Ants, alkaloids synthesis

Previous treatment of the indolizidine and quinohzidine alkaloid constituents of ant secretions may be found in Volume 55 of this series. An important review describing the defensive chemistry of ants, by Leclerq et al., deals with the occurrence, stmcture, function, and total synthesis of all the major groups of ant alkaloids, especially monomorine I vide infra. Section 6.1.2)... 

MacDonald, T. L. Indolizidine alkaloid synthesis. Preparation of the pharaoh ant trail pheronlone and gephyrotoxin 223 stereoisomers. J. Organ. Chem. (USA) 45,193—195 (1980). 

Two examples of synthesis of ant venom alkaloids via the Seebach (162) W-nitroso methodology have been published (163, 164). They start with N-nitrosopyrrolidine (125), which is sequentially alkylated at positions 2 and 5 (Schemes 14 and 15). 

The venom of ants of the genus Myrmicaria is made up of indolizidine or pyrrole-indolizidine alkaloids [188,189]. The synthesis of some of these alkaloids has already been reported in the review of Leclercq et al. [114]. Thus, we will report here only on the syntheses published since 1999. 

A related oxime 304 was prepared for the total synthesis of 305, an unusual pyrrolizidine alkaloid isolated from the venom of a variety of thief ant... 

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. 

The heterocyclic hemi-aminal 44 was formed as a model for the synthesis of the marine alkaloids zoanthamine and zoanthenol and is derived from the cyclic imine formed by the reduction of an appropriated substituted azide <07H(72)213>. A pyrrolidine-fused azepine has been isolated from the venom of the ant Myrmicaria melanogaster and assigned as 45 based upon GC and FT-IR comparison with synthetic material <07JNP160>. The axially chiral doubly bridged biphenyl azepine 46 has been synthesised and used with oxone as an epoxidation catalyst in a biphasic system <070BC501>. 

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... 

CioH.jN, Mr 147.22, oil, bp. 100-103 °C(1 kPa),[a]i, -7.2° (CHCI3), a monoterpene alkaloid ( iridoids) from the east Asian creeper Actinidia polygama and other Actinidiaceae, Bignoniaceae, and Valerianaceae. It is a component of the defensive secretion of black beetles, ants, grasshoppers, and flies. Only the (5) enantiomer occurs in nature. A. exhibits antimicrobial properties and a deterrent effect against birds and arthropods , while cats are strongly attracted Synthesis There are various syntheses of the racemate and the unnatural (/I) enantiomer, but only three for the (5) enantiomer. The biosynthesis presumably proceeds from iridodial. 

Hayashi K, Tanimoto H, Zhang H, Morimoto T, Nishiyama Y, Kakiuchi K. Efficient synthesis of alpha, beta-unsaturated alkylimines performed with allyl cations and azides Applications to the synthesis of an ant venom alkaloid. Org Lett 2012 14 (22) 5726-31. 

Recently, a high yielding synthesis of a,p-unsaturated alkyhmines was developed using azides tethered to an allyhc alcohol (i.e., 123) (2012OL5728). Thus, treatment of 123 with p-toluenesulfbnic acid gave rise to unsaturated imines of type 125. A very reasonable pathway to explain this result would involve an initial 1,3-dipolar cycloaddition to give triazoline 124 as a transient intermediate which is easily dehydrated to produce the observed product (Scheme 29). The efficiency of the method was nicely demonstrated by the total synthesis of the Costa Rica ant venom alkaloid 127 from the MOM-masked cycHzation precursor 126. 

The indolizidine alkaloid swainsonine 412, a potential anticancer drug, has been the target of a number of syntheses. Pearson [99] started with 2,3-O-isopro-pylidene-D-erythronolactone 413, which afforded in three steps the allyUc alcohol 414. This compound was in turn submitted to Claisen-Johnson rearrangement and afforded ester 415. Selective dihydroxylation followed by functional group manipulations led to the target alkaloid (Scheme 6.68). An aminyl radical cycHza-tion was the key step in an ant venom alkaloid 416 synthesis [100]. The Claisen-Johnson rearrangement was used in the preparation of both side chains of this pyrroUdine alkaloid (Scheme 6.68). 

---