycloaddition approach has allowed many successful syntheses of complex molecules which would be difficult to obtain by different routes. For instance, Cha and co-workers developed a general approach to functionalized indolizidine and pyrrolizidine alkaloids such as (-i-)-crotanecine [17] and (-)-slaframine [18]. The key step of the enantioselective synthesis of (-)-swainsonine (41), starting from 36, involves the construction of the bicyclic imine 38 by an intramolecular 1,3-dipolar cycloaddition of an azide derived from tosylate 36, as shown in Scheme 6 [ 19). 

Hua has recently extended this methodology as a route toward the asymmetric total synthesis of alkaloids including (+)-epilupinine (43) and (—)-lupimne (44) [34], and (-)-slaframine (45) and (-)-6-epislaframine (46), in enantiomerically pure form [35]. 

The alkaloid slaframine (38) is produced by cultures of Rhizoctonia leguminocola grown on nontoxic red clover extract. This alkaloid is responsible for a series of characteristics such as slobbering (excessive salivation) and lacrima-tion. This disease has been determined to result from consumption of the fungal mycelia (Elbein and Molyneux, 1987 Fellows et al, 1989 Howard and Michael, 1986). 

Differences in configuration of swainsonine (35) and slaframine (38) appear to arise by involvement of an iminium ion similar to the situation involved in conversion of (-f-)-reticuline to ( — )-reticuline in the benzylisoquinoline alkaloid series (see Chapter 32) (Harris et al, 1987). 

Harris CM, Schneider MJ, Ungemach FS, HiU JE, Harris TM (1998) Biosynthesis of the toxic alkaloids slaframine and swainsonine in Rhizoctonia leguminicola Metabolism of 1-hydroxy-indolizidines. J Am Chem Soc 110 940-949... 

In alkaloid synthesis, cyclization strategies have been mediated by (TMS)3SiH. An example is given by the total synthesis of (—)-slaframine starting from a phenylseleno derivative (eq 31). ... 

Several other general reviews dealing with aspects of indoHzidine and quinolizidine alkaloid chemistry were pubHshed during the period under consideration. The series of annual reports in the Royal Society of Chemistry s journal Natural Product Reports, which provided regular coverage of both simple and various more complex indolizidine and quinolizidine alkaloids, ended in 2008.Another important review that dealt principally with pertinent alkaloids from ants and amphibians, slaframine, polyhydroxy-lated indolizidine alkaloids, and the lupin quinolizidine alkaloids was published in the series Studies in Natural Product Chemistry in 2002, and covered the period 1994 to 1999. ... 

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