Trail pheromone of the Pharaoh ant

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). 

This reaction was used to synthesize faranal (1), the trail pheromone of the pharaoh ant.2... 

The seco-phenanthroindolizidine alkaloid septicine has been synthesized by a nitrone route. A cycloaddition of 1-pyrroline 1-oxide with 2,3-bis-(3,4-dimethoxyphenyl)butadiene gives two stereoisomeric isoxazolidines, one of which is converted into ( ) septicine.10 ( )-Tylophorine and 5-coniceine have been prepared by a new route that makes use of an intramolecular imino-Diels-Alder reaction.11 A stereoselective synthesis of 3,5-dialkyl-indolizidines has been applied to the synthesis of a stereoisomer of the trail pheromone of the Pharaoh ant and to a stereoisomer of gephyrotoxin 223.12 A stereoselective total synthesis of ( )-perhydrogephyrotoxin (21)13 and a simple synthesis of ( )-gephyran14 have been reported. 

Certain 2,5-dialkyl-pyrrolidines, which are trail pheromones of the pharaoh ant (Monomorium pharaonis L.), have been synthesized by application of the Hofmann-Loffler reaction to 5-aminotridecane and 7-aminopentadecane. The same type of compound results from Seebach alkylation of TV-nitrosopyrrolidines.4... 

Reduetive alkylation of heteroaromatic rings is possible using catalytic hydrogenation. 34 Cyclization of the substituted pyridine 442 was induced by treatment with triphenylphosphine bromine, and generated pyridinium salt 443. Isolation of 443 by Sonnet was followed by hydrogenation with platinum, generating the trail pheromone of the Pharaoh ant (3-butyl-5-methyloctahydroindolizine, 444). 35... 

Mori reported an improved synthesis of (3S,4P,6 ,10Z)-faranal (37), the trail pheromone of the Pharaoh s ant (Monomorium pharaonis) [84]. As summarized in Scheme 55, the key-reaction was the coupling of iododiene A with iodide E. The geometrically pure A was prepared by the zirconocene-mediated carbo-alumination reaction, and E was prepared from B by the asymmetric cleavage of its epoxy ring to give C (77% ee), which could be purified via its crystalline 3,5-dinitrobenzoate D. 

In a review of current work on the trail pheromone of the Pharaoh s ant, Monomorium pharaonis, it is reported that natural monomorine III is the all-cw-... 

A few years ago the complete structure of periplanone-B, apart from its stereochemistry, was elucidated and published by our research team (32,33,34) with Persoons as the principal investigator, who included this work in his doctoral thesis (35), and shared the Royal Dutch Shell Prize for 1978 with Ritter for this work and the structure elucidation of faranal, the trail pheromone of the Pharaoh s ant, Monomorium pharaonis (36,37). 

Urethanes analogous to the amides of the previous section undergo similar deprotonation followed by alkylation and condoisation reactions. For example, 2,4,6-tri-r-butylphenol may be converted into the corresponding urethane which can be further functionalized (equation 32). N-Carbomethoxy-3-pyrroline has been convoted into both the trail pheromone for the Pharaoh ant and gq)hyrotoxin 223 by using regiospecific alkylations (Scheme 3). ° Similar tqjproaches were used in the preparation of the natural product supinidine. Piperidines also have been alkylated via the r-BOC-protected amines. ... 

This is the most common relationship, and the majority (about 60%) of the chiral pheromones belong to this category. (lR,5S,7R)- xo-Brevicomin (76), the aggregation pheromone of the western pine beetle, and (35,4/ )-faranal (95), the trail pheromone of the Pharaoh s ant, are the typical members of this group. 

The same methodology is applied in the enantioselective synthesis of iodo ether 23, a key precursor of ( + )-faranal (24) (a trail pheromone of the Pharaoh s ant)969. 

A high degree of chiral transmission is observed in the synthesis of iodo acetal 19, a key intermediate in the total synthesis of ( + )-faranal (a trail pheromone of the Pharaoh s ant). The [2,3] Wittig process ot 16 followed by cis hydrogenation gives oxy-Cope substrate 17 with 100% E and Z and >99% threo. The oxy-Cope process of 17 affords en7//ro-aldehyde 18 as a single product with 91 % ee966. 

