Indolizidine alkaloids from ants

Scheme 10.13).110 New alkaloids from ants, (3R, 5.S, 9fl)-3-butyl-5-(l-oxopropyl)indolizidine and (3R, 5R, 9/ )-3-butyl-5-(l-oxopropyl)indolizidine, are identified and synthesized as outlined in Scheme 10.14.111... 

Tables I through VIII summarize the occurrences of alkaloids from ants and other insects. Each table presents chemical structures as well as specific sources of particular types of alkaloids e.g.. Table I covers piperidines and pyridines. Table II, pyrrolidines, pyrroles, and indolizidines.

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... 

Figure 27 Piperidine and Indolizidine alkaloids from Solenopsis ants.

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. ... 

Figure 9.10 More complex alkaloids from ants The indolizidines where R is butyl, hexyl and 3-hexenyl have been known from the venom o/Monomorium pharaonis, pharaoh s ant, for some time. The 2-heptyl-8-methyl-pyrrolizidine is from a Soienopsis ant. The keto-indolizidine is from an African Myrmicaria ant. There are eight of the tetraponerines from Tetraponera species from New Guinea...

Carbon-13 n.m.r. assignments have been reported for a number of isomeric 3-butyl-5-methyloctahydroindolizines that were synthesized in studies of the trial pheromone of the Pharaoh ant, and for some closely related indolizidines. This work includes a detailed discussion of the preferred conformations of these compounds.15 Securinegine, a minor alkaloid from Securinega suffruticosa Rehd., is isomeric with securinine, and the structure (22) has been proposed.16... 

INDOLIZIDINE AND QUINOLIZIDINE ALKALOIDS FROM AMPHIBIANS AND ANTS... 

Table 1. Mass Spectra of Newly Identified Indolizidine and Quinolizidine Alkaloids from Amphibians And Ants.

All the currently known indolizidine and quinolizidine alkaloids isolated from ants are illustrated in Fig. 6. (+ )-Monomorine I (427), the well-studied trail pheromone constituent of the Pharaoh ant Monomorium pharaonis), and the analogs 428-431 were described in the earlier volumes in this series. These five compounds are 3,5-disubstituted indolizidines bearing short saturated or mono-unsaturated hydrocarbon chains. The relative stereochemistry in monomorine VI (430) still remains unknown, while that of 431 was atypical for the class at the time of its isolation 380). The structural resemblance of fiiis group of alkaloids to the... 

Fig. 6. Indolizidines and related alkaloids isolated from ants.

The most common indolizidine and quinolizidine alkaloids from amphibians and ants are usually identified by their GC-MS and GC-FTIR spectral characteristics. These spectral features were collected by Garraffo and co-workers [18,19], and can be summarized as follows ... 

The indolizidine alkaloid (+ )-monomorine I (373), isolated from Pharaoh s ant Mono-morium pharaonis, is the first example of an indolizidine alkaloid found in the animal kingdom. One enantioselective total synthesis of 373 exploits an asymmetric cycloaddition of nitrone 370 to the chiral allylic ether 369, which is prepared from 349. The conversion of 349 to a tosylate followed by treatment with -propylmagnesium bromide in the presence of... 

A series of substituted piperidine alkaloids have been isolated from the legume genera Cassia (subfamily Caesalpini-oideae) mdProsopis (subfamily Mimosoideae) (Fig. 29.16). (Strunz and Findlay, 1985). Based on the structures of these compounds, it seems possible that they are derived from acetate-malonate precursors. These compounds are quite similar in structure to the venoms of fire ants (Nahrstedt, 1982). Indolizidine alkaloids also have been isolated from Prosopis species (Howard and Michael, 1986). 

Recently a whole series of indolizidine and pyrrolo-indolizidine alkaloids have been found in Myrmicaria ants (Figure 9.12), which evidently have a similar origin to the indolizidines in Figure 9.10. Note that they are all constructed from straight carbon chains. The structures of the complex dimer and trimer were deduced from NMR and mass spectral studies. 

Hydroamination has been found to be useful in racemic synthesis of various natural products. Helquist and coworkers recently synthesized ( ) momomorine I using Ag-catalyzed hydroamination/cyclization of amino-diyne as the key step. Monomorine I is an indolizidine alkaloid isolated from ant Monomorium pharaoins. Beller and coworkers found hydroamination useful in the synthesis of amphetamines. It is worth mentioning that amphetamine is a class of compounds having several biological activities such as a stimulant to the central nervous system, an antiinflammatory agent, and inhibitors of enzymes. ... 

Disubstituted indolizidines, unlike many classes of amphibian alkaloids, are not unique to amphibians. 3,5-Disubstituted indolizidines such as monomorine I [(5Z,9Z)-195B] occur in ants of the genera Monomorium and Solenopsis (125,129,134). Some of the ant indolizidines are as follows (5Z,9Z)-3-n-butyl-5-methylindolizidine (monomorine I), (5Z,9Z)-3- -ethyl-5-methylindolizidine, (5Z,9Z)-3-hexyl-5-methylindolizidine, and (5 ,9Z)-3-butyl-5-(4-pentenyl)indolizidine. A series of 5-substituted indolizidines, the piclavines, were reported recently from a marine tunicate (Clavelina picta) (135). 

Indolizidine and quinolizidine alkaloids have been found in different natural sources and have been isolated from amphibians, ants, fungi, marine organisms and plants. Most of them have noxious or toxic properties and... 

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