3- -5-methylindolizidine

Examination of the venom content of the workers of Solenopsis maboya revealed the presence of (5Z,9Z)-3-butyl-5-methylindolizidine (107), (5E,9E)-3-butyl-5-methylindolizidine (108) and frans-2-methyl-6-nonylpiperidine (109), while analysis of the extract of the queens revealed the presence of a single alkaloid, ris-2-heptyl-5-methylpiperidine (110) (Fig. 19) [117]. Such caste-specific alkaloidic contents has been already been found in other Solenopsis ants [ 118,119] and suggest different roles for these compounds in each caste. 

Stractures of 3-alkyl-5-methylindolizidines, found in thief ants, Solenopsis species (Table II), arrived at by gas chromatographic and mass spectral analysis were confirmed by coinjection and direct comparison with the synthetic sample. Indolizidine 15a from S. conjurata exhibits characteristic peaks at miz 152 (M — CHj) and 138 (M — C2H5, a base peak) as well as a parent peak at m/z 167 in the mass spectram. It corresponds to an isomer of 3-ethyl-5-methylindolizidine (15) which was prepared as a mixture of four stereoisomers by reductive amination of triketone 391 with ammonium acetate-sodium cyanoborohydride and sodium borohydride (Scheme 47). 

Z,9Z)-3-Hexyl-5-methylindolizidine (17a) from a Solenopsis sp. exhibits characteristic peaks at miz 208 (M — CH3) and 138 (M - CgHjj, a base peak) as well as a parent peak at m/z 223 in the mass spectrum. The stereochemistry has been determined by synthesis. Racemic (5Z,9Z)-3-hexyl-5-methylindolizidine (17a) was prepared by the above-mentioned methodology, using octene-1-oxide instead of butene-1-oxide (Scheme 47) (134). 

Monomorine VI (18), 3-(5-hexenyl)-5-methylindolizidine, has been isolated from M. pharaonis workers (Table II), but its stereochemistry is unknown and synthesis has not yet been conducted (22,23b). 

Indolizidine and 3-methylindolizidine have been obtained in a Loffler-Freitag reaction from N- chloro-2-propylpiperidine and AT-chloro-2-butylpiperidine, respectively, by the action of sulfuric acid in the presence of UV light. The reaction is stereospecific, giving almost entirely one diastereomer of 3-methylindolizidine (63JCS3898). It is a key reaction in a synthesis of the steroid alkaloid leptidine (69CB4080). 

A trail pheromone of the Pharaoh ant was identified as 3-butyl-5-methylindolizidine of the stereochemistry given in (219) (75JHC289). Slaframine (220) is a metabolite isolated from Rhizoctonia leguminicola responsible for producing excessive salivation in cattle. A stereoselective synthesis was reported (73JOC3848). Swainsonine (221), a potent inhibitor of a-mannosidase, has been isolated from Swainsona caneszens. The stereochemistry was derived from the NMR spectrum (79AJC2257). 

Recently, a glandular secretion of the Pharaoh ant has been isolated and identified as 3-butyl-5-methylindolizidine.257 Oliver and Sonnet have successfully synthesized its four stereoisomers.258,259 Routes are shown in Scheme 27.258... 

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). 

The isolation of indolizidine 207A in sufficient quantity for nuclear magnetic resonance spectroscopy (87) established a 5-(pent-4-enyl)-8-methylindolizidine structure as shown in IX. The (5R,8R,9S) absolute configuration shown is the same as that of 205A, which contains a terminal... 

The 5-substituted 8-methylindolizidines appear to be unique to amphibians. However, a 5-(3-furyl)-8-methylindolizidine has been reported as a... 

Three new diastereomers of 3-hexyl-5-methylindolizidine, (5Z,9Z)-, (5E,9E)- and (5Z,9 ), Fig. (8), were identified in different collections of thief ants Solenopsis (Diplorhoptrum) species from Cahfomia. The identification of these alkaloids resulted from the analysis of their MS spectra and comparison of their GC-FTIR spectra. The authors also emphasised the chemotaxonomic value of the stereochemistry of these alkaloids [23]. 

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