Another natural product, (+ )-faranal (27), a trail pheromone of the Pharaoh s ant, has also been synthesized starting with 2 (see Scheme 3) [11].The crucial transformation in the sequence is a [2,3] Wittig rearrangement of 24 which, after cw-hydrogenation, gives diene 25 in > 96% ee. This intermediate, when treated with potassium hydride, undergoes an anionic oxy-Cope rearrangement to afford the erythro aldehyde 26 in 91% ee. 

Ritter, F. J., Bruggeman-Rotgans, I. E. M., Verweil, P. E. J., Persoons, C. J. and Tal-man, E. (1977) Trail pheromones of the Pharaoh s ant, Monomorium pharaonis isolation and identification of faranal, a terpenoid related to juvenile hormone II. Tetrahedron Letters, 2617-18. 

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... 

The octahydroindolizine trail pheromone (412) of the Pharaoh ant (Monomorium pharaonis) was first prepared by Ritter et al. (181) as a mixture of stereoisomers, beginning with a termolecular condensation (Scheme 74). Oliver and Sonnet (182) then unambiguously synthesized the four stereoisomers from 2,6-lutidine (413) (Scheme 75) and 2-butyl-pyrrole (418) (Scheme 76). 

An alternative strategy for (1) would have been to reconnect both substituents into a ring to ensure their ais arrangement. This strategy was used in syntheses of the antibiotic methylenomycin (4) and the trail pheromone of pharaoh s ant, faranal (5). 

We end with an example that includes methods from this chapter as well as some revision and a reminder of stereochemistry. Monomorine I 71 is the trail pheromone of Pharaoh s ant (Monomorium pharaonis). These ants are pests in hospitals as they spread infections and they follow a trail of monomorine as they go about their evil work. Synthetic monomorine might be... 

Anodic oxidation of amides and carbamates on the other hand are far more useful than those of amines. Scheme 46 shows the synthesis of a pharaoh ant trail pheromone in which the anodic oxidation of 2-pyrrolidone is an important step [270]. 

In 1977, Ritter and coworkers in the Netherlands isolated and identified faranal (95, Figure 4.46), the trail-following pheromone of the workers of the Pharaoh s ant (.Monomorium pharaonis). The detection threshold of 95 is about 1 pg/cm of a trail. This remarkable bioactivity of 95 attracted the attention of... 

Pheromones.—Further use has been made of Bestmann s unitized construction principle to synthesize a variety of 1,5- and 1,6-alkadiene pheromones. Standard Wittig methods have been used to synthesize (3Z,6Z,9Z)-1,3,6,9-nonadecatetraene (142) (Scheme 19) (now identified as a sex pheromone of the winter moth O. brumata), sex attractants (143) of Lasiocampidae species, and the trail pheromone (144) of Pharaoh s ant. A variety of 2,4-dienoic ester insect juvenile hormone analogues (145) with terminal cyclohexene, cyclohexane, or pinene rings have been prepared by phosphonate olefination. The queen... 

OZ)-3,4,7,11 -tetramethyltrideca-6,10-dienal (faranal), the trail pheromone of Pharaoh s ant, Monomorium pharaonis, In one approach, racemic (3S,47 /3/ ,45) faranal (54) was synthesised by a route in which stereospecific formation of a trisubstituted double-bond and a substituted vinyl iodide was controlled by addition of alkyl-copper complexes to terminal acetylenic derivatives. The relative configuration of the methyl groups at C-3 and C-4 was established by the use of c fs-4,5-dimethyl cycl ohexene as an important intermediate (Scheme 8). ... 

Faranal (Figure 6.25) is the trail pheromone of Pharaoh s ant Mono-morium pharaonis, a tropical species that has become a pest inside warm buildings in temperate climates. It contains two homomevalonate... 

From the above survey of results the synthetic potential of the oxazinolactam intermediate 46 in hand, we envisaged to synthesize monomorine I (62) which constitutes of an extension of the methodology based on intramolecular nitroso Diels-Alder cycloaddition. The relative stereochemistry of this substance, isolated as one of the trail pheromones from Pharaoh ants (Monomorium pharaonis L.) (ref. 19), has been determined its relative stereochemistry by nonstereoselective synthesis (ref. 20). More recently, a stereospecific synthesis of racemic 62 (ref. 21) and a chiral synthesis of the (-)-enantiomer of natural 62 (ref. 22) were reported. 

